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Biomedical subjects

N Bhat

Publications and source records attributed to N Bhat.

At least 19 recordsLinked to original sources
PubMed2003

Should patients with asymmetrical noise-induced hearing loss be screened for vestibular schwannomas?

The Peterborough ENT department receives many referrals for MoD personnel who have suffered hearing loss from occupational noise exposure. Those patients with asymmetrical sensorineural hearing loss are routinely screened for vestibular schwannomas by MRI scanning. Scan reports from the past 5 years have been reviewed and out of 152 scans, four revealed vestibular schwannomas giving a pick-up rate of 2.5%, which compares favourably with other published pick-up rates. Review of the audiograms in these cases suggests that they can be misleading in this context. The conclusion is that patients with noise-induced asymmetrical hearing loss should be screened for acoustic neuromas.

Adult↗
PubMed2002

Bipolar scissors versus cold dissection for pediatric tonsillectomy--a prospective, randomized pilot study.

OBJECTIVE: To evaluate bipolar scissors tonsillectomy by comparing it with traditional cold dissection tonsillectomy. The outcome measures used were: (1) intra-operative bleeding; (2) operative time; (3) post-operative pain; and (4) complication rates including reactionary and secondary hemorrhage. METHOD: A prospective, randomized multiunit study involving three teaching hospitals in Belfast. Fifty consecutive children aged 10-16 years undergoing tonsillectomy for recurrent or chronic tonsillitis, between March 2000 and September 2000 were recruited as a subgroup of 200 patients selected for this study. These children were analysed separately from the adults, in a pilot study for the above parameters. RESULTS: The mean age of the study population was 14.3 years. Sixty-eight percent of the children were girls. Median intra-operative blood loss was 6 ml for bipolar scissors tonsillectomy and 86 ml for cold dissection tonsillectomy (P<0.001). The median operative time was 10.5 min for bipolar scissors tonsillectomy compared to 14.5 min for the cold dissection method (P=0.001). There was no statistically significant difference in the pain scores between the two methods (P>0.05). The overall reactionary hemorrhage rate was 4% while the overall secondary hemorrhage rate was 14%. The hospital readmission rate was 4%. The reactionary and secondary hemorrhage rates were unaffected by the surgical method. CONCLUSIONS: This pilot study has shown that bipolar scissors tonsillectomy is a relatively safe technique in children aged 10-16 years with a similar morbidity to the cold dissection method. Its use is associated with a significant decrease in surgical time and blood loss compared to the cold dissection method. These advantages make it a favourable instrument for pediatric tonsillectomy especially in this age group.

Adolescent↗
PubMed2002

Chromobacterium violaceum infection: A rare but frequently fatal disease.

The authors report a rare case of Chromobacterium violaceum infection in a 2-month-old child. She presented with an apparently localized abscess, which appeared to respond well to therapy. However, the infection recurred later with a fulminant course. The organism frequently is dismissed as a contaminant or not identified properly, and the fatality rates are high. A high degree of awareness about this infection needs to be created, especially among pediatricians and pediatric surgeons, because children appear to be infected more commonly than adults, and aggressive therapy is needed to save these patients.

Abscess↗
PubMed2001

Spontaneous biliary perforation presenting as gastric outlet obstruction.

Spontaneous biliary perforation (SBP) is a rare, surgically correctable cause of jaundice in neonates. The presenting feature is usually biliary ascites, and in rare cases, biliary peritonitis. This article reports a case of SBP, which presented with features of gastric outlet obstruction, leading to an erroneous preoperative diagnosis. Most probably this is the first report of such an unusual presentation of SBP. The child underwent exploratory laparotomy and a bilio-enteric bypass with drainage of the right subhepatic space, which led to a prompt resolution of the symptoms.

Bile Ducts↗
PubMed2001

Bipolar scissors versus cold dissection tonsillectomy: a prospective, randomized, multi-unit study.

OBJECTIVE: To evaluate bipolar scissors tonsillectomy by comparing it with traditional cold dissection tonsillectomy. STUDY DESIGN: A prospective, randomized, multi-unit study. SETTINGS: Belfast City Hospital, Royal Victoria Hospital Belfast, and Ulster Hospital Dundonald. PATIENTS: Two hundred consecutive patients undergoing tonsillectomy for recurrent or chronic tonsillitis between March 2000 and September 2000. OUTCOME MEASURES: (1) Intraoperative bleeding, (2) operative time, (3) postoperative pain, and (4) complication rates, including primary and secondary hemorrhage. RESULTS: Seventeen patients were excluded from the study for various reasons. The mean age of the study population was 22 years (range, 10-54 y). Seventy-two percent of patients were female. Twenty-seven percent of patients were children aged 16 years or under. Median intraoperative blood loss was 5 mL for bipolar scissors tonsillectomy and 115 mL for cold dissection tonsillectomy (P < .001). The mean operative time was 13 minutes for bipolar scissors tonsillectomy compared with 20 minutes for the cold dissection method (P < .001). There was no statistically significant difference in the pain scores between the two methods (independent samples t = 1.35; P > .05). The overall primary hemorrhage rate was 2.1%, whereas the overall secondary hemorrhage rate was 16.9%. The hospital readmission rate was 10.3%. The primary and secondary hemorrhage rates were unaffected by the surgical method. CONCLUSIONS: Bipolar scissors tonsillectomy is a safe technique with a similar morbidity to the cold dissection method. Its use is associated with a significant decrease in both surgical time and blood loss compared with the cold dissection method.

Adolescent↗
PubMed2000

Rapid activation of lymph nodes and mononuclear cell HIV expression upon interrupting highly active antiretroviral therapy in patients after prolonged viral suppression.

OBJECTIVE: To compare the architecture and HIV-1 RNA and Gag p24 protein expression in lymph nodes (LN) excised from individuals during chronic highly active antiretroviral therapy (HAART) with LN removed from the same patient after plasma virus rebound following the interruption of HAART. MATERIALS AND METHODS: Six HIV-1-infected patients on HAART, with CD4 cell counts greater than 350 cells/microl, and plasma HIV-1 RNA less than 50 copies/ml, underwent inguinal LN excision upon discontinuation of HAART, and again after rebound of plasma virus. Lymph nodes were evaluated by immunohistochemical staining for Gag p24 antigen and Ki67, in-situ hybridization for HIV-1 RNA and H3-histone, and transmission electron microscopy (TEM). RESULTS: LN at baseline were quiescent to mildly hyperplastic and generally contained more primary than secondary follicles. Only one LN had detectable follicular dendritic cell (FDC)-associated p24 antigen, none had HIV RNA. Few mononuclear cells (MNC) expressed RNA or p24 antigen. Plasma virus at the second biopsy ranged from 329 to 3.2 x 10(6) copies/ml. CD4 cell count decline ranged from 5 to 51% during drug hiatus, and was greatest in patients with highest viral rebound. Four of six of the second LN were more hyperplastic than the initial LN, two showed paracortical hyperplasia. MNC expression of HIV RNA in the second LN paralleled the level of plasma viremia. Increased Ki67 and H3-histone signal occurred in the second LN. CONCLUSION: Quiescent LN from individuals on HAART rapidly become hyperplastic and activated within 1-2 months after treatment interruption. As in acute HIV infection, virus expression by LN MNC parallels the rebound in plasma viremia and fall in CD4 cell count.

Antiretroviral Therapy, Highly Active↗
PubMed2000

Etiologic and early marker studies in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial.

The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, which is randomizing 74,000 screening arm participants (37,000 men, 37,000 women; ages 55-74) and an equal number of nonscreened controls, is a unique setting for the investigation of the etiology of cancer and other diseases and for the evaluation of potential molecular markers of early disease. At entry, baseline information is collected by questionnaire on dietary intake, tobacco and alcohol use, reproductive history (for women), family history of cancer, use of selected drugs, and other selected risk factors. Blood samples collected at the baseline screening exam are aliquoted to serum, plasma, red blood cell, and buffy coat fractions. At the next two annual screening visits, serum samples are collected. At the third annual reexamination, cryopreserved whole blood is obtained, in addition to serum, plasma, red blood cell, and buffy coat fractions. At the fourth and fifth years, serum, plasma, and buffy coat are collected. All blood samples are shipped to a central repository for long-term storage at -70 degrees C. Dietary questionnaires and buccal cells for DNA analysis are obtained from nonscreened controls. Cancer cases are identified through annual follow-up questionnaires, and all deaths are identified through vital status tracing mechanisms. Procedures are being developed to obtain archival pathologic material for selected cases of cancer and related diseases. Initial investigations are focusing on the etiology of colorectal cancer and on the operative characteristics of tests for the early detection of colorectal and prostate cancer.

Aged↗
PubMed2000

Mediation of Cryptosporidium parvum infection in vitro by mucin-like glycoproteins defined by a neutralizing monoclonal antibody.

The protozoan parasite Cryptosporidium parvum is a significant cause of diarrheal disease worldwide. Attachment to and invasion of host intestinal epithelial cells by C. parvum sporozoites are crucial steps in the pathogenesis of cryptosporidiosis. The molecular basis of these initial interactions is unknown. In order to identify putative C. parvum adhesion- and invasion-specific proteins, we raised monoclonal antibodies (MAbs) to sporozoites and evaluated them for inhibition of attachment and invasion in vitro. Using this approach, we identified two glycoproteins recognized by 4E9, a MAb which neutralized C. parvum infection and inhibited sporozoite attachment to intestinal epithelial cells in vitro. 4E9 recognized a 40-kDa glycoprotein named gp40 and a second, >220-kDa protein which was identified as GP900, a previously described mucin-like glycoprotein. Glycoproteins recognized by 4E9 are localized to the surface and apical region of invasive stages and are shed in trails from the parasite during gliding motility. The epitope recognized by 4E9 contains alpha-N-acetylgalactosamine residues, which are present in a mucin-type O-glycosidic linkage. Lectins specific for these glycans bind to the surface and apical region of sporozoites and block attachment to host cells. The surface and apical localization of these glycoproteins and the neutralizing effect of the MAb and alpha-N-acetylgalactosamine-specific lectins strongly implicate these proteins and their glycotopes as playing a role in C. parvum-host cell interactions.

Animals↗
PubMed2000

A risk-benefit assessment of interleukin-2 as an adjunct to antiviral therapy in HIV infection.

Immunomodulation has become a major focus of HIV research in an effort to augment, boost or restore the patient's damaged immune system. Recombinant interleukin-2 is currently being studied in phase II/III trials in HIV-infected patients. Several clinical studies have demonstrated that intermittent regimens are associated with marked rises in CD4+ cell counts without an increase in viral load. Most of these studies employ 5 consecutive days of interleukin-2 therapy by continuous intravenous infusion or subcutaneous injection, repeated every 8 weeks. An alternative strategy is the daily administration of low doses of interleukin-2, but clinical experience with this regimen is limited. Interleukin-2 administration can adversely affect virtually every organ system, requiring aggressive supportive care. A variety of administration strategies and interventions are being evaluated to minimise toxicity. Currently, no clinical end-point data are available for interleukin-2 in HIV-infected patients. Until phase III studies are completed, interleukin-2 can be used in the research setting as an immunomodulator and adjunct to antiretroviral therapy. Its potential to activate latently infected cells and promote HIV eradication from reservoir sites is also an important area for further study. If clinical benefit can be demonstrated, interleukin-2 could be useful as an adjunct to antiretroviral therapy if adverse effects can be minimised and therapy can be given infrequently on an outpatient basis.

Anti-HIV Agents↗
PubMed2000

Paediatric airway endoscopy.

OBJECTIVES: To review all paediatric endoscopies performed in a tertiary referral unit over a three-year period. METHODS OF STUDY: Retrospective analysis of case-notes of all paediatric endoscopies performed between May 1993 and June 1996. RESULTS: 333 paediatric airway endoscopies were performed on 146 children, of which 52% were GP referrals and the remainder secondary referrals. 70% were diagnostic endoscopies, 30% therapeutic procedures, with the commonest indication being stridor and respiratory distress (82%). Routine chest radiographs, lateral neck X-rays, and barium swallows were unhelpful in the management of the commoner upper-airway conditions. The commonest findings were laryngomalacia (44%) and subglottic stenosis (22%) and 17% of all cases had multiple airway abnormalities. Tracheotomy was performed on 18.4%, laryngotracheoplasty on 7.5%, and laryngotracheal reconstruction on 2.5%. There were no major complications in this series. CONCLUSIONS: All children with airway symptoms should have a thorough rigid-endoscopic evaluation of their upper and lower airways. Radiology has a limited role in the diagnosis of the more common airway pathologies. These patients need to be assessed and managed in regional centres.

Adolescent↗
PubMed1999

HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression.

Identifying the immunologic and virologic consequences of discontinuing antiretroviral therapy in HIV-infected patients is of major importance in developing long-term treatment strategies for patients with HIV-1 infection. We designed a trial to characterize these parameters after interruption of highly active antiretroviral therapy (HAART) in patients who had maintained prolonged viral suppression on antiretroviral drugs. Eighteen patients with CD4(+) T cell counts >/= 350 cells/microliter and viral load below the limits of detection for >/=1 year while on HAART were enrolled prospectively in a trial in which HAART was discontinued. Twelve of these patients had received prior IL-2 therapy and had low frequencies of resting, latently infected CD4 cells. Viral load relapse to >50 copies/ml occurred in all 18 patients independent of prior IL-2 treatment, beginning most commonly during weeks 2-3 after cessation of HAART. The mean relapse rate constant was 0.45 (0.20 log(10) copies) day(-1), which was very similar to the mean viral clearance rate constant after drug resumption of 0.35 (0.15 log(10) copies) day(-1) (P = 0.28). One patient experienced a relapse delay to week 7. All patients except one experienced a relapse burden to >5,000 RNA copies/ml. Ex vivo labeling with BrdUrd showed that CD4 and CD8 cell turnover increased after withdrawal of HAART and correlated with viral load whereas lymphocyte turnover decreased after reinitiation of drug treatment. Virologic relapse occurs rapidly in patients who discontinue suppressive drug therapy, even in patients with a markedly diminished pool of resting, latently infected CD4(+) T cells.

Adult↗
PubMed1999

Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy.

The nuclear lamina is a protein meshwork lining the nucleoplasmic face of the inner nuclear membrane and represents an important determinant of interphase nuclear architecture. Its major components are the A- and B-type lamins. Whereas B-type lamins are found in all mammalian cells, A-type lamin expression is developmentally regulated. In the mouse, A-type lamins do not appear until midway through embryonic development, suggesting that these proteins may be involved in the regulation of terminal differentiation. Here we show that mice lacking A-type lamins develop to term with no overt abnormalities. However, their postnatal growth is severely retarded and is characterized by the appearance of muscular dystrophy. This phenotype is associated with ultrastructural perturbations to the nuclear envelope. These include the mislocalization of emerin, an inner nuclear membrane protein, defects in which are implicated in Emery-Dreifuss muscular dystrophy (EDMD), one of the three major X-linked dystrophies. Mice lacking the A-type lamins exhibit tissue-specific alterations to their nuclear envelope integrity and emerin distribution. In skeletal and cardiac muscles, this is manifest as a dystrophic condition related to EDMD.

Animals↗
PubMed1999

Use of a photoactivatable taxol analogue to identify unique cellular targets in murine macrophages: identification of murine CD18 as a major taxol-binding protein and a role for Mac-1 in taxol-induced gene expression.

Taxol, a potent antitumor agent that binds beta-tubulin and promotes microtubule assembly, results in mitotic arrest at the G2/M phase of the cell cycle. More recently, Taxol was shown to be a potent LPS mimetic in murine, but not in human macrophages, stimulating signaling pathways and gene expression indistinguishably from LPS. Although structurally unrelated to LPS, Taxol's LPS-mimetic activities are blocked by inactive structural analogues of LPS, indicating that despite the species-restricted effects of Taxol, LPS and Taxol share a common receptor/signaling complex that might be important in LPS-induced human diseases. To identify components of the putatively shared Taxol/LPS receptor, a novel, photoactivatable Taxol analogue was employed to identify unique Taxol-binding proteins in murine macrophage membranes. Seven major Taxol-binding proteins, ranging from approximately 50 to 200 kDa, were detected. Although photoactivatable Taxol analogue failed to bind to CD14, the prominent Taxol-binding protein was identified as CD18, the approximately 96-kDa common component of the beta2 integrin family. This finding was supported by the concomitant failure of macrophage membranes from Mac-1 knockout mice to express immunoreactive CD18 and the major Taxol-binding protein. In addition, Taxol-induced IL-12 p40 mRNA was markedly reduced in Mac-1 knockout macrophages and anti-Mac-1 Ab blocked secretion of IL-12 p70 in Taxol- and LPS-stimulated macrophages. Since CD18 has been described as a participant in LPS-induced binding and signal transduction, these data support the hypothesis that the interaction of murine CD18 with Taxol is involved in its proinflammatory activity.

Amino Acid Sequence↗
PubMed1999

Epignathus: a germ-cell tumour presenting as neonatal respiratory distress.

A full-term neonate developed acute upper airway obstruction immediately after birth secondary to a polypoidal mass in the oropharynx. After the child's airway had been secured, the mass was excised and found to be a nasopharyngeal teratoma, a rare congenital germ cell tumour which is frequently associated with other congenital malformations. It is sometimes possible to diagnose these tumours in utero, thereby enabling appropriate precautions to be taken during the delivery, otherwise if the diagnosis is unknown, then it is essential for any attending clinician to urgently secure the airway by means of either intubation or tracheostomy. Such a case is presented with a review of the possible management options. This case emphasises the fact that although many conditions are uncommon, the total incidence of rare conditions is surprisingly high, and that care needs to be taken at all times in the management of patients, in order not to overlook such life-threatening diagnoses.

Female↗
PubMed1999

Antifungal activity of voriconazole (UK-109,496), fluconazole and amphotericin B against hematogenous Candida krusei infection in neutropenic guinea pig model.

Voriconazole (UK-109,496) is a new triazole with in vitro activity against a wide spectrum of fungi including yeasts intrinsically resistant to fluconazole such as Candida krusei. In this study the efficacy of voriconazole was compared to amphotericin B and fluconazole in a neutropenic guinea pig model of hematogenously disseminated C. krusei infection. In guinea pigs, neutropenia was established by using cyclophosphamide (intraperitoneally, i.p., 100 mg/kg on day 1 and 4), and dexamethasone (orally, 2 mg/kg/day, for 8 days). Neutropenic guinea pigs were infected with 0.5 ml of yeast cell suspension (1 x 10(8) CFU) intravenously. Challenged animals were treated with antifungals starting 1 h postinfection for 7 days. The animals were divided into five groups: untreated control, amphotericin B (1 mg/kg i.p. on alternate days), fluconazole (20 mg/kg orally twice daily), and voriconazole (two groups: 5 and 10 mg/kg orally twice daily) groups. Guinea pigs were sacrificed 1 day after the last treatment. Brain, liver, and kidneys were removed and weighed, tissues were homogenized and fungal burden determined by serial quantitative counts. Voriconazole at dosages of 5 or 10 mg/kg b.i.d. was shown to be significantly more efficacious than either amphotericin B or fluconazole in eradicating C. krusei from brain, liver and kidney tissue. These data indicate that voriconazole could be efficacious for the treatment of infections caused by fluconazole-resistant Candida, such as C. krusei.

Amphotericin B↗
PubMed1999

Generation of a polyclonal Fab phage display library to the protozoan parasite Cryptosporidium parvum.

We had developed a technology for creation of recombinant polyclonal antibody libraries, standardized perpetual mixtures of polyclonal whole antibodies for which the genes are available and can be altered as desired. We report here the first phase of generating a polyclonal antibody library to Cryptosporidium parvum, a protozoan parasite that causes severe disease in AIDS patients, for which there is no effective treatment. BALB/c mice, immunized by neonatal oral infection with oocysts followed by intraperitoneal immunization with a sporozoite/oocyst preparation of C. parvum, were used for construction of a Fab phage display library in a specially-designed bidirectional vector. This library was selected for reactivity to an oocyst/sporozoite preparation, and was shown to be antigen-specific and diverse. Following mass transfer of the selected variable region gene pairs to appropriate mammalian expression vectors, such anti-C. parvum Fab phage display libraries could be used to develop chimeric polyclonal antibody libraries, with mouse variable regions and human constant regions, for passive immunotherapy of C. parvum infection.

Animals↗
PubMed1998

Vancomycin-resistant enterococcal colonization in nonhospitalized HIV-infected patients.

We studied fecal colonization with vancomycin-resistant enterococci (VRE) in 89 HIV-infected nonhospitalized patients ages 24 to 62 years, including 70 (79%) men (including 41 homosexual and 5 bisexual men) and 19 (21%) women. Of the 89 patients, 61 (69%) were black, 25 (28%) Hispanic, and 3 (3%) white; 53 (60%) had history of ongoing or recent antibacterial therapy with trimethoprim/sulfamethoxazole (29), clarithromycin (18), amoxicillin (7), ofloxacin (3), and metronidazole, doxycycline, dicloxacillin, and cephalexin (1 each). VRE were not isolated from any of the patients studied.

AIDS-Related Opportunistic Infections↗