Long-term follow-up of patients with candiduria

Candiduria is commonly encountered in hospitalized patients, particularly those with indwelling urinary catheters. While risk factors and therapy are well described in previous studies, little is known about long-term outcomes and recurrence rates of candiduria. We studied 188 patients with candiduria in a retrospective chart review at a single institution from January 1999 to December 2000. Data were collected regarding risk factors and underlying disease, therapy, follow-up cultures until December 2003, and mortality. Ninety-one patients with at least one follow-up culture >1 month after the initial culture (range 2–48) were available for further study. In this group, patients receiving antifungal therapy for asymptomatic candiduria were paradoxically more likely to have subsequent positive urine cultures than patients who never received antifungal therapy. Six patients developed candidemia during follow-up, although in none was this considered to represent a consequence of candiduria. Mortality rate at the end of the follow-up period (mean of 18 months) was 43%, including one death attributed to candidemia. Therapy for candiduria does not appear to reduce candiduria recurrence rates through 48 months of follow-up and little evidence of treatment benefit was identified.     

Pharmacokinetics of primaquine in patients withP. Vivax malaria

Summary The pharmacokinetics of primaquine (PQ) and its major carboxylic acid metabolite (PQC) have been studied in seven Indian patients withP. vivax malaria following PQ 15 mg/day p.o. for 14 days. After a single oral dose on Day 1, a mean peak blood concentration of 50.7 ng/ml PQ was attained after 2.3 h, which declined monoexponentially with a half-life of 5.6 h. The mean total body clearance was 37.6 l/h and the volume of distribution was 2921. The mean renal excretion (0–24 h) of the drug was only 0.54% of the dose and renal clearance was 0.189 l/h. Following chronic administration, none of the pharmacokinetic parameters was affected, and a steady state blood concentration of 2.5–4.2 ng/ml PQ was attained. After the first dose of PQ, PQC had a mean area under the blood concentration — time curve 11-fold higher than that of the parent drug. In contrast to the rapid distribution and elimination of PQ, the metabolite showed a longer mean residence time and accumulation in the body. The mean C_max and AUC of the metabolite on Day 14 were 48 and 40% higher than the corresponding Day 1 values. The metabolite could not be detected in urine at any time in any patient. PQ and its metabolite did not show any accumulation in blood cells.Communication No.797 from Hindustan CIBA-GEIGY Limited, Research Centre     

Leprosy teaching in medical colleges in Bombay--a questionnaire study

An attempt was made to study the adequacy of leprosy teaching at the undergraduate level of the four medical colleges in Bombay, and to suggest possible routes towards the reorientation of leprosy teaching. Over 55% of the medical faculty contacted expressed dissatisfaction with the existing pattern of leprosy teaching. The survey reveals ample evidence pointing to the necessity of redesigning the curriculum at the undergraduate level, so as to provide increased weightage to both the theoretical and the practical aspects of leprosy. A heartening feature of the study is the inclination shown by a majority of medical teachers to associate themselves with the PSM Department in order to help improve leprosy teaching and thereby help in leprosy control. This offer should definitely be taken advantage of for furthering the cause of leprosy eradication as a part of achievement of "Health for All by 2000 AD".     

Effect of Tinospora cordifolia on experimental diabetic neuropathy

Objectives:

To evaluate the effect of aqueous extract of stem of Tinospora cordifolia (TC) on hyperalgesia in streptozotocin induced diabetic rats and in- vitro aldose reductase inhibition.

Materials and Methods:

Wistar albino rats, rendered diabetic with streptozotocin, were divided into 5 groups, namely the diabetic control treated with vehicle (DC), standard control which received glibenclamide+metformin (SC), test groups treated with 100, 200and 400 mg/kg b.w. of Tinospora cordifolia (TC1, TC2 and TC3 respectively). A group of five normal animals served as normal control (NC). Fasting blood glucose, body weight and reaction time to tail flick were measured one week after induction of diabetes. The animals were then treated orally for two weeks after which the same parameters were repeated. In-vitro aldose reductase inhibition assay was carried out at concentrations of 5, 10, 25, 50, 100 and 200 mcg/ml of Tinospora cordifolia using rat lens from normal rats. The in-vivo results were analysed with Mann Whitney test.

Results:

The DC group demonstrated a decrease in the reaction time (hyperalgesia) compared to NC while a significant increase in the reaction time was observed with SC, TC2 and TC3 groups (p<0.05) as compared to the DC group. TC1 and TC2 showed a significant reduction in body weight compared to their baseline values (p<0.05). There was no significant change in the fasting blood glucose (FBS) in any of the groups. In-vitro aldose reductase inhibition was observed with TC with an IC₅₀ of 103 mcg/ml.

Conclusions:

Tinospora cordifolia prevents the hyperalgesia in experimental diabetic neuropathy. It has an aldose reductase inhibitory activity in-vitro which may contribute to the beneficial effects.KEY WORDS: Aldose reductase, hyperalgesia, neuropathy, Tinospora cordifolia     

Phaeohyphomycosis

Phaeohyphomycosis is an uncommon infection, but has become increasingly recognized in a wide variety of clinical syndromes. Many species are associated with human infection, though a few are responsible for most cases. Because these are typically soil organisms and common laboratory contaminants, they are often disregarded from clinical specimens as non-pathogenic. The clinical setting in which they are isolated, however, should always be carefully considered before making decisions regarding therapy. Bipolaris and Curvularia are often associated ith allergic disease. Diagnosis depends on a high degree of clinical suspicion and appropriate pathologic and mycologic examination of clinical specimens. Therapy is evolving for many of the clinical syndromes described, and randomized clinical trials are unlikely given the sporadic nature of cases. Case reporting of successful and unsuccessful clinical experiences is important in attempting to better define optimal therapy for the more refractory infections. Itraconazole and voriconazole demonstrate the most consistent in vitro activity against this group of fungi. Itraconazole should be considered the drug of choice for most situations, given the greater clinical experience associated with its use for these infections. Given the lack of comparative clinical data, however, decisions over which azole to use in particular setting are largely empiric. Much additional work is needed to better understand the pathogenic mechanisms underlying phaeohyphomycosis and optimize therapy for these often refractory infections.     

Synthesis and biological evaluation of certain C-4 substituted pyrazolo[3,4-b]pyridine nucleosides

A series of C-4 substituted pyrazolo[3,4-b]pyridine nucleosides have been synthesized and evaluated for their biological activity. Successful synthesis of various C-4 substituted pyrazolo[3,4-b]pyridine nucleosides involves nucleophilic displacement by a suitable nucleophile at the C-4 position of 4-chloro-1H-pyrazolo[3,4-b]pyridine (5), followed by glycosylation of the sodium salt of the C-4 substituted pyrazolo[3,4-b]pyridines with a protected alpha-halopentofuranose. Use of this methodology furnished a simple and direct route to the beta-D-ribofuranosyl, beta-D-arabinofuranosyl, and 2-deoxy-beta-D-erythro-pentofuranosyl nucleosides of C-4 substituted pyrazolo[3,4-b]pyridines, wherein the C-4 substituent was azido, amino, methoxy, chloro, or oxo. The regiospecificity of these glycosylations was determined on the basis of UV data and the anomeric configuration was established by 1H NMR analysis. Conclusive structural assignment was made by a single-crystal X-ray diffraction study of three compounds, 15, 31, and 42, as representatives of ribo-2'-deoxy-, and aranucleosides, respectively. The stereospecific attachment of all three alpha-halogenoses appears to occur by a Walden inversion (SN2 mechanism) at the C-1 carbon of the halogenose by the anionic N-1 of pyrazolo[3,4-b]pyridine. All deprotected nucleosides were tested against various viruses and tumor cells in culture. The effects of these compounds on de novo purine and pyrimidine nucleotide biosynthesis was also evaluated. Among the compounds tested, 4-chloro-1-beta-D-ribofuranosylpyrazolo[3,4-b]pyridine (16) and 1-beta-D-ribofuranosyl-4,7-dihydro-4-oxopyrazolo[3,4-b]pyridine (19) were found to be moderately cytotoxic to L1210 and WI-L2 in culture.