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Biomedical subjects

K R Patel

Publications and source records attributed to K R Patel.

At least 55 records · Page 3Linked to original sources
PubMed1989

Dose-response study of nebulised nedocromil sodium in exercise induced asthma.

Ten patients with exercise induced asthma, in whom inhaled nedocromil sodium 4 mg by metered dose inhaler attenuated the exercise fall in forced expiratory volume in one second (FEV1) by at least 40%, participated in a double blind dose response study to compare the protective effect of nedocromil sodium given 15 minutes before exercise challenge via a nebuliser (Wright) in concentrations of 0.5, 5, 10, and 20 mg/ml with that of placebo (saline). Response was assessed as the maximum fall in FEV1 after the patient had run on a treadmill for six to eight minutes. Plasma concentrations of nedocromil sodium were measured at the time of challenge. After exercise challenge the mean (SEM) maximum percentage falls in FEV1 were 30.3 (1.6) for the control run and 28.0 (4.1) after placebo. The percentage fall was attenuated by pretreatment with all concentrations of nedocromil sodium to 12.8 (2.8), 11.2 (2.1), 12.8 (2.1), and 14.1 (3.5) for the 0.5, 5, 10, and 20 mg/ml concentrations respectively (p less than 0.001). There were no significant differences between the different nedocromil concentrations. Mean plasma concentrations of nedocromil were proportional to dose. Thus concentrations of nebulised nedocromil sodium that ranged from 0.5 to 20 mg/ml gave a similar degree of protection (50-60%) against exercise induced asthma. This appears to be the maximum protection that can be achieved with nedocromil sodium and is similar to the protection obtained with 4 mg nedocromil administered by metered dose aerosol.

Adolescent↗
PubMed1989

Effect of inhaled leukotriene C4 on cardiopulmonary function.

The changes in transcutaneous oxygen saturation (SaO2%) and airway responses to inhaled histamine and leukotriene C4 (LTC4) were examined in 10 asthmatic patients, and the effect of inhaled LTC4 (16 nmol) on cardiopulmonary hemodynamics was examined in seven nonasthmatic patients undergoing diagnostic cardiac catheterization. In asthmatic patients, LTC4 produced oxygen desaturation on two occasions. At a lower dose (2.0 nmol) LTC4 produced a marked fall in SaO2% that lasted less than 15 min and occurred in the absence of significant bronchoconstriction as measured by changes in FEV1, FEF25-75, and SGaw. At a higher cumulative dose (7 nmol), LTC4 caused prolonged oxygen desaturation with slow recovery and this was associated with significant bronchoconstriction. In contrast, histamine inhalation produced a single response with a fall in both FEV1 and SaO2% of short duration. The dose-response characteristics of LTC4 and histamine on oxygen desaturation in asthmatic patients appear to differ significantly and probably are dependent on relative sensitivities of pulmonary vascular and bronchial smooth muscle to these agonists. A single inhaled dose of LTC4 in nonasthmatic subjects produced a marked drop in PaO2 with significant increase in AaPO2, and this was associated with a mean (SEM) decrease in FEV1 of 14% (2.5) from the baseline. The mean cardiac output fell by 15% (3.4) without significant changes in blood pressure and heart rate. There was no electrocardiographic evidence of myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1989

A microcomputer-based respiratory heat exchange facility for use in the diagnosis of thermally induced asthma.

Exercise-induced asthma is prevalent in many asthmatics and during the winter months can be exacerbated by cold air inhalation. A laboratory facility was required to permit early diagnosis of cold air sensitivity in these patients. This paper describes the development of a modular air conditioning system to produce a range of inhalative thermal burdens and the microcomputer interfacing to measure the rate of airway heat loss imposed. A single-stage refrigerator was built capable of cooling 150 l/min air to -25 degrees C. This was also used to generate dry ambient temperature air by rewarming the chilled air supply. An air humidifier was developed based upon natural convection and evaporation. It was capable of raising 150 l/min ambient air to 37 degrees C, 100 per cent relative humidity. In two pilot studies of 18 asthmatics it was found that the rate of respiratory heat exchange could be correlated with the magnitude of post exertional bronchoconstriction (lung dysfunction) and that exercise-induced asthma could be minimized by attenuating the rate of airway heat loss.

Adult↗
PubMed1988

Role of cooling and drying in hyperventilation induced asthma.

Respiratory heat loss has been proposed as a mechanism of exercise induced asthma. Whether the predominant stimulus is airway drying or cooling remains unclear. We have measured changes in FEV1 after isocapnic cold air hyperventilation (CAH) (-23.4 degrees (SD 0.43 degrees) C) and dry ambient air hyperventilation (AAH) (18.7 degrees (0.52 degrees)C) in seven asthmatic patients (mean age 31 (SD 9) years and baseline FEV1 3.2(0.9)1) and in seven normal subjects (age 28(6) years and FEV1 3.6(0.7)1). The inspired water content in both cases was 0.3 mg/l air. The rate of respiratory heat exchange per breath was calculated in watts (W) with microcomputer based equipment. Cold air hyperventilation caused a fall in FEV1 almost twice that of ambient air hyperventilation at each level of ventilation: CAH v AAH (% fall) 8.0 (5.1) v 3.9 (4.0) at 15 l/min, 11.6 (7.8) v 7.0 (4.4) at 30 l/min, and 20.7 (10.9) v 12.4 (6.3) at 60 l/min. Identical latent heat loss (evaporative drying) was imposed on the airway during the two challenges. Sensible heat loss (convective cooling) in cold air hyperventilation was 41 W at 15 l/min, 63 W at 30 l/min, and 114 W at 60 l/min; whereas in ambient air hyperventilation the loss was 6, 13, and 23 W respectively. It is concluded that the rate of cooling of the upper airway is the predominant stimulus in hyperventilation induced asthma.

Adult↗
PubMed1988

Effect of azelastine on bronchoconstriction induced by histamine and leukotriene C4 in patients with extrinsic asthma.

Azelastine, a new oral agent with antiallergic and antihistamine properties, has been shown to inhibit the effect of histamine and leukotriene (LT) in vitro, though not a specific leukotriene receptor antagonist. The effect of both a single dose (8.8 mg) and 14 days' treatment (8.8 mg twice daily) with azelastine on bronchoconstriction induced by LTC4 and histamine has been examined in 10 patients with mild asthma in a placebo controlled, double blind, crossover study. LTC4 and histamine were inhaled in doubling concentrations from a dosimeter and the results expressed as the cumulative dose (PD) producing a 20% fall in FEV1 (PD20FEV1) and 35% fall in specific airways conductance (PD35sGaw). The single dose of azelastine produced a significantly greater FEV1 and sGaw values than placebo at 3 hours, but this bronchodilator effect was not present after 14 days of treatment. Azelastine was an effective H1 antagonist; after a single dose and 14 days' treatment with placebo the geometric mean PD20FEV1 histamine values (mumol) were 0.52 (95% confidence interval 0.14-1.83) and 0.54 (0.12-2.38), compared with 22.9 (11.5-38.3) and 15.2 (6.47-35.6) after azelastine (p less than 0.01 for both). LTC4 was on average 1000 times more potent than histamine in inducing bronchoconstriction. Azelastine did not inhibit the effect of inhaled LTC4; the geometric mean PD20FEV1 LTC4 (nmol) after a single dose and 14 days' treatment was 0.60 and 0.59 with placebo compared with 0.65 and 0.75 with azelastine. The PD35sGaw LTC4 was also unchanged at 0.66 and 0.73 for placebo compared with 0.83 and 0.74 for azelastine. Thus prolonged blockade of H1 receptors did not attenuate the response to LTC4, suggesting that histamine and LTC4 act on bronchial smooth muscle through different receptors. Four patients complained of drowsiness while taking azelastine but only one who was taking placebo and three patients complained of a bitter, metallic taste while taking azelastine.

Adult↗
PubMed1988

Felodipine, a new calcium antagonist, modifies exercise-induced asthma.

Recently, calcium antagonists have been reported to have a clinically beneficial effect in patients with asthma. Felodipine is a new calcium antagonist of the dihydropyridine group with a high selectivity for arteriolar smooth muscle; it is under clinical investigation for the treatment of hypertension. In this double-blind, randomized crossover trial in 9 patients, the effect of 10 mg felodipine in oral solution on exercise-induced asthma was compared with a placebo on separate days. The FEV1 was at least 80% of the predicted normal value, with variation between study days of less than 10%. Heart rate, blood pressure, and FEV1 were measured before and at 15 and 30 min after each treatment. The exercise test consisted of steady state running at submaximal work loads for 6 to 8 min and started at 30 min after treatments. FEV1 was measured at 1, 2, 5, 10, 15, and 30 min after the end of exercise. The predrug baseline FEV1 values were comparable on the 2 days of the study, and felodipine had no effect on the resting lung function. The mean percentage fall in FEV1 (SEM) after exercise with placebo was 27.0 (4.5)%, and with felodipine it was 13.5 (3.7)%. The difference between felodipine and placebo was statistically significant. While receiving felodipine, the resting heart rate was increased by 15%, with a tendency to lower systolic and diastolic blood pressures. The heart rate after exercise was higher during felodipine treatment than during placebo treatment. One patient receiving placebo and 7 receiving felodipine noted a transient headache. Two patients receiving felodipine also noticed lightheadedness after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Routine revascularization with resection of infection femoral pseudoaneurysms from substance abuse.

Infected femoral artery pseudoaneurysms in narcotic addicts present challenging management options. Our policy of routine revascularization is based on the concern that a high rate of amputations must follow ligation and resection alone or with selective delayed revascularization. Fifteen of 16 patients with infected pseudoaneurysms of femoral arteries, treated with resection and bypass grafts, were observed from 1 to 44 months. Obturator bypass grafts were used in 10 patients, iliac-femoral grafts in three, axillopopliteal in one, and right external iliac crossover to left popliteal in one patient. One limb, unsalvageable at presentation, was amputated primarily, along with resection of pseudoaneurysm and femoral artery ligation, without bypass grafting. One iliac-femoral graft became infected and then thrombosed 4 months after operation. Unsuitable distal arteries and impending necrosis led to above-knee amputation. One late failure among 15 revascularization attempts (7%) is significantly lower than the 11% to 33% amputation rates reported in the literature with resection of pseudoaneurysm alone and delayed selective revascularization. The other 14 patients had functioning limbs without claudication or rest pain. Our experience indicates that revascularization at the time of resection of infected pseudoaneurysm offers better prospects for limb salvage.

Adult↗
PubMed1988

Extended reconstruction rate for limb salvage with intraoperative prereconstruction angiography.

A prospective study was performed between May 1982 and March 1987 to assess the value of intraoperative prereconstruction angiography (IPA) in limb salvage. Eligibility was limited to patients with rest pain, ischemic ulcers, or gangrene limited to the toes: only candidates for infrapopliteal bypass were included. Seventy-eight such patients were examined with preoperative angiography. Delayed films, selective catheterization, reactive hyperemia, or vasodilators were used routinely. In only 11 of 78 patients (14%) was the runoff adequately visualized, demonstrating the tibial vessels and the pedal arch. The remaining 67 patients (86%) (with nonreconstructable disease by currently accepted outflow criteria) had surgical exposure of a tibial or pedal artery for IPA. In 56 of these patients (84%) good runoff was demonstrated and bypass was performed. The reconstruction rate was 86% (67 of 78 patients), significantly higher than the 33% rate reported by others. The operative mortality rate was 2.8% (2 of 78 patients). We concluded that in severe ischemia preoperative angiography is often inadequate in demonstrating runoff, even with adjunctive measures to dilate the outflow vessels. IPA through the tibial and pedal vessels eliminates all of the proximal vascular resistance, thereby providing a "completion angiogram" before reconstruction. This in turn extends reconstructability to many patients who would otherwise undergo primary amputation.

Angiography↗
PubMed1987

Adequacy of central hemodynamics versus restoration of circulation in the survival of patients with acute aortic thrombosis.

Acute aortic thrombosis is an infrequent clinical occurrence, but when it does occur, it is a true cardiovascular catastrophe. Our experience with 34 patients over a 12 year period was reviewed and factors influencing outcome were analyzed. Seventeen women and 17 men had various clinical presentations, although 74 percent of the patients had the classic picture of ischemia. Preoperative assessment of left ventricular function was carried out in all but one patient with intraoperative and perioperative monitoring to guide therapy in addition to revascularization procedures. While extent of the preexisting disease and number of additional operations did influence the outcome, the predominant factor for survival was the left ventricular functional state perioperatively. Fifteen of the 16 patients with adequate left ventricular function survived, whereas 15 of the 17 patients with a failing myocardium died (88 percent). Extraanatomic operations are preferable in patients with demonstrated inadequate left ventricular function. Expeditious restoration of circulation alone does not ensure a favorable outcome. The key to successful therapy is understanding, preventing, and effectively treating the mechanical and metabolic dysfunction of the heart. Review of the literature on acute aortic thrombosis revealed only few isolated case reports except for a recent report of eight patients. Our report of 34 patients over a 12 year period represents the largest experience to date from a single institution. Detailed analysis of hemodynamic parameters and the significance of determination of left ventricular function has not been reported so far in this subset of critically ill patients.

Acute Disease↗
PubMed1987

Effect of terfenadine on methacholine-induced bronchoconstriction in asthma.

The dose-response effect of nonsedating H1 histamine-receptor antagonist, terfenadine, administered orally in single doses, was studied on methacholine-induced bronchoconstriction in nine patients with extrinsic bronchial asthma in a double-blind, placebo-controlled, crossover trial. The doses of terfenadine used were 60 mg, 120 mg, and 180 mg, producing small but significant bronchodilator effect with all three doses at 2 hours. This response was still present at 4 hours. However, the provocative dose causing a 20% fall in FEV1 for methacholine was unaffected by all three doses of terfenadine. The bronchodilator response induced by antihistamines, including terfenadine, suggests an increased resting tone mediated by the constant presence of free histamine in the vicinity of H1 receptors in the airways and that methacholine acts directly on the airway muscarinic receptors and is not involved in local histamine release.

Adolescent↗
PubMed1987

Management of kinked extracranial cerebral arteries.

Kinked extracranial carotid and vertebral arteries are observed in 10% to 16% of cerebral angiograms. The hemodynamic significance of some kinked carotid arteries has been shown by investigators who documented oculoplethysmographic and angiographic differences accompanying flexion, extension, or rotation changes of the neck and head. In the 3-year period ending November 1985, we performed operations on seven patients to correct six kinked internal carotid arteries and one kinked vertebral artery at the C-2 level. The final decision regarding optimal operative technique was determined during operation, after observing the relative lengths of dissected arteries, envisioning the results of the procedures selected. We performed five segmental resections and end-to-end anastomoses (one vertebral, two common carotid, and two internal carotid arteries). Transection of the internal carotid artery with reimplantation into the side of the common carotid artery was performed twice. All patients became asymptomatic up to 4 years, irrespective of head and neck positions. There were no complications or deaths in these patients. This experience suggests that arterial kinks may constitute tenable indications for operative treatment in patients with transient cerebral ischemia who lack typical stenotic or ulcerative plaques to account for their symptoms. Kinked arteries can be corrected safely and effectively by appropriate surgical procedures.

Aged↗
PubMed1987

The nucleotide sequence and genome organization of bovine papillomavirus type 4.

The nucleotide sequence of bovine papillomavirus type 4 (BPV-4) was determined. The viral genome is 7261 base pairs long. Several overlapping open reading frames (ORFs) have been identified both on the basis of amino acid comparison with other papillomaviruses and on their transcriptional pattern. Eight early ORFs (E1 to 8) were recognized, coding for DNA replication and cell transformation functions, and three late ORFs (L1 to 3), coding for structural proteins. Like the E5 ORF of human papillomavirus type 6 the E5 ORF of BPV-4 is discontinuous. Unlike other papillomaviruses, the non-coding region upstream of the early ORFs (ncr-1) is short (385 base pairs), but there is another non-coding region (ncr-2) of nearly 500 base pairs between the L2 and L1 ORFs. Most of the putative regulatory sites are located in the ncr-1, although potential controlling elements are also found in other parts of the genome. Polyadenylation sites are present at the 3' end of both the early and the late transcription units. Comparison between the polypeptides of BPV-4 and other papillomaviruses showed that BPV-4 is evolutionarily closer to the epitheliotropic human and rabbit viruses than to BPV-1.

Animals↗
PubMed1987

Mouse erythrocyte carriers osmotically loaded with methotrexate.

The mouse red blood cell (RBC) and red blood cell ghost (RBCG) have been studied as carriers of methotrexate (MTX). When incubated with high concentrations of MTX, RBCs take up significant quantities of it. However, when active loading techniques, such as the slow dialysis and preswell methods, are applied to those cells, up to 15 times more MTX can be entrapped. We have studied factors critical to the incorporation, leakage, and morphology of RBCGs during their loading with MTX by the slow dialysis and preswell methods. Compounds added to the buffers to maintain the ATP content of the cells and osmolarity play functional roles in this process. The fate of the material entrapped within the ghosts after in vivo administration was shown to be capture by the reticuloendothelial system. The pharmacological efficacy of MTX-loaded RBCGs in treating mice bearing hepatoma ascites tumors was demonstrated by increases in average survival time of 28.5-42.8%.

Animals↗
PubMed1986

Second hepatoma developing 13 years after resection of first tumor.

A patient underwent a left-sided hepatic lobectomy for primary hepatocellular carcinoma 13 years ago and remained symptom free. He then presented with spontaneous rupture of a large tumor in the right lobe of the liver. Although this tumor proved to be primary hepatocellular carcinoma, there were significant histological differences between the two lesions, suggesting that this was a second primary liver tumor. Bleeding from the tumor was controlled by selectively ligating the branches supplying the area of hemorrhage.

Aged↗
PubMed1986

In vitro regeneration of plantlets from embryonic and seedling explants of Engelmann spruce (Picea engelmannii Parry).

A protocol has been developed for the in vitro production of plantlets of Engelmann spruce. Embryos and various parts of Engelmann spruce seedlings formed multiple shoots when cultured on defined media containing a cytokinin. The site and time of occurrence of the shoot buds, as well as their number, differed in the various explants. The frequency of shoot-forming explants was influenced by the salt formulation used, the type and concentrations of cytokinins and their mode of application. Development of buds was achieved by transferring the explants to basal medium containing no growth regulators. Elongation of shoots was stimulated by reducing the concentration of salts and sugar, addition of activated charcoal and transferral to increased photoperiod and lower temperature regimes. Maximum rooting was induced by giving a pulse of high concentration of indolebutyric acid to the shoots. The roots developed within 8-10 weeks and the regenerated plantlets were transferred to soil under non-sterile conditions.

Journal Article↗
PubMed1986

Transcriptional organization of bovine papillomavirus type 4.

Seven virus-specific RNA transcripts have been identified in tumours induced by bovine papillomavirus type 4 (BPV-4). The RNAs measured 4.2, 3.6, 3.0, 2.8, 1.9, 1.6 and 1.0 kilobases (kb). They were mapped on the viral genome by Northern blot hybridization to subgenomic probes, by cDNA hybridization to viral DNA fragments and by S1 analysis of unlabelled and 3' and 5' end-labelled DNA fragments. All the RNA species are transcribed from the same DNA strand, are polyadenylated and with the exception of the 1.0 kb RNA internally spliced. The 3.0, 1.9, 1.6 and 1.0 kb RNAs share the same 3' polyadenylation site at nucleotide 4009 whereas the 4.2 kb RNA and the 2.8 kb RNAs terminate near a polyadenylation site at nucleotide 7187. The 4.2 kb and the 2.8 kb RNAs are transcribed from the late open reading frames and encode the structural polypeptides; the 3.0, 1.9, 1.6 and 1.0 kb RNAs are transcribed from the early open reading frames and are the transcripts involved in viral replication and cellular transformation.

Animals↗
PubMed1986

Plasma concentrations of sodium cromoglycate given by nebulisation and metered dose inhalers in patients with exercise-induced asthma: relationship to protective effect.

Plasma sodium cromoglycate (SCG) concentrations were measured in 11 patients at regular intervals before and after exercise in a double-blind study to assess the protective effect in exercise-induced asthma (EIA) of 2, 10 and 20 mg SCG aerosol and placebo, and (on an open basis) nebulised SCG (10 g l-1). There was a dose related increase in plasma concentration and AUC (0-1 h) with the aerosol formulations; values with nebulised SCG were significantly higher than with any aerosol dose. Protection from EIA increased to a maximum of 66% at plasma concentrations of 4 ng ml-1 and above. Thus measurement of plasma concentration can allow a comparison to be made between the protective effects of SCG following different methods of inhalation. It is important to note, however, that plasma concentration per se is almost certainly not related directly to protective effect.

Adult↗