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Biomedical subjects

H Khan

Publications and source records attributed to H Khan.

At least 19 recordsLinked to original sources
PubMed2006

Outcome of pregnancy in renal allograft recipients: SIUT experience.

The course of pregnancy and its outcome was studied in renal allograft recipients. Between November 1985 and November 2005, a total of 1481 renal transplants were carried out at the Sindh Institute of Urology and Transplantation (SIUT); among them were 348 females, with 73 potential females for pregnancy. All patients received cyclosporine and prednisolone, with 82% also receiving azathioprine and 4 patients mycophenolate mofetil as a third immunosuppressant drug. We evaluated incidence of hypertension, diabetes, pre-eclampsia, urinary tract infection (UTI), rejection during pregnancy and during 3 months' postdelivery as well as outcomes of pregnancy. Among 73 potential candidates, 31 had 47 pregnancies, after an average of 31 months (8-86 months). Of 31 subjects, 21 subjects were hypertensive on one or two drugs prior to conception. A rise in blood pressure during pregnancy was noticed in 7 patients. Albuminuria from trace to 3+ appeared in 13 patients and glycosuria in one other. Blood sugar levels remained within normal range in all subjects. UTIs occurred during pregnancy in 7 patients. Among 47 pregnancies, 9 had abortions (7 spontaneous, 2 therapeutic) and 6 had preterm deliveries. The others were full-term deliveries: 12 via a lower segment caesarean section and 20 were normal vaginal deliveries. Average birth weight was 4.8 lbs. At an average follow-up of 38 months the serum creatinine values ranged from 0.94 to 2.3 mg %. One patient developed acute irreversible graft dysfunction soon after delivery. Our study demonstrated that pregnancy did not reduce renal graft survival, but newborns are at greater risk of premature birth and low birth weight.

Albuminuria↗
PubMed2005

Routine database registration of biological therapy increases the reporting of adverse events twentyfold in clinical practice. First results from the Danish Database (DANBIO).

OBJECTIVE: To present from the Danish Database for Biological Therapies in Rheumatology (DANBIO) the frequencies and types of adverse events as well as risk factors during treatment with biological agents in clinical practice. METHODS: Adverse events during the first 2 years of clinical use of biological agents in Denmark were reported to the nationwide DANBIO and compared to the mandatory reports to the Danish Medicines Agency. RESULTS: Almost 90% of the patients treated with biological agents were registered in the DANBIO, and the database picked up 20 times as many adverse events as the Danish Medicines Agency. Infections and hypersensitivity reactions were the most prevalent adverse events. Age, disease duration, and previous number of disease-modifying anti-rheumatic drugs (DMARDS) were found to be risk factors for bacterial infections. CONCLUSION: A routine-based Danish database for biological therapies covers approximately 90% of patients and improves the reporting of adverse events.

Adult↗
PubMed2004

Ethnic differences in patient perceptions of heart failure and treatment: the West Birmingham heart failure project.

OBJECTIVE: To investigate further the hypothesis that ethnic groups would have different levels of knowledge and perceptions of congestive heart failure (CHF) and treatments for this condition, a cross sectional survey was conducted of patients who were attending the heart failure clinics in two teaching hospitals of Birmingham, UK, that serve a multiethnic population. METHODS: 103 patients with CHF (66 men, 37 women) were surveyed by standard questionnaire: 42 were white, 34 Indo-Asian, 22 Afro-Caribbean, and 5 Oriental. RESULTS: When asked about their beliefs about control of one's health, 22 (64.7%) of Indo-Asians felt that God/fate controlled their health. The majority of white patients tended to believe that the greatest factor influencing their health was the doctor (15 (35.7%)). Of the total study cohort, only 68 (66%) of patients were aware of their primary diagnosis of heart failure; the majority of Indo-Asians (21 (61.8%)) were not aware of their diagnosis. Half of Indo-Asians (17 (50%)) felt that heart failure was not severe, in contrast to 40.9% (n = 9) of Afro-Caribbeans and only 19.1% (n = 8) of white patients. Of the study cohort, 38 (36.9%) were taking their drugs because their doctor told them to, a response most common among the Indo-Asians. The majority of Indo-Asians (22 (64.7%)) and Afro-Caribbeans (14 (63.6%)) stated that they did not have, or did not know whether they had enough, information about their drug. The corresponding figure for white patients was 21.4% (n = 9). When asked whether they took their medication regularly as prescribed, 7 (31.8%) of Afro-Caribbeans reported that they did not take their drugs regularly. CONCLUSIONS: Our study has highlighted deficiencies in the knowledge of CHF among patients from ethnic minority groups, as well as deficiencies in the information being given to these patients. There is a clear need to invest more in patient education for CHF, with special emphasis on certain high risk subgroups.

Aged↗
PubMed2002

Comparison between clinical and radiologic outcome measures after reconstruction of acetabular fractures.

OBJECTIVES: To compare clinical and radiologic outcome measures in patients after reconstruction of acetabular fractures and to investigate whether an objective radiologic outcome could be used as a proxy for a clinical outcome. DESIGN: Follow-up survey with retrospective analysis of consecutive case records. PATIENTS AND INTERVENTION: Over a ten-year period, 201 consecutive patients had open reduction and internal fixation of acetabular fractures performed by a single surgeon. The outcome measures on 166 fractures were available for analysis when the twenty-six patients who were lost to follow-up and the fourteen patients who had salvage total hip replacement were excluded. MAIN OUTCOME MEASUREMENTS: The assessment of patients was performed by one of two independent assessors, who used the Merle d'Aubigné (1954) clinical outcome score and a radiologic score of degenerative hip disease (Matta, 1994). RESULTS: Although the overall correlation between the clinical and radiologic outcome grades was good (r = 0.63, p < 0.001), their agreement (i.e., the prediction of a specific clinical outcome by a corresponding radiologic one) was poor (Kappa = 0.24). The authors found that the clinical scoring system was difficult to apply specifically to acetabular trauma in 29 percent of fractures because of complications related to associated injuries. When the individual Merle d'Aubigné scores for pain, range of motion, and walking were correlated with the radiologic score, it was found that the walking score had a significant association with the radiologic score and the pain and range of movement scores. CONCLUSIONS: The Merle d'Aubigné score has shortcomings as an outcome measure for acetabular fractures. Our aim to use a radiologic outcome as a proxy for this clinical grading system was not realized, but we propose that the patient's walking ability could be used as an objective local outcome measurement.

Acetabulum↗
PubMed2002

Alpha-1 antitrypsin deficiency in emphysema.

Human plasma contains a number of proteinase inhibitors which together form 10% of the total plasma proteins. Serine proteases are a group of closely related proteolytic enzymes, with serine in their active site. These play a key role in coagulation, fibrinolysin, kinin and complement activation. Serine protease inhibitors or "serpins" are specific inhibitors which control the activities of these enzymes. Among the serine protease inhibitors. Alpha-1 antitrypsin (alpha1 ATD) is found in highest concentration in plasma. It is the major physiologic inhibitor for neutrophil elastase. It has control over the elastase mediated degradation of elastic tissue in the lung. Alpha1ATD deficiency is a common genetic disorder and potentially lethal disease predominantly found in North European population--where the incidence is one in 2500; worldwide figures suggest that one in 6000 people have classic alpha1ATD. In cases of deficiency, antielastase activity is reduced in the lungs which results in increased elastin breakdown and development of emphysema. Cigarette smoking contributes to destructive changes in emphysema by suppressing the proteinase inhibitory activity of human serum and by inducing certain bronchoalveolar changes. Prevalence and severity of asthma increases in persons with abnormal alpha1ATD phenotype.

Humans↗
PubMed2001

Daytime sleepiness and other sleep disorders in Parkinson's disease.

BACKGROUND: PD is associated with a variety of sleep problems. The dopamine agonists (DA) pramipexole and ropinirole were recently implicated in causing "sleep attacks" and motor vehicle accidents. METHODS: In order to determine the overall rate of subjective sleep problems in PD and to determine if any factors, including specific medications, correlate with sleep pathology, the authors surveyed consecutive patients with PD seen over a 3-month period in a Movement Disorders Clinic. The authors collected demographic and medication data, and the patients completed the Epworth Sleepiness Scale (ESS), questions assessing the presence of restless legs syndrome (RLS), a modified National Sleep Foundation sleep survey, and specific questions regarding falling asleep while driving. RESULTS: A total of 320 patients completed the questionnaire. The authors eliminated 17, six for incomplete data and 11 for having a primary diagnosis other than PD. The mean age of the remaining 303 patients was 67.1 +/- 10.7 years, and the mean duration of PD was 9.1 +/- 5.7 years. The ESS scores averaged 11.1 +/- 5.9, and in 50.2% of patients the score was abnormally high (>10). Stepwise regression analysis found that sleepiness correlated with longer duration of PD (p < 0.001), more advanced PD (p < 0.004), male sex (p < 0.001), and the use of any DA (p < 0.003). The soporific effects of the three most common DA (pramipexole, ropinirole, and pergolide) were similar. Falling asleep while driving was reported by 63/279 (22.6%) of current drivers and correlated with higher ESS scores (p < 0.05). Other sleep disorders, including RLS, were also frequently reported. CONCLUSION: Daytime sleepiness is common in PD and correlates with more advanced and longer duration of PD, and male sex. The DA were also independently associated with daytime sleepiness, but in this group, no single DA was more culpable than the others.

Adult↗
PubMed2001

The influence of additives on the spreading coefficient and adhesion of a film coating formulation to a model tablet surface.

The surface energies of film coating formulations based on hydroxypropyl methylcellulose and containing microcrystalline cellulose, lactose and Tween 20, respectively, have been assessed. The approach taken allowed the components of the surface energy, in terms of the Lifshitz-van der Waals and the acid-base contributions, to be determined. Spreading coefficients of these coating formulations were determined on a model tablet surface whose surface energy had been similarly characterised. The determined spreading coefficients were high and positive indicating that spreading and wetting would not be a controlling factor in the formation of an adequate film coat. The adhesion of the coats to the core was measured and showed that the inclusion of additives influenced the adhesion of the film. Maximum adhesion was obtained when microcrystalline cellulose was included in the coating formulation that presumably allowed a strong interaction with the same component in the tablet core. Adhesion was enhanced when the tablet cores were made at a higher compaction force. Atomising air pressure had little influence on the adhesion.

Chemistry, Pharmaceutical↗
PubMed2001

Catheter ablation in patients with multiple and unstable ventricular tachycardias after myocardial infarction: short ablation lines guided by reentry circuit isthmuses and sinus rhythm mapping.

BACKGROUND: Extensive lines of radiofrequency (RF) lesions through infarct (MI) can ablate multiple and unstable ventricular tachycardias (VTs). Methods for guiding ablation that minimize unnecessary RF applications are needed. This study assesses the feasibility of guiding RF line placement by mapping to identify a reentry circuit isthmus. METHODS AND RESULTS: Catheter mapping and ablation were performed in 40 patients (MI location: inferior, 28; anterior, 7; and both, 5) with an electroanatomic mapping system to measure the infarct region and ablation lines. The initial line was placed in the MI region either through a circuit isthmus identified from entrainment mapping or a target identified from pace mapping. A total of 143 VTs (42 stable, 101 unstable) were induced. An isthmus was identified in 25 patients (63%; 5 with only stable VTs, 5 with only unstable VTs, and 15 with both VTs). Inducible VTs were abolished or modified in 100% of patients when the RF line included an isthmus compared with 53% when RF had to be guided by pace mapping (P=0.0002); those with an isthmus identified received shorter ablation lines (4.9+/-2.4 versus 7.4+/-4.3 cm total length, P=0.02). During follow-up, spontaneous VT decreased markedly regardless of whether an isthmus was identified. VT stability and number of morphologies did not influence outcome. CONCLUSIONS: A 4- to 5-cm line of RF lesions abolishes all inducible VTs in more than 50% of patients. Less ablation is required if a reentry circuit isthmus is identified even when multiple and unstable VTs are present.

Aged↗
PubMed2001

Crystal structure of pentaerythritol tetranitrate reductase: "flipped" binding geometries for steroid substrates in different redox states of the enzyme.

Pentaerythritol tetranitrate reductase (PETN reductase) degrades high explosive molecules including nitrate esters, nitroaromatics and cyclic triazine compounds. The enzyme also binds a variety of cyclic enones, including steroids; some steroids act as substrates whilst others are inhibitors. Understanding the basis of reactivity with cyclic enones requires structural information for the enzyme and key complexes formed with steroid substrates and inhibitors. The crystal structure of oxidised and reduced PETN reductase at 1.5 A resolution establishes a close structural similarity to the beta/alpha-barrel flavoenzyme, old yellow enzyme. In complexes of oxidised PETN reductase with progesterone (an inhibitor), 1,4-androstadiene-3,17-dione and prednisone (both substrates) the steroids are stacked over the si-face of the flavin in an orientation different from that reported for old yellow enzyme. The specifically reducible 1,2 unsaturated bonds in 1,4-androstadiene-3,17-dione and prednisone are not optimally aligned with the flavin N5 in oxidised enzyme complexes. These structures suggest either relative "flipping" or shifting of the steroid with respect to the flavin when bound in different redox forms of the enzyme. Deuterium transfer from nicotinamide coenzyme to 1,4-androstadiene-3,17-dione via the enzyme bound FMN indicates 1alpha addition at the steroid C2 atom. These studies rule out lateral motion of the steroid and indicate that the steroid orientation is "flipped" in different redox states of the enzyme.

Androstadienes↗
PubMed2001

Familial steroid-responsive nephrotic syndrome and HLA antigens in Bengali children.

We investigated the major histocompatibility complex class I and II loci in three Bengali families with nine children affected with steroid-sensitive nephrotic syndrome (SSNS). A sequence-specific primer (SSP) of DNA typing method was used to detect human leukocyte antigens (HLA). The unaffected siblings and their parents were also studied. Similar to previous reports, there was a high frequency of HLA-DR7.1 (DRB1*0701), DR53 (DR B4*01011-0104) and DQ2 (DQB2*0201-3) antigens in the affected children. However, there was a similar finding in the unaffected children and their parents. HLA-DR7.1 probably was not a causative factor, since it had no predictive value for the occurrence or the severity of SSNS in the affected families. Siblings with identical HLA typing behaved differently (they either had or did not have SSNS). In these families there was no correlation between predisposition to the nephrotic syndrome and the genetic determinant responsible for HLA.

Adolescent↗
PubMed2001

Acute effects of pulmonary artery banding in sheep on right ventricle pressure-volume relations: relevance to the arterial switch operation.

The first stage of the two-stage arterial switch operation (ASO) for transposition of the great arteries (TGA) is associated with depressed ventricular function and an unstable immediate post-operative course. It is unclear if this is because of the acute increase in afterload of the thin-walled, low-pressure ventricle by pulmonary artery banding (PAB). To determine the acute effects of afterload increase on the contractile function of thin-walled ventricles, we studied the right ventricular pressure-volume relations of seven sheep before and 30 min after PAB using combined pressure-conductance catheters during inflow reduction. Load independent indices of systolic and diastolic performance were derived from these relations. Pulmonary artery banding increased the mean ratio between right and left ventricular systolic pressure from 0.34 +/- 0.05 to 0.64 +/- 0.10, P < 0.05 (mean +/- SD). There were no significant changes in heart rate and end-systolic volume after banding although there was an incremental trend in the end-diastolic volume and stroke volume. Right ventricular output (530 +/- 163-713 +/- 295 mL min (-1), P < 0.05), slope of the end-systolic pressure-volume relation (ESPVR) (3.7 +/- 2.8-10.0 +/- 4.8 mmHg mL (-1), P < 0.05) and slope of the pre-load recruitable stroke work (PRSW) relation (9.6 +/- 1.8-15.0 +/- 3.1 mmHg, P < 0.05) were significantly increased indicating improved contractile state after banding. The diastolic function curve was unchanged after banding although the right ventricle (RV) was operating at a larger end-diastolic volume. Hence, the RV of sheep responded to acute pressure overload by demonstrating enhanced contractility and evidence of the Frank-Starling mechanism without associated change in right ventricular diastolic performance.

Animals↗
PubMed1999

The PTEN/MMAC1/TEP tumor suppressor gene decreases cell growth and induces apoptosis and anoikis in breast cancer cells.

The PTEN/MMAC1/TEP (PTEN) tumor suppressor gene at 10q23.3 is mutated in multiple types of sporadic tumors including breast cancers and also in the germline of patients with the Cowden's breast cancer predisposition syndrome. The PTEN gene encodes a multifunctional phosphatase capable of dephosphorylating the same sites in membrane phosphatidylinositols phosphorylated by phosphatidylinositol 3'-kinase (PI3K). We demonstrate herein that loss of PTEN function in breast cancer cells results in an increase in basal levels of phosphorylation of multiple components of the P13K signaling cascade as well as an increase in duration of ligand-induced signaling through the P13K cascade. These alterations are reversed by wild-type but not phosphatase inactive PTEN. In the presence of high concentrations of serum, enforced expression of PTEN induces a predominant G1 arrest consistent with the capacity of PTEN to evoke increases in the expression of the p27Kip1 cyclin dependent kinase inhibitor. In the presence of low concentrations of serum, enforced PTEN expression results in a marked increase in cellular apoptosis, a finding which is consistent with the capacity of PTEN to alter the phosphorylation, and presumably function, of the AKT, BAD, p70S6 kinase and GSK3 alpha apoptosis regulators. Under anchorage-independent conditions, PTEN also induces anoikis, a form of apoptosis that occurs when cells are dissociated from the extracellular matrix, which is enhanced in conjunction with low serum culture conditions. Together, these data suggest that PTEN effects on the PI3K signaling cascade are influenced by the cell stimulatory context, and that depending on the exposure to growth factors and other exogenous stimuli such as integrin ligation, PTEN can induce cell cycle arrest, apoptosis or anoikis in breast cancer cells.

Apoptosis↗
PubMed1999

Plasma insulin-like growth factor-I and serum IGF-binding protein 3 can be associated with the progression of breast cancer, and predict the risk of recurrence and the probability of survival in African-American and Hispanic women.

In vitro studies have shown that insulin-like growth factor (IGF) is a mitogen for breast cancer cells. However, the associations of plasma IGF-I with tumor histopathology in high-risk groups need further investigation. We hypothesize that plasma IGF-I and serum IGFBP3 concentrations in breast cancer patients may provide useful information on the progression of their disease, and determine the probability of recurrence and survival. We have carried out a retrospective study on 130 minority breast cancer patients. Plasma IGF-I and serum IGFBP3 were correlated with tumor histopathology, menopausal status, treatment modality, recurrence rates, and probability of survival. Plasma IGF-I and serum IGFBP3 were measured by radioimmunoassay. Our studies show that breast cancer patients have elevated plasma IGF-I and serum IGFBP3 levels. In addition we observed the following: IGF-I did not correlate with age and nodal stage. IGF-I and IGFBP3 increased with tumor size (T4). IGF-I did not correlate with estrogen receptor status, but did increase in progesterone-receptor-positive patients. IGF-I levels were higher in premenopausal patients and in women with cancer recurrence. Tamoxifen reduced IGF-I levels significantly and reduced the risk of recurrence. The survival probability was greater in patients with plasma IGF-I levels <120 ng/ml. In conclusion, lowering of plasma IGF-I may offer the following benefits: (a) reduce the risk of developing breast cancer in high-risk groups; (b) slow the progression of breast cancer in patients at early stages of cancer; (c) lower the risk of recurrence, and (d) increase the probability of survival.

Adult↗
PubMed1999

Prognostic value of plasma HER-2/neu in African American and Hispanic women with breast cancer.

We examined the significance of plasma HER-2/neu as a clinical or biological marker for assessing the progression of breast cancer in African American and Hispanic women with similar socioeconomic status, similar health insurance, and similar access to health care delivery. Base line studies show the following: average age of our breast cancer patients was 48 for Hispanic and 53 for African American women. Most of our patients presented invasive ductal carcinoma, and there was no ethnic difference. A larger number of Hispanic women had stage III/IV disease at the time of diagnosis. There was no significant difference in the number of African American or Hispanic patients with ER positive or negative receptors. However, a larger number of Hispanic women had PR positive tumors, and a larger number of African American women had PR negative tumors. In general, there was no difference in the levels of HER-2/neu between the two ethnic groups. Patients with tumors >5 cm had elevated plasma HER-2/neu. However, there was no ethnic difference between tumor size and HER-2/neu levels. In addition, regional node status had no impact on plasma HER-2/neu. Patients with stage III/IV tumors had elevated plasma HER-2/neu. No ethnic difference was observed at either stage I/II or III/IV. ER positive or negative status had no significant impact on plasma HER-2/neu in either ethnic group. In contrast, PR positive patients showed elevated plasma HER-2/neu. Plasma HER-2/neu (>60 U/ml) was the strongest predictor of overall survival, visceral site metastasis, and local recurrence.

Adult↗
PubMed1999

Overexpression of edg-2/vzg-1 induces apoptosis and anoikis in ovarian cancer cells in a lysophosphatidic acid-independent manner.

Lysophosphatidic acid (LPA) is one of the major growth factors in ascites from ovarian cancer patients and appears to play an important role in proliferation, survival, and invasion of ovarian cancer cells. Recently, several groups have shown that Edg-2, which belongs to the G-protein coupled receptor family, is a functional LPA receptor. Northern blot analysis showed that most ovarian cancer cell lines express Edg-2. Edg-2 expression was especially high in the cisplatin-resistant and slowly proliferating 2780cp cell line and was almost absent from the cisplatin-sensitive and rapidly proliferating A2780 cell line. We thus assessed whether Edg-2 could contribute to changes in cell viability, cell proliferation, or cisplatin resistance. Stable overexpression of Edg-2 in A2780 cells induced an exogenous LPA-independent decrease in proliferation but did not alter cisplatin sensitivity. The LPA-independent decrease in growth rate induced by overexpression of Edg-2 could be explained, at least in part, by Edg-2-induced apoptosis rather than by effects on cell cycle progression. In agreement with the results in stably transfected A2780 cells, transient expression of Edg-2 in Jurkat T cells also induced apoptosis. When cells were separated from the extracellular matrix, they underwent a specialized form of apoptosis called anoikis, which is particularly important in survival of cells in the circulation during metastasis. A2780 cells engineered to overexpress Edg-2 were particularly sensitive to anoikis. These observations suggest that Edg-2 may be a negative regulator for ovarian epithelial cell growth and metastasis.

Animals↗