Unmasking immune reconstitution inflammatory syndrome: a report of tuberculous epididymo-orchitis mimicking a testicular tumour in a Caucasian AIDS patient.

Worldwide, it is estimated that 14.8% of all new tuberculosis cases in adults are attributable to HIV infection. Genitourinary tuberculosis is a known complication and is considered to be a severe form of extrapulmonary tuberculosis. Isolated tuberculous epididymo-orchitis is rare. We report a Caucasian HIV-positive heterosexual male with a clinical diagnosis of testicular tumour for which he underwent a right orchidectomy. Tuberculous epididymo-orchitis was confirmed by histology. In this case, all Immune Reconstitution Inflammatory Syndrome (IRIS) criteria were met. We want to convey the message that in HIV-positive patients presenting with testicular swelling, an infective aetiology should be considered. This will increase the possibility of early diagnosis and proper management.

Gargantulide A, a complex 52-membered macrolactone showing antibacterial activity from Streptomyces sp.

Gargantulide A (1), an extremely complex 52-membered macrolactone, was isolated from Streptomyces sp. A42983 and displayed moderate activity against MRSA. The planar structure of 1 was determined using 2D NMR, and its stereochemistry was partially established on the basis of NOESY correlations, J-based configuration analysis, and Kishi's universal NMR database.

Autonomic neuropathy resulting in recurrent laryngeal nerve palsy in an HIV patient with Hodgkin lymphoma receiving vinblastine and antiretroviral therapy.

Hoarseness of voice due to vocal cord paresis as a result of recurrent laryngeal nerve palsy has been well recognised. Recurrent laryngeal nerve palsy is commonly caused by compression due to tumour or lymph nodes or by surgical damage. Vinca alkaloids are well known to cause peripheral neuropathy. However, vinca alkaloids causing recurrent laryngeal nerve palsy has been reported rarely in children. We report a case of an adult patient with HIV who developed hoarseness of voice due to vocal cord paralysis during vinblastine treatment for Hodgkin lymphoma. Mediastinal and hilar lymph node enlargement in such patients may distract clinicians from considering alternative causes of recurrent laryngeal nerve palsy, with potential ensuing severe or even life-threatening stridor.

Corynanthean, eburnan, secoleuconoxine, and pauciflorine alkaloids from Kopsia pauciflora.

Eleven indole alkaloids, comprising four corynanthean, two eburnane, one aspidofractinine, one secoleuconoxine, one andranginine, and two pauciflorine type alkaloids were isolated from the stem-bark and leaf extracts of Kopsia pauciflora. Their structures were determined using NMR and MS analyses. The catharinensine type alkaloid kopsirensine B and the secoleuconoxine alkaloid arboloscine A showed moderate to weak activity in reversing MDR in vincristine-resistant KB cells. The alkaloid content was markedly different compared to that of a sample from Malaysian Borneo.

Cushing's syndrome with adrenal suppression induced by inhaled budesonide due to a ritonavir drug interaction in a woman with HIV infection.

A 48-year-old woman with HIV infection developed Cushingoid features while she was taking ritonavir-boosted darunavir. Cushing's syndrome was confirmed due to the drug interaction between ritonavir and budesonide. Diagnosis of iatrogenic Cushing's syndrome in HIV-positive patients who are on ritonavir-boosted protease inhibitors (PIs) presents a clinical challenge due to similar clinical features of lipohypertrophy related to ritonavir-boosted PIs. Although this complication has been widely described with the use of inhaled fluticasone, the interaction with inhaled budesonide at therapeutic dose is not widely recognized.

Haemorrhagic transformation of cerebral infarction in an AIDS patient--thrombophilia screen essential!

Patients with advanced HIV disease with low CD4 count are more prone to thrombo-embolism and various predisposing factors have been identified. These include the presence of anticardiolipin antibodies and the lupus anticoagulant, deficiencies of proteins C and S, heparin co-factor II and antithrombin. Increased levels of Von Willebrand factor and d-dimers have also been linked with thrombo-embolism, as has the presence of concurrent infections and malignancies. We report a case of an AIDS patient who presented with acute hemiparesis. He was severely immunosuppressed. Computed tomography of the head confirmed cerebral infarction with haemorrhagic transformation. He had no known risk factors apart from being severely immunocompromised and had high anticardiolipin antibodies and low free protein S.

Long-term suppressive therapy for pulmonary aspergilloma in an immunocompromised man with AIDS. Is it always necessary?

Aspergillus infections are rare opportunistic infections in the course of AIDS and they mostly present as invasive pulmonary disease. Owing to the prolonged survival of profoundly immunocompromised patients with AIDS, invasive pulmonary aspergillosis is being reported with increased frequency. However, although pulmonary aspergilloma has been well described in immunocompetent patients, it has been rarely reported in AIDS patients. The treatment for pulmonary aspergilloma remains challenging and often needs lifelong treatment to minimize fatal haemoptysis, which can occur in up to 25%, and progression to secondary invasive aspergillosis. We report a case of pulmonary aspergilloma in a severely immunocompromised patient with AIDS who stopped taking systemic antifungal treatment in April 1998 and remained well with little progression of invasive aspergillosis up until March 2002 when he died of acute pancreatitis related to a drug interaction of didanosine and tenofovir.

Pyrrole carboxamidine tryptase inhibitors from Leptonychia pubescens.

The root and stem bark extracts of a Nigerian sample of Leptonychia pubescens Keay (Sterculiaceae) were found to inhibit the serine protease tryptase, a potential therapeutic target for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Bioassay-guided isolation led to the identification of 1-beta-ribofuranosylbrunfelsamidine as the active component with a tryptase IC (50) of 3 microM. Brunfelsamidine was also isolated, but was only weakly active.

NMR spectral assignments of three aspidofractinine alkaloids, kopsine, fruticosine and fruticosamine.

1D and 2D NMR techniques were used to assign fully the spectra of three aspidofractinine alkaloids, kopsine (1), fruticosamine (2) and fruticosine (3), isolated from a cultivated specimen of the plant Kopsia fruticosa (Apocynaceae). The assignment of the NMR data for 1, 2 and 3 will help in the future assignments of related alkaloids.

Inhibition of the human chemokine receptor CCR5 by variecolin and variecolol and isolation of four new variecolin analogues, emericolins A-D, from Emericella aurantiobrunnea.

An extract from the fungus Emericella aurantiobrunnea was found to compete with macrophage inflammatory protein (MIP)-1alpha for binding to human CCR5 in a scintillation proximity assay (SPA). Bioassay-guided fractionation led to the isolation of variecolin (1) and variecolol (2), which had IC50 values of 9 and 32 microM, respectively. An X-ray crystal structure of variecolin (1) was obtained for the first time. Also isolated were four new inactive analogues, emericolin A (3), B (4), C (5), and D (6), and the relative stereochemistry of these compounds was determined by NMR methods using ROESY spectra and 1H/1H coupling constants.

Sustained efficacy of nevirapine in combination with two nucleoside analogues in the treatment of HIV-infected patients: a 48-week retrospective multicenter study.

BACKGROUND: Nevirapine, a nonnucleoside analogue, has demonstrated suppression of human immunodeficiency virus (HIV) replication alone and in combination therapy. However, the durable suppression of HIV with nevirapine when used along with other nucleosides in HIV-infected patients who are treated in clinical practice needs further evaluation. PURPOSE: To evaluate the sustained efficacy of nevirapine in combination with two nucleoside analogues in the treatment of HIV-infected patients in routine clinical practice. DESIGN: A multicenter study from January 1997 to December 2000, with follow-up through 48 weeks, was conducted at four different genitourinary medicine clinics in the United Kingdom. Forty-four HIV-infected patients received nevirapine and two nucleoside analogues. Information from case notes regarding age, sex, side effects, viral load, and CD4 lymphocyte counts at baseline, 24 weeks, and 48 weeks was collected and analyzed. Virologic suppression, defined as HIV RNA concentration of less than 400 copies/mL at Weeks 24 and 48, was considered as the main outcome measure. RESULTS: Out of 44 patients, 41 were men with a mean age of 39.3 years (95% CI 36.7-41.8). The baseline viral load was 2.11 x 10(2) to 9.74 x 10(5) copies/mL (median 7.7 x 10(4) and CD4 counts 6 to 605 cells/dL (M = 247; 95% CI 198-295). Of 39 patients who completed 48 weeks of treatment, viral load suppression was attained in 31 patients (79.4%; 95% CI 66.8-92.0) at 24 weeks and in 27 patients (69.2%; 95% CI 54-83) at 48 weeks. The CD4 lymphocyte count increased in 32 (82%) patients (mean 106 cells/dL, 95% CI 73-139, p =.0001, Wilcoxon signed rank test) after 24 weeks and in 33 (84.6%) patients (mean 160 cells/dL, 95% CI 115-204, p =.0001, Wilcoxon signed rank test) after 48 weeks of treatment. Of 20 patients whose baseline viral load was <100000, 16 had viral load suppressed at 24 weeks and 15 at 48 weeks (p =.6, chi-square test). CONCLUSION: A regime of nevirapine with two nucleoside analogues provided durable suppression of plasma viral load in HIV infected patients, with significant improvement in the CD4 cell count.

10-Methoxydihydrofuscin, fuscinarin, and fuscin, novel antagonists of the human CCR5 receptor from Oidiodendron griseum.

Two new compounds, 10-methoxydihydrofuscin (1) and fuscinarin (2), and one known compound, fuscin (3), have been isolated from the soil fungus Oidiodendron griseum. These compounds were found to compete effectively with macrophage inflammatory protein (MIP)-1 alpha for binding to human CCR5, an important anti HIV-1 target that interferes with HIV entry into cells. The structures of these compounds were elucidated by spectroscopic methods.

Ardisiaquinones from Ardisia teysmanniana.

Bioassay-guided fractionation of a CHCl(3) extract from the leaves of Ardisia teysmanniana Scheff. (Myrsinaceae) has led to the isolation of three new alkyldibenzoquinone derivatives that showed inhibitory activity in an in vitro assay for UDP-MurNac synthesis. The structures of ardisiaquinone G, H and I were established using MS and NMR spectroscopic methods.

Cardiovascular effects of aspidofractinine-type alkaloids from Kopsia.

Intravenous injection of the aspidofractinine alkaloid, kopsingine (1, 0.2-10.0 mg/kg) from Kopsia teoi, produced dose-related decreases in the mean arterial blood pressure and heart rate in anesthetized spontaneously hypertensive rats, which were similar to those seen in normotensive controls. Minor modifications in the molecular structure of kopsingine, as in kopsaporine (2, the 12-demethoxy derivative of kopsingine) and 14,15-dihydrokopsingine (4), did not significantly alter the hypotensive responses, whereas a more drastic change in the structure, as in the heptacyclic kopsidine A (3) and the 3-to-17 oxo-bridged compound 5, resulted in an increase in blood pressure. The antihypertensive effects of kopsingine (1) and its congeners (2 and 4) along with the pressor effects produced by the heptacyclic oxo-bridged compounds (5 and 3) could be ascribed to central as well as peripheral actions.

Reversal of multidrug resistance (MDR) by aspidofractinine-type indole alkaloids.

A series of indole alkaloids of the aspidofractinine-type was assessed for their potential in reversing MDR in vincristine-resistant KB cells. Of the compounds tested, kopsiflorine, kopsamine, pleiocarpine, 11-methoxykopsilongine, lahadinine A and N-methoxycarbonyl-11,12-methylenedioxy-delta 16,17-kopsinine were found to show appreciable activity.