Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study.

BACKGROUND: The prevalence and severity of lipodystrophy syndrome with long-term therapy for HIV-1 infection that includes a protease inhibitor is unknown. We studied the natural course of the syndrome to develop diagnostic criteria and identifying markers that predict its severity. METHODS: We assessed 113 patients who were receiving HIV-1 protease inhibitors (mean 21 months) and 45 HIV-1-infected patients (28 with follow-up) never treated with a protease inhibitor. Lipodystrophy was assessed by questionnaire (including patients' rating of severity), physical examination, and dual-energy x-ray absorptiometry. Body composition and fasting lipid and glycaemic variables were compared with data obtained 8 months previously. Oral glucose tolerance was investigated. FINDINGS: There was 98% concordance between patients' reports of the presence or absence of lipodystrophy (reported by 83% of protease-inhibitor recipients and 4% of treatment-naïve patients; p=0.0001) and physical examination. Patients' ratings of lipodystrophy were significantly associated with declining total body fat (p=0.02). Lower body fat was independently associated with longer duration of protease-inhibitor therapy and lower bodyweight before therapy, and more severe lipodystrophy was associated with higher previous (p < 0.03) and current (p < or = 0.01) triglyceride and C-peptide concentrations, and less peripheral and greater central fat (p=0.005 and 0.09, respectively). Body fat declined a mean 1.2 kg over 8 months in protease-inhibitor recipients (p=0.05). The prevalence of hyperlipidaemia remained stable over time (74% of treated patients vs 28% of naïve patients; p=0.0001). Impaired glucose tolerance occurred in 16% of protease-inhibitor recipients and diabetes mellitus in 7%; in all but three patients these abnormalities were detected on 2 h post-glucose load values. INTERPRETATION: Diagnosis and rating severity of lipodystrophy is aided by the combination of physical examination, patient's rating, and measurement of body fat, fasting triglycerides, and C-peptide. Weight before therapy, fasting triglyceride, and C-peptide concentrations early in therapy, and therapy duration seem to predict lipodystrophy severity. Lipodystrophy was common and progressive after almost 2 years of protease inhibitor therapy, but was not usually severe. Hyperlipidaemia and impaired glucose tolerance were also common.

Epidemiology of liver cirrhosis morbidity and mortality in Iceland.

BACKGROUND: The mortality from liver cirrhosis in Iceland is the lowest in the Western world. OBJECTIVE: To study the epidemiology of liver cirrhosis mortality and morbidity in Iceland and to obtain a reliable separation between alcoholic cirrhosis (AC) and non-alcoholic cirrhosis (NAC) by using multiple data sources. METHODS: The study included the whole population of Iceland. Mortality was studied through death certificate data for the period 1951-90 and morbidity (clinical incidence) through hospital, autopsy and biopsy records for the period 1971-90. RESULTS: The average mortality for AC in age group 20 years and older was 8.6 and for NAC 19.2 per 10(6)/year and the average clinical incidence was 22.1 per 10(6)/year for AC and 25.9 per 10(6)/year for NAC. In the morbidity study 44% of cases were due to AC. In the mortality study 24% of cases were due to AC but the data suggested an underreporting of AC for males at a rate of 30%. There was a significant decrease in AC mortality with time but no change in NAC. Average alcohol consumption of inhabitants aged over 15 years increased from 2.1 to 4.9 litres per year (130%) during the period 1951-90. CONCLUSION: The incidence of cirrhosis in Iceland is very low for both AC and NAC, accounting for only 0.2% of total deaths. The reasons are unknown. The low incidence of AC in Iceland is probably partly due to low alcohol consumption. The decreasing incidence of AC despite 130% increase in alcohol consumption is thought to be due to intensive treatment of alcoholism. A low prevalence of hepatitis B and C probably contributes to the low incidence of NAC.

[Epidemiology of liver cirrhosis morbitity and mortality in Iceland.].

BACKGROUND: The mortality from liver cirrhosis in Iceland is the lowest in the Western world. OBJECTIVE: To study the epidemiology of liver cirrhosis mortality and morbitity in Iceland and to obtain a reliable separation between alcoholic cirrhosis (AC) and non alcoholic cirrhosis (NAC) by using multiple data sources. METHODS: The study included the whole population of Iceland. Mortality was studied through death certificate data for the period 1951-1990 and morbidity (clinical incidence) through hospital, autopsy and biopsy records for the period 1971-1990. RESULTS: 1) The average mortality for AC in age group 20 years and older was 8.6 and for NAC 19.2 per 106 per year and the average clinical incidence was 22.1 for AC and 25.9 for NAC. 2) In the morbitity study 44% were due to AC. In the mortality study 24% were due to AC but the data suggested an underreporting of AC for males at a rate of 30%. 3) There was a significant decrease in AC mortality with time but no change in NAC. 4) Alcohol consumption per inhabitant over 15 years increased from 2.1 to 4.9 litre (130%) during the period 1951-1990. CONCLUSION: The incidence of cirrhosis in Iceland is very low for both AC and NAC accounting for only 0.2% of total deaths. The reasons are unknown. The low incidence of AC in Iceland is probably partly due to a low population alcohol consumption. The decreasing incidence of AC despite 130% increase in alcohol consumption is thought to be due to intensive treatment of alcoholism. A low prevalence of hepatitis B and C probably contributes to the low incidence of NAC.

IS6770, an enterococcal insertion-like sequence useful for determining the clonal relationship of clinical enterococcal isolates.

Enterococci expressing resistance to antimicrobial agents are increasingly important nosocomial pathogens. Effective strategies to prevent or abort outbreaks of resistant enterococcal infection will rely on an accurate understanding of the mechanisms by which these organisms spread. A 1065-bp insertion-like sequence (IS6770) is present in varying copy numbers in > 90% of enterococcal strains thus far examined. Hybridization patterns resulting from hybridization of enterococcal genomic DNA with an internal IS6770 probe vary considerably between unrelated strains and correlate well with results of pulsed-field gel electrophoresis and field-inversion gel electrophoresis in identifying clonal relationships among enterococcal isolates. IS6770 analysis of several outbreaks of resistant enterococci has confirmed the spread of single resistant clones rather than the emergence of resistance within the resident flora. These results suggest that IS6770 hybridization will be a useful tool for tracing the epidemiology of nosocomial enterococcal infections.

The prevalence of sequences homologous to IS256 in clinical enterococcal isolates.

Using dot blot hybridization techniques and an internal IS256 probe, we screened 103 clinical enterococcal isolates for the presence of sequences homologous to IS256. Most screened isolates exhibited resistance to one or more antimicrobial agents. Overall, hybridization to the internal IS256 probe was demonstrable in 88/103 (85%) isolates. 49/53 (92%) gentamicin-resistant isolates hybridized with the IS256 probe. In addition, 34/45 (76%) gentamicin-susceptible, aph2"(-) strains possessed sequences homologous to IS256. Southern hybridization experiments indicated that IS256 was frequently present in multiple copies in gentamicin-susceptible strains. These results suggest that IS256 is highly prevalent in clinical enterococcal isolates and that we may anticipate the emergence of novel, IS256-based composite mobile elements.