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Biomedical subjects

K R Patel

Publications and source records attributed to K R Patel.

At least 19 recordsLinked to original sources

Impaired pulmonary diffusion during exercise in patients with chronic heart failure.

BACKGROUND: Pulmonary diffusion is impaired at rest in patients with chronic heart failure (CHF) and has been implicated in the generation of symptoms and exercise intolerance. The aim of this study was to determine whether pulmonary diffusion is impaired during exercise in CHF, to examine its relationship to pulmonary blood flow, and to consider its functional significance in relation to metabolic gas exchange. METHODS AND RESULTS: Carbon monoxide transfer factor (TLCO) and pulmonary blood flow (Q(C)) were measured by a rebreathe technique at rest and during steady-state cycling at 30 W in 24 CHF patients and 10 control subjects. Both patients and control subjects were able to raise TLCO and Q(C) during exercise. However, the patient group had a lower diffusion for a given blood flow (TLCO/Q(C)) both at rest (3.6+/-0.16 and 4.8+/-0.23 mL x L(-1) x mm Hg(-1); P<0.001) and during exercise (2.8+/-0.16 and 3.4+/-0.13 mL x L(-1) x mm Hg(-1) for CHF patients and control subjects, respectively; P<0.05). TLCO/Q(C) was related to the ventilatory equivalent for carbon dioxide (VEVCO(2)) production at 30 W (TLCO/Q(c) versus VEVCO(2), r = -0.58, P<0.01) and to peak exercise oxygen consumption measured during a progressive test (TLCO/Qc versus VO(2peak), r = 0.57, P<0.01) in these patients. CONCLUSIONS: Patients with CHF are able to recruit reserves of TLCO and Q(C) during exercise. However, the TLCO/Q(C) ratio is consistently impaired in these patients and relates to both exercise hyperpnea and peak exercise oxygen consumption. Whether this impairment in alveolar gas exchange is reversible in CHF and therefore is a potential target for therapy has yet to be determined.

Cardiac Output, Low

Predictors of nocturnal oxygen desaturation in patients with COPD.

The aim of this study was to identify factors which might predict nocturnal desaturation (defined as a fall of > 4% from awake baseline level for > or = 5 min) in normoxic or mildly hypoxic patients with stable COPD [arterial O2 saturation (SaO2) > or = 91%]. The study was prospective in nature, had full ethical approval and was performed in the Respiratory Department of a city teaching hospital. Thirty-three patients [mean (SD) age 67.2 (9) years] with stable COPD [mean (SD) FEV1 36.8 (11.0)% pred.] were recruited via the respiratory outpatient clinics and through the respiratory wards. The following parameters were measured: daytime arterial blood gases; spirometry; lung volumes (helium dilution); single breath CO transfer factor (TLCO and KCO); maximum inspiratory (IMP) and expiratory mouth pressures; pulse oximetry (SpO2) across a 6-min walk test, and SpO2 during sleep. Seventeen patients who experienced nocturnal desaturation had significantly lower mean PaO2 and SaO2, and higher PaCO2 values compared to non-desaturators. There was a positive correlation between mean nocturnal SpO2 and daytime PaO2, SaO2, and minimum exercise SpO2, and a negative correlation between mean nocturnal SpO2 and PaCO2, and FRC. Regression analysis revealed that daytime SaO2 was the only independent predictor of mean nocturnal saturation (accounting for 61% of the variability in the mean nocturnal SpO2). We observed nocturnal desaturation in all patients with a daytime SaO2 < or = 93% but in no patient with SaO2 > or = 95%. We conclude that daytime SaO2 can be used to predict nocturnal desaturation in normoxic or mildly hypoxic patients with stable COPD. Nocturnal desaturation is likely in patients with COPD where daytime SaO2 < or = 93%, and unlikely where daytime SaO2 > or = 95%.

Exercise

Sputum cellular and cytokine responses to inhaled endothelin-1 in asthma.

BACKGROUND: Endothelin (ET)-1 is a 21-amino acid peptide which has potent bronchoconstrictor activity. Animal studies show elevation of ET-1 during experimental airway inflammation, and inhibition of inflammation by endothelin-antagonists, suggesting pro-inflammatory activity for ET-1. OBJECTIVE: We wanted to assess any acute influence that bronchoconstrictor doses of inhaled ET-1 might have on cells, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, nitrite (NO2) and albumin in induced sputum in asthma. METHODS: Bronchial challenge was performed using nebulized ET-1 (nebulized dose range 0.96-15.36 nmol) and placebo in 10 adult asthmatic subjects in a randomized double-blind placebo-controlled cross-over study. Sputum induction was performed 30 min and 4 h after placebo or ET-1 bronchial challenge. RESULTS: All subjects experienced dose-dependent bronchoconstriction to inhaled ET-1 with a mean (range) PC15 forced expiratory volume in 1 s (FEV1) to ET-1 of 9.45 (1.2-21.7) nmol. Comparing ET-1 with placebo inhalation, there was no change in sputum differential cell counts, TNFalpha, IL-1beta, NO2 or albumin at 30 min or 4 h after inhalation, nor was there a difference in these parameters at 4 h compared with 30 min after ET-1 inhalation. There was no fall in FEV1 at 4 h after ET-1 inhalation, suggesting that ET-1 inhalation is not associated with a late bronchoconstrictor response. CONCLUSIONS: We conclude that inhaled ET-1 does not appear to stimulate an acute inflammatory response in asthma as assessed by differential cell count, TNFalpha, IL-1beta, NO2 and albumin concentrations in induced sputum.

Adult

Is high-dose fluticasone propionate via a metered-dose inhaler and Volumatic as efficacious as nebulized budesonide in adult asthmatics?

The efficacy and tolerability of fluticasone propionate (FP) 2 mg daily via a metered-dose inhaler and Volumatic (Glaxo Wellcome) spacer device was compared with nebulized budesonide (nBUD), 2 and 4 mg daily, in a multi-centre, open-label, cross-over study of adult asthmatics. Patients received, in random order, either 4 weeks of treatment with FP followed by 4 weeks of treatment with nBUD, or vice versa, with an intervening 4 week 'wash-out' period between treatments. Thirty patients completed the study, of whom 24 were evaluable. In terms of the primary efficacy parameter, change in mean morning peak expiratory flow (PEF) (l min-1) from baseline to the fourth week of each treatment period, FP was more effective than nBUD [mean difference (FP-nBUD) 21.1 l min-1, P = 0.007, 95% CI (6.5, 35.7)]. Sub-group analysis demonstrated FP to be superior to the 4 mg nBUD [mean treatment difference (FP-nBUD) 42.9 l min-1, P = 0.026, 95% CI (7.1, 78.8)] and at least as efficacious as the 2 mg nBUD sub-group [mean treatment difference (FP-nBUD) 10.2 l min-1, P = 0.211, 95% CI (-6.5, 26.9)]. Furthermore, larger reductions in diurnal variation were observed during FP treatment [mean treatment difference (FP-nBUD) -4.4 percentage points, P = 0.028, 95% CI (-8.4, -0.5)]. There was no significant difference between the treatments for the proportion of symptom-free 24 h periods. Of those expressing a preference, significantly more patients found FP via a metered-dose inhaler and spacer device both easier to administer (78%, P = 0.007) and more convenient to take (76%, P = 0.008) than nebulized budesonide. In addition, cost per patient analysis showed that nebulized budesonide was from 1.7 to 3.5 times more expensive than FP.

Adolescent

Massive osteolytic bone metastases from a primary aortic sarcoma: a case report.

We present an unusual case of an aortic intimal sarcoma, which originally manifested itself by the presence of extensive radiologically osteolytic lesions in the long bones of the lower limbs. The histology of these was puzzling and was first considered to represent a low grade sarcoma of vasoformative tissue and subsequently skeletal angiomatosis. Despite a good initial clinical response to disodium etidronate, the patient ultimately developed small bowel infarction and the true diagnosis only came to light at autopsy. This revealed a tumour in the lower thoracic aorta which, unusually for aortic sarcoma, consisted of loosely packed bland spindle cells with no necrosis and infrequent mitoses. Immunocytochemistry was unhelpful but electron microscopy suggested myofibroblastic differentiation. The majority of previous reports of the tumour in the literature lack information on electron microscopy and immunocytochemistry and have suggested that these tumours are generally pleomorphic in appearance. Embolic phenomena and post mortem diagnosis are usual although occasional antemortem diagnosis has been made using computed tomography (CT) and magnetic resonance imaging (MRI) scanning with the latter being the investigation of choice.

Aorta, Thoracic

Femorocaval bypass with femoral crossover bypass for iliofemoral and caval occlusion.

Progress in the management of major venous obstruction has lagged far behind advances in arterial reconstruction. As a result, literature reports consist of small numbers of patients, and most vascular surgeons have little or no experience in performing bypass procedures for major venous obstruction. In this setting, individual reports add to our cumulative knowledge in treating this disease. We therefore present our experience in the management of a patient with extensive bilateral femoropopliteal, iliac, and vena caval occlusion.

Constriction, Pathologic

Endothelin-1 levels in induced sputum samples from asthmatic and normal subjects.

BACKGROUND: Endothelin-1 (ET-1) is a potent bronchoconstrictor which may have a role in the pathogenesis of asthma. The levels of ET-1 in saliva, induced sputum, and plasma from asthmatic and non-asthmatic subjects were compared. METHODS: Sputum induction was performed on 28 asthmatic subjects and nine normal volunteers. ET-1 levels were measured in plasma, saliva, and sputum samples and reversed phase high performance liquid chromatography (RP-HPLC) was performed on saliva and sputum samples. RESULTS: ET-1 was present in the following order of concentration in both normal and asthmatic subjects: saliva > sputum > plasma (saliva, median 30.1 and 23.9 pg/ ml, respectively; sputum, median 15.5 and 11.2 pg/ml; plasma, median 3.1 and 3.6 pg/ ml). There were no differences between asthmatic and normal subjects in the levels of ET-1 in each fluid. The levels of ET-1 in asthmatic subjects were not influenced by whether or not they were taking inhaled steroids. RP-HPLC of sputum and saliva confirmed the presence of ET-1 in these fluids. CONCLUSIONS: Levels of ET-1 can be measured in saliva and sputum obtained by sputum induction in asthmatic and healthy subjects and, although no difference was found in basal levels of ET-1 in sputum, saliva and plasma between normal subjects and asthmatics without bronchoconstriction, it is apparent that ET-1 is produced or released locally within the respiratory tract in concentrations higher than those in plasma.

Adult

Endothelin-1-induced bronchoconstriction in asthma.

Endothelin-1 (ET-1) has been indirectly implicated in the pathophysiology of asthma, and it is a potent bronchoconstrictor both in vitro and by inhalation in animal models in vivo. We examined the effect of inhaled ET-1 on airway tone in comparison with methacholine in eight asthmatics and five healthy volunteers in a double-blind randomized fashion. After a screening methacholine challenge each asthmatic had two ET-1 (doubling dose range, 0.96 to 15.36 nmol) and one methacholine (doubling dose range, 0.33 to 21.0 mumol) challenge, and normal subjects had a single ET-1 challenge. Inhalations were delivered using a dosimeter, and lung function measurements were made using constant-volume body plethysmography, with end points being a 35% fall in specific airway conductance (SGaw) and a 15% fall in FEV1. Samples for plasma ET-1 were taken before and after the inhalations, and pulse, blood pressure and oxygen saturation were monitored throughout the inhalations. All the asthmatic subjects displayed rapid-onset (< 5 min) dose-dependent bronchoconstriction to ET-1 across the dose range used, with mean (range) ET-1 PC35SGaw values of 5.15 (1.4 to 13.9) nmol, and 4.3 (1.2 to 8.3) nmol for the two ET-1 inhalations, and 0.42 (0.2 to 0.7) mumol for methacholine. Albuterol completely and rapidly reversed ET-1-induced bronchoconstriction, and in two patients not given albuterol, bronchoconstriction lasted 60 to 90 min. No significant bronchoconstriction was observed in any of the healthy volunteers across the ET-1 dose range used (mean PC35SGaw > 15.36 nmol). Oxygen saturation did not alter in either group, and plasma ET-1 did not change after ET-1 inhalation. Noninvasive blood pressure measurements revealed a fall in systolic blood pressure in normal subjects, with no change in asthmatics. Endothelin-1 is a potent bronchoconstrictor in asthma, with a bronchoconstrictor potency around 100 times that of methacholine in asthma. Asthmatics exhibit bronchial hyperreactivity to ET-1, and inhaled ET-1 can safely be given to asthmatics and normal subjects in the nebulized dose range 0.96 to 15.36 nmol.

Adult

Clinical features and epidemiology of malignant pleural mesothelioma in west Glasgow 1987-1992.

Malignant pleural mesothelioma is almost exclusively caused by exposure to asbestos dust. Recent epidemiological studies have suggested that the national incidence of disease may continue to rise until 2020 and that asbestos exposure in the building trade may be replacing shipyard related exposure as the main source of disease. The objective of the study was to determine if the incidence of malignant pleural mesothelioma was rising in the west of Glasgow from 1987-1992 and whether there had been a change in clinical features compared to previous studies from the same population. Case notes identified from coded returns and the local cancer registry were retrospectively examined: 144 cases were identified. This is an increase in incidence of over 50% compared to the previous study but the yearly incidence did not rise over the period studied. The clinical features and survival times have not changed since previous studies: median survival remains 30 weeks. Only three patients were given definitive treatment reflecting the lack of effective therapy. We suggest that the incidence of mesothelioma in the population studied may already have peaked resulting from the decline in the local shipyard industry over 20 years ago. Non-shipyard sources of asbestos exposure may be less important in this area.

Adult

Metabolic and histologic effects of recombinant canine somatotropin on bone healing in dogs, using an unstable ostectomy gap model.

OBJECTIVE: To investigate the effect of recombinant canine somatotropin (STH) on the metabolic and histologic aspects of bone healing in dogs, using an unstable ostectomy gap model. ANIMALS: 8 mature dogs. PROCEDURE: A 3-mm ostectomy of the mid portion of the radius was performed in all dogs. Implants designed to release STH at a rate of 4 mg/d were placed SC in 4 dogs (treated group [STHG]), and another 4 dogs received no implants (control group [CG]). Serum concentrations of STH, insulin-like growth factor I, and osteocalcin were determined before surgery, and weekly for 8 weeks. Scintigraphic evaluation of the ostectomy sites was performed before surgery, and at weeks 2, 4, 6, and 8 after surgery. Histologic evaluation ofthe ostectomy sites was performed at the conclusion of the study at week 8. RESULTS: Significant (P < 0.05) increases in serum STH, insulin-like growth factor I, and osteocalcin concentrations were observed in dogs of the STHG during the 8-week study period. Scintigraphic activity of the ostectomy sites was increased in dogs of both groups, but dogs of the STHG had significantly (P < 0.05) greater activity, compared with dogs of the CG. Coalescence of nuclear activity across the ostectomy site was observed in dogs of the STHG, whereas dogs of the CG maintained 2 distinct areas of metabolic activity. Histologically, dogs of the STHG had bridging calluses with areas of endochondral ossification and ongoing osteogenic activity, whereas dogs of the CG had nonossified fibrocartilage typical of nonunion fractures. CONCLUSION: Using the ostectomy gap model, recombinant canine STH enhanced the metabolic and histologic aspects of bone healing in dogs.

Animals

Management of chronic airflow obstruction: differences in practice between respiratory and general physicians.

An audit of inpatient care of diseases characterized by chronic airflow obstruction namely chronic bronchitis, emphysema and chronic obstructive airways disease (ICD Code Nos. 490-2 & 496) was performed and the practice of respiratory and general physicians compared. One hundred cases were sampled at random from 279 cases admitted to hospitals serving the West of Glasgow in 1988. Fifty cases were selected from those admitted under the care of respiratory physicians and 50 from those under general physicians; 89 were suitable for analysis. The main outcome measurements consisted of the use of routine respiratory investigations, comparison of the use of standard therapies during the admission and at discharge, length of stay, inpatient deaths, follow up and readmission rates. The groups were similar in age, smoking history, gender and there was no significant difference in admission arterial blood gas values. The pulse rate on admission was higher in the general group (102 beats per min) in comparison to the respiratory group (91 beats per min) (P < 0.004). A similar use of chest radiograph and arterial blood gas analysis was noted between the groups. Ninety-six per cent of respiratory patients had either spirometry or peak expiratory flow measured compared to 62% in the general group (P = 0.0001). No significant differences were noted in the use of antibiotics, bronchodilators, corticosteroids, oxygen or respiratory stimulants. The mean length of stay was similar. Two patients (4%) in the respiratory group compared with seven (18%) in the general group died during the admission (P = 0.01); there were no further early deaths at 1 month from discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

The effect of physiological manoeuvres on the absorption of inhaled nedocromil sodium.

In a previous study we showed, in both asthmatic patients and in healthy subjects, a marked increase in plasma concentration of nedocromil immediately following an exercise challenge with associated FEV1 measurements. To identify which component of the exercise challenge is responsible, we have now studied the effect of various manoeuvres on plasma nedocromil concentration in eight healthy subjects after inhalation of 1 ml nedocromil solution (1% w/v) via a Wright nebuliser. Each patient was dosed on six occasions, separated by at least 3 days. Between 15 and 23 min after dosing one of the following manoeuvres was performed: control (no manoeuvre); steady exercise for 8 min, a series of FEV1 measurements, exercise plus FEV1 measurements, three Valsalva manoeuvres and hyperventilation for 3 min. Mean plasma drug concentrations under control conditions were similar at 15 and 23 min after dosing. However, there were significant increases in plasma drug concentration following exercise, FEV1 manoeuvres and exercise plus FEV1 manoeuvre. There were no significant changes in plasma drug concentration following Valsalva manoeuvres and hyperventilation. The results suggest that certain manoeuvres increase the absorption of nedocromil sodium, probably as a consequence of an increase in lung volume.

Absorption

Functional foot salvage after extensive plantar excision and amputations proximal to the standard transmetatarsal level.

PURPOSE: It is generally accepted that when necrosis extends proximal to the transmetatarsal level a viable and functional foot can no longer be preserved and a major (above- or below-knee) amputation must be performed. However, with continuing advances in operations for limb salvage we felt the need to reexamine this concept. METHODS: In 1983 we initiated a prospective study to evaluate the role of extended foot amputations. All ambulatory patients with necrosis extending proximal to the transmetatarsal level (but not involving the whole foot) were included in the study. Among the 21 patients studied amputations ranged from open guillotine transmetatarsal amputation to removal of the medial or lateral three fifths of the foot. Five of these patients had adequate pedal circulation by clinical and laboratory criteria. The remaining 16 required vascular reconstruction to improve pedal flow. RESULTS: Eighteen (86%) of 21 patients had complete healing of the foot amputations and were ambulatory at the time of discharge from the hospital. Two patients required early above- or below-knee amputations. Three additional patients sustained limb loss in the follow-up period. The cumulative graft patency rate was 94% at 12 months. The cumulative limb salvage rate at 24 months was 84%. The operative mortality rate was 1 (5%) of 21. CONCLUSION: Our experience in a small number of patients suggests that functional foot salvage is possible even when necrosis or gangrene extends proximal to the transmetatarsal level.

Aged

Effect of cetirizine, a potent H1 antagonist, on platelet activating factor induced bronchoconstriction in asthma.

Effect of cetirizine, a potent and specific H1 receptor antagonist, was examined on platelet activating factor-induced bronchoconstriction in 10 patients (5 male, mean [s.e.m.] aged 37.4 [3.6] years) with mild asthma in a placebo controlled, double-blind cross-over study. Airway responses were assessed by measuring specific airway conductance (SGaw). Patients were challenged with a single dose (12-96 micrograms) of PAF that had previously produced a 35% fall in SGaw. PAF challenges were performed after single dose (15 mg) and 1 week's treatment (15 mg twice daily) of cetirizine. There was no significant difference in pre- and post-treatment baseline values of SGaw on different study days and the percentage changes after cetirizine were 38.7 (7.01) and 45.6 (5.52) compared to 50.2 (2.89) and 43.9 (7.26) with placebo respectively. Similarly mean (s.e.m.) area under curve (AUC-SGaw/time course response) was 391 (143) and 514 (85) with cetirizine compared to 565 (37) and 461 (94) with placebo respectively. The difference was not statistically significant. There was no difference in facial flushing and feeling of warmth between cetirizine and placebo. We conclude that PAF induced bronchoconstriction in humans is not mediated by histamine release and that H1 receptor antagonists do not modify PAF induced bronchoconstriction.

Adult

Effect of oral and inhaled cetirizine in allergen induced bronchoconstriction.

Cetirizine is a potent, selective H1 histamine receptor antagonist. The effect of oral and inhaled cetirizine was assessed on the early bronchoconstrictor response to inhaled allergen in 10 mild atopic asthmatic patients in a double-blind, randomized, placebo controlled trial. All were sensitive to Dermatophagoides pteronyssinus and this was used as the provoking allergen. The geometric mean PD20 FEV1 values obtained at allergen challenge were measured as cumulative breath units (c.b.u.) and following oral cetirizine, inhaled cetirizine and placebo were 124.5, 75.7 and 76.7 c.b.u. respectively. These did not differ significantly. We conclude that neither oral nor inhaled cetirizine significantly attenuates the early response to inhaled allergen in atopic asthmatic subjects. However, the method of repeated allergen challenge is likely to be relatively insensitive.

Administration, Inhalation

Phlegmasia cerulea dolens: the role of non-operative therapy.

Thrombectomy and thrombolysis are often advocated in the treatment of phlegmasia cerulea dolens, but frequently result in incomplete clot removal, recurrence of thrombosis, local and systemic hemorrhagic complications and chronic venous stasis; this state is associated with a rate of major amputation and death of up to 50%. Non-operative therapy includes elevation, hydration and heparinization and excludes all methods aimed at surgical removal or chemical lysis of the thrombus. In 1982 it was decided to use non-operative therapy as the first line of treatment for phlegmasia cerulea dolens. In the last 9 years seven extremities in six patients with this condition have been treated. One patient had advanced gangrene on presentation and one underwent emergency thrombectomy. Five extremities (in five patients) were treated with non-operative therapy. Ischemia was rapidly corrected in all five patients. Edema resolved completely after 3-4 days in four patients. There were no complications attributable to the therapy. Two of six (33%) patients died from terminal disease. Non-operative therapy appears to be effective in preventing limb loss and avoiding the risks of thrombectomy and thrombolysis in critically ill patients.

Adult

Cervical aortic arch associated with tetralogy of Fallot.

Forty-seven cases of cervical aortic arch have been reported in the literature. Eleven of these patients had congenital cardiac defects, including tetralogy of Fallot in three. An additional case of cervical aortic arch and tetralogy of Fallot is presented along with a brief review of the literature pertaining to this rare condition.

Adult