Is TNFalpha really a good therapeutic target in motoneuronal degeneration? A case of amyotrophic lateral sclerosis in a patient with RA receiving infliximab.
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Biomedical subjects
Publications and source records attributed to S Rahman.
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Cyclophosphamide (CP) is a commonly used anti-cancer drug which causes toxicity by its reactive metabolites such as acrolein and phosphoramide mustard. In the present study modulation of toxicity caused by concomitant exposure to CP and l-buthionine-SR-sulfoximine (BSO) by fenugreek (Trigonella foenum-graecum L.) extract was evaluated by measuring lipid peroxidation (LPO) and anti-oxidants in urinary bladder in mice. Fenugreek, a common dietary and medicinal herb, showed protective effect not only on LPO but also on the enzymatic anti-oxidants. CP-treated animals exhibited a significant decrease in the activities of glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GP) and catalase (CAT) when compared to the controls. Level of reduced glutathione (GSH) was also reduced with an increase in LPO in CP-treated animals. BSO treatment depicted an additive toxic effect in CP-treated animals. Pre-treatment of herbal extract restored activities of all the enzymes and thus showed an overall protective effect on additive effect of CP and BSO. Restoration of GSH by extract treatment may play an important role in reversing CP-induced apoptosis and free radical-mediated LPO in urinary bladder. Fenugreek, known for its hypoglycemic, anti-inflammatory and immunomodulatory activity, may be a promising protective medicinal herb for consideration in complementary therapy in cancer patients under chemotherapeutic interventions.
Significant progress has been made in reducing the risk from exposure to radon and its progeny all over the world as a result of efforts made by different organisations which are working together to educate public about the harmful effects of radon. During the past several surveys, it was found that uneducated people were totally ignorant of radon in Pakistan. Even a large number of science graduates knew very little about radon and its hazards. Therefore, a nationwide survey was conducted to measure general awareness and factual knowledge about radon and its health hazards. In this regard, a questionnaire was prepared and distributed among different classes of the society including students, government employees and general public throughout the country. A total of 7000 people with different educational backgrounds participated in this survey, which includes uneducated people (1000), science and humanities graduates (2000 each) and under graduate (2000). Statistical analysis, excluding uneducated people, revealed that 30.4% of the total respondents were aware of radon and 69.6% had even not heard of radon. Only approximately 8.4% of the total respondents were knowledgeably aware of radon.
A 40 years old, married Govt. servant from Sadar upazila, Mymensingh was admitted in Mymensingh Medical College Hospital on 9(th) February, 2005 with the complaints of excessive sweating for 1 year, gradual loss of weight for 6 months, swelling in front of the neck for 1(1/2) months, and hoarseness of voice for 1 month. He was nervous, irritable, emotionally labile. Thyroid gland was symmetrically enlarged, firm in consistency with scalloped surface. Palms were warm and sweaty with fine tremor in outstretched hands. Lid lag, lid retraction and proptosis were the occular manifestations. All the reflexes were exaggerated. Radioactive iodine uptake showed enlarged gland with homogenously increased radiotracer concentration, ultrasonogram findings were enlarged gland with hypoechoic parenchyma with fibrous septa, T(3), T(4), TSH values were 6.56 nmol/L, 241.09 nmol/L and 0.14 mIU/L respectively. Thyroid microsomal antibody level was 32.87%. Thyroid FNAC findings were sheets of regular follicular cells, some large cells with granular basophilic cytoplasm, macrophages, a few inflammatory cells and giant cells. All the above findings were in favour of a diagnosis of hyperthyroid Graves' with Hashimoto's thyroiditis.
A prospective study was done on 54 patients aged over 6 months with cleft lip with or without cleft palate admitted in the department of pediatric surgery of Mymensingh Medical College Hospital during the period from Oct 2002 to Dec 2004. The anthropometrical surgical outcome was evaluated by measuring the length, diameter and thickness of hemilip and diameter of nostril both pre and postoperatively (according to schedule). Patients were categorized into three groups according to their age. Mean Corrective rate was evaluated and it was shown 95% in the 1(st) age group, 93% in 2(nd) age group and 95.55% in the 3(rd) group. Complication was evaluated in only 16.66% of patients. Regarding the out come scar, cupid's bow, notching, labial and nasal symmetry were taken in consideration. Beside these this study might play a comparative role with the results of correction of cleft lip in early age.
Prospective study was carried out on 100 patients since May 2005 in my private practice and in the department of pediatric surgery of MMCH. Under caudal anesthesia along with or without ketaminie induction and gas inhalation all the patients underwent different surgical procedure namely anorectal surgery (eg. anoplasty, rectal polyp), urogenital surgery (Circumcision, hypospadias, meatotomy), groin surgery (hernia, hydrocele) and foot & leg surgery. Calculated dose schedule of drugs used in anesthesia and volume were maintained. Time of giving anesthesia and time of starting analgesia were recorded. Per-operative and postoperative analgesia were evaluated. Every parent was explained regarding the merit of caudal anesthesia calculated and compared with that of general anesthesia. Application of caudal anesthesia with or without ketamine & diazepam induction can be used safely and cost effectively and may be put into protocol in many of the pediatric surgical practice both in institute and also in private practice.
The purpose of the study was to formulate biodegradable intrapocket dental films, which could be easily placed into the periodontal pocket, and be capable of delivering therapeutic concentrations of amoxycillin and metronidazole for prolonged period of time with a much lower dose, hence obviating untoward side effects. A biodegradable intrapocket device containing amoxycillin and metronidazole was prepared using 69.29 mg each of amoxycillin and metronidazole, 2.0% diethyl phthalate plasticizer and 750 mg poly (L-lactide-co-glycolide). The device was optimized on the basis of evaluation parameters such as weight variation, content uniformity, surface pH, and in vitro and in vivo release studies. The films showed sustained in vitro release for a period of 16 days. In vivo release studies showed that drug concentrations were maintained above the MIC value for the entire period of the release studies. The samples from this study were capable of inhibiting the growth of most test strains. The combination of amoxycillin and metronidazole in the carrier polymer poly (L-lactide-co-glycolide) not only showed an extended spectrum of antimicrobial activity but also showed a synergistic effect against E. limosum, which had been reported the resistant to metronidazole in earlier studies. Stability studies were conducted on the optimized formulation and the degradation rate constant was found to be 4.6 x 10(-4)/day for metronidazole and 4.8 x 10-4)/day for amoxycillin. The drug was released locally and had a high benefit to low risk ratio as compared to systemic administration which is unacceptable due to, low benefit to high-risk ratio. Hence low-dose site-specific films present a better alternative.
We performed detailed clinical, histopathological, biochemical, in vitro translation and molecular genetic analysis in patients from two unrelated families harbouring the tRNA(SerUCN) 7472C-insertion mutation. Proband 1 developed a progressive neurodegenerative phenotype characterised by myoclonus, epilepsy, cerebellar ataxia and progressive hearing loss. Proband 2 had a comparatively benign phenotype characterised by isolated myopathy with exercise intolerance. Both patients had the 7472C-insertion mutation in identical proportions and they exhibited a similar muscle biochemical and histopathological phenotype. However, proband 2 also had a previously unreported homoplasmic A to C transition at nucleotide position 7472 in the tRNA(SerUCN) gene. This change lengthens further the homopolymeric C run already expanded by the 7472C-insertion. These data extend the phenotypic range associated with the 7472C-insertion to include isolated skeletal myopathy, as well as a MERRF-like phenotype.
AIM: To test the null hypothesis that Carisolv is no more effective than 1% sodium hypochlorite in cleaning uninstrumented, immature root canals. METHODOLOGY: A total of 240 uniform, immature ovine incisors were decoronated at the CEJ level and randomly divided into four groups of 60. After gross pulp extirpation, canals were flooded with normal saline (negative control), 1% NaOCl, Carisolv or 5% NaOCl (positive control) and incubated for 10 min (group 1), 20 min (group 2), 30 min (group 3) or 30 min, refreshing irrigant at 10 and 20 min (group 4). SEM photomicrographs of canal wall debris in the apical, middle and coronal thirds were scored against a 5-point scale. Internal consistency was assessed by kappa statistics. Debris scores for different irrigant regimes at different canal levels were analysed by non-parametric tests (P < 0.05). RESULTS: Canals were consistently cleaner in the coronal and middle than apical thirds. NaOCl (5%) was consistently most effective. Carisolv and NaOCl (1%) were no more effective than normal saline in group 1 (P > 0.05), but significantly more effective than normal saline in groups 2 (middle and apical 1/3), 3 and 4 (P < 0.05). Carisolv and NaOCl (1%) had comparable activity in groups 1, 2 (middle and apical thirds) and 3, but NaOCl (1%) was significantly more effective than Carisolv in group 4 (coronal and middle thirds). CONCLUSIONS: 1. The ovine incisor model presents opportunities to investigate irrigation regimes under controlled ex-vivo conditions. 2.NaOCl (5%) remains the most effective irrigant for rapid debris removal in immature root canals. 3. Carisolv cleans pulp debris from the walls of immature root canals as effectively as NaOCl (1%) during static, unrefreshed wall contact for between 20 and 30 min. 4. Refreshment of NaOCl (1%) enhances its cleaning ability above that of Carisolv.
The purpose of this study was to compare the echocardiographic outcome of percutaneous transvenous metallic mitral commissurotomy (PMMC) and Percutaneous transvenous balloon mitral commissurotomy (PTMC). This prospective comparative study was carried out during the period of January 1999 to June 2000 in the department of Cardiology, National Institute of cardiovascular diseases (NICVD) and national heart foundation hospital, Dhaka Bangladesh. Two dimension, M-mode, spectral and colour Doppler studies were done to all patient of mitral stenosis both before and after PMMC and PTMC. The increased in mitral valve area in PMMC was statistically significant than PTMC. (P<0.047).
The aim of this study is to evaluate the effectiveness of lamivudine treatment in both precore mutant and wild type of chronic hepatitis B (CHB) patients. The study was done on sixty CHB patients of both sexes seeking treatment in the Outpatient Department and admitted patients of Mymensingh Medical College Hospital. The patients were divided into two groups. Group A included chronic hepatitis B patients with raised ALT (> 80 u/l ) with HBeAg positivity, and group B included precore mutant variety of CHB patients with raised ALT (> 80 u/l) with HBeAg negativity. In Group-A, after 1 year of completion of lamivudine therapy there was 86.67% normalization of ALT, 23.33% HBeAg loss, 16.67% anti-HBeAg development and 73.33% HBV DNA loss. In Group-B, there was 76.67% normalization of ALT and 73.33% HBV DNA loss after 1 year of completion of therapy. In the present study, it was observed that lamivudine is equally effective in both wild and precore mutant variety of CHB patients. This was reflected by normalization of ALT and loss of HBV DNA. This study also shows the reappearance of HBV DNA during the later half of Lamivudine therapy which is due to YMDD mutation.
Coronary angiographic characteristics of fifty patients with type 2 diabetes mellitus and coronary artery disease (CAD) were compared with fifty non diabetic patients with CAD. Type 2 diabetic patients undergoing clinically indicated elective coronary angiography were individually matched with fifty non diabetic coronary artery disease patients for age, sex and major risk factors. No significant difference was present between the mean age, presenting complains and other coronary risk factors between the two groups. Severity and extent of coronary artery involvement was assessed by a coronary artery score (CAS) using the segmental distribution method for coronary artery lesions and morphometric analysis of atherosclerotic lesion was done. Type 2 diabetic patients had a higher CAS (11.74+/-5.04 vs 8.72+/-4.87; P<0.001) as compared to the non-diabetic patients. Multivessel disease were more prevalent in both the groups (82% vs 68%; P>0.05) but diabetic patients had significantly higher number of triple vessel disease (58% vs. 38%; P<0.001). Normal coronary arteries and single vessel disease were more prevalent in non-diabetic patients (32% vs. 18%; P<0.05). As compared to non-diabetic group diabetic patients had a higher total number of diseased vessels (78.66% vs. 68%; P<0.01), a higher lesion per patient ratio (3.94+/-1.80 vs 3+/-1.67:P<0.001) and more proximal lesions (40.83% vs. 34.70%; P>.05) though not statistically significant. Morphometric analysis of coronary artery lesions revealed that diabetic patients had significantly higher number of multiple irregularity lesions (24.37% vs. 15.33%; P<0.01) and lesions were more obstructive (lesion involving 70-90% of coronary lumen: 70.53.% vs. 57.33%; P<0.05). Though there was no significant difference between the systolic left ventricular function between the two groups but significant higher regional wall motion abnormality was found more in diabetic patients (76%vs 62%; P<0.01). So type 2 diabetic patients had more severe and extensive atherosclerotic lesion in their coronary arteries than the matched non diabetic control on coronary angiography suggesting an independent effect of diabetic mellitus on atherosclerotic process specially in our population.
Eighteen adult patients of systemic sclerosis were included in this prospective study from Rheumatology Clinic of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka during the period of July 1997 to December 1999 to observe the effectiveness of treatment with methotrexate (MTX) versus placebo. Among the eighteen patients 9 patients were randomly assigned to MTX and 9 to placebo therapy. Nine patients were dropped out (6 in placebo and 3 in the MTX group), because of toxicity and non-compliance. Clinical improvement following treatment was observed in 33.33% of the patient in MTX group but none in placebo group, but this difference was not statistically significant. Anorexia, nausea and occasional vomiting were common side effects in MTX group and subsided in most cases with the passage of time despite the continuation of therapy.
A 30 years old, non-alcoholic farmer from Trishal, Mymensingh was admitted in Mymensingh Medical College Hospital on 7 February, 2004 with the complaints of gradual swelling of abdomen, both legs and upper abdominal pain for 3 months. For the last 6 years, he was treated as a case of chronic liver disease (CLD) with spironolactone and frusemide. He was non-icteric, mildly anaemic with mild oedema, clubbing, gynaecomastia and engorged vein over anterior abdominal wall, flanks and back. Direction of venous flow was from below upward. There were mild hepatosplenomegaly, ascites and bilateral testicular atrophy. He was diagnosed as a case of Budd-Chiari Syndrome (BCS) on the basis of physical examination and it was confirmed by the findings of ultrasonography, liver scan and doppler study. The patient was managed by medical therapy alone.
Association of serum Interleukin -2 (IL-2) levels with the activity of chronic hepatitis B (CHB) was evaluated in this study. We studied 45 subjects in the Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka. They were divided into three groups. Group A consisted of 15 CHB patients with raised Alanine aminotrasferase (ALT) (> 80 iu/L), Group B consisted of 15 CHB carrier with normal ALT (< or =40 iu/L) and Group C consisted of 15 healthy subjects with normal ALT. Serum IL-2 level was measured in all groups. IL-2 level was detected in 14(93.33%) subjects in group A and 2(13.33%) subjects in group B. IL-2 level was undetectable in all the subjects in group C. The association between IL-2 level and activity of chronic hepatitis B was observed by statistical analysis (Z-test). There is significant difference between group A and group B (p<0.001) and also in group A and group C (p<0.001), but no significant difference between group B and group C (p>0.05). Our results support the observation that IL-2 level can be used as a marker of activity in CHB patients as IL-2 level was significantly detected in the patients of group A.
Hormone Replacement Therapy (HRT), once considered as the gold standard of treatment of menopausal symptoms and osteoporosis, introduced about seventy years ago still continuing with lot of controversies. Menopause, a transitional period of women's life, is not an illness when oestrogen level falls leading to its consequences. Results of earlier observational studies showed beneficial effects of HRT including cardiovascular protection. But all recent randomized controlled trials have failed to prove these positive effects, rather increases the cardiovascular risk and breast cancer. Women's Health Initiative(WHI), one of the recent randomized controlled trials was stopped prematurely in 2002 due to unfavorable risk-benefit ratio. HRT is not the only way of treating the menopausal symptoms and other consequences of estrogen deficiency. There are suitable alternatives without bearing the risk of HRT. Vasomotor symptoms with hot flushes and sweating experienced by about 75 percent of menopausal women can be treated with alternatives like phyto-estrogens, selective estrogen receptor modulators (SERMs), clonidine, selective serotonin reuptake inhibitors, acupuncture, exercise, behavioral therapy etc. HRT is no longer considered as the first line of treatment of postmenopausal osteoporosis. It can be treated with alternatives like regular weight bearing exercise, balanced calcium rich diet, maintaining weight, avoidance of bone robbers, (like excess alcohol, caffeine, smoking), use of SERMs etc. Use of HRT should be individualized and rationalized considering its risks and benefits.
OBJECTIVES: In May 2001, a maximum exposure limit (MEL) for flour dust was set in the UK at 10 mg/m(3) [8 h time-weighted average (TWA)] with a short-term exposure limit (STEL) of 30 mg/m(3) (15 min reference period). The purpose of this study was to produce a benchmarking baseline of current control measures and exposure levels, in addition to assessing the provision of training and the knowledge of the UK regulations amongst the bakeries. METHODS: A total of 208 long-term personal inhalable dust samples (8 h TWA) were collected from workers in 55 bakeries (covering a wide range of industry types and sizes) between October 2002 and December 2003 in England, Wales and Scotland. Standardized occupational hygiene reports were produced for each establishment to provide information about the site (such as the size of the bakery) and the control measures employed (including ventilation, good working practices, knowledge of UK regulations and the extent of training provided). RESULTS: Median inhalable dust exposure (8 h TWA) for the bakery workers was 3.7 mg/m(3) (75th percentile at 7.7 mg/m(3)) and 17% of the dust results exceeded the MEL. Although information about the MEL has been available in the trade press and through recognised trade associations, only 27% of the bakeries were aware of the MEL and STEL. Mixed model regression analysis suggested that determinants of higher exposure included the job category (particularly weighing/sieving or mixing), medium to large bakery size (50 or more employees) and bakeries being located in Scotland. However, having an appointed safety representative was associated with lower exposure. CONCLUSIONS: The conclusions derived here are based upon the use of a statistical model, but clearly, if bakeries and individuals employ good working practices, with correct use of local exhaust ventilation, they should be able to comply with the MEL.
This paper reports the characterization of the low-molecular-weight (LMW) glutenin gene family of Aegilops tauschii (syn. Triticum tauschii), the D-genome donor of hexaploid wheat. By analysis of bacterial artificial chromosome (BAC) clones positive for hybridization with an LMW glutenin probe, seven unique LMW glutenin genes were identified. These genes were sequenced, including their untranslated 3' and 5' flanking regions. The deduced amino acid sequences of the genes revealed four putative active genes and three pseudogenes. All these genes had a very high level of similarity to LMW glutenins characterized in hexaploid wheat. The predicted molecular weights of the mature proteins were between 32.2 kDa and 39.6 kDa, and the predicted isoelectric points of the proteins were between 7.53 and 8.06. All the deduced proteins were of the LMW-m type. The organization of the seven LMW glutenin genes appears to be interspersed over at least several hundred kilo base pairs, as indicated by the presence of only one gene or pseudogene per BAC clone. Southern blot analysis of genomic DNA of Ae. tauschii and the BAC clones containing the seven LMW glutenin genes indicated that the BAC clones contained all LMW glutenin-hybridizing bands present in the genome. Two-dimensional gel electrophoresis of an LMW glutenin extract from Ae. tauschii was conducted and showed the presence of at least 11 distinct proteins. Further analysis indicated that some of the observed proteins were modified gliadins. These results suggest that the actual number of typical LMW glutenins may in fact be much lower than previously thought, with a number of modified gliadins also being present in the polymeric fraction.