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Objectives: The aim of this study was to assess the outcome of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) patients treated with an implantable cardioverter-defibrillator (ICD)., Background: Arrhythmogenic right ventricular dysplasia/cardiomyopathy is associated with tachyarrhythmia and an increased risk of sudden death., Methods: This study included 42 ARVD/C patients with ICDs (52% male, age 6 to 69 years, median 37 years) followed at our center., Results: Mean follow-up was 42 +/- 26 months (range 4 to 135 months). Complications associated with ICD implantation included need for lead repositioning (n = 3) and system infection (n = 2). During follow-up, one patient died of a brain malignancy and one had heart transplantation. Lead replacement was required in six patients as a result of lead fracture and insulation damage (n = 4) or change in thresholds (n = 2). During this period, 33 of 42 (78%) patients received a median of 4 (range 1 to 75) appropriate ICD interventions. The median period between ICD implantation and the first firing was 9 months (range 0.1 to 66 months). The ICD firing storms were observed in five patients. Inappropriate interventions were seen in 10 patients. Predictors of appropriate firing were induction of ventricular tachycardia (VT) during electrophysiologic study (EPS) (84% vs. 44%, p = 0.024), detection of spontaneous VT (70% vs. 15%, p = 0.001), male versus female gender (91% vs. 65%, p = 0.04), and severe right ventricular dilation (39% vs. 0%, p = 0.013). Using multivariate analysis, VT induction during EPS was associated with increased risk for firing in ARVD/C patients; odds ratio 11.2 (95% confidence interval 1.23 to 101.24, p = 0.031)., Conclusions: Patients with ARVD/C have a high arrhythmia rate requiring appropriate ICD interventions. The ICD therapy appears to be well tolerated and important in the management of patients with ARVD/C.

The autosomal-dominant giant platelet syndromes (Fechtner, Epstein, and Sebastian platelet syndromes and May-Hegglin anomaly) represent a group of disorders characterized by variable degrees of macrothrombocytopenia with further combinations of neutrophil inclusion bodies and Alport-like syndrome manifestations, namely, deafness, renal disease, and eye abnormalities. The disease-causing gene of these giant platelet syndromes was previously mapped by us to chromosome 22. Following their successful mapping, these syndromes were shown to represent a broad phenotypic spectrum of disorders caused by different mutations in the nonmuscle myosin heavy chain 9 gene (MYH9). In this study, we examined the potential role of another gene, fibulin-1, encoding an extracellular matrix protein as a disease modifier. Eight unrelated families with autosomal-dominant giant platelet syndromes were studied for DNA sequence mutations and expression of the four fibulin-1 splice variants (A-D). A mutation in the splice acceptor site of fibulin-1 exon 19 was found in affected individuals of the Israeli Fechtner family, whereas no MYH9 mutations were identified. Unexpectedly, fibulin-1 variant D expression was absent in affected individuals from all eight families and coupled with expression of a putative antisense RNA. Transfection of the putative antisense RNA into H1299 cells abolished variant D expression. Based on the observation that only affected individuals lack variant D expression and demonstrate antisense RNA overexpression, we suggest that these autosomal-dominant giant platelet syndromes are associated, and may be modified, by aberrant antisense gene regulation of the fibulin-1 gene., (Copyright 2003 Wiley-Liss, Inc.)

Objectives: The Swimmer Assistantship in Patient Education was developed to teach principles and techniques of brief preventive health counseling and patient education to medical students who have finished their first year., Description: Students complete an intensive training program and are then placed in family practice settings to educate and counsel patients full-time for 5 to 7 weeks., Evaluation: Students evaluated the program after completion each year A survey of participants was conducted in fall 2000., Conclusions: Participants gained valuable experience with patient education and counseling techniques and a favorable experience in a family practice setting; many entered family practice residency training.

Aim: To compare the performance of steroid eluting epicardial and endocardial leads in infants and children requiring permanent pacing., Methods: Evaluation of pacing and sensing characteristics, impedances, and longevity of 159 steroid eluting leads implanted in 95 children. Group A consisted of 24 children weighing less than 15 kg with 15 endocardial leads (five atrial, 10 ventricular) and 19 epicardial leads (five atrial, 14 ventricular). Group B consisted of 71 children weighing more than 15 kg with 106 endocardial leads (56 atrial, 58 ventricular) and 19 epicardial leads (nine atrial, 10 ventricular)., Results: Group A: Stimulation thresholds were lower for ventricular endocardial leads at implant (mean (SD) 0.84 (0.54) v 1.59 (0.64) V, p < 0.014) and at two year follow up (ventricular 0.64 (0.24) v 1.65 (0.69) V, p < 0.003). Impedance and sensing thresholds did not differ significantly at implant and follow up. Group B: Stimulation thresholds were lower for ventricular endocardial leads at implant (0.72 (0.48) v 1.48 (0.58) V, p < 0.001) and at follow up (0.88 (0.46) v 1.55 (0.96) V, p < 0.009). Impedance did not differ. Sensing thresholds were also better for ventricular endocardial leads at follow up (9.1 (5.2) v 14.2 (6.4) mV, p < 0.02). Complications requiring intervention occurred in both groups (n = 7 for endocardial v n = 18 for epicardial leads)., Conclusions: Endocardial and epicardial steroid eluting leads have comparable performance in the paediatric population.

Background: Ischemia-reperfusion injury (IRI) is the main cause of acute renal failure in both allograft and native kidney. Studies using T cell knockout mice have established an important role for T cells in renal IRI. T cell depletion strategies are effective in human allograft rejection. However, it is not known whether those are effective in renal IRI. Therefore, the effect of T cell depletion in a murine model of renal IRI using well-characterized antibodies (Abs) that have been effective in preventing experimental allograft rejection was studied., Methods: T cell depleting Abs to CD4 (GK1.5), CD8 (2.43) or pan-T cells (30.H12) were purified from hybridoma culture supernatant. Thymectomized C57BL/6 mice, treated with different combinations of T cell depleting Abs, underwent 30 min of bilateral renal IRI, followed by assessment of renal function, structure, and degree of T cell depletion in spleen, lymph nodes, and peripheral blood by flow cytometry., Results: Mice given both GK1.5 and 2.43 had considerable CD4 and CD8 cell depletion but no protection of renal function after ischemia-reperfusion (I/R) as measured by the rise in serum creatinine. However, when GK1.5 and 2.43 was administered combined with 30.H12, which more effectively depleted CD4 T cell numbers, a significant protection of renal function and structure was observed after I/R. Antibody combinations did not significantly alter other leukocyte populations., Conclusions: These data demonstrate that T cell depletion can improve the course of experimental renal IRI. However, more aggressive T cell depletion strategies were required compared with that needed to prevent experimental allograft rejection.

Objective: The teaching OSCE (objective structured clinical examination) was developed from existing OSCE materials to provide direct observation and feedback to students on their doctor-patient relationship skills, students' abilities to do a focused history and physical examination, and to familiarize students with this type of examination., Description: Existing OSCE cases were modified to ten minutes and to focus on case scenarios using standardized patients. Faculty facilitators were trained in giving feedback and oriented to the new OSCE format. Clerkship students are told in advance the general topics of the Teaching OSCE stations, so they can prepare. Students are divided in three groups of six to eight students and each group is assigned a faculty facilitator. Each student performs a ten-minute OSCE station and is observed directly by the faculty facilitator and the remaining students in the group using a video monitor. The faculty facilitator then leads a 12-minute feedback session on focused history-taking skills, physical examination skills, and the doctor-patient relationship skills. Students selected at random by the faculty facilitator also give feedback to their peer. Teaching OSCEs take three hours and are held twice during the clerkship such that each student is actively observed twice and watches a total of ten to 14 additional interactions. Facilitators grade students on attendance, participation, and evidence of preparation. The actual interaction with the standardized patient is used entirely for formative purposes and is not graded., Discussion: Our department has used OSCEs for six years to evaluate students at the end of the third-year family medicine clerkship. Even after continuous improvement, our OSCE did not meet higher standards of reliability and would need at least three hours of testing per student to meet those standards. The low number of students in the rotation and limited resources to increase the duration of the OSCE made it very difficult to construct a more reliable examination. At the same time, both faculty and students wanted more direct observation and feedback on performance with clinical scenarios. Using existing OSCE resources to change the OSCE to a teaching tool proved to be an efficient use of teaching resources while increasing our educational impact. Students report that they appreciate the opportunity to have constructive discussions of their strengths and weaknesses in clinical encounters, observe a variety of doctor-patient interaction styles, and practice for future OSCE-type examinations. Faculty members enjoy this active teaching format and find the process of students giving feedback to their peers educationally useful. The teaching OSCE has been extremely well rated in the end-of-rotation evaluations and will be continued in future clerkships.

Background and Objectives: Taking National Board of Medical Examiners (NBME) subject examinations later in the year is known to lead to higher scores. The effect of taking these exams in a particular order is not well understood., Methods: Scores on family medicine and internal medicine examinations from 312 students in 2 academic years were analyzed to determine the effect of clerkship order on student performance. US Medical Licensing Examination (USMLE) Step 1 scores were used to control for prior academic achievement. Students were separated into groups based on the time of year they took each clerkship and prior experiences., Results: When controlling for USMLE scores, NBME scores varied in relation to time of year and order of clerkship experiences. Students who took internal medicine first performed better on the family medicine exam. Taking psychiatry, obstetrics-gynecology, or surgery clerkships prior to the internal medicine exam improved scores on the internal medicine examination., Conclusions: The timing and order of family medicine and internal medicine clerkship experiences affects performance on the NBME family medicine and internal medicine exams. Clerkship directors should consider this effect when evaluating medical students.

The authors describe a validated instrument to measure instructional quality, using responses from first- and third-year medical students to assess ambulatory training sites.

Background: Instructional quality in ambulatory settings may vary. The MedEd IQ is an instrument that measures unique aspects of the clinical instructional process. This study assesses the construct and factorial validity of the MedEd IQ., Methods: First-year students (n = 764) in Introduction to Clinical Medicine courses and third-year students (n = 711) in family medicine clerkships evaluated 249 clinical teaching sites affiliated with two medical schools, using MedEd IQ questionnaires at the conclusion of clinical training (1996-2000). Factor structures were identified and relationally defined through exploratory and confirmatory factor analytic techniques, and a measurement model for assessing instructional quality was refined., Results: Four unique factors were identified that contribute to instructional quality: preceptor activities, learning environment, learner involvement, and learning opportunities. Of 33 items within the instrument, 22 were retained in the final structural model. Two indices of fit, a comparativefit index of .935, and a root mean square error of approximation of .063 indicated close agreement between the defined model and the observed relationships between items., Conclusions: The MedEd IQ measures four factors important to ambulatory medical education and provides a basis for a new measurement approach to assessing instructional quality.

The corrected count increment (CCI) can standardize assessment of platelet transfusions by correcting for patient's body surface area (BSA) and platelet dose (PD). By using a fixed CCI and a desired post-transfusion platelet count, CCI formula can be used to calculate PD. Our transfusion service has used the following formula since May 1990, to determine the number of platelet units to transfuse in non-bleeding patients: 1 where, 7,000 is expected platelet count increment per unit transfused, and 1.7 is BSA in square meters in a normal adult. To evaluate its usefulness, a retrospective review was performed of all 2,202 platelet transfusions at our level-one trauma center, between 1/1/98 and 12/31/00. Eighty-three transfusions in 69 adult patients, in which a calculated PD was determined prior to transfusion, were evaluated for platelet increments at 1, 1-18, or 18-24 hours post-transfusion. Transfusions that used the calculated PD (n = 49) were compared with those that were based on clinical judgment alone (n = 34). These two groups were comparable in their pre-transfusion platelet counts, ABO compatibility, and unit storage duration. The mean calculated PD transfused in the first group was 6 U +/- 1 standard deviation, which was not different from the second group (P = 0.2). There was no difference in the platelet count increments at 1, 1-18, or 18-24 hours post-transfusion. This study suggests that using a PD based on the CCI formula does not reduce platelet usage when the routine PD is six or less platelet concentrates., (Copyright 2002 Wiley-Liss, Inc.)

Background: The pathophysiologic and potential therapeutic role of selectins in renal ischemia-reperfusion injury (IRI) is not fully understood, due in part to redundancy in the roles of individual selectins. We hypothesized that blockade of ligands for all three selectins using a novel small molecule (TBC-1269) would improve the course of renal IRI by overcoming redundancy issues. This was investigated in a rat model of renal IRI., Methods: Rats were treated with TBC-1269 either during or post-IRI. The effects of TBC-1269 were investigated in two models of renal IRI: moderate IRI (30 minutes bilateral renal artery clamping) and severe IRI (45 minutes clamping). The combination of anti-E- and anti-P-selectin antibodies also was investigated in rats subjected to moderate IRI. Renal function, histological injury and mortality were assessed., Results: Rats treated with TBC-1269 during moderate IRI showed significantly reduced serum creatinine (SCr) and tubular necrosis post-ischemia compared to control animals. By contrast, delayed treatment (post-IRI) did not show a reduction in SCr. In rats with severe IRI, TBC-1269 treatment during IRI significantly reduced mortality at 48 hours post-ischemia. Rats with moderate IRI and treated with the combination of anti-E- and anti-P-selectin antibodies showed significantly reduced SCr compared to control rats at 24 hours post-ischemia., Conclusions: Small molecule selectin ligand inhibition provides a novel and effective approach to attenuate ischemic acute renal failure. Timing of treatment is crucial to success.

The authors devised a nonthoracotomy defibrillation system for a patient with a prosthetic tricuspid valve using existing technology and previously established implantation techniques. Their lead configuration deviates substantially from existing designs in its primary use of a coronary sinus defibrillation coil and a left-sided subcutaneous array to distribute current across the ventricular myocardium.

Objectives: We sought to identify the risk factors predicting the development of dilated cardiomyopathy (DCM) in patients with isolated congenital complete atrioventricular block (CCAVB)., Background: Recently evidence has emerged that a subset of patients with CCAVB develop DCM., Methods: This was a retrospective study of 149 patients with CCAVB who had heart size and left ventricular (LV) function assessed by echocardiography and chest radiography over a follow-up period of 10 +/- 7 years., Results: Nine patients developed DCM at the age of 6.5 +/- 5 years. No definite cause could be identified. In these nine patients, CCAVB was diagnosed in eight at 23 +/- 2.3 weeks gestation and in one at birth. Maternal SSA/SSB antibodies were confirmed in seven of the nine patients. Pacemakers were implanted in eight patients in the first month and in one patient at five years of age. The initial left ventricular end-diastolic dimension (LVEDD) was in the 96th +/- 2.6 percentile and the cardiothoracic (CT) ratio was 64 +/- 3.8% in the nine patients who developed DCM, and differed significantly in patients with CCAVB (p < 0.005) who did not develop DCM. The LVEDD and CT ratio did not decrease in the patients with CCAVB and DCM, but decreased significantly in the patients with CCAVB without DCM (p < 0.001) once pacing was initiated. Two patients with DCM died within two months of diagnosis; one patient is neurologically compromised; two patients received a heart transplant; and four patients are listed for heart transplantation., Conclusions: Isolated CCAVB is associated with a long-term risk for the development of DCM. Risk factors may be SSA/SSB antibodies, increased heart size at initial evaluation and the absence of pacemaker-associated improvement.

The authors report the case of a 25-year-old white woman at 7 months' gestation who died suddenly and unexpectedly at home. Anatomic findings at autopsy included a tongue contusion, glomerulonephritis, changes indicative of systemic hypertension, and trophoblastic microemboli in the lungs. Review of the prenatal care record disclosed 3+ proteinuria 2 days before death. The features of the postmortem examination were consistent with clinically undiagnosed preeclampsia-eclampsia and glomerulonephritis. The authors discuss the rarity of fatal preeclampsia-eclampsia, the contribution of concomitant glomerulonephritis, and the significance of trophoblastic microemboli in the lungs.

Propofol, a central-acting sedative agent, has been implicated in the development of rhabdomyolysis in children. We describe two adults who developed rhabdomyolysis after receiving high rates of propofol infusion. Rhabdomyolysis of both skeletal and cardiac muscle was suggested in both patients by marked increases of creatine kinase (>170 000 U/L) and cardiac troponin I (11 and 46 microg/L in patients one and two, respectively). Creatine kinase and cardiac troponin I values were highly correlated in each patent (r = 0.786 and 0.988 in patients one and two, respectively). Autopsy of one patient confirmed the diagnosis of skeletal and cardiac rhabdomyolysis.

A young woman developed minocycline-related lupus erythematosus with associated autoimmune hepatitis. All clinical and laboratory abnormalities returned to normal when the drug was stopped. The symptoms worsened dramatically upon rechallenge, strongly suggesting the reaction was related to the minocycline.

The management of patients receiving large amounts of blood is often difficult. The complications associated with massive transfusion are reviewed. Methods for preventing or treating these complications are presented. Excessive involvement of the transfusion medicine specialist provides the optimum way of managing patients undergoing massive transfusion.

The purpose of this study was to determine the frequency of atrioventricular (AV) node reentry tachycardia in infants undergoing transesophageal electrophysiological study for paroxysmal tachycardia. The records of all 52 infants < 1-year-old with structurally normal hearts who underwent transesophageal study for paroxysmal tachycardia over a 3-year period were reviewed. Those with a diagnosis of AV node reentry tachycardia underwent complete data review, and follow-up of > 12 months was obtained. Six of 52 infants had a diagnosis of the common type of AV node reentry tachycardia. Tachycardia was diagnosed at a mean age of 2.1 months (range 1 day to 10 months), and 3 of 6 underwent transesophageal study within the first month. Although no patient had structural heart disease, three patients had significant noncardiac disease. Follow-up of 15-38 months (mean 24 +/- 7.8) revealed recurrences in 2 of 6 patients. The mean tachycardia cycle length was 240 ms (range 200-310 ms), and the transesophageal ventriculoatrial intervals ranged from < 30 to 55 ms. All patients had a inducible reentrant tachycardia with a ventriculoatrial interval that remained constant even when tachycardia cycle length increased following verapamil or adenosine administration, or decreased following isoproterenol infusion. Five of 6 had evidence for discontinuous AV node conduction curves. In our patients the substrate for AV node reentry tachycardia was present early in life, and AV node reentry tachycardia can be a clinical problem even in the newborn period.

A 59-year-old man with end-stage renal failure from systemic vasculitis developed de novo immunotactoid glomerulopathy of the renal allograft, with clinical evidence of hematuria, proteinuria, and acute renal failure 6 weeks after cadaveric renal transplantation. The morphologic lesion of immunotactoid glomerulopathy and the clinical renal disease resolved during the following 2 weeks. The disease had not recurred in the subsequent 20 months of posttransplant follow-up. During the same period, the patient also developed systemic cytomegalovirus (CMV) infection with viremia, acute hepatitis, and bone marrow suppression. The clinical manifestations of CMV illness and the renal disease have subsided following the withdrawal of immunosuppressive agents and simultaneous treatment with ganciclovir. Although there is no direct proof that CMV infection was responsible for the development of immunotactoid glomerulopathy, the circumstantial evidence in this patient strongly suggests that these two disease were temporally linked. To our knowledge, the association between CMV infection and immunotactoid glomerulopathy has not been documented previously.

During an electrophysiological study in a patient with a concealed accessory connection, there was no evidence of electrical or mechanical alternans during tachycardia until propranolol was administered, but both forms of alternans developed with tachycardia of a slower rate following propranolol. Echocardiographic, arterial pressure, and electrocardiographic data obtained prior to and following propranolol administration are presented.

Membranous nephropathy (MN) is characterized by subepithelial immune complex formation and progressive thickening of the glomerular basement membrane (GBM). Kidney tissues from 21 patients stratified according to morphology (stage I: 5 patients; stage II: 5 patients, stage III: 11 patients) were studied by immunohistochemical techniques using antibody probes to matrix components of recently described (novel) chains of type IV collagen [alpha 3(IV)NC, alpha 4(IV)NC, Alport antigen] and of traditional type IV collagen [alpha 1(IV)NC, alpha 2(IV)NC, 7S(IV), triple helix]; as well as laminin B2, nidogen and fibronectin. In Stage I, there were no detectable changes when compared with normal tissue. In Stage II and early Stage III, the subepithelial projections of GBM (spikes) and the thickened GBM consisted predominantly of the novel type IV collagen chains as well as laminin B2 and nidogen, with no detectable changes in traditional type IV collagen. In late Stage III, an increase in the latter was observed in the subendothelial region of the thickened GBM with narrowing of the capillary lumen. At this stage, there was close apposition of novel and traditional type IV collagen molecules. The expression of these two groups of molecules is spatially and temporally distinct during the evolution of MN. It is hypothesized that immune complex formation in the subepithelial region of the GBM leads to increased formation of the novel type IV collagen network by visceral epithelial cells resulting in the formation of spikes and thickening of GBM between and surrounding immune deposits. These changes precede and are distinct from detectable alterations in traditional type IV collagen. With progression and time, the deposits become embedded in the novel collagen network and increased subendothelial formation of traditional type IV collagen molecules occurs with narrowing of the capillary lumen.

Successful surgical ablation of atrioventricular (AV) accessory connections may be confirmed during postoperative electrophysiologic testing by the absence of accessory connection conduction in both the anterograde and retrograde directions. Whereas the former may be readily apparent by examination of the surface electrocardiogram during sinus rhythm or atrial pacing, assessment of the latter may be complicated by the frequent presence of enhanced retrograde AV nodal conduction in the postoperative period. Consequently, availability of interventions that selectively affect AV nodal conduction and refractoriness without concomitant effects on accessory connections may be helpful for assessing the success of the surgical procedure. In this study the effects of combined propranolol and verapamil administration on electrophysiologic properties of the AV node and the accessory AV connection were assessed both pre- and postoperatively in 17 patients (12 men and 5 women, mean age 33 years) undergoing surgical ablation of accessory connections. Preoperatively, electrophysiologic characteristics of all but 1 of the accessory AV connections were unaffected by propranolol and verapamil administration. Postoperatively, on the other hand, propranolol and verapamil significantly prolonged both the retrograde AV node effective refractory period (baseline: 272 +/- 34 ms vs after drugs: 384 +/- 70 ms [p less than 0.0001]) and the shortest cycle length maintaining 1:1 ventriculoatrial conduction (baseline: 357 +/- 99 ms vs after drugs: 485 +/- 64 ms [p less than 0.0001]). Late postoperative electrophysiologic evaluation (7 +/- 3 weeks) revealed no evidence of residual accessory AV connection conduction, and all patients remain asymptomatic at 21 +/- 10 months follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Purpose: Currently, there is no established therapy for chronic fatigue syndrome (CFS), a recently defined illness that has been associated with a variety of immunologic abnormalities. Based on the hypothesis that a chronic viral infection or an immunoregulatory defect is involved in the pathogenesis of CFS, the therapeutic benefit of intravenous immunoglobulin G (IV IgG) was evaluated in a group of patients with CFS. Additionally, serum immunoglobulin concentrations and peripheral blood lymphocyte subset numbers were measured at the outset of the study, and the effect of IV IgG therapy on IgG subclass levels was determined., Patients and Methods: Thirty patients with CFS were enrolled in a double-blind, placebo-controlled trial of IV IgG. The treatment regimen consisted of IV IgG (1 g/kg) or intravenous placebo (1% albumin solution) administered every 30 days for 6 months. Participants completed a self-assessment form prior to each of the six treatments, which was used to measure severity of symptoms, functional status, and health perceptions. Patients were also asked to report adverse experiences defined as worsening of symptoms occurring within 48 hours of each treatment., Results: Twenty-eight patients completed the trial. At baseline, all 28 patients complained of moderate to severe fatigue, and measures of social functioning and health perceptions showed marked impairment. Low levels of IgG1 were found in 12 (42.9%), and 18 (64.3%) had low levels of IgG3. At the end of the study, no significant therapeutic benefit could be detected in terms of symptom amelioration or improvement in functional status, despite restoration of IgG1 levels to a normal range. Major adverse experiences were observed in 20% of both the IV IgG and placebo groups., Conclusion: The results of this study indicate that IV IgG is unlikely to be of clinical benefit in CFS. In addition to the ongoing need for placebo-controlled trials of candidate therapies for CFS, an expanded research effort is needed to define the etiology and pathogenesis of this disorder.

Despite the recommended 28 weeks' gestation antenatal, postnatal, and postabortion prophylaxis with Rh immune globulin, residual Rh immunization still occurs in Rh-negative women. We describe a patient whose history suggests development of an anti-D antibody after first-trimester bleeding. To our knowledge, this is the first such case reported in the English literature.

Direct immunofluorescence employing goat anti-human IgG, IgA, IgM, C3 component of complement, fibrinogen, albumin, and polyvalent immunoglobulins was performed on postmortem samples of gingiva, parotid gland, thyroid, kidney, and pancreas tissue of 15 diabetic and 15 control patients. Basement membrane thickness quantification of kidney tubules, gingival capillaries, and parotid gland ducts and acini was also done utilizing a calibrated magnifier on uniformly enlarged photomicrographs which had been specially stained to highlight basement membranes. Results revealed binding of IgG, albumin, and polyvalent immunoglobulin to kidney glomerular and tubular basement membranes and parotid ductal and acinar basement membranes in all diabetic subjects. Thyroid follicular basement membranes were positive in 8 of 15 diabetic patients for the same antisera. All gingival and pancreatic tissue from diabetic and control patients was negative for binding of all serum proteins tested. Basement membrane thickening in kidney tubules and gingival capillaries was observed in diabetic subjects; however, there was no apparent difference between diabetic and control patients in thickness of ductal or acinar basement membranes of the parotid gland.

A single 45-g dose of intravenous ascorbic acid, a metabolic precursor of oxalate, was administered to a patient as adjuvant therapy for primary amyloidosis and the nephrotic syndrome. Acute oliguric renal failure occurred. Postmortem histopathologic examination of renal tissue revealed extensive intratubular deposition of crystalline material, which was confirmed as calcium oxalate by a microincineration technique. There were no extrarenal deposits of calcium oxalate. Plasma oxalate and ascorbic acid concentrations were increased. We conclude that therapy with high-dose ascorbic acid is a potential cause of oxalate nephropathy.

Radiation injury to the renal parenchyma is an unusual cause of renal insufficiency. Light, immunofluorescence and electron microscopic studies were performed on the renal tissue from two patients in whom renal insufficiency developed within a year after they received abdominal irradiation. The glomerular lesion in both patients was similar. Mild endothelial cell swelling and basement membrane splitting were noted consistently on light microscopy. The electron microscopic examination revealed marked subendothelial expansion with electron-lucent material associated with deposition of basement membrane-like material adjacent to the endothelial cells. In some capillary loops, the endothelial cell lining appeared to be completely lost. The pathogenesis of radiation-induced renal injury is still uncertain. It is speculated that local activation of the coagulation system with consequent thrombosis of the renal microvasculature may be extremely important.

Three adults with diabetes mellitus and nephrotic syndrome of recent onset underwent renal biopsies because of certain unusual clinical features. Despite heavy proteinuria, one patient had no evidence of diabetic retinopathy, one had preservation of normal renal function, while the third had sudden onset of renal failure. Microscopic examination of renal biopsy material disclosed pure membranous nephropathy in one, membranous nephropathy and nodular glomerulosclerosis in two. Because of significant differences in the natural history of these two glomerulopathies and the possible beneficial effects of steroid therapy in membranous nephropathy, we suggest that renal biopsies be performed in diabetic patients having persistent hematuria, sudden onset of renal failure, massive proteinuria without azotemia, retinopathy, or other evidence of microvascular disease, to uncover superimposed and treatable disorders that may influence the course of renal disease.

An infant with transposition of the great arteries and a coexistent pneumothorax, developed a pneumopericardium during balloon atrial septostomy.

Clearance techniques were employed to examine glomerulotubular relationships in a model of chronic glomerulonephritis in the rat. Clearance ratios were found to be equal in both kidneys in the same animals, indicating that the nephron population was functioning in a homogeneous manner. Glucose titration curves were normal and this finding also indicates that glomerulotubular relationships were intact for the composite nephron population. In contrast to models of chronic renal disease with nonglomerular lesions, nephron filtration rate was reduced in these animals. However, the animals still exhibited a capacity to respond to contralateral nephrectomy by increasing filtration rate in the residual nephrons.

During a four-year period, 17 massively obese patients without clinically apparent systemic disease underwent renal biopsy for marked proteinuria. Clinical information and biopsy results were compared with those in 34 normal-body-weight controls matched for age, sex, and similar presentation. Histopathologic changes characteristic of focal glomerulosclerosis were found in nine (53%) of the obese patients and two (6%) of the controls. In addition, five (29%) of the obese patients had occult diabetic nephropathy, while no diabetic changes were seen in controls. Clinically, obese patients resembled controls in most respects. Serum albumin level, however, was higher than in controls (3.5 +/- 0.2 vs 2.5 +/- 0.1 g/dL). Indeed, obese patients with focal glomerulosclerosis had normal serum albumin levels (4.0 +/- 0.1 g/dL). Thus, primary renal disease in massively obese patients with marked proteinuria differed in several important respects from that seen in normal-body-weight patients with a similar degree of proteinuria.

A 26-year-old woman, who had undergone jejunoileal bypass surgery six years previously for obesity, had symptoms of intermittent fever, myalgia, polyarthralgia, and aseptic joint swelling. These symptoms commenced one year after her surgery and gradually grew in intensity and frequency of occurrence. The patient, observed to have moderately decreased renal function, hyperoxaluria, and circulating cryoglobulins, underwent liver and renal biopsies. Both organ specimens demonstrated granulomatous involvement, but the kidneys exhibited no evidence of oxalate deposition. The findings of circulating cryoglobulins and suppression of symptoms with doxycycline, taken collectively with the circumstances surrounding this case, suggest that the observed granulomatous disease may be due to systematically adsorbed bacterial antigen(s).

This study evaluated the utility of the immunoperoxidase method as applied to bone marrow sections in the diagnosis of patients with monoclonal gammopathies. Intracellular immunoglobulin light chains were identified in fixed, decalcified bone marrow biopsy sections from 66 patients with monoclonal proteins, using an avidin-biotin-peroxidase complex immunoperoxidase method. In all cases the predominant light chain identified in the bone marrow biopsy correlated with the monoclonal light chain identified in the serum. In addition, a light chain ratio was defined that correlated with the clinical diagnoses. The light chain ratios were highest in patients with multiple myeloma and were significantly different from those with monoclonal gammopathy of undetermined significance. There was no correlation between level of serum monoclonal protein and light chain ratios. The ratios were also high in patients with macroglobulinemia, primary amyloidosis, and renal disease secondary to monoclonal proteins but without overt myeloma. Determination of light chain ratios differentiated patients with multiple myeloma from those with monoclonal gammopathy of undetermined significance and helped identify patients with end organ damage secondary to monoclonal proteins but without overt myeloma.

This study reports a family comprising four generations in whom nephritis, deafness, congenital cataracts, macrothrombocytopenia, and leukocyte inclusions were observed in varying combinations in eight of 17 members. The family differs from others reported in that their hematologic abnormalities include not only macrothrombocytopenia, but also small, pale blue cytoplasmic inclusions in the neutrophils and eosinophils. Light microscopic appearance of the inclusions resembled that of toxic Döhle bodies and inclusions of May-Hegglin anomaly, but their ultrastructural appearance was unique. The inclusions consisted of clusters of ribosomes and small segments of rough endoplasmic reticulum (RER). They lacked the parallel 10-nm filaments characteristic of May-Hegglin anomaly and the parallel strands of RER seen in toxic Döhle bodies. Platelets were large, but their light and ultrastructural appearance was not significantly different from normal platelets. Platelet aggregation in response to epinephrine, arachidonate, thrombin, adenosine diphosphate, collagen, and ristocetin was normal. Levels of nucleotides and serotonin were elevated in proportion to cell volume. The concentration of adenosine triphosphate secreted and the percentage of arachidonic acid converted to thromboxane B2 were proportional to cell number. Deafness was high-tone sensorineural. Renal disease ranged from microscopic hematuria to end-stage renal failure necessitating dialysis and kidney transplantation. All affected adults had cataracts. This family represents a variant of Alport's syndrome with cataracts and leukocyte inclusions that, because of the associated macrothrombocytopenia, may be confused with May-Hegglin anomaly.

A 43-year-old woman developed progressive renal insufficiency while receiving cyclosporin A after live donor kidney transplantation. Despite the discontinuation of this drug and substitution with azathioprine, the renal function continued to deteriorate leading to eventual graft loss. The other causes of chronic renal failure such as allograft rejection, recurrent or 'de novo' glomerulonephritis or obstructive uropathy were not evident. There is a high frequency of acute reversible nephrotoxicity from cyclosporin A, but this patient's clinical course suggests that chronic irreversible renal failure can also occur in patients receiving this drug.

Anti-NDP has been detected in the sera of 38 of 430 patients on regular hemodialysis at the Regional Kidney Disease Program in Minneapolis. It developed in these patients from 7 to 58 months after commencement of dialysis. Bacterial infection appeared temporally related to the development of anti-NDP in 12 patients. Hemolytic episodes, possibly related to anti-NDP, occurred in 11. Fifty-five percent of the patients never reused dialyzers. The antibody preceded the insertion of a bovine graft in seven. We postulate that anti-NDP is recognizing an antigenic site similar to that recognized by Vicia graminea lectin, and that this site might become immunogenic by alteration of M and N antigens on red blood cell surfaces. Though formaldehyde might be involved in this alteration, dialysis membrane reuse does not seem to be required for the formation of anti-NDP.