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Biomedical subjects

M Ahmed

Publications and source records attributed to M Ahmed.

At least 127 records · Page 7Linked to original sources

Closed reduction of posterior dislocation of the elbow: a simple technique.

A simple technique is described for closed reduction of posterior dislocation of the elbow in the supine position without anesthesia or the help of an assistant. The main feature of this technique is gentle disengagement of the coronoid process from the lower humerus and control over the olecranon during reduction. There is less likelihood of soft tissue damage by avoiding traction and hyperextension. This technique is safe, simple, and easily learned and has a high success rate.

Humans↗

Factors associated with progression of the disease before transplantation in patients with autoimmune hepatitis.

AIMS/BACKGROUND: Studies on transplanted patients may provide clinically useful data on factors influencing progression of autoimmune hepatitis (AIH) since transplantation rather than death may now be considered as the most likely end-point of the disease. The aim of this work was to analyze risk factors related to progression of AIH before transplantation and provide guidelines for further prognostication with regards to the timing of transplantation. METHODS: 80 liver transplants in 68 patients with AIH were performed in our unit. The diagnosis was established on conventional clinical criteria. Parameters such as sex, age at diagnosis and transplantation or duration of the disease were evaluated in relation to: patient HLA DR status, disease presentation (aggressive or non-aggressive), presence of anti-LKM antibodies and concurrent immune disease. RESULTS: AIH with concurrent immune disease occurred more commonly in females (90 vs. 61%; p = 0.0075) and was linked with markedly slower progression of the disease (125 vs. 66 mo; p = 0.002) as compared to subjects without such association. AIH without concurrent autoimmune disease occurred significantly more commonly in patients with DR3 phenotype (p = 0.01). Patients with positive anti-LKM autoantibodies were younger at transplantation (25.6 vs. 43.5 yr; p = 0.006) and had more rapid progression of their disease (14.3 vs. 103 mo; p = 0.001). Unlike previously reported series of non-transplanted patients, all anti-LKM positive subjects had no concurrent autoimmune disease. CONCLUSIONS: Coincidence with another autoimmune disease is associated with a significantly longer disease history prior to transplantation and may possibly reflect greater responsiveness to immunosuppressive therapy before grafting. AIH without concurrent autoimmune disease, particularly if associated with DR4 negative phenotype, male sex and anti-LKM antibodies may characterize patients with rapid progression of the disease. None of these factors had a significant influence on 5 year survival after surgery.

Adult↗

Antimicrobial susceptibilities and plasmid contents of Neisseria gonorrhoeae isolates from commercial sex workers in Dhaka, Bangladesh: emergence of high-level resistance to ciprofloxacin.

Commercial sex workers (CSWs) serve as the most important reservoir of sexually transmitted diseases (STD), including gonorrhea. Periodic monitoring of the antimicrobial susceptibility profile of Neisseria gonorrhoeae in a high-risk population provides essential clues regarding the rapidly changing pattern of antimicrobial susceptibilities. A study concerning the prevalence of gonococcal infection among CSWs was conducted in Bangladesh. The isolates were examined with regards to their antimicrobial susceptibility to, and the MICs of, penicillin, tetracycline, ciprofloxacin, cefuroxime, ceftriaxone, and spectinomycin by disk diffusion and agar dilution methods. The total plasmid profile of the isolates was also analyzed. Of the 224 CSWs, 94 (42%) were culture positive for N. gonorrhoeae. There was a good correlation between the results of the disk diffusion and agar dilution methods. Some 66% of the isolates were resistant to penicillin, and 34% were moderately susceptible to penicillin. Among the resistant isolates, 23.4% were penicillinase-producing N. gonorrhoeae (PPNG). 60.6% of the isolates were resistant and 38.3% were moderately susceptible to tetracycline, 17.5% were tetracycline-resistant N. gonorrhoeae, 11.7% were resistant and 26.6% had reduced susceptibility to ciprofloxacin, 2.1% were resistant and 11.7% had reduced susceptibility to cefuroxime, and 1% were resistant to ceftriaxone. All PPNG isolates contained a 3.2-MDa African type of plasmid, and a 24.2-MDa conjugative plasmid was present in 34.1% of the isolates. Since quinolones such as ciprofloxacin are recommended as the first line of therapy for gonorrhea, the emergence of significant resistance to ciprofloxacin will limit the usefulness of this drug for treatment of gonorrhea in Bangladesh.

Anti-Infective Agents↗

Clinical significance of cytomegalovirus-specific T helper responses and cytokine production in lung transplant recipients.

Cytomegalovirus (CMV) disease continues to be a major problem for lung transplant recipients. In CMV-seropositive individuals, we detected two types of CMV-specific responses: a self-restricted response stimulated by soluble CMV antigen (sCMV-Ag) and a non-self-restricted response induced by CMV-infected cells (cCMV-Ag). Lung transplant recipients who develop the CMV-specific self-restricted T helper response have a low risk of recurrent CMV disease. In contrast, during CMV disease, lung transplant recipients exhibit only the non-self-restricted T helper responses. We characterized the T cell activation and the kinetics of cytokine production of sorted CD4+ and CD8+ T cells from PBLs of CMV seropositive donors. The two types of CMV antigens induced cytokine production in both T cell subsets. We also performed competitive RT-PCR for Granzyme B (GB) in BAL cells of lung transplant recipients prior to, during and following CMV disease. CMV disease was associated with increase in GB gene expression when was accompanied by acute cellular rejection while it remained low in patients with CMV disease that did not have a complicated course. In summary, CMV-activated T cells within the allograft may produce inflammatory cytokines and effector molecules that may promote allograft rejection.

Antigens, CD↗

Hydrogen peroxide in the lung parenchyma stimulates vagally mediated phrenic activity.

STUDY OBJECTIVE: To elucidate the mechanism of hyperpnea and tachypnea, which are the common findings in cardiopulmonary patients. RATIONALE: Recently, it was found that activating pulmonary afferents by directly injecting hypertonic saline solution into the lung periphery causes a vagally mediated neural hyperpnea and tachypnea, ie, the excitatory lung reflex. Since reactive oxygen species are released during a variety of pulmonary diseases, we examined whether hydrogen peroxide (H(2)O(2)), a common mediator in cardiopulmonary diseases, can initiate the same excitatory lung reflex. MEASUREMENTS AND RESULTS: We recorded phrenic efferent activity in anesthetized, open chest, artificially ventilated rabbits as an index of respiratory drive and examined the respiratory responses to injections of H(2)O(2) (10 micromol in 0.1 mL). The responses were compared with those to hypertonic saline solution (8.1%, 0.1 mL). H(2)O(2) and hypertonic saline solution increased both the rate (mean [+/- SEM], 43 +/- 8% and 61 +/- 10%, respectively; n = 30; p = 0.001) and the amplitude of phrenic bursts (12 +/- 2% and 20 +/- 4%, respectively; n = 30; p = 0.033). These responses were abolished by bilateral vagotomy. CONCLUSION: H(2)O(2) can initiate the excitatory lung reflex. Therefore, mediator(s) released in pulmonary diseases could be one of the mechanisms causing hyperpnea and tachypnea.

Animals↗

Amino acid transformation of oscillatory Ca2+ signals in mouse pancreatic beta-cells.

Glucose-induced increase of cytoplasmic Ca2+ in pancreatic beta-cells is usually manifested as slow oscillations from the basal level. The significance of this rhythmicity for maintaining normal beta-cell function with periodic variations of circulating insulin made it of interest to investigate how the oscillatory Ca2+ signal was affected by various amino acids. Individual mouse beta-cells were very sensitive to alanine, glycine and arginine, sometimes responding with a transformation of the oscillations into sustained elevation of cytoplasmic Ca2+ at amino acid concentrations as low as 0.1 mM. Stimulation of the entry of Ca2+, obtained either by raising the extracellular concentration or by prolonging the open state of the voltage-dependent Ca2+ channels with BAY K 8644, resulted in reappearance of the rhythmic activity in the presence of the amino acids. Oscillatory Ca2+ signals in intact islets were more resistant to transformation by amino acids than those of individual beta-cells. It is therefore suggested that signals from the adjacent cells make it possible for beta-cells situated in islets to overcome a suppression of the oscillatory activity otherwise seen in the presence of alanine, glycine or arginine.

Alanine↗

Murine antibodies against E2 and hypervariable region 1 cross-reactively capture hepatitis C virus.

The absence of readily available animal and cell culture models for hepatitis C virus (HCV) replication has bottlenecked research on protective immunity to HCV infection. Antibodies reactive with HCV virions in vitro are assumed to be candidates for neutralizing or inhibitory antibodies against HCV. To find potentially neutralizing or inhibitory antibody candidates, anti-C, anti-E1, anti-E2, and anti-HVR1 antisera acquired from mice immunized with corresponding recombinant proteins or synthetic peptides were used to capture HCV viral particles in vitro based on antibody-virus interaction assays. Both anti-E2 and anti-HVR1 antibodies effectively captured HCV in vitro. Furthermore, it was found that anti-E2 and anti-HVR1 antibodies could immunoprecipitate an isolate of HCV unrelated to the original antigenic HCV isolate. ELISA confirmed that anti-HVR1 antibodies cross-reactively bind to these unrelated HVR1 peptides. These findings suggest that anti-E2 and anti-HVR1 antibodies induced in mice have the ability to bind with HCV particles in an isolate cross-reactive manner and highlight the possible application of combining several sequences of HVR1 to generate broadly reactive anti-HVR1 antibodies.

Amino Acid Sequence↗

Neuropeptide Y concentrations in experimental Leishmania major cutaneous leishmaniasis.

Neuropeptide Y (NPY) concentrations were investigated by radioimmunoassay and immunohistochemistry in a murine model of cutaneous leishmaniasis, using a susceptible (BALB/c) and a resistant (C57BL/6) mouse strain. The analyses were performed on the skin, secondary lymphoid organs and dorsal root ganglia (DRG) at 1, 3, 6 and 9 weeks postinfection. An overall reduction in the NPY concentrations in the studied organs was observed in both mouse strains; the reduction in the skin and draining lymph nodes was more evident and progressive in the susceptible strain. Using immunohistochemistry there seemed to be a reduction in NPY immunoreactivity in all inflamed tissues analysed compared to the controls. These observations might indicate a possible pathophysiological role for NPY in murine cutaneous leishmaniasis.

Animals↗

Decreased concentrations of CGRP in Leishmania major murine cutaneous leishmaniasis.

The expression of the sensory neuropeptide calcitonin gene-related peptide (CGRP) in the skin, secondary lymphoid organs and dorsal root ganglia (L4-L6) in Leishmania major-induced inflammation was evaluated by radioimmunoassay. The investigation was conducted on two mouse strains, the susceptible BALB/c and the resistant C57BL/6. The CGRP concentration in the inflamed skin of both mouse strains was decreased as early as 1 week postinfection, compared to controls. A further reduction was observed in both mouse strains throughout the 9-week study period, but was more evident in the susceptible strain. The CGRP concentration was increased in the ipsilateral dorsal root ganglia (L4-L6) of mice of the resistant strain 1 week postinfection, while no change was observed in the susceptible strain. In the remaining part of the study period there was a reduction in CGRP in the ipsilateral dorsal root ganglia of both mouse strains. In the spleen, a reduction was noted in the infected BALB/c at all measurement times (significant at 6 and 9 weeks), while no change was observed in C57BL/6 strain. These findings may indicate a regulatory function of CGRP in the pathophysiology of murine cutaneous leishmaniasis and hence in the disease outcome. The reduction in CGRP might also explain the defective nociception observed in patients with cutaneous leishmaniasis.

Animals↗

BCR-ABL and constitutively active erythropoietin receptor (cEpoR) activate distinct mechanisms for growth factor-independence and inhibition of apoptosis in Ba/F3 cell line.

The interleukin-3 dependent murine Ba/F3 cell line has been widely used as an experimental model of cell transformation by BCR-ABL oncogenes as assessed by induction of growth-factor-independence and inhibition of apoptosis in vitro. The signaling pathways used by BCR-ABL oncogenes to exert these effects are unknown. To gain insights into this phenomenon, we have introduced the p190- and p210-encoding BCR-ABL oncogenes as well as the constitutively activated oncogenic murine erythropoietin receptor (cEpoR) into Ba/F3 and compared the behavior of individual clones in response to apoptotic stimuli. Both p210 and p190 BCR-ABL vectors induced IL-3-independent growth and the same result was obtained with the cEpo-R vector. Individual clones of Ba/F3 cells expressing BCR-ABL exhibited significant resistance to apoptosis induced by either etoposide, serum deprivation or growth-factor withdrawal. In contrast, Ba/F3 cells expressing the constitutively active cEpoR behaved like parental Ba/F3 cells undergoing apoptosis when similarly treated with etoposide or upon serum deprivation. Bc12 and Bax levels were similar in all BCR-ABL and cEpoR-transfected clones. However, in band-shift assays, nuclear extracts from growth-factor-independent Ba/F3 clones expressing cEpoR had no detectable STAT activity as opposed to the constitutive STAT activation detected in all Ba/F3 clones expressing p210 or p190 BCR-ABL. Our results indicate that although both constitutively activated cEpoR and BCR-ABL oncogenes induce growth-factor independence in Ba/F3 cells, only BCR-ABL is able to protect cells from etoposide and serum-deprivation-induced apoptosis and induce a strong constitutive activation of STAT factors, suggesting a role for these molecules in the anti-apoptotic activity of BCR-ABL.

Animals↗

High dose intravenous oestrogen (fosfestrol) in the treatment of symptomatic, metastatic, hormone-refractory carcinoma of the prostate.

OBJECTIVE: High dose intravenous stilboestrol has a direct cytotoxic effect on prostatic carcinoma cells. The purpose of this study was to assess subjective and objective responses in a select group of patients with metastatic, hormone-refractory carcinoma of the prostate with severe generalized bone pain in association with symptoms of advanced local disease. PATIENTS AND METHODS: Seventeen patients with metastatic carcinoma of the prostate, who had relapsed following a good initial response to androgen ablation, were treated as inpatients with once daily intravenous injection of 1104 mg diethylstilboestrol diphosphate (Honvan, Asta Medica, Cambridge, UK) for 7 days. The hormone-refractory status was confirmed by castrate serum testosterone levels. All the patients had failed to respond to second-line hormone manipulation and had progressive disease. All the patients had generalized bone pain, 11 also had symptoms of bladder outlet obstruction, 3 had recurrent haematuria and 3 had both. The mean age was 74 years (range 59-83), mean time to chemical relapse (rising PSA) was 29 months (range 1-70), and mean time to clinical relapse was 37 months (range 6-98). The WHO pain score, performance status score, and a patient-specific quality of life (daily living activity) were used as the subjective measures and the serum PSA as an objective marker. All the parameters were recorded before, during and up to three months after treatment. RESULTS: Two patients had a transient relief of bone pain with the pain score reducing by two points. Overall, the pain and performance scores and the local symptoms did not improve. The PSA level continued to rise in all patients. Despite parenteral pre-medication with pethidine and cyclizine, all the patients suffered nausea and pain following the injection. One patient died on the fifth day of treatment from a myocardial infarction and 4 developed deep vein thrombosis. All the patients required further symptom control measures. CONCLUSION: High dose intravenous stilboestrol causes considerable morbidity without any objective or subjective response in the treatment of patients with symptomatic, hormone-refractory metastatic carcinoma of the prostate.

Aged↗

Prostatic infarction/infection in acute urinary retention secondary to benign prostatic hyperplasia.

PURPOSE: We assess the role of acute prostatic infarction and prostatic inflammation in causing acute urinary retention in patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A prospective controlled clinicopathological study was undertaken comparing 35 patients who presented with acute urinary retention secondary to BPH with another 35 patients with symptomatic BPH. All 70 patients were treated with transurethral resection. The prostatic chips in each group were examined by 1 histopathologist, who was unaware of the clinical presentation of the patient, for changes of infarction, acute and chronic inflammation, and predominant histological pattern. RESULTS: There was a higher incidence of glandular pattern in the retention group compared to a stromal pattern in the control group, which was statistically significantly different (p < 0.001). A 5-fold higher incidence of prostatic carcinoma was noted in the acute retention group, which was also statistically significant (p < 0.05). CONCLUSIONS: Prostatic infarction and inflammation had no role in the etiology of acute urinary retention due to BPH.

Acute Disease↗

Combination alpha-interferon and lamivudine therapy for alpha-interferon-resistant chronic hepatitis B infection: results of a pilot study.

BACKGROUND/AIMS: Alpha-interferon achieves seroconversion in about one third of naive patients. Attempts to achieve seroconversion in patients who have previously failed alpha-interferon have proved disappointing. Combination chemotherapy (alpha-interferon with a nucleoside analogue) might provide a treatment alternative for these patients. We have undertaken a phase 2 study in 20 patients who had previously failed at least one course of alpha-interferon. The study was designed to assess the safety, tolerability and efficacy of the combination. METHODS: All patients were treated for 16 weeks with alpha-interferon in combination with 12 or 16 weeks of Lamivudine (3'TC). Patients were followed for 16 weeks post-treatment. Pharmacokinetic studies were performed to identify/exclude significant pharmacokinetic drug interaction. RESULTS: The combination was well tolerated, and side-effects of the combination were indistinguishable from the recognised side-effects of alpha-interferon. Pharmacokinetic studies performed on days 1 and 29 did not show any significant interaction. All patients achieved HBV DNA clearance during treatment, but 19 relapsed at the end of treatment. HBeAg/anti-HBe seroconversion was observed for four patients, but was sustained for a single patient (who also had sustained DNA clearance). CONCLUSIONS: Combination therapy with alpha-interferon and lamivudine given for 16 weeks appears safe and is well tolerated. However, for this group of patients who had previously failed interferon monotherapy, the efficacy of combination interferon/lamivudine therapy appears disappointing, and other treatment strategies should be investigated.

Adult↗

Profile of Kangari cancer: a prospecive study.

Kangari, an earthenware brazier containing burning charcoal, is used for personal warming during the winter months by most of the people in Kashmir valley. Kangari is usually held close to the lower abdomen or in between the legs while squatting on the ground. The use of kangari is associated with development of skin cancer at the sites of prolonged exposure. In the present study 43 patients with Kangari cancer were analyzed prospectively with the objective of understanding their clinico-pathological profile and the response to various treatment modalities. Variables such as age, gender, grade, site of lesion etc., were evaluated for their prognostic significance.

Abdominal Neoplasms↗

An unusual cause of obstructive sleep apnoea presenting during pregnancy.

We describe a case of lingual thyroid (LT) with primary hypothyroidism, presenting during pregnancy and continuing beyond it with oropharyngeal obstructive symptoms and sleep apnoea syndrome (SAS) of mixed type. Although SAS of a combined obstructive and central type should not be too surprising in a case of LT with hypothyroidism, we were unable to find such a documentation previously. Only four weeks of L-thyroxin treatment resulted in a dramatic improvement in dysphagia, disturbed phonation, haemoptysis, arterial desaturation, sleep apnoea and overall sleep efficiency, in conjunction with a regression in the size of the lingual mass. This case highlights the vagaries confronted in the management of such a case and focuses on efforts towards accurate diagnosis and treatment.

Adult↗