The meddling microbes midst our medicines

It is not surprising that the complex metabolic machinery of the gut microbiome has accidental, or directed, ability to alter our medicines and influence their efficacy. What is not known is the extent to which this has contributed to drug failures or contraindications, or to the derailment of clinical trials. Some studies are unraveling the mechanisms by which the microbiota alter specific drugs, such as digoxin, and contribute to variations in efficacies between patient populations. Microbiome profiling, therefore, may well become an inevitable arm of all clinical trials in the future.     

Thrombophilic conditions in non-cirrhotic portal vein thrombosis.

OBJECTIVE: To study the prevalence of thrombophilic conditions in patients with acute and chronic portal vein thrombosis (PVT) and to compare it with those in patients suffering from deep vein thrombosis (DVT) after lower limb arthroplasty and in healthy subjects. METHODS: Twenty-six patients with spontaneous PVT (20 chronic, 6 acute) with normal liver function and not receiving anticoagulants were evaluated for thrombophilic conditions. Levels of protein C, protein S and antithrombin were compared with those in 50 healthy controls. Factor V gene 'Leiden' mutation (FVL) and high homocysteine levels were looked for in patients with PVT and in 18 patients developing post-arthroplasty lower limb DVT despite anticoagulation. RESULTS: Of 26 patients with PVT, 19 had at least one thrombotic condition (acute PVT 5/6, chronic PVT 14/20) and 12 had more than one such condition; in comparison, of 18 patients with DVT, eight had one thrombophilic condition and one had two such conditions (p=0.03). Patients with PVT had significantly lower levels of protein C, protein S and antithrombin than healthy subjects and those with DVT. Six patients had Factor VIII levels above 150%; four had elevated homocysteine levels and three had detectable anti-cardiolipin antibodies. Three patients with PVT (acute 2, chronic 1) were heterozygous for FVL mutation. CONCLUSIONS: Underlying thrombophilic conditions are common in Indian patients with spontaneous PVT. In many patients, multiple thrombophilic conditions are present and these may play a role in the pathogenesis of PVT.     

Japanese Encephalitis Outbreak, India, 2005

An outbreak of viral encephalitis occurred in Gorakhpur, India, from July through November 2005. The etiologic agent was confirmed to be Japanese encephalitis virus by analyzing 326 acute-phase clinical specimens for virus-specific antibodies and viral RNA and by virus isolation. Phylogenetic analysis showed that these isolates belonged to genogroup 3.     

Serum concentration and urinary excretion of ethambutol administered alone and in combination with isoniazid in patients of pulmonary tuberculosis

Ethambutol (20 mg/kg) was administered orally to 10 patients of pulmonary tuberculosis for seven consecutive days at 8 a.m. after over night fast. On 7th day serum levels were measured at 2, 4, 6, 8 and 24 hr intervals and urinary excretion was estimated at 2, 4, 6 and 24 hr following ethambutol administration. Simultaneous administration of isoniazid (300 mg, orally) for next seven days to the same patients significantly raised the serum levels of ethambutol at 4, 6 and 8 hr and the cumulative per cent dose excreted was decreased significantly at 4, 6 and 24 hr. The serum levels and urinary elimination was not significantly different at 2 hr.