Pathology of fungal infections of the central nervous system: 17 years' experience from Southern India

Aims:  To describe the pathology of central nervous system (CNS) fungal infections with particular reference to India.
Methods and results:  This was a retrospective study from 1988 to 2004 constituting 130 cases. The diagnosis was based on morphology of biopsy/autopsy material. These included aspergillosis ( n  = 73), zygomycosis ( n  = 40), cryptococcosis ( n  = 2), rhodotorulosis ( n  = 1), candidiasis ( n  = 5), maduramycosis ( n  = 1), pheohyphomycosis ( n  = 3) and mixed infections ( n  = 5). Predisposing risk factors were present in 49 (38%) patients only. The majority of the patients were immunocompetent. The commonest risk factor was diabetes mellitus, the commonest route of infection was from a contiguous site and the commonest pathology was granuloma. Culture positivity was seen in only 31%.
Conclusion:  Environmental factors in tropical countries such as India play a significant role in the pathogenesis of CNS fungal infections.     

Pilot randomized controlled trial of interpersonal counseling for subsyndromal depression following miscarriage

OBJECTIVE: Miscarriage, which occurs in 10% to 20% of clinically recognized pregnancies, is associated with an increased risk for subsyndromal depression. We examined whether Interpersonal Counseling (IPC) was superior to treatment as usual (TAU) in reducing subsyndromal depression among miscarrying women and, secondarily, superior to TAU in improving role functioning. METHOD: Nineteen of 20 eligible women participated in a randomized controlled trial of 1 to 6 weekly telephone sessions of IPC versus TAU, which consisted of whatever lay counseling or professional care women sought on their own initiative, from October 2001 to April 2002. The 2 trial arms were compared on mean within-subject change in Hamilton Rating Scale for Depression-17-item (HAM-D-17) scores and in role functioning scale scores (a 5-item modification of the 36-item Medical Outcomes Study questionnaire) from baseline to post-intervention. RESULTS: In the primary intent-to-treat analysis, the baseline mean HAM-D-17 scores were 18.0 (SD +/- 8.4) and 14.8 (SD +/- 6.6) in the IPC (N = 10) and TAU (N = 9) arms, respectively; post-intervention, the corresponding means were 11.6 (SD +/- 8.2) and 12.9 (SD +/- 8.3). The mean within-subject decline in HAM-D-17 scores was significantly greater in the IPC (6.4) than in the TAU (1.9) arm (difference in mean within-subject score decline, adjusted for design features, baseline HAM-D-17 scores and for baseline ethnic imbalance between study arms, 6.2 [95% CI = 0.4 to 12.0]). In a subordinate completers' analysis (N = 15), the corresponding mean decline and difference in adjusted mean decline were 8.0, 2.4, and 6.7 (95% CI = 0.4 to 13.1), respectively. Treatment was unrelated to improved role functioning. CONCLUSION: The efficacy of telephone-administered IPC for subsyndromal depression after miscarriage warrants testing in a full-scale randomized controlled trial.     

Early Infant Formula Feeding Impacts Urinary Metabolite Profile at 3 Months of Age

There is a growing consensus that nutritional programming may persist and influence risk for several chronic diseases in adulthood. In the present study, we used urinary metabolic analysis in assessing diet effects on early-life metabolism. Urine samples from healthy three-month-old infants fed human milk (HM; n = 93), cow’s milk-based infant formula [MF; n = 80], or soy protein-based infant formula (SF; n = 76) were analyzed with an untargeted metabolomics approach using GC-TOF MS. PLS-DA and ANOVA analyses were performed using MetaboAnalyst (v4.0). A total of 150 metabolites differed significantly among the feeding groups, including dietary-specific patterns of urinary metabolites of sugars, sugar alcohols, amino acids, and polyphenols. Urinary metabolites may mirror the infant’s overall metabolism and serve as a noninvasive tool to examine the neonatal effects of diet on early-infant metabolism.     

Alveolar rhabdomyosarcoma of paranasal sinus with cervical metastasis-a case report

Rhabdomyosarcoma (RMS) is a rare tumour in adults and involvement of paranasal sinuses is extremely rare comprising only 1.5% of reported head and neck rhabdomyosarcomas. Alveolar type, a rarer form of RMS, mainly seen in adults, has the worst prognosis. Incidence of lymph node metastases is more common in this type, compared to the other forms. An aggressive combined modality of treatment has dramatically improved the poor survival statistics noted previously. Our experience with one such case occurring in paranasal sinus and orbit which was managed by surgery multidrug chemotherapy & radical radiotherapy is discussed and relevant literature has been reviewed.     

Mutagenic events induced by 4-hydroxyequilin in supF shuttle vector plasmid propagated in human cells

Increased incidence of breast, ovarian and endometrial cancers are observed in women receiving estrogen replacement therapy (ERT). Equilin and equilenin are the major components of the widely prescribed drug used for ERT. These equine estrogens are metabolized primarily to 4-hydroxyequilin (4-OHEQ) and 4-hydroxyequilenin, respectively, which are autoxidized to react with DNA, resulting in the various DNA damages. To explore the mutagenic potential of equine estrogen metabolites, a double-stranded pMY189 shuttle vector carrying a bacteria suppressor tRNA gene, supF, was exposed to 4-OHEQ and transfected into human fibroblast. Plasmids containing mutations in the supF gene were detected with indicator bacteria and mutated colonies obtained were analyzed by automatic DNA sequencing. The proportion of plasmids with the mutated supF gene was increased dose-dependently. The majority of the 4-OHEQ-induced mutations were base substitutions (78%); another 22% were deletions and insertions. Among the base substitutions, 56% were single base substitutions and 19% were multiple base substitutions. The majority (86%) of the 4-OHEQ-induced single base substitutions occurred at the C:G site. C:G --> G:C and C:G --> A:T mutations were detected preferentially with lesser numbers of C:G --> T:A transitions. Sixty-two percent of base substitutions were observed particularly at C:G pairs in (5')-TC/AG-(5') sequences. Using (32)P-post-labeling/gel electrophoresis analysis, 4-OHEN-dC was a major adduct, followed by lesser amounts of 4-OHEN-dA adduct. Mutations observed at C:G pairs may result from 4-OHEN-dC adduct. These results indicated that 4-OHEQ is mutagenic, generating mutations primarily at C:G pairs in (5')-TC/AG-(5') sequences.     

Sinocranial aspergillosis: a form of central nervous system aspergillosis in south India

Of the 21 patients with aspergillosis of central nervous system seen during the years 1990-1997, 16 (76%) had aspergillosis of sino-cranial origin. The occupation in patients with sino-cranial aspergillosis was either agricultural or manual work and predisposing risk factors were present in only two (12.5%) patients. Skull-base syndromes were the presenting features in 13 patients and three patients presented with features of intracranial space-occupying lesion. Paranasal sinus mass lesions were seen in all the 16 patients. Computerized tomography showed intracranial extradural-enhancing mass lesions in the anterior, middle or posterior cranial fossa in nine (68%) patients, intracranial and orbital lesions in four and orbital lesions in three. Well-formed granuloma with dense fibrosis was the histological feature. Survival rates were not good even after surgical and antifungal chemotherapy. Surgical treatment was subradical in our series. The majority of cases of sinocranial aspergillosis are reported from countries with temperate climates and the high incidence in these regions is probably related to constant exposure to the high spore content of pathogenic Aspergillus species in the 'mouldy' work environment.     

Serum nitrate levels as an index of endothelial function in pre-eclamsia and normal pregnancy

The study was conducted in St. John's Medical College Hospital and Department of Physiology, with the aim of studying the serum nitrate levels in pre-eclampsia and normal pregnancy. The total number of subjects studied in various groups were 159, control (n = 55), first trimester (n = 13), second trimester normal (n = 42), second trimester pre-eclampsia/PET (n = 5), third trimester normal (n = 32), third trimester pre-eclampsia/PET (n = 12). The serum nitrate was measured by one step enzymatic assay using Nitrate reductase from Aspergillus species. The nitrate levels in the third trimester pre-eclamptic group was found to be significant lower (P = 0.02), as compared to normal subjects, however the renal functions were normal in all the subjects.