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Biomedical subjects

S Ahmed

Publications and source records attributed to S Ahmed.

At least 289 records · Page 16Linked to original sources

The efficacy of neoadjuvant chemotherapy compared to postoperative therapy in the treatment of locally advanced breast cancer.

The current approach to the treatment of locally advanced breast cancer is sequential chemotherapy, surgery and/or radiation, and consolidation chemotherapy. Although significant tumor response is seen with this regimen, there are few studies that compare this approach to postoperative chemotherapy. The purpose of this study was to compare the disease-free and overall survival of patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and surgery to patients treated with surgery followed by adjuvant chemotherapy. Ninety-four patients with stage IIB, IIIA, and IIIB breast cancer were treated with a standardized chemotherapy regimen. The first group, 60 patients who were followed prospectively, was treated with neoadjuvant chemotherapy (NCT) consisting of vincristine, prednisone, cytoxan, methotrexate, and 5-FU (CVFMP) followed by surgery and consolidation chemotherapy with adriamycin. The second group, 34 patients evaluated retrospectively, had surgery followed by postoperative chemotherapy (PCT) with CVFMP followed by adriamycin. Overall median follow-up was 38 months. In the NCT group, 45/60 (75%) patients had a clinical response to induction therapy and the median reduction in tumor size was 50%. The rates of local recurrence, distant recurrence, and death from disease were similar in the two groups. The time to local recurrence was similar for the two groups. However, the median time to distant recurrence was shorter in the NCT group (19 month vs. 31 months, p = NS). Overall median survival among the NCT patients was shorter than for the PCT group (30 vs. 47 months, p = NS). The current study suggests that postoperative therapy is comparable to a neoadjuvant regimen in patients with locally advanced breast cancer with regard to local recurrence, distant recurrence, and overall survival.

Antineoplastic Combined Chemotherapy Protocols↗

The human phase response curve (PRC) to melatonin is about 12 hours out of phase with the PRC to light.

Melatonin's timekeeping function is undoubtedly related to the fact that it is primarily produced during nighttime darkness; that is, melatonin and light occur at opposite times. The human phase response curve (PRC) to melatonin appears to be about 12h out of phase with the PRC to light. These striking complementarities, together with light's acute suppressant effect on melatonin production, suggest that a function for endogenous melatonin is to augment entrainment of the circadian pacemaker by the light-dark cycle. The melatonin PRC also indicates correct administration times for using exogenous melatonin to treat circadian phase disorders.

Adult↗

Clozapine withdrawal-emergent dystonias and dyskinesias: a case series.

BACKGROUND: Severe psychotic decompensation during clozapine withdrawal has been reported previously. Less attention has been paid to movement disorders following abrupt clozapine withdrawal. This report describes 4 subjects who experienced severe dystonias and dyskinesias upon abrupt clozapine withdrawal. METHOD: Current and past medical records of 4 subjects with DSM-IV schizophrenia or schizo-affective disorder were reviewed. RESULTS: All subjects had a history of neuroleptic-induced extrapyramidal symptoms, 1 had a history of severe dystonias, and 1 had neuroleptic malignant syndrome. All had mild orolingual tardive dyskinesia prior to clozapine treatment. All subjects had received clozapine for several months, and 3 of the 4 subjects stopped clozapine abruptly. Two subjects experienced cholinergic rebound symptoms within hours, which resolved quickly. These subjects had severe limb-axial and neck dystonias and dyskinesias 5 to 14 days after clozapine withdrawal. Two subjects were unable to ambulate, and 1 had a lurching gait. Two gagged while eating or drinking. Two subjects were returned to clozapine, 1 was started on low-dose risperidone treatment, and 1 was started on olanzapine treatment. All experienced significant improvements in their mental state and movement disorders. CONCLUSION: Severe movement disorders, which may be worse than the movements prior to clozapine treatment, and cholinergic rebound symptoms may occur upon abrupt clozapine withdrawal and must be recognized in addition to the severe psychotic decompensation noted in some patients. Patients, families, and caregivers must be alerted to this possibility. Where possible, a slow clozapine taper, the use of anticholinergic agents, and symptomatic treatment may help minimize these withdrawal symptoms, and reintroduction of clozapine or treatment with the newer atypical agents can help in the clinical management of these symptoms.

Acute Disease↗

Evaluation of the effect of haemodialysis on cardiac dysfunction in patients of chronic renal failure.

Thirty-eight patients with end stage renal disease who were on haemodialysis and had recurrent congestive cardiac failure were analysed. Echocardiographic findings were evaluated at start of haemodialysis and after 6 dialysis sessions. Seventeen cases (48%) had diastolic dysfunction, 11 (29%) systolic dysfunction 8 (18%) had normal echocardiogram and 2 (5%) had dilated left ventricle with normal ejection fraction. In the systolic dysfunction group the end diastolic diameter decreased after 6 dialysis sessions. In the diastolic dysfunction group the end diastolic diameter and ejection fraction decreased minimally. In the systolic dysfunction group 8 patients (42%) expired within 18 months with a mean survival of 5 months and in the diastolic dysfunction group 5 patients (28%) died within 18 months with a mean survival of 12 months.

Evaluation Studies as Topic↗

Review of the molecular modelling studies of the cytochrome P-450 estrogen synthetase enzyme, aromatase.

The biosynthesis of the family of female hormones, the estrogens, is mediated by the cytochrome P-450 based enzyme Aromatase (AR), an enzyme which has been the focus of extensive research for some time and has resulted in the synthesis of numerous inhibitory compounds with varying structural properties. The crystal structure of this membrane-bound enzyme has not been determined, although that of the bacterial P-450 camphor hydroxylase enzyme has, and the latter has been used for homology modelling of AR and other related enzymes. Several workers have attempted to obtain an approximate model of the active site of AR through the use of various molecular modelling techniques using inhibitors of this enzyme, as well as a combination of experiments involving active site mutagenesis of specific areas of the P-450 backbone together with molecular modelling. In this report these studies are reviewed. In summary, although the crystal structure of AR has yet to be determined, the use of molecular modelling studies has provided useful information in the design and synthesis of its inhibitors.

Aromatase↗

Heavy metals: leaching from glazed surfaces of tea mugs.

Heavy metals (zinc, lead, cadmium, iron, chromium, copper, manganese, nickel and cobalt) were found to leach from the glazed surfaces of tea mugs collected from 13 different pottery units of Khurja (U.P.) and one each from Ghaziabad (U.P.) and Calcutta (West Bengal) determined under different conditions. The leachates used were: tea at 80 degrees C, orange juice at room temperature and 4% acetic acid at room temperature, 40 degrees C and 60 degrees C, respectively. The volume (capacity) of mugs ranged between 200 and 250 ml. The duration for leaching was 24 h in each case without stirring. The concentrations of metals leached in tea at 80 degrees C were found in the range (in microgram/l): Zn, 236-730; Fe, 98-925; Cr, 62-119; Cu, 63-299; Mn, 710-2670; and Ni, 70-80 micrograms/l. The concentrations of metals leached in orange juice at room temperature were in the range (in microgram/l): Zn, 393-1262; Cd, 25-349; Fe, 122-342; Cr, 66-945; Cu, 135-853; Mn, 166-424; and Ni, 70-134 micrograms/l. The concentrations of heavy metals extracted by 4% acetic acid at room temperature were found in the range (in microgram/l): Zn, 18-192; Fe, 143-372; Cu, 51-190; and Mn, 0-48 micrograms/l; at 40 degrees C (in microgram/l): Zn, 118-837; Fe, 124-639; Cu, 230-722; and Mn, 30-63 micrograms/l and at 60 degrees: Zn, 33-900; Fe, 83-576; Cu, 90-685; and Mn, 43-778 micrograms/l, respectively.

Acetic Acid↗

Fluorescent probes attached to Cys 35 or Cys 84 in cardiac troponin C are differentially sensitive to Ca(2+)-dependent events in vitro and in situ.

The goal of the current study was to generate recombinant cTnC proteins with single Cys residues as sites for attachment of fluorescent probes that can distinguish between the structural effects of myosin cross bridges and direct Ca2+ binding to cTnC (cardiac and slow skeletal troponin C) in skinned fibers. We anticipated that cTnC proteins which retain the endogenous Cys 35 (cTnC(C35)) or Cys 84 (cTnC(C84)) would provide fluorescent probes with distinct microenvironments, since these residues are on opposite sides of the globular regulatory domain. In vitro experiments that showed IAANS (2-(4'-(iodoacetamido)anilino)naphthalene-6-sulfonic acid) coupled to Cys 35 can induce unwanted structural perturbations as evidenced by a decreased affinity of site II for Ca2+ when IAANS-labeled cTnC(C35) is bound to cTnI. Important structural features involving Cys 35 in the inactive site I are suggested by a Ca(2+)-dependent increase in reactivity of Cys 35 with sulfhydryl specific reagents when cTnC(C35) is associated with cTnI. These characteristics are not seen for cTnC(C84). When incorporated in situ into skinned cardiac muscle fibers, native cTnC with IAANS bound to both Cys 35 and Cys 84 showed a pCa50 of fluorescence which preceded that of force, while the pCa50 values of both force and fluorescence were coincident for IAANS-labeled cTnC(C84). Disruption of force-producing myosin cross bridges had no effect on the pCa50 of fluorescence for IAANS-labeled cTnC(C84), but induced a rightward shift in the pCa50 of fluorescence for IAANS-labeled native cTnC. These data can be interpreted to indicate that cTnC with IAANS bound to both Cys 35 and C84 senses either myosin cross bridges or direct Ca2+ binding and myosin-induced cooperativity, while IAANS bound to Cys 84 alone senses conformations that are tightly coupled with force generation.

Amino Acid Sequence↗

Abundance and Distribution of Bacillus thuringiensis in the Agricultural Soil of Bangladesh

Bacillus thuringiensis is distributed ubiquitously in the agricultural soil of Bangladesh. Simple correlation and regression analyses showed that the soil sand percentage and the available copper levels had significant negative and positive contributions, respectively, to the abundance and distribution of B. thuringiensis in the agricultural soil. Among the isolates, only 2.5% of strains showed larvicidal activity against the mosquito Culex quinquefasciatus. The larvicidal potency LD50 varied from 3.5 x 10(3) to 9.5 x 10(7) spores per milliliter among the isolates. Copyright 1997 Academic Press. Copyright 1997 Academic Press

Journal Article↗

Non-intubated pyeloplasty for pelviureteric junction obstruction in children.

Sixty-one consecutive patients undergoing pyeloplasty (5 bilateral) were reviewed retrospectively; 54 pyeloplasties were non-intubated (NIP) and 12 were intubated. NIPs were managed by an extrarenal wound drain, which was removed after 2-4 days in 44 repairs with minimal or no urinary leakage and after 6-8 days in 10 with significant leakage. Fifty-two were successful after the primary procedure. One patient who developed a urinoma after drain removal required a percutaneous nephrostomy followed by a revision pyeloplasty. A second revision pyeloplasty was necessary for persistent postoperative obstruction. The results of NIP compared favorably with series where intubation was used routinely and were superior to alternative methods of management such as endopyelotomy.

Adult↗

Further observations on histological changes at the ureteroileal junction in ileal conduits.

Seventy-two ureteroileal anastomoses taken from ileal conduits removed from 62 patients were examined histologically to characterize the range of mucosal and stromal changes at these sites. All 72 demonstrated variable amounts of subepithelial chronic inflammation and fibrosis. Other histological features included: cystic spaces lined by transitional epithelium (N = 29; 40%; average diameter 1.2 mm); cystic spaces lined by mixed intestinal/transitional epithelium (N = 5; 7%; average diameter 0.77 mm); and cystically dilated intestinal glands (N = 21; 29%; average diameter 0.24 mm). The latter were associated with overgrowth by transitional epithelium, which had prevented mucus drainage. Twenty-one (29%) had mucus pools with no epithelial lining (average diameter 1.2 mm), and polypoidal protrusions into the lumen of the anastomosis were found containing mucus pools (N = 4; 6%; average diameter 1.4 mm), transitional-lined cysts (N = 5; 7%; average diameter 2.2 mm), and mixed intestinal/transitional-lined cysts (N = 2; 3%; average diameter 2.5 mm). Focal rupture of dilated intestinal glands with interstitial pooling of mucus was not uncommon, and marked dystrophic calcification was found in 1 case within a large collection of extracellular mucus. This series confirms that inflammation, fibrosis, and glandular overgrowth by transitional epithelium are common occurrences at ureteroileal anastomosis sites. Subsequent gland rupture may result in sizable accumulations of interstitial mucus, and rarely in marked dystrophic calcification.

Adolescent↗

Female bladder exstrophy.

Bladder exstrophy is one of the most challenging congenital urinary tract abnormalities. Apart from the open bladder the patient also has various other abnormalities, including urogenital, musculoskeletal and anorectal defects. The size of the exstrophic bladder varies from patient to patient. In the female the clitoris to bifid and the vagina is anteriorly placed. In this paper various aspects of female bladder exstrophy are reviewed in detail, including incidence, etiology, anatomy and clinical features, together with early, medium-term and long-term surgical management. The aim is to achieve a functional bladder closure, although some patients are better off with a urinary diversion. Considering the complexity of the urogenital problems and the surgical management thereof, all patients require lifelong follow-up.

Abnormalities, Multiple↗

Multicystic kidney in siblings.

Two siblings (one girl and one boy), with a left multicystic kidney in whom a renal abnormality had been recognized prenatally, are reported. A large renal mass was present in both patients and the second sibling also had hypertension. Early surgical resection was carried out with satisfactory clinical progress and resolution of the hypertension. Multicystic kidney is considered a developmental abnormality with a sporadic incidence. These cases and other reports of familial incidence in the literature indicate that there may also be a genetic basis for the abnormality.

Female↗

Stereospecific activity and nature of metabolizing esterases for propranolol prodrug in hairless mouse skin, liver and plasma.

Cutaneous stereoselective hydrolyses of ten ester prodrugs of propranolol in hairless mouse were compared to those in liver and plasma. On the basis of protein content, the hydrolysis rate was greatest with liver homogenate followed by plasma and skin homogenate. The buffer showed the slowest and non-stereoselective hydrolysis. However, skin showed very high stereoselectivity (R/S ratio: 6.7-18.4) as compared with liver (0.7-2.0) and plasma (1.7-4.7). The microsomal esterase activity was higher than cytosolic esterase in liver, while an opposite relation was observed in skin. The smaller Km and larger Vmax values of the (R) isomer than those of the (S) isomer of caproyl- and/or butyryl-propranolol were found in skin and plasma, while Km was the same between (R) and (S) isomers in liver. Enzyme inhibition studies indicated that the carboxylesterases were primarily involved in prodrug hydrolysis in liver. On the other hand, skin and plasma were found to be rich in both carboxylesterases and cholinesterases. Interestingly, the (R) isomer was more sensitive towards butylcholinesterase in skin and plasma, while (S) isomer was more sensitive towards carboxylesterase in plasma. Moreover, no stereoselective inhibition was observed in liver. These data indicated that the hydrolyzing nature of skin esterases responsible for propranolol prodrug was sensitive against stereochemical configuration and more similar to those in plasma esterases than liver esterases.

Adrenergic beta-Antagonists↗

Patients with mild heart failure worsen during withdrawal from digoxin therapy.

OBJECTIVES: We investigated whether patients with mild heart failure due to left ventricular systolic dysfunction were at risk of worsening during digoxin withdrawal. BACKGROUND: Deterioration during digoxin withdrawal is often believed to be restricted to patients with moderate to severe clinical evidence of heart failure. To test this hypothesis, we studied the outcome of patients categorized by treatment assignment and a clinical signs and symptoms heart failure score in two rigorously designed clinical heart failure trials: the Prospective Randomized Study of Ventricular Function and Efficacy of Digoxin (PROVED) and the Randomized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme (RADIANCE) trial. METHODS: Potential differences in treatment failure, left ventricular ejection fraction and exercise capacity were evaluated in three groups of patients: those with mild heart failure (score < or = 2) who were withdrawn from digoxin (Dig WD Mild); those with moderate heart failure (score > 2) who were withdrawn from digoxin (Dig WD Moderate); and patients who continued receiving digoxin regardless of heart failure score (Dig Cont). RESULTS: Heart failure score at randomization did not predict outcome during follow-up in Dig Cont-group patients. Dig WD Mild-group patients were at increased risk of treatment failure and had deterioration of exercise capacity and left ventricular ejection fraction compared with that in Dig Cont-group patients (all p < 0.01). Patients in the Dig WD Moderate group were significantly more likely to experience treatment failure than patients in either the Dig WD Mild or Dig Cont group (both p < 0.05). CONCLUSIONS: Patients with systolic left ventricular dysfunction were at risk of clinical deterioration after digoxin withdrawal despite mild clinical evidence of congestive heart failure.

Aged↗