Biomedical subjects
Publications and source records attributed to S Nair.
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BACKGROUND: More than 95% of lung cancers occur in the bronchi, appearing as adenocarcinoma, squamous carcinoma, large-cell and small-cell carcinoma, or mixed types. Generally, the least aggressive form is squamous cell lung cancer, suggesting the possibility that promotion of squamous cell differentiation may have therapeutic potential for non-small-cell lung cancer, a disease having no effective systemic therapy. Interferons are a group of glycoproteins with known antiproliferative effects, including the ability to induce differentiation in certain cases. PURPOSE: These studies were conducted to determine whether interferon beta induces squamous cell differentiation in non-small-cell lung cancer in vitro. METHODS: NCI-H596 adenosquamous cells were grown to confluence to maximize their differentiation potential. Growth and parameters for squamous differentiation (cross-linked envelope competence, transglutaminase activity, and relative involucrin expression) were then measured when the cells were exposed to various concentrations of interferon beta. RESULTS: Interferon beta inhibited growth of the NCI-H596 cell line and stimulated envelope competence, involucrin expression, and type 2 transglutaminase activity. Alterations in transglutaminase activity and involucrin expression preceded induction of envelope competence and growth suppression. CONCLUSIONS: Interferon beta suppresses the growth and stimulates markers of squamous differentiation in NCI-H596. While the mechanism(s) for such effects are unknown, the sequence of effects suggests a causal relationship between differentiation induction and subsequent growth suppression. IMPLICATIONS: Interferon beta may have clinical usefulness in squamous differentiation strategies for the treatment of non-small-cell lung cancer. More must be learned about the mechanisms whereby interferons and other biologic agents induce differentiation, and clinical trials will be needed to determine whether in vitro results are pertinent in vivo.
Assessing the immunobiological function of the individual proteins of herpes simplex virus-type 1 (HSV-1) continues to be important in elucidating virus-host interactions and for the rational design of subunit vaccines. In this report, the non-structural, immediate-early protein ICP47 of HSV-1 was examined for its ability to induce virus-specific immune responses. The ICP47 protein, when expressed from a recombinant vaccinia virus or when produced by cell-free, in vitro translation, induced a vigorous HSV-1-specific lymphoproliferative response. However, other common parameters of immunity such as neutralizing antibody, delayed-type hypersensitivity, and class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL) were not induced by ICP47. Moreover, mice immunized with vaccinia-expressed ICP47 were unable to survive lethal challenge with virulent HSV, indicating that in spite of its ability to induce significant HSV-1-specific lymphoproliferation, ICP47 appears unable to afford protective immunity in vivo. Possible reasons for this failure and the implications of these results in terms of vaccine design are discussed.
The epileptogenic and neurodegenerative effects induced by intra-hippocampal injection of a selective K+ channel inhibitor, alpha-dendrotoxin (DTx), were investigated in normal rats and those bearing a monolateral surgical lesion of the Schaffer collaterals that causes degeneration of their nerve terminals and also, isolates the CA3 area. In addition, these effects have also been studied in rats pretreated with NBQX, an AMPA receptor antagonist. Injection of DTx (35 pmol) into one dorsal hippocampus induced motor and electrocortical (ECoG) seizures in all the treated animals that were rapid in onset (within 2-3 min). The seizures were accompanied at 24 h by significant neuronal cell loss which occurred in the CA1, CA3 and CA4 pyramidal cell layers of the hippocampus, ipsilateral to the side of injection. This neuronal loss was paralleled by a significant decrease in the density of radioiodinated DTx labelled acceptors. Lesioning of the excitatory afferents to the CA1 pyramidal cells, gave a substantial reduction in the density of radioiodinated DTx labelled acceptors in the strata oriens and radiatum, revealing that a proportion of these K+ channels are present on the Schaffer collateral terminals. Under these conditions, motor and ECoG seizures persisted. As expected, the lesion prevented loss of the isolated CA3 pyramids, normally produced by the administration of DTx, leaving unaffected CA1 and CA4 pyramidal cell damage, consistent with an observed diminution of DTx binding sites in the latter areas. In unlesioned rats pre-treated with NBQX (30 mg/kg i.p.), subsequent injection of DTx evoked epileptogenic effects after a latency of 15 min and caused significant cell loss in the CA1 but not in the CA3 and CA4 pyramidal cell layers, ipsilateral to the side of toxin injection. A lower dose of NBQX (15 mg/kg i.p.) proved ineffective. In conclusion, these data together with our published results on NMDA antagonists indicate that motor and ECoG seizures and CA1 pyramidal cell loss elicited by intra-hippocampal injection of the K+ channel blocker, DTx, are independent from mechanisms involving glutamate-mediated excitotoxicity whereas CA3 and CA4 pyramidal cell loss may be the consequence of excessive activation of AMPA receptors.
Metastatic choriocarcinoma of the kidney is a rare entity, and its primary presentation with hematuria and renal mass is even less common. Two cases are presented with a review of the literature.
The genomic DNA of 39 strains of Salmonella typhi isolated from local residents and patients who had visited countries in the Asian region was analysed for restriction fragment length polymorphisms (RFLP). Pulsed-field gel electrophoretic (PFGE) analysis of Xba I- and Spe I-generated genomic restriction fragments established 22 PFGE types whereas phage typing differentiated the 39 isolates into 9 distinct phage types. This study showed that PFGE is more discriminatory than phage typing as it is capable of subtyping S. typhi strains of the same phage types. Genetic relatedness among the isolates was determined. Seven major clusters were identified at SABs of > 0.80 and the remaining 13 isolates were distributed into minor clusters which were related at SABs of less than 0.80. In conclusion, PFGE analysis in conjunction with distance matrix analysis served as a useful tool for delineating common S. typhi phage types of diverse origins from different geographical locales and separated in time.
Wound infection after lumbar, thoracic, or cervical laminectomies is a rare but potentially devastating complication. It can range in severity from superficial wound infection to an extensive wound dehiscence. The usual treatment of these wounds consists of intensive local care, debridement, and appropriate antibiotic therapy. Secondary healing can result in chronic, painful wounds that are difficult to manage and can create the potential for osteomyelitis. Seven cases of infected dehiscent laminectomy wounds are presented. Either critical structures were exposed, or the patients did not heal after secondary or delayed primary closures. In each case, full healing was attained by means of reconstruction with a regional muscle flap. We propose that muscle flap reconstruction offers an excellent alternative for the reconstruction of difficult postlaminectomy wounds.
Endopeptidase-24.11 (neutral endopeptidase, neprilysin, 'enkephalinase', EC 3.4.24.11) and endopeptidase-24.18 (endopeptidase-2, meprin, EC 3.4.24.18) are cell-surface zinc-dependent metallo-endopeptidases able to cleave a variety of bioactive peptides including growth factors. We report the first study of the cellular and tissue distribution of both enzymes and of the mRNA for NEP during embryonic development in the rat. Endopeptidase-24.11 protein was first detected at E10 in the lining of the gut and, at E12, the enzyme was present on the notochord, medial and lateral nasal processes, otocyst, mesonephros, heart and neuroepithelium. In contrast, at this time endopeptidase-24.18 was present only on the apical surface of the neuroepithelial cells. By E14 and E16, NEP was also detected in a wide range of craniofacial structures, notably the palatal mesenchyme, the choroid plexus, tongue and perichondrium. The distribution of endopeptidase-24.18 at these stages was restricted to the inner ear, the nasal conchae, and ependymal layer of the brain ventricles and the choroid plexus. Although endopeptidase-24.11 had been detectable in the craniofacial vasculature at E12 and E14, this was no longer apparent at E16. Significantly, the distribution of endopeptidase-24.11 mRNA closely matched the immunolocalization of the protein at all stages investigated. In order to explore the functional role of these enzymes, inhibition studies were carried out using two selective inhibitors of endopeptidase-24.11, phosphoramidon and thiorphan. E9.5 and E10.5 embryos exposed to either inhibitor displayed a characteristic, asymmetric abnormality consisting of a spherical swelling, possibly associated with a haematoma, predominantly on the left side of the prosencephalon, and the severity of this defect appeared to be a dose-dependent phenomenon. This study suggests that these enzymes play previously unrecognized roles during mammalian embryonic development.
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The clamor for data to study the impact of care, to evaluate clinical performance and justify resource utilization is increasing. The data in demand normally should exist in the record of a clinical encounter. Advances in information technology and software techniques have provided us with tools to develop and implement computer-based patient record systems. The issues that constrain development are integral issues of clinical medicine, such as the variability in medical data, specialized practice of medicine, and differing demands of the numerous end-users of a medical record. This paper describes an approach to develop a computer-based patient record. The focus is on identification of the essential data set by infological data modeling and its implementation in a commercially available package for a physician's office.
Four patients aged between 9 months and 17 years were detected to have congenital ocular motor apraxia (COMA) over a 10-month period. Three of them were siblings. All exhibited the classical signs of a horizontal saccadic palsy. However, the signs were less pronounced with increasing age of the patient. This supports the observations of other authors who have noted an age-related resolution. There was no evidence of other motor developmental delay in any of the patients and computed tomography revealed no abnormalities. Both these findings are in contradistinction to prior reports of central nervous system abnormalities and motor and speech difficulties in COMA. The family of three appears to be the largest sibling cluster reported so far.
Patients with malignant brain tumors requiring multiple craniotomies and external beam radiotherapy are at risk of scalp wound breakdown secondary to fibrosis and radiation damage. We present three cases to illustrate the nature of the problem and the surgical approaches to scalp repair. When a bicoronal incision has been used for the initial craniotomy, the plastic repair can be performed with a bipedicle visor scalp flap and split-thickness skin graft to cover the pericranium at the donor site. When a curvilinear (U-shaped or horseshoe) flap has been used for the initial craniotomy, a single-pedicle flap may be rotated to achieve closure without tension. In anticipation of the risk of scalp wound breakdown in patients with malignant brain tumors, the planning of the operative incision for the first craniotomy needs to take into account the long-term viability of the scalp. We recommend linear scalp incisions parallel to the arterial distribution instead of the traditional curvilinear (U-shaped or horseshoe) flaps; linear incisions are less likely to break down, and in the event of breakdown, linear wounds offer better therapeutic surgical options for plastic repair.
We assessed all patients (n = 120) who underwent left ventricular aneurysmectomy as part of a cardiac surgical procedure at the Groby Road Hospital subregional cardiothoracic centre (1980-1990). Of these, 71% had had only one prior myocardial infarction and 84% had symptoms generally associated with aneurysms (congestive cardiac failure, ventricular arrythmias or systemic embolism). The indication for surgery was a combination of angina and aneurysm-related symptoms in 43%, one or more aneurysm-related symptoms in 35%, and angina alone in 22%. The majority of patients (57%) underwent aneurysmectomy and coronary artery bypass grafting, although 35% underwent aneurysmectomy alone. Most (61%) aneurysms were > 6 cm in size, and 75% were located at the apex of the left ventricle. Forty per cent had a mural thrombus, and there was no relationship between prior warfarin use and occurrence of mural thrombus. Overall perioperative mortality was 17% (20 patients), although mortality halved between the first and second halves of the study period. The main reason for perioperative was pump failure. Seventeen patients died late during follow-up (mean 52.5 months), the main cause being further myocardial infarction. Nevertheless, 65% were still alive at 5 years, and 81% and 66% of survivors were still better than pre-operatively at 5 and 8 years, respectively. Post-operative improvement was equally as good in patients who underwent aneurysmectomy alone, or those operated on for aneurysm-related symptoms, as in the whole group. In logistic regression analysis, the only predictor of adverse long-term outcome was the number of previous myocardial infarctions.(ABSTRACT TRUNCATED AT 250 WORDS)
Retrospective clinical experience with our first 46 patients monitored with a fiberoptic intracranial pressure device is described. In 43 of 46 patients, the transducer was introduced into brain parenchyma. A ventriculostomy system was used in 3 of 46 patients. The monitoring system was generally characterized by ease of placement and system maintenance and by technical simplicity. Several problems were encountered, including breakage of system components (12%), erroneous readings requiring transducer repositioning (8.6%), epidural hematoma (3.4%), and infection (1.7%). No infections or hematomas occurred in the 3 cases in which the ventriculostomy system was used. Overall, our experience with the Camino intracranial pressure fiberoptic monitoring system confirms previous reports of its favorable features.
Immunotherapy with Mycobacterium w vaccine was attempted in patients with borderline-borderline, borderline lepromatous (BL), or lepromatous leprosy (LL) to determine whether immunization can hasten recovery and reduce treatment time by invigorating cell-mediated immunity. Mycobacterium w, a nonpathogenic, rapidly growing, atypical mycobacterium, shares a number of common B and T cell determinants with Mycobacterium leprae and Mycobacterium tuberculosis. Patients receiving the vaccine had rapid clinical improvement and accelerated bacteriologic clearance. After treatment with vaccine for 2 years, 13 of 31 BL and LL patients were bacteriologically negative as were 5 of 25 controls. Vaccinated patients had one of two distinct histologic features, either an upgrading in the disease spectrum or complete clearance of granuloma. Some 80% of lepromin conversions were in BL and LL patients who received vaccine versus none and 14.3% of BL and LL controls, respectively. Thirteen of 17 vaccinated LL patients were released from treatment after 2 years in contrast to 2 of 15 controls.