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Biomedical subjects

S Aziz

Publications and source records attributed to S Aziz.

At least 19 recordsLinked to original sources

Cardiovascular surgery in the elderly.

The elderly segment of the population is increasing rapidly, and surgeons are more frequently being requested to operate on this group of patients. A number of reports suggest that elderly patients have a significantly higher incidence of operative mortality and 30-day hospital mortality as compared with younger patients. Elderly patients also had a significantly higher increased incidence of complications, such as renal failure, prolonged ventilation, and incidence of strokes and postoperative cardiac arrest. Regarding coronary artery disease, elderly patients are more acutely sick on admission, are more likely to have triple-vessel disease, more likely have comorbid disease, and are usually less likely to receive an internal mammary artery graft. The presence of valvular disorders with concomitant coronary disease (especially mitral ischemic related valve disease) increases operative time, morbidity, and mortality. Efforts must continue to be made to gather data on outcomes of cardiac surgery in the elderly. Consideration must be given to modify the operative approach that minimizes cardiopulmonary bypass time, mitigates the multisystem organ injury associated with cardiopulmonary bypass, and decreases the likelihood of embolization from the ascending aorta. Future efforts must be made to develop measures to decrease the complications rate identified in elderly patients.

Aged

Generation and characterization of human smooth muscle cell lines derived from atherosclerotic plaque.

The study of atherogenesis in humans has been restricted by the limited availability and brief in vitro life span of plaque smooth muscle cells (SMCs). We describe plaque SMC lines with extended life spans generated by the expression of the human papillomavirus (HPV)-16 E6 and E7 genes, which has been shown to extend the life span of normal adult human aortic SMCs. Resulting cell lines (pdSMC1A and 2) demonstrated at least 10-fold increases in life span; pdSMC1A became immortal. The SMC identity of both pdSMC lines was confirmed by SM22 mRNA expression. pdSMC2 were generally diploid but with various structural and numerical alterations; pdSMC1A demonstrated several chromosomal abnormalities, most commonly -Y, +7, -13, anomalies previously reported in both primary pdSMCs and atherosclerotic tissue. Confluent pdSMC2 appeared grossly similar to HPV-16 E6/E7-expressing normal adult aortic SMCs (AASMCs), exhibiting typical SMC morphology/growth patterns; pdSMC1A displayed irregular cell shape/organization with numerous mitotic figures. Dedifferentiation to a synthetic/proliferative phenotype has been hypothesized as a critical step in atherogenesis, because rat neonatal SMCs and adult intimal SMCs exhibit similar gene expression patterns. To confirm that our pdSMC lines likewise express this apparent plaque phenotype, osteopontin, platelet-derived growth factor B, and elastin mRNA levels were determined in pdSMC1A, pdSMC2, and AASMCs. However, no significant increases in osteopontin or platelet-derived growth factor B expression levels were observed in either pdSMC compared with AASMCs. pdSMC2 alone expressed high levels of elastin mRNA. Lower levels of SM22 mRNA in pdSMC1A suggested greater dedifferentiation and/or additional population doublings in pdSMC1A relative to pdSMC2. Both pdSMC lines (particularly 1A) demonstrated high message levels for matrix Gla protein, previously reported to be highly expressed by human neointimal SMCs in vitro. These results describe 2 novel plaque cell lines exhibiting various features of plaque SMC biology; pdSMC2 may represent an earlier plaque SMC phenotype, whereas pdSMC1A may be representative of cells comprising an advanced atherosclerotic lesion.

Animals

Prospective trial of catheter irrigation and muscle flaps for sternal wound infection.

BACKGROUND: Sternal wound infection is a relatively rare but potentially devastating complication of open heart operations. The most common treatments after debridement are rewiring with antibiotic irrigation and muscle flaps. Here we present the results of a prospective trial to determine the appropriate roles of closed-chest catheter irrigation and muscle flap closure for sternotomy infection and to assess the effect of internal mammary artery bypass grafting on the outcome of each treatment modality. METHODS: Between 1990 and 1994, 5,658 sternotomies were performed at the University of Washington Medical Center. Sternal dehiscence occurred in 43 patients, 25 of whom had infection (overall incidence, 0.44%). Because of the infrequency of this complication, a prospective, randomized trial was developed in which the initial approach to sternal dehiscence was rewiring and catheter irrigation. Muscle flaps were used as the primary treatment if the sternum could not be restabilized or as secondary treatment if catheter irrigation failed. Wound resolution, length of hospital stay, and complications were evaluated. RESULTS: Sterile dehiscences were successfully closed with irrigation in 17 of 18 patients; the other patient required flap closure. Of the 25 patients with infection, 19 had irrigation and 6, closure with flaps primarily. In the group of infected patients, 17 of the 19 who received irrigation also had internal mammary artery bypass grafting. Irrigation failed in 15 (88.2%) of these 17 patients, and salvage was accomplished with muscle flap closure. All 6 patients with infection who were closed primarily with muscle flaps had a successful outcome. Hospitalization averaged 10.2 days when muscle flaps were used primarily and 14.3 additional days for unsuccessful irrigation. When irrigation was successful, the hospital stay averaged 11.2 days. CONCLUSIONS: Catheter irrigation should be reserved for patients without infection or patients with infection but without internal mammary artery bypass grafts in whom dehiscence occurs less than 1 month after sternotomy. All others should have closure with muscle flaps.

Anti-Bacterial Agents

Snake bite experience at Pakistan Institute of Medical Sciences.

We reviewed 40 cases of snake bite seen from January, 1996 to December, 1996. Most of the cases survived uneventfully but many developed complications which were either haematologic, (23 patients) or neurological (5 patients). Appropriate treatment was offered in every case. Polyvalent antisnake venom was administered to 30 patients (75%). Premedication used was steroids and antihistamines to prevent anaphylactic reactions. Antifibrinolytic therapy (tranxemic acid) was given to every bleeding patient. The species of offending snake could be recognized in one patient while in all others, it was not possible due to night time incidence and poor description by the patient.

Adolescent

The clinical significance of flow cytometry crossmatching in heart transplantation.

BACKGROUND: Flow cytometry crossmatching is more sensitive than cytotoxic methods in identifying preformed antibodies to donor alloantigens. However, the significance of a positive flow crossmatch remains unknown for a recipient of a heart transplant who has a negative anti-human globulin crossmatch. METHODS: Flow crossmatching was performed retrospectively for 92 recipients of a primary cardiac allograft who underwent transplantation with a negative AHG crossmatch. RESULTS: Forty-six patients were flow crossmatch-positive for alloantibody: 20 were positive on both T and B lymphocytes, 12 were positive only on B lymphocytes, and 13 were positive only on T lymphocytes. Eleven had autoantibody invalidating the flow crossmatch with donor cells. Thirty-six patients had negative flow crossmatch. A significantly higher incidence of graft dysfunction with vascular rejection by 6 months was found for patients who had a positive flow crossmatch on B lymphocytes. This group also had an increased incidence of mortality within this same period. Patients who were flow crossmatch-positive on T and B lymphocytes were more likely to experience greater than two episodes of treated cellular rejection within the first 6 months. Flow crossmatch-positive patients stayed longer in the hospital in comparison to the other two groups, although the increases were not statistically significant. There were no differences between groups with regard to time to first rejection, absence of rejection episodes, episodes of decreased cardiac index (<2.3 L/m2), depressed left and right ventricular ejection fraction, or development of transplant atherosclerosis. CONCLUSION: A positive flow crossmatch identified a subset of patients who are predisposed to development of vascular rejection or are more likely to have frequent cellular rejection.

Female

Pattern of tuberculosis in general practice.

An audit of 690 cases of tuberculosis out of 46,276 patients seen during the last 25 years in a busy general practice is reported. Of the 690 cases, 67% were pulmonary, 33% extra-pulmonary TB. Modes of both types of tuberculosis are described and the reason for increased incidence of extra-pulmonary tuberculosis are discussed.

Adolescent

Donor left ventricular hypertrophy increases risk for early graft failure.

A review of factors contributing to early mortality after cardiac transplantation revealed that up to 25% of deaths were due to primary graft dysfunction unrelated to rejection or infection. In light of this finding, evaluation of a donor heart with regard to its suitability for transplantation takes on added importance. In an effort to screen the suitability of donor hearts in the region covered by the Northwest Organ Procurement Agency (USA), all donors are evaluated by two-dimensional transthoracic echocardiography as part of the initial evaluation. A total of 110 donor echocardiograms were reviewed and an attempt was made to correlate the 30-day outcome with the parameters measured. An unexpected finding was that the presence of left ventricular hypertrophy in the donor heart was associated with an increase in the incidence of donor heart dysfunction compared with donors with normal echocardiographic profiles (33% vs 3%, P = 0.007).

Adult

Corticosteroid use and abuse by medical practitioners for arthritis and related disorders in Pakistan.

A total of 256 consecutive patients attending our out-patient clinic in Islamabad, Pakistan, with complaints of pain in or around the joints were evaluated for use of corticosteroids prescribed by medical practitioners they had seen earlier. The appropriateness of such prescriptions and their consequent effects were assessed. Of the 256 patients, 110 (i.e. 42.5%) were identified as steroid users; some of them were suffering from conditions known to be unresponsive to this form of therapy. One hundred and one of the 256 patients had rheumatoid arthritis and 67% of these had been using steroids, mostly in an irrational manner. The general practitioners and consultants (all non-rheumatologists) were responsible for the majority of steroid prescriptions. Steroid side-effects were observed in 42/110 (38.2%) cases. This prevalent practice in Pakistan is a reflection of the state of affairs in developing countries, and indicates a need for improvement and better regulation of health care in such countries.

Adrenal Cortex Hormones

Oral presentation of posttransplantation lymphoproliferative disorders. An unusual manifestation.

Cyclosporine, an immunosuppressive agent widely used in organ transplantation, has several undesirable side effects, including gingival hyperplasia, which occurs in up to 70% of patients. Another complication associated with use of cyclosporine and other immunosuppressants is an increased incidence of malignancies. Long-term use of cyclosporine also is associated with a spectrum of hyperproliferative disorders ranging from reactive lymphoid hyperplasia to aggressive malignant lymphomas. While cyclosporine-related lymphoproliferative disorders have been widely reported, they have not been described in the oral cavity as the first manifestation of this disease. We report on two cardiac transplantation patients with a history of cyclosporine use who presented initially with oral symptoms of lymphoproliferative disorder. Both had erythematous to cyanotic and hyperplastic gingiva. On gingivectomy, the fixed tissue was soft, glistening, and tan colored, in contrast to the usual firm, white, cyclosporine-associated, benign gingival fibrous hyperplasia. Histologically, a dense, diffuse infiltrate of lymphoplasmacytoid cells with vesicular nuclei, prominent nucleoli, a moderate amount of cytoplasm, and high mitotic activity was observed. Immunocytochemical studies confirmed that the cells were monoclonal for lambda light chains in one patient and kappa light chains in the other. The cells from one patient were positive for CD45, while both patients were negative for CD20 and all nonhematopoietic antigens tested. Both tissues were strongly positive for Epstein-Barr virus. Morphology and immunocytochemistry findings are consistent with a posttransplant lymphoproliferative disorder. These are the first two reported cases of cyclosporine-associated posttransplant lymphoproliferative disorders presenting as gingival hyperplasia.

Adult

Regulation of polyamine synthesis and transport by fibroblast growth factor in aortic smooth muscle cells.

Basic-FGF (FGF2) is implicated as a regulator of smooth muscle cell proliferation that develops after arterial injury. Polyamines are essential for cell growth and differentiation and may mediate some of the FGF2-elicited responses. To examine this possibility, the effect of FGF2 on polyamine synthesis and uptake was tested on rat arterial smooth muscle cells. Exposure of cells to FGF2 for 24 and 48 h resulted in increased intracellular polyamine content. Ornithine decarboxylase (ODC) activity increased in FGF2-treated cells after 6 h of treatment, whereas no increases were detected in ODC mRNA steady-state levels. Basic-FGF increased maximal polyamine transport rate without changes in Km. Treatment with actinomycin D decreased polyamine transport. The effect of cyclohexamide on polyamine uptake was dose dependent. These studies indicate that treatment of vascular smooth muscle cells with FGF2 results in increases in intracellular polyamine content, polyamine synthetic activity, and polyamine transport.

Animals

Serum alpha 1 antitrypsin and pulmonary emphysema.

Using isoelectric focusing (IEF) and radial immunodiffusion (RID) techniques, serum samples from 100 normal healthy adults and 21 patients with pulmonary emphysema were analysed to identify various alpha 1 antitrypsin phenotypes and the serum concentrations. Ten percent of the patients had low serum values. The normal or most common genetic form, MM, is the predominant phenotype in both controls and patients.

Adolescent

Endothelial loss and regeneration in a model of transplant arteriosclerosis.

Early endothelial injury may play a role in the development of transplant arteriosclerosis. The present study documents early endothelial changes using a rat aortic graft model. Abdominal aortic allografts from PVG rats were orthotopically transplanted to DA rats. Controls were DA to DA transplants. Endothelial cell (EC) injury, regeneration, and leukocyte infiltration in the intima were evaluated using scanning electron microscopy and histological and immunocytochemical techniques. Nontransplanted aortic segments showed partial loss of ECs after 1 or 2 hr of preservation. Control isografts demonstrated extensive EC denudation and neutrophil adherence to residual ECs at 1 day post-transplantation. After 3 days, isografts showed continued regeneration of ECs in the central area and ingrowth of endothelium from both clamped sites in the recipient aorta. Reendothelialization was complete by day 14. Allografts showed similar findings to isografts up to day 3. In contrast to isografts, however, there was a secondary EC loss beginning at day 7. Monocytes/macrophages and T cells were noted to be adherent to residual ECs in 7- and 14-day allografts. At 20 days, ECs were absent from the luminal surface in the center of allografts. Endothelium did extend from clamped sites toward the midgraft region as in isografts. By 60 days allografts were completely reendothelialized. These results demonstrate that in both isografts and allografts there is initial EC loss due to mechanical trauma and ischemia/reperfusion injury, followed by partial reendothelialization. This latter process continues unabated in isografts, whereas in allografts the secondary EC loss occurs due to an allogenic response. This is followed by complete reendothelialization that occurs during the concurrent development of significant intimal hyperplasia.

Animals

Inhibition of pulmonary surfactant biophysical activity by cationic polyamino acids.

PURPOSE: The purpose of this study is to investigate the interaction of cationic polyamino acids, polylysine and polyarginine, with rat pulmonary surfactant at the air/water interface. METHODS: Surface pressure measurements of rat pulmonary surfactant in the presence and absence of polyamino acids were carried out in both dynamic and static modes. RESULTS: In dynamic cycle studies, compression and expansion of adsorbed surfactant films in the presence of the cationic polyamino acids resulted in a delayed attainment of the plateau surface pressure. In area studies of spread surfactant films at constant surface pressure, cationic polyamino acids in the subphase resulted in an increase in film area. Increased film area was also observed when a polyamino acid was injected beneath films of dipalmitoyl-phosphatidylcholine/phosphatidylglycerol. In the presence of the cationic polyamino acids, the equilibrium surface pressure (at constant film area) of pulmonary surfactant was elevated in a concentration- and molecular weight-dependent manner. CONCLUSIONS: These data indicate that the model cationic peptides interact with surfactant lipid, possibly electrostatically with phosphatidylglycerol. It is concluded that the surface activity of pulmonary surfactant is significantly inhibited by the presence of the polycations, possibly by the formation of a mixed lipid/polyamino acid film.

Animals

Home environment and peer relations of addicted and nonaddicted university students.

This study was designed to examine the differences between addicted and nonaddicted university students on measures of home environment and peer relations. Participants were 45 addicts and 45 nonaddicts with mean ages of 23 years drawn from three Pakistani universities located in Islamabad, Lahore, and Peshawar. The two groups were matched for age, gender, education, area of residence, and marital status. A booklet containing an Index of Family Relations and a Peer Relations Questionnaire was administered. Results showed that the addicts perceived more stress in their families than the non-addicts did. Family income of the addicts was greater than that of the nonaddicts. Addicts were under greater peer influence and had more deviant and drug-using friends than the nonaddicts.

Adult