Treatment of relapsing Mycobacterium avium infection with interferon-gamma and interleukin-2 in an HIV-negative patient with low CD4 syndrome.

A patient with idiopathic CD4 T-lymphopenia was diagnosed with a recurrent disseminated Mycobacterium avium infection. Because of progressive disease, treatment with interferon-gamma (IFN-γ) and interleukin-2 (IL-2) was started. The patient was successfully treated with IFN-γ-1b and IL-2 in addition to anti-mycobacterial combination therapy. To our knowledge, this is the first report of successful combination therapy with IFN-γ-1b and IL-2 in a patient with idiopathic CD4 T-lymphopenia. Short-term IFN-γ-1b and IL-2 might be considered as therapeutic options in refractory mycobacterial infections in patients with idiopathic CD4 lymphopenia.

Acute measles infection triggering an episode of liver transplant rejection.

We report the case of a 31-year-old immunosuppressed, liver transplanted man, with acute measles infection. The vaccinated patient had been exposed to measles during a known measles epidemic in public schools in Austria between January and April 2008. Measles infection triggered an episode of acute liver transplant rejection. The diagnosis of measles infection was made clinically and by serologic tests. Transplant rejection was diagnosed by liver biopsy. The transplant rejection was treated successfully. Liver transplant patients are at an increased risk for infection during epidemic outbreaks, even after pre-transplant vaccination, as immunity may wane over time.

[(13)C]Methionine breath test as a marker for hepatic mitochondrial function in HIV-infected patients.

Metabolic disturbances such as dyslipidemia, lipodystrophy syndrome, visceral obesity, hyperlactatemia, diabetes mellitus, and hepatic steatosis have been recognized as serious complications in long-term antiretroviral-treated HIV-infected patients. The oxidative capacity of liver mitochondria plays a central role in their pathogenesis and can be analyzed using the [(13)C]methionine breath test. We analyzed hepatic mitochondrial function using the [(13)C]methionine breath test in antiretrovirally treated and untreated HIV-infected patients as well as HIV-negative controls. Patients with hepatic steatosis, hypertriglyceridemia, lipohypertrophy, and older age showed reduced methionine metabolism. Hepatic mitochondrial function is impaired in antiretroviral-treated HIV-infected patients with disturbances of lipid metabolism.

[A 17 year old adolescent with chronic neutropenia, recurrent infections, severe dysphagia and peroneus palsy]. / 17-jähriger Mann mit jahrelanger Neutropenie und Infektneigung, schwerer Dysphagie und Peroneuslähmung.

A 17-year-old German adolescent with a four year history of neutropenia and repeated infections presented with severe dysphagia and progressive right-sided peroneus palsy. In the past four years, extensive medical workup had been performed, and despite conspicuous findings, no diagnosis was made. Finally we diagnosed HIV related CMV esophagitis and HIV associated polyneuropathy. The CMV esophagitis was treated antivirally, and highly active antiretroviral HIV therapy was initiated. The mode of HIV transmission remained obscure until further research revealed a probable nosocomial infection during early childhood in Romania.

[Recurring disseminated Mycobacterium avium infections in an HIV-negative patient]. / Rezidivierende disseminierte Mycobacterium-avium-Infektionen bei einem HIV-negativen Patienten.

HISTORY AND ADMISSION FINDINGS: A 64 year old man complained about progressive pain in his right upper leg and pelvis since 4 weeks without any history of trauma. He noticed a reduced general health status for several months with weight loss and subfebrile temperatures. The patient's medical history revealed several malignant tumours and recurrent infections with atypical mycobacteria and herpes viruses. INVESTIGATIONS: Laboratory findings showed signs of chronic inflammation. Multiple disseminated osteolytic bone lesions, hepatosplenomegaly, lymphadenopathy and multiple splenic lesions were detected by CT scan. Mycobacterium avium was isolated from an osteolytic lesion of the pelvic bone. Malignant disease and acquired immunodeficiency syndrome were excluded. Lymphocyte counts showed lymphocytopenia with reduced T cells, B cells and a reduced CD4-/CD8-ratio. Interferon-gamma-pathway defects as described in patients with susceptibility to atypical mycobacteria could not be identified. TREATMENT AND COURSE: Clinical and immunologic findings indicated a link between recurrent Mycobacterium avium infections and an idiopathic CD-4 T-cell lymphopenia (low CD4 syndrome). Antimycobacterial treatment at standard doses was started according to the resistance test obtained from microbiological culture. Medical and radiological checkup after 3 months of therapy showed signs of progressive disease. CONCLUSIONS: Osteolytic lesions can be caused by mycobacterium avium infection. Disseminated atypical mycobacteriosis is an opportunistic disease in patients with congenital or acquired immunodeficiency syndrome.

Kinetics of lactate metabolism after submaximal ergometric exercise in HIV-infected patients.

OBJECTIVES: It is unknown whether high levels of lactate result from enhanced production or decreased degradation. We therefore investigated differences in the kinetics of plasma lactic acid in HIV-infected patients receiving or not receiving highly active antiretroviral therapy (HAART) and in uninfected controls after submaximal ergometric exercise. METHODS: Ten healthy controls, 11 HIV-infected therapy-naïve patients, 15 HIV-infected patients on HAART with normal baseline lactate levels, and nine HIV-infected patients on HAART with elevated baseline lactate levels >2 mmol/L performed 10 min of ergometric exercise, with a heart rate of 200 beats/min minus age. Lactate levels were measured at baseline, at the end of exercise and 15, 30, 45, 60 and 120 min thereafter. RESULTS: Mean baseline lactate levels were 1.4, 1.5, 1.5 and 2.8 mmol/L in the controls, the therapy-naïve patients, the patients on HAART with normal lactate levels and the patients on HAART with elevated lactate levels, respectively. Maximum lactate levels after exercise were similar in all groups (9.7, 9.4, 9.0 and 10.1 mmol/L, respectively). Significant differences were found in the slope of lactate decline between controls and untreated individuals (P=0.038) and between patients on HAART with normal baseline lactate and patients on HAART with elevated baseline lactate (P=0.028). CONCLUSIONS: Differences in lactate metabolism do exist between healthy controls and HIV-infected therapy-naïve individuals. Thus, HIV infection in itself may influence lactate levels. Elevated baseline lactate levels are associated with a delayed decline of lactate after exercise. These results could be explained by impaired lactate clearance. Lactate production upon exercise does not seem to be affected by baseline lactate levels.

Pharmacokinetic and tolerability profile of twice-daily saquinavir hard gelatin capsules and saquinavir soft gelatin capsules boosted with ritonavir in healthy volunteers.

OBJECTIVE: To evaluate the pharmacokinetics and safety of a boosted saquinavir (SQV)/ritonavir (RTV) combination, administered as either the hard gelatin capsule (HGC) or soft gelatin capsule (SGC) formulation of SQV, in 24 healthy volunteers. METHODS: This was a single-centre, open-label, randomized, 2 x 2 crossover study. Twelve subjects were randomized to receive SQV/RTV 1000 mg/100 mg twice daily (BID) orally for 10 days, as either the HGC or SGC formulation. The pharmacokinetic profile of SQV was determined on day 10. Subjects then crossed over to the opposite SQV formulation, and the pharmacokinetic profile was determined again on day 20. The primary analysis was the assessment of bioequivalence based on logarithmically transformed values for AUC(0-24 h) and Cmax for the two formulations. RESULTS: There was a statistically significant increase in the geometric means of all the pharmacokinetic variables evaluated for SQV-HGC/RTV compared with SQV-SGC/RTV. A mean AUC0-24 h-value of 15.798 micro g/mL/h was reported for the HGC formulation compared with 11.655 micro g/mL/h for the SGC formulation (P = 0.0043). The SQV-HGC/RTV combination was better tolerated in terms of gastrointestinal system disorders. Furthermore, no elevations in triglycerides or total cholesterol were reported with SQV/RTV during the entire study period. CONCLUSION: In healthy volunteers, RTV boosting of SQV-HGC produces plasma exposures at least comparable to SQV-SGC, which is accompanied by an improvement in gastrointestinal system disorders.

The prognostic significance of tumor vascularization in patients with localized colorectal cancer.

Angiogenesis is essential for tumor growth and metastasis, and vascular density is known as an independent prognostic factor in several tumor entities. We studied the prognostic relevance of vascular density in colorectal cancer, examining 146 patients treated surgically for cure. Tumor sections were immunostained with JC70, an endothelial cell marker. Microvessel quantification used light microscopy. The slides were scanned at a low magnification, and individual microvessel counts were made on a x200 field in the area of the most dense neovascularization. Vascular density was found to be 75+/-27/visual field and to be independent of age, sex, pT and pN categories, tumor recurrence, and overall survival. Overall survival in the subgroup of patients with tumor recurrence was significantly shorter with tumors of greater vessel density (>75) than in those of less vessel density (<75). Multivariate analysis showed microvessel count to be an independent prognostic factor for the overall survival rate of patients with tumor recurrence; among these patients there was also a significant difference in the relapse-free survival rates between the hypovascular and the hypervascular groups. Our findings suggest that the microvessel density of the primary tumor determines the speed of tumor recurrence after metastatic disease has been triggered by other, unknown mechanisms. Although tumor vascularization can be linked to the aggressiveness of colorectal cancer, it has no value as a new prognostic marker in clinical practice.