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There is a well-established literature indicating a relationship between iron in brain tissue and Alzheimer's disease (AD). More recently, it has become clear that AD is associated with neuroinflammatory and oxidative changes which probably result from microglial activation. In this study, we investigated the correlative changes in microglial activation, oxidative stress, and iron dysregulation in a mouse model of AD which exhibits early-stage amyloid deposition. Microfocus X-ray absorption spectroscopy analysis of intact brain tissue sections prepared from AβPP/PS1 transgenic mice revealed the presence of magnetite, a mixed-valence iron oxide, and local elevations in iron levels in tissue associated with amyloid-β-containing plaques. The evidence indicates that the expression of markers of microglial activation, CD11b and CD68, and astrocytic activation, GFAP, were increased, and were histochemically determined to be adjacent to amyloid-β-containing plaques. These findings support the contention that, in addition to glial activation and oxidative stress, iron dysregulation is an early event in AD pathology.

Ion channel trafficking and gating are often influenced by interactions with auxiliary subunits. Tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) is an auxiliary subunit for neuronal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. TRIP8b interacts directly with two distinct sites of HCN channel pore-forming subunits to control channel trafficking and gating. Here we use mutagenesis combined with electrophysiological studies to define and distinguish the functional importance of the HCN/TRIP8b interaction sites. Interaction with the last three amino acids of the HCN1 C terminus governed the effect of TRIP8b on channel trafficking, whereas TRIP8b interaction with the HCN1 cyclic nucleotide binding domain (CNBD) affected trafficking and gating. Biochemical studies revealed that direct interaction between TRIP8b and the HCN1 CNBD was disrupted by cAMP and that TRIP8b binding to the CNBD required an arginine residue also necessary for cAMP binding. In accord, increasing cAMP levels in cells antagonized the up-regulation of HCN1 channels mediated by a TRIP8b construct binding the CNBD exclusively. These data illustrate the distinct roles of the two TRIP8b-HCN interaction domains and suggest that TRIP8b and cAMP may directly compete for binding the HCN CNBD to control HCN channel gating, kinetics, and trafficking.

Introduction: Harrison's class IV calvarial burns with greater than 75% exposure present a special problem in flame injury. This problem is compounded in small children and or those with a large total body surface area burn, thus limiting the possibility of local flaps and free tissue transfers for coverage and leaving only wound care and skin grafts as options for closure. The literature suggests trephination with a high speed drill until viable bone is reached, then autografting the subsequent granulation tissue. In the most severe cases when the calvarium is deeply thermally injured and drilling down to the level of the Dura does not yield any sign of viability; should the surgeon proceed with removal of the clearly compromised calvarium down to Dura or leave it in place?, Methods: At a pediatric burn center, we reviewed all Harrison's class IV flame burns to the head with more than 75% exposure of the calvarium for a 2.5-year period. Five cases fit our inclusion criteria., Results: All five patients had drilling of the calvarium to debride dead bone. Three of the children had drilling that reached viable bone and were treated with a combination of early grafting and allowing granulation tissue to form then grafting. Two of the patients had extreme flame burns to the head with large areas having no clinical evidence of viability down to the Dura. The photographic record and CT reconstructions of these two cases are presented. The figures show the progression of healing of the calvarium in each child. A persistent calvarial defect only in the area of complete removal of calvarium to Dura is seen in each child's record. The remaining areas demonstrate progressive wound closure with remodeling of the skull in long term follow-up., Conclusion: In deep massive calvarial burns to the head it is difficult to achieve wound closure. Trepanation with subsequent grafting and expectant management while awaiting granulation tissue bed is the current recommended treatment for this clinical problem. The aggressiveness of surgical debridement of dead bone is largely based on clinical appearance of the tissue. In the cases presented here, complete removal of clinically non-viable burned calvarium resulted in calvarial defects that were avoided when some deep calvarium was left in place despite its poor clinical appearance. The clinical challenge of closing calvarial defects in the reconstructive phase of care should not be underestimated. Therefore, avoidance of a defect if possible by allowing some bone to remain during trephination is recommended., (Copyright © 2010 Elsevier Ltd and ISBI. All rights reserved.)

Novel phosphorylated dihydroceramide (PDHC) lipids produced by the periodontal pathogen Porphyromonas gingivalis include phosphoethanolamine (PE DHC) and phosphoglycerol dihydroceramides (PG DHC) lipids. These PDHC lipids mediate cellular effects through Toll-like receptor 2 (TLR2) including promotion of IL-6 secretion from dendritic cells and inhibition of osteoblast differentiation and function in vitro and in vivo. The PE DHC lipids also enhance (TLR2)-dependent murine experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. The unique non-mammalian structures of these lipids allows for their specific quantification in bacteria and human tissues using multiple reaction monitoring (MRM)-mass spectrometry (MS). Synthesis of these lipids by other common human bacteria and the presence of these lipids in human tissues have not yet been determined. We now report that synthesis of these lipids can be attributed to a small number of intestinal and oral organisms within the Bacteroides, Parabacteroides, Prevotella, Tannerella and Porphyromonas genera. Additionally, the PDHCs are not only present in gingival tissues, but are also present in human blood, vasculature tissues and brain. Finally, the distribution of these TLR2-activating lipids in human tissues varies with both the tissue site and disease status of the tissue suggesting a role for PDHCs in human disease.

Common bile duct stenosis owing to extrahepatic portal varices is termed "portal hypertensive biliopathy" (PHB) and is a rare occurrence. We report a case of PHB owing to portal vein thrombosis with cavernous transformation successfully managed by mesocaval shunt and endoscopic retrograde cholangiopancreatography (ERCP) biliary stent placement. A 44-year-old male, who presented with hematemesis, melena, jaundice, and abdominal pain, underwent gastroscopy, which revealed bleeding gastric varices. Computed tomography with arterial and venous imaging demonstrated portal vein thrombosis with cavernous transformation and extensive extrahepatic varices within the porta hepatis causing common bile duct obstruction from extrinsic compression. Biliary decompression was achieved with ERCP, and a small common bile duct stone was retrieved. A mesocaval shunt with a 16 mm Dacron graft successfully treated the portal hypertension. PHB is rare. We report a case successfully treated by mesocaval shunt and ERCP.

Background: The pulmonary artery catheter (PAC) has been fraught with controversy over issues of safety and impact on outcomes variables for many years. Multiple attempts to quantify the utility of this diagnostic instrument have failed to resolve the matter. Previous investigations have focused on either quantifying inter-rater variability of waveform output interpretation from PACs or on clinical outcomes when PACs are used in care. We tested the hypothesis that the true link between a diagnostic tool and outcomes is treatment selection, and an instrument that minimizes or eliminates the need for data interpretation would also minimize the variability of treatment selections., Study Design: We performed a prospective, single institutional, single blinded survey study., Results: The inter-rater variability of waveform interpretation among all raters was notable (p < 0.01); for continuous end diastolic volume index interpretation, there was no notable inter-rater variability (p=1.0). Inter-rater variability of treatment selections based on waveform interpretation was notable for all raters (p < 0.01). Continuous end diastolic volume index data presentation of hemodynamic status did not result in notable inter-rater variability in treatment selections (p=0.10). Treatment choices based on continuous end diastolic volume index among raters with 5 or more years of experience are not different from clinical practice guideline-directed choices (p > 0.05), independent of patient ventilator status., Conclusions: Digital output volumetric PACs eliminate inter-rater variability of data interpretation, decrease inter-rater variability of data-driven treatment selections, and improve rater agreement with clinical practice guidelines when compared with traditional waveform output PACs.

On August 29, 2005, the Gulf Coast was hit by Hurricane Katrina, a category 4 storm. The storm was responsible for more than 1000 deaths and the displacement of hundreds of thousands of people. Hospitals in the city of New Orleans evacuated because of the complete collapse of infrastructure. This event influenced the decisions and actions taken to protect patients, families, and staff of a 30-bed pediatric burn center in the projected path of a second catastrophic hurricane 3 weeks later. Approximately 80 hours before projected landfall, the local government announced that a mandatory evacuation of the community surrounding the burn center would occur. A coordinated decision was made by administration, nursing, and medical staff to cancel upcoming clinics and elective surgery and to evacuate all 14 inpatients, 52 outpatients, and 66 guardians to other facilities. The evacuation plan was successfully completed in 32 hours. The eye wall of the hurricane passed 65 miles east of the burn center. No significant damage to the physical plant was noted. Repopulation of the hospital by patients and acceptance of new acute burn referrals began approximately 40 hours after the local government permitted the population to return to the area. No morbidity or mortality was attributed to the evacuation. Emergent evacuation of threatened burn centers can be safely accomplished with adequate prior planning of evacuation sites, and modes of transportation. An established communication command center plays a key role in this process.

The properties of neoplastic proliferation and hormonal dysregulation are tightly linked in primary hyperparathyroidism (HPT). However, whether abnormal parathyroid proliferation is the cause or result of a shift in calcium-sensitive parathyroid hormonal regulation has been controversial. We addressed this issue by analyzing the temporal sequence of these fundamental abnormalities in a mouse model of primary HPT. These transgenic mice (PTH-D1) harbor a transgene that targets overexpression of the cyclin D1 oncogene to parathyroid cells, resulting in parathyroid hypercellularity with a phenotype of chronic biochemical HPT and, notably, an abnormal in vivo PTH-calcium set point. We examined parathyroid cell proliferation and biochemical alterations in PTH-D1 and control wild-type mice from ages 1-14 months. Strikingly, abnormal parathyroid proliferation regularly preceded dysregulation of the calcium-PTH axis, supporting the concept that disturbed parathyroid proliferation is the crucial primary initiator leading to the development of the biochemical phenotype of HPT. Furthermore, we observed that decreased expression of the calcium-sensing receptor in the parathyroid glands occurs several months before development of biochemical HPT, suggesting that decreased calcium-sensing receptor may not be sufficient to cause PTH dysregulation in this animal model of primary HPT.

Transcatheter embolization of hypogastric artery aneurysms has become an attractive therapeutic alternative for many patients with this difficult lesion. Because of the increasing use of stent grafting for treatment of abdominal aortic aneurysms, transcatheter embolization of normal-caliber hypogastric arteries has become an almost routine procedure, usually accomplished with little morbidity. Applying this treatment to aneurysmal hypogastric arteries, however, involves greater technical complexity and a significantly higher risk of ischemic complications. We present three cases to illustrate the technical challenges of hypogastric aneurysm embolization, the potentially devastating ischemic complications, and the clinical situations that may predispose to poor outcomes.

To evaluate the outcome of patients with renal insufficiency undergoing endovascular repair of abdominal aortic aneurysm (AAA), data were prospectively collected between 1998 and 2003 on patients undergoing elective repair of their AAA with a stent graft. The patients were divided into 2 groups: those with serum creatinine (Crs) concentrations <1.2 (Group A) and those with Crs > or =1.2 mg/dL not requiring hemodialysis (Group B). The outcomes of the procedure for these 2 groups were compared. Different variables that existed between the 2 groups and contributed to mortality included estimated blood loss (EBL), volume of contrast used in the operating room, incidence of diabetes (DM), tobacco use, and history of myocardial infarction (MI). In total, 213 patients underwent elective repair of their AAA with use of a stent graft: 61% who had a Crs <1.2 mg/dL (Group A) and 39% who had a Crs > or =1.2 mg/dL not requiring dialysis (Group B). Among 129 patients with normal renal function there was an 18.6% complication rate and 1.6% mortality rate. Of 83 patients with renal insufficiency not on hemodialysis 30.1% (Fisher's Exact Test = 0.076) had 1 or more complications and there was a 6% (Fisher's Exact Test = 0.166) mortality rate. One patient in Group A (0.8%) progressed to hemodialysis and 5 (6%) patients in Group B progressed to end-stage renal disease requiring hemodialysis (p=0.068). A statistically significant higher proportion of the patients in Group B had a history of MI (p<0.001). There was no difference in the amount of EBL between the 2 groups, but a significantly lower amount of contrast (p<0.05) was used in patients with renal insufficiency.

Background: In order to study the mechanisms of action of Troglitazone (TGZ) in vivo in Type 2 diabetes, its effects were studied on glucose metabolism, lipolysis and very low-density lipoprotein (VLDL) apolipoprotein B100 (apoB) kinetics., Materials and Methods: A placebo-controlled, double-blind study was performed in 24 diet-treated patients randomized to receive TGZ 600 mg day(-1), TGZ 200 mg day(-1) or placebo for 8 weeks. Glucose and glycerol turnover were assessed after an overnight fast, and during sequential low-dose insulin infusions (0.01 U kg(-1) h(-1) followed by 0.015 U kg(-1) h(-1)) using 6,6-2H Glucose and 1,2,3-2H Glycerol. Very low-density lipoprotein apoB secretion was measured using l-13C-leucine, monitoring isotopic enrichment by gas chromatography-mass spectrometry. Treatment effects were analyzed by analysis of covariance, adjusting for baseline., Results: Therapy resulted in a significant group differences in fasting plasma glucose adjusting for baseline (P=0.039). This was most evident at TGZ 600 mg daily [glucose decrease from (mean +/- SD) 9.2 +/- 2.7 to 6.6 +/- 0.9 mmol L(-1)]. HbA1c and insulin levels did not change significantly. Plasma nonesterified fatty acid (NEFA) levels decreased (P=0.045), most evidently at TGZ 200 mg daily, but glycerol was not significantly affected. Although no significant effects were observed on VLDL apoB or triglyceride concentrations, there were treatment differences in the absolute secretion rate of VLDL apoB of borderline (P=0.056) statistical significance, with a decrease observed at TGZ 600 mg daily [geometric mean, SD range, 0.94 (0.41-2.15) to 0.40 (0.14-1.13 mg kg(-1) h(-1))]. Very low-density lipoprotein apoB fractional secretion rate and pool size were unaffected. The VLDL triglyceride: apoB molar ratio differed between treatment groups (P=0.013), being higher in the TGZ 600 mg group [5714 (4128-7741) to 8092 (5669-11552)]. Neither glucose nor glycerol rates of appearance were significantly altered by TGZ and nor did TGZ affect their suppression by insulin., Discussion: The PPARgamma agonist, troglitazone, decreases fasting glucose and NEFA levels in diet-treated Type 2 diabetes. It may also decrease VLDL particle secretion. These effects would be considered beneficial. The biological importance of the increase in VLDL-triglyceride enrichment warrants further study.

Background: Patients with the manifest Brugada syndrome have an inordinate risk of sudden death and are candidates for implantation of a defibrillator. The Brugada type electrocardiogram (ECG) abnormality (the "Brugada sign"), however, is known to be associated with a wide range of conditions, many of which may not pose such a threat. Clinicians need guidance in choosing a rational approach for the evaluation and treatment of patients with a finding of the Brugada sign., Methods: A systematic literature search was performed to identify publications on the Brugada syndrome and the Brugada-type ECG abnormality, with special emphasis on analyzing outcomes data. In addition, the ECG database of our institution was reviewed for tracings consistent with the Brugada sign, and, when possible, clinical correlations were made., Results: Patients with the Brugada sign and a family history of sudden death or a personal history of syncope are at a high risk of sudden death and therefore should be strongly considered for implantation of a defibrillator. In patients who are hospitalized and critically ill, the Brugada sign is frequently the result of severe hyperkalemia, drug toxicity, or right ventricular injury. In most individuals with no symptoms and without a family history of sudden death, the Brugada sign is likely a normal variant., Conclusions: Most patients with the Brugada sign can be risk-stratified with simple clinical tools. Specific testing for the Brugada syndrome should be reserved for questionable cases and for the research setting. A provisional diagnostic-therapeutic algorithm is offered as a means of assisting the clinician in the evaluation and treatment of patients with the Brugada sign.

Microsatellite instability (MSI) is the form of genomic instability associated with defective DNA mismatch repair (MMR) in human tumorigenesis. Recent reports have suggested a role for MSI in the pathogenesis of sporadic parathyroid adenomas. However, because of their small sample sizes and/or lack of systematic analysis of genome-wide MSI, these studies have not provided conclusive evidence that MMR defects are a common occurrence in parathyroid neoplasia. To further investigate whether MSI plays an important role in parathyroid tumorigenesis, we analyzed 49 sporadic parathyroid adenomas for MSI using a panel of 5 microsatellite DNA markers that has been recommended for sensitive detection of MSI by the NCI Workshop and validated in other tumor types. These microsatellite loci were amplified by PCR using fluorescent-labeled primers from the 49 samples of template tumor DNA and matching normal DNA isolated from the same patients' peripheral blood leukocytes. None of the 49 tumors showed evidence of MSI at any of the analyzed loci of the NCI marker panel. These observations strongly suggest that defective DNA MMR plays a minor role, if any, in the pathogenesis of sporadic parathyroid adenomas.

Primary arterial dissection of the peripheral vessels is a rare condition. We report a case of spontaneous dissection of the distal superficial femoral artery compounded by distal embolization leading to ischemic symptoms. The patient was successfully treated with exploration of the superficial femoral artery over the area of the dissection, distal embolectomy, and reconstruction by way of an interposition graft. Awareness of this condition leads to potentially earlier diagnosis and expands the therapeutic options.

Isolated left lower extremity swelling secondary to left iliac vein compression was first described by McMurrich in 1908, and defined anatomically by May and Thurner in 1957 and clinically by Cockett and Thomas in 1965. The left iliac vein is usually located posterior to the right iliac artery and can be compressed between the artery and the fifth lumbar vertebrae. Symptoms include left lower extremity edema, pain, varicosities, venous stasis changes, and deep venous thrombosis. Evaluation of these patients historically included a venous duplex scan to rule out deep venous thrombosis and an abdominal computed tomography scan to rule out pelvic mass. This paper describes the use of magnetic resonance imaging and venography in the evaluation of patients with isolated left lower extremity swelling. A retrospective analysis of a series of 24 patients who presented with symptomatic left lower extremity edema was performed. Infrainguinal deep venous thrombosis and valvular reflux was evaluated by duplex scan. The presence of suprainguinal deep venous thrombosis and pelvic mass was evaluated by magnetic resonance imaging. Magnetic resonance imaging was used to define the anatomic characteristics of the May-Thurner syndrome. Patients identified with the syndrome were treated either conservatively with lower extremity compression and elevation or with angioplasty and stenting. Follow-up of this subset of patients was performed with clinical assessment of the resolution of their symptomatic lower extremity edema as well as quality of life assessments via phone interviews. Twenty-four patients were evaluated for isolated left lower extremity swelling. Seven patients had positive results on duplex scans for deep venous thrombosis. Magnetic resonance imaging results demonstrated 1/24 (4%) had a pelvic mass compressing the iliac vein; 2/24 (8%) patients had iliac vein thrombosis; 1/24 (4%) patients with a history of deep venous thrombosis demonstrated a long stenotic segment of the left iliac vein unrelated to its association with the right iliac artery; 9/24 patients (37%) had anatomic evidence of May-Thurner syndrome; and 2/24 patients (8%) had isolated left lower extremity swelling of unknown etiology. Five patients diagnosed with May-Thurner syndrome were treated conservatively with compression stockings and leg elevation. Four patients with May-Thurner syndrome underwent iliac vein angioplasty and stenting. Technical success was 100%. On clinical follow-up, the patients with May-Thurner syndrome have had improvement/resolution of their symptoms. There have been no complications from either therapy. May-Thurner syndrome is a clinical entity of left iliac vein compression by the right iliac artery, resulting in isolated left lower extremity swelling and may be a precipitating factor for iliofemoral deep venous thrombosis. Magnetic resonance imaging is the best modality for diagnosis of this entity as it can rule out the presence of pelvic masses and deep venous thrombosis while simultaneously demonstrating the anatomy characteristic of this syndrome.

Purpose: Iliac artery anatomy is a central factor in endoluminal abdominal aortic aneurysm therapy. It serves as the conduit for graft deployment and as the region of distal graft seal. Thirty-eight percent of iliac vessels in our patients require special treatment because of aneurysms, tortuosity, or small size. Bilateral hypogastric artery exclusion has been avoided because of concerns of colorectal ischemia, hip/buttock claudication, and impotence. We suggest that elective, staged, bilateral hypogastric embolization can be performed safely with reasonably low morbidity and can expand the anatomic boundaries for stent-graft abdominal aortic aneurysm repair., Methods: This study was performed as a retrospective chart review of patients requiring hypogastric artery embolization for endovascular repair of abdominal aortic aneurysms between June 1998 and June 2000. Patients with otherwise appropriate anatomy and common iliac artery aneurysms were informed of the option for stent-graft repair with internal iliac artery embolization with its risks of impotence, hip/buttock claudication, and bowel ischemia. Patients underwent unilateral or staged bilateral coil embolizations of their proximal hypogastric arteries with an approximate 1-week interval between procedures. Hospital and office records were reviewed; phone interviews were performed. Follow-up ranged from 1 to 12 months., Results: During a 24-month period, 65 patients underwent endovascular abdominal aortic aneurysm repair; 18 patients (28%) required hypogastric artery embolization. Seven (39%) of these patients underwent bilateral embolization. There were no episodes of clinically evident bowel ischemia. Lactate levels were normal in all measured patients. Postoperative fevers (> 101.0 degrees F) were documented in 10 (56%) of 18 patients. The average white blood cell count was 12.8 x 10(9)/L (range, 8.5-22.9). There were no positive blood culture results. The return to the full preoperative diet occurred in 1 to 3 days. Hip/buttock claudication occurred in approximately 50% of patients with persistent but improved symptoms at 6 months. Eighty-seven percent of patients had preoperative erectile dysfunction. Only two patients noted worsening of erectile function postoperatively., Conclusions: Preliminary results indicate that bilateral hypogastric artery embolization can be performed, when necessary, with reasonable morbidity in patients undergoing stent-graft abdominal aortic aneurysm repair.

Professionals in the fields of mental retardation and giftedness have much to teach each other as well as the field of human development in general. Examining the commonalities and differences between the fields in social issues, definitions, developmental differences from the norm, values and policy issues, and educational and long-term implications deepens insights about both normal and deviant development. The authors stress the importance of individual differences in the differential design of educational strategies and the application of approaches developed with specialized populations to normally developing children. Current social inequalities affect both of these fields in particular ways. Finally, numerous research agendas can be enhanced by including representatives of both ends of the normal curve.

Adult hypopituitarism is associated with hyperlipidemia, mainly due to an increase of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels. Recent studies have shown that such patients exhibit increased hepatic secretion of VLDL apolipoprotein B100 (VLDL apo B100). To examine the effects of growth hormone (GH) replacement on VLDL apo B100 turnover, 13 GH-deficient hypopituitary patients (8 women and 5 men; aged 47 +/- 3 years, mean +/- SEM; body mass index [BMI], 30 +/- 2 kg/m2) entered a double-blind placebo-controlled study for 6 months (GH 0.125 IU/kg/wk for 4 weeks, and then 0.25 IU/kg/wk). GH was subsequently used in all patients for a further 6 months. A 6-hour [1-13C] leucine infusion was administered at baseline and at 6 months. The secretion rate of VLDL apo B100 was derived by kinetic analysis following quantitation of isotopic enrichment by gas chromatography/mass spectrometry. The GH-treated group (6 patients) demonstrated a similar fractional secretion rate (FSR) for VLDL apo B100 at 0 and 6 months. The pool size and absolute secretion rate (ASR) also were unaffected significantly by GH therapy. No significant changes were observed in the placebo group (7 patients). Treatment with GH for 6 months caused an increase in the high-density lipoprotein (HDL) cholesterol concentration (13 patients, 1.27 +/- 0.13 v 1.16 +/- 0.10 mmol/L, respectively, P = .05), whereas total cholesterol and triglyceride concentrations did not change. Nonesterified fatty acids (NEFAs) increased during GH therapy (471 +/- 43 micromol/L at 6 months v 349 +/- 49 micromol/L at baseline, P < .0005). The data suggest that GH does not affect VLDL apo B100 turnover in a significant way.

Hypopituitarism is associated with hyperlipidemia, the mechanisms of which are not fully known. One possible mechanism is an increased hepatic secretion of very-low-density lipoprotein (VLDL) apolipoprotein B100 (apo B100). To investigate this, 13 hypopituitary patients (seven women and six men; age, 46 +/- 3 years [mean +/- SEM]; body mass index [BMI], 29 +/- 2 kg/m2) and 13 matched controls (seven women and six men; age, 43 +/- 3 years; BMI, 28 +/- 2 kg/m2) were investigated in a stable-isotope study. [1-(13)C]leucine (1 mg/kg body weight) was administered, followed by a continuous 6-hour infusion of [1-(13)C]leucine (at a rate of 1 mg/kg/h). Patients had a similar fractional secretion rate (FSR) of VLDL apo B100 versus controls (0.37 +/- 0.05 v 0.38 +/- 0.06 pools/h, respectively), but they had a significantly larger pool size (3.4 +/- 0.3 v 1.9 +/- 0.3 mg/kg) and higher absolute secretion rate ([ASR] 27.8 +/- 2.9 v 16.0 +/- 2.5 mg/kg/d). The increase in hepatic VLDL production may explain the lipid abnormalities found in hypopituitarism. Fasting circulating nonesterified fatty acids (NEFAs) were decreased in the patients (284 +/- 26 v 664 +/- 92 micromol/L, P < .001) despite the increase in VLDL secretion. An inverse relationship was observed between the NEFA level and VLDL apo B100 FSR in the patients (r(s) = -.85, P < .005).

Left ventricular (LV) cavity dilation during stress myocardial perfusion imaging has been associated with multivessel disease, and may be an independent prognostic marker in addition to perfusion defects. The present study examines the predictive value for future cardiac events of transient or fixed LV dilation during dipyridamole technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) imaging. The study included 512 consecutive patients who underwent SPECT imaging with Tc-99m sestamibi after dipyridamole infusion. Transient LV dilation was seen in 70 patients (14%) and 74 had fixed cavity dilation (14%); cavity size was normal in 368 patients (72%). Each perfusion scan was classified as normal or abnormal, and if abnormal, defects were categorized as transient or fixed, and as small, medium, or large (depending upon the number of abnormal vascular territories). Events during a mean follow-up of 12.8 +/- 6.8 months were tabulated by direct review of hospital charts and death certificates. The cardiac event rate (cardiac death or nonfatal infarction) was 1.9% in patients with normal cavity size, 11.4% with transient LV dilation, and 13.5% with fixed LV dilation (p < 0.01). Compared with patients with normal cavity size, those with transient LV dilation were more likely to sustain a myocardial infarction (p < 0.01) and those with fixed dilation more frequently suffered cardiac death (p < 0.01) and hospitalization for heart failure (p < 0.01). The group with the highest risk had both a large perfusion defect and cavity dilation. By Cox proportional hazard regression analysis, both transient and fixed LV dilation were strong independent predictors of cardiac events. Transient or fixed LV dilation are commonly seen during dipyridamole Tc-99m sestamibi SPECT imaging (14% incidence for each) and are useful predictors of cardiac events.

The purpose of this study was to determine the safety and efficacy of transcatheter embolization in the management of bleeding visceral artery pseudoaneurysms. Eight patients (four women and four men) whose mean age was 61.0 years (range 44 to 77 years) underwent emergency transcatheter embolization for acute hemorrhage from a visceral artery pseudoaneurysm. Arteriographic technique was used to localize and selectively embolize these seven visceral artery pseudoaneurysms (three inferior pancreaticoduodenal, one gastroduodenal, two hepatic, and one splenic) by means of intravascular steel coils. Arteriography demonstrated visceral artery pseudoaneurysms in all eight patients. Acute hemorrhage was documented by endoscopy, falling hematocrit levels, CT scans, and arteriography. Successful embolization of these visceral artery pseudoaneurysms was achieved in seven (88%) of eight patients. In one patient embolization was not attempted because of a worsening clinical status, and this patient subsequently underwent emergency surgical resection. There was no significant morbidity associated with the procedures and seven patients remain asymptomatic with no further bleeding at a mean follow-up of 21.1 months (range 11 to 46 months). Arteriographic embolization of visceral artery pseudoaneurysms is a safe and highly successful technique for the effective identification and treatment of hemorrhage even in critically ill patients.

Apolipoprotein B-100 (apo B-100) is the protein component of low density lipoprotein (LDL) responsible for its binding and clearance by LDL receptors (LDL-R). In familial defective apo B-100 (FDB), a mutation in apo B-100 at residue 3500 markedly reduces its affinity for LDL-R, often causing accumulation of defective LDL particles, and an increased proneness to coronary artery disease (CAD). In FDB heterozygotes, about 70% of the LDL particles are mutant, which may alter their atherogenicity relative to LDL containing normal apo B. Therefore, we compared CAD in heterozygous FDB with CAD in heterozygous familial hypercholesterolemia (FH), since raised LDL is usually present from birth in both conditions, and in FH the LDL particles that accumulate have normal apo B, as the inherited defect involves the LDL-R. The clinical presentation of coronary atherosclerosis and its angiographic appearance were examined in FDB and FH patients matched for conventional cardiac risk factors (hypertension, smoking, sex) and serum lipid levels. There was no significant difference between the FDB and FH patients (n=11 pairs) in the type of cardiac symptoms or their ages of onset (50 +/- 9 vs. 45 +/- 11 years). Coronary angiographic appearance was also similar in both groups (n=9 pairs). These observations suggest that LDL particles with the 3500 mutation in apo B have the same atherogenicity as LDL particles with normal apo B.

We have identified two familial defective apo B-100 (FDB) homozygotes by DNA sequencing and have measured affinity of low-density lipoproteins (LDL) and very-low-density lipoprotein (VLDL) remnants for the LDL receptor in vitro. The patients were a 66-year-old man with coronary heart disease (plasma cholesterol level, 9.5 mmol/l before treatment) and his 69-year-old sister, without signs of cardiovascular disease (plasma cholesterol, 12.0 mmol/l before treatment). In both patients, treatment with statins caused a marked fall in plasma cholesterol level. Binding affinity of LDL from the two patients was 10%-20% of normal at 4 degrees C and 37 degrees C. Binding affinity of VLDL remnants was normal. We conclude that (1) residual affinity of LDL in homozygous FDB is high enough to permit significant catabolism via the LDL-receptor pathway, and (2) normal affinity of VLDL remnants permits normal hepatic clearance of precursors of LDL and increased clearance of LDL precursors when receptor activity is stimulated by statins. Residual affinity of LDL and normal affinity of remnants could explain why expression of the FDB mutation is generally milder than that of LDL receptor mutations causing familial hypercholesterolaemia.

Case reports of three patients presenting with acute limb-threatening lower extremity ischemia as a result of thrombosed popliteal artery aneurysms are described. Intra-arterial urokinase was administered to each patient prior to definitive surgery. This improved the infrapopliteal runoff in each case, allowing for successful arterial reconstruction without limb loss.

The overall purpose of this study was to describe the developmental and functional status of young Latino children. We analyzed data from the Hispanic Health and Nutrition Examination Survey and estimated the percentages of young Mexican-American and mainland Puerto Rican children with indicators of developmental need for special services, i.e., low birth weight, use of neonatal intensive care, congenital problems, chronic conditions of developmental concern, functional limitations, and physician diagnoses of medical conditions. Estimates suggest that Puerto Rican children had substantially poorer status than Mexican-American children who, in turn, have indicators that are comparable with those reported for the general population. The difference in status between the two Latino groups merits further investigation.

The purpose of this study was to evaluate prospectively the efficacy and safety of mobile cardiac catheterization. Mobile cardiac catheterization was introduced into clinical practice in 1989, but there has been no systematic study of its performance and safety. A registry was established in 1989 to monitor outcomes with mobile cardiac catheterization and is reported here. Patients were screened for eligibility for mobile cardiac catheterization using the joint AHA/ACC criteria for outpatient angiography. Eligible patients underwent mobile catheterization at eight hospitals within 120 miles of the base tertiary center. Helicopter evacuation services were available at each mobile site. The indications, findings, dispositions, and complications of mobile cardiac catheterization were recorded by means of a checklist, telephone follow-up and chart review. A total of 1,001 consecutive patients were entered into the registry in the first 20 months of operation, including 436 females and 565 males aged 22 to 84 years. Angina (Canadian Classes II-IV) was the most frequent primary indication for catheterization (46.4%), followed by atypical chest pain (36.9%), or a positive exercise stress test (25.6%). Infrequent indications for catheterization included a history of myocardial infarction (5.6%), congestive heart failure (7.1%), arrhythmias (4.1%), and valvular heart disease (0.7%). Catheterization was accomplished in 99.9% of patients. Angiographically normal studies were observed in 22.8%, and mild (< or = 50%) coronary artery disease in 13.6% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The study group included 1,553 consecutive patients from areas serviced by our mobile catheterization laboratories: 719 procedures were performed in the mobile unit at their local hospitals, 277 were performed at a tertiary hospital with less than a 24 hr hospital stay, and 557 were performed at a tertiary hospital as inpatients. The indications for mobile catheterization were predominantly atypical chest pain, angina pectoris, or positive treadmill stress test, whereas patients with less than 24 hr hospitalization at the tertiary center had their catheterization performed for additional reasons. The majority of the inpatient indications were for recent myocardial infarction or unstable angina. Using the American College of Cardiology/American Heart Association (ACC/AHA) criteria for outpatient catheterization, the mobile catheterizations were performed safely with a complication rate of only 0.7% compared to a complication rate of 3.1% for inpatients demonstrating that a low risk group of patients can be prospectively identified and catheterized safely in the mobile setting. An extremely high risk group of patients with ongoing unstable angina and recent myocardial infarction was also identified which should undergo catheterization only at a tertiary center.

Extraction of chronic pacemaker leads has been recommended for infections, prevention of venous thrombosis, migration, and possible perforation. Success with constant traction techniques has been variable, and the cost and morbidity of open chest surgical procedures are prohibitive. Efficacy of a new system for lead extraction using intravascular techniques was analyzed. The system (Cook Pacemaker) uses a locking stylet, which is secured at the distal electrode by counterclockwise rotation to reinforce the lead and facilitate traction, and dilator sheaths that are used to free the lead from adhesions in the venous system. In a series of 56 patients (ages 19-88) who presented for lead extraction because of erosion (5), infection (14), lead replacement (35), or other (2), 86 leads were extracted. Thirty-two were atrial leads and 54 ventricular; 23 had active fixation and 63 passive. Average duration of implant was 58 +/- 42 months (range 1-264). Eighty-four leads were totally removed and two partially removed. For these two leads, the distal tip was not removed; in both cases the locking stylet was not secured at the distal electrode due to obstruction within the lead. Two patients developed arm edema following the procedure, which resolved with elevation. One patient developed a subclavian thrombosis, which resolved with warfarin anticoagulation. Four patients have expired due to unrelated causes. In conclusion, this intravascular approach for extraction of chronic leads is effective, and the procedure is safe when performed by experienced personnel.

We have compared the affinity for low density lipoprotein (LDL) receptors of LDL and very low density lipoprotein (VLDL) remnants from patients with familial defective apo B-100 (FDB) with that of LDL and VLDL remnants from normal subjects. The binding affinity of FDB LDL was markedly reduced in all 14 FDB patients examined, hut the affinity of FDB remnants did not differ significantly from that of remnants prepared from normal subjects. Since the mutant form of apo B-100 present in FDB is recognized by LDL receptors with greatly reduced efficiency, we suggest that apo B plays only a minor role in the receptor-mediated uptake of VLDL remnants by the liver in man. These results are consistent with our previous suggestion that the ability of drugs that stimulate hepatic receptor activity to lower the plasma LDL level in FDB is due in part to increased hepatic uptake of lipoprotein precursors of LDL, including remnant particles with normal apo B-100 and those with mutant apo B-100.

Although most subjects with familial defective apolipoprotein B-100 (FDB) have raised plasma low-density lipoprotein (LDL) levels, a few have LDL levels within the normal range. We have previously identified two normocholesterolemic FDB heterozygotes in an affected family. Results obtained from a study of this family are compatible with a major genetic contribution to the normocholesterolemia in the two heterozygotes. However, our findings are not compatible with inheritance of a variant normal allele at the apolipoprotein B locus in this family that neutralizes the effect of an FDB allele on the plasma LDL level. Polymorphic variations at the apolipoprotein E and LDL receptor loci did not explain the presence of normal LDL levels in the two heterozygous FDB subjects.

Background: Ebstein's anomaly is the most commonly occurring congenital abnormality associated with the Wolff-Parkinson-White (WPW) syndrome. However, the effects of Ebstein's anomaly on the risks and benefits of surgical ablation of accessory pathways in patients with WPW syndrome are unknown., Methods and Results: This study compared the long-term outcome of 38 WPW patients with Ebstein's anomaly undergoing accessory pathway ablation to a reference population of 384 similarly treated patients without the anomaly. Ebstein's anomaly was mild in 21 patients (55%) and moderate-to-severe in 17 patients (45%). Sixteen patients (42%) required tricuspid valve surgery, and 23 (61%) had an atrial septal defect or patent foramen ovale repaired. Baseline clinical characteristics and preoperative clinical arrhythmias were similar in both groups. Ten-year survival was 92.4% and 91.2% for patients with and without Ebstein's anomaly, respectively (p = NS). During a mean follow-up of 6.2 +/- 3.8 and 5.3 +/- 3.6 years, 82% of patients with and 90% without Ebstein's anomaly had either clinically insignificant or no arrhythmias, and 18% versus 10% reported symptoms suggesting arrhythmias lasting longer than 1 minute, respectively. Atrial fibrillation was reduced postoperatively to 9% (p less than 0.001) in patients with and to 4% (p less than 0.001) in those without the anomaly. Fewer hospitalizations were reported postoperatively by 90% versus 96% of patients with and without Ebstein's anomaly; 9.4% versus 6.0% of patients were disabled at follow-up, respectively (p = NS)., Conclusions: Patients with Ebstein's anomaly are improved significantly after accessory pathway ablation. The presence of this anomaly should not preclude accessory pathway ablation in these patients.

Background: Directed surgery for the definitive treatment of drug resistant ventricular tachycardia (VT) due to coronary artery disease carries a significant operative mortality. Surgical failure to cure VT remains a problem, especially in patients without anterior left ventricular myocardial infarcts and aneurysms. A method has been developed in which Nd:YAG laser is used to photocoagulate myocardium responsible for the initiation of VT using a "sequential" approach intended to improve operative results and gain insight into the variable substrates causing VT., Methods: Under normothermic cardiopulmonary bypass, VT is induced and then extensive endocardial and epicardial mapping performed to localize and characterize that form of VT. Nd:YAG is applied to the areas of myocardium from which that form of VT originates until it disappears and is no longer inducible. Next attempts are made to induce other forms of VT and when successful, mapping and lasing repeated until finally VT is no longer inducible., Results: Fifty-one patients were operated on and have been followed for at least 1 year. Operative mortality in 12 patients with preoperative ejection fractions less than 20% was 41%; in 39 patients with ejection fractions greater than 20% operative mortality was 8%. Eighty-eight percent of the 43 operative survivors are free of recurrent sustained VT at 1 year. There have been no arrhythmic mortalities. In a group of 30 patients evaluated for epicardial VT, 9 of 14 patients with inferior infarcts without left ventricular aneurysms had at least one form of epicardial VT., Conclusions: Nd:YAG laser photocoagulation of myocardial VT using a sequential approach is a viable method that permits an ongoing study of this entity. Operative mortality remains high in patients with diffusely poor left ventricular function. Epicardial VT is frequent in patients with inferior infarcts and may account for inferior results in these patients when conventional endocardial approaches are used alone.

The clinical response to long-term reduction of the plasma LDL cholesterol concentration was studied in a man with severe coronary artery disease associated with familial defective apolipoprotein B-100 (FDB). Plasma exchange repeated at 2-week intervals, combined with lipid-lowering drugs, led to remission of angina and improved exercise test performance. A similar clinical response was achieved after LDL apheresis with dextran sulphate columns repeated once every 2 weeks in combination with drug treatment. The reduction in plasma LDL cholesterol level brought about by LDL apheresis was at least as marked in the FDB patient as in 5 patients with familial hypercholesterolaemia. We conclude that FDB patients with coronary artery disease may derive clinical benefit from prolonged reduction of their plasma cholesterol levels and that LDL containing apo B-100 in which arginine at position 3500 is replaced by glutamine is removed from plasma by dextran sulphate columns as efficiently as is normal LDL.

The records of 342 patients who received surgical treatment for the Wolff-Parkinson-White syndrome between 1968 and 1986 were reviewed to evaluate the characteristics of atrial fibrillation. The patients were classified into two groups according to the presence (n = 166) or absence (n = 176) of documented episodes of atrial fibrillation preoperatively. The mean follow-up duration was 6 years (range 2 to 20). As compared with reports based on smaller patient groups and shorter follow-up, the study revealed several new findings. 1) During follow-up, nine patients in the atrial fibrillation group developed recurrent atrial fibrillation after a successful operation; five of these nine patients did not have associated heart disease. 2) All three patients with a history of atrial fibrillation and an accessory pathway conducting in the anterograde direction only had a successful surgical procedure and no postoperative atrial fibrillation. 3) The cycle length of atrioventricular (AV) reciprocating tachycardia was significantly shorter in the atrial fibrillation group (304 +/- 42 ms, mean +/- SD) than in the no-atrial fibrillation group (321 +/- 54 ms, p less than 0.005), and the cycle length of AV reciprocating tachycardia that degenerated into atrial fibrillation (289 +/- 26 ms) was shorter than that for the AV reciprocating tachycardia without subsequent atrial fibrillation (316 +/- 51 ms, p less than 0.005). 4) Sustained atrial fibrillation was induced in 30% of patients without a history of atrial fibrillation. 5) Atrial fibrillation occurred in four patients with an accessory pathway that conducted only in the retrograde direction.(ABSTRACT TRUNCATED AT 250 WORDS)

Neodymium:yttrium-aluminum-garnet (YAG) photocoagulation during ventricular tachycardia allows the electrophysiologic effects of the temporal and spatial sequence of energy delivery to be correlated with local activation times. A retrospective analysis was performed of the termination of 19 episodes of ventricular tachycardia for which the local diastolic activation time was known for all successful ablation sites and for 95% of all ablation sites. The mode of termination was compared with that of 26 episodes of spontaneously terminating ventricular tachycardias. Spontaneous terminations occurred without a change in cycle length (54%) or with a 7 +/- 15% change in cycle length over one to three terminal beats (46%). In contrast, laser ablation-induced terminations resulted in a 39 +/- 55% increase in cycle length over nine or more cycles. The effect of attempted laser ablation was compared with the local presystolic activation time and the local activation time expressed as a percent of the diastolic interval (end of QRS complex = 0%, onset of next QRS complex = 100%). With one exception, no tachycardia terminated at ablation sites activating less than -50 ms before the QRS complex. All 8 successful first ablation attempts and 13 of all 19 successful ablations occurred in the 35% to 50% interval of diastolic activation. All successful ablations at sites activating at greater than 50% of the diastolic interval required multiple ablation attempts. Successful ablation was performed from the epicardium in 6 and from the endocardium in 13 episodes of ventricular tachycardia. These results are most consistent with a macroreentrant mechanism with a region of high vulnerability represented by the 35% to 50% interval of diastolic activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Although the anatomic "substrate" for the occurrence of antidromic reciprocating tachycardia (ART) has been previously examined, the underlying physiological substrate for this unusual arrhythmia in patients with the Wolff-Parkinson-White syndrome has not been thoroughly characterized., Methods and Results: The electrophysiological properties of the accessory pathway and normal ventriculoatrial conduction system in 30 patients with ART and a single accessory pathway were compared with those observed in a control group of 36 patients without this arrhythmia to elucidate the critical physiological substrate essential for the development and maintenance of ART. Inducible ART had a mean cycle length of 286 +/- 31 msec. The average retrograde ventriculoatrial conduction system effective refractory period in ART patients was significantly less than that in the control group (244 +/- 32 versus 291 +/- 46 msec, p = 0.0002). All of the ART patients showed retrograde conduction over the normal conduction system at cycle lengths of less than or equal to 360 msec; 23 had 1:1 conduction to less than or equal to 300 msec, and 16 showed 1:1 propagation at cycle lengths of less than or equal to 260 msec. The shortest cycle length accompanied by 1:1 retrograde propagation over the normal conduction system in patients with ART was also significantly less than that observed in the control group (274 +/- 39 versus 347 +/- 73 msec, p less than 0.001). The accessory pathway anterograde ERP in ART patients with 1:1 retrograde conduction over the normal ventriculoatrial conduction system at cycle lengths of less than or equal to 360 was significantly less than that seen in comparable control patients (247 +/- 23 versus 284 +/- 56 msec, p = 0.001), and the accessory pathway location was significantly further from the atrioventricular node in 21 patients with ART undergoing surgery than that in 22 operated control patients (3.8 +/- 0.8 versus 2.9 +/- 0.8 mapping units, p = 0.0025) who also had retrograde ventriculoatrial conduction to cycle lengths of less than or equal to 360 msec. No significant differences in anterograde atrioventricular conduction system properties, retrograde accessory pathway refractoriness, or shortest ventricular pacing cycle lengths maintaining 1:1 conduction via the accessory pathway were observed between groups., Conclusions: This quantitative characterization of the properties of conduction and refractoriness of both the accessory pathway and ventriculoatrial conduction system and the relation between these characteristics and the accessory pathway location in ART patients provides additional insight into the prerequisites for the initiation and maintenance of this rhythm disturbance.

The plasma lipoprotein(a) (Lp(a)) concentration and apolipoprotein(a) (apo(a)) phenotype were determined in the members of two families affected with familial defective apo B100 (FDB), resulting from the Arg3500----Gln mutation in apo B that disrupts binding to LDL receptors. Eleven different phenotypic species of apo A were identified, five of which were present in both families. Although there was a general increase in Lp(a) concentration as the size of the predominant apo(a) component decreased, there was considerable variability and in three clear instances the concentration of an inherited phenotypic species was atypically low. In five cases where a direct comparison could be made, the plasma Lp(a) concentration was significantly higher in heterozygous FDB subjects than in their non-FDB siblings or close relatives with the same phenotype. However, in vitro competition studies using purified Lp(a) that had been reduced with dithiothreitol to remove the apo(a) component, indicated that the Lp(a) from FDB heterozygotes contained a smaller proportion of defective particles than their LDL. Lp(a) particles containing normal and binding-defective apo B were present at approximately the same concentration, suggesting that the increase in Lp(a) concentration observed in FDB subjects could not be explained by the inability of the particles containing the defective apo B100 to be cleared through LDL-receptor mediated processes.

In human populations, there is an association between coronary artery disease and a polymorphism in the apolipoprotein B (apo B) gene detected with the enzyme EcoRI. This polymorphism gives rise to two apo B alleles, one (E+) encoding glutamic acid and the other (E-) encoding lysine at position 4,154 in apo B-100, the protein of low density lipoprotein (LDL). We have tested the hypothesis that this amino acid substitution indirectly influences proneness to coronary artery disease by affecting the binding of LDL to LDL receptors. The receptor-binding affinities of LDLs from eight pairs of subjects with genotypes E+/+ and E-/- who were matched for other apo B genotypes were determined in vitro. There was no significant difference between the binding affinities of LDLs from the two groups of subjects. Our results strongly suggest that the amino acid at position 4,154 does not influence the function of the receptor-binding domain in apo B-100 and that the association between coronary artery disease and the EcoRI polymorphism is not mediated by an effect of the polymorphism on serum LDL concentration. In view of our findings, it would be of interest to examine the effect of the amino acid substitution on the binding of LDL to arterial proteoglycans and on the oxidizability of LDL by cells in culture.

The effect of cholestyramine and simvastatin, given separately or in combination, on serum lipid concentrations in 11 patients with heterozygous familial defective apolipoprotein B-100 was compared with that in 11 matched patients with heterozygous familial hypercholesterolaemia. In both groups of patients there was a substantial fall in serum lipid levels in response to treatment. There were no significant differences between the reductions in serum total or low-density lipoprotein cholesterol levels in the two groups.

A new modified surgical approach for the division of posterior septal accessory pathways is described. This method incorporates some of the desirable components of previously reported techniques, while eliminating difficult and unreliable aspects of those same techniques. Interestingly this procedure was initially illustrated by Sealy and Mikat in 1983, although it has not been used clinically until now. The recognized intent of this dissection is to totally separate atrial and ventricular structures within the posterior septal space so that all accessory pathways encountered are permanently interrupted.

In a previous study (Tybjaerg-Hansen et al, Atherosclerosis 1990;80:235-242), we identified nine patients heterozygous for the apolipoprotein B (apo B) arginine-to-glutamine (Arg3,500----Gln) mutation (familial defective apolipoprotein B-100 [FDB]). Six of these had been diagnosed clinically as familial hypercholesterolemic (FH) heterozygotes. We have since examined low density lipoprotein (LDL) receptor function in the FDB index patients and in three of their families. Skin fibroblasts from seven of seven unrelated FDB patients from whom cell lines were established exhibited normal high-affinity binding and degradation of normal LDL in vitro. In the three families, a raised plasma LDL concentration did not segregate with a haplotype of two polymorphic restriction sites at the LDL receptor locus. We conclude that the clinical and biochemical signs of classical FH can occur in the presence of the FDB mutation and a normal LDL receptor gene. In a four-generation family with 11 proven or presumed FDB heterozygotes, expression of the mutation ranged from normal plasma LDL concentrations and no clinical signs in two individuals, to hypercholesterolemia and death from myocardial infarction at age 31. Variable expression of the FDB mutation could not be explained conclusively by variation in diet, body mass index, smoking habit, apo E genotype, or plasma Lp(a) concentration.

Background: Conventionally, monomorphic sustained ventricular tachycardia in patients with remote myocardial infarction is believed to originate from the subendocardium. In a previous study, we demonstrated that electrical activation patterns during ventricular tachycardia occasionally suggest a subepicardial rather than subendocardial reentry., Methods and Results: This study prospectively evaluated the functional role of the epicardium in postinfarction ventricular tachycardia with complex intraoperative techniques including computerized electrical activation mapping, entrainment, observation of changes in activation pattern during successful epicardial laser photoblation, and histological study. Five of 10 consecutive patients undergoing intraoperative computerized activation mapping had 10 ventricular tachycardia morphologies displaying epicardial diastolic activation These 10 "epicardial" ventricular tachycardias revealed the following global activation patterns: monoregional spread (two), figure-eight activation (five), and circular macroreentry (three). Entrainment of ventricular tachycardia using epicardial stimulation was successfully performed from an area of slow diastolic conduction in four tachycardia morphologies. During entrainment, global activation remained undisturbed with recordings showing a long stimulus to QRS interval, unchanged QRS morphology, and pacing capture of all components of the reentry circuit. Neodymium:yttrium aluminum garnet laser photocoagulation was delivered during ventricular tachycardia to epicardial sites of presumed reentry. Epicardial photoablation terminated five of five figure-eight tachycardias, two of three circular macroreentry tachycardias but not the monoregional tachycardias. Electrophysiological recordings during epicardial laser photocoagulation demonstrated progressive prolongation of ventricular tachycardia cycle length and apparent interruption of the presumed reentrant circuit. Histological evaluation of the reentrant region (three patients) showed a rim of surviving myocardium under the epicardial surface., Conclusions: This study suggests that 1) chronic postinfarction ventricular tachycardia may result from subepicardial macroreentry, 2) slow conduction within the reentry circuit can be localized by computerized mapping and epicardial entrainment, and 3) ventricular tachycardia interruption by laser photocoagulation results from conduction delay and block within critical elements of the reentrant pathway. Viable subepicardial muscle fibers may constitute the underlying pathology.

The purpose of this study was to test the feasibility of neodymium-yttrium-aluminum-garnet (Nd-YAG) laser photocoagulation of the atrioventricular (AV) node to control the ventricular rate during rapid atrial rhythms without creating AV block. In 12 dogs on normothermic cardiopulmonary bypass, short laser pulses were delivered to an area between the coronary sinus orifice and the site of the most proximally recorded His deflection until second degree AV block occurred at a paced atrial rate of 200 beats/min. Long-term effects on AV node function were followed up for 3 months. Three animals developed chronic high grade AV block. In nine animals with preserved 1:1 conduction, the mean (+/- SEM) critical atrial cycle length resulting in AV node Wenckebach periodicity increased from 183 +/- 6 to 261 +/- 24 ms (+43%), the mean RR interval during induced atrial fibrillation increased from 248 +/- 14 to 330 +/- 27 ms (+32%) and the shortest RR interval during atrial fibrillation increased from 215 +/- 11 to 275 +/- 20 ms (+28%). Laser effects were not reversed by isoproterenol infusion. Histologic examination of the irradiated area showed fibrotic changes in the AV node and fatty metamorphosis. This study suggests that 1) graded Nd-YAG laser photocoagulation of the AV node region in dogs results in long-term modification of anterograde AV node transmission properties; 2) 1:1 conduction during sinus rhythm usually remains preserved, but ventricular rate during rapid atrial rhythms is chronically reduced; and 3) progression to high grade AV block occurs in a minority of animals.(ABSTRACT TRUNCATED AT 250 WORDS)

The present investigation evaluates the ability of several electrocardiographic (ECG) and electrophysiologic methods to identify multiple accessory pathways in 47 patients in whom the presence and sites of multiple accessory pathways were confirmed intraoperatively. To establish ECG features that suggested the presence of multiple accessory pathways in these patients, we initially studied the 12-lead ECG during maximal preexcitation in 101 patients with single accessory pathways. Distinctive 12-lead ECG patterns were noted for six defined anatomic areas around the right and left atrioventricular groove. Multiple preexcited QRS morphologies, each typical for a separate accessory pathway, and atypical preexcited QRS morphologies were recorded during atrial fibrillation in 31 of 47 (66%) patients with multiple accessory pathways. By comparison, the ECG during sinus rhythm and rapid atrial pacing identified 14 (32%) and 26 (55%) of the patients, respectively. In 12 (26%) patients in whom evidence for multiple accessory pathways was absent from endocardial mapping data, atrial fibrillation provided the diagnosis. In five (11%) patients, atrial fibrillation was the only method that demonstrated the presence of multiple accessory pathways. A combination of ECG findings during atrial fibrillation and rapid atrial pacing plus endocardial mapping data identified 43 (91%) of the patients with multiple accessory pathways. There were two unique fusion patterns on the 12-lead ECG that were characteristic of specific multiple accessory pathway combinations.(ABSTRACT TRUNCATED AT 250 WORDS)