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Biomedical subjects

P Kumar

Publications and source records attributed to P Kumar.

At least 433 records · Page 24Linked to original sources

Interjugular neck dissection and post-operative irradiation for neck control in advanced glottic cancers--are we justified?

At the Kidwai Memorial Institute of Oncology, advanced laryngeal cancers are subjected routinely to primary surgery and/or post-operative radiotherapy (RT). The surgery consists of wide field laryngectomy which entails total laryngectomy, ipsilateral/bilateral thyroid lobectomy, bilateral paratracheal clearance, and bilateral clearance of levels 2, 3 and 4 lymphatics. Post-operative RT is indicated in event of the following histopathological (HPE) situations to consolidate local-regional control: (1) T4 primary; (2) significant subglottic extension; and (3) jugular/paratracheal metastatic deposits. This prospective study highlights the therapeutic efficacy of this protocol at our centre in 45 consecutive T4/T3 glottic cancers and specifically evaluates the role of interjugular dissection and/or post-operative RT in prevention of regional recurrence. Fifty-two per cent of primary lesions needed a post-surgical upstaging as against 14 per cent of the neck lesions. Accordingly 91 per cent of the cases (41/45) qualified for post-operative RT and 82 per cent (37/41) complied with the prescribed schedule. Recurrent disease in the lateral neck was noted in 2/37 who received the prescribed schedule and 1/4 non-compliant cases; while a recurrent central neck disease was noted in 1/37 and 1/4 of these cases respectively. All cases were followed-up for a period of two years and 66 per cent of the evaluable cases for a period of five years. This study confirms conclusively that our treatment schedule yields extremely gratifying two-year local-regional control rates of 89 per cent which translates into a two and five-year actuarial survival rate of 92 and 70 per cent respectively.

Combined Modality Therapy↗

Transfusion of blood components to persons infected with human immunodeficiency virus type 1: relationship to opportunistic infection.

BACKGROUND: Although a recent study reported shorter survivals in human immunodeficiency virus type 1 (HIV-1)-infected patients who received transfusions, no study has analyzed the relationship in such patients between the frequency of opportunistic infection and transfusion. STUDY DESIGN AND METHODS: Records of 196 HIV-1-infected subjects with CD4 lymphocyte counts below 250 cells per mm3 were reviewed to determine if there were more opportunistic infections in patients who previously received transfusions than in those who received no transfusions. The decline in CD4 cells was also compared, and the frequency of transfusion reactions and red cell alloantibodies was assessed. RESULTS: The frequency of cytomegalovirus (CMV), wasting, and bacterial infections (p < 0.01), but not the frequency of Pneumocystis carinii pneumonia (PCP) (p > 0.2), was significantly increased in the patients who had previously received transfusions, and this effect was independent of CD4 count, race, or risk factor. The frequency of CMV infection, but not of PCP, was also related to the number of units of blood received (p < 0.01). Significant bacterial infections occurred primarily in persons with CMV infection, of whom there were more in the transfusion cohort. When analyzed separately in the group of patients without CMV infection, the frequency of bacterial infection was unrelated to transfusion. The death rate in those who received transfusions was also greater than that in patients who had never received a transfusion. None of the 130 patients who received red cell transfusions developed red cell alloantibodies. CONCLUSION: The higher incidence of certain infectious complications in HIV-1-infected patients who received transfusions indicates that the relationship of transfusion to virus activation in patients with acquired immunodeficiency syndrome and the potential benefits of modifying the preparation of blood components should be investigated further.

AIDS-Related Opportunistic Infections↗

Effect of amphotericin B and fluconazole on platelet membrane glycoproteins.

BACKGROUND: Fever, chills, and reduced platelet recovery may result when platelets are transfused simultaneously with amphotericin B. Amphotericin B reportedly increases the pitting of membranes in stored platelets. STUDY DESIGN AND METHODS: The effects of amphotericin B and another antifungal agent, fluconazole, on platelet membrane glycoproteins (GP) were examined by the incubation of split aliquots of fresh and stored platelet concentrates (PCs) with these drugs for 3 days in storage bags. To determine the effect of storage, PCs were stored for 5 days, and aliquots removed on Days 1 through 5 were placed in platelet storage bags with 4 micrograms per mL of amphotericin B for 2 to 6 hours. Membrane glycoprotein expression was assessed by flow cytometry with fluorescein isothiocyanate-labeled monoclonal antibodies (MoAbs) directed against the following antigens: GPIb (CD42b), CD63 (an activation protein), P-selectin (CD62), and GPIIb/IIIa (CD41a). RESULTS: Amphotericin B produced a concentration-dependent decrease in the surface binding of CD42b MoAb with no consistent changes in the binding of CD41a, CD63, or CD62 MoAbs after a 3-day exposure. Stored but not fresh PCs showed decreased binding of MoAb CD42b after a 6-hour exposure to amphotericin B (4 micrograms/mL). Fluconazole produced no changes. When the binding of MoAb CD42b to permeabilized platelets was used to measure total platelet content, amphotericin B (4 micrograms/mL) decreased MoAb CD42b binding to a similar degree in fresh and stored platelets. Inhibition of aggregation to ADP and collagen and ADP and epinephrine was seen in stored but not fresh PCs. CONCLUSION: Therapeutic levels of amphotericin B resulted in partial loss of total platelet GPIb in fresh and stored PCs, but decreased surface expression of platelet membrane GPIb only in stored platelets. This difference between fresh and stored platelets may be related to the limited reservoir of GPIb available for redistribution to the membrane in the previously stored PCs and may account for the decreased recovery of transfused platelets observed in some patients receiving amphotericin B.

Amphotericin B↗

Melatonin prevents the suppression of cardiac Ca(2+)-stimulated ATPase activity induced by alloxan.

The effects of melatonin treatment on cardiac sarcolemmal membrane function were investigated in alloxan-injected rats. Ca(2+)-stimulated adenosine-triphosphatase (ATPase, Ca2+ pump) and Mg(2+)-ATPase activities were depressed significantly in sarcolemmal preparations from alloxan-injected rats compared with levels in control rats. These deficits were observed 2 days after alloxan injection, and they were accompanied by an increase in the density of voltage-sensitive calcium channels, as measured by the [3H]nitrendipine-binding assay. In a dose-dependent manner, treatment of rats with melatonin before alloxan injection significantly overcame the suppression of Ca(2+)-stimulated ATPase in cardiac sarcolemma. Melatonin (1, 5, and 10 mg/kg) overcame Ca(2+)-stimulated ATPase suppression by 13, 35, and 70%, respectively. In addition, melatonin at a dose of 10 mg/kg also prevented the suppression of the Mg(2+)-ATPase by 31%. The number of [3H]nitrendipine-binding sites was not influenced by melatonin. The patent Na(+)-K(+)-ATPase and ouabain-sensitive Na(+)-K(+)-ATPase activities were not different between the control and experimental groups. The results indicate that Ca2+ pump activity is suppressed by acute alloxan treatment, whereas the density of voltage-sensitive calcium channels is increased. These changes may be a consequence of alloxan toxicity to the cardiac sarcolemma. Melatonin, likely because of its antioxidant capacity, exerts a protective effect on heart sarcolemmal membrane function in alloxan-injected rats.

Adenosine Triphosphatases↗

Role of angiogenesis in patients with cerebral ischemic stroke.

BACKGROUND AND PURPOSE: Stroke is one of the most common causes of mortality and morbidity in the Western world. It results from the occlusion of a cerebral artery followed by severe disturbances in blood supply through microvessels to brain tissue. Despite an extensive literature its pathophysiology is poorly understood, and this has severely impeded the logical development of therapy. METHODS: Brains were obtained from 10 patients aged 46 to 85 years with survival times of 5 to 92 days after their stroke. Infarcted areas and representative control tissues from the contralateral uninvolved brain hemisphere were collected. Microvessel density was measured microscopically. A total of 6520 microvessels were scored in 10,801 areas. The level of activation of the endothelial cells was studied by immunohistochemistry using three monoclonal antibodies, viz, E-9, raised against activated endothelial cells; IG11, recognizing vascular cell adhesion molecule-1; and anti-proliferating cell nuclear antigen. Angiogenic activity in tissue extracts was examined using an in vivo chicken chorioallantoic membrane assay. RESULTS: There was a statistically significant increase in the number of microvessels (Wilcoxon log-rank test; P < or = .01) in 9 of 10 infarcted brain tissues when compared with their contralateral normal hemisphere. In these patients the higher blood vessel counts correlated with longer survival, as ascertained by Spearman's p analysis (P < .02). The number of microvessels filled with blood cells was significantly lower in the infarcted hemispheres (P < .01). In contrast, statistically significant increased numbers of empty microvessels occurred in infarcted tissues compared with the contralateral hemisphere. Monoclonal antibody E-9 reacted weakly with normal-brain vascular endothelial cells; anti-proliferating cell nuclear antigen and IG11 were virtually negative. All three antibodies strongly stained the blood vessels of stroke tissues. The stroke tissues contained angiogenic activity, as shown by the induction of new blood vessels in a chorioallantoic membrane assay. CONCLUSIONS: We have shown that stroke causes active angiogenesis that is more developed in the penumbra. Further experiments are needed to determine if this angiogenesis has beneficial effect.

Aged↗

The respiratory response of healthy term infants to breath-by-breath alternations in inspired oxygen at two postnatal ages.

We have studied the reflex respiratory responses to breath-by-breath alternations in fractional inspired oxygen in a group of healthy term infants at two ages, 43 +/- 7 h (study 1) and 47 +/- 3 d (study 2). Respiration was measured noninvasively using inductance plethysmography. Responses to alternations of fractional inspired oxygen between 0.16 and 0.21 (test runs) were compared with responses to alternating the inspired gas between two lines each containing a fractional inspired oxygen concentration of 0.21 (control runs). The respiratory response was measured as the mean percentage breath-by-breath alternation for inspiratory tidal volume (VTI), expiratory tidal volume (VTE), inspiratory time (TI), expiratory time (TE), frequency (f), mean inspiratory flow (VTI/TI), mean expiratory flow (VTE/TE), timing (TI.f), and ventilation. A significant chemoreflex response was present in the infants at the time of study 1, as shown by test runs that were significantly different from control for TI, TE, f, mean inspiratory flow, mean expiratory flow, timing, and ventilation (p < 0.05), and at study 2 for VTI, VTE, TE, f, mean inspiratory flow, mean expiratory flow, timing, and ventilation (p < 0.05). When control and test runs were compared separately with respect to age, there were no significant differences for any respiratory variable between study 1 and study 2. Thus, we did not observe significant maturation of respiratory chemoreflex responses to hypoxia after an age at which we could detect an established response, and this suggests that the "resetting" of chemoreceptor responses to hypoxia is essentially complete within approximately 24-48 h of birth in humans.

Age Factors↗

Absence of ventilatory responses to alternating breaths of mild hypoxia and air in infants who have had bronchopulmonary dysplasia: implications for the risk of sudden infant death.

Infants who have had bronchopulmonary dysplasia (BPD) are at an increased risk of sudden infant death syndrome. Because failure of the cardiorespiratory response to hypoxia is suggested to play a key role in sudden infant death syndrome, we tested the hypothesis that infants who have had BPD have a reduced respiratory chemoreflex response to hypoxia. We examined the reflex respiratory responses to breath-by-breath alternations in fractional inspired oxygen concentration in eight infants who had had BPD (mean gestation = 27 wk, mean postnatal age = 93 d) who were no longer on supplemental oxygen and compared the responses with those of 12 preterm infants who had not required supplemental oxygen or been mechanically ventilated since birth (mean gestation = 30 wk, mean postnatal age = 38 d). For test runs we alternated fractional inspired oxygen concentration through two gas delivery lines between 0.21 and 0.16 on a breath-by-breath basis, and for control runs we alternated the inspirate between the two gas lines with a fractional inspired oxygen concentration of 0.21 in each. Respiration was measured using inductance plethysmography infants with BPD showed no significant differences between test and control responses for any respiratory variable. In contrast, all respiratory variables in the preterm infants showed test responses significantly greater than control. We speculate that the "blunted" chemoreflex respiratory response seen in infants with BPD may predispose them to subsequent respiratory failure, but we do not known which component of the chemoreflex is impaired.

Bronchopulmonary Dysplasia↗

Melatonin reduces 3H-nitrendipine binding in the heart.

The effect of melatonin on cardiac and brain voltage-sensitive calcium channels, as measured by 3H-nitrendipine binding, was examined in rats 3 hr after melatonin administration (either 0.5 or 1.0 mg/kg given subcutaneously). Scatchard analysis of the data on specific binding of 3H-nitrendipine with crude cardiac membranes from melatonin treated rats revealed significant decreases (P < 0.05 and P < 0.01 for the 0.5 and 1.0 mg/kg melatonin doses, respectively) in the density of Ca2+ channels without a change in their affinity for the ligand. At doses of 0.5 and 1.0 mg/kg of melatonin, Bmax values were 157 and 142 fmoles/mg protein, respectively, compared with a control value of 199 fmoles/mg protein in crude cardiac membranes. In brain, melatonin treatment did not statistically significantly influence either 3H-nitrendipine binding or its affinity when compared with control animals. These results suggest that melatonin modulates the functional status of voltage sensitive calcium channels in the heart, changes that may have implications for normal cardiac physiology and for the pharmacological manipulation of the heart.

Animals↗

Post extracorporeal membrane oxygenation single photon emission computed tomography (SPECT) as a predictor of neurodevelopmental outcome.

OBJECTIVE: To determine the incidence and site of single photon emission computed tomography scan (SPECT) abnormalities in survivors of neonatal extracorporeal membrane oxygenation and to evaluate the efficacy of SPECT scan as a predictor of neurodevelopmental outcome in these infants. SETTING: Tertiary care neonatal intensive care unit in Detroit, MI. PATIENT POPULATION: Survivors of neonatal extracorporeal membrane oxygenation who had a SPECT scan of the brain performed after decannulation and before their discharge from the neonatal intensive care unit were included if they had at least 12 months of follow-up in our developmental assessment clinic. OUTCOME MEASURES: The neurological outcome was reported as normal, suspect, and abnormal on the basis of neurological examination and developmental milestones. The developmental outcome was assessed by Bayley mental development index or McCarthy general cognitive index scores. RESULTS: A total of 59 patients met study criteria. SPECT scan abnormalities were noted in 45 (76%) infants. Global hypoperfusion was the most frequent abnormality followed closely by bilateral focal perfusion defects. The distribution of perfusion abnormalities was not significantly different for right and left hemispheres. Among 14 infants with normal SPECT scans, 13 infants had normal neurological outcome and all had a normal developmental outcome. Of the 45 infants with an abnormal SPECT scan, 7 infants had an abnormal neurological outcomes and 4 infants had an abnormal developmental outcome. SPECT scan abnormalities had no significant correlation with neurodevelopmental outcome of these infants. CONCLUSION: Although a normal SPECT scan was more likely to predict a normal neurodevelopmental outcome, an abnormal SPECT scan did not predict an abnormal outcome in these infants.

Brain↗

VCAM-1 expression on reactive and tumour astrocytes.

In our studies we used a monoclonal antibody recognizing the vascular adhesion molecule (VCAM-1). Tissue samples were collected at autopsy from human brain infarcts and from brain tumours, removed during surgical procedure (Neurological and Neurosurgical Clinic, Cracow). A novel, unexpected finding were VCAM-1-positive fibrous astrocytes in the stroke tissue, and astrocyte-like cells in the tumours. No staining was obtained either in the contralateral hemisphere or outside of ischemic areas. Likewise, no positive staining of cells was seen outside the tumour tissue. The above findings, taken together, strongly support the concept that astrocytes take part in the immune defense during various pathological processes in the human brain.

Astrocytes↗

Efficacy of magnesium sulphate in aluminium phosphide poisoning--comparison of two different dose schedules.

The results of an open randomised study on the efficacy of magnesium sulphate therapy in aluminium phosphide poisoning are presented. One hundred and fifty five patients divided in three groups and matched for age, sex, dose, duration and severity of poisoning constituted the subject matter. Significant hypomagnesemia was observed in patients who did not receive magnesium sulphate (group 1). Two dose schedules of MgSO4 therapy were tried. The dose schedule No.1 given to patients of group 2 did not raise the magnesium levels significantly as compared to controls (group 4). The difference in the mortality between groups 1 & 2 was also not significant. On the other hand, the dose schedule No.2 given to patients of group 3 raised the magnesium levels significantly and these remained above normal limits throughout the observed period. This dose schedule brought down the mortality significantly than dose schedule No.1 (p < 0.001). It was also found that dose schedule No.2 has been effective in reducing the mortality irrespective of dose of pesticide consumed and its efficacy was due to rapid rise in magnesium levels. It is suggested that hypomagnesemia might be responsible for high mortality of patients of aluminium phosphide poisoning and its correction has beneficial effect on the management and ultimate favourable outcome of the illness.

Adolescent↗

Activity of some Mannich bases of conjugated styryl ketones against Candida albicans.

A number of Mannich bases of conjugated styryl ketones displayed activity against Candida albicans strains 3153A and B311. Antifungal potency was influenced by the relative hydrophobicities of the molecules and on occasions by the electronic nature of the aryl substituents. The compounds inhibited one or more of the following enzymes in the glutathione metabolic pathway namely glutathione S-transferases, glutathione reductase, gamma-glutamyl transpeptidase and glutathione peroxidase. Nearly half of the compounds examined on the yeast-to-mycelium transition in C. albicans 3153A prevented this conversion from occurring.

Antifungal Agents↗

Indigenous free radical scavenger MAK 4 and 5 in angina pectoris. Is it only a placebo?

Thirty patients were evaluated to study the effect of Maharishi Amrit Kalsh (MAK) 4 & 5 on Angina pectoris. The mean angina frequency per month was 8.87. Twelve lead ECG, computerized TMT and echo studies were done initially, at 6 months, and after 2 years in all cases. Ten grams of MAK 4 paste was given daily in two divided doses, each followed by a MAK 5 tablet, for six months. Vasodilator and antihypertensive drugs were continued on ethical grounds. Twenty-four patients (80%) out of the total 30 reported a significant improvement after 6 months of therapy. The mean angina frequency per month improved from 8.87 to 3.03. All patients reported a sense of well being. Five out of 11 hypertensive patients reported a fall in systolic blood pressure. Lipid profile showed a rise in HDL which was statistically insignificant. Improved exercise tolerance was observed in 10 cases (33.33%) after 6 months of therapy and this effect was sustained even at 2 years. ECG and echo studies were inconclusive. No side effects or drug interactions were seen. This beneficial effect observed is probably as a result of free radical scavenging property of MAK on 'Reactive Oxygen Species' or an inhibitory effect on lipid peroxidation; or by its inhibitory action on platelet aggregation or all these in synergism.

Adult↗

Treatment of nephrotic syndrome.

There are well defined therapeutic protocols for childhood nephrotic syndrome. Appropriate therapy helps in minimizing side effects besides decreasing referrals to tertiary care centres. We have analysed the appropriateness of therapy of primary care physicians in 111 children with nephrotic syndrome referred to our Institute from January 1989 to December 1991. Prednisone was administered in adequate doses in 51 (52.6%), and for adequate duration in 41 children (42.2%). Adjunctive cyclophosphamide therapy was administered in the recommended doses and duration in 33% of the cases. On evaluation of the therapy it was observed that inappropriate treatment had been administered by 39.4% of the pediatricians, 59% of internists and 80% of general practitioners. This study highlights the lacunae in the current state of knowledge amongst the primary physicians and highlights the need for creating greater awareness regarding the therapy of children with nephrotic syndrome.

Adolescent↗