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Biomedical subjects

I Aziz

Publications and source records attributed to I Aziz.

29 records · Page 2Linked to original sources
PubMed1999

Beta2-adrenoceptor polymorphism and bronchoprotective sensitivity with regular short- and long-acting beta2-agonist therapy.

The aim of the present study was to investigate bronchoprotective sensitivity in patients receiving regular treatment with short- and long-acting beta2-agonists and to evaluate any possible association with genetic polymorphism. Thirty-eight patients with stable mild to moderate asthma and receiving inhaled corticosteroids were randomized in a parallel group, double-blind, double-dummy fashion to receive 2 weeks of treatment with either formoterol (12 microg once daily, 6 microg twice daily or 24 microg twice daily) or terbutaline (500 microg four times daily). Bronchoprotection against methacholine challenge (as a provocative dose to produce a 20% fall in forced expiratory volume in 1.0 s: PD20) was measured at baseline (unprotected) after an initial 1 week run-in without beta2-agonist, and at 1 h after the first and last doses of each treatment. The PD20 values were log-transformed and calculated as change from baseline. Percentage desensitization of log PD20 for first- versus last-dose bronchoprotection was calculated and analysed according to effects of treatment and beta2-adrenoceptor polymorphism at codon 16 or 27. The mean degree of desensitization for bronchoprotection was comparable with all four treatments and there were no significant differences in absolute PD20 values after 2 weeks of chronic dosing. The PD20 values were (as microg of methacholine, geometric means+/-S. E.M.): formoterol, 12 microg once daily, 99+/-42 microg; formoterol, 6 microg twice daily, 107+/-44 microg; formoterol, 24 microg twice daily, 108+/-45 microg; terbutaline, 500 microg four times daily, 88+/-37 microg. All patients receiving formoterol, 24 microg twice daily, exhibited a loss of protection greater than 30% which was unrelated to polymorphism at codon 16 or 27. For codon 16, the use of lower doses of formoterol (12 microg once daily or 6 microg twice daily) showed wider variability in the propensity for protection loss in patients who were heterozygous, in contrast to a more uniform protection loss seen with homozygous glycine patients. The amount of protection loss was not significantly related to polymorphism at codon 16 or 27, expressed as values (mean+/-S.E.M.) for percentage desensitization according to each genotype (pooled treatments): Gly-16, 66+/-11%; Het-16, 53+/-8%; Arg-16, 69+/-18%; Glu-27, 68+/-12%; Het-27, 58+/-8%; Gln-27, 52+/-12%. The results of this preliminary study showed that bronchoprotective desensitization occurred readily in response to short- or long-acting beta2-agonist exposure irrespective of beta2-adrenoceptor polymorphism at codon 16 or 27. Further studies with larger patient numbers are required to further evaluate the effects of polymorphisms with lower doses of regular formoterol.

Adolescent↗
PubMed1999

Determinants of survival after inferior vena cava trauma.

Inferior vena cava (IVC) injuries continue to be associated with mortality rates of 21 to 66 per cent despite advances in prehospital, surgical, and critical care. The purpose of this study was to evaluate outcome of patients with IVC injury after treatment at a major urban trauma center and to identify factors predictive of survival. Between 1989 and 1995, 158 patients presented to the Los Angeles County + University of Southern California Medical Center with IVC injuries. One hundred thirty-six patient records were available for review, and 69 data points were collected and analyzed. Mean age was 26 years (range, 6-54), and 122 (90%) patients were male. Mechanism of injury included gunshot in 88 (65%) patients, stab in 23 (17%) patients, shotgun in 7 (5%) patients, and blunt trauma in 18 (13%) patients. The mean Injury Severity Score was 25. Seventy (52%) patients were hypotensive. Eleven (8%) patients died before surgical intervention, and 25 (18%) patients died before operative repair. Repair (79), ligation (20), or observation (1) was accomplished in 100 (74%) patients. Overall survival was 48 per cent and 65 per cent in the 100 patients surviving to operative repair, including 5 of 20 patients requiring IVC ligation. Significant differences (P<0.001) between survivors and nonsurvivors included Injury Severity Score, Glasgow Coma Score, hematocrit, hypotension, emergent thoracotomy, blood loss, level of injury, tamponade, and associated aortic injury. Logistic regression analysis identified hypotension, anatomic level of injury, and associated aortic injury as significant predictors of outcome (P = 0.001). Survival is predominantly determined by severity and anatomic accessibility of the IVC injury and by the absence of associated major vascular injuries. Ligation may control otherwise exsanguinating injuries and should be considered early in the management of complex injuries.

Adolescent↗
PubMed1998

Concomitant inhaled corticosteroid resensitises cardiac beta2-adrenoceptors in the presence of long-acting beta2-agonist therapy.

OBJECTIVE: The aim of the present study was to evaluate the effects of concomitant inhaled corticosteroid therapy on the sensitivity of cardiac beta2-adrenoceptors in patients receiving regular long-acting beta2-agonists. METHODS: Twelve healthy subjects (6 female), mean age 29 years, were randomised in a double-blind cross-over study to receive either inhaled placebo or inhaled budesonide 1.2 mg twice daily, each for 7 days, with a minimum of 7 days washout period between the two treatments. Patients also received concomitant treatment with inhaled eformoterol 24 microg twice daily during each of the 2 treatment periods. The patients attended the laboratory during both treatment periods at 0730 hours, when a dose-response curve for systemic beta2-adrenoceptor responses to inhaled salbutamol (0.8-3.2 mg) was constructed before and after completing 7 days of each treatment. Early morning (0800 hours) plasma cortisol was also evaluated as a marker of systemic glucocorticoid activity. RESULTS: There was a significant fall in 0800 hours plasma cortisol induced by budesonide comparing pre- and post-values (407 vs 322 nmol.1(-1), but not with placebo. There were no differences in the response to salbutamol prior to treatment when comparing eformoterol with placebo versus eformoterol with budesonide. Comparing before and after within-treatment heart rate response, there was a significant reduction in peak salbutamol response with eformoterol and placebo, which was partially reversed by eformoterol and budesonide. For between-treatment comparisons after eformoterol treatment, the heart rate was significantly higher in the presence of budesonide in comparison with placebo for peak salbutamol response (change from baseline), i.e. 24.2 vs 34.7 beats min(-l). There was, however, no significant difference in the peak delta potassium response to salbutamol after eformoterol treatment when comparing budesonide with placebo (-0.39 vs -0.48 mmol.1(-1)). CONCLUSION: Concomitant therapy with inhaled budesonide resensitised the cardiac beta2-adrenoceptor response to salbutamol in subjects who were receiving regular twice-daily eformoterol. This may be of clinical relevance in terms of the propensity for systemic beta2-mediated adverse effects with repeated puffs of salbutamol, which might conceivably occur in the setting of acute asthma.

Administration, Inhalation↗
PubMed1998

Beta2-adrenoceptor regulation and bronchodilator sensitivity after regular treatment with formoterol in subjects with stable asthma.

OBJECTIVE: We have previously found that beta2-adrenoceptor downregulation and bronchodilator desensitization to albuterol occurred at 36 hours after stopping regular treatment with twice daily salmeterol. In this study we have evaluated these same effects with formoterol given once or twice daily on a regular basis. METHODS: In a randomized, placebo-controlled, double-blind, double-dummy crossover study, 16 subjects with mild-to-moderate stable asthma (mean [SD] age, 32.5 [15.3] years; mean [SD] FEV1, 73.2 [12.1] percent predicted) receiving regular inhaled corticosteroid therapy received 1 week of treatment with formoterol dry powder (24 microg twice daily [8 AM/8 PM]), formoterol (24 microg once daily [8 PM]), or identical placebo. Lymphocyte beta2-adrenoceptor parameters and a dose-response curve to inhaled albuterol (200 to 1600 microg) were evaluated at 36 hours after the last dose of each treatment period. RESULTS: There were no significant differences in the mean values for albuterol dose-response effects among the three treatment regimens. Comparison of maximal bronchodilator responses between treatments (mean and SEM as change from baseline) revealed no significant differences between treatments for FEV1 (0.47 L [0.06 L] for placebo vs 0.48 L [0.07 L] for 24 microg once daily formoterol vs 0.51 L [0.08 L] for 24 microg twice daily formoterol) or for forced expiratory flow, mid-expiratory phase (FEF25-75) (0.80 L/sec [0.12 L/sec] for placebo vs 0.80 L/sec [0.16 L/sec] for 24 microg once daily formoterol vs 0.89 L/sec [0.14 L/sec] for 24 microg twice daily formoterol). Formoterol also had no significant effect on mean lymphocyte beta2-adrenoceptor density. However, in five of seven patients with the homozygous Gly-16 polymorphism, beta2-adrenoceptor density was downregulated by twice daily formoterol, whereas only two such cases exhibited a reduction in maximal FEV1 response to albuterol. CONCLUSIONS: The results of this study showed that for patients taking inhaled corticosteroids, overall beta2-adrenoceptor regulation and associated bronchodilator sensitivity to inhaled albuterol were unaltered at 36 hours after stopping regular treatment with formoterol. However, in a subset of patients who were Gly-16 homozygous, there was a tendency towards downregulation but not desensitization. Further studies in subjects with more severe asthma are required to assess the clinical relevance of these findings.

Administration, Inhalation↗
PubMed1998

Subsensitivity to bronchoprotection against adenosine monophosphate challenge following regular once-daily formoterol.

Regular treatment with inhaled long-acting beta2-agonists leads to subsensitivity to their bronchoprotective effects, although the effect of dosing frequency on this subsensitivity is not known. The aim of this study was to assess whether a once-daily dosing regimen with formoterol might be associated with a lesser degree of subsensitivity. In a randomized placebo-controlled double-blind, double-dummy crossover study 10 asthmatics treated with inhaled steroids (mean age 31 yrs, forced expiratory volume in one second (FEV1) 82% predicted) received 1 week of treatment with: formoterol dry powder 24 microg twice daily (08:00 and 20:00 h); formoterol 24 microg once daily (20:00 h); or identical placebo. Adenosine monophosphate (AMP) bronchial challenge was performed 12 h after the first and the last dose of each treatment. There was significant loss of protection with formoterol twice daily between the first and last dose (geometric mean provocative concentration causing a 20% fall in FEV1 (PC20)): 475 versus 129 mg x mL(-1) (a 3.7-fold loss, p=0.006) and with formoterol once daily: 367 versus 127 mg x mL(-1) (a 2.9-fold loss, p=0.005), compared with placebo: 71 versus 75 mg x ml(-1) (nonsignificant). There was no significant difference in the degree of loss of protection between formoterol once and twice daily. For first-dose protection there was a significant difference between active treatments and placebo, but after the last dose the residual protection between active treatments and placebo was not significant. Thus, in patients taking inhaled corticosteroids, regular formoterol 24 micreog once daily induces a similar degree of subsensitivity to adenosine monophosphate bronchial challenge as with formoterol 24 microg twice daily. This in turn suggests that even with a 24-h dosing interval there is the development of tolerance to formoterol by prolonged occupancy of airway beta2-adrenoceptors.

Adenosine Monophosphate↗
PubMed1996

Intraoperative color duplex scanning for infrainguinal vein grafts.

We compared the findings of intraoperative color duplex scanning and completion arteriography in patients undergoing infrainguinal vein bypasses to identify hemodynamic abnormalities that could result in a predisposition to early or late graft failure. We reviewed the records of 72 patients who underwent 81 vein bypass graft procedures. Three intraoperative diagnostic methods were used. In 28 procedures (group I) both color duplex and completion arteriography were used, in 21 procedures (group II) only color duplex was used, and in 26 procedures (group III) only completion arteriography was used. Grafts were followed using a duplex surveillance protocol for a mean interval of 16.1 months. Nine grafts in group I showed an abnormality on the duplex scan but not on the completion arteriogram. Seven grafts had a peak systolic velocity (PSV) greater than 200 cm/sec and two had a PSV less than 45 cm/sec. These findings led to six immediate repairs, one early revision, and two late revisions. Arteriography demonstrated additional defects in two procedures but repairs were not performed. In group II duplex scans showed an abnormality in eight procedures (seven grafts with PSV 200 to 250 cm/sec and one graft with a retained valve) resulting in three immediate repairs and five late revisions. In the remaining 13 procedures in group II, duplex scans were normal and no revisions were required during follow-up. In group III defects were detected by arteriography in four procedures (> 50% stenosis in three grafts and one arterial spasm) leading to three immediate repairs. In the remaining 22 studies arteriograms were interpreted as normal; however, seven of these grafts required late revisions. Our data suggest that grafts that appear normal on intraoperative duplex scans are not likely to develop a stenosis requiring revision. Intraoperative duplex ultrasound may be superior to completion arteriography.

Adult↗
PubMed1996

A comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in humans: a study of once daily administration by intramuscular and intravenous routes.

Pleural fluid and serum pharmacokinetics of ceftriaxone were performed in thirteen patients with pleural effusion. One gram of ceftriaxone was administered once daily intravenously in six patients and intramuscularly in seven patients. Ceftriaxone concentrations were measured in serum and pleural fluids in both groups on the first day of administration and in four patients of the intramuscular group on the fourth day of administration. The mean serum peak concentration at 1 h was 199 mg/L (S.E.M. 63.2) in the iv group and 80.5 mg/L (S.E.M. 12.0) in the im group. The mean serum trough concentrations in the two groups at 24 h were 27.5 mg/L (S.E.M. 12.6) and 29.7 mg/L (S.E.M. 5.2) respectively. In the pleural fluid, mean peak concentration was 20.1 mg/L (S.E.M. 4.7) at 6 h in the iv group and 15.3 mg/L (S.E.M. 5.1) at 12 h in the im group. The mean trough concentration was 9.6 mg/L (S.E.M. 1.9) and 13.3 mg/L (S.E.M. 3.1) at 24 h in the two groups respectively. On the fourth day of intramuscular administration the serum and pleural fluid peak and trough concentrations were higher when compared with the first day, consistent with a cumulative effect. The serum and pleural fluid concentrations of ceftriaxone following intravenous and intramuscular administration were well above the MIC90 of most common respiratory pathogens indicating good penetration into extracellular spaces. Further, these serum and pleural fluid antibiotic concentrations could be maintained even after a single intramuscular injection of the drug, thus indicating its usefulness as a parenteral mode of therapy on a domicilliary basis with a significant cost-saving potential. In conclusion, intramuscular administration of ceftriaxone would appear to be a convenient method of administering parenteral therapy in lower respiratory tract infections in the hospital and community, with pharmacokinetics very similar to those exhibited by the intravenous route.

Adult↗
PubMed1991

[Diagnosis of streptococcal pharyngo-tonsillitis: clinical criteria or coagglutination?].

With the purpose of evaluating the usefulness of clinical data and a coagglutination test for the diagnosis of streptococcal pharyngeal tonsillitis, a study was carried out comparing both methods with the standard pharynx culture (gold standard). One hundred and forty-one patients clinically diagnosed with pharyngeal tonsillitis were analyzed. 80 other patients diagnosed with rhino-pharyngitis were used as control groups as well as a group of 66 healthy patients. It was found that the presence of pus in the tonsils and the absence of rhinorrhea and/or a productive cough were isolated clinical variables which showed a significant difference when comparing those cases with a positive or a negative culture (P less than 0.01). These clinical data had a sensitivity and adequate negative predictive values (68 to 83% and 90 to 92%, respectively); specificity was 44 to 74% and the positive predictive value from 24 to 36%. The gathering of combined clinical indexes with different symptoms and signs, were not greater than isolated data. The coagglutination test in those cases of pharyngeal tonsillitis showed greater better specificity (98%) and positive predictive value (93%), but saw no improvement in sensitivity (72%) nor in the negative predictive value (91%), which is why when faced with a negative coagglutination test, it is still necessary to perform a throat culture due to the risk which the patient may be exposed to when no treatment is given. The analysis of the advantages and disadvantages in the routine use of coagglutination and cultures in their particular cases, allows us to conclude that in daily clinical practice the use of clinical criteria is of greater usefulness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

Analysis of human erythrocyte 5'-nucleotidases in healthy individuals and a patient deficient in pyrimidine 5'-nucleotidase.

Electrophoretic and quantitative analysis of pyrimidine 5'-nucleotidase in human erythrocytes from healthy individuals and a patient deficient in pyrimidine 5'-nucleotidase, using a range of substrates, has shown that the patient has a marked deficiency with UMP, CMP and dCMP as substrates but near normal levels of activity with dUMP and dTMP as substrates. The observations suggest that two separate structural gene loci coding for distinct 5'-nucleotidases with similar electrophoretic mobility exist in man. The genetic determination of these enzymes seems therefore to be homologous with that found in rodents.

5'-Nucleotidase↗