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Background: Phototherapy is a well-known method to treat vitiligo and is able to repopulate the skin with new melanocytes. Examination of the pathological changes in vitiligo after ultraviolet therapy revealed the presence of unusual cells., Aim of Study: This study intended to investigate and confirm the repopulation of epidermis with new spindle cells, possibly as precursors for melanocytes after UV therapy., Methods: Retrospective study was carried out on paraffin sections of biopsies obtained from 30 vitiligo patients treated successfully with ultraviolet therapy. Routine, special and immune staining were utilized to examine these biopsies., Results: Amelanotic spindle cells with slightly eosinophilic cytoplasm and dark flattened nuclei were characteristically demonstrated in all examined sections after ultraviolet therapy. These cells were abundant near infundibular portion of hair follicles. They subsequently developed dendrites and became melanized., Conclusions: Melanocyte precursors can be demonstrated pathologically and immunologically on tissue samples after ultraviolet therapy. They are capable of proliferation and migration into depigmented epidermis to repopulate it with new generations of melanocytes., (© 2013 European Academy of Dermatology and Venereology.)

Background: The Pfannenstiel incision, widely used in gynecological surgery, has been reported to be associated with lower rates of wound complications than midline incisions in open surgery. However, its effect on wound complications in minimally invasive surgery (MIS) is not well understood. We hypothesize that use of a Pfannenstiel incision in MIS colorectal cancer resections would be associated with fewer short-term wound complication rates., Methods: A retrospective cohort study was performed on 171 patients who had undergone MIS colorectal cancer surgery requiring a specimen extraction/hand-access site, divided into a Pfannenstiel and a midline group depending on the type of incision used. Wound complications compared included disruption, infection, dehiscence, evisceration, and fistula formation. The Mann-Whitney U and Fisher's exact tests were used to analyze differences in risk factors between the groups. Logistic regression was performed to determine factors associated with prevention of wound complications., Results: Patients in the Pfannenstiel group had significantly lower rates of wound disruption (0 vs. 13%, p = 0.02), superficial surgical site infection (7 vs. 22%, p = 0.03), and overall wound complications (13 vs. 30%, p = 0.04). Using multivariate logistic regression, Pfannenstiel incisions and colon rather than rectal resections were significant predictors of prevention of wound complications., Conclusions: The use of a Pfannenstiel incision in MIS colorectal cancer resections is associated with a decreased risk of short-term wound complications., (© Springer-Verlag 2012)

Background and Aims: Vitiligo is an acquired pigmentary disorder of skin and hair. Active melanocytes in hair follicles can be detected by DOPA and immunohistochemical staining, while amelanotic melanocytes can only be detected by the latter. None of the studies on hair melanocytes in vitiligo discussed the effect of disease duration on these melanocytes. Here, we study the presence of melanotic and amelanotic melanocytes in vitiligo hair follicles and statistically correlating their presence with the disease duration., Methods: This study was conducted on 30 patients with vitiligo and 10 normal volunteers. Three biopsies were taken from each patient: two from black and white hairs from vitiliginous areas and the third from apparently normal skin of the same patients. Sections were stained by DOPA reaction and NKI/beteb then examined for the presence of melanocytes. The presence of melanocytes and the disease duration were correlated statistically using the t-test., Results: Active melanocytes were detected in black hairs of 6.7% of vitiligo patients and in 100% of apparently normal skin of the same patients and controls. On examining black hairs of the 28 vitiligo patients with negative DOPA reaction, 19 of them (67.9%) showed positive NKI/beteb stain. Disease duration was inversely correlated with the melanocytes' presence within hair follicles. Melanocytes were absent from 100% of white hairs., Conclusions: The melanotic melanocytes were the first target of the disease process followed by the amelanotic melanocytes. Since the disappearance of the latter was inversely correlated with the disease duration, early treatment in vitiligo is advised.

Beta-bungarotoxin, a neurotoxic phospholipase A2 is a major fraction of the venom of kraits. The toxin was inoculated into one hind limb of young adult rats. The inoculated hind limb was paralysed within 3 h, and remained paralysed for 2 days. The paralysis was associated with the loss of synaptic vesicles from motor nerve terminal boutons, a decline in immunoreactivity of synaptophysin, SNAP-25 and syntaxin, a loss of muscle mass and the upregulation of NaV(1.5) mRNA and protein. Between 3 and 6 h after the inoculation of toxin, some nerve terminal boutons exhibited clear signs of degeneration. Others appeared to be in the process of withdrawing from the synaptic cleft and some boutons were fully enwrapped in terminal Schwann cell processes. By 12 h all muscle fibres were denervated. Re-innervation began at 3 days with the appearance of regenerating nerve terminals, a return of neuromuscular function in some muscles and a progressive increase in the immunoreactivity of synaptophysin, SNAP-25 and syntaxin. Full recovery occurred at 7 days. The data were compared with recently published clinical data on envenoming bites by kraits and by extrapolation we suggest that the acute, reversible denervation caused by beta-bungarotoxin is a credible explanation for the clinically important, profound treatment-resistant neuromuscular paralysis seen in human subjects bitten by these animals.

Background: Medical student performance evaluations have historically contained a significant subjective component. Multiple tools are used to assess fund of knowledge including subjective evaluation by faculty and residents as well as objective evaluations through standardized written and oral exams. We hypothesized that subjective evaluation of medical student knowledge would correlate with objective evaluation through written and oral exams., Methods: Records of consecutive medical students assigned to the surgery clerkship from January 1999 and March 2001 were reviewed. The core surgical rotation consisted of two 4-week blocks on a private, county, or VA hospital service. Surgical knowledge was assessed subjectively by both faculty (FES) and senior residents (RES) using a 10-point scale with verbal anchors. Objective measures of student surgical knowledge included the National Board shelf exam (WE) and a semistructured oral exam (OE). Data are reported as mean +/- SEM. Spearman rank correlation coefficient (r) was used to assess relationships between groups (r > or = 0.5 --> positive correlation)., Results: A total of 354 students were evaluated. The mean FES was 7.8 +/- 0.05 (median = 7.75, range 4.75 to 9.75). The mean RES was 7.7 +/- 0.06 (median = 8.0, range 3.5 to 10.0). There was poor correlation between the subjective perception and objective measures of surgical knowledge (Table 1). Comparison of the FES and RES also showed poor correlation (r = 0.38)., Conclusions: Subjective evaluation of surgical knowledge by faculty and residents correlates poorly with performance measured objectively. These results question whether subjective evaluation of surgical knowledge should be included as part of the evaluation process.

Voltage-gated sodium channels (VGSCs) are highly concentrated at the neuromuscular junction (NMJ) in mammalian skeletal muscle. Here we test the hypothesis that local upregulation of mRNA contributes to this accumulation. We designed radiolabeled antisense RNA probes, specific for the "adult" Na(V)1.4 and "fetal" Na(V)1.5 isoforms of VGSC in mammalian skeletal muscle, and used them in in situ hybridization studies of rat soleus muscles. Na(V)1.4 mRNA is present throughout normal adult muscles but is highly concentrated at the NMJ, in which the amount per myonucleus is more than eightfold greater than away from the NMJ. Na(V)1.5 mRNA is undetectable in innervated muscles but is dramatically upregulated by denervation. In muscles denervated for 1 week, both Na(V)1.4 and Na(V)1.5 mRNAs are present throughout the muscle, and both are concentrated at the NMJ. No Na(V)1.5 mRNA was detectable in denervated muscles stimulated electrically for 1 week in vivo. Neither denervation nor stimulation had any significant effect on the level or distribution of Na(V)1.4 mRNA. We conclude that factors, probably derived from the nerve, lead to the increased concentration of VGSC mRNAs at the NMJ. In addition, the expression of Na(V)1.5 mRNA is downregulated by muscle activity, both at the NMJ and away from it.

Background: We have previously reported the clearance of protein-bound and water-soluble hepatic toxins, in vitro and in an animal model, using albumin dialysis as an extracorporeal hepatic support (ECHS) device., Objective: The objective of this study was to evaluate albumin dialysis through a phase I clinical trial. We hypothesized that albumin dialysis would (1) decrease elevated levels of hepatic toxins, (2) increase the Fischer ratio, and (3) decrease hepatic encephalopathy (HES) and intracranial pressure (ICP), while (4) maintaining stable hemodynamics., Methods: Patients with acute liver failure were treated with an ECHS device utilizing continuous hemodiafiltration with continuous albumin dialysis. Mean arterial blood pressure (MAP), heart rate (HR), systemic venous oxygen saturation (Svo(2)), ICP, and HES were recorded. Blood samples were evaluated for hepatic toxins and factor VII levels., Results: Nine patients were enrolled (status I, n = 5; status IIA, n = 4). There was no significant change in MAP, HR, or Svo(2) (MAP: Pre = 81 +/- 5.6 mm Hg, Post = 79 +/- 5.9 mm Hg, P =.70; HR: Pre = 104 +/- 5.2 bpm, Post = 107 +/- 6.2 bpm, P =.62; Svo(2): Pre = 72 +/- 3.5, Post = 71 +/- 1.7, P =.77). There was a decrease in the ammonia and total bilirubin levels (NH(3): Pre = 129.8 +/- 23.8 mg/dL, Post = 63.9 +/- 16.1 mg/dL, P =.01; total bilirubin: Pre = 20.3 +/- 2.5 mg/dL, Post = 17.6 +/- 2.7 mg/dL, P =.4). There was a significant increase of the Fischer ratio and factor VII levels (Fischer ratio: Pre = 0.98 +/- 0.2, Post = 2.17 +/- 0.5, P =.038; factor VII: Pre = 13.9 +/- 4.9, Post = 23.2 +/- 4.8, P =.015). There was a significant decrease in the HES and ICP (HES: Pre = 3.8 +/- 0.1, Post = 2 +/- 0.7, P =.02; ICP: Pre = 37 +/- 3.9, Post = 13.3 +/- 2.8, P =.048). Of 5 status I patients, 1 recovered native hepatic function and 3 were bridged to transplantation., Conclusions: This phase I study suggests that albumin dialysis as a liver support device is safe and effective in clearing hepatic toxins, with an associated decrease in the HES and ICP. This encouraging efficacy data warrant further investigation with a phase II/III trial.

Background: Stable and reproducible large animal models of hepatic failure, which allow the assessment of liver-assist devices, are not available. Our objective was to develop a physiologically stable animal model of hepatic failure on which the safety and efficacy of an extracorporeal liver-assist device can be tested. We hypothesized that a surgical model which consists of an end-to-side portocaval shunt combined with common bile duct ligation and transection would create hepatic failure with: (1) elevations in amino transferases, total bilirubin, and ammonia; (2) a decrease in the ratio of branched chain to aromatic amino acids; and (3) histologic evidence of hepatic injury., Methods: Eleven mongrel dogs underwent common bile duct transection and an end-to-side portocaval shunt. Aminotransferases (AST, ALT), total bilirubin, ammonia, and branched chain and aromatic amino acids were measured prior to operation (baseline) and after 9 days. A necropsy was performed on Postoperative Day 9 and liver biopsies were obtained for histology., Results: By Postoperative Day 9, AST, ALT, total bilirubin, and ammonia values were significantly elevated compared to baseline (P < 0.02). The ratio of branched chain to aromatic amino acids was significantly reduced compared to baseline (P < 0.003). There was histologic evidence of cholestasis and inflammation., Conclusion: Portocaval shunt with common bile duct transection produces liver failure with elevations in aminotransferases, total bilirubin, and ammonia, a decreased branched chain to aromatic amino acid ratio, and histologic inflammation. Unlike ischemic or chemically induced models of liver failure, the dogs were hemodynamically and neurologically stable. This model can be used to test the safety and efficacy of liver-assist devices aimed at temporizing the detoxification functions of the failing liver., (Copyright 2000 Academic Press.)

Background: We examined the effects of decreasing respiratory rate (RR) at variable inspiratory times (It) and reducing inspiratory flow on the development of ventilator-induced lung injury., Methods: Forty sheep weighing 24.6+/-3.2 kg were ventilated for 6 hours with one of five strategies (FIO2 = 1.0, positive end-expiratory pressure = 5 cm H2O): (1) pressure-controlled ventilation (PCV), RR = 15 breaths/min, peak inspiratory pressure (PIP) = 25 cm H2O, n = 8; (2) PCV, RR = 15 breaths/min, PIP = 50 cm H2O, n = 8; (3) PCV, RR = 5 breaths/min, PIP = 50 cm H2O, It = 6 seconds, n = 8; (4) PCV, RR = 5 breaths/min, PIP = 50 cm H2O, It = 2 seconds, n = 8; and (5) limited inspiratory flow volume-controlled ventilation, RR = 5 breaths/min, pressure-limit = 50 cm H2O, flow = 15 L/min, n = 8., Results: Decreasing RR at conventional flows did not reduce injury. However, limiting inspiratory flow rate (LIFR) maintained compliance and resulted in lower Qs/Qt (HiPIP = 38+/-18%, LIFR = 19+/-6%, p < 0.001), reduced histologic injury (HiPIP = 14+/-0.9, LIFR = 2.2+/-0.9, p < 0.05), decreased intra-alveolar neutrophils (HiPIP = 90+/-49, LIFR = 7.6+/-3.8,p = 0.001), and reduced wet-dry lung weight (HiPIP = 87.3+/-8.5%, LIFR = 40.8+/-17.4%,p < 0.001)., Conclusions: High-pressure ventilation for 6 hours using conventional flow patterns produces severe lung injury, irrespective of RR or It. Reduction of inspiratory flow at similar PIP provides pulmonary protection.

Objective: To present a series of 30 adult trauma patients who received extracorporeal life support (ECLS) for pulmonary failure and to retrospectively review variables related to their outcome., Methods: In a Level I trauma center between 1989 and 1997, ECLS with continuous heparin anticoagulation was instituted in 30 injured patients older than 15 years. Indication was for an estimated mortality risk greater than 80%, defined by a PaO2: FIO2 ratio less than 100 on 100% FIO2, despite pressure-mode inverse ratio ventilation, optimal positive end-expiratory pressure, reasonable diuresis, transfusion, and prone positioning. Retrospective analysis included demographic information (age, gender, Injury Severity Score, injury mechanism), pulmonary physiologic and gas-exchange values (pre-ECLS ventilator days [VENT days], PaO2:FIO2 ratio, mixed venous oxygen saturation [SvO2], and blood gas), pre-ECLS cardiopulmonary resuscitation, complications of ECLS (bleeding, circuit problems, leukopenia, infection, pneumothorax, acute renal failure, and pressors on ECLS), and survival., Results: The subjects were 26.3+/-2.1 years old (range, 15-59 years), 50% male, and had blunt injury in 83.3%. Pulmonary recovery sufficient to wean the patient from ECLS occurred in 17 patients (56.7%), and 50% survived to discharge. Fewer VENT days and more normal SvO2 were associated with survival. The presence of acute renal failure and the need for venoarterial support (venoarterial bypass) were more common in the patients who died. Bleeding complications (requiring intervention or additional transfusion) occurred in 58.6% of patients and were not associated with mortality. Early use of ECLS (VENT days < or = 5) was associated with an odds ratio of 7.2 for survival. Fewer VENT days was independently associated with survival in a logistic regression model (p = 0.029). Age, Injury Severity Score, and PaO2:FIO2 ratio were not related to outcome., Conclusion: ECLS has been safely used in adult trauma patients with multiple injuries and severe pulmonary failure. In our series, early implementation of ECLS was associated with improved survival. Although this may represent selection bias for less intractable forms of acute respiratory distress syndrome, it is our experience that early institution of ECLS may lead to improved oxygen delivery, diminished ventilator-induced lung injury, and improved survival.

Patients with acute hepatic failure (AHF) have elevated levels of inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6). Recently, we have shown selective hemodiafiltration with albumin dialysis, as an extracorporeal liver support device (ECLVS), to be effective in the clearance of multiple toxins that are elevated in AHF. Our objective was to evaluate whether ECLVS would be effective in the clearance of TNF-alpha and IL-6. An in vitro continuous hemodiafiltration circuit was used with single pass counter-current dialysis. A known amount of recombinant rat TNF-alpha and IL-6 was added to heparinized bovine blood and filtered across a polyalkyl sulfone hemofilter using matched filtration and dialysate flow rates. During 4 hours, the serial TNF-alpha and IL-6 concentrations were measured in the circulating blood, and the content of each cytokine was calculated using mass balance. For each cytokine, clearance was determined for two dialysate groups at constant temperature and pH (group 1: dialysate = 0.9 normal saline, n = 5; group 2: dialysate = albumin 2 gm/dl, n = 5). Analysis of data was performed using ANOVA and Student's t-test. There was improved clearance of TNF-alpha and IL-6 when albumin was used in the dialysate (81+/-0.09% of the initial TNF-alpha and 77+/-0.04% of the IL-6 quantities) compared with when 0.9 normal saline was used as the dialysate (58+/-0.14% of the initial TNF-alpha and 56+/-0.18% of the IL-6 quantities); p < 0.03. An ECLVS utilizing hemodiafiltration with albumin dialysis is more effective than conventional hemofiltration in the clearance of TNF-alpha and IL-6 and, therefore, may benefit patients with acute hepatic failure.

Introduction: In the United States, venovenous extracorporeal life support has traditionally been performed with atrial drainage and femoral reinfusion (atrio-femoral flow). Although flow reversal (femoro-atrial flow) may alter recirculation and extracorporeal flow, no direct comparison of these 2 modes has been undertaken., Objective: Our goal was to prospectively compare atrio-femoral and femoro-atrial flow in adult venovenous extracorporeal life support for respiratory failure., Methods: A modified bridge enabling conversion between atrio-femoral and femoro-atrial flow was incorporated in the extracorporeal circuit. Bypass was initiated in the direction that provided the highest pulmonary arterial mixed venous oxygen saturation, and the following measurements were taken: (1) maximum extracorporeal flow, (2) highest achievable pulmonary arterial mixed venous oxygen saturation, and (3) flow required to maintain the same pulmonary arterial mixed venous oxygen saturation in both directions. Flow direction was then reversed, and the measurements were repeated. Data were compared with paired t tests and are presented as mean +/- standard deviation., Results: Ten patients were studied, and 9 were included in the data analysis. Femoro-atrial bypass provided (1) higher maximal extracorporeal flow (femoro-atrial flow = 55.6 +/- 9.8 mL/kg per minute, atrio-femoral flow = 51.1 +/- 11.1 mL/kg per minute; P = .04) and (2) higher pulmonary arterial mixed venous oxygen saturation (femoroatrial flow = 89.9% +/- 6.6%, atrio-femoral flow = 83.2% +/- 4.2%; P = .006); (3) furthermore, it required less flow to maintain an equivalent pulmonary arterial mixed venous oxygen saturation (femoro-atrial flow = 37.0 +/- 12.2 mL/kg per minute, atrio-femoral flow = 46.4 +/- 8.8 mL/kg per minute; P = .04)., Conclusions: During venovenous extracorporeal life support, femoro-atrial bypass provided higher maximal extracorporeal flow, higher pulmonary arterial mixed venous oxygen saturation, and required comparatively less flow to maintain an equivalent mixed venous oxygen saturation than did atrio-femoral bypass.

Traditionally, adult sepsis has been considered a contraindication to extracorporeal life support (ECLS). The objective of this study was to review the authors' institutional experience with a subgroup of adult patients requiring ECLS for severe respiratory failure and sepsis. Hospital records from 100 consecutive adult patients with respiratory failure placed on ECLS between 1990 and 1996 were retrospectively reviewed. Patients with sepsis as a primary indication were identified, and blood culture data reviewed. Data were analyzed with t tests and chi-square and are presented as mean +/- standard deviation. Multiple logistic regression determined the impact of sepsis and positive blood cultures (PBCs) on survival. Fourteen patients required ECLS for sepsis; 36 had PBCs during hospitalization (15 before or during ECLS). Septic patients had lower pre-ECLS PaO2/FIO2 ratios (septic: 53 +/- 14 mmHg, nonseptic: 70 +/- 68 mmHg, p = 0.04). Patients with PBCs before or during ECLS were younger (PBC: 29 +/- 6 years, no PBC: 35 +/- 13 years, p = 0.003), remained on ECLS longer (PBC: 485 +/- 336 hours, no PBC: 232 +/- 212 hours, p = 0.01), and were more frequently cannulated within 12 hours (PBC: 15/15, no PBC 60/85 p = 0.02). Neither group differed in organ dysfunction (incidence or type), frequency of respiratory recovery, or survival. Neither sepsis nor positive blood cultures were independently predictive of mortality. Sepsis and positive blood cultures do not adversely affect outcome in adult patients with respiratory failure requiring ECLS.

Objectives: The purpose of this article is to evaluate outcome in adult patients with severe respiratory failure managed with an approach using (1) limitation of end inspiratory pressure, (2) inverse ratio ventilation, (3) titration of PEEP by SvO2, (4) intermittent prone positioning, (5) limitation of FiO2, (6) diuresis, (7) transfusion, and (8) extracorporeal life support (ECLS) if patients failed to respond., Patients and Methods: This study was designed as a retrospective review in the intensive care unit of a tertiary referral hospital. One-hundred forty-one consecutive patients with hypoxic (n = 135) or hypercarbic (n = 6) respiratory failure referred for consideration of ECLS between 1990 and 1996. Overall, initial PaO2/FiO2 (P/F) ratio was 75+/-5 (median = 66)., Results: Lung recovery occurred in 67% of patients and 62% survived. Forty-one patients improved without ECLS (83% survived); 100 did not and were supported with ECLS (54% survived). Survival was greater in patients cannulated within 12 hours of arrival (59%) compared with those cannulated after 12 hours (40%, P < .05). Multiple logistic regression identified age, duration of mechanical ventilation before transfer, four or more dysfunctional organs, and the requirement for ECLS as independent predictors of mortality., Conclusions: An approach that emphasizes lung protection and early implementation of extracorporeal life support is associated with high rates of survival in patients with severe respiratory failure.

Objective: The authors retrospectively reviewed their experience with extracorporeal life support (ECLS) in 100 adult patients with severe respiratory failure (ARF) to define techniques, characterize its efficacy and utilization, and determine predictors of outcome., Summary Background Data: Extracorporeal life support maintains gas exchange during ARF, providing diseased lungs an optimal environment in which to heal. Extracorporeal life support has been successful in the treatment of respiratory failure in infants and children. In 1990, the authors instituted a standardized protocol for treatment of severe ARF in adults, which included ECLS when less invasive methods failed., Methods: From January 1990 to July 1996, the authors used ECLS for 100 adults with severe acute hypoxemic respiratory failure (n = 94): paO2/FiO2 ratio of 55.7+/-15.9, transpulmonary shunt (Qs/Qt) of 52+/-22%, or acute hypercarbic respiratory failure (n = 6): paCO2 84.0+/-31.5 mmHg, despite and after maximal conventional ventilation. The technique included venovenous percutaneous access, lung "rest," transport on ECLS, minimal anticoagulation, hemofiltration, and optimal systemic oxygen delivery., Results: Overall hospital survival was 54%. The duration of ECLS was 271.9+/-248.6 hours. Primary diagnoses included pneumonia (49 cases, 53% survived), adult respiratory distress syndrome (45 cases, 51 % survived), and airway support (6 cases, 83% survived). Multivariate logistic regression modeling identified the following pre-ECLS variables significant independent predictors of outcome: 1) pre-ECLS days of mechanical ventilation (p = 0.0003), 2) pre-ECLS paO2/FiO2 ratio (p = 0.002), and 3) age (years) (p = 0.005). Modeling of variables during ECLS showed that no mechanical complications were independent predictors of outcome, and the only patient-related complications associated with outcome were the presence of renal failure (p < 0.0001) and significant surgical site bleeding (p = 0.0005)., Conclusions: Extracorporeal life support provides life support for ARF in adults, allowing time for injured lungs to recover. In 100 patients selected for high mortality risk despite and after optimal conventional treatment, 54% survived. Extracorporeal life support is extraordinary but reasonable treatment in severe adult respiratory failure. Predictors of survival exist that may be useful for patient prognostication and design of future prospective studies.

Extraction of protein bound liver failure toxins, such as unconjugated bilirubin, short chain fatty acids, and aromatic amino acids has been reported using hemodiafiltration with albumin in the dialysate, but the characteristics of such a system have not been described. Therefore, bilirubin clearance using albumin dialysate hemodiafiltration was evaluated in the setting of different dialysate albumin concentrations, varying temperature and pH. An in vitro continuous hemodiafiltration circuit was used with single pass countercurrent dialysis. Unconjugated bilirubin was added to bovine blood and filtered across a polyalkyl sulfone (PAS) hemofilter using matched filtration and dialysate flow rates. The serial bilirubin content was measured and first order clearance kinetics verified. The clearance rate constants were calculated for three dialysate groups of different albumin concentration at constant temperature and pH (group 1: 10 g/dl albumin, n = 5; 2 g/dl albumin, n = 5; normal saline, n = 5), and three groups of different temperature and pH at constant albumin dialysate concentration (group 2: pH = 7.0, temperature = 20 degrees C, n = 5; pH = 7.5, temperature = 20 degrees C, n = 5; pH = 7.0, temperature = 40 degrees C, n = 5). Comparisons were made with ANOVA and Tukey post hoc analysis. When albumin was used in the dialysate, the 2 g/dl group cleared bilirubin 3.1 times faster than saline alone (p = 0.001), and the 10 g/dl group was superior to both (p = 0.001). There were no measurable differences between the 2 g/dl groups at the various temperatures tested (p = 0.08), but the clearance was less at a pH of 7.5 (p = 0.015). The clearance of unconjugated bilirubin is greatly enhanced with the use of albumin containing dialysates when compared to traditional crystalloid hemodiafiltration, is greater at lower pH, and seems to be unaffected by temperature.

Few patients with pancreatic cancer have resectable disease at the time of diagnosis, and a variety of nonsurgical techniques are available to provide effective palliation of jaundice and pain. Accurate preoperative staging is essential to identify patients with unresectable disease, thereby minimizing unnecessary surgery. Currently used diagnostic tests include contrast-enhanced computerized tomography (CT), visceral angiography, endoscopic ultrasound, and laparoscopy, but their utility remains controversial. To evaluate the accuracy of these various diagnostic tests, 30 consecutive patients with histologically proven pancreatic or ampullary adenocarcinoma treated between 1992 and 1996 were evaluated. All 30 patients had contrast-enhanced CT and laparoscopy, 22 patients (73%) had visceral angiography, and 16 patients (53%) had endoscopic ultrasound. Individual and combined predictive values of resectability and unresectability as well as the sensitivities and specificities were determined for all diagnostic tests and compared with intraoperative findings. When CT, visceral angiography, and laparoscopy were combined, the predictive values of resectability and unresectability were 75 and 90 per cent, respectively, with a sensitivity of 75 per cent and a specificity of 90 per cent. Therefore, the combined use of selected diagnostic tests proved more effective than any single diagnostic test for accurately staging patients with pancreatic head and ampullary cancers and should be considered to minimize unnecessary surgery.

We describe here the expression of the ryanodine receptor isoforms RyR2 and RyR3 in human non-pregnant and pregnant (non-labouring) myometrium, and in isolated cultured myometrial cells. The mRNA encoding the RyR3 isoform was found in both non-pregnant and pregnant myometrial tissue samples; however, the mRNA for RyR2 was found only in pregnant samples. It can be speculated that the appearance of this additional isoform in the pregnant myometrium may increase the ability of this tissue to contract at term. Control of expression of the RyR2 gene may therefore be another example of an up-regulated signalling system in pregnancy. Although the mRNA for RyR3 was expressed in cultured myometrial cells, the mRNA for RyR2 could not be detected. Thus cultured myometrial cells appear to be similar to the non-pregnant myometrium. The cytokine transforming growth factor beta (TGF-beta) has been reported to alter RyR mRNA expression in many cell types. After treatment with TGF-beta, both RyR2 and RyR3 mRNAs could be detected in cultured myometrial cells. These observations support the idea that the expression of the RyR2 isoform is up-regulated both in pregnancy and in TGF-beta-treated cultured myometrial cells. Using measurements of 45Ca2+ release, we have further demonstrated that cultured human myometrial cells show a significant augmentation of both the Ca2+-induced Ca2+ release (CICR) mechanism and ryanodine-induced Ca2+ release after treatment with TGF-beta. Additionally, caffeine was able to induce Ca2+ release and sensitize the CICR mechanism to ryanodine. Thus we suggest that the appearance of RyR2 mRNA leads to the expression of this receptor/channel protein with identifiable pharmacological characteristics. These results are discussed in the context of the potential role of gene activation in the process of maturation of the human myometrium during pregnancy.

1. Comparisons of the effects of 4 and 16 weeks of exercise were made on; cardiac output, stroke volume, heart rate, left intraventricular systolic and diastolic pressures, dP/dt, and heart calcium in the Bio 14.6 cardiomyopathic and F1 B hamsters. 2. In the cardiomyopathic hamster the cardiac output, stroke volume, left intraventricular systolic pressure and dP/dt, which were all depressed in the age related sedentary animals, were increased by both periods of exercise. The left intraventricular diastolic pressure which was elevated was likewise decreased by both exercise periods. Only the 16 week exercise period decreased the resting heart rate. 3. In the normal F1 B hamster, both periods of exercise increased the cardiac output and stroke volume while the left intraventricular systolic pressure was decreased. Only the 16 week exercise decreased the resting heart rate and left intraventricular diastolic pressure and increased the left ventricular dP/dt. 4. Both periods of exercise increased the total heart calcium in the Bio 14.6 hamster while the heart calcium in the F1 B was increased only by the 16 week exercise period.

1. Comparisons of left intraventricular end diastolic and systolic pressures, cardiac output, dP/dt, stroke volume and heart rate were made between the Bio 14.6 cardiomyopathic and F1B normal hamster at 45, 80, 150 and 240 days of age. 2. Comparisons of the ventricular calcium and taurine contents were made between the two strains of hamsters at similar ages. 3. Interstrain comparisons of the 240 day Bio 14.6 with age matched F1B hamsters and intrastrain comparisons with 45 day Bio 14.6 hamsters showed a decreased stroke volume, cardiac output and dP/dt with an increased left intraventricular end diastolic pressure, ventricular weight, ventricular weight/body weight ratio, heart calcium and taurine. 4. Despite the decreased left ventricular systolic pressure and cardiac output in the 80 day and older groups of Bio 14.6 hamsters, no compensatory increase in heart rate was observed.