Cutaneous non-tuberculous Mycobacterial infections: a clinical and histopathological study of 17 cases from Lebanon.

BACKGROUND: Only a few studies characterized cutaneous non-tuberculous Mycobacterium (NTM) infections in this region of the world. Objective The aim of this study was to describe the epidemiological, clinical and histological findings of cutaneous NTM infections in Lebanon. PATIENTS/METHODS: Retrospective study of 17 patients (19 histological specimens) diagnosed with cutaneous NTM infections and confirmed by culture-based partial sequencing of the 16S rRNA gene at the American University of Beirut Medical Center between 2005 and 2008. RESULTS: Of 17 cases, 14 were caused by Mycobacterium marinum. All patients were immunocompetent except for one. Clinically, the most common presentation was multiple sporotrichoid lesions over an extremity (8/17). Many patients had peculiar presentations including bruise-like patches, herpetiform lesions, annular ulcerated plaques, symmetrical nodules over the buttocks and locally disseminated lesions with surrounding pale halo. Almost all patients cleared their infection on either minocycline or clarithromycin monotherapies. Histologically, a dermal small vessel proliferation with mixed inflammation (granulation tissue-like changes) was identified in 58% of specimens. The most common type of granulomatous inflammation was the suppurative (47%) followed by the tuberculoid (30%), sarcoidal (11%), and palisading (5%) types. Lichenoid granulomatous dermatitis was noted in 42% of cases. Special staining highlighted mycobacteria in only two specimens. CONCLUSIONS: The incidence of cutaneous NTM infections is high in our area. Many patients had peculiar clinical presentations. Our study is the second to report the common presence of granulation tissue-like changes as a good histological indicator of cutaneous NTM infections. Minocycline and clarithromycin remain the drugs of choice in our area.

Evaluation of anhydride oligomers within polymer microsphere blends and their impact on bioadhesion and drug delivery in vitro.

The effect of the addition of small molecular weight anhydride oligomers to polymer microspheres was evaluated and increased bioadhesion of the composite was demonstrated. Blends of low molecular weight anhydride oligomers with thermoplastic poly(fumaric-co-sebacic anhydride) [p(FASA)] and polycaprolactone were examined. The effects of anhydride oligomers on polymer microsphere degradation, crystallinity, and surface morphology were also explored. The results demonstrated that fumaric anhydride oligomer remained within polymer microspheres for several hours after exposure to phosphate buffer, formed a homogenous crystalline blend, increased bioadhesion as measured on rat intestine, and enhanced drug delivery in vitro as measured by the everted sac technique.

Problems and practical considerations in assessing accuracy with NIST SRM 909a: report of defective vials.

During an experimental period of 12 months in 1992-1993, while we were comparing the effectiveness of monthly vs quarterly use of the National Institute for Standards and Technology Standard Reference Material (NIST SRM) 909a as an accuracy material for the projected 30-year Fernald Medical Monitoring Program, we encountered three random defective vials with a glucose recovery of less than 30% of the NIST-assigned value. Analysis with five different multichannel instruments confirmed the original finding. Concomitant glucose recovery from adjacent vials was 97%-104%, as determined by using the same instruments, reagents, calibrators, and quality-control criteria on the same days. Recoveries of uric acid and cholesterol were also low (53-75% and 75-80%, respectively) in the three defective vials. Other analytes were unaffected. Studies to identify the cause of the defective vials were carried out with microbiological, electron microscopic, and biochemical techniques. When used for accuracy studies, each vial of NIST SRM 909a should have a concomitant check for glucose recovery to detect whether the vial is defective.

The impact of age on alcohol toxicity in the rat.

This study was performed to determine whether the severity of chronic alcohol toxicity is altered by age and duration of drinking. Alcohol as 35% of calorie intake (ED treatment) was administered to Sprague-Dawley rats at predetermined ages beginning at 1, 6, 12, 18, 24 and 27 months for a duration of treatment varying from 1 to 3 months. The degree of injury was compared to controls (CD treatment) of comparable age and duration of treatment. ED was associated with significantly higher serum levels of AST, total bilirubin and alkaline phosphatase (P < 0.0001 for each test) without detectable differences due to age and duration of treatment. Liver triglycerides (as a measure of alcoholic fatty steatosis) were significantly increased by ED (P < 0.0001) and influenced by both age and duration of treatment. The greatest toxicity was observed in young animals. ED treatment beginning at 1 month of age was associated with an AST level 69% above CD and liver triglycerides 463% above CD; beginning at 18 months of age, ED produced an increase of 24% in AST and 175% in liver triglycerides. The hepatic regenerative capacity, as measured by 3H-thymidine uptake into nuclear DNA, was similarly affected by both ED and age. Regeneration was significantly higher in youth. ED produced a 62% increase above CD at 1 month compared to an 11% increase beginning at 18 months of age. These observations suggest that juveniles develop more severe injury from alcohol but that a greater regenerative capacity exists in youth. This may explain the observed clinical relationship between age and prognosis seen in patients with severe alcoholic liver injury.

Impact of chronic alcoholism on the aging rat: changes in nutrition, liver composition, and mortality.

The adverse effects of chronic alcohol consumption (mean 6.68 g/kg/d) were assessed in 150 male Sprague-Dawley rats over their life span (25 months). Evaluations were performed at 2, 3, 8, 13, 19, and 25 months of age for changes in nutrition status, biochemical tests for liver injury, compositional changes in liver, and hepatic regenerative capacity. In spite of nearly identical caloric intake, alcohol treatment was associated with nutritional levels 10-30% lower than controls. Maximal changes were observed at the two extremes of ages (2-3 months and 19-25 months). Hence, a nutritional contribution to other adverse changes could not be excluded. Fatty compositional increases (triglycerides) occurred early (5-fold increases after 1 month of treatment) then declined to levels only slightly above controls. Biochemical tests on sera for liver injury (AST and total bilirubin) were consistently higher with alcohol treatment. Regenerative capacity measured by [3H]thymidine uptake after partial hepatectomy was initially elevated in the alcoholic then rapidly declined beyond 7 months of age. In control animals, an age-related decline was also observed but occurred later beyond 12 months of age. Consistent with these adverse effects, ethanol diet survival was poorer than the pair-fed control groups by 15% (median survival for alcoholics, 17 months vs. 20 months in controls.

Antibodies to hepatitis B virus and hepatitis C virus in alcoholic hepatitis and cirrhosis: their prevalence and clinical relevance. The VA Cooperative Study Group (No. 119)

Patients with overt alcoholic liver disease who had participated in a multicenter therapeutic trial and subgroups of controls (i.e., alcoholic patients without liver disease and patients with neither alcoholism nor liver disease) were tested for hepatitis B virus and hepatitis C virus antibodies to determine the prevalence of these antibodies to determine the prevalence of these antibodies and any clinical association in the progression and outcome of alcoholic liver disease. Antibodies to hepatitis B (anti-HBs and/or anti-HBc) were found in 29.2% of patients with alcoholic liver disease, in 26.1% of hospitalized alcoholic patients without liver disease and in 24.2% of hospitalized nonalcoholic patients without liver disease; frequencies were not significantly different from one another. HBsAg was not evaluated because HBsAg+ patients had been excluded from the original trial. The presence of these antibody markers correlated with ethnic origin of and immunoglobulin levels in the patients. In contrast, antibody to hepatitis C, as detected by enzyme immunoassay, was positive in 27.1%, 4.8% and 3.0% of the three groups, respectively, the first differing significantly from the other two. Antibody to hepatitis C virus positivity correlated significantly with clinical severity of the disease and with the presence of histological features that imply chronic viral infection (periportal inflammation, cirrhosis), despite the fact that the supplementary assay for antibody to hepatitis C virus, using recombinant immunoblot assay, reduced the positive rate by 79%.(ABSTRACT TRUNCATED AT 250 WORDS)

Host response to mycobacterial infection in the alcoholic rat.

Animals, chronically treated with alcohol, were inoculated with mycobacteria (bacillus Calmette-Guérin, 10.2 x 10(6) organisms) into the spleen to produce a granulomatous hepatitis. Before infection, chronic alcohol ingestion was associated with a depressed skin test response to phytohemagglutinin, 71.7% of baseline (P = 0.009). Mycobacterial (bacillus Calmette-Guérin) infection stimulated phytohemagglutinin skin test response to 417% of baseline in controls and 299% in alcoholics (P less than 0.001). The hepatic granuloma response was altered with smaller but more numerous granulomas (mean +/- SEM, 81.2 +/- 1.5 microns2 of area with a frequency of 1.8 granulomas per field in alcoholics vs. 129.8 +/- 5.71 microns2 and 1.2 granulomas per field in controls; P less than 0.001). These changes were associated with a 10-fold increase in colony-forming units per gram of liver (54.5 +/- 18.2 in alcoholics vs. 5.6 +/- 1.83 in controls; P = 0.0006). This model offers precise parameters for host response to infection and indicates that alcohol significantly impairs the clearing capacity for mycobacteria from the liver.