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Biomedical subjects

V Joshi

Publications and source records attributed to V Joshi.

At least 37 records · Page 2Linked to original sources

Radionuclide development at BNL for nuclear medicine therapy.

Radionuclides with medium energy beta emission and a several day half-life have often been viewed as attractive candidates for radioimmunotherapy. Among the most promising in this category are 47Sc, 67Cu, 153Sm, 188Re, and 199Au. The production of 67Cu, 153Sm, 199Au at BNL is summarized and the development of the latest candidate for this application, 47Sc, is described in detail. We also summarize the development of another important therapeutic radionuclide, 117mSn for bone pain palliation.

Copper Radioisotopes↗

Radiochemical purification of no-carrier-added scandium-47 for radioimmunotherapy.

A procedure, adaptable to large-scale remote operation, was developed to purify no-carrier-added (NCA) 47Sc from irradiated Ti targets. Methods based on extraction chromatography and cation-exchange chromatography were compared. Results of this comparison led to the development of an optimized procedure based on cation-exchange with Dowex AG 50W-X4 and 47Sc elution with HCl/HF. This method gave 90-97% overall 47Sc recovery, with a Ti separation factor greater than 2.4 x 10(-5), and specific activities > or = 0.9 GBq microgram-1. Use of the 47Sc product, for labeling monoclonal antibodies, resulted in consistent labeling yields of > or = 90%.

Chromatography, Ion Exchange↗

Immunohistochemical detection of Listeria antigens in the placenta in perinatal listeriosis.

Listeria monocytogenes, a worldwide pathogen, causes significant perinatal mortality and morbidity and has been implicated in spontaneous abortions, still-births, premature delivery, and neonatal sepsis, often with meningitis. Maternal symptoms are frequently minimal, and diagnosis is made only if the suspicion is high and diagnostic maternal blood or amniotic fluid cultures are performed. Because cultures are not routinely performed on spontaneously aborted fetuses, many authors feel that the true incidence of the disease may be underestimated. To date, the absence of a test to retrospectively diagnose Listeria infection has contributed to the lack of accurate estimates of the incidence of the disease. Seven cases in which immunohistochemical stains were used to confirm the diagnosis of placental listeriosis are described. All placentas showed the characteristic lesions with severe chorioamnionitis, numerous microabscesses, and focal necrotizing villitis. Immunohistochemical localization of Listeria antigen was made to the amnion (focally in areas with no inflammatory infiltrate), the abscesses, and the areas with villitis. In general, the antigen was extracellular and intracellular, predominantly within macrophages or the amnion epithelium. Listeria antigen was often found where definite identification of the organism was not possible on Brown-Hopps or Warthin-Starry stains. The immunohistochemical technique may therefore show an increase in sensitivity of detection of L monocytogenes compared with routine bacterial stains. Moreover, the ability to retrospectively evaluate placental specimens for evidence of this organism should permit the true incidence of perinatal listeriosis to be determined.

Adult↗

Indoor air quality and acute lower respiratory infection in Indian urban slums.

The present prospective study was conducted at two urban slums of Delhi, Kusumpur Pahari and Kathputly Colony, in the peak winter season from November 1994 through February 1995. We studied 642 infants to determine the incidence of acute lower respiratory infection (ALRI) and its relationship to indoor air pollution due to fuel used for cooking (wood or kerosene). In Kusumpur Pahari, there were 317 children (142 wood and 175 kerosene), including 64 controls and 78 cases of ALRI in the wood fuel group and 81 controls and 94 ALRI cases in the kerosene group (p > 0.05). Out of 316 children in Kathputly Colony (174 wood and 142 kerosene), there were 33 and 45 ALRI cases in the wood and kerosene groups, respectively (p < 0.05). Controls were children without ALRI and were used as controls in different groups. The demographic data and risk factors, namely, nutritional and immunization status, were comparable in ALRI cases and controls in both study areas. Pneumonia was the most common ailment in all the groups. Bronchiolitis was reported in 22.5% of the wood group and 27.1% of the kerosene group in Kathputly Colony versus 13.7% in the wood group and 12.1% in the kerosene group in Kusumpur Colony. Only one case of croup was reported from Kusumpur Pahari among wood users. The duration of illness was longer in the Kusumpur Pahari due to poor compliance, feeding, and child rearing habits. In conclusion, a higher incidence of ALRI was reported in kerosene users in Kathputly Colony, a high pollution area; however, the reasons for the differences observed need further elucidation.

Acute Disease↗

Genetic staging of unresectable or metastatic neuroblastoma in infants: a Pediatric Oncology Group study.

BACKGROUND: Current staging systems for unresectable or metastatic neuroblastoma do not reliably predict responses to chemotherapy in infants under 1 year of age. Previous studies have indicated that the DNA content, or ploidy, of malignant neuroblasts can discriminate between good and poor responders in this group of patients, but the clinical utility of ploidy assessment has remained in question. PURPOSE: We tested, in a prospective nonrandomized study, the hypothesis that neuroblast ploidy could be used as the sole guide for treatment selection in infants with unresectable or metastatic tumors and could differentiate between those who would respond to our previous standard regimen and those who would benefit from an immediate switch to another therapy. METHODS: One hundred seventy-seven infants were enrolled in this trial. Five of these infants were subsequently excluded (two ineligible, two lacking ploidy information, and one protocol violation); therefore, 172 patients were included in the study. One hundred thirty infants with hyperdiploid tumors (DNA index > 1.0; better prognosis in retrospective studies) were treated with a well-tolerated regimen of cyclophosphamide (150 mg/m2 per day orally or intravenously on days 1-7) and doxorubicin (35 mg/m2 intravenously on day 8). Forty-two infants with diploid tumors (DNA index = 1.0; worse prognosis in retrospective studies) received cisplatin (90 mg/m2 intravenously on day 1) and teniposide (100 mg/ m2 intravenously on day 3) after an initial course of cyclophosphamide plus doxorubicin. Statistical end points were response and long-term survival. In addition, we assessed within each ploidy group (i.e., patients with hyperdiploid tumors and those with diploid tumors) the prognostic significance of NMYC gene copy number, tumor stage, and other variables commonly measured in this disease. RESULTS: Of the 127 assessable infants with hyperdiploid tumors, 115 (91%) had complete responses--85 after receiving five courses of cyclophosphamide plus doxorubicin and 30 after receiving further therapy including cisplatin plus teniposide. The 3-year survival estimate for the entire hyperdiploid group was 94% (95% confidence interval [CI] = 89%-98%). Nineteen (46%) of 41 assessable infants with diploid tumors were complete responders. The overall 3-year survival estimate for this group was 55% (95% CI = 39%-70%). Prognostic factor analysis indicated that NMYC gene amplification and an elevated serum lactate dehydrogenase level were statistically significant markers of higher risk disease within the diploid group (two-sided P values of .005 and .003, respectively). Only NMYC was predictive in the hyperdiploid group (P = .003). CONCLUSION: Use of a prognostic staging system based on tumor cell ploidy, augmented with the NMYC gene copy number and serum level of lactate dehydrogenase, would very likely improve the treatment of infants with unresectable or metastatic neuroblastoma. Patients with diploid tumors characterized by an amplified NMYC locus represent a particularly unfavorable risk group that may benefit from innovative new therapies.

Antibiotics, Antineoplastic↗

Inhibition of parietal cell acid secretion is mediated by the classical epidermal growth factor receptor.

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) inhibit gastric acid secretion both in vivo and in vitro. Previous studies have indicated that EGF and TGF-alpha bind to the same EGF/TGF-alpha receptor. Nevertheless, we and others have previously demonstrated that inhibition of acid secretion by these growth factors requires concentrations of the peptides that are 10-fold higher than those necessary for induction of mitogenesis. Therefore, we have sought to investigate whether gastric parietal cells may possess a second EGF/TGF-alpha receptor class. Two systems were studied: First, [125I]TGF-alpha was cross-linked to the receptor in isolated rabbit parietal cell membranes, and labeled species were resolved on SDS-PAGE. Second, acid secretion was evaluated in pylorus-ligated waved-2 mutant mice, which carry a disabling point mutation in their classical EGF/TGF-alpha receptor. In isolated parietal cells, [125I]TGF-alpha was cross-linked into a single species of 170 kDa. Cross-linking was inhibited in the presence of unlabeled TGF-alpha with an IC50 of 80 nM. In the pylorus-ligated mice, control littermate mice demonstrated a dose-dependent inhibition of acid secretion by EGF with an IC50 of 20 micrograms/kg. In contrast, EGF had no inhibitory effect on acid secretion in waved-2 mice at concentrations up to 100 micrograms/kg. No alterations in parietal cell or gastrin cell numbers were observed. These results in both isolated rabbit parietal cells and waved-2 mice support the existence of only a single class of EGF/TGF-alpha receptors in parietal cells. Differences in growth factor affinity are likely due to the modification of the receptor or one of its coordinate regulators.

Animals↗

Haemophilus influenzae type b vaccine in India: need and timing, immunogenecity and tolerance.

OBJECTIVE: (i) To assess the natural immunity and susceptibility to Haemophilus influenzae type b (Hib) infections in children in India. (ii) To study the immunogenecity and tolerance of Hib vaccine (ACTHIB) in young infants. DESIGNS: (i) Cross sectional study. (ii) Prospective trial. SETTING: Well baby and immunization clinics. METHODS: (i) PRP antibody titers against Hib estimated in 172 healthy infants and children aged 1 month to 10 years. (ii) Antibody titres estimated before and after ACTHIB vaccine given with primary immunization (age group 6 to 8 weeks) in 50 babies. RESULTS: (i) Naturally protective levels of Hib antibodies found in less than 20% of infants under one year, but in over 80% above 4 years. (ii) Seroconversion after ACTHIB vaccination was 100% with very high protective levels. There were no significant adverse reactions. CONCLUSIONS: ACTHIB vaccine proved to be safe and highly immunogenic. As susceptibility to Hib is highest in the first year of life, the vaccine should be recommended in the primary immunization schedule (combined with DPT). The very high titers achieved suggest the possibility of decreasing the number of doses or the amount of antigen to reduce the prevalent high cost.

Child↗

Repair of an unusual type of total anomalous pulmonary venous connection.

A 9-day-old, 4.5-kg female infant was diagnosed with total anomalous pulmonary venous connections by echocardiography. The unusual nature of the pulmonary veins and their connections led to cardiac catheterization and angiography. Angiography demonstrated the left-sided veins connected, via a retropulmonary artery vertical vein, to the left inominate vein whereas the right-sided pulmonary veins connected to the right superior vena cava. We repaired this lesion uneventfully by creating a neo-common pulmonary vein and anastomosing this confluence to the left atrium.

Cardiac Catheterization↗

Intestinal distribution of human Na+/H+ exchanger isoforms NHE-1, NHE-2, and NHE-3 mRNA.

The identity of Na+/H+ exchanger (NHE) isoforms in the human small intestine and colon and their role in vectorial Na+ absorption are not known. The present studies were undertaken to examine the regional and vertical axis distribution of NHE-1, NHE-2, and NHE-3 mRNA in the human intestine. Ribonuclease protection assays were used to quantitate the levels of mRNA of these isoforms in various regions of the human intestine. In situ hybridization technique was used to localize NHE-2 and NHE-3 mRNA in the colon. The NHE-1 isoform message was present uniformly throughout the length of the human intestine. In contrast, mRNA levels for human NHE-2 and NHE-3 isoforms demonstrated significant regional differences. The NHE-3 abundance was found in decreasing order: ileum > jejunum > proximal colon = distal colon. The NHE-2 message level in the distal colon was significantly higher than in the proximal colon but was evenly distributed in the small intestine. In addition, NHE-2 mRNA was present in surface epithelial cells as well as in cells of the crypt region, suggesting the presence of NHE-2 message throughout the vertical axis of the colonic crypts. In contrast, NHE-3 mRNA was localized to surface colonocytes in the proximal colon. On the basis of this tissue-specific localization of NHE-2 and NHE-3 mRNA, it can be speculated that the relative contribution of NHE-2 and NHE-3 isoforms in Na+ absorption in the human intestine may be region specific, and these putative apical isoforms may be differentially regulated.

Amino Acid Sequence↗

Entomological studies in a dengue endemic area, Jalore, Rajasthan.

Entomological studies on prevalence of adult and immatures of Aedes aegypti along with associated ecological factors have been conducted in a dengue endemic area of Jalore, Rajasthan from 1992 to 1993. Studies in two areas; reportedly affected and unaffected revealed more adults and higher breeding indices in the affected area as compared to the unaffected one. Mosquitoes harbouring dengue antigen were found only in the affected locality. Presence of dengue antigen in field caught mosquitoes in the affected locality was observed mainly during the months of January to April in both the years. Statistical analysis of data has shown a correlation to be significant between adult house index and breeding index in the affected area while this association was found insignificant in the unaffected locality. Water storage practices of the population due to irregular water supply in the affected area is the possible cause for a higher vector concentration in the locality. Seasonality of occurrence of dengue fever patients in a particular period of the year is associated with a relatively higher vector density and the presence of infected mosquitoes which is due to favourable temperature, relative humidity, water temperature and pH.

Aedes↗

Unusual acute and chronic complications of malaria.

32 cases (21 acute severe malaria and 11 chronic malaria syndrome), who developed unusual complications and/or manifestations are reported. The acute manifestations were unexplained tachypnoea 4, pulmonary oedema 5 and shock due to multiple organ dysfunction syndrome 3, melena 2 and E coli septicaemia in one. The other features were concomitant salmonellosis 2, meningitis 1, renal failure 3, hepatorenal syndrome 2, hepatitis like illness 7, neck stiffness with normal CSF 3, urticaria and subconiunctival haemorrhage 2 each, apyrexial spell with anaemia 4, thromocytopenia 3, and hypoglycaemia 3 (two pretreatment and one while on quinine in 5% glucose drip). The chronic syndrome noted were hyperreactive malaria syndrome (Tropical splenomegaly) 3, repeated haemolysis 2, chronic simple malaria with positive parasitaemia and normal Igm levels 4, and cerebellar ataxia with tremors 3. Bone marrow in these cases was hypercullular with increase plasma cells. Liver biopsy revealed lymphocytic infiltration. There was no case with permanent neurogical deficit. All patients with pulmonary oedema and multiple organ dysfunction died but chronic syndrome patients recovered fully. Early recoginition of atypical manifestation and prompt treatment will decrease the mortality and morbidity due to malaria.

Acute Disease↗

Cytogenetic and flow cytometric analysis of a pancreatoblastoma.

A pancreatoblastoma from a 4-year old male was examined by flow cytometric ploidy analysis and cytogenetics. To detect differences within the tumor, the specimen was divided into four portions and sampled separately. Flow analysis revealed that each sample contained a diploid and a tetraploid population of tumor cells. These findings correlated well with the cytogenetic analysis, which also revealed differences in structural rearrangements between samples. A t(13;22)(q10;q10) was the only rearrangement found in near-diploid cells as well as one near-tetraploid line. Other common structural changes in near-tetraploid cells included t(13;13)(q10;q10), i(6p)(p10), and del(1). Chromosomes 1, 6, 13, and 22 were consistently missing from all near-tetraploid cells lines. To our knowledge, this is the first flow cytometric and cytogenetic study of a pancreatoblastoma.

Child, Preschool↗

Phase II investigational window using carboplatin, iproplatin, ifosfamide, and epirubicin in children with untreated disseminated neuroblastoma: a Pediatric Oncology Group study.

PURPOSE: Children less than 1 year of age with metastatic neuroblastoma NB are at high risk of death. The need to identify new and effective chemotherapy agents is clear. A study was conducted by the Pediatric Oncology Group (POG) to determine the efficacy and safety of administering two courses of a single phase II agent before conventional treatment as a means to evaluate new agents in this setting. PATIENTS AND METHODS: One hundred seventy-three eligible patients more than 1 year of age with disseminated neuroblastoma received two courses of one of the following: ifosfamide (IFOS) 2 g/m2/d for 4 days intravenously (IV) plus mesna; carboplatin (CARB) 560 mg/m2 i.v. over 1 hour; iproplatin (CHIP) 325 mg/m2 IV over 2 hours; or epirubicin (EPIR) 90 mg/m2 i.v. push. Following evaluation for response and toxicity, eligible patients were randomized to receive either cisplatin 90 mg/m2 i.v. on day 1, etoposide 200 mg/m2 i.v. on day 3, cyclophosphamide 150 mg/m2/d orally on days 7 to 13, doxorubicin 35 mg/m2 i.v. on day 14 (CECA), or cisplatin 40 mg/m2 IV on days 1 to 5 and etoposide 200 mg/m2 i.v. on days 2 to 4 alternating at 3-week intervals with cyclophosphamide 150 mg/m2/d orally on days 1 to 7 and doxorubicin 35 mg/m2 IV on day 8 (HDP/VP/CA). An additional 86 patients were randomized to receive either CECA or HDP/VP/CA without initial phase II therapy. RESULTS: After phase II therapy, only 20% of patients experienced grade 3/4 hematopoietic toxicity. No toxic deaths occurred. Objective response rates (partial responses [PRs] plus minor responses [MRs]) following IFOS, CARB, CHIP, and EPIR were 70%, 77%, 67%, and 26%, respectively. Following phase III treatment, there was no statistically significant difference in rates of complete response (CR)/PR or progressive disease (PD), or in time to PD of patients who participated in the phase II window versus those who received only CECA or HDP/VP/CA. CONCLUSION: IFOS, CARB, and CHIP are efficacious in neuroblastoma, are well tolerated, and should be incorporated into primary treatment regimens. Combination regimens using these agents may be possible, since most repeat courses were given within 2 weeks. Administering phase II therapy to untreated patients with high-risk tumors provides a unique and sensitive method to assess new agents without compromising patient outcome.

Adolescent↗

Familial glioma.

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Astrocytoma↗

Ranitidine for the prevention of complications following endoscopic sclerotherapy for esophageal varices.

Thirty one patients with significant esophageal variceal bleed were allocated alternately to receive endoscopic sclerotherapy along with ranitidine 300 mg daily or endoscopic sclerotherapy alone till eradication of varices. The mean sclerotherapy sessions, time and volume of sclerosant required for obliteration of varices were similar for the two groups. The esophageal varices were eradicated in all the patients except three in sclerotherapy alone group. There was statistically significant reduction in frequency of post sclerotherapy mucosal ulcers (P < 0.05) after addition of ranitidine to sclerotherapy. Rebleeding was not only significantly reduced (P < 0.05) in the sclerotherapy with ranitidine group but was minor and did not even require blood transfusion. In sclerotherapy alone group rebleeding was controlled by surgery in two patients and one died due to massive bleeding. The results of this study suggest a beneficial role of ranitidine in reducing post sclerotherapy mucosal ulcers and rebleeding. This effect of ranitidine emphasises the role of acid-pepsin in pathogenesis of these ulcers and its associated morbidity.

Adult↗

Serum lactate dehydrogenase in childhood neuroblastoma. A Pediatric Oncology Group recursive partitioning study.

On the basis of an extensive recursive partitioning analysis of 668 patients with newly diagnosed neuroblastoma registered on Pediatric Oncology Group (POG) studies between October 1981 and May 1987, four major subsets of patients were created. Important prognostic factors included the patient's stage of disease, age, and level of serum lactate dehydrogenase (LDH). After adjusting for these factors, no other clinical prognostic factors were significant. The implications for protocol design are that (a) fine tuning of current therapy should be sought for the two favorable disease patient subsets, while (b) novel aggressive therapies are needed for the two unfavorable disease patient subsets where the overwhelming majority are dying. This article may serve as a model for others investigating prognostic factors. The data were divided into two subsets: one was used for an exploratory analysis; the other was used to confirm the exploratory findings. Despite spite the large number of statistical tests performed, the likelihood that the findings can be attributed to chance can be dismissed as virtually zero.

Adolescent↗