Herpes simplex virus hepatitis: an analysis of the published literature and institutional cases.

Hepatitis is a rare complication of herpes simplex virus (HSV), often leading to acute liver failure (ALF), liver transplantation (LT), and/or death. Our aim was to identify variables associated with either survival or progression (death/LT), based on an analysis of cases in the literature and our institution. A total of 137 cases (132 literature, 5 institutional) of HSV hepatitis were identified. The main features at clinical presentation were fever (98%), coagulopathy (84%), and encephalopathy (80%). Rash was seen in less than half of patients. Most cases (58%) were first diagnosed at autopsy and the diagnosis was suspected clinically prior to tissue confirmation in only 23%. Overall, 74% of cases progressed to death or LT, with 51% in acyclovir-treated patients as compared to 88% in the untreated subjects (P=0.03). Variables on presentation associated with death or need for LT compared to spontaneous survival: male gender, age>40 yr, immunocompromised state, ALT>5,000 U/L, platelet count<75x10(3)/L, coagulopathy, encephalopathy, and absence of antiviral therapy. In conclusion, HSV hepatitis has a high mortality and is often clinically unsuspected. Patients who are male, older, immunocompromised, and/or presenting with significant liver dysfunction are more likely to progress to death and should thus be evaluated for LT early. Based on the frequent delay in HSV diagnosis, low risk-benefit ratio, and significantly improved outcomes, empiric acyclovir therapy for patients presenting with ALF of unknown etiology is recommended until HSV hepatitis is excluded.     

Referral pattern of patients with oral mucosal lesions in The Netherlands

The referral pattern of 140 Dutch patients with oral mucosal lesions, who had been referred to a Department of Oral & Maxillofacial Surgery and Oral Pathology, shows that patients with oral mucosal lesions consult the dentist as often as the family doctor as the first source of help or information. Furthermore, family doctors were much more used to refer patients with oral mucosal disease to medical specialists rather than to the dentist or the oral and maxillofacial surgeon.     

The combination oral and nutritional treatment of late-onset diabetes mellitus (CONTROL DM) trial results.

OBJECTIVE: To examine the effect of short-term improvements in glycaemic control on brachial artery endothelial function as a marker of cardiovascular health. METHODS: Persons with Type 2 diabetes who were poorly controlled on oral therapy were randomly assigned to monotherapy with repaglinide or combination therapy with repaglinide plus metformin. Brachial artery flow-mediated vasodilation was assessed by ultrasonography at randomization and following 16 weeks of therapy. The primary outcome was change in brachial artery endothelial function from baseline. Comparison of randomized groups was a secondary aim. RESULTS: Eighty-six participants were randomized, and 83 were followed to study completion. Post occlusion brachial artery vasodilation was 3.74% at baseline and 3.82% following 16 weeks of therapy (P = 0.77). The treatment effect was 0.08% (95% CI: -0.48%, 0.64%). No difference was seen between treatment groups (P = 0.69). Overall, A1C was reduced from 8.3% to 7.0%, with a greater reduction in the combination therapy group (from 8.4% to 6.7%) than in the monotherapy group (from 8.3% to 7.3%, p for difference between groups = 0.01). Statistically significant reductions were observed in fasting glucose, and plasminogen activator inhibitor-1. Statistically significant increases were observed for fasting insulin, uric acid, weight and BMI. CONCLUSIONS: Brachial artery endothelial function was not influenced by short-term improvements in glycaemic control. The CONTROL DM group was successful in lowering A1C. Future research should explore more intensive and longer-lasting improvements in glycaemic control on endothelial function. Some data previously published in abstract form (Diabetes 2001; 50 (Suppl. 2): A217).     

Marfan syndrome with aortic dissection and triple-barrel aorta.

A case of Marfan syndrome with spontaneously and subsequently developed dissections of the aorta, one in the form of triple-barrel aorta, three times corrected by grafts is described. The autopsy revealed "healed" and acute dissections in almost the entire aorta outside the grafts. "Healed" thoracoabdominal dissection had true lumen (with entry and re-entry intimal tears), and old false lumen and in addition in its distal portion of a triple-barrel aorta was formed (dissection of healed aortic dissection). Lethal adventitial rupture occurred in the portion with an old false lumen. Dissection of the left subclavian artery, the right common carotid artery, resulting in saccular aneurysm, and avulsion of the right renal artery were also found.     

Blood-group-related antigen Lewis(x) and Lewis(y) in the differential diagnosis of cholangiocarcinoma and hepatocellular carcinoma

Distribution of Lewis(x) (Le(x)) and Lewis(y) (Le(y)) blood-group antigens was studied in nine formaldehyde-fixed, paraffin-embedded cholangiocarcinomas (CCs), 26 hepatocellular carcinomas (HCCs), and eight normal livers. All CCs, with one exception, expressed both Le(x) and Le(y) antigens on few or many cells. In HCCs Lex was expressed infrequently (8%), while Le(y) was detected in 31% of cases. Both markers, when present in HCCs, tended to be spotty. Fibrolamellar carcinomas and normal livers did not react with either Le(x) or Le(y) antigens; however, Le(y) antigen was observed occasionally in bile duct epithelial and ductular cells. In conclusion, inappropriate tissue distribution of Le(y) blood-group antigens was observed in CCs and, much less frequently, in HCCs. The high frequency of Le(x) antigen in CCs but not in HCCs may help in the differential diagnosis of these two tumors.     

Analysis of factors influencing chronic renal failure progression

One of the most important characteristics of chronic renal failure (CRF) is its progression to end stage renal disease. CRF progression depends of many factors indicated in numerous experimental and clinical studies. The present study was undertaken with the aim to examine the role of sex, etiology of CRF, renal function at the beginning of the study, hypertension and protein intake on CRF progression. Ninety-two patients (47 female and 45 male) aged between 17 and 70, with various underlying kidney diseases and various degrees of CRF were followed for 8 years. CRF progression was expressed as Creatinine clearance (CCr) and reciprocal values of serum Creatinine (SCr) against time. CRF progression was slower in women than in men, but not significantly. Patients with diabetic nephropathy (b = 0.00006) and glomerulonephritis (b = 0.00005) had faster progression of CRF than patients with nephrosclerosis (b = 0.00002), tubulointerstitial nephritis (b = 0.00003) and polycystic kidney disease (b = 0.00003). The fastest progression of CRF was in patients with the lowest SCr values at the beginning of the study. Proper regulation of blood pressure was the most important factor in slowing down CRF progression, independently of kind of antihypertensive drugs. Neither angiotensin converting enzyme inhibitors (b = -0.00001) nor calcium channel blockers (b = -0.00002) showed better effects on CRF progression slowing down in comparison with other antihypertensive drugs (b = -0.00001). Low protein diet slowed down CRF progression, but not significantly. In conclusion, our retrospective study confirms that CRF progression depends on sex, underlying renal diseases and serum Creatinine levels at the beginning of the study. Good regulation of blood pressure and low protein diet can slow down CRF progression.     

Competing causes of death and second primary tumors in patients with locoregionally advanced head and neck cancer treated with chemoradiotherapy.

PURPOSE: The purpose of this retrospective analysis was to evaluate the emergence of second primary malignancies and the contribution of different causes of death to the outcome of patients with locoregionally advanced head and cancer receiving primary chemoradiotherapy. EXPERIMENTAL DESIGN: We studied 324 patients with stage IV squamous cell head and neck cancer who were enrolled on five consecutive multicenter Phase II studies of concurrent chemoradiotherapy. All of the regimens included concurrent 5-fluorouracil and hydroxyurea on an alternate week schedule with radiotherapy, either alone (FHX) or with cisplatin (C-FHX) or paclitaxel (T-FHX). The cumulative incidence of second primary tumors or death from any cause was estimated using methods of competing risk analysis. RESULTS: Median follow-up of surviving patients was 5.2 years (2-10.6 years). The 5-year overall survival and progression-free survival of the cohort were 46% and 65%, respectively. Causes of death and median time of occurrence were as follows: disease (n = 88; 1.5 years), treatment-associated acute or late complications (n = 30; 4 months), second primary tumors (n = 18; 3.5 years), comorbidities (n = 41; 1.9 years), and unknown (n = 20; 5.1 years). Predominant causes of death from comorbidities were cardiac and respiratory illnesses. Twenty-six patients (8%) developed a second primary tumor at a median time of 2.8 years (4 months to 10 years). The cumulative incidence of second primary tumors was 5%, 7%, and 13% at 3, 5, and 10 years, respectively. The most frequent site of second primaries was the lung (n = 13), followed by the esophagus (n = 3) and head and neck (n = 2) CONCLUSIONS: Patients with locoregionally advanced head and neck cancer treated with concurrent chemoradiotherapy are potentially curable but face significant risks of mortality from causes other than disease progression. Ameliorating toxicity, and implementing secondary screening and chemoprevention strategies are major goals in the management of head and neck cancer.     

Peripheral blood mononuclear cell responses from type 1 diabetic patients and subjects at-risk for type 1 diabetes to human fetal pancreatic tissue proteins

BACKGROUND: Fetal pancreatic tissue has been suggested to be less immunogenic than adult islets. Thus, transplantation of human fetal pancreatic tissue as treatment for type 1 diabetes has been gaining interest. To investigate this question, we tested the peripheral blood mononuclear cell (PBMC) responses from different subject populations to human adult islet proteins (AIP) versus human fetal pancreatic proteins (FPP). METHODS: PBMC responses to FPP and AIP from normal controls (n=14), newly diagnosed type 1 diabetes patients (n=5), long-term type 1 diabetes patients (n=9), and subjects at-risk for development of type 1 diabetes (n=3) were studied. RESULTS: We observed that normal controls demonstrated PBMC reactivity to 0-3 molecular weight regions (mwr) for both the AIP (mean+/-SD, 0.8+/-1.1) and the FPP (0.6+/-0.7). In contrast, newly diagnosed type 1 diabetic patients (<1 year) demonstrated PBMC responses to 9-16 mwr for the AIP (12.8+/-2.5) and 0-14 mwr for the FPP (6.8+/-5.0). The PBMCs from long-term type 1 diabetes patients (> 3 years) were responsive to 2-11 mwr for AIP (6.0+/-2.8) and 0-11 mwr for FPP (4.9+/-4.0). Three nondiabetic ICA positive subjects at-risk for development of type 1 diabetes demonstrated positive PBMC reactivity to 9-18 mwr for the AIP (12.7+/-3.9) and 4-18 mwr for the FPP (10.0+/-5.9). CONCLUSIONS: We conclude that human fetal pancreatic proteins are not significantly less stimulatory than human adult islet proteins to PBMCs of subjects with or at risk for type 1 diabetes.