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Biomedical subjects

A Alam

Publications and source records attributed to A Alam.

At least 19 recordsLinked to original sources

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↗

Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma.

PURPOSE: To evaluate the safety and efficacy of fludarabine plus rituximab in treatment-naive or relapsed patients with low-grade and/or follicular non-Hodgkin's lymphoma. PATIENTS AND METHODS: This was an open-label, single-arm, single-center phase II study enrolling 40 patients. During the first week of the study, patients received two infusions of rituximab 375 mg/m2 administered 4 days apart. Seventy-two hours after the second infusion of rituximab, patients received the first of six cycles of fludarabine chemotherapy (25 mg/m2/d for 5 days on a 28-day cycle). Single infusions of rituximab were administered 72 hours before the second, fourth, and sixth cycles of fludarabine, and two infusions of rituximab were given 4 weeks after the last cycle of fludarabine. Treatment duration was 26 weeks. RESULTS: An overall response rate of 90% (80% complete response rate) was achieved in the intent-to-treat population. Similar response rates were seen in treatment-naive and previously treated patients. The median duration of response has not been reached at 40+ months. The median follow-up time in this study is 44 months (range, 15 to 66 months). In patients positive for the 14;18 translocation in blood and/or marrow at enrollment, molecular remission was achieved in 88% of cases, with patients remaining negative for up to 4 years to date. Hematologic toxicity was manageable, and except for a 15% incidence of herpes simplex/zoster infections, infectious complications were rare. Nonhematologic toxicities were minimal. CONCLUSION: Rituximab plus fludarabine was well tolerated and associated with an excellent complete response rate, including molecular remissions, in patients with low-grade or follicular lymphoma.

Adult↗

A prognostic model for prolonged event-free survival after autologous or allogeneic blood or marrow transplantation for relapsed and refractory Hodgkin's disease.

There are several prognostic models for Hodgkin's disease (HD) patients, but none evaluating patient characteristics at time of blood and marrow transplantation (BMT). We developed a prognostic model for event-free survival (EFS) post-BMT based on HD patient characteristics measured at the time of autologous (auto) or allogeneic (allo) BMT. Between 1/1991 and 12/2001, 64 relapsed or refractory HD patients received an auto (n=46) or allo (n=18) BMT. A multivariate prognostic model was developed measuring time to relapse, progression or death. Median follow-up was 51.7 months; median EFS for auto and allo BMT was 36 and 3 months, respectively (P=0.001). Significant multivariate predictors of shorter EFS were chemotherapy-resistant disease, KPS <90 and > or =3 chemotherapy regimens pre-BMT. Patients with two to three adverse factors had significantly shorter EFS at 2 years (58 vs 11% in auto; 38 vs 0% in allo BMT patients). Despite a selection bias favoring auto BMT, the model was valid in both auto and allo BMT groups. We were able to differentiate patients at high vs low risk for adverse outcomes post-BMT. This prognostic model may prove useful in predicting patient outcomes and identifying high-risk patients for novel treatment strategies. Validation of this model in a larger cohort of patients is warranted.

Adult↗

Sixteen years follow up of achalasia: a prospective study of graded dilatation using Rigiflex balloon.

Pneumatic balloon dilatation is the treatment of choice for esophageal achalasia. Rigiflex (Microvasive, Watertown, MA) polyethylene balloon dilators have been used with varying success and complications. The aim of this study was to evaluate the efficacy of graded balloon dilatation, to achieve symptomatic improvement in patients with achalasia. From January 1987 until the end of December 2003, 300 patients were evaluated and treated for achalasia, with 30 mm balloons. Patients who did not achieve satisfactory symptomatic responses during follow up underwent repeat dilatation with 35-mm balloons. They were studied at the onset then at 1 and 6 month intervals and then yearly for postdilatation symptom evaluation for dysphagia, regurgitation, night cough and heartburn. Baseline and 5-min postdilatation barium swallow studies were obtained to compare barium height and width for efficacy of dilatation and to evaluate for complications. No patients developed cancer of the esophagus in 16 years follow up. Barium height, width, composite symptom score and weight improved significantly during follow up. Two patients, who needed repeat dilatation with 35-mm balloons, developed esophageal perforation; one was successfully managed with intensive medical care management, whereas the other patient died despite surgical intervention. The authors conclude that pneumatic balloon (Rigiflex) dilatation for achalasia of the esophagus is a successful first option, when applied in an incremental balloon size to achieve desired results in symptomatic relief.

Adolescent↗

The MRI diagnosis and management of incomplete intertrochanteric fractures of the femur.

Incomplete intertrochanteric fractures do not extend across to the medial femoral cortex and are stable, without rotational deformity or shortening of the lower limb. The aim of our study was to establish whether they can be successfully managed conservatively. A total of 68 patients over a five-year period presented with a suspected fracture of the femoral neck and underwent an MRI scan for further assessment. From these, we retrospectively reviewed eight patients with normal plain radiographs but with an incomplete, intertrochanteric fracture on MRI scan. Five were managed conservatively and three operatively. The mean length of hospital stay was 16 days for the conservatively-treated group and 15 days for those who underwent surgery; this was not statistically significant (p > 0.5) and all patients were mobilised on discharge. Although five patients were readmitted at a mean of 3.2 years after discharge, none had progressed to a complete fracture. We believe that patients with incomplete intertrochanteric fractures should be considered for conservative treatment.

Aged↗

Nerve growth factor-induced protein kinase C stimulation contributes to TrkA-dependent inhibition of p75 neurotrophin receptor sphingolipid signaling.

Previous studies have established that reciprocal interactions between the low-affinity p75 nerve growth factor (NGF) receptor (p75(NTR)) and the high-affinity TrkA NGF receptor can dictate the cellular response to NGF. As the most important interaction, TrkA signaling was found to inhibit p75(NTR)-mediated sphingomyelinase (SMase) stimulation, ceramide production, and apoptosis. However, the mechanism by which TrkA counteracts p75(NTR)-coupled sphingolipid signaling is still unclear. Considering the stimulatory effect of NGF on protein kinase C (PKC) activity, we investigated the role of PKC in TrkA/p75(NTR) signaling interaction. In this study, we found that, in SK-N-BE cells, which selectively express p75(NTR), phorbol ester-induced PKC stimulation resulted in the abrogation of SMase stimulation and ceramide production induced by NGF. Moreover, in SK-N-BE neuroblastoma cells, which selectively express TrkA, NGF stimulated global PKC activity through two independent pathways involving phospholipase Cgamma (PLCgamma) and phosphoinositide-3 kinase (PI3K). In SH-SY5Y, another neuroblastoma cell line, which coexpresses TrkA and p75(NTR), NGF induced PKC stimulation through a TrkA/PI3K signaling pathway, whereas there was no ceramide production. However, in these cells, the inhibition of TrkA, PI3K, and PKC resulted in the restoration of NGF-induced ceramide production. Thus, our study demonstrates for the first time that TrkA interferes with p75(NTR) signaling through a PI3K/PKC-dependent mechanism.

Cell Line, Tumor↗

Goezia bangladeshi n. sp. (Nematoda: Anisakidae) from an anadromous fish Tenualosa ilisha (Clupeidae).

A total of 1432 hilsa shad, Tenualosa ilisha (=Hilsa ilisha) from 11 fresh water, brackish water and marine localities in Bangladesh yielded 13 adult Goezia bangladeshi n. sp., all specimens being found in the intestine of a single fish host caught in the lower Ganges. A total of 2372 Goezia juveniles were recovered from 490 infected fish (prevalence 34.2%). This is the first Goezia species recorded from Bangladesh, and it differs from other valid species by the number of caudal papillae (pre 7-9, para 3, post 6); encircled by tiny spines, the position of double papillae, the arrangement of body spines, and the length ratio of the intestinal caecum and the ventricular appendix (1: 3.33-4.72). Juveniles were free in the gut, embedded in the gut wall and encapsulated in mesenteries. Tenualosa ilisha serves as the definitive host, but the predominance of juveniles may indicate that piscivorous hosts may also serve as such. A list of the nominal Goezia species with important characters is provided.

Animals↗

Distribution of T4 TSH values in children--the Shifa experience.

OBJECTIVE: To evaluate the distribution of Thyroxin (T4) and Thyroid Stimulating Hormone (TSH) values in children of various age groups attending our hospital. METHOD: We have retrospectively reviewed the T4, TSH levels recorded at our hospital in children from birth to 5 years and evaluated the reference intervals for T4 TSH amongst different ages. Non parametric methods were used to establish a 97.5th, 95th, 50th, 5th and 2.5th centiles. RESULTS: In T4 (n=1148) and TSH (n=1142) samples reviewed a TSH surge following delivery showed a sharp decline in the first 4 days of life. This was followed by a more gradual downward trend. Data on T4 estimations showed a similar but more gradual downward trend in advancing age groups. The 5th-95th centile reference range for TSH showed values between 1.7-22.5 (0-4 days; n=992), 0.6-13.3 (5-7 days; n=38), 0.9-14.0 (1 week-1 month; n=38), 0.5-13.6 (1 month-1 year, n=38) and 0.4-12.8 (1-5 years; n=38) microlU/mL. The 5th-95th centile reference range for T4 showed values between 10.7-25.0 (0-4 days; n=995), 6.5-20.4 (5-7 days; n=35), 8.0-18.1 (1 week-1 month; n=38), 6.0-16.1 (1 month-1 year; n=41), 6.9-15.3 (1-5 years; n=39) micro gm/dl. CONCLUSION: We recommend using separate T4 and TSH reference values for children in different age groups. Further large-scale studies should be done in Pakistan to establish these reference values within age groups. A national center for neonatal thyroid screening is highly recommended.

Age Distribution↗

HIV-1 protease processes procaspase 8 to cause mitochondrial release of cytochrome c, caspase cleavage and nuclear fragmentation.

Infection of T cells with HIV-1 induces apoptosis and modulates apoptosis regulatory molecules. Similar effects occur following treatment of cells with individual HIV-1 encoded proteins. While HIV-1 protease is known to be cytotoxic, little is known of its effect on apoptosis and apoptosis regulatory molecules. The ability of HIV-1 protease to kill cells, coupled with the degenerate substrate specificity of HIV-1 protease, suggests that HIV-1 protease may activate cellular factor(s) which, in turn, induce apoptosis. We demonstrate that HIV-1 protease directly cleaves and activates procaspase 8 in T cells which is associated with cleavage of BID, mitochondrial release of cytochrome c, activation of the downstream caspases 9 and 3, cleavage of DFF and PARP and, eventually, to nuclear condensation and DNA fragmentation that are characteristic of apoptosis. The effect of HIV-1 protease is not seen in T cell extracts which have undetectable levels of procaspase 8, indicating a specificity and requirement for procaspase 8.

Apoptosis↗

A method for measuring particle number emissions from vehicles driving on the road.

Earlier research has demonstrated that the conditions of dilution of engine exhaust gases profoundly influence the size distribution and total number of particles emitted. Since real world dilution conditions are variable and therefore difficult to simulate, this research has sought to develop and validate a method for measuring particle number emissions from vehicles driving past on a road. This has been achieved successfully using carbon dioxide as a tracer of exhaust gas dilution. By subsequent adjustment of data to a constant dilution factor, it is possible to compare emissions from different vehicles using different technologies and fuels based upon real world emission data. Whilst further optimisation of the technique, especially in terms of matching the instrument response times is desirable, the measurements offer useful insights into emissions from gasoline and diesel vehicles, and the substantial proportion of particles emitted in the 3-7 nanometre size range.

Air Pollutants↗

Carpal tunnel syndrome despite negative neurophysiological studies.

The purpose of the present study was to compare the results of conservative and operative treatment for patients with carpal tunnel syndrome having normal neurophysiological studies. We studied 125 patients with normal neurophysiological studies and analysed eight symptoms and signs as "prognostic factors". Ninety-six patients were treated conservatively (splintage, steroid injection, antiinflammatory medications, activity modification) and 29 were treated surgically (open decompression). One year after initiation of treatment we assessed the outcome and statistically analysed (chi-square test) the differences between the two groups. We did not find any statistically significant correlation between "prognostic factors" and outcome. Twenty four percent of the group treated non-operatively had a good or excellent outcome, whereas 90% of the group treated operatively had a good or excellent outcome. This difference was statistically significant (p < 0.0001). Our study supports the view that the diagnosis of carpal tunnel syndrome is clinical and not neurophysiological. We now recommend operative treatment for these patients.

Adult↗

Neonatal thyroid screening--the Shifa experience.

OBJECTIVE: To evaluate the results of T4, TSH analysis and pattern of presentation in babies born at our hospital. METHOD: We retrospectively reviewed the data collected from T4, TSH screening on all babies delivered at our Hospital, where the blood was drawn within the first 4 days of life. Period under evaluation was from October 1995 to October 1998. Shifa Reference values were used. RESULTS: Blood sample were collected from 997 babies within 4 days of birth. Nine hundred and forty nine (95.2%) were evaluated after 24 hours. and 48(4.8%) in less than 24 hours of age. A high TSH was reported on 166 (16.8%) babies and a low T4 was reported on 78 (7.9%) babies. Statistical analysis showed a similar sensitivity for T4 and TSH (100%) but a higher specificity for T4 (93.1%) as compared to TSH (86%). A high-TSH with a low T4 was reported in 5 (0.5%) babies out of which 1 case was confirmed as congenital hypothyroidism requiring permanent thyroxin replacement and one case manifested a picture consistent with transient hypothyroidism. A low TSH with a low T4 was seen in 2 cases, however, they were all premature babies on antibiotics. CONCLUSION: Congenital hypothyroidism may be more frequent in our population and for the purpose of screening babies T4 values would carry a higher positive predictive value than TSH. Combining T4 TSH assays would however reduce the call back rate quite significantly but may prove to be a bit more expensive.

Congenital Hypothyroidism↗

Correlation of Helicobacter pylori in dental plaque and gastric mucosa of dyspeptic patients.

OBJECTIVE: To establish the prevalence of Helicobacter pylori colonization of dental plaque and its correlation with Helicobacter pylori infection of the antral mucosa in patients with symptomatic dyspepsia. METHODS: Seventy eight adult dyspeptic patients undergoing upper gastrointestinal tract endoscopy were prospectively enrolled. Four air dried dental plaque cytology slides and four gastric antral mucosal biopsies were stained with Giemsa stain. CLO test was used for detection of urease activity of Helicobacter pylori in the dental plaque specimens and antral mucosal biopsies. Data on endoscopic findings and orodental hygiene were recorded. RESULTS: Dental plaque colonization using CLO test and cytology was found to be 100% and 88% respectively. Antral biopsy for H. pylori was positive in 61% cases by CLO test and 57% cases on histopathology. Forty four out of 69 patients (63%) had both dental plaque and antral biopsy positive for H. pylori. No patient with negative dental plaque cytology was positive for H. pylori in gastric mucosa. A statistically significant correlation was found between H. pylori colonization of dental plaque and gastric antrum. The sensitivity and specificity of dental plaque cytology in diagnosing H. pylori antral colonization was 100% and 26% while the positive and negative predictive values were 64% and 100% respectively. CONCLUSION: The prevalence of H. pylori in dental plaque of patients with dyspepsia was very high in our patients indicating it to be a major reservoir of infection.

Adult↗

Direct cleavage of the human DNA fragmentation factor-45 by granzyme B induces caspase-activated DNase release and DNA fragmentation.

The protease granzyme B (GrB) plays a key role in the cytocidal activity during cytotoxic T lymphocyte (CTL)-mediated programmed cell death. Multiple caspases have been identified as direct substrates for GrB, suggesting that the activation of caspases constitutes an important event during CTL-induced cell death. However, recent studies have provided evidence for caspase-independent pathway(s) during CTL-mediated apoptosis. In this study, we demonstrate caspase-independent and direct cleavage of the 45 kDa unit of DNA fragmentation factor (DFF45) by GrB both in vitro and in vivo. Using a novel and selective caspase-3 inhibitor, we show the ability of GrB to process DFF45 directly and mediate DNA fragmentation in the absence of caspase-3 activity. Furthermore, studies with DFF45 mutants reveal that both caspase-3 and GrB share a common cleavage site, which is necessary and sufficient to induce DNA fragmentation in target cells during apoptosis. Together, our data suggest that CTLs possess alternative mechanism(s) for inducing DNA fragmentation without the requirement for caspases.

Apoptosis↗

Asafoetida inhibits early events of carcinogenesis: a chemopreventive study.

Ferula (a genus of many species) commonly known as asafoetida is used as a flavoring agent in food and is used as a traditional medicine for many diseases in many parts of world. In the current investigation, we report the antioxidant and anticarcinogenic potential of asafoetida (Ferula narthex) in swiss albino mice. A single dose of TPA (20 nmol/0.2 ml acetone/animal), a known tumor promoter decreased the cellular antioxidant level significantly (p<0.01) when applied topically to mice skin. It also induced the ODC activity, rate of DNA synthesis, hydrogen peroxide level, xanthine oxidase activity and protein carbonyl content in mice skin significantly (p<0.01). These events are early biomarkers of carcinogenesis. However, the pretreatment of animals with asafoetida (300, 400 and 500 microg/200 microl acetone/animal) caused the reversal of all events significantly (p<0.01). The pretreament of animals with asafoetida recovered the antioxidant level and reversed the induced ODC activity and DNA synthesis significantly (p<0.01). We conclude that asafoetida is a potent antioxidant and can afford protection against free radical mediated diseases such as carcinogenesis.

Administration, Topical↗

Treatment failure with the use of ciprofloxacin for gonorrhea correlates with the prevalence of fluoroquinolone-resistant Neisseria gonorrhoeae strains in Bangladesh.

Although ciprofloxacin is one of the recommended drugs of choice for the treatment of gonorrhea, in vitro resistance to this drug has been observed in surveillance studies and case reports from many parts of the world, including Bangladesh. However, to our knowledge, there have been no prospective studies of the correlation between in vitro response to the drug and treatment outcome. Therefore, a prospective study of 217 female sex workers in Dhaka, Bangladesh, was conducted to examine the correlation between the in vitro response of Neisseria gonorrhoeae and the outcome of ciprofloxacin treatment. Overall, 37.8% of the gonococcal isolates recovered from female sex workers were resistant to ciprofloxacin, and there was a good correlation between in vitro resistance and treatment failure. These findings suggest that in vitro resistance to ciprofloxacin is predictive of clinical treatment failure in patients with gonorrhea.

Adult↗