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Biomedical subjects

T Ahmed

Publications and source records attributed to T Ahmed.

At least 253 records · Page 14Linked to original sources
PubMed1983

Modification of airway histamine-receptor function with methylprednisolone succinate.

The purpose of the present study was to investigate whether glucocorticosteroids alter airway histamine-receptor function. We measured pulmonary resistance in six conscious sheep before and after inhalation challenge with 100 breaths of 5% histamine solution, without and with intravenous pretreatment with the specific H1- and H2-receptor antagonists. Inhalation of histamine (combined H1 and H2 stimulation) increased mean pulmonary resistance (RL) to 290% of baseline (p less than 0.05). Pretreatment with the H2 antagonist, metiamide (selective H1 stimulation), enhanced the effect of histamine, with a mean RL increase to 760% of baseline (p less than 0.05). Histamine challenge after pretreatment with the H1 antagonist, chlorpheniramine (selective H2 stimulation), decreased RL to 40% of chlorpheniramine value (p less than 0.05). A single intravenous bolus injection of methylprednisolone succinate (30 mg/kg) 30 min before histamine challenge suppressed the airway responsiveness to histamine, with a mean RL increase to only 186% of baseline. After methylprednisolone, selective H1-receptor stimulation with histamine elicited a blunted H1-receptor response; mean RL increased to only 248% of baseline. Both changes were significantly lower than that with histamine alone (p less than 0.05). Methylprednisolone per se blunted the chlorpheniramine-induced increase in RL which made it difficult to evaluate H2-receptor function (RL decreased to 67% of postchlorpheniramine value). However, in the presence of increased airway tone with carbachol, selective H2 stimulation with histamine decreased RL to 26% of postcarbachol value (p less than 0.05), thus excluding suppression of H2 receptors. Methylprednisolone had no effect on carbachol-induced increase in RL. In conscious sheep, methylprednisolone blunts airway responsiveness to histamine by suppressing H1 receptors without significantly altering H2 receptors or cholinergic-receptor function.

Animals↗
PubMed1983

Effect of positive end-expiratory pressure on breathing patterns of normal subjects and intubated patients with respiratory failure.

The aims of this study included assessment of accuracy of respiratory inductive plethysmography when pulmonary hyperinflation was induced by application of PEEP, and examination of breathing patterns of normal subjects, intubated patients requiring mechanical ventilation and intubated patients immediately before extubation during application of PEEP by demand valve and high gas flow reservoir bag systems. Validation of tidal volume (VT) and end-expiratory level measured with respiratory inductive plethysmography to simultaneous spirometry (SP) was achieved with PEEP levels up to 12.5 cm H2O in 7 normals. In 17 intubated patients, almost all VT values measured with respiratory inductive plethysmography fell within +/- 10% of SP even with 2 to 3 changes of body posture. In normal subjects, increasing levels of PEEP from the demand valve system produced nonprogressive rises of VT and mean inspiratory flow, falls of frequency and fractional inspiratory time (TI/TTOT), and no changes of minute ventilation (Vmin) nor mean expiratory flow. PEEP from the high gas flow reservoir bag system produced nonprogressive rises of VT and rib cage (RC) contribution to VT, and rises of Vmin and mean inspiratory and expiratory flows between 10.0 and 12.5 cm H2O of PEEP. Intubated patients requiring intermittent mandatory ventilation (IMV) had a rapid, shallow breathing pattern unaltered by PEEP levels delivered by either system up to 12.5 cm H2O despite increases of end-expiratory level. Intubated patients who were about to be extubated breathed with patterns closer to ambulatory normal subjects with the exception of their elevated RC contribution to VT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Variability of hypoxic pulmonary vasoconstriction in sheep. Role of prostaglandins.

In a minority of conscious sheep, the hypoxic pulmonary vasoconstrictor response is blunted ("nonresponders"). The purpose of this investigation was to determine if this blunted response is related to an increased activity of H2-histamine receptors, beta-adrenergic receptors, or the generation of inhibitory prostaglandins. We measured pulmonary arterial pressure, pulmonary arterial wedge pressure, and pulmonary blood flow for the calculation of pulmonary vascular resistance (PVR) in 5 "nonresponders" and 5 sheep with a typical hypoxic pulmonary vasoconstrictor response ("responders") while breathing room air and 13% O2 (balance, N2). Arterial oxygen tension (PaO2) was also determined as a measure of the severity of hypoxia. During hypoxia, mean PVR increased by 6% (p = NS) in the "nonresponders" (PaO2, 49 +/- 4 mmHg), and by 70% (p less than 0.01) in the "responders" (mean PaO2, 46 +/- 4 mmHg). Metiamide (H2-blocker) and propranolol (beta-adrenergic blocker) pretreatments did not restore the hypoxic pulmonary vascular response in the "nonresponders," whereas pretreatment with indomethacin (prostaglandin synthetase inhibitor) caused mean PVR to increase by 48% (p less than 0.01) during hypoxia, indicating a partial restoration of hypoxic pulmonary vasoconstriction. In the "responders," the hypoxic pulmonary vascular response was not potentiated by indomethacin pretreatment (68% increase in mean PVR). We conclude that some sheep exhibit a blunted hypoxic pulmonary vasoconstrictor response caused by enhanced production of inhibitory prostaglandins.

Animals↗
PubMed1983

Does slow-reacting substance of anaphylaxis mediate hypoxic pulmonary vasoconstriction?

We have previously established a relationship between mast cell degranulation and hypoxic pulmonary vasoconstriction (HPV). In the present study, we investigated the possible role of slow-reacting substance of anaphylaxis (SRS-A) in the mediation of HPV. In 18 conscious sheep, pulmonary artery pressure, pulmonary arterial wedge pressure, and cardiac output were measured for the calculation of pulmonary vascular resistance (PVR) along with arterial oxygen tension (PaO2) while breathing room air and while breathing 13% O2 (balance, N2). Before and during 13% O2 breathing (pretreatment), Group 1 received an intravenous infusion of cromolyn sodium (3 mg/kg-1/min-1) and Group 2 was infused with FPL-57231, a SRS-A antagonist (2 mg/kg-1/min-1); Groups 3 and 4 received infusions of cromolyn sodium or FPL-57231 after induction of HPV. During 13% O2 breathing (mean PaO2, 47 mmHg), mean PVR increased to 190% of baseline. Pretreatment with cromolyn sodium prevented HPV, whereas infusion of cromolyn sodium after induction of HPV failed to reverse it; FPL-57231 both prevented HPV (pretreatment) and reversed it when infused after induction of HPV. Pretreatment with the prostaglandin synthetase inhibitor indomethacin (2 mg/kg) 1 h before the experiment failed to modify the FPL-57231-induced reversal of hypoxic vasoconstriction, thus excluding the release of inhibitory prostaglandins by this compound. We conclude that cromolyn sodium prevented HPV, presumably by inhibiting the release of SRS-A, which mediates pulmonary vasoconstriction directly or indirectly through other mechanisms.

Animals↗
PubMed1983

Modification of allergic bronchoconstriction by a calcium antagonist: mode of action.

Because both degranulation of mast cells and contraction of airway smooth muscle are dependent upon the influx of calcium, a calcium blocking agent might modify allergic bronchoconstriction by at least these two mechanisms. We treated sheep allergic to Ascaris suum antigen with the calcium antagonist Verapamil prior to airway challenge with an aerosol of Ascaris suum antigen and also investigated the response without pretreatment. Aerosolized Ascaris suum antigen increased mean pulmonary resistance (RL) to 530% of baseline (n = 6). Pretreatment with intravenously administered Verapamil (150 micrograms/kg) increased mean RL to 225% of baseline but bronchoconstriction produced by subsequent antigen challenge was completely prevented. Verapamil did not modify bronchoconstriction produced by aerosols of histamine and carbachol, agents that act upon airway smooth muscle. Further, it did not reverse the increase in RL induced by an intravenous infusion of carbachol. These results suggest that verapamil, at the dosage used, did not prevent allergic bronchoconstriction by a direct action on smooth muscle and therefore was effective by inhibiting the release of mast cell mediators.

Airway Resistance↗
PubMed1983

Phase II trial of 4'epi-adriamycin for advanced hypernephroma.

4'Epi-adriamycin in doses of 85-110 mg/m2 I.V. Q3W was given to 20 patients with advanced bidimensionally measurable hypernephroma. Forty-five doses were administered, with 10 patients receiving 3-7 doses. Myelosuppression (WBC nadir 2600 cells/mm3, range 1000-3400) occurred in 63% and thrombocytopenia in 16% of cases. There was no objective response in 19 adequately treated cases.

Adenocarcinoma↗
PubMed1982

West Nile virus in Pakistan. 1. Sero-epidemiological studies in Punjab Province.

Serum samples collected during 1978-79 from residents of the Chiniot and Changa Manga National Forest (CMF) areas of Punjab Province, Pakistan, had over-all neutralizing (N) antibody positive rates for West Nile (WN) virus of 32.8% (n = 192) and 38.5% (n = 239), respectively. Comparison of the age-specific antibody rates indicated that the pattern of exposure to infection was different in the two areas. Samples from a 1968 serosurvey of residents of the CMF area had an age-specific N antibody profile similar to the 1978 CMF sample, but both the over-all N and haemagglutination-inhibition (HI) antibody positive rates were much higher in the 1968 sample. When tested against antigen prepared from the Pakistan I-746 strain of WN virus, the percentage of sera HI antibody positive and the geometric mean titre of the sera were significantly higher than when tested against the Egypt-101 antigen. One of 124 and 11 of 50 sera from the 1978 and 1968 samples from CMF exhibited detectable HI antibody against dengue-3 virus, respectively, indicating cross-reacting flavivirus antibody was present. None of the positive sera had a higher titre against dengue-3 than against WN virus, but four of the 1968 sera reacted to equal titre against both antigens. During the 1978-79 CMF survey, serum samples from domestic and wild animals were tested for WN virus antibody. Of the 317 wild birds captured, 85 were N-antibody positive. The only frequently bled mammal was the Indian cow, from which 21 of 58 samples were positive for WN antibody.

Animals↗
PubMed1982

Characterization of H1- and H2-receptor function in pulmonary and systemic circulations of sheep.

We investigated the histamine H1- and H2-receptor function in the pulmonary and systemic circulations of sheep by in vivo and in vitro techniques. Combined H1 and H2 stimulation (by intravenous histamine) in vivo increased pulmonary vascular resistance (PVR) to 435% of base line and decreased systemic vascular resistance (SVR) to 49% of base line. Selective H2 stimulation (histamine after chlorpheniramine pretreatment) decreased PVR and SVR to 86 and 82% at base line, respectively, while selective H1 stimulation (histamine after metiamide pretreatment) increased PVR to 424% of base line and decreased SVR to 64% of base line. Combined H1- and H2-antagonist pretreatment completely blocked the effects of histamine on SVR, while PVR still decreased to 85% of base line, suggesting a mild "atypical" H2-receptor response in the pulmonary circulation under conditions of resting vascular tone. With increased pulmonary vascular tone (hypoxia), histamine decreased PVR to 55% (H1-antagonist pretreatment) and to 58% (combined H1- and H2-antagonist pretreatment) of posthypoxia values, respectively, demonstrating a marked atypical H2-receptor response. In vitro, both pulmonary arterial and venous strips showed a contractile dose-response to histamine, which was blocked by the H1-antagonist pyrilamine (mepyramine). In precontracted strips, both histamine and the H2-agonists (dimaprit and impromidine) elicited a relaxant response, which was neither blocked by H1-antagonist alone nor by combined H1- and H2-antagonists. We conclude that in sheep the histamine-induced pulmonary vasoconstrictor response is mediated by H1-receptors, while the pulmonary vasodepressor response is mediated by atypical H2-receptors. The systemic vasodepressor response is mediated by both H1- and typical H2-receptors.

Animals↗
PubMed1982

Hypoxic pulmonary vasoconstriction in conscious sheep: role of mast cell degranulation.

We used pharmacologic and histologic techniques to investigate the role of mast cells in the mediation of hypoxic pulmonary vasoconstriction in conscious sheep. Breathing a hypoxic gas mixture (13%, 02, 87% nitrogen) caused hypoxic pulmonary vasoconstriction (HPV) with increases in mean pulmonary artery pressure and pulmonary vascular resistance by 97 and 90%, respectively. Intravenous pretreatment with the mast cell membrane stabilizing agent cromolyn sodium (3 mg/kg/min) completely blocked HPV, whereas the H1-histamine receptor antagonist chlorpheniramine, alone or in combination with the H2-receptor antagonist metiamide and the prostaglandin synthetase inhibitor indomethacin, failed to prevent HPV. Cromolyn sodium failed to modify the pulmonary pressor response to infusions of norepinephrine (alpha-agonist), tyramine (catecholamine-releasing agent), and histamine, indicating the specificity of cromolyn sodium action on the mast cells. Electromicroscopic studies of pulmonary perivascular mast cells showed that a 90-min exposure to the hypoxic gas mixture reduced the total number of granules per mast cell to 75% of control. This was blocked by cromolyn sodium pretreatment. We conclude that in conscious sheep], HP[V is initiated by the liberation of a mast cell product (other than histamine) that either directly or indirectly causes pulmonary vasoconstriction.

Animals↗
PubMed1981

Airway responses to antigen challenge in allergic rhinitis and allergic asthma.

The density dependence of the maximum expiratory flow-volume curve, functional residual capacity (FRC), and specific airway conductance (SGaw) were determined before and during bronchial provocation with ragweed extract in 27 subjects with ragweed hypersensitivity and a history of either bronchial asthma (16 subjects) or allergic rhinitis (11 subjects). Mean baseline SGaw was significantly lower while mean volume of isoflow (Visov) and FrC were significantly higher in subjects with bronchial asthma. During antigen challenge, 10 of 16 subjects with bronchial asthma (63%) and five of 11 subjects with allergic rhinitis (45%) showed a greater than 35% decrease in SGaw ("reactors"): mean relative decreases in SGaw from baseline were 46% and 53%, respectively. The remaining subjects showed a less than 35% decrease in SGaw ("nonreactors") with mean relative decreases of 9% (allergic asthma) and 6% (allergic rhinitis). Mean Visov increased in all subjects with bronchial asthma and in eight of 11 subjects with allergic rhinitis. A significant increase in FRC (6%) was seen only in the "reactors" with bronchial asthma. Following antigen challenge, the beta adrenergic agonist, isoetharine, increased SGaw and decreased Visov. We conclude that in asymptomatic subjects with ragweed hypersensitivity, (1) central and peripheral airway function is more abnormal in subjects with bronchial asthma than in subjects with allergic rhinitis, (2) subjects of both groups show quantitatively and qualitatively comparable airway responses during antigen challenge with a decrease in SGaw or an increase in Visov, possibly representing increase in central and/or peripheral airflow resistance, respectively, (3) Visov may be a more sensitive indicator of airway response to antigen challenge than SGaw, and (4) the bronchodilator effects of a beta adrenergic agonist on antigen-induced bronchospasm are similar in both groups.

Adrenergic beta-Agonists↗
PubMed1981

Acute pulmonary hemodynamic effects of intravenous copper sulfate: role of alpha-adrenergic system.

We investigated the acute pulmonary hemodynamic effects of intravenous copper sulfate (CuSO4) infusion and its mechanism of action in six groups of conscious sheep (total 40). After 300 mg CuSO4 alone, mean pulmonary artery pressure (Ppa) increased from 10.3 to 22.5 Torr and pulmonary artery wedge pressure (Ppaw) from 3.5 to 7.6 Torr, whereas systemic arterial pressure (Psa) increased from 95 to 102 Torr. Cardiac output (Qp) decreased from 4.7 to 3.3 l/min. Pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) increased to 320 and 160% of base line, respectively. The hemodynamic changes correlated well with serum copper, which increased from a base-line value of 0.12 to 3.5 mg/dl after the CuSO4. Serum dopamine beta-hydroxylase increased from 3.2 U/l before CuSO4 injection to 5.7 after its administration, signifying activation of adrenergic nervous system. H1-histamine receptor blockade with chlorpheniramine failed to prevent the effects of CuSO4. Pretreatment with methysergide, a serotonin antagonist, partially attenuated the effects of CuSO4. Phenoxybenzamine, an alpha-adrenergic receptor blocker, and 6-hydroxydopamine, a catecholamine depleting agent, completely blocked the effects of CuSO4. beta-Adrenergic receptor blockade with propranolol enhanced the effects of CuSO4. We conclude, that, in conscious sheep, acute infusion of CuSO4 caused a marked reversible increase in PVR with a slight transient increase in SVR, and this pulmonary hypertension was produced by stimulation of the alpha-adrenergic nervous system.

Animals↗
PubMed1981

Abnormal mucociliary transport in allergic patients with antigen-induced bronchospasm: role of slow reacting substance of anaphylaxis.

We evaluated the possible role of slow reacting substance of anaphylaxis (SRS-A) in mediating mucociliary dysfunction in allergic asthma. In 6 asymptomatic nonsmokers with ragweed asthma, we measured specific airway conductance (SGaw) and tracheal mucous velocity (TMV) before and after bronchial challenge with ragweed extract, with or without pretreatment with 0.5% and 1% FPL-55712 (SRS-A antagonist). Mean baseline TMV was 8.9 mm/min (SD, 1.1). Placebo and FPL-55712 per se had no effect on TMV. With placebo pretreatment, the doses of ragweed extract that resulted in a decrease in SGaw by more than 35% from baseline, led to an immediate decrease in TMV to 74% of baseline (p less than 0.05), returning to baseline within 2 h. With 0.5% and 1% FPL-55712 pretreatment, doses of ragweed extract that resulted in a similar decrease in SGaw led to an increase in TMV to 130% and 126% of baseline (p less than 0.05), respectively, immediately after antigen challenge and returned to baseline 2 h postchallenge. Inhalation of 1% FPL-55712 immediately after antigen challenge prevented the decrease in TMV. These results indicate that (a) SRS-A liberated during airway anaphylaxis impairs mucous transport, and (b) the antigen-induced increase in TMV after pretreatment with an SRS-A antagonist may reflect a stimulatory effect of other chemical mediators of anaphylaxis.

Adolescent↗
PubMed1980

Role of H1- and H2-receptors in airway reactions to histamine in conscious sheep.

We investigated the role of histamine H1- and H2-receptors in the control of airway function in six conscious sheep. In five of these, inhalation of histamine (combined H1- and H2-receptor stimulation) caused an increase in pulmonary resistance (RL) and functional residual capacity and had a variable effect on distribution of ventilation as measured by N2-clearance delay. Pretreatment with the H1-antagonist, chlorpheniramine, prevented these functional effects of histamine challenge, whereas pretreatment with the H2-antagonist, metiamide, potentiated the effects of histamine on RL and caused a uniform increase in N2-clearance delay. Pretreatment with both chlorpheniramine and metiamide prevented the effects of histamine on all parameters indicating effective blockade of H1- and H2-receptors at the dosages used. In one sheep, an increase in RL and N2-clearance delay in response to histamine was only observed after metiamide pretreatment. With or without pretreatment, histamine failed to alter the static pressure-volume curve of the lung. We conclude that in conscious sheep a) inhalation of histamine produces bronchoconstriction and pulmonary hyperinflation without changing lung elastic recoil, b) the observed effects of histamine are mediated by H1-receptors, and H2-receptors have a modulating role, and c) variable effects of histamine on RL and distribution of ventilation may be related to differences in the distribution of H1- and H2-receptors in central and peripheral airways.

Aerosols↗
PubMed1979

Clinical experience with the Lillehei-Kaster valve prosthesis.

The Lillehei-Kaster valve was used in 215 patients over a 7-year period. The aortic valve was replaced in 81 of them. Hospital mortality was 21% (17 patients). Ten patients were lost to follow-up and long-term mortality was 5% (3 patients). The incidence of thromboembolism was 2.6 per 100 patient-years, and actuarial survival was 96% at 5 and 87% at 7 years. Mitral valve replacement was performed in 108 patients. Hospital mortality was 20% (22 patients), 24 patients were lost to follow-up, and long-term mortality was 13% (11 patients). The combined incidence of thromboembolism was 5.0 per 100 patient-years, and actuarial survival was 81% at 5 years and 75% at 7 years. In both groups, the majority of patients improved clinically. Fifteen patients had double-valve replacement, and 11 had coronary revascularization in addition to valve replacement.

Adolescent↗
PubMed1979

Determination of pulmonary blood flow by the rebreathing technique in airflow obstruction.

To test the hypothesis that the effect of nonuniform gas distribution on the uptake of inhaled soluble gases in the lung is minimized by rebreathing, we measured pulmonary blood flow by the thermodilution technique, and pulmonary capillary blood flow, combined pulmonary tissue and capillary blood volume, diffusing capacity of the lung for CO, and alveolar volume by a rebreathing technique in conscious sheep before and immediately after inhalation of a histamine aerosol (4% solution). We also measured pulmonary resistance, distribution of ventilation by multiple-breath N2 washout, and arterial blood gases to monitor airway responses. Histamine inhalation produced a mean pulmonary resistance increase to 621% of baseline accompanied by uneven distribution of ventilation and a decrease in arterial Po2. Despite these alterations in airway function, there were no concomitant changes in pulmonary capillary blood flow, combined pulmonary tissue and capillary blood volume, diffusing capacity of the lung for CO, alveolar volume, or the ratio of diffusing capacity for CO to alveolar volume. Mean pulmonary capillary blood flow and pulmonary blood flow did not differ from each other before and after histamine inhalation. We conclude that the rebreathing technique for noninvasive measurement of pulmonary hemodynamics is satisfactory in the presence of airflow obstruction.

Airway Obstruction↗
PubMed1979

Effect of local radioactivity on trachael mucous velocity of sheep.

The effects of local isotope radiation and x-ray radiation on mucociliary transport of sheep were investigated. X-ray radiation from fluoroscopy equivalent to that used to determine tracheal mucous velocity in intact animals (approximately 3 min) did not alter transport of teflon discs in an isolated sheep trachael preparation. In conscious sheep, 2 ml of a solution containing 8 mCi of macroaggregates of albumin labeled with technetium-99m (99mTc) and 99mTc-pyrophosphate were instilled under direct vision into the trachea via a fiberoptic bronchoscope, providing an actual deposition on the tracheal epithelium of 1.8 to 2 mCi. Physiologic saline and unlabeled macroaggregates of albumin were instilled as control solutions. Tracheal mucous velocity measured by movement of teflon discs increased by 93.2 per cent with 99mTc-labeled macroaggregated albumin and 86.7 per cent with 99mTc-pyrophosphate (P less than 0.01), but no significant increase occurred after saline or unlabeled macroaggregates of albumin. Discrepancies in the values of trachael mucous velocity determined using inert particles and radioactive tracer solution or aerosols might be related in part to the local effects of the tracer radiation.

Animals↗