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Biomedical subjects

S Rao

Publications and source records attributed to S Rao.

At least 181 records · Page 10Linked to original sources
PubMed1998

Botulinum toxin injections for voiding dysfunction following SCI.

Botulinum toxin (BT) injections have been used successfully to treat spastic muscle conditions, including detrusor-sphincter dyssynergia (DSD) seen in spinal cord injury (SCI) patients. In our urology clinic, we used BT to treat three SCI patients who had voiding dysfunction, using a transperineal needle with electromyographic (EMG) monitoring. Two of the patients reported excellent results following the treatment. One patient, with whom the staff had difficulty doing intermittent catheterization (IC), improved significantly. The other patient had improved voiding with an external catheter and minimal urinary residual. The third patient had no improvement of leg spasms with his voiding dysfunction and required a sphincterotomy. Although patients may need repeat injections, BT is minimally invasive and easy to administer with no side effects. Overall, BT injection is an excellent method of managing voiding in SCI patients, especially those on continuous external catheters and with IC management who refuse or are not good candidates for surgery.

Adult↗
PubMed1998

The Arabidopsis abscisic acid response locus ABI4 encodes an APETALA 2 domain protein.

Arabidopsis abscisic acid (ABA)-insensitive abi4 mutants have pleiotropic defects in seed development, including decreased sensitivity to ABA inhibition of germination and altered seed-specific gene expression. This phenotype is consistent with a role for ABI4 in regulating seed responses to ABA and/or seed-specific signals. We isolated the ABI4 gene by positional cloning and confirmed its identity by complementation analysis. The predicted protein product shows homology to a plant-specific family of transcriptional regulators characterized by a conserved DNA binding domain, the APETALA 2 domain. The single mutant allele identified has a single base pair deletion, resulting in a frameshift that should disrupt the C-terminal half of the protein but leave the presumed DNA binding domain intact. Expression analyses showed that despite the seed-specific nature of the mutant phenotype, ABI4 expression is not seed specific.

Abscisic Acid↗
PubMed1998

Controlled comparative evaluation of BacT/Alert FAN and ESP 80A aerobic media as means for detecting bacteremia and fungemia.

During a one-year period, a total of 6,305 blood cultures were processed in a tertiary-care teaching hospital; 6 to 12 ml of blood was inoculated into both a BacT/Alert Fan aerobic bottle and an ESP 80A aerobic bottle. The FAN aerobic bottle contains an antimicrobial-absorbing material; the 80A aerobic bottle does not. Bottles were processed on their respective continuous-monitoring blood culture instruments for up to five days of incubation. Four hundred thirty-three cultures (6.9%) representing 301 septic episodes in 235 different patients yielded 490 bacteria or yeasts thought to be clinically significant. Two hundred seventy-five of the 433 presumed clinically significant positive cultures (63.5%) representing 195 septic episodes and yielding 301 isolates were positive in both FAN and 80A bottles. One hundred nine significant positive cultures (25.2%) (i.e., cultures positive with an organism judged to be of probable clinical significance) from 70 septic episodes yielded 126 isolates only in FAN bottles. Conversely, the 80A bottle was exclusively positive in 49 instances (11.3%), representing 36 septic episodes and yielding 63 isolates. The higher rates of significant positive blood cultures, numbers of septic episodes documented, and numbers of isolates recovered in FAN bottles versus 80A bottles were all statistically significant (P < 0.05). Enhanced rates of detection of presumed clinically significant isolates in FAN bottles were largely accounted for by Staphylococcus aureus, members of the Enterobacteriaceae, and non-Pseudomonas aeruginosa miscellaneous gram-negative bacilli from patients receiving antimicrobial therapy at the time blood cultures were obtained. Enhanced recovery of one organism group, the beta-hemolytic streptococci, occurred in 80A. With one exception, detection times were essentially equivalent in the two systems. The single exception pertained to streptococci and enterococci, which were recovered significantly faster in 80A bottles. Three hundred thirty-eight of the 6,305 blood cultures evaluated in this study (5.4%) were judged likely to be contaminated. The percentages of probable contaminated cultures were as follows: 26.6% FAN and 80A; 42.3% FAN only; 31.1% 80A only (P < 0.05). Finally, the instrument false-positive rates for the two systems were 0.7% with FAN and 3.0% with 80A (P < 0.05). We conclude that while contamination rates were slightly higher with FAN than with 80A, use of FAN aerobic bottles in conjunction with the BacT/Alert system will yield significantly higher numbers of clinically significant blood culture isolates than 80A bottles and the ESP system. Furthermore, this enhanced detection is most conspicuous in patients receiving antimicrobial therapy at the time blood cultures are performed, probably due to the presence of an antimicrobial-absorbing material in FAN aerobic bottles.

Bacteremia↗
PubMed1998

Height velocity, body fat and menarcheal age of Indian girls.

OBJECTIVE: To understand the onset of menarche in relation to changes in physical measurements that take place during adolescence, especially the changes in height velocity and changes in body fat. DESIGN: Adolescent girls in the 9-16 year age group were observed longitudinally every six months for a period of two years. SETTING: Girls from schools catering to urban high socio-economic class (HSE, n = 135) and those catering to low socio-economic class (LSE, n = 398) were evaluated. METHODS: Six monthly measurements of weight, height and triceps skinfold thickness (TSFT) were done. Menarcheal age was recorded by recall method for the girls who were menstruating at the beginning of the study and prospectively for girls whose onset was after the initiation of the study. Body fat (%) was estimated using weight, height and TSFT. RESULTS: The girls from LSE not only had lower attained weight, height, skinfold thickness at triceps and body fat but also had a significant difference (p < 0.05) in menarcheal age (15.4 yr) as compared to girls from HSE (12.1 yr). Although social class differences delayed the occurrence of the event by chronological age, the time between peak height velocity (PHV) and onset of menarche remained similar (1.5 yr) irrespective of social class. The mean weight at menarche, at group level (but not at individual level), was around 38 kg in both socio-economic classes, irrespective of age at onset. Further menarche represented the point of maximum deceleration in height velocity and maximum acceleration in body fat in both social classes. CONCLUSION: Our data indicated a partial support for critical weight hypothesis and suggested that these limits vary from community to community. The analysis revealed that rather than absolute values of weight, height and body fat, changes in these measurements are of significance with regard to onset of menarche.

Adipose Tissue↗
PubMed1998

Repetitive bone marrow transplantation in nonmyeloablated recipients.

Transplantation of 200 million male BALB/c marrow cells into normal nonmyeloablated female BALB/c hosts results in relatively high levels of engraftment, whether the cells are infused repetitively over time or in a single infusion. These high engraftment rates suggested that repetitive injections of high levels of male BALB/c cells might be able to totally replace host marrow. Accordingly, we transplanted 40x10(6) male BALB/c bone marrow cells into female BALB/c recipients over a 7-week period for a total of 20 injections (800x10[6] marrow cells). Engraftment in this experimental group was compared to that seen when female recipients received 2x10(6) male marrow cells or phosphate-buffered saline (PBS) over the same injection schedule. Engraftment was quantitated at 5 and 7 weeks after the final infusion by detection of male-specific sequences in female host marrow, spleen, and thymus by Southern blot analysis using a Y-specific cDNA probe. Male DNA levels were quantitated with a Molecular Dynamics phosphorimager. Engraftment of male cells into female marrow at 5 and 7 weeks posttransplantation ranged from 19 to 88%, whereas that in spleen and thymus ranged between 30 and 100% and 28 and 50%, respectively. The mean percent engraftments for marrow, spleen, and thymus were 41, 69, and 39%, respectively. Mean percent engraftments for 2x10(6) cell infusions at 5 and 7 weeks for marrow, spleen, and thymus were 4, 6, and 4%, respectively. Marrow and spleen cellularity and total high proliferative potential colony-forming cell numbers were determined in PBS- and cell-injected mice. No significant differences between these groups were observed. For marrow engraftment, 20 injections of 40x10(6) cells was not more effective than five, but donor DNA in thymus and spleen was increased with 20 injections. Primitive progenitor cell levels and marrow cellularity do not increase in mice injected with large numbers of marrow cells, suggesting that host marrow cells are replaced rather than augmented by infused donor cells.

Animals↗
PubMed1998

Immunohistochemical analysis of the T-cell receptor beta-chain variable regions expressed by T lymphocytes infiltrating primary human melanoma.

The T-cell receptor beta-chain variable (TCRBV) region repertoire expressed by tumor-infiltrating lymphocytes was characterized by immunohistochemical analysis using a panel of 18 monoclonal antibodies on cryosectioned specimens of 14 primary vertical growth phase (VGP) melanomas with a T-cell infiltrate histopathologically defined as brisk or nonbrisk. T lymphocytes present in the VGP of all patients displayed a restricted T-cell receptor usage, with a pattern of reactivity similar in brisk versus nonbrisk infiltrates. No evidence of restriction was found in the extra-VGP lymphocytic infiltrates, when available, within the same specimen. Furthermore, the repertoire of TCRBV expressed in nodal metastases was similar to that of the corresponding primary melanomas in the two cases tested. The results obtained by this in situ analysis indicate that the TCRBV repertoire in VGP is determined by a preferential migration of T lymphocytes, possibly indicative of an immune response to melanoma-associated antigens.

Adult↗
PubMed1997

RAR alpha1/RAR alpha2-PML mRNA expression in acute promyelocytic leukemia cells: a molecular and laboratory-clinical correlative study.

In addition to the major fusion gene PML-RAR alpha, the t(15; 17) in acute promyelocytic leukemia (APL) produces the reciprocal fusion gene RAR alpha-PML. To determine the scope of RAR alpha-containing mRNA expression in APL cells, we tested PML-RAR alpha-positive APL cells for the presence of mRNAs initiated from two distinct RAR alpha gene promoters, alpha1 and alpha2. From the normal allele, both RAR alpha1 and RAR alpha2 mRNAs were expressed in all APL cases (N = 24). From the translocated allele, RAR alpha1-PML mRNA was expressed in 77% and RAR alpha2-PML mRNA in 28% of cases (N = 98). RAR alpha2-PML mRNA was not observed in the absence of RAR alpha1-PML mRNA. There was no association between RAR alpha1-PML or RAR alpha2-PML mRNA expression and the type of PML-RAR alpha mRNA formed by either 5' or 3' breaksites in the PML gene. RAR alpha1-PML mRNAs and RAR alpha2-PML mRNAs from 5' PML breaksite cases coded for full-length RAR alpha-PML proteins but RAR alpha2-PML mRNAs from 3' PML breaksite cases encoded a truncated RAR alpha2 peptide. RAR alpha1/alpha2-PML mRNA expression was not associated with differences in APL cell sensitivity to all-trans retinoic acid(tRA)-induced differentiation in vitro or in clinical outcome after tRA or chemotherapy induction therapy (protocol E2491). Our analysis indicated that RAR alpha1/alpha2-PML mRNA expression markedly differs from normal RAR alpha1/alpha2 mRNA expression, that the difference in RAR alpha1-PML and RAR alpha2-PML mRNA expression frequency is primarily related to the genomic separation of the RAR alpha1 and RAR alpha2 coding exons, and that variations in RAR alpha1/alpha2-PML mRNA expression likely have no clinically relevant function in APL cells.

Adolescent↗
PubMed1997

Lovastatin induction of cyclin-dependent kinase inhibitors in human breast cells occurs in a cell cycle-independent fashion.

Cyclin-dependent kinase inhibitors (CKIs) p21, p27, p16, and p15 are an essential and integral part of cell cycle regulation. Studies on the expression of these inhibitors in normal versus tumor human breast cancer cells revealed that although p27 and p16 are expressed at higher levels in tumor cells, p21 and p15 expression were higher in normal cells. Analysis on the expression pattern of these proteins throughout the cell cycle in synchronized cells demonstrated a substantial increase in p21 during the S-phase in normal cells and barely detectable expression of p21 in any phase of the tumor cell cycle. Levels of p15, p16, and p27 remained relatively constant throughout the cell cycle of normal and tumor cells. Synchronization of tumor cells by lovastatin, which arrests cells in G1, resulted in increased levels of p21 and p27 with a concomitant decrease in cyclin-dependent kinase 2-associated kinase activity. Synchronization of cells by double-thymidine block did not result in the induction of p21 or p27. These observations suggest that lovastatin causes a profound cell cycle-independent alteration of CKI expression which is distinct from growth factor deprivation or thymidine block.

Breast↗
PubMed1997

Distinct mdm2/p53 expression patterns in liposarcoma subgroups: implications for different pathogenetic mechanisms.

Recent findings have indicated that TP53 inactivation in sarcomas may result from mutation and/or deletion of the TP53 gene or, alternatively, from binding to the MDM2 gene products. To investigate further a possible role of the two genes in sarcomas, 24 large and deep-seated lipomas and 74 liposarcomas of various subtypes were analysed for mdm2 and p53 overexpression by immunocytochemistry. Nineteen cases of the same series were also molecularly analysed for both MDM2 gene amplification and TP53 mutations, and a further ten cases for non-random chromosomal abnormalities. In the retroperitoneal well-differentiated-dedifferentiated (WD-DD) group, 15/16 WD and 8/8 DD liposarcomas displayed the mdm2+/p53+ phenotype, consistent with MDM2 gene amplification in the absence of TP53 mutations. In the non-retroperitoneal WD-DD group, 5/11 WD liposarcomas also retained the mdm2+/p53+ phenotype whereas all DD liposarcomas showed an immunophenotype and, when assessed, a genotype consistent with mutant TP53. Null mdm2 immunophenotype, coupled with evidence of a specific chromosome translocation t(12;16), was constantly observed in both the usual and the cellular subtypes of myxoid liposarcoma, three cases of which also showed TP53 alterations at the genetic or protein level. Neither mdm2 nor p53 overexpression was observed in the lipomas. The results show the existence of three main pathogenetically distinct groups of liposarcoma. The first retroperitoneal WD-DD group, which represents a novel class of tumours within a single histological category of sarcoma, where MDM2-mediated inactivation of p53 could be related to the pathogenetic mechanism. The second is the non-retroperitoneal WD-DD group, where the TP53 mutations appear to correlate with the dedifferentiation process. The third is the myxoid group, which is characterized by its own unique cytogenetic profile and never shows any involvement of TP53 or MDM2 genes. As for diagnostic significance, the absence of mdm2 and p53 reactivity in lipomas seems to represent a useful marker for differential diagnosis from lipoma-like WD liposarcomas.

Adolescent↗
PubMed1997

Recommendations from the National Multiple Sclerosis Society Clinical Outcomes Assessment Task Force.

This article provides recommendations from the National Multiple Sclerosis Society's Clinical Outcomes Assessment Task Force. The Task Force was appointed in 1994 and charged with recommendending improved approaches for clinical outcomes assessment in future controlled clinical trials. The recommendations herein follow extensive deliberation and data analysis during 2.5 years. General principles and desirable measurement attributes were used to assess alternative measurement techniques and clinical scales. On the basis of the analysis of existing multiple sclerosis (MS) data sets, a new measurement approach is proposed. The approach is based on quantitative functional composites that consist of simple quantitative measures from the major clinical dimensions of MS combined into a single score. Quantitative functional composites are likely to provide improved precision and sensitivity in future MS clinical trials. Studies necessary to further refine quantitative functional composites as useful MS clinical trial outcomes are delineated.

Clinical Trials as Topic↗
PubMed1997

Engraftment of hematopoietic stem cells in nonmyeloablated and myeloablated hosts.

Hematopoietic stem cell engraftment has traditionally been assessed in irradiated murine hosts. More recently, we and others have shown that engraftment is virtually quantitative in host animals who have received no preconditioning myeloablation. It appears that at the stem cell level, engraftment may even be favored in the normal host. The final phenotypic readout in the engrafted animal is then determined by competition between the engrafted stem cells and the number of residual host stem cells. Further studies have indicated that with cytokine exposure in vitro, in vivo or 5-fluorouracil exposure and consequent stimulation of primitive hematopoietic stem cells to enter cell cycle, an engraftment defect relating to long-term engraftment occurs. This occurs in the face of an expansion of cycling surrogate stem cells as mirrored by the high proliferative potential colony-forming cell. These data indicate that the phenotype of the hematopoietic stem cell, as assessed in vitro, may not give insight into the phenotype of these cells in vivo.

Animals↗
PubMed1997

Papillomatosis of the gallbladder in metachromatic leukodystrophy.

A 2-year-old boy who presented with a cystic gallbladder mass was found histologically to have metachromatic leukodystrophy. Diffuse hyperplasia of the gallbladder mucosa, multiple tendrillar fronds extending into the lumen, extensive papillomatosis, and the presence of large numbers of macrophages bearing metachromatic material confirmed the diagnosis. The child developed progressive degeneration of the central nervous system, refractory bronchopneumonia, and generalized muscular atrophy. A computed tomographic scan of the brain demonstrated hypodense areas of white matter suggestive of demyelination. This report describes the rare association of gallbladder papillomatosis with a storage disorder and reviews the relevant literature.

Child, Preschool↗
PubMed1997

Active immunization of metastatic melanoma patients with interleukin-2-transduced allogeneic melanoma cells: evaluation of efficacy and tolerability.

From January 1994 to July 1996 we immunized metastatic melanoma patients with HLA-A2-compatible, interleukin-2 (IL-2)-secreting, immunogenic melanoma lines in an attempt to induce a systemic reaction that might also affect distant melanoma lesions. Twelve patients (6 male and 6 female) aged from 28 to 72 years, affected with visceral and/or subcutaneous (s.c.) melanoma metastases, were treated. Two different HLA-A2+ melanoma lines were transduced with the human IL-2 gene (14932/IL-2 and 1B6/IL-2) and used as vaccine. Two groups of 4 patients each were injected s.c. with 5 x 10(7) and 15 x 10(7) irradiated 14932/IL-2 melanoma cells respectively, whereas a third group received 5 x 10(7) cells of the second line (1B6/IL-2). All patients received the vaccine on days 1, 13, 26; if no progression was evident, further immunizations were administered at monthly intervals. All patients were assessable for clinical response after at least three injections of the vaccine. In 4 cases a stabilization of disease lasting from 2 to 6 months was observed: in 2 of them a mixed type of response to treatment was noted with simultaneous evidence of regressing and non-responding lesions in the same patients. No signs of clinical response were found in the remaining patients. Nine patients died of disease between 3 and 24 months after the onset of therapy, whereas 3 were alive 3 months after the end of therapy. The local and systemic side-effects of treatment were mild. These results indicate that vaccination with cells bearing the appropriate antigens and releasing IL-2 locally can produce weak clinical responses, but also indicate that better results may be achieved through modifications of the vaccine, the schedule of immunization and/or a more appropriate selection of patients.

Adult↗
PubMed1997

Cloning and stable expression of the mGluR1b subtype of human metabotropic receptors and pharmacological comparison with the mGluR5a subtype.

We isolated and characterized a cDNA encoding the human metabotropic glutamate receptor subtype 1b (hmGluR1b). In situ hybridization studies in human brain regions revealed a higher distribution of mGluR1 mRNA in the dentate gyrus of the hippocampus, the substantia nigra pars compacta and the Purkinje cell layer of the cerebellum compared to other regions studied. We established stable expression of recombinant hmGluR1b in L(tk-) mouse fibroblast and Chinese hamster ovary (CHO-dhfr-) cells. In both expression systems, agonist activation of hmGluR1b stimulated inositol phosphate (InsP) formation and elevation of the cytosolic free calcium ([Ca2+]i), and both responses were blocked by (S)-MCPG. The rank order of potency for agonists was quisqualate > glutamate > (1S,3R)-ACPD in both expression systems. Comparison of the agonist profiles of hmGluR1b and hmGluR5a, both stably expressed in L(tk-) cells, indicated the same rank order of potency (quisqualate > glutamate > or = (RS)-3,5-DHPG > or = (1S,3R)-ACPD), but each of the four agonists were more potent on hmGluR5a than on hmGluR1b. In antagonist studies, (S)-MCPG inhibited the agonist-induced InsP formation and elevation of [Ca2+]i in both hmGluR1b- and hmGluR5a-expressing cells. (S)-4CPG and (S)-4C3HPG both inhibited agonist responses only in hmGluR1b-expressing cells. However, in hmGluR5a-expressing cells the antagonist activity of (S)-4CPG and (S)-4C3HPG was dependent on the agonist used in the study, since they inhibited responses to glutamate but not to quisqualate. Stable cell lines expressing specific subtypes of human mGluRs represent valuable tools for the study of the mechanism of action of mGluRs at the molecular and cellular level and as screening targets for identification of subtype-selective agonists or antagonists.

Animals↗
PubMed1997

Severity of AIDS and the response to EPO in uremia.

To determine the factors that govern their response to erythropoietin (EPO), we conducted a cross-sectional study of all patients in four outpatient hemodialysis facilities in Brooklyn, NY, who had end-stage renal disease (ESRD) and human immunodeficiency virus (HIV) infection and were receiving recombinant EPO. We also compared the hematocrit and EPO requirements of these patients to those of a control group of hemodialysis patients without HIV infection. We documented known duration of HIV infection, and total CD4 count was measured once. In both groups, hematocrit was measured weekly for 5 weeks and a mean value calculated for each subject. Transferrin saturation was measured twice and a mean value calculated for each subject. Intensity of hemodialysis was assessed by measuring both percent reduction of urea and serum albumin concentration twice; mean values were calculated for each subject. Twenty-nine (88%) of 33 study subjects had acquired immunodeficiency syndrome. Mean known duration of HIV infection was 49 +/- 32.5 months (median, 48 months), and mean total CD4 count was 143 +/- 152.4 cells/mm3 (median, 72 cells/mm3). Mean hematocrit in the study subjects was 27.4% +/- 4.7% compared with 27.6% +/- 3.7% in the controls (P = 0.69). Mean thrice-weekly EPO dose was higher in the study subjects (90 +/- 52 U/kg body weight) than in the controls (62 +/- 36 U/Kg body weight) (P = 0.001). Among the study subjects, hematocrit had direct univariate correlations with serum albumin concentration (r = 0.43; P = 0.02), transferrin saturation (r = 0.4; P = 0.03), and percent reduction of urea (r = 0.4; P = 0.02), but not with total CD4 count (r = -0.05; P = 0.8) or known duration of HIV infection (r = -0.11; P = 0.55). There was an inverse correlation between hematocrit and dose of EPO (r = -0.5; P = 0.003). Multiple regression analysis showed that transferrin saturation (P = 0.01) and percent reduction of urea (P = 0.003) had direct correlations with hematocrit after adjustment for other factors. There was an inverse relationship between hematocrit and dose of EPO (P = 0.0006). We conclude that in patients with ESRD and HIV infection receiving hemodialysis, the response to EPO (hematocrit) is modulated by the dose of EPO, quantity of hemodialysis, and transferrin saturation, but not by the severity of HIV disease. Hemodialysis patients infected with HIV receive a higher dose of EPO than those without HIV infection.

Adult↗
PubMed1997

Analgesic effect of intra-articular bupivacaine or diamorphine after arthroscopic surgery of the knee joint in day-case patients.

A prospective, randomized, double-blind, controlled study was conducted to assess the efficacy of intra-articular bupivacaine and diamorphine. Ninety-six day-case patients were allocated randomly to receive intra-articular injections of either 20 mL 0.9% saline (control, n = 35), 20 mL 0.5% plain bupivacaine (n = 31), or 20 mL 0.9% saline with 5 mg diamorphine (n = 30) prior to tourniquet release. Visual analogue scales (VAS) were completed at 1 h, 3 h (discharge) and 24 h, and supplementary analgesia noted. Intra-articular analgesics conferred a noticeable improvement in patient comfort. First, the quantity of supplementary analgesia required prior to discharge was significantly reduced (P = 0.016); second, patients reported a less disturbed night's sleep (P = 0.034).

Adolescent↗