Current concepts in the diagnosis and management of metabolic complications of HIV infection and its therapy.

Changes in fat distribution, dyslipidemia, disordered glucose metabolism, and lactic acidosis have emerged as significant challenges to the treatment of human immunodeficiency virus (HIV) infection. Over the past decade, numerous investigations have been conducted to better define these conditions, identify risk factors associated with their development, and test potential therapeutic interventions. The lack of standardized diagnostic criteria, as well as disparate study populations and research methods, have led to conflicting data regarding the diagnosis and treatment of metabolic and body shape disorders associated with HIV infection. On the basis of a review of the medical literature published and/or data presented before April 2006, we have prepared a guide to assist the clinician in the detection and management of these complications.

Development of procedures for rapid detection of E. coli O157:H7 from source and finished water samples.

Enterohaemorrhagic Escherichia coli (EHEC) O157:H7, the causative agent for haemolytic uraemic syndrome, has become a significant health concern, due to an increasing number of cases. The focus of this project was rapid (<8 h) detection of E. coli O157:H7 from source and finished waters samples, either directly or indirectly, by dovetailing the procedures with existing total coliform procedures. Evaluation of four immunological lateral diffusion assays determined a detection range between 1 x 10(4) and 1 x 10(6) CFU, with the Reveal E. coli O157:H7 Test System (Neogen) being the most sensitive for detecting E. coli O157:H7. Evaluation of the BAX System for molecular detection determined that as few as 10 CFU could be reproducibly detected. Coupling either of these detection procedures with organism propagation using Tryptic Soy Broth (TSB) enabled sufficient quantities of E. coli O157:H7, such that the Reveal and BAX detection methods could be used with the 8 h time frame. Examination of matrix effects on the overall procedure indicated little impact on method performance.

Minocycline treatment for HIV-associated cognitive impairment: results from a randomized trial.

OBJECTIVE: We conducted a study of minocycline to assess its safety, tolerability, and efficacy for the treatment of HIV-associated cognitive impairment. METHODS: HIV-1-infected individuals with progressive neurocognitive decline were enrolled in a double-blind, placebo-controlled study of minocycline. Participants were randomized to receive minocycline 100 mg or matching placebo orally every 12 hours. The primary efficacy measure was change in a neuropsychological test composite z score (NPZ-8) from baseline to week 24. Measures of safety included the frequency of adverse events and changes over time in laboratory tests. After 50% of participants completed the double-blind phase, an interim analysis of futility for the primary outcome measure was performed, and our Data and Safety Monitoring Board recommended early study termination. RESULTS: A total of 107 HIV-1-infected individuals with cognitive impairment were enrolled. The minocycline group did not show improvement in the primary outcome measure (NPZ-8) (mean 24-week change = 0.12) compared to placebo (mean 24-week change = 0.17) (95% confidence interval = [-0.26, 0.39], p = 0.70). There were few severe adverse events or laboratory abnormalities in either treatment group. CONCLUSION: Minocycline was safe and well-tolerated in individuals with HIV-associated cognitive impairment, but cognitive improvement was not observed. Classification of evidence. This interventional study provides Class II evidence for the safety, tolerability, and efficacy of minocycline for the treatment of HIV-associated cognitive impairment.

A multicenter trial of selegiline transdermal system for HIV-associated cognitive impairment.

BACKGROUND: Cognitive impairment continues to be a significant neurologic complication of HIV infection and has been associated with oxidative stress-induced neuronal injury. Selegiline is an MAO-B inhibitor with antioxidant and neurotrophic properties. This rationale has led to the design and implementation of this Selegiline Transdermal System (STS) study with the primary aims of assessing safety and tolerability of STS as well as improvement in cognitive performance. METHODS: HIV-1 infected individuals with impaired cognitive functioning were enrolled in this placebo-controlled, three-arm study of STS across 17 sites. Cognitive impairment was determined using a standard battery of neuropsychological tests. Subjects were randomized to receive STS 3 mg/24 hours, STS 6 mg/24 hours, or matching placebo patches daily. The primary efficacy endpoint was defined as the change in neuropsychological composite Z-score (NPZ-6) from baseline to week 24. Measures of safety included frequencies of adverse experiences and abnormal results on laboratory tests. RESULTS: A total of 128 subjects (88% men, 51% white) were enrolled, median age 45 years. Most subjects (62%) had mild to moderate AIDS dementia complex. The 24-week NPZ-6 median (interquartile range) changes were 0.22 (-0.28, 0.55) for the selegiline 3 mg/24 hours arm, 0.21 (-0.18, 0.62) for the selegiline 6 mg/24 hours arm, and 0.28 (-0.16, 0.64) for the placebo arm (a positive score indicates improvement from baseline) (p = 0.914). Severe laboratory abnormalities were few and occurred in similar proportion among the three treatment arms. CONCLUSION: Selegiline was safe and well tolerated by HIV-infected individuals with cognitive impairment and mild to moderate immune suppression; however, no cognitive or functional improvement was observed in this phase II study.

[Metronidazole-resistant trichomoniasis and successful therapy following high dosage]. / Metronidazol-resistente Trichomoniasis und erfolgreiche Therapie nach hoher Dosierung.

A patient is reported who suffered for several months from a Trichomonas vaginalis infection that was resistant to the usual low-dose treatment with 5-nitro-imidazole derivatives. Following various ineffective therapeutic trials, the agent was isolated in order to determine its sensitivity to 5-nitro-imidazole. The resistance of the isolate to metronidazole was confirmed in vitro and in an animal experiment; the patient was therefore treated with high daily doses of metronidazole, 3 x 750 mg orally as well as 2 x 100 mg topically for 14 days. Substitution therapy with zinc was administered in order to normalize the patient's relatively low zinc serum levels. These measures finally led to a clinical cure and elimination of the pathogenic agent. This is the first confirmed case of a metronidazole-resistant Trichomonas vaginalis infection reported in the Federal Republic of Germany.

[Calcinosis cutis: cutaneous manifestations of generalized calcinosis in renal hyperparathyroidism]. / Calcinosis cutis: kutane Manifestationen generalisierter Kalzinose bei renalem Hyperparathyreoidismus.

In 2 female patients suffering from chronic renal insufficiency and secondary hyperparathyroidism total parathyroidectomy with autotransplantation was performed, but shortly afterwards tertiary hyperparathyroidism developed. Together with numerous generalized metastatic foci of severe smooth tissue calcification, extensive calcification of the skin occurred. Some of the hard painful areas with papules, nodules and large plaques of calcium deposits were inflamed and ulcerated, and the histological picture was that of severe disseminated calcification of the middle and deep reticular dermis, spreading over into the subcutaneous adipose tissue. Conventional X-ray examinations and computer tomography revealed large asymmetrical areas of bone-dense calcification of the soft tissue. After total excision of the autografts the severe calcifications of the skin diminished or disappeared completely.