In vitro downregulation of growth factors by insulin-like growth factor binding protein-3 in cervical cancer

OBJECTIVES: Our hypothesis is that insulin-like growth factor binding protein 3 (IGF-BP3) would downregulate epidermal growth factor receptor (EGF-R) levels in cervical cancer cell lines, thereby reducing cellular IGF-II and angiogenesis-related vascular endothelial cell growth factor (VEGF). As folate deficiency is a risk factor in cervical cancer, we sought to determine if folic acid treatment might increase IGF-BP3 production, thereby inhibiting malignant cell proliferation. METHODS: We determined the cellular levels of EGF-R, IGF-II, and VEGF in the cervical cancer cell lines HeLa, ME-180 (both positive for human papilloma virus; HPV), and HT-3 (HPV-negative), following their treatment with IGF-BP3. Levels of IGF-BP3 in these cells before and after treatment with folic acid and VEGF were also enumerated, using a computerized semiquantitative immunofluorescent antibody assay. RESULTS: Treatment with IGF-BP3 significantly reduced the levels (mean intensity per pixel) of EGF-R, IGF-II, and VEGF in all three cell lines and IGF-I receptor (IGF-IR) in representative ME-180 cell line. Treatment with antiproliferative folic acid increased IGF-BP3 levels while the proliferative VEGF depleted cellular IGF-BP3 in all the cell lines. CONCLUSIONS: Levels of EGF-R, IGF-II, IGF-IR, and VEGF are significantly reduced following treatment with IGF-BP3 in cervical cancer. We observed increased levels of IGF-BP3 by folic acid, and decreased IGF-BP3 levels by VEGF. Downregulation of EGF-R by IGF-BP3 suggests an IGF-independent action. Folate deficiency is a risk factor in cervical cancer. Our results suggest that folic acid supplementation can lead to inhibition of cervical cancer cell growth by promoting increased IGF-BP3 levels.     

Local and systemic effects of intralaryngeal injection of cidofovir in a canine model

OBJECTIVE: The safety of intralaryngeal injection of cidofovir remains a concern. Our goal was to evaluate local and systemic effects of intralaryngeal injection of cidofovir. STUDY DESIGN: Animal study using a canine model. METHODS: Two groups of three young beagle dogs (6 vocal folds in each group) were used. Subepithelial vocal fold injections were performed in each group biweekly for 6 months with 0, 2.5, 5, 10, 20, and 37.5 mg cidofovir in a 0.5 mL volume. Direct laryngoscopy was performed at each injection interval. Complete blood cell count and renal parameters were measured at baseline and monthly thereafter. Histopathologic examination of the vocal folds was performed after the 6-month injection period in one group of animals and after an additional 6-month observation period in the second group. RESULTS: Endomysial edema with muscle fiber separation and dose-dependent atrophy and scarring of the vocal folds was present. Onset of atrophy and scarring was observed after 3, 7, and 11 injections in the vocal folds injected with 37.5, 20, and 10 mg cidofovir, respectively. After the 6-month observation period, recovery of histologic abnormalities was complete in the low-dose (0, 2.5 mg) vocal folds, near complete in the intermediate-dose (5, 10 mg) vocal folds, and no apparent recovery was seen in the high-dose (20, 37.5 mg) vocal folds. Leukocyte count and renal parameters remained unchanged at up to 4.26 mg/kg body weight of systemic dose of cidofovir. CONCLUSIONS: Intralaryngeal cidofovir leads to dose-dependent scarification of the vocal folds that appears irreversible at higher doses. Lower concentrations of this drug should be used in intralesional intralaryngeal use.     

Congenital fibrolipoma of anal canal

Although rare, congenital lipomatosis presents during first few months of life as large sub-cutaneous fatty masses on chest with extension into skeletal muscle bundles. Only a few such cases have been reported in the literature. A rare case of congenital fibrolipoma of anal canal in a 3-day-old male child is being documented in the present report.     

Expression of cyclooxygenase-2 in cervical,endometrial, and ovarian malignancies

OBJECTIVE: This study was undertaken to compare the presence of cyclooxygenase-2 (COX-2) levels between normal and malignant cervix, endometrium, and ovary. STUDY DESIGN: Semiquantitative immunofluorescent assays for COX-2 were performed on sections of cervical squamous cell carcinoma (n = 12), endometrial adenocarcinoma (n = 13), and ovarian serous adenocarcinoma (n = 9). Levels of immunofluorescence for each sample were objectively measured, categorized as high, moderate, or negative expression and compared with normal cervical (n = 14), endometrial (n = 15), and ovarian (n = 13) tissue with the Fisher exact test. RESULTS: Normal cervical tissue expressed COX-2 more frequently than cervical cancer (50% vs 23%), but the difference was not significant (P =.247). COX-2 was rarely present in normal endometrium (7%) and normal ovarian epithelium (0%) and was usually present in endometrial adenocarcinoma (69%, P <.001) and ovarian serous cystadenocarcinoma (89%, P <.001). CONCLUSION: In this cohort, COX-2 expression is significantly more common in endometrial adenocarcinoma and ovarian serous cystadenocarcinoma, but not in cervical squamous carcinoma, compared with normal tissue.     

Hypophosphatemic rickets and osteomalacia in polyostotic fibrous dysplasia

A 17 year-old girl with polyostotic fibrous dysplasia and hypophosphatemia had inappropriately low tubular reabsorption of phosphate. She had radiological evidence of rickets and osteomalacia. The patient showed clinical improvement after treatment with phosphate supplementation, active vitamin D (calcitriol) and alendronate. It is postulated that either a phosphaturic substance elaborated from the dysplastic bone or target-organ (kidney) unresponsiveness may interfere with phosphate reabsorption in the renal tubule.     

Hemicraniectomy for large middle cerebral artery territory infarction: outcome in 19 patients

BACKGROUND: Large space-occupying middle cerebral artery infarction accounts for 10-15% of all supratentorial infarctions and carries a mortality of 50% to 80%. Hemicraniectomy may be useful when optimal medical management has failed. METHODS: Between June 1997 and June 2000, 19 patients who fulfilled the clinical and imaging criteria for large middle cerebral artery infarction underwent hemicraniectomy because of impending herniation despite best medical therapy. The National Institute of Health Stroke Scale (NIHSS) assessed neurological status on admission and at one week after surgery. At 3 month follow up, The Barthel Index (BI) and Rankin Scale (RS) were used to assess the functional outcome among survivors. RESULTS: There were 15 males and 4 females with a mean age of 46.5 years (range 27-76 years). Ten patients (53%) had dominant hemisphere stroke. The mean interval between stroke onset and surgery was 60.3 hours (range 20-103 hours). The mean NIHSS score before surgery was 20.5 (range 17-26) and 10.5 (range 6-22) after surgery. One patient (5.2%) died due to post-operative meningitis. At follow up, mean BI was 56.4 (range 25-90) and RS revealed severe handicap in 4 patients (21%). Patients under 50 years of age had a significantly better outcome with mean BI of 60.7 as compared to only 41.3 (p=<0.048) in older patients. Speech function, especially comprehension improved in all patients with dominant hemisphere infarction. CONCLUSION: These findings add to previous studies suggesting hemicraniectomy may be a useful procedure in patients with large middle cerebral artery territory infarction. The functional outcome is good in younger patients. A randomised controlled trial is required to substantiate these findings.     

Clinical,radiological and neurophysiological spectrum of JEV encephalitis and other non-specific encephalitis during post-monsoon period in India

AIMS: To study the spectrum of encephalitis during the post-monsoon period in a tertiary care centre of India. METHODS: Clinical, neurophysiological and radiological features of patients with encephalitis are reported in this communication. The patients were subjected to clinical examination, CT or MRI scan, EEG, motor and somatosensory evoked potentials in both upper and lower limbs bilaterally and concentric needle electromyography. The laboratory studies for Japanese encephalitis (JE) comprised virus isolated, IgM capture ELISA, mercaptoethanol test and hemagglutination inhibition titre in paired sera against JE virus. Patients were classified into JEV encephalitis and non-specific encephalitis. On the basis of radiological features, they were classified into group I (thalamic or basal ganglia involvement), group II (brainstem involvement only) and group III (normal MRI). The outcome was defined into poor (bedridden), partial (dependent for daily activities) and complete (independent) recovery at the end of 3 months. RESULTS: Out of 26 patients (Age 7-70 years, mean 24.8 years), laboratory evidences of JEV infection was present in 14 patients and one patient had herpes simplex encephalitis. The patients with JEV encephalitis had more severe illness as evidenced by lower GCS score, higher frequency of anterior horn cell involvement, movement disorders and more extensive MRI changes. The EEG and MEP changes were also more frequently abnormal in the JEV group. On radiology, 15 patients had thalamic or basal ganglia involvement (group I), 3 isolated midbrain involvement (group II) and 8 had normal MRI (group III). Laboratory evidence consistent with JE were present in 11 out of 12 patients in group I and 3 out of 8 in group III, however, there was no laboratory evidence of JE virus infection in patients with isolated brainstem involvement. There was overlap in the neurologic and systemic manifestations in all the 3 radiological groups as well as in the groups with and without laboratory evidences of JEV infection. CONCLUSION: The observed overlap in neurological and systemic involvement in different subgroups of encephalitis may be due to JE or JE-like viral infection. The possibility of strain variation, change in virulence of organism or immunity of host needs further studies.     

Angiographic and immunologic studies in acute necrotizing jejunoileitis

Eighteen cases of laparotomy-proven acute necrotizing jejunoileitis were treated during the period 1992-1998. Routine laboratory investigations and bacteriological studies were non-contributory towards establishing an etiological basis for the diagnosis. Superior mesenteric artery digital subtraction angiography, carried out in five patients, demonstrated extensive neovascularization. IgG, IgM and IgA were normal in all eight children in whom it was measured; IgE levels were grossly elevated (mean 900 IU/ml; normal range 0-100 IU/ml). Four cases had evidence of hypersensitivity reactions (type I in one patient and type III in three patients) on histopathological examination of the resected small bowel. In addition, histopathological examination also showed the neovascularization observed on angiography. The evidence suggests an immunologically mediated insult resulting in intense vasculitis, which in turn causes ischemic damage to the bowel wall.     

Nasopharyngeal carriage of Haemophilus influenzae

OBJECTIVE: Nasopharyngeal colonization of Haemophilus influenzae (H. influenzae) in young children may be important in developing countries. METHOD: In this study, we screened school going children for carriage of H. influenzae. A total of 44 H. influenzae isolates out of a collection of 162 were characterized for biotypes, capsular serotypes and antibiotic resistance. RESULTS: A significant proportion of H. influenzae (25/44) isolates were serotype b. High antibiotic resistance was observed against commonly administered antibiotics like ampicillin (79%), chloramphenicol (20%), trimethoprim sulfamethoxazole (84%) and erythromycin (95%). Comparison of antibiotic resistance profile of nasopharyngeal isolates was observed to be correlated with those of H. influenzae from disease. CONCLUSION: Multidrug resistant nasopharyngeal H. influenzae in young healthy children may act as reservoir. Monitoring of antibiotic resistance among nasopharyngeal H. influenzae as a surrogate for invasive H. influenzae seems an attractive option.