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Biomedical subjects

S Hussain

Publications and source records attributed to S Hussain.

At least 37 records · Page 2Linked to original sources

Methicillin resistant Staphylococcus aureus: a multicentre study.

OBJECTIVE: To determine the frequency of Methicillin resistance Staphylococcus aureus infection in major cities of Pakistan. SETTING: Various laboratories of the country with one as the central Laboratory. MATERIALS AND METHODS: Seven hundred and ninety two consecutive clinical isolates of Staphylococcus aureus were collected from 8 laboratories all over Pakistan i.e. Karachi, Peshawar, Lahore, Sukkhur, Islamabad, Quetta, and Mirpur, Azad Kashmir. Antibiotic sensitivity was done by Kirby Bauer disc diffusion method and MIC of Vancomycin was determined by 'E' test. RESULTS: Forty two percent of the isolates were found to be Methicillin resistant staphylococcus aureus (MRSA) while no Vancomycin resistance was encountered. CONCLUSION: Methicillin resistant Staphylococcus aureus (MRSA) are seen in the local population with frequencies varying between 2-61% highest incidence is seen in the major cities of the country. Fortunately no Vancomycin resistant Staphylococcus has been isolated from any of the major cities.

Developing Countries↗

Faecal empyema.

Explore the source record for details and available documents.

Cecal Diseases↗

The direct cost of treating bronchial asthma in a teaching hospital in Malaysia.

A pilot study to evaluate the direct cost of treating 51 adults and 50 children with bronchial asthma was conducted. All aspects of the medical care provided over a 6-month period were considered. The mean treatment costs per month were US dollars 22.97 (adults) and US dollars 15.56 (children). The cost of maintenance therapy accounted for 55.5% and 73.4% of the total direct cost treatment for adults and children respectively. Only 27 (52.9%) adults and 17 (34.0%) children paid for their inhaled prophylactic drugs, amounting to 12.3% of the total maintenance therapy costs. Thirteen (25.4%) adults and 9 (18.0%) children were using alternative therapy at a monthly cost of US dollars 41.50 and US dollars 16.77 respectively. A substantial proportion of the direct cost of asthma treatment is heavily subsidized in Malaysia. Adequate attention to the allocation of the health budget, to ensure the optimal provision of health care, is warranted.

Adult↗

Genetically engineered macrophages expressing IFN-gamma restore alveolar immune function in scid mice.

Reversal of immunodeficiency in the lung by gene therapy is limited in part by the difficulty of transfecting lung cells in vivo. Many options exist for successfully transfecting cells in vitro, but they are not easily adapted to the in vivo condition. To overcome this limitation, we transduced macrophages in vitro with the murine IFN-gamma (mIFN-gamma) gene and intratracheally delivered the macrophages to express mIFN-gamma in vivo. A recombinant retroviral vector pSF91 system was modified to encode mIFN-gamma and enhanced green fluorescent protein (EGFP). A murine macrophage cell line J774A.1 transduced with the retroviral supernatant increased secretion from undetectable levels to 131.6 +/- 4.2 microg/ml mIFN-gamma at 24 h in vitro. The mIFN-gamma-producing macrophages were intratracheally instilled into mechanically ventilated scid mice. mIFN-gamma levels in the bronchoalveolar lavage increased from undetectable levels at baseline to 158.8 +/- 5.1 pg/ml at 48 h (P < 0.001). Analysis of the lavaged cells for EGFP expression revealed that EGFP expression was directly proportional to the number of transduced macrophages instilled into the lung. Immune function was partially restored in the alveolar spaces of scid mice with evidence of enhanced MHC class II antigen expression and increased phagocytosis (P < 0.05). Tumor necrosis factor alpha was increased from undetectable at baseline to 103.5 +/- 11.4 pg/ml. In contrast, i.p. administration of the engineered macrophages did not enhance IFN-gamma levels in the lung. Our study suggests airway delivery of genetically engineered macrophages expressing mIFN-gamma gene can partially restore significant immune activity in the lungs of immunodeficient mice.

Animals↗

Variation in aspects of cysteine proteinase catalytic mechanism deduced by spectroscopic observation of dithioester intermediates, kinetic analysis and molecular dynamics simulations.

The possibility of a slow post-acylation conformational change during catalysis by cysteine proteinases was investigated by using a new chromogenic substrate, N-acetyl-Phe-Gly methyl thionoester, four natural variants (papain, caricain, actinidin and ficin), and stopped-flow spectral analysis to monitor the pre-steady state formation of the dithioacylenzyme intermediates and their steady state hydrolysis. The predicted reversibility of acylation was demonstrated kinetically for actinidin and ficin, but not for papain or caricain. This difference between actinidin and papain was investigated by modelling using QUANTA and CHARMM. The weaker binding of hydrophobic substrates, including the new thionoester, by actinidin than by papain may not be due to the well-known difference in their S2-subsites, whereby that of actinidin in the free enzyme is shorter due to the presence of Met211. Molecular dynamics simulation suggests that during substrate binding the sidechain of Met211 moves to allow full access of a Phe sidechain to the S2-subsite. The highly anionic surface of actinidin may contribute to the specificity difference between papain and actinidin. During subsequent molecular dynamics simulations the P1 product, methanol, diffuses rapidly (over<8 ps) out of papain and caricain but 'lingers' around the active centre of actinidin. Uniquely in actinidin, an Asp142-Lys145 salt bridge allows formation of a cavity which appears to constrain diffusion of the methanol away from the catalytic site. The cavity then undergoes large scale movements (over 4.8 A) in a highly correlated manner, thus controlling the motions of the methanol molecule. The changes in this cavity that release the methanol might be those deduced kinetically.

Catalysis↗

The effects of N-methyl-D-aspartate antagonist 2-amino-7-phosphonoheptanoic acid microinfusions into the adult male rat substantia nigra pars reticulata are site-specific.

We examined the effects of regional infusions of 2-amino-7-phosphonoheptanoic acid (AP7) into the substantia nigra pars reticulata (SNR) in adult male rats on flurothyl-induced clonic seizures. AP7 infusions in the SNR had dose- and region-specific effects. In the SNR(anterior), both doses of AP7 (0.1 and 5 nmol) produced an anticonvulsant effect. In the SNR(posterior), the lower dose (0.1 nmol) did not influence the seizure threshold whereas the higher dose (5 nmol) of AP7 had a proconvulsant effect. The data indicate that there are two distinct regions within the SNR which differentially respond to pharmacological manipulations of the glutamatergic system. The region-specific effects in the SNR may provide an explanation for the previous conflicting reports regarding infusions of N-methyl-D-aspartate antagonists into this structure.

2-Amino-5-phosphonovalerate↗

Sepsis from dropped clips at laparoscopic cholecystectomy.

We report seven patients in whom five dropped surgical clips and two gallstones were visualized in the peritoneal cavity, on radiological studies. In two, subphrenic abscesses and empyemas developed as a result of dropped clips into the peritoneal cavity during or following laparoscopic cholecystectomy. In one of these two, a clip was removed surgically from the site of an abscess. In two other patients dropped gallstones, and in three, dropped clips led to no complications. These were seen incidentally on studies done for other indications. Abdominal abscess secondary to dropped gallstones is a well-recognized complication of laparoscopic cholecystectomy (LC). We conclude that even though dropped surgical clips usually do not cause problems, they should be considered as a risk additional to other well-known causes of post-LC abdominal sepsis.

Abdominal Abscess↗

Transcatheter intraarterial infusion of rt-PA for acute lower limb ischemia: results and complications.

PURPOSE: To determine the success and complication rates of intraarterial recombinant tissue-type plasminogen activator (rt-PA) infusion for the treatment of acute lower extremity artery and bypass graft occlusions. MATERIALS AND METHODS: The results of 74 limbs in 70 patients (mean age, 66 y) treated with catheter-directed rt-PA infusion for the treatment of acute lower extremity ischemia were retrospectively evaluated. The group included 42 bypass grafts and 32 native arteries. All limbs were viable at presentation. The mean duration of symptoms was 11.9 days. rt-PA was infused for a mean of 27.9 hours for a mean total dose of 38.7 mg. Initial infusion rates of 3-6 mg/h were lowered to a preferred rate of 1.5 mg/h. Thrombolytic success was defined as 95% thrombolysis of an occluded segment with return of antegrade flow. Major bleeding complications were defined as any hemorrhagic event leading to surgery, extended or unexpected hospitalization, transfusion, death, intracranial hemorrhage, or a decrease in hemoglobin of 5 g/dL or in hematocrit of 15%. Thirty-day mortality and amputation rates were calculated. Patient characteristics and infusion parameters were evaluated as to whether they contributed to thrombolytic success or major bleeding events. RESULTS: Thrombolytic success was achieved in 64 limbs (86%). Major bleeding complications occurred in 33 (47%) patients. In 22 of these patients, bleeding occurred at a vascular puncture site, whereas remote bleeding occurred in seven patients. Remote bleeding complications included two retroperitoneal hematomas, two rectus sheath hematomas, one lower gastrointestinal hemorrhage, one episode of hemoptysis, and one dehiscence of a femoral-popliteal bypass graft revision. No parameters were found to be predictive of thrombolytic success, whereas a negative history of smoking, increasing duration of infusion, and a low preprocedural ankle-brachial index (ABI) were found to be associated with major hemorrhagic events. Four patients (6%) underwent amputation and one patient (1%) died, resulting in a 30-day amputation-free survival rate of 93%. CONCLUSION: Catheter-directed rt-PA infusion is effective in achieving thrombolysis. Despite a significant number of bleeding complications, 30-day mortality and amputation rates were favorable. Nonetheless, complication rates related to bleeding were not trivial and further evaluation with use of variable dosing regimens is indicated.

Adult↗

Impaired venous hemodynamics in a minority of patients with chronic leg ulcers due to sickle cell anemia.

BACKGROUND: Chronic or recurrent leg ulceration occurs in 25% of sickle cell anemia patients, but not in the remaining 75%. Doppler studies of venous function were normal in 16 sickle cell anemia patients with leg ulcers. PATIENTS AND METHODS: Venous Duplex Ultrasound was used to study 33 sickle cell anemia patients with chronic leg ulcers. RESULTS: Six of the 33 patients had venous reflux in at least one leg. CONCLUSIONS: Venous insufficiency may contribute to the development of leg ulcers in a minority of sickle cell anemia patients. A minority of sickle cell anemia patients with chronic leg ulcers can be shown to have leg venous reflux by duplex ultrasound imaging.

Adult↗

Studies on the inactivation of soluble and immobilized papain by the ascorbic acid-Cu2+ system: a model to propose the effect of free radicals on membrane-bound enzymes in vivo.

Free radicals have been suggested to be widely implicated as the species responsible for harmful biological processes, such as aging, carcinogenesis and numerous other diseases. The mechanism of biological damage produced in such processes has been investigated in a wide variety of systems, including studies on proteins, enzymes, nucleic acids and carbohydrates. In the present study we selected an ascorbic acid-transition-metal ion (ASA-Cu(2+)) system in order to understand the mechanism of soluble and membrane-bound enzyme inactivation by generating free radicals. Papain, a thiol protease, was immobilized on an immobilized-metal-ion carrier and used as a model to examine the inactivation behaviour of membrane-bound enzymes. A comparison was made between the inactivation of soluble and immobilized papain by free radicals, and the potential of different radical scavengers to prevent the inactivation of enzyme was examined.

Ascorbic Acid↗

Prevention of severe ovarian hyperstimulation syndrome in IVF with or without ICSI and embryo transfer: a modified 'coasting' strategy based on ultrasound for identification of high-risk patients.

Ovarian hyperstimulation syndrome (OHSS) can be a severe and potentially life-threatening complication of ovarian stimulation for IVF. Coasting or withholding gonadotrophin stimulation relies on frequent estimation of serum oestradiol to identify patients at risk. A modified coasting protocol was developed in which identification of patients at risk of severe OHSS was based on ultrasound monitoring. Serum oestradiol concentrations were measured only in patients with >20 follicles on ultrasound (high risk). If serum oestradiol concentrations were <3000 pmol/l, the gonadotrophin dose was maintained; if concentrations were >/=3000 pmol/l but <13200 pmol/l and >/=25% of the follicles had a diameter of >/=13 mm, the gonadotrophin dose was halved; and if serum oestradiol concentrations were >/=13 200 pmol/l and >/=25% of the follicles had a diameter of >/=15 mm, patients were coasted. In the latter group, human chorionic gonadotrophin (HCG) 10000 IU was administered when at least three follicles had a diameter of >/=18 mm and serum oestradiol concentrations were <10000 pmol/l. Over a 10 month period, serum oestradiol concentrations were measured in 123 out of 580 cycles (24%) and in 50 cycles, gonadotrophins were withheld. Overall, moderate OHSS occurred in three patients (0.7%) and severe OHSS in one patient (0.2%). The pregnancy rates in the cycles where the gonadotrophin dose was reduced or withheld were 39.6 and 40% per cycle respectively; corresponding implantation rates were 30.7 and 25.6%. It is concluded that the modified coasting strategy is associated with a low risk of moderate and severe OHSS to a minimum without compromising pregnancy rates. Identification of patients at risk by ultrasound reduces the number of serum oestradiol measurements and thus inconvenience to patients as well as costs and workload.

Adult↗

Does laparoscopic ovarian diathermy affect the outcome of IVF-embryo transfer in women with polycystic ovarian syndrome? A retrospective comparative study.

Controlled ovarian stimulation for IVF and embryo transfer and outcome parameters were compared retrospectively in 31 women with clomiphene-resistant polycystic ovarian syndrome (PCOS). Of these women, 15 had previously undergone laparoscopic ovarian diathermy before IVF (group A, total 22 cycles) and 16 had not had surgical treatment (group B, total 24 cycles). No statistically significant differences were observed in the number of oocytes retrieved, although the number of embryos available for transfer was significantly higher in group B (7.1 +/- 3.8 versus 4.6 +/- 2.7, P < 0.01). The clinical pregnancy rate per embryo transfer appeared to be higher in group B (63.2 versus 41.2%), as did the miscarriage rate (66.7 versus 28.6%), giving an apparent improved ongoing pregnancy rate per embryo transfer in group A (29.4 versus 10.5%), but this was not statistically significantly different. The incidence of severe ovarian hyperstimulation syndrome (OHSS) was apparently higher in group B (4.2 versus 0%), but this difference was not statistically significant. No cases of severe OHSS were seen in group A. Ovarian diathermy does not appear to have a deleterious effect on controlled ovarian stimulation, and the outcome of IVF-embryo transfer may be beneficial in decreasing the risk of severe OHSS and improving the ongoing clinical pregnancy rate.

Adult↗

F-18 FDG positron emission tomography in primary breast non-Hodgkin's lymphoma.

A 50-year-old woman had an irregular, mobile, firm right breast mass that became progressively larger in the past 3 months that measured 18 x 15 cm at the time of examination. She had no nipple discharge or skin changes. A 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) showed a ring-shaped breast uptake consisting of high peripheral glycolytic activity and a cold center most likely representing necrosis or hemorrhage despite the absence of a history of trauma, surgical intervention, chemotherapy, or radiation to the breast. Whole-body images did not show any evidence of lymph node involvement or distant metastases. These results were confirmed by computed tomography of the chest, abdomen, and pelvis. Cytologic examination of a fine-needle aspiration of the breast mass showed diffuse large B-cell, intermediate grade, non-Hodgkin's lymphoma. Although it occurs infrequently, primary breast lymphoma should be considered in patients with a breast mass that shows a ring-shaped FDG uptake. A PET scan, in contrast to other imagining techniques, offers the advantage of screening the entire body, excluding the presence of metastases, and confirming the primary origin of the breast lymphoma.

Breast Neoplasms↗

Analysis of the steroid receptor coactivator 1 (SRC1)-CREB binding protein interaction interface and its importance for the function of SRC1.

The transcriptional activity of nuclear receptors is mediated by coactivator proteins, including steroid receptor coactivator 1 (SRC1) and its homologues and the general coactivators CREB binding protein (CBP) and p300. SRC1 contains an activation domain (AD1) which functions via recruitment of CBP and and p300. In this study, we have used yeast two-hybrid and in vitro interaction-peptide inhibition experiments to map the AD1 domain of SRC1 to a 35-residue sequence potentially containing two alpha-helices. We also define a 72-amino-acid sequence in CBP necessary for SRC1 binding, designated the SRC1 interaction domain (SID). We show that in contrast to SRC1, direct binding of CBP to the estrogen receptor is weak, suggesting that SRC1 functions primarily as an adaptor to recruit CBP and p300. In support of this, we show that the ability of SRC1 to enhance ligand-dependent nuclear receptor activity in transiently transfected cells is dependent upon the integrity of the AD1 region. In contrast, the putative histone acetyltransferase domain, the Per-Arnt-Sim basic helix-loop-helix domain, the glutamine-rich domain, and AD2 can each be removed without loss of ligand-induced activity. Remarkably, a construct corresponding to residues 631 to 970, which contains only the LXXLL motifs and the AD1 region of SRC1, retained strong coactivator activity in our assays.

Amino Acid Motifs↗

Ultrasonographic appearance of Ascaris lumbricoides in the small bowel.

Roundworm infestation, one of the most common helminthic diseases worldwide, is caused by Ascaris lumbricoides, one of the largest parasites that infests the human bowel. A lumbricoides is virtually universal at some stage of childhood in semitropical and tropical regions. This study describes our experience with the ultrasonographic appearance of intestinal ascariasis in 84 patients, 2.5 to 42 years of age, examined over 2 years beginning October 1997. The patients' conditions ranged from acute intestinal obstruction to no clinical features pertaining to obstruction. Ultrasonographic examination was performed with an Echocee power Doppler real-time unit with a variable-frequency 3.7-MHz convex, 7.5-MHz linear probe. In longitudinal section the Ascaris worm presented as a linear intraluminal mass with 3 or 4 linear echogenic interfaces; in the cross section, it was round, sometimes appearing as a "target" sign. Some worms also showed serpentine movements. Sonographic examination of the patients in the left lateral decubitus position after ingestion of water improved detection and visualization of the worms in some cases. It is concluded that A lumbricoides in the small bowel has a sonographic appearance that can be recognized by the wary observer.

Adolescent↗

Virus-directed, enzyme prodrug therapy with nitroimidazole reductase: a phase I and pharmacokinetic study of its prodrug, CB1954.

CB1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide] is converted by the bacterial enzyme nitroimidazole reductase (NTR) into a potent cytotoxic bifunctional alkylating agent, which can be delivered to tumors in adenoviral vectors as virus-directed, enzyme prodrug therapy. This report summarizes a Phase I and pharmacokinetic study of the prodrug, CB1954. Thirty patients, ages 23-78 years (median 62 years), with predominantly gastrointestinal malignancies were treated. CB1954 was administered by i.v. injection every 3 weeks or i.p. followed by 3-weekly i.v. injections, toward a maximum of six cycles. The dose was escalated from 3 to 37.5 mg/m2. No significant toxicity was seen until 24 mg/m2 (recommended i.v. dose). Dose-limiting toxicities (DLT) were diarrhea and hepatic toxicity, seen at 37.5 mg/m2. DLT has not been observed at the current i.p. dose of 24 mg/m2. There was no alopecia, marrow suppression, or nephrotoxicity. Clearance data suggest hepatic metabolism, and <5% of CB1954 was renally excreted. There was a nonlinear relationship between i.v. dose and area under the curve (AUC). At the recommended i.v. dose of 24 mg/m2, the AUC was 5.8 microM/h. Intraperitoneal administration (24 mg/m2) achieved an AUC of 387 microM/h, giving a considerable regional advantage. In vitro, the AUC required to achieve the IC50 for CB1954, in NTR-expressing cancer cells, ranges from 10-50 microM/h. Thus, CB1954 is well tolerated at a dose of 24 mg/m2, and sufficient serum/peritoneal levels are achieved for an enzyme-prodrug approach to be feasible. We are now conducting a Phase I trial combining adenovirus-mediated NTR and i.v. CB1954 (24 mg/m2) in patients with primary and secondary liver tumors.

Abdominal Pain↗

Outcome of high-volume cataract surgery at an academic hospital.

OBJECTIVE: This study aimed to review the results of high-volume cataract surgery performed at Umtata General Hospital, an academic hospital, during an 'eye surgery camp' held over a weekend. SUBJECTS AND DESIGN: Ninety-eight cataract operations were performed over 3 days at Umtata Hospital during an eye camp to reduce backlog of cataract surgery in the Eastern Cape. After media announcement, patients were selected for cataract surgery and comprehensive pre-operative evaluation was done. Three qualified surgeons operated on the patients. OUTCOME MEASURES: Patients were reviewed at day 1 and at 3- and 6-week intervals in order to study the outcome of such operations. RESULTS: A total of 92.4% of patients achieved visual acuity of 6/60 or better at 6 weeks postoperatively. The surgical complication rate was minimal and overall satisfactory surgical outcome was observed in these cases. CONCLUSION: Teaching hospitals with dedicated ophthalmic operating facilities can be utilised for high-volume cataract surgery over designated short-term periods and can provide a good alternative to mobile eye camp surgery. Until primary and secondary care facilities are optimal for cataract screening and surgery, such camps are recommended to reduce backlog of cataract surgery in the country.

Academic Medical Centers↗