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Biomedical subjects

A K Mandal

Publications and source records attributed to A K Mandal.

At least 19 recordsLinked to original sources
PubMed1995

Is quinine effective and safe in leg cramps?

Muscle cramp is a recurrent and painful condition and a common complaint among elderly subjects and patients treated with hemodialysis. It is commonly nocturnal and can disturb a good night's sleep. No specific cause can be identified; therefore, therapy is mostly symptomatic. Quinine sulfate, an antimalarial drug, is widely used as an effective therapy for idiopathic leg cramps. Several double-blind, randomized, placebo-controlled studies have questioned the effectiveness of quinine in leg cramps; whereas other studies have shown significantly more benefit with use of quinine in reducing the frequency and severity of cramps compared with placebo or vitamin E. The mechanism of this beneficial effect is obscure, however. Quinine appears to decrease the excitability of the motor end plate, thereby reducing the muscle contractility. Most patients consider quinine beneficial for their leg cramps, which is difficult to refute by scientific data. More important, cramp is a subjective symptom, therefore difficult to measure objectively. Consequently, scientific studies designed to prove or disprove the effectiveness of quinine can be subject to flaws. Further, a dosage of 200 to 300 mg of quinine every night has not been shown to cause significant side effects. Nevertheless, quinine should be used in a small dose and cautiously, especially in the elderly and patients with renal failure, and should be avoided in patients with liver disease.

Aged↗
PubMed1995

Sympathetic nervous system mediated cardiovascular effects of cocaine are primarily due to a peripheral site of action of the drug.

Currently, augmentation of sympathetic nervous system function produced by cocaine is thought to be due primarily to stimulation of sympathetic centers in the brain (central effect) and to inhibition of catecholamine uptake into postganglionic sympathetic nerve terminals (peripheral effect). In this review of our work, we present the following evidence that cocaine-induced changes in cardiovascular function, particularly those that peak within 1 to 5 min after an i.v. bolus injection of the drug, are due to a peripheral effect of the drug: (1) In both dogs and cats, cocaine potentiates the tachycardiac effect of neurally-released and injected norepinephrine (NE). The time course of action and dosage range of cocaine that produces potentiation follows that which increases blood pressure (BP), heart rate (HR), rate-pressure product and coronary vasoconstriction. (2) Cocaine given in i.v. doses that increase BP in decerebrate cats (0.25-1.0 mg/kg) has no significant effect on directly monitored spontaneous cardiac sympathetic nerve activity (SNA). In fact, higher doses of cocaine (2-4 mg/kg, i.v.) consistently inhibit preganglionic cardiac and splanchnic nerve activity. (3) Cocaine (0.1-1.0 mg) administered directly into the blood supply of the hindbrain via the vertebral artery produces no increase in BP, HR or SNA in cats; instead, decreases in BP and sympathetic activity occur. The same dose (1 mg), injected i.v., does not depress BP or SNA. In addition, cocaine injected into the forebrain via the carotid artery or into the cerebral ventricles (0.1-1.0 mg) has very little effect on BP. Our results indicate that there is no significant excitatory effect of cocaine on CNS sympathetic centers, and that the sympathomimetic effects of cocaine on the cardiovascular system are likely to be mediated at peripheral sites.

Animals↗
PubMed1994

Gunshot wounds of the male external genitalia.

The explosive increase of violence in our society has imposed hazards of gunshot injuries on the civilian population. The genitourinary system is no longer exempted from such assaults. Although male external genitalia are amongst less commonly involved organs, in a span of 14 months, 4 such cases were managed at our institute. Our experience of such injuries is being highlighted so as to draw attention to their increasing incidence and association with injuries of other organs. Three patients had haemorrhagic shock at initial presentation. They were managed by resuscitation, debridement and repair of wounds Urethral injuries were dealt initially by diversion and subsequently urethroplasty was performed. In a follow-up of 6-12 months, all the patients were reported to be having normal erections and none of them have developed urethral stricture.

Adolescent↗
PubMed1993

Effect of heparin on endothelin-1 production by cultured human endothelial cells.

Heparin shows a blood pressure-lowering effect in various hypertensive rat models. This study was designed to examine the effect of heparin on vasoconstrictor endothelin-1 (ET-1) production by cultured human umbilical vein endothelial cells (HUVECs). ET-1 and cyclic GMP levels in the medium were determined by radioimmunoassay. ET-1 mRNA was quantified by densitometric Northern blot analysis. ET-1 was released into the medium in a time-dependent manner, and its release was augmented by thrombin (10 U/ml). Heparin suppressed both basal and thrombin-stimulated ET-1 secretion and its mRNA expression in a dose-dependent manner. Heparin suppressed ET-1 mRNA expression in a time-dependent fashion. Heparin did not suppress both basal and thrombin-stimulated ET-1 production in the presence of NG-monomethyl-L-arginine (L-NMMA) (10(-5) M). The production of cGMP stimulated by thrombin was significantly enhanced by heparin, but not in the presence of L-NMMA (10(-5) M). Heparin may suppress vasoconstrictor ET-1 production mediated by the enhancement of endothelium-derived nitric oxide in HUVECs.

Blotting, Northern↗
PubMed1992

The effect of acute and chronic hematocrit changes on cardiovascular hemodynamics in spontaneously hypertensive rats.

Heparin given over a long term by a subcutaneous route consistently lowers blood pressure in the hypertensive rat models. The decrease in blood pressure is accompanied by a parallel decrease in hematocrit suggesting a causal relationship between hematocrit and blood pressure. The aim of this study was to define the relationships between acute and chronic hematocrit changes and blood pressure in the normotensive and hypertensive states. Normotensive Wistar (NWR) and spontaneously hypertensive (SHR) rats were used. Hematocrit was decreased acutely by blood-letting, and chronically by treatment with either heparin (H) or phenylhydrazine (P) for 4 weeks. Acute and chronic hematocrit increase was accomplished by packed cells transfusion. Systolic blood pressure was measured weekly; and at the end of the experimental period, plasma volume, cardiac output, and mean arterial pressure were obtained. Acute hematocrit decrease or increase (hematocrit ranging from 25 to 65%) did not affect blood pressure in either strain of rats; whereas chronic hematocrit changes (hematocrit ranging from 35 to 61%) significantly affected blood pressure only in SHR. Thus, chronic hematocrit decrease induced by H or P resulted in a significant fall in blood pressure compared to control (201 +/- 3 v 175 +/- 4, 167 +/- 4 mm Hg, respectively; P < .05). Conversely, a chronic hematocrit increase resulted in a significant rise in blood pressure (201 +/- 3 v 219 +/- 4 mm Hg; P < .05). Similar hematocrit changes produced in NWR, as in SHR, did not affect blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Heparin suppresses endothelin-1 action and production in spontaneously hypertensive rats.

Previous studies have shown that chronic subcutaneous administration of heparin significantly reduces blood pressure in hypertensive rats. The intracellular mechanisms of how heparin prevents smooth muscle cell proliferation remain unclear. This study was designed to examine whether heparin affects endothelin-1 action and production, to further elucidate the mechanism of the antihypertensive effect of heparin. Four-week treatment with heparin (300 U/day sc) significantly decreased blood pressure in spontaneously hypertensive rats (SHR; 199 +/- 8 vs. 164 +/- 9 mmHg; P < 0.001) and completely blunted pressor response to endothelin-1 in SHR. Heparin treatment did not decrease blood pressure response nor did it attenuate blood pressure responses to endothelin-1 in Wistar-Kyoto rats (WKY). Heparin significantly suppressed endothelin-1-induced increase in intracellular calcium concentration and inositol 1,4,5-trisphosphate level in cultured vascular smooth muscle cells in a dose-dependent manner and endothelin-1 release from cultured endothelial cells. These inhibitions were significantly more pronounced in SHR than in WKY. In conclusion, our findings indicate that the antihypertensive effect of heparin is mediated, at least in part, by the inhibition of endothelin-1 action on vascular smooth muscle cells and endothelin-1 production from endothelial cells.

Animals↗
PubMed1992

Giant calculus in anterior urethral diverticulum.

The case of probably the largest stone in a giant anterior urethral diverticulum presenting with septicemia and renal failure is reported. Stage surgical reconstruction had an excellent result.

Diverticulum↗
PubMed1992

Treatment considerations in acute renal failure.

Acute renal failure (ARF) is characterised by progressive azotaemia, and for therapeutic purposes consideration of prerenal, intrinsic renal and postrenal types still holds good. Prerenal azotaemia is generally caused by loss of body fluids or blood, whereas postrenal azotaemia is effected by acute or chronic urinary tract obstruction. Provided these conditions are recognised on time and treated, they are reversible. However, delay in recognition or treatment could result in renal parenchymal damage and sustained ARF. Therefore utmost attention should be focused on identifying reversible factor(s) in the setting of ARF. Once reversible factors have been excluded, and ARF becomes sustained, a diagnosis of acute intrinsic renal failure is almost certain. Lack of natriuretic and diuretic responses to fluid challenge or infusion of furosemide (frusemide) and dopamine are further indications of this possibility. Management of acute intrinsic renal failure essentially consists of dietary control and dialysis therapy. The latter facilitates fluid and electrolyte management, but does not reduce the overall mortality. The potential benefit of parenteral hyperalimentation to promote renal function recovery must be carefully weighed against the risk of severe infectious complications.

Acute Kidney Injury↗
PubMed1991

Antimicrobial activity of intravenous quinolones on the intestinal microflora in dogs.

The antimicrobial activity of intravenously given quinolones on the intestinal microflora was unknown and therefore studied in dogs with a surgically isolated loop of the jejunum. Ciprofloxacin, enoxacin and norfloxacin were actively excreted by the intestinal mucosa and achieved therapeutic levels within the lumen of this isolated jejunal loop. Also the total counts of enterococci and Escherichia coli decreased in this loop of the jejunum as well as in the stool. All three quinolones, when given intravenously, decreased the total counts of anaerobic bacteria including Bacteroides fragilis.

Animals↗
PubMed1991

An electron microscopy study of urinary sediment: relationship between myeloid body excretion and gentamicin nephrotoxicity in the rat.

We studied renal function, urinary enzymes, urinary sediment, and renal histopathology in Fischer 344 rats that were treated with one dose of mercuric chloride (HgCl2) alone, HgCl2 followed by gentamicin, gentamicin alone, or gentamicin, followed by HgCl2. HgCl2 was administered intraperitoneally at 1 mg/kg body weight. Gentamicin was injected subcutaneously at 40 mg/kg body weight. Renal function was assessed by creatinine clearance. Urinary sediment was examined using transmission electron microscopy; particular attention was given to the numbers by myeloid bodies in the urinary sediment. Renal tissue was assessed using light microscopy for acute tubular necrosis (ATN). In either HgCl2- or saline-treated rats urinary sediment showed no myeloid bodies, and renal morphology was essentially normal. The rats given HgCl2 48 h prior to initiation of gentamicin therapy showed significant decrease of myeloid bodies excretion. This was accompanied by significantly less impairment of renal function, mild renal lesion, and no necrotic tubule cells in urinary sediment. The rats treated with either gentamicin alone or gentamicin followed by HgCl2 developed significant impairment of renal function in association with marked elevation of the urinary enzymes, and variable extent of ATN. In both of these groups, urinary sediment showed a profusion of free myeloid bodies and many necrotic renal tubule cells. The urinary sediment findings, however, did not aid in distinguishing between these two treatment groups. From these data we conclude that (1) a tentative relationship exists between the concentration of the urinary myeloid bodies and severity of gentamicin nephrotoxicity; (2) prior treatment with compound(s) analogous to HgCl2 which could minimize urinary excretion of the myeloid bodies might be useful in the mitigation of gentamicin nephrotoxicity.

Animals↗
PubMed1991

The role of serotonin-1A receptor activation and alpha-1 adrenoceptor blockade in the hypotensive effect of 5-methyl-urapidil.

Our study had three purposes: 1) to determine whether 5-methyl-urapidil, topically applied to the ventrolateral medulla, produces hypotension by activating serotonin-1A (5-HT1A) receptors, 2) to determine whether 5-methyl-urapidil given i.v. produces hypotension in part by activating 5-HT1A receptors in the ventrolateral medulla, and 3) to determine the specific site within the ventrolateral medulla where 5-methyl-urapidil elicits a hypotensive response. In terms of the first purpose, 5-methyl-urapidil applied bilaterally to the intermediate area of the ventral surface of the medulla (1.2 micrograms/side) of chloralose-anesthetized cats produced a decrease in mean arterial pressure of -39 +/- 4 mm Hg (N = 8). Prior blockade of 5-HT1A receptors at this site with bilateral application of spiperone (30 micrograms/side) prevented the hypotensive effect of 5-methyl-urapidil (mean blood pressure now increased by 5 +/- 4 mm Hg). Pretreatment with the alpha-1 adrenoceptor antagonist, prazosin, did not prevent the hypotensive effect of 5-methyl-urapidil. In terms of the second purpose, spiperone applied bilaterally to the ventral surface of the medulla counteracted a significant portion of the hypotensive effect of 5-methyl-urapidil given by the i.v. route. The dose of 5-methyl-urapidil given intravenously was below the dose that produces alpha-1 adrenoceptor blockade. In terms of the third purpose, microinjection of 5-methyl-urapidil into central nervous system sites associated with the intermediate area was found to have its greatest hypotensive effect at the subretrofacial nucleus. Mean arterial pressure decreased by 74 +/- 14 mm Hg (N = 3) after bilateral microinjection of 25 ng of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1991

Erythrocyte deformation in ischemic acute tubular necrosis and amelioration by splenectomy in the dog.

Bilateral renal artery occlusion (RAO) for 120 minutes in dogs results in acute tubular necrosis (ATN) and peritubular capillary (PTC) congestion with rapidly deteriorating renal function. We have shown that prior splenectomy minimizes RAO-induced renal functional and histopathologic changes. The purpose of this study was to examine whether this renal protection is due to prevention of red blood cell echinocyte formation and resultant renal PTC congestion. Echinocytes (burr cells) are poorly deformable, impart high viscosity to the blood, and may hinder reperfusion by increasing resistance to renal capillary blood flow. Splenectomized (SPLX) or sham-SPLX dogs were treated with bilateral RAO for 120 minutes. After RAO, renal function and renal blood flow were monitored, and peripheral blood red blood cells were examined at 1 hour and at 24-hour intervals for 96 hours. Renal biopsies were taken 1 hour after RAO and the kidneys removed 96 hours after RAO. The RBCs and renal tissues were studied using scanning electron microscopy. Renal function was assessed by endogenous creatinine clearance. Sham-SPLX animals showed a marked and sustained decrease in creatinine clearance, consistently elevated serum creatinine levels and fractional excretion of sodium, and diffuse ATN and PTC congestion with echinocytes. These animals had a peak in circulating echinocytes 1 hour after RAO (p less than 0.05), which showed an excellent negative correlation with creatinine clearance (r = -0.999; p less than 0.001). On the contrary, SPLX animals had essentially no change in serum creatinine or fractional excretion of sodium, minimal tubular changes, no PTC congestion, and no rise in circulating echinocytes during the 96-hour observation. In vitro treatment of the postischemic red blood cells from sham animals with adenosine-inosine or fresh postischemic plasma from the SPLX animals showed almost complete reversal to discocytes (normal red blood cells), whereas in vitro treatment of postischemic red blood cells from the SPLX animals with fresh postischemic plasma from the sham animals resulted in a marked echinocytic response. We conclude that 1) a marked echinocyte response in the immediate postischemic period is an important mechanism in initiating ischemic ATN, 2) an echinocyte inducing factor may reside in the plasma of spleen-intact animals, and 3) mitigation of ATN and PTC congestion by splenectomy is, at least in part, consequential to attenuated echinocytic response in the immediate postischemic period.

Animals↗
PubMed1991

Primary tumors of small bones: a clinicopathological and radiological study.

Primary small bone tumors are rare. Most of them have been reported as solitary case reports in the literature. In this retrospective study of small bone tumors over the period of five years, the commonest tumor encountered was enchondroma. Next in frequency were exostosis, giant cell tumor, benign chondroblastoma. Solitary cases of benign osteoblastoma, mesenchymal chondrosarcoma and glomus tumors were encountered. All these cases were analysed clinically, radiologically and correlated with histopathology in each case.

Adolescent↗
PubMed1991

Risk of aortocoronary bypass surgery in a low-volume inner city hospital.

Incidence of coronary heart disease deaths has been reported to be higher in low socioeconomic groups compared to affluent subjects. In addition, a higher mortality rate has been reported at centers doing fewer open heart surgeries. This article presents evidence in variance with these convictions. We report a single team's experience with coronary artery surgery on 76 low socioeconomic, predominantly black patients (84%) over a period of 8 years. The volume of open heart surgery per year was less than 20. The overall mortality rate of 5.3%, infection rate of 1.3%, and perioperative infarction rate of 7.9% are not significantly different from the reported experience of high-volume surgical centers on similar patients during the same period. Thus, it is possible to obtain comparable results of myocardial revascularization surgery in low-volume, socioeconomically disadvantaged, inner city minority populations.

Adult↗
PubMed1991

Cocaine acts in the central nervous system to inhibit sympathetic neural activity.

Cocaine was administered i.v. to decerebrate cats while monitoring cardiac preganglionic sympathetic nerve activity (SNA), arterial blood pressure (BP) and heart rate (HR). Cocaine, 4 mg/kg i.v., reduced SNA by 55 +/- 6%, but did not significantly affect BP or HR. Cocaine, in doses that were ineffective by the i.v. route, was administered into the vertebral artery and produced decreases in SNA, BP and HR in anesthetized cats. Administration of cocaine into the carotid artery was without effect. Topical administration of cocaine to the intermediate area of the ventrolateral medullary surface (25 micrograms/side) evoked hypotension and bradycardia. Nisoxetine, an inhibitor of norepinephrine uptake, applied bilaterally to the intermediate area (30 micrograms/side) exerted a similar hypotensive effect. Lidocaine administered in doses equivalent to those of cocaine had no significant effect on SNA when given i.v. or on BP when given into the vertebral artery. These results indicate that cocaine inhibits central sympathetic outflow and that the site of action appears to be in the hindbrain at a site that is reached by placement of the drug at the intermediate area of the ventrolateral medulla. The data also indicate that the mechanism of action of cocaine to inhibit sympathetic outflow may be unrelated to its local anesthetic action and may involve inhibition of catecholamine uptake in the ventrolateral medulla.

Animals↗
PubMed1991

Bacteriology of the appendix and the ileum in health and in appendicitis.

The bacteriology of the ileum and the appendix in appendicitis patients with or without perforation and compared with patients who had "incidental appendectomy" was studied. Of 42 appendicitis patients, 24 (57%) of them had anaerobic bacteria in the appendix compared with two of eight (25%) with normal appendix. Anaerobes were found in the ileal aspirates of 20 of 42 (47.6%) appendicitis patients and two of eight (25%) in normal persons. This suggests that anaerobic bacteria increasingly colonize the appendix and the ileum in cases of appendicitis.

Adolescent↗