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Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 343 records · Page 19Linked to original sources

Hypothalamic-pituitary-adrenal axis following glucocorticoid prophylaxis against acute mountain sickness.

The pituitary-adrenocortical and adrenomedullary response to high altitude (HA) stress was studied following daily single dose administration of prednisolone as a prophylaxis against altitude-induced acute mountain sickness (AMS). Forty healthy men, randomly divided into two groups of twenty, received placebo or prednisolone 20 mg once a day at 08.00 h for two days prior to induction to HA and during an initial three days stay at an altitude of 3450 m. The AMS score and circulatory levels of ACTH, cortisol, epinephrine and norepinephrine were measured at sea level (SL) and during residency at HA. The sensitivity of the hypothalamic-pituitary-adrenal axis in subjects receiving prednisolone therapy was evaluated at SL and on day four of stay at HA. Administration of prednisolone significantly (p < 0.01) decreased the severity of AMS in all the subjects. The steroid dose used did not inhibit endogenous secretion of ACTH, cortisol, epinephrine or norepinephrine, as HA response to adrenocortical and adrenomedullary hormones was identical in placebo and prednisolone treated subjects. The integrity of the hypothalamic-pituitary-adrenal axis was maintained well in subjects receiving low dose prednisolone therapy. These observations suggest that short-term administration of prednisolone is able to curtail AMS without causing suppression of the hypothalamic-pituitary-adrenal axis.

Adrenal Glands↗

Surgical clipping of basilar aneurysms: relationship between the different approaches and the surgical corridors.

BACKGROUND: Surgical clipping for basilar artery aneurysm (BAA) is a technically demanding procedure due to the depth of the surgical field and the presence of vital perforating arteries in the vicinity. The incorporation of various modifications in the conventional approaches has expanded the surgical armamentarium in dealing with these difficult lesions. METHODS AND FINDINGS: 87 patients of BAA were operated at our center, out of which in 48 patients, a pterional transsylvian approach was used. In 12 patients, this approach had to be extended to incorporate the anterior temporal approach in 6 cases, transzygomatic subtemporal approach in 2 cases and transcavernous approach in 4 cases. The surgical indications for the additional approaches and the relationships between the surgical corridors gained by their inclusion were studied. The use of neuroendoscopy facilitated adequate clipping in one case of high BAA without the incorporation of bone drilling, thus opening new surgical corridors. INTERPRETATION: The variable situation of the BAA makes it mandatory for the surgeon to be prepared to simultaneously work through multiple surgical corridors. Neuroendoscopic-assisted microneurosurgery occasionally utilizes a narrow surgical corridor to facilitate BAA clipping using the conventional approaches and eliminates the need to gain access using additional surgical corridors.

Basilar Artery↗

Embolization of cranial/spinal tumours and vascular malformations with hydrogel microspheres. An experience of 69 cases.

OBJECTIVE: To evaluate polymethyl methacrylate hydrogel microspheres (HMs) as an embolization material in the management of hypervascular craniofacial and spinal lesions. MATERIAL AND METHODS: Sixty-nine patients with vascular lesions of the craniofacial and spinal regions underwent embolization with HM. The pathologies included craniofacial tumours (n=38), cranial arteriovenous malformations (AVMs) (n=7), dural AVM (n=1), cavernous carotid fistula (n=1), spinal tumours (n=7), spinal AVMs (n=6), orbital lesions (n=4) and scalp AVMs (n=5). Surgery was done in 56 patients. The blood loss at surgery, tumour shrinkage, surgical cleavage and ease of removal of tumour was noted from the records. Histopathology was available in 39 patients. A follow-up of 3 months to 6 years was available in 13 patients in whom embolization was the sole treatment. Surgical and histopathological findings were correlated with angio-embolization findings. RESULTS: HMs were easy to inject through the microcatheter with good control. Good devascularization was obtained in 61 patients and partial in 8 patients. Two patients developed complications due to presence of anastomoses between intra- and extracranial circulation and 1 patient due to tumor swelling. Histopathology showed presence of HMs in all the lesions, with minimal inflammatory reaction in 2 patients. Patients with spinal lesions treated with embolization only stabilised in neurologic deficits. CONCLUSION: HMs are highly suitable as embolization agents in the management of craniofacial and spinal hypervascular lesions.

Antimutagenic Agents↗

The Willgerodt-Kindler reaction on lupenone: unusual oxidative dimerization.

In continuation of our interest in chemical modification of triterpenoids, the Willgerodt-Kindler reaction of a lupane type triterpenoid lupenone provided a novel dimerized product 2. Formation of 2 is associated with an unusual oxidative dimerization of lupenone under Willgerodt-Kindler reaction conditions. The structure 2 was confirmed by extensive analysis of spectroscopic data including ES-MS and 2D-NMR.

Dimerization↗

Polarized expression of Tamm-Horsfall protein by renal tubular epithelial cells activates human granulocytes.

In renal bacterial infections granulocytes are of major importance in the primary immune defense against invading pathogens. However, the mechanisms of granulocytic activation in renal interstitial invasion have not been clarified. Renal tubular epithelial cell mechanisms inducing granulocytic activation and bacterial killing may include tubular cell expression of Tamm-Horsfall protein (THP), a urinary protein that is known to enhance cytokine expression in monocytes. We studied the role of THP in granulocytic activation. A strong binding of THP to human granulocytes was demonstrated by fluorescence-activated cell sorter analysis. Urinary THP and supernatants of THP-expressing cultured tubular epithelial cells (MDCK) enhanced interleukin-8 (IL-8) expression by human granulocytes. Renal tubular cells growing polarized on polycarbonate membranes were used to study apical versus basal THP expression. By electron microscopy THP immunoreactivity was exclusively found on the apical surfaces of tubular cells and was absent on the basolateral cell membrane. In the apical cell culture compartment we found significantly more stimulatory activity for granulocytic IL-8 expression. CD62L, a selectin less expressed in activated granulocytes, was decreased in granulocytes incubated with urinary THP and in supernatants of THP-producing renal tubular cells but not in supernatants from THP-negative cells. Again, the effect on CD62L expression was found only in apical culture media and was absent in the basal compartment. In summary our data give evidence that renal tubular cell THP expression may be relevant in kidney diseases since THP is a potent activator of human granulocytes. The regulation of apical versus basal THP expression and release in vivo may be crucial in the induction of the inflammatory response, e.g., in bacterial renal diseases.

Animals↗

Transferrin regulates transcription of the MBP gene and its action synergizes with IGF-1 to enhance myelinogenesis in the md rat.

Myelin-deficient (md) rats and their unaffected littermates were injected at postnatal day 4 either with a single dose of transferrin (Tf) or insulin-like growth factor one (IGF-1) singly or combined. Two weeks later, their brains were perfused and coronal sections were analyzed for MBP by in situ hybridization and for transferrin and myelin basic protein (Tf and MBP) by double immunofluorescence. Each of the factors separately had an effect on mutant animals as seen by both increased OL maturation, and MBP mRNA and protein synthesis. The combination of factors resulted in a profound enhancement of the myelinogenic properties of oligodendrocytes (OL) with a consequent increase in the number of MBP-labeled fibers. The brains of unaffected littermates also responded to growth factor(s) injection either by increasing myelination in some brain areas or by regulating the synthesis of MBP in OL. Using rat OL cultures we studied the site of transferrin action for the expression of MBP gene. We found by run off transcription that the MBP mRNA was significantly increased at the nuclear level but the PLP message was unaffected. Thus, transferrin selectively regulates MBP at the transcriptional level and together with IGF-1 synergizes to increase both the maturation and myelinogenic properties of md and normal OL.

Animals↗

The management of obesity in type 2 diabetes mellitus.

Prevalence of obesity in the United Kingdom has tripled in the last 20 years and this is driving an epidemic of type 2 diabetes. Indeed, today the vast majority of patients with type 2 diabetes are overweight or obese. Effective weight management leading to modest weight loss to the order of 5-10% of body weight can lead to significant clinically meaningful benefits provided it can be maintained. Thus weight management can lead to improved glycaemic control, better blood pressure control and lipid control in addition to other benefits. Management of diabetic patients who are obese requires management also of other associated co-morbid conditions and it is important to ensure that glycaemic control does not deteriorate during weight management. An integrated approach to weight management in the diabetic patient is recommended which helps to promote lifestyle modification for all patients. Drug therapy may be appropriate for many obese patients who do not reach target weight loss with lifestyle modification alone. Surgery should be reserved for those wfth BMI >40 only after failed medical therapy.

Cardiovascular Diseases↗

Molecular expression systems for anti-DNA antibodies--2.

Antibodies to double-stranded DNA are the best-known serological markers of systemic lupus erythematosus, and are closely associated with its renal pathogenesis. How these antibodies recognize DNA is not fully understood. An understanding of the relationship between the functional attributes of an antibody with the three-dimensional structure of its antigen-combining site would allow an insight into the rules that dictate auto-antibody-nucleic acid interaction and consequent pathogenicity of the autoantibody. Data from such studies could assist the development of novel drugs as an approach to specific therapies that can inhibit or disrupt protein-nucleic acid interactions. A full understanding of the binding specificities can be achieved only by experimental determination of detailed three-dimensional structure of these antibodies alone, and of their complexes with specific DNA antigens. A prerequisite of such a study is the ability to produce multimilligram quantities of the antibody protein. However, these antibodies are particularly difficult to express, probably due to their DNA-binding activity. This review attempts to focus on the recent developments on the over-expression of anti-DNA antibody fragments in heterologous cell expression systems and their purification to homogeneity that would in turn allow their structural studies via crystallization.

Animals↗

Anti-DNA antibodies--structure and function.

Expression of monoclonal anti-DNA antibodies in vitro can be used to study the relationships between molecular structure, binding properties and pathogenicity. Bacterial and yeast systems can be used to produce antibody fragments such as Fab. The yields are potentially sufficient to allow structural studies such as crystallization, but purification of the anti-DNA Fab from the bacterial periplasm may be challenging. Mammalian cell expression systems produce lower yields, but the products are whole antibodies, which can be used in assays of pathogenicity. This article describes some recent experiments in which bacterial and mammalian systems were used to study human monoclonal anti-DNA antibodies. Light chain sequence motifs were found to be important both in binding to antigens and in determining pathogenicity of the antibodies in severe combined immunodeficiency mice. The distribution of B cell subpopulations is disturbed in patients with systemic lupus erythematosus (SLE). These patients, like those with infectious mononucleosis, have an overall B cell lymphopenia but an increased frequency of plasmablasts/early plasma cells in their blood. Some of these early plasma cells belong to clones that have rearranged the V(H) gene V4-34. There is a selective rise in immunoglobulins encoded by this gene in both infectious mononucleosis and SLE.

Animals↗

Haemangioma of the frontal sinus.

A 71-year-old lady underwent successful excision of a haemangioma of the frontal sinus, via an osteoplastic flap approach. Haemangioma of the paranasal sinuses is an extreme rarity. A case is presented and the literature reviewed.

Aged↗

Bioactivities of the leaf essential oil of Curcuma longa (var. ch-66) on three species of stored-product beetles (Coleoptera).

Essential oil extracted from the leaves of turmeric, Curcuma longa L., was investigated for contact and fumigant toxicity and its effect on progeny production in three stored-product beetles, Rhyzopertha dominica F. (lesser grain borer), Sitophilus oryzae L. (rice weevil), and Tribolium castaneum Herbst (red flour beetle). Oviposition-deterrent and ovicidal actions of C. longa leaf oil were also evaluated against T. castaneum. The oil was insecticidal in both contact and fumigant toxicity assays. The adults of R. dominica were highly susceptible to contact action of C. longa leaf oil, with LD50 value of 36.71 microg/mg weight of insect, whereas in the fumigant assay, adults of S. oryzae were highly susceptible with LC50 value of 11.36 mg/liter air. Further, in T. castaneum, the C. longa oil reduced oviposition and egg hatching by 72 and 80%, respectively at the concentration of 5.2 mg/cm2. At the concentration of 40.5 mg/g food, the oil totally suppressed progeny production of all the three test insects. Nutritional indices indicate >81% antifeedant action of the oil against R. dominica, S. oryzae and T castaneum at the highest concentration tested.

Animals↗

Familial trigeminal neuralgia.

Familial trigeminal neuralgia is infrequent. A report of a couple and their son being afflicted by this malady is presented. The clinical features, radiological findings and surgical management are discussed and literature reviewed.

Adult↗

Respiratory distress in neonates with special reference to pneumonia.

OBJECTIVE: (i) To find causes of respiratory distress in neonates brought to a referral neonatal unit with symptoms suggestive of respiratory disorder; (ii) to evaluate clinical signs for diagnosis of neonatal pneumonia; (iii) To determine bacterial etiology of neonatal pneumonia; and (iv) To determine indicators of fatality in neonatal pneumonia. DESIGN: Prospective descriptive. SETTING: Referral neonatal unit of a teaching hospital. SUBJECTS: 150 neonates admitted with respiratory symptoms consecutively. METHODS: All neonates presenting with respiratory symptoms were included in the study. The diagnosis of the cause of respiratory distress was based on guidelines recommended by the National Neonatology Forum. Clinical features, FiO2 requirement, sepsis screen, X-ray chest, blood culture and antibiotic sensitivity, arterial blood gases and other relevant investigations were documented in a structured proforma. The neonates were regularly followed up for outcome. Multivariate unweighted logistic regression was done to find out the indicators of fatality in neonatal pneumonia for those variables which were significantly associated with outcome on univariate analysis. RESULTS: Pneumonia was found to be the most common cause (68.6%) of respiratory distress in neonates. Other conditions included hydline membrane disease (HMD), transient tachypneia of new born (TTNB), birth asphyxia with hypoxic ischemic encephalopathy (HIE) and meconium aspiration syndrome (MAS). Clinical signs and symptoms were non specific and did not differentiate between pneumonia and other causes of respiratory distress. Respiratory rate was less than 60 per minute in 11.6% neonates with pneumonia. The most common organism responsible for neonatal pneumonia was Klebsiella pneumoniae. Chest X-ray was clear in 15% of neonates with pneumonia. On univariate analysis weight < 2000 g, gestation age < 34 weeks, age at presentation < 72 hours, lethargy, absent neonatal reflexes, shock, positive C-reactive protein, positive ventilatory support, blood culture positivity, Silverman Score >3, FiO2 >40%, pH < 7.2, alveolar arterial gradient (AaDO2) > 250 mmHg and arterial alveolar tension ratio (a/A) of < 0.25 were significantly associated with mortality in neonates with pneumonia. However, on multivariate analysis, only AaDO2 of > 250 mmHg was found to be independent predictor of fatality in neonatal pneumonia. CONCLUSION: Pneumonia was the most common cause of respiratory distress in neonates. Clinical features and X-ray chest missed the diagnosis of pneumonia in 15 cases and had to be corroborated with sepsis screen and blood culture. AaDO2 > 250 mmHg was an independent predictor of fatality in neonatal pneumonia

Analysis of Variance↗