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S A Hussain

Publications and source records attributed to S A Hussain.

At least 19 recordsLinked to original sources

Hypoxia-regulated carbonic anhydrase IX expression is associated with poor survival in patients with invasive breast cancer.

Tumour hypoxia is a microenvironmental factor related to poor response to radiation, chemotherapy, genetic instability, selection for resistance to apoptosis, and increased risk of invasion and metastasis. Hypoxia-regulated carbonic anhydrase IX (CA IX) has been studied in various tumour sites and its expression has been correlated with the clinical outcome. The purpose of this study was to investigate the correlation of CA IX expression with outcome in patients with invasive breast cancer. We conducted a retrospective study examining the effects of carbonic anhydrase IX (CA IX) on survival in patients with breast cancer. To facilitate the screening of multiple tissue blocks from each patient, tissue microarrays were prepared containing between two and five representative samples of tumour per patient. Immunohistochemistry was used to examine expression of CA IX in patients with breast cancer. The study includes a cohort of 144 unselected patients with early invasive breast cancer who underwent surgery, and had CA IX expression and follow-up data available for analysis. At the time of analysis, there were 28 deaths and median follow-up of 48 months with 96% of patients having at least 2 years of follow-up. CA IX was negative for 107 patients (17 deaths) and positive for 37 patients (11 deaths). Kaplan-Meier survival curves show that survival was superior in the CA IX-negative group with a 2-year survival of 97% for negatives and 83% for positives (log-rank test P=0.01). Allowing for potential prognostic variables in a Cox regression analysis, CA IX remained a significant independent predictor of survival (P=0.035). This study showed in both univariate and multivariate analysis that survival is significantly inferior in patients with tumour expressing CA IX. Prospective studies are underway to investigate this correlation in clinical trial setting.

Adult↗

The cardiothoracic ratio in AGA and SGA very low birth weight newborn infants.

BACKGROUND: Cardiothoracic (CT) ratio is a common measurement used to assess heart size in chest radiographs of pediatric patients, but no recent studies have analyzed the standards for CT ratios in very low birth weight (VLBW) infants. OBJECTIVE: The aim of this study was to provide improved standards for CT ratios measured from chest radiographs of VLBW (<1500 g) infants, and to compare CT ratios between small for gestational age (SGA) and appropriate for gestational age (AGA) infants in this population. DESIGN/METHODS: Among VLBW infants admitted to the Jacobi Medical Center NICU from 2002 to 2004, CT ratios were calculated from anteroposterior supine chest radiographs taken of 54 VLBW infants (18 SGA and 36 AGA group-matched on the basis of birthweight and sex) during the first 24 h of life. RESULTS: There were no significant differences between the two groups with respect to birthweight, sex, 1-min Apgar score, 5-min Apgar score, intubation status and degree of inspiration. Median GA of the SGA infants was significantly greater than the AGA infants (30 and 27 weeks, respectively; P<0.001). CT ratios among SGA infants were significantly larger than those among AGAs. Using the widest internal width of the bony thorax, the mean CT ratio among SGA and AGA infants was 0.523 and 0.479, respectively (P=0.00102). CONCLUSIONS: VLBW SGA infants have larger CT ratios than VLBW AGA infants, suggesting that existing standards for normal CT ratios may be inappropriate for use among SGA infants.

Female↗

Genotoxic evaluation of workers employed in pesticide production.

Pesticides are widely used throughout the world in agriculture to protect crops and in public health to control diseases. Nevertheless exposure to pesticides can represent a potential risk to humans. Pesticide manufacturing unit workers are prone to possible occupational pesticide exposure. Therefore, this study was performed to evaluate the genotoxic effect of pesticide exposure in these workers. In the present investigation 54 pesticide workers and an equal number of control subjects were assessed for genome damage in blood lymphocytes utilizing the chromosomal aberration analysis and the buccal epithelial cell by adopting the micronucleus test. The results suggested that pesticide workers had a significantly increased frequency of chromosomal aberrations when compared with controls (mean+/-S.D., 8.43+/-2.36 versus 3.32+/-1.26; P<0.05). Similarly, the pesticides exposed workers showed a significant increase in micronucleated cells compared with controls (1.24+/-0.72 versus 0.32+/-0.26; P<0.05). Analysis of variance revealed that occupational exposure to pesticides had a significant effect on frequency of micronuclei (P<0.05), whereas smoking, age, gender and alcohol consumption had no significant effect on genetic damage (P>0.05). However, no association was found between years of exposure, smoking, age, gender, alcohol consumption and higher levels of genetic damage as assessed by the chromosomal aberration assay (P>0.05). Our findings indicate that occupational exposure to pesticides could cause genome damage in somatic cells.

Adult↗

Incidence of epilepsy in a racially diverse, community-dwelling, elderly cohort: results from the Einstein aging study.

OBJECTIVE: To determine age-specific incidence and cumulative incidence of epilepsy in a well-defined cohort of elderly people, and to examine how rates of epilepsy are modified by sex, race, stroke, dementia, head injury, and depression. METHODS: The authors examined data from a reconstructed cohort based on 1919 community-dwelling volunteers, followed as part of a large ongoing prospective aging study. RESULTS: Age-specific incidence was 10.6 (per 100,000 person-years) between ages 45 and 59, 25.8 between ages 60 and 74, and 101.1 between ages 75 and 89. Cumulative incidence was 0.15% from age 45 to age 60, 0.38% to age 70, 1.01% to age 80, and 1.47% to age 90. In addition, the difference in cumulative incidence among African-American subjects approached statistical significance (57.6/100,000 person-years versus 26.1 in Caucasian, p=0.10), and the difference in incidence among subjects reporting a history of stroke was significantly elevated (p=0.029). Incidence of epilepsy was not statistically elevated among males, those with dementia, or individuals reporting a history of head injury or treatment for depression. Among "healthy" subjects without history of stroke, head injury, or dementia, we observed a cumulative risk of epilepsy with onset after age 60 of only 1.1%. CONCLUSIONS: The incidence of epilepsy was low in this relatively healthy cohort of elderly people, especially among subjects without known risk factors. In this study we identified African-American race as a risk factor in the elderly for epilepsy independent of stroke.

Black or African American↗

Role of microenvironment in the mixed Langmuir-Blodgett films.

This paper reports the pi-A isotherms and spectroscopic characteristics of mixed Langmuir and Langmuir-Blodgett (LB) films of nonamphiphilic carbazole (CA) molecules mixed with polymethyl methacrylate (PMMA) and stearic acid (SA). pi-A isotherm studies of mixed monolayer as well as the remarkable change in collapse pressure of the mixed monolayer isotherms definitely show that CA is incorporated into PMMA and SA matrices. However, CA is stacked in the PMMA/SA chains and forms microcrystalline aggregates, as is evidenced from the scanning electron micrograph picture. The nature of these aggregated species in the mixed LB films has been revealed by UV-vis absorption and fluorescence spectroscopic studies. The presence of two different kinds of band systems in the fluorescence spectra of the mixed LB films have been observed. This may be due to the formation of low-dimensional aggregates in the mixed LB films. Intensity distribution of different band systems is highly sensitive to the microenvironment of two different matrices as well as also on the film thickness.

Journal Article↗

Formation of complex films with water-soluble CTAB molecules.

This communication reports the formation of complex Langmuir monolayer at the air-water interface with the water-soluble N-cetyl N,N,N-trimethyl ammonium bromide (CTAB) molecules when interacted with the stearic acid (SA) molecules. The reaction kinetics of the formation of the CTAB-SA complex was monitored by observing the surface pressure versus time graph. Multilayered LB films of this complex doped with Congo red was successfully formed onto a quartz substrate. UV-Vis absorption and steady-state fluorescence spectroscopic characteristics of this doped LB films confirms the successful incorporation of Congo red molecules in to the CTAB-SA complex films.

Absorption↗

Langmuir-Blodgett films of 9-phenyl anthracene molecules incorporated into different matrices.

This communication reports the surface pressure (pi) versus area per molecule (A) isotherm characteristics of the mixed films of 9-phenyl anthracene (PA) in stearic acid (SA) and polymethyl methacrylate (PMMA) matrices, at the air-water interface. The mixed Langmuir films at the air-water interface have been observed to be easily transferred onto solid substrates to form uniform Langmuir-Blodgett films. By changing various parameters, namely molefraction, surface pressure of lifting and number of layers, the mixed Langmuir-Blodgett (LB) films of various types have been fabricated successfully and their spectroscopic characteristics have been reported. From the isotherm characteristics and the area per molecule versus molefraction plot, it is evident that the PA molecules are successfully incorporated into mixed Langmuir-Blodgett films. UV-vis absorption spectroscopic study of the mixed LB films at various molefractions of PA in two different matrices reveal that formation of I-type aggregate in PMMA matrix whereas both I- and H-type aggregates are playing their dominant role in SA matrix. Moreover, fluorescence spectroscopic study reveals reabsorption effect. Molecular movement persists in the freshly prepared LB films, as is evident from the time dependent changes in both UV-vis absorption and fluorescence spectra of the mixed LB films in both matrices. From our observation it is evident that about 200 h is required to get the LB films in a stable condition. Dimers and higher order n-mers are formed at a higher surface pressure of 30 mNm(-1).

Air↗

A phase I/II study of gemcitabine and fractionated cisplatin in an outpatient setting using a 21-day schedule in patients with advanced and metastatic bladder cancer.

A randomised phase III trial of MVAC (methotrexate, vincristine, doxorubicin, cisplatin) vs gemcitabine and cisplatin (GC) (G 1000 mg m(-2) days 1, 8, and 15 plus C 70 mg m(-2) day 2, q 4 wks) indicated GC had similar efficacy and lower toxicity (JCO 2000). Significant haematologic toxicities in the GC arm occurred on day 15, necessitating dose adjustments in 37% of cycles. We conducted a phase I/II dose escalation trial using GC on a 21-day cycle, with G and C split between days 1 and 8. The objective of the study to define maximum-tolerated dose and dose-limiting toxicity (DLT), objective response rate, and overall survival. In all, 32 patients with locally advanced, relapsed, or metastatic disease received: dose level 1, G/C 1000/35; level 2, 1100/35; level 3, 1200/35; level 4, 1200/45 mg m(-2) (G and C given on days 1 and 8 every 3 wks). A total of 19 patients had glomerular filtration rate <60 ml min(-1) and 19 patients had metastatic disease. Dose-limiting toxicity was haematologic (grade 4 thrombocytopenia) at dose level 2. Of 151 cycles, at day 15, platelets were <100 in 61 cycles; neutrophils <0.5, platelets <50 in 26 cycles. Only seven cycles were deferred due to haematological toxicity; four for renal toxicity (chemotherapy instituted posthydration). Overall response rate was 65.5% on an intention-to-treat analysis (75% [21/28] for assessable patients), with four complete responses (12.5%) and 17 partial responses (53%). After the median follow-up of 17.2 months (range 13.1-32.4 months), 12 patients remain alive. The overall median survival was 16 months (range 10.1-26.6 months). G plus C every 3 weeks is active and well tolerated in an outpatient setting, even in patients receiving prior platinum-based regimens and with poor renal reserve.

Adult↗

Long-term results of a phase II study of synchronous chemoradiotherapy in advanced muscle invasive bladder cancer.

We conducted a phase I/II study investigating synchronous chemoradiotherapy with mitomycin C and infusional 5-fluorouracil (5-FU) in muscle invasive bladder cancer. Early dose escalation results were previously published. We report the long-term toxicity and efficacy results with the optimised regimen. Patients with muscle invasive bladder cancer with glomerular filtration rate >25 ml min(-1) were eligible. Mitomycin (12 mg m(-2) on day 1 only) and infusional 5-FU (500 mg m(-2) day(-1)) for 5 days were administered during weeks 1 and 4 of radiotherapy of 55 Gy in 20 fractions. A total of 41 patients were enrolled, median age was 68 years, 33 were male and eight female patients. Out of the 41 patients, 20 (49%) had hydronephrosis at presentation and 25 (62%) had T3b or T4 disease. Four patients experienced Grade III thrombocytopenia and three patients had Grade III neutropenia. There were no episodes of febrile neutropenia. Four patients experienced Grade III diarrhoea and 1 Grade III urgency and dysuria. Six patients did not undergo cystoscopic evaluation due to early metastatic spread although there was no clinical suggestion of bladder failure. In all, out of 35 evaluable patients, 25 (71%) had macroscopic complete response at 3-month cystoscopy, and biopsy confirmed in 24 out of 25. A total of 16 (39%) patients remain alive with a median follow-up of 50.7 (range 23.5-68.8) months, 14 with a functioning bladder with no reported long-term treatment-related bladder or bowel toxicity. Five out of 41 patients have undergone salvage cystectomy: two for persistent CIS, two T1 and one muscle invasive recurrence. Four patients have received intravesical chemotherapy, of whom two remain alive with a functioning bladder. Overall 12-, 24- and 60-month (m) survival rates were 68, 49 and 36%. Local and distant progression free rates were 82 and 86% at 12-m and 79 and 75% at 24-m. Organ preservation using multimodality therapy is feasible and safe, even in patients with poor renal reserve, and does not compromise salvage therapies. A national phase III trial BC2001 (www.bc2001.org.uk) exploring the effects of synchronous chemoradiotherapy with this regimen is currently recruiting.

Aged↗

Management of upper limb arterial injury without angiography--Chennai experience.

We present our experience and observations in the management of upper limb arterial injury in a tertiary trauma care centre of a University Hospital in a developing country from January 2000 to January 2002. In this retrospective study, we had treated 27 patients (identified from trauma register) with upper extremity vascular injuries. Clinical examination and Doppler pressure studies were our prime modalities of investigation. Angiography was not employed. Our immediate limb salvage rate was 100%. Two patients developed complications during a mean follow up of 70 days with one requiring amputation. We thereby emphasise the fact that good results can be obtained by thorough clinical examination and Doppler evaluation and prompt surgery without the need for angiography in upper limb vascular trauma.

Adult↗

CD40 expression in prostate cancer: a potential diagnostic and therapeutic molecule.

CD40, a member of the TNF receptor superfamily, is widely expressed on human immune cells. It is also frequently expressed on epithelial malignancies, suggesting that CD40 may contribute to the pathogenesis of some cancers. Activation of CD40 in cancer cells induces growth inhibition and sensitization to apoptotic stimuli. This study investigates CD40 expression in archival tissue from patients with prostate cancer. In all cases, normal prostatic acini expressed CD40, however, in 56 of 57 cases of prostate cancer no CD40 expression was detected. In the one other case, patchy CD40 expression was associated with prostatic in situ neoplasia. In conclusion, invasive prostate cancer is a CD40-negative tumour. These data may be relevant as a diagnostic tool; in providing insight into progression of cancer from normal epithelium; and in identifying novel therapeutic strategies for prostate cancer.

Aged↗

The use of self-expandable metal stents in the palliation of malignant bowel obstruction.

Palliation of malignant gastrointestinal obstruction is a major aspect of oncology. We assessed the efficacy of stents in the palliation of gastric outlet, duodenal and colonic obstruction. We undertook a retrospective study of 35 consecutive patients who were referred for stent insertion with palliative intent from June, 1999 to March, 2003. Thirty-two stents were successfully placed in 30 patients. Technical success rate was 86% (30/35 patients). Of the patients who had successful insertion, 83% had complete relief of symptoms. In 1 patient the stent failed to expand. There was no procedure related mortality. Median survival was 1.6 months (range, 0-14.8). The conclusion was that self-expandable metal stents provide an effective method of palliation in malignant gastrointestinal obstruction, with high clinical and technical success rates and low complication rates.

Adult↗

Proapoptotic genes BAX and CD40L are predictors of survival in transitional cell carcinoma of the bladder.

The purpose of the study was to investigate the effects of expression of a range of genes involved in apoptosis on outcome in bladder cancer. Immunohistochemistry was used to examine expression of BCL2, BAX, P53, CD40 and CD40L in archival tissues of patients included in various treatment trials for transitional cell carcinoma (TCC) of the bladder. Data were collected on 94 patients who first presented with either invasive or superficial bladder cancer. Median follow-up for alive patients was 83 months (m) (range 12-195 m). Median survival was 80 m (95% CI=56-128 m). Median survivals for the various markers were as follows: BAX-positive patients 110 m vs BAX-negative patients 18 m (P=0.0002); CD40L-positive patients 95 m vs CD40L-negative patients 45 m (P=0.04); BCL2-positive patients 44 m and BCL2-negative patients 74 m, (P=0.64); CD40-positive patients 110 m and CD40 negative patients 45 m (P=0.12); and P53 positive patients 80 m and P53 negative patients 45 m (P=0.58). In conclusion, it was seen that overexpressions of BAX and CD40L are prognostic of better survival in TCC of the bladder. Our results also raise the possibility of the future development of CD40- and CD40 ligand-based immunotherapy for bladder cancer. This study links proapoptotic and antiapoptotic markers to overall survival.

Adult↗

Immediate dual energy X-ray absorptiometry reveals a high incidence of osteoporosis in patients with advanced prostate cancer before hormonal manipulation.

OBJECTIVE: To examine the incidence of osteoporosis in patients with advanced prostate cancer (using forearm densitometry) before commencing androgen deprivation therapy (ADT), as osteoporotic fractures are more frequent in patients with prostate cancer who have undergone either medical or surgical castration, because of rapid loss of bone mass. PATIENTS AND METHODS: In all, 174 patients (mean age 74.6 years, range 46-90) with advanced prostate cancer presented over 2 years. Their forearm bone densitometry values were compared with those from 106 age-matched controls (mean age 74.3 years, range 66-90). RESULTS: Of the 174 patients, 73 (42%) were osteoporotic (t score <or=- 2.5) and 65 (37%) were osteopenic (t score - 1 to - 2.4). This compares with a 27% incidence of osteoporosis in the control group (P = 0.022). There were also no significant correlations between prostate specific antigen levels, Gleason score, tumour stage, biochemical markers and the presence or absence of osteoporosis risk factors. CONCLUSION: Patients with advanced prostate cancer requiring ADT have a high incidence of osteoporosis before treatment. In addition, osteoporosis in these men cannot be predicted from clinical or biochemical values. Therefore, bone densitometry should be used in all patients with advanced cancer requiring ADT, as the results have implications for the choice of cancer therapy and the prophylaxis for osteoporosis.

Absorptiometry, Photon↗

Cauda equina syndrome: outcome and implications for management.

A retrospective review of all patients who had surgery for cauda equina syndrome (CES) due to a herniated lumbar disc between January 1996 and November 1999 was undertaken. All underwent laminectomy and discectomy, and had been admitted as emergencies with cauda equina syndrome. Ten women and 10 men with a mean age of 45 years (range 33-67) had their diagnosis verified with MRI in 19 cases and CT in one case. Only half the patients had been catheterized at the time of admission to the neurosurgical unit. Nine patients had emergency decompressive surgery within 5 h of presentation to our unit. The others had surgery on the next available list, but within 24 h of admission. No difference was found between urgently operated patients and those operated on the next available list when urological outcome and quality of life assessments were made using a validated questionnaire at a mean time of 16 months after surgery (range10-48). Twenty per cent of a control group who had undergone laminectomy and discectomy for large disc herniations, but without CES had new urological symptoms when questioned postoperatively, but similar quality of life status. Emergency decompressive surgery did no significantly improve outcome in CBS compared with a delayed approach.

Adult↗

Hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the sixth most common cancer of men and eleventh most common cancer of women world-wide. However, because almost every individual who develops liver cancer dies of the disease, HCC is the third most common cause of the cancer deaths in men and seventh most common in women. The treatment of choice for hepatocellular carcinoma remains surgical resection or liver transplantation, in carefully selected cases. In patients with hepatocellular carcinoma not amenable to surgical intervention a variety of different therapeutic interventions have been investigated. These include direct ablation of the tumour using agents such as ethanol or acetic acid, transcatheter arterial chemoembolization, or systemic chemotherapy. The evaluation of their efficacy is compromised by the paucity of adequately powered randomised clinical trials. The main challenge facing the research community over the next decade is to prioritise the most promising treatments and take these forward into multicentre controlled trials. Even if these fail to improve results, they will help reduce the variation in clinical practice by eliminating anecdotal treatment.

Carcinoma, Hepatocellular↗

Pre-clinical and clinical study of QC12, a water-soluble, pro-drug of quercetin.

BACKGROUND: Quercetin is a naturally occurring flavonoid with many biological activities including inhibition of a number of tyrosine kinases. A phase I, dose-escalation trial of quercetin defined the maximum tolerated dose (MTD) as 1700 mg/m2 three weekly, but the vehicle, dimethyl sulphoxide (DMSO) is unsuitable for further clinical development of quercetin. PATIENTS AND METHODS: A water-soluble, pro-drug of quercetin (3'(N-carboxymethyl)carbomyl-3,4',5,7-tetrahydroxyflavone), QC12 has been synthesised. Six cancer patients received 400 mg of QC12 (equivalent to 298 mg of quercetin), orally on day 1 and intravenously (i.v.) in normal saline on day 14. RESULTS: Following oral administration of QC12 we were unable to detect QC12 or quercetin in plasma. After i.v. administration, we detected peak plasma concentrations of QC12 of 108.7 +/- 41.67 microMolar (microM). A two-compartment model with mean t(1/2)alpha of 0.31 +/- 0.27 hours and mean t(1/2)beta of 0.86 +/- 0.78 hours best described the concentration-time curves for QC12. The mean AUC was 44.54 +/- 13.0 microM.hour and mean volume of distribution (Vd) of 10.0 +/- 6.2 litres (l). Quercetin was found in all patients following i.v. infusion of QC12, with peak levels of quercetin 19.9 +/- 11.8 microM. The relative bioavailability of quercetin was estimated to be 20%-25% quercetin released from QC12. CONCLUSIONS: QC12 is not orally bioavailable. This water-soluble pro-drug warrants further clinical investigation; starting with a formal phase I, IV, dose-escalation study.

Adult↗