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Molluscum contagiosum is a cutaneous poxviral infection that is rarely associated with other skin diseases, such as cutaneous neoplasms. Such associations are likely to be coincidental, except in immunocompromised patients. Kaposi sarcoma, an angioproliferative neoplasm derived from lymphatic endothelium, is mediated by human herpes virus-8 infection and occurs with increased frequency in immunocompromised individuals. We report an unusual case of molluscum contagiosum with underlying cutaneous Kaposi sarcoma diagnosed in a single skin biopsy of a human immunodeficiency virus-positive patient. Our case highlights the importance of adequate sampling to avoid missing secondary diagnoses in histopathologic sections and alerts pathologists and dermatologists to the possibility of coinfection in high-risk patients by 2 virally-mediated skin conditions.

Objective: Pneumocystis pneumonia (PCP) is a severe infection of the immunocompromised host, resulting in diffuse alveolar damage and life-threatening respiratory failure. We analyzed pulmonary surfactant composition and function in bronchoalveolar lavage fluid (BALF) from ventilated and spontaneously breathing HIV-positive patients with PCP., Design: Prospective clinical trial., Setting: University hospital intensive care unit., Patients: Thirty-four spontaneously breathing (SB-PCP) and 20 ventilated HIV-positive patients with PCP (V-PCP), ten patients with acute respiratory distress syndrome (ARDS), 11 spontaneously breathing patients with bacterial pneumonia (PNEU), and 22 healthy volunteers., Interventions: None., Measurements and Main Results: Total phospholipid in BALF did not differ between any category vs. controls, whereas total protein increased approximately 14-fold in V-PCP and five-fold in SB-PCP compared with controls (p < .001). The relative content of large surfactant aggregates (LA) was reduced in SB-PCP and V-PCP compared with controls (p < .05). The phospholipid and fatty acid profiles showed a significant reduction in the relative content of phosphatidylcholine (PC), phosphatidylglycerol, and palmitic acid in PC in all patient categories compared with controls, with more in V-PCP (p < .001) compared with SB-PCP (p < .05). The neutral lipid-to-phospholipid ratio in LA was three-fold elevated in V-PCP (p < .01 compared with control) but not in SB-PCP. Analysis of neutral lipid classes showed a significant increase in the relative content of triglycerides and a reduction in free fatty acids in V-PCP compared with controls. BALF surfactant protein (SP)-A and SP-D significantly increased in V-PCP and SB-PCP, but not in ARDS and PNEU, compared with controls (p < .05). SP-B and SP-C content in LA remained unchanged in PCP compared with controls but decreased significantly in ARDS and PNEU. The minimum surface tension of LA was impaired (p < .001) in V-PCP more than in SB-PCP and was strongly correlated with the reduction in palmitic acid levels in PC LA (r = -.81). Reductions in phosphatidylglycerol strongly correlated with decreased Pao2/Fio2 values (r = .72)., Conclusions: We conclude that severe alterations in surfactant function and composition occur in patients with PCP and are even more pronounced in ventilated patients than in nonventilated patients. Surfactant lipid changes in PCP, but not surfactant protein profiles, closely resemble those found in ARDS.

The clearance of cytomegalovirus viraemia in HIV-1-infected patients may partly result from the inhibition of cytomegalovirus protease by HIV-1 protease inhibitors contained in highly active antiretroviral therapy. We used a computational method to calculate the binding affinity of six HIV-1 protease inhibitors to cytomegalovirus protease based on its X-ray crystallography structure. The calculations showed that amprenavir and indinavir occupy the substrate-binding site of the cytomegalovirus protease with high affinity, and may be implicated in alleviating cytomegalovirus infection.

The anatomic distribution and rate of progression vary significantly between acquired immunodeficiency syndrome (AIDS)-related Kaposi sarcoma (KS) and classic KS. The reasons are unclear, but cyclin D1 overexpression is associated with tumor progression in other malignancies. Cyclin D has an important regulatory role in the progression of cell cycle at the G1-S phase due to its effect in phosphorylating the retinoblastoma gene product. Forty-one paraffin-embedded surgical specimens (31 AIDS-related, 10 classic) were examined using streptavidin-biotin-peroxidase immunohistochemistry with monoclonal antibody to cyclin D1. A scoring system based on the intensity and extent of staining was used. The correlations among cyclin D1 expression and clinicopathologic parameters were statistically analyzed. Cyclin D1 overexpression was found in 29% (12/41) of all KS cases. There was a strong correlation between cyclin D1 overexpression and pathologic stage (0% in patch stage, 13% in plaque stage, 50% in nodular stage; P = 0.0017). Classic KS lesions had a higher incidence of cyclin D1 overexpression than AIDS-related lesions (70% vs 16%, P = 0.001). Cyclin D1 overexpression was detected in 78% of the classic nodular lesions and 31% of the AIDS-related nodular lesions (P = 0.03). On multivariate analysis, negative human immunodeficiency virus status (P = 0.001) and nodular lesions (P = 0.007) were strong predictors of cyclin D1 overexpression. Age, gender, recurrence of the tumor, multiplicity, and site of the lesions hold no statistically significant association with cyclin D1 expression on multivariate analysis. In summary, cyclin D1 overexpression was more prevalent in classic lesions and more advanced nodular stage. These findings raise the possibility of a different pathogenetic mechanism in the progression of AIDS-related KS and classic KS.

The saliva/plasma concentration ratio of fluconazole was investigated in 22 HIV-1-infected individuals with an oropharyngeal Candida infection to determine whether saliva fluconazole concentrations could provide useful information for therapeutic drug monitoring in this population. Steady-state paired plasma and saliva samples were obtained after approximately 1 week of treatment with 50-or 100-mg fluconazole as capsules. A significant correlation between plasma and salivary levels of fluconazole was observed. The median saliva/plasma concentration ratio was 1.3 and was independent of the ingested dose and the plasma fluconazole concentration. The prediction of fluconazole concentrations in plasma from the concentrations in saliva was, although unbiased, not precise. From these findings, the authors conclude that although stimulated salivary fluconazole concentrations are significantly correlated with plasma concentrations, it is not possible to predict plasma fluconazole levels from the salivary concentrations with adequate precision. However, saliva fluconazole concentrations have sufficient value to test for compliance and even semiquantitative prediction of plasma concentrations.

Objectives: A 12-week course of recombinant human growth hormone is an effective but expensive therapy for established HIV-related wasting. Wasting in HIV disease is often episodic, coinciding with bouts of acute opportunistic infection. We hypothesized that a short course of growth hormone, targeted at the time of opportunistic infection, might improve protein metabolism thereby reducing lean tissue loss., Methods: HIV-infected men with acute opportunistic infections, who received standard antimicrobial treatment for their infection as well as intensive nutritional counselling and oral energy supplements, were randomized to receive growth hormone or placebo for 14 days. Principal assessments were protein metabolism (measured by 13C-leucine infusion), body composition (measured by DEXA) and safety., Results: There were no significant changes in outcome parameters in the placebo group (n = 11). In the growth hormone group (n = 9), protein catabolic rate decreased by 60% in the fasted state (P = 0.02 versus placebo), lean body mass increased by 2.2 kg (P = 0.03 versus baseline) and fat mass decreased by 0.7 kg (P = 0.002 versus baseline). There was no increase in adverse or serious adverse events in the growth hormone as compared with the placebo group., Conclusions: A two-week course of growth hormone at the time of acute opportunistic infection in HIV-infected patients improves protein metabolism and body composition during therapy and appears to be safe. This may represent a rational and economical approach to the use of growth hormone therapy.

A population pharmacokinetic model of intravenously and orally administered trimethoprim in patients with acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia has been made using a parametric iterative two-stage Bayesian and a nonparametric expectation maximization computer program. When good information was present in the serum level data, both methods obtained similar results. With the nonparametric expectation maximization program, the median apparent rate constant for absorption (Ka) was 1.602 hr-1, median slope (Ks) of the relationship between creatinine clearance and elimination was 0.001168 hr-1, median apparent volume of distribution (Vs) was 1.058 l/kg, and median fraction of oral dose absorbed (Fa) was 0.955. These results permit dosage individualization adjusted to body weight and renal function to achieve chosen serum level peak and trough goals. Peak goals of 9 ug/ml and trough goals of 5 ug/ml appear reasonable for most patients in this population, and should permit most to complete an effective course of therapy with a reduced risk for treatment-terminating hematologic toxicity. However, therapeutic goals should always be selected based on each patient's apparent need for the drug and the risk of toxicity that is justifiably acceptable to obtain the expected benefits of the drug.

Objective: The metabolic response to AIDS-defining opportunistic infections was examined to provide a logical basis for the management of associated weight loss., Design: A prospective study of metabolism in AIDS., Setting: HIV outpatients' department and wards at the Chelsea and Westminster Hospital, London., Patients: Ten asymptomatic Centers for Disease Control and Prevention stage II HIV-seropositive control subjects and 36 HIV-seropositive patients with a single newly diagnosed and untreated opportunistic infection [10 with microsporidial or cryptosporidial diarrhoea, 10 with Pneumocystis carinii pneumonia, nine with cytomegalovirus enteritis and seven with systemic Mycobacterium avium-intracellulare]., Main Outcome Measurements: Subjects had measurements of resting energy expenditure using indirect calorimetry and of body composition using dual energy X-ray absorptiometry., Results: Subjects with protozoal diarrhoea had a decreased resting energy expenditure (P < 0.05) and decreased body fat (P < 0.01). Subjects with P. carinii pneumonia had an elevated resting energy expenditure (P < 0.05). Subjects with systemic M. avium-intracellulare had an elevated resting energy expenditure (P < 0.05) and decreased skeletal muscle mass (P < 0.05). Subjects with cytomegalovirus enteritis had a non-significant elevation of resting energy expenditure with a non-significant loss of both fat and lean tissue., Conclusion: Subjects with protozoal diarrhoea show a starvation response to infection and subjects with systemic M. avium-intracellulare show a cachectic response. Since there is a variation in the metabolic response to opportunistic infection in AIDS patients, nutritional management should be directed according to the specific cause.

Objective: HIV-related gastrointestinal infection is associated with diarrhoea, weight loss, mucosal inflammation and increased intestinal permeability. As tumour necrosis factor (TNF)-alpha may mediate these features this cytokine was measured in the faeces of HIV-seropositive individuals with diarrhoea to assess its role in the pathogenesis of HIV-related gastrointestinal disease and the association with specific intestinal pathogens., Design: Prospective study., Methods: Two hundred and four HIV-seropositive individuals provided stool samples that were analysed for faecal TNF-alpha (FTNF-alpha) using a standard sandwich enzyme-linked immunosorbent assay., Results: Stool from patients with bacterial, cytomegalovirus (CMV) and microsporidial diarrhoea had significantly elevated FTNF-alpha compared with those who had pathogen-negative diarrhoea (P < 0.05). FTNF-alpha was not raised in cryptosporidiosis, pathogen-negative or solid stool. In subjects with diarrhoea of more than 2 weeks duration and three stool samples negative for enteric pathogens, FTNF-alpha greater than 15 U/ml has a sensitivity of 88% and a specificity of 66% for the diagnosis of diarrhoea-related CMV enteritis., Conclusion: TNF-alpha production may have a role in the pathogenesis of bacterial, microsporidial and CMV-related diarrhoea in HIV-seropositive individuals. Thus, anti-TNF-alpha agents may have a therapeutic role in the management of these conditions. FTNF-alpha greater than 15 U/ml in apparently pathogen-negative diarrhoea may suggest endoscopic gastrointestinal biopsy to diagnose CMV enteritis.