Biomedical subjects

A Syed

Publications and source records attributed to A Syed.

At least 19 recordsLinked to original sources

PubMed2006

The conservative management of cervical ectopic pregnancies.

OBJECTIVE: To evaluate the role of conservative management in the treatment of cervical ectopic pregnancies. METHODS: This was a retrospective analysis of all cervical ectopic pregnancies diagnosed in women attending our early pregnancy unit between April 1997 and September 2004 inclusive. The diagnosis of cervical ectopic pregnancy was made using transvaginal ultrasound. Clinical and demographic data were recorded in all cases. Serum human chorionic gonadotropin levels were measured at presentation and monitored subsequently to determine the rate of successful resolution. Conservative management was in the form of medical or expectant management. Medical management involved administration of systemic or intra-amniotic methotrexate, with or without intra-amniotic potassium chloride. Systemic methotrexate was either a single dose of 50 mg/m2 or an alternate-day regimen of methotrexate at 1 mg/kg (days 1,3,5) with folinic acid rescue (days 2,4,6). If intra-amniotic treatment was required, this was either 50 mg methotrexate or 5 mmol/L potassium chloride. RESULTS: Seven cervical ectopic pregnancies were diagnosed during the study period. Three cases were managed successfully with a single dose of methotrexate. One case was managed successfully using a multiple-dose methotrexate regimen. Another case failed medical management with both the single- and multiple-dose regimens but was successfully treated after potassium chloride was given intra-amniotically under ultrasound guidance. One case was successfully treated with intra-amniotic methotrexate and another was managed expectantly. There was no associated morbidity or mortality during the study period. We also performed a review of the current literature. CONCLUSION: The conservative management of cervical ectopic pregnancy is effective and safe.

Abortifacient Agents, Nonsteroidal↗

PubMed2006

Understanding operative intervention in childbirth: a patient perspective.

A study was undertaken to ascertain patients' understanding of the operative interventions in labour and to assess follow-up by the operator. A total of 200 consecutive women who had undergone caesarean section or instrumental delivery were selected. These women were questioned postoperatively. Questions were asked to ascertain the patients' understanding of the procedure and to assess follow-up by the operator. Seven patients had a forceps delivery, 64 had a ventouse delivery and 129 had a caesarean section. The majority of patients felt that the reason for the operative delivery had been explained to them at delivery and that they fully understood the need for this intervention. A total of 26 women were not seen postoperatively by the doctor who delivered them. Women who underwent forceps or ventouse delivery were less likely to be seen post-delivery, although this difference did not reach statistical significance.

Adolescent↗

PubMed2005

Do levels of serum cancer antigen 125 and creatine kinase predict the outcome in pregnancies of unknown location?

BACKGROUND: The aim of this study was to evaluate the role of maternal serum cancer antigen 125 (CA 125) and creatine kinase (CK) levels in predicting the outcome of pregnancies of unknown location (PUL). METHODS: Prospective observational study. Women classified as PUL were recruited. Final outcome of each PUL was established: failing PUL, intrauterine pregnancy (IUP), ectopic pregnancy (EP) or persisting PUL. The persisting PUL group almost certainly represent ultrasonically missed EP and were included in EP group. Serum CK and CA 125 were measured at 0 and 48 h. The values at presentation and the change in levels after 2 days were used in the analysis. We incorporated the most significant of variables into a multinomial logistic regression model to predict all outcomes. The performance of this model was evaluated using receiver operating characteristic (ROC) curves. RESULTS: In all, 4698 consecutive women were scanned; 403 were classified as PUL, 27 were lost to follow-up. Of the 376 women eligible, 297 had complete data and therefore were recruited. Mean age and mean gestation were 30.0 years and 43.3 days respectively. Final outcomes: 153 failing PUL (51.5%), 116 IUP (39.1%) and 28 EP (9.4%). Mean serum CK levels at 0 and 48 h were 88.5 and 86.8 IU/l respectively. Mean serum CA 125 levels at 0 and 48 h were 43.8 and 40.1 kIU/l respectively. 81.1% of women had CK and CA 125 ratios (CK 48 h/CK 0 h, CA 125 48 h/CA125 0 h) between 0.7 and 1.3. CA 125 ratio was the only significant variable in the three outcome groups (P < 0.0001). Logistic regression analysis incorporating CA 125 ratio gave an area under ROC curve of 0.782 (SE = 0.041) for failing PUL, 0.768 (SE = 0.043) for IUP and 0.560 (SE = 0.078) for EP. This model was capable of distinguishing failing PUL from IUP, but was not able to detect EP. CONCLUSIONS: Absolute levels of serum CK and CA 125 at the defined times cannot be used to predict the outcome of PUL. Although the CA 125 ratio when incorporated into logistic regression model can distinguish failing PUL from IUP, its inability to detect the high risk PUL, i.e. the developing EP, renders it inappropriate for use in the clinical setting.

Age Factors↗

PubMed2005

Depression in the elderly: pathological study of raphe and locus ceruleus.

Depressive symptoms in the elderly are common and disabling and constitute a risk factor for the development of Alzheimer's disease (AD). One hypothesis worth exploring is that depression in the elderly is related to development of AD pathology at subcortical sites before such pathology develops in the hippocampus and neocortex. We describe here an autopsy study of the locus ceruleus (LC) and raphe nuclei (RN) in nine subjects with depression and 18 age and sex matched controls that were included in a community-based study of cognitive function and ageing (MRC-CFAS). We found no relationship between depression and (1) mean counts of serotonergic or total RN neuronal profiles (2) noradrenergic or total LC neuronal profiles (3) counts of neurofibrillary tangles in these nuclei, or (4) size of neurones in the RN. Nor were these parameters related to age or sex of the subjects. We conclude that depression in the elderly is unlikely to be related to RN or LC neurone counts or RN cell size or to AD-type pathology in these nuclei. However, because of the small numbers of cases studied and our inability to carry out a full stereological study because of tissue limitations the findings are preliminary.

Age Factors↗

PubMed2003

Sequential VATS lung volume reduction surgery: prolongation of benefits derived after the initial operation.

OBJECTIVE: Sequential lung volume reduction (LVR) is thought to provide additional and prolonged benefit compared with unilateral LVR. We tested this hypothesis by reviewing physiological, subjective and survival outcome data on patients who underwent sequential or unilateral LVR. METHODS: LVR was performed as a unilateral video-assisted thoracoscopic surgery (VATS) procedure, with bilateral reduction being undertaken in a staged manner. Pulmonary function data were collected prospectively. A telephone survey of patients and general practitioners was used to determine quality of life and survival. RESULTS: Fifty patients underwent LVR. Twenty-one patients had staged reduction of the contra-lateral lung at a median interval of 9 months. Pre-operatively, patients undergoing sequential LVR were not significantly different from patients undergoing unilateral LVR: forced expiratory volume in 1 s (FEV1) 23% predicted vs. 27% predicted, KCO 40% vs. 45%, total lung capacity (TLC) 124% vs. 121%, residual volume (RV) 217% vs. 214%, health score 34.5 vs. 30.8. After single-side LVR, both groups demonstrated equivalent and significant improvement in spirometric and subjective health scores: FEV1 +15% predicted (P<0.01), TLC -5% (P=0.03), health score +80% (P<0.01). Patients undergoing sequential reduction demonstrated no further significant improvements using either an intragroup comparison with their pre-second operation values or an intergroup comparison with the unilateral LVR patients. However, sequential LVR appeared to prolong the benefits experienced after the initial surgery by 1 year. Overall, 12 patients (24%) died during follow-up with no survival difference between the two groups (P=0.65). CONCLUSION: Sequential LVR is a safe strategy. Undertaking LVR to the second side does not further improve spirometric or subjective performance but does prolong the benefits achieved with the initial reduction.

Aged↗

PubMed2002

The effect of smoking on tumour oxygenation and treatment outcome in cervical cancer.

AIM: Tumour hypoxia is associated with an increased risk of cervical tumour recurrence and death. Because smoking is a modifiable behaviour, it is important to establish the importance of smoking as a prognostic factor. We hypothesized that there is an association between smoking and tumour hypoxia, and that smoking adversely affects radiation response and survival. METHODS: A smoking history was obtained from 100 of 115 patients with cervical cancer entered into a prospective study of tumour oxygenation. Eighty-seven of these had clinically evident disease and radiation therapy alone was the planned treatment. Patients who smoked within 2 weeks of commencing radiation therapy were considered smokers, and the amount that they smoked was recorded in packs per day. Patients who had never smoked or quit at least 2 weeks prior to radiation therapy were considered non-smokers. Tumour oxygenation was determined using the Eppendorf polarographic oxygen electrode and tumour oxygenation is represented by the hypoxic proportion HP5 (% of pO2 measurements <5 mmHg). RESULTS: There was no significant association between smoking and tumour hypoxia (P=0.3), haemoglobin (P=0.6) nor tumour size (P=0.1). Progression-free survival at 3 years was 56% for non-smokers and 44% for smokers (P=0.23). In both univariate and multivariate analysis, neither smoking status nor amount smoked were significant predictors of progression-free survival or local control. CONCLUSIONS: There was no significant association between smoking and tumour hypoxia, treatment response or survival in this study of patients with cervix cancer.

Adult↗

PubMed2001

Non-union of the capitate with associated triangular fibrocartilage tear.

We report a case of a 19-year-old boy who presented with a painful wrist 3 months after a fall. Plain radiographs demonstrated a non-union of a capitate fracture which was unrecognised at the time of injury. Magnetic resonance imaging confirmed the diagnosis and also demonstrated a tear of the triangular fibrocartilage complex. This combination of injuries has not been previously described.

Adult↗

PubMed2001

Single-dose pharmacokinetics of bupropion in adolescents: effects of smoking status and gender.

Sustained-release (SR) bupropion (Zyban) is approved as a smoking cessation aid for adults. Since smoking often begins in adolescence, we determined the single-dose pharmacokinetics of bupropion SR in 75 adolescent subjects ranging from 13 to 18 years old. Subjects self-reported their smoking status. Urinary cotinine concentration was used to verify smoking status. Thirty-seven subjects (18 males, 19 females) were classified as cigarette smokers and 38 were nonsmokers (19 males, 19 females). Fasted subjects received one tablet (150 mg) of bupropion SR, and plasma samples were collected before (0) and 1/2, 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours after dosing. Plasma samples were analyzed for bupropion and its three major metabolites (hydroxybupropion and the aminoalcohol isomers, erythrohydrobupropion plus threohydrobupropion, expressed as a composite) by solid-phase extraction, followed by LC/MS/MS. Factorial analysis of variance (ANOVA) was used to evaluate the effects of smoking and gender on pharmacokinetic parameters. Smokers and nonsmokers differed significantly (p < 0.05) in age and urinary cotinine (p < 0.01) concentration but did not differ significantly in mean weight, height, body surface area, or body mass index. The pharmacokinetic (PK) parameters for bupropion and hydroxybupropion did not differ between smokers and nonsmokers, but differences were found between male and female subjects. Mean values for area under the plasma concentration versus time curve (AUC0-->infinity), volume of distribution (Vd beta) normalized to body weight, maximum plasma concentration (Cmax), and elimination half-life (t1/2 beta) for bupropion were significantly (p < 0.05) greater in females than males, while clearance of bupropion normalized to body weight (CL/f) did not differ between males and females. Females also exhibited significantly (p < 0.05) larger values for hydroxybupropion mean AUC0-->infinity and Cmax than males. The mean ratio of hydroxybupropion to bupropion AUC for adolescents was approximately 4 to 5, which is lower than that previously reported for adults. In conclusion, smoking status does not affect the single-dose pharmacokinetics of bupropion SR in adolescents. However, females differ from males in several potentially important PK parameters for bupropion and its major metabolite, hydroxybupropion.

Adolescent↗

PubMed2000

Interrelationship of proliferation and hypoxia in carcinoma of the cervix.

PURPOSE: In human cervix cancer treated with radiotherapy, we have previously shown from separate groups of patients that tumor hypoxia and proliferation rate as measured by bromodeoxyuridine (BrdU) labeling index (LI) are important determinants of clinical outcome. We now examine the relationship of these two pre-treatment predictive assays in 43 patients studied prospectively from 1994-98 where both tests were performed for each patient. MATERIAL AND METHODS: Newly diagnosed patients with carcinoma of the cervix were examined under anesthesia for staging purposes. Patients were given BrdU (200 mg) by intravenous route prior to the procedure. Tumor oxygenation was measured with the Eppendorf pO2 histograph. Biopsy of tumor was then performed and the BrdU LI was obtained by flow cytometry. The degree of tumor hypoxia for each tumor was expressed as median pO2 values, and as the percentage of pO2 readings <5 mm Hg (HP5). RESULTS: The median age was 53 years (range 23-79 years). There were 32 squamous, and 11 non-squamous carcinomas. FIGO stages were: IB and IIA, 8; IIB, 17; IIIB, 18; with a median tumor size of 6 cm (range 2-10 cm). The patients received uniform treatment with radical radiation therapy. There were 22 diploid and 21 aneuploid tumors. The median LI, pO2, and HP5 were 8.0%, 5.4 mm Hg, and 46.8%, respectively. Tests for linear associations showed no significant correlation between median pO2 vs. LI (r = 0.078, p = 0.62), and HP5 vs. LI (r = -0.14, p = 0.38). CONCLUSIONS: The clinical outcome in this group of patients is immature, but these results suggest that tumor hypoxia and proliferation measurements are independent and potentially complementary predictive assays in cervix carcinoma. Further investigations are required to examine the distribution of proliferating tumor cells and its relationship with hypoxic tumor cells in tissue sections with the use of immunohistological techniques and image analysis systems.

Adenocarcinoma↗

PubMed2000

Anemia, hypoxia and transfusion in patients with cervix cancer: a review.

BACKGROUND AND PURPOSE: With the recent development of hemopoietic growth factors and alternatives to transfusion, there has been a renewed interest in the relationships between anemia, tumor hypoxia and treatment outcome in a number of human malignancies. This review is intended to provoke a reconsideration of these issues and their effect on clinical trials, aimed at improving treatment outcome in patients with cervix cancer. MATERIALS AND METHODS: Using data from the literature and from our own prospective series of tumor oxygenation in cervix cancer, we modeled the impact of anemia on tumor blood flow and hypoxia in animal models and human tumors, examined the relationship between anemia and hypoxia and treatment outcome in patients, and reviewed the impact of transfusion on tumor hypoxia and treatment outcome in cervix cancer. RESULTS: Anemia may result in a significant reduction in oxygen delivery to tumors, but compensatory mechanisms reduce the impact on tumor oxygenation. Anemia is associated with inferior treatment outcome in cervix cancer, but hemoglobin levels prior to and during treatment are strongly correlated with tumor size, and this may explain the prognostic impact of anemia in older studies. Transfusion and erythropoietin ameliorate hypoxia in only a proportion of anemic patients. Critical analysis of the published data from the Princess Margaret Hospital randomized trial of transfusion in cervix cancer reveals that, when analyzed by intention-to-treat, transfusion did not result in a benefit to patients. CONCLUSIONS: This review suggests that the relationships among anemia, hypoxia, transfusion and treatment outcome are complex. Further study of anemia as an independent prognostic factor is required and randomized studies of transfusion alternatives, such as erythropoietin, must be of sufficient size to detect small treatment effects.

Anemia↗

PubMed1999

Antegrade crystalloid cardioplegia vs antegrade/retrograde cold and tepid blood cardioplegia in CABG.

BACKGROUND: This study evaluated the myocardial protective strategies in isolated coronary bypass surgeries. METHODS: One hundred and twenty-eight patients were prospectively randomized to 3 techniques of myocardial protection; group I (n = 47) antegrade/retrograde tepid blood cardioplegia, group II (n = 40) antegrade/retrograde cold blood cardioplegia with topical cooling, group III (n = 41) antegrade crystalloid cardioplegia with topical cooling. RESULTS: The incidence of spontaneous defibrillation was significantly higher in group I (p < 0.001) while the incidence of low cardiac output was not different between the 3 groups. The incidence of ventricular arrhythmia was higher in group III (p < 0.016 group III vs I). There was no significant statistical difference in hemodynamic recovery between the 3 groups. CK-MB levels were significantly lower in group I versus the other 2 groups, (p = 0.0013, 0.04). Acid release and oxygen extraction were higher in group II than in group I (p = 0.06) during cardioplegia and reperfusion. Lactate release was less in group I at the release of aortic cross-clamp, and reperfusion. There was no significant difference between the 3 groups in ICU stay, ventilation time, or hospital complications. CONCLUSIONS: Tepid blood cardioplegia showed superiority in metabolic and functional recovery, whereas crystalloid cardioplegia had the highest incidence of postoperative arrhythmias. There was no significant statistical difference between the 3 groups in hospital mortality and morbidity.

Adult↗

PubMed1999

Olanzapine response in psychotic depression.

BACKGROUND: Psychotic depression is more common than is generally realized, occurring in an estimated 16% to 54% of depressed patients. In controlled studies of patients with schizophrenia, the atypical antipsychotic olanzapine has been shown to be superior in efficacy to haloperidol at doses of 10 mg/day. Since olanzapine may have antidepressant effects in addition to its antipsychotic properties, the purpose of this study was to assess the safety and efficacy of olanzapine in the treatment of psychotic depression. METHOD: Hospitalized patients with the discharge diagnosis of DSM-IV psychotic depression (major depression with psychotic features or bipolar I disorder, depressed phase...with psychotic features) who had been treated with olanzapine during the first 9 months of its availability in the United States were identified. An age- and sex-matched sample of hospitalized patients with psychotic depression treated with other antipsychotics during the same time period was also identified. The medical records were expunged of all references to medication treatment and then reviewed and scored in a blind fashion for indications, doses, response, and side effects. RESULTS: Fifteen psychotic depression patients (10 women, 5 men), aged 36.9 +/- 10.1 years, who were treated with olanzapine were retrospectively compared with 15 psychotic depression patients (10 women, 5 men), aged 35.0 +/- 8.2 years, treated with other antipsychotics. Ten (67%) of 15 patients taking olanzapine were much or very much improved upon discharge compared with only 4 (27%) of 15 patients taking other antipsychotics (Fisher exact test, p = .037). Olanzapine was well tolerated: no patient discontinued the medication because of side effects. Twelve (80%) of 15 patients in each group were taking antidepressants in addition to the antipsychotic. Of the 3 patients taking olanzapine but not taking an antidepressant, 2 were much or very much improved (1 patient taking olanzapine alone, 1 taking olanzapine plus valproate sodium). CONCLUSION: Olanzapine appears to be effective and safe for patients with psychotic depression. Further prospective studies are warranted to ascertain whether olanzapine's unique pharmacologic profile may make it particularly useful for the treatment of psychotic depression either alone or in combination with antidepressants.

Adult↗

PubMed1998

Risk factors for typhoid fever in an endemic setting, Karachi, Pakistan.

We conducted a study to evaluate risk factors for developing typhoid fever in a setting where the disease is endemic in Karachi, Pakistan. We enrolled 100 cases with blood culture-confirmed Salmonella typhi between July and October 1994 and 200 age-matched neighbourhood controls. Cases had a median age of 5.8 years. In a conditional logistic regression model, eating ice cream (Odds ratio [OR] = 2.3; 95% confidence interval [CI] 1.2-4.2, attributable risk [AR] = 36%), eating food from a roadside cabin during the summer months (OR = 4.6, 95% CI 1.6-13.0; AR = 18%), taking antimicrobials in the 2 weeks preceding the onset of symptoms (OR = 5.7, 95% CI 2.3-13.9, AR = 21%), and drinking water at the work-site (OR = 44.0, 95% CI 2.8-680, AR = 8%) were all independently associated with typhoid fever. There was no difference in the microbiological water quality of home drinking water between cases and controls. Typhoid fever in Karachi resulted from high-dose exposures from multiple sources with individual susceptibility increased by young age and prior antimicrobial use. Improving commercial food hygiene and decreasing unnecessary antimicrobial use would be expected to decrease the burden of typhoid fever.

Adolescent↗

PubMed1998

Identification of an N-terminal region of sigma 54 required for enhancer responsiveness.

Sigma 54 associates with bacterial core RNA polymerase and converts it into an enhancer-responsive enzyme. Deletion of the N-terminal 40 amino acids is known to result in loss of the ability to respond to enhancer binding proteins. In this work PCR mutagenesis and genetic screens were used to identify a small patch, from amino acids 33 to 37, that is required for proper response to activator in vivo. Site-directed single point mutants within this segment were constructed and studied. Two of these were defective in responding to the enhancer binding protein in vitro. The mutants could still direct the polymerase to bind to DNA and initiate transient melting. However, they failed in directing activator-dependent formation of a heparin-stable open complex. Thus, amino acid region 33 to 37 includes critical activation response determinants. This region overlaps the larger leucine patch negative-control region, suggesting that anti-inhibition and positive activation are closely coupled events.

Amino Acid Sequence↗

PubMed1997

Multiple pathways to bypass the enhancer requirement of sigma 54 RNA polymerase: roles for DNA and protein determinants.

Sigma 54 is a required factor for bacterial RNA polymerase to respond to enhancers and directs a mechanism that is a hybrid between bacterial and eukaryotic transcription. Three pathways were found that bypass the enhancer requirement in vitro. These rely on either deletion of the sigma 54 N terminus or destruction of the DNA consensus -12 promoter recognition element or altering solution conditions to favor transient DNA melting. Each of these allows unstable heparin-sensitive pre-initiation complexes to form that can be driven to transcribe in the absence of both enhancer protein and ATP beta-gamma hydrolysis. These disparate pathways are proposed to have a common basis in that multiple N-terminal contacts may mediate the interactions between the polymerase and the DNA region where melting originates. The results raise possibilities for common features of open complex formation by different RNA polymerases.

Amino Acid Sequence↗

PubMed1997

Isolation and properties of enhancer-bypass mutants of sigma 54.

The N-terminal activation domain of Escherichia coli sigma 54 was randomly mutated to provide a library of changes that might allow the required enhancer function to be bypassed. Five clones harbouring mutant sigma factors were obtained that exhibited this property in that they enhanced growth under nitrogen-limiting conditions in cells lacking NtrC. DNA sequence analysis located all mutations to four leucines in a small region between amino acids 25 and 31. No mutant sigma factors retained the hydrophobic character of the leucine residues. Mutant sigma factors were shown to transcribe in vitro without the need for enhancer binding activator or ATP hydrolysis, confirming the in vivo phenotype. These and other data suggest that a very small set of leucines is critical for keeping polymerase function in check, allowing high responsiveness to physiological induction via enhancer proteins such as NtrC.

Adenosine Triphosphate↗

PubMed1996

Knee pain amongst the poor and affluent in Pakistan.

The frequency of joint symptoms was determined amongst 2022 affluent and 2210 poor adults in Karachi, Pakistan. Joint pain was significantly (P = 0.025) more common amongst the affluent (6.6%) compared with the poor (5%) and this was due to a significantly greater frequency of knee pain in the richer community (3% vs 1.8%; P = 0.008). The prevalence increased with age and was more common in females. Almost half were associated with varus deformity, suggesting the presence of associated OA in a high proportion. The overall frequency of knee pain seemed no greater than in series reported from the West. Compared with age- and sex-matched controls, body weight was significantly greater amongst those with knee pain, both amongst the affluent (P = 0.005) and the poor (P = 0.02). Control subjects were heavier in the affluent population, suggesting that the greater frequency of knee symptoms in this community was due to their relative obesity. Knee bending at prayer was most common amongst the affluent controls and may indicate that religious observance also contributed to the problem in the richer population. Squatting was a characteristic of the poor who had less knee pain than the affluent. Knee flexing could not therefore be confidently implicated. No relationship could be demonstrated between knee pain and joint laxity.

Adolescent↗

PubMed1995

Converting Escherichia coli RNA polymerase into an enhancer-responsive enzyme: role of an NH2-terminal leucine patch in sigma 54.

The protein sigma 54 associates with Escherichia coli core RNA polymerase to form a holoenzyme that binds promoters but is inactive in the absence of enhancer activation. Here, mutants of sigma 54 enabled polymerases to transcribe without enhancer protein and adenosine triphosphate. The mutations are in leucines within the NH2-terminal glutamine-rich domain of sigma 54. Multiple leucine substitutions mimicked the effect of enhancer protein, which suggests that the enhancer protein functions to disrupt a leucine patch. The results indicate that sigma 54 acts both as an inhibitor of polymerase activity and as a receptor that interacts with enhancer protein to overcome this inhibition, and that these two activities jointly confer enhancer responsiveness.

Adenosine Triphosphate↗