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Biomedical subjects

S Ahmed

Publications and source records attributed to S Ahmed.

At least 19 recordsLinked to original sources

Toluene induces rapid and reversible rise of hippocampal glutamate and taurine neurotransmitter levels in mice.

Toluene, a widely used aromatic organic solvent, has been well characterized as a neurotoxic chemical. Although the neurobehavioral effects of toluene have been studied substantially, the mechanisms involved are not clearly understood. Hippocampus, which is one of the limbic areas of brain associated with neuronal plasticity, and learning and memory functions, may be a principal target of toluene. In the present study, to establish a mouse model for investigating the effects of acute toluene exposure on the amino acid neurotransmitter levels in the hippocampus, in vivo microdialysis study was performed in freely moving mice after a single intraperitoneal administration of toluene (150 and 300 mg/kg). Amino acid neurotransmitters in microdialysates were measured by a high performance liquid chromatography system. The extracellular levels of glutamate and taurine were rapidly and reversibly increased within 30 min after the toluene administration in a dose-dependent manner and returned to the basal level by 1h. Conversely, the extracellular level of glycine and GABA were stable, and no significant change was observed after the toluene administration. To further investigate the brain toluene level in the hippocampus of toluene-administered mice, we used a solid-phase microextraction (SPME) method and examined the time course changes of toluene in the hippocampus of living mice. The brain toluene level reached the peak at 30 min after injection and returned to the basal level after 2h. In the present study, we observed the relationship between brain toluene levels and amino acid neurotransmitter glutamate and taurine levels in the hippocampus. Therefore, we suggest that toluene may mediate its action through the glutamatergic and taurinergic neurotransmission in the hippocampus of freely moving mice.

Animals↗

Immunogenicity of the P-8 amastigote antigen in the experimental model of canine visceral leishmaniasis.

The P-8 proteoglycolipid complex (P-8 PGLC), an amastigote antigen of Leishmania pifanoi, has been demonstrated to induce protection in mouse models, as well as to induce Tc1/Th1-like cellular responses in American cutaneous leishmaniasis patients. Because the immunization with P-8 PGLC in the murine model does not appear to be genetically restricted, we have studied the reactivity of the P-8 PGLC in Leishmania infantum infected dogs. In this study, it is shown that PBMC from experimentally infected dogs (asymptomatic, oligosymptomatic) significantly proliferated in response to soluble leishmanial antigen (SLA) or the P-8 PGLC. Further, quantification of the gene expression induced by the stimulation with P-8 in asymptomatically infected dogs showed an up-regulation of IFN-gamma and TNF-alpha, which were three to 4-fold higher than that induced by soluble Leishmania antigen (SLA). While no measurable induction of IL-10 was observed, low levels of IL-4 mRNA were observed in response to both P-8 and SLA antigens. Thus, our studies establish that P-8 is recognized by infected canines and elicits a potentially curative/protective Th1-like immune response. The identification of Leishmania antigens that elicit appropriate immune responses across different host species (humans, canine) and disease manifestations (cutaneous or visceral) could be an advantage in generating a general vaccine for leishmaniasis.

Animals↗

Stable multibubble sonoluminescence bubble patterns.

Multibubble standing wave patterns can be generated from a flat piezoceramic transducer element radiating into water. By adding a second transducer positioned at 90 degrees from the transducer generating the standing wave, a 3-dimensional volume of stable single bubbles can be established. Further, the addition of the second transducer stabilizes the bubble pattern so that individual bubbles may be studied. The size of the bubbles and the separation of the standing waves depend on the frequency of operation. Two transducers, operating at frequencies above 500 kHz, provided the most graphic results for the configuration used in this study. At these frequencies stable bubbles exhibit a bright sonoluminescence pattern. Whereas stable SBSL is well-known, stable MBSL has not been previously reported. This paper includes discussions of the acoustic responses, standing wave patterns, and pictorial results of the separation of individual bubble sonoluminescence in a multibubble sonoluminescence environment.

Journal Article↗

Stromal cell-derived factor-1 and CXCR4 receptor interaction in tumor growth and metastasis of breast cancer.

Stromal cell-derived factor-1 (SDF-1)/CXCR4 interaction is critical for the trafficking of lymphocytes, homing and retention of hematopoietic stem cells within the bone marrow and is essential in fetal hematopoiesis. Binding of SDF-1 to CXCR4 activates a variety of intracellular signal transduction pathways and effector molecules that regulate cell survival, proliferation, chemotaxis, migration and adhesion. Recently, intensive research has demonstrated that SDF-1/CXCR4 interaction also regulates several key events in wide variety of cancers. Serum-depleted media in the presence of SDF-1 protected the breast cancer cells from apoptosis. CXCR4-low-expressing MCF-7 formed small tumor at inoculated site in SCID mice 8-9 weeks after inoculation while completely failed to metastasis into various organs. In contrast, CXCR4-high-expressing MDA-231 cells were most efficient in the formation of a large tumor and organ-metastasis within 3 weeks in SCID mice. This review briefly focuses on the role of SDF-1/CXCR4 interaction in tumor growth and metastasis of breast cancer cell both in vitro and in vivo.

Animals↗

Effects of NOS inhibition on the cardiopulmonary system and brain microvascular markers after intermittent hypoxia in rats.

We previously demonstrated that rats subjected to intermittent hypoxia (IH) by exposure to 10% O(2) for 4 h daily for 56 days in a normobaric chamber, developed pulmonary hypertension, right ventricular hypertrophy and wall-thickening in pulmonary arterioles, compared with normoxic (N) controls. These changes were greater in rats subjected to continuous hypoxia (CH breathing 10% O(2) for 56 days). Cerebral angiogenesis was demonstrated by immunostaining with glucose transporter 1 (GLUT1) antibody, in viable vessels, in CH and to a lesser degree in IH. In this study, adult Wistar rats were subjected to the same hypoxic regimes and given the nitric oxide synthase (NOS) inhibitor N(6)-nitro-L-arginine methyl ester (L-NAME) in drinking water (NLN, IHLN and CHLN regimes) to induce hypertension. There was significant systemic hypertension in NLN and IHLN rats, compared with N and IH, but surprisingly not in CHLN compared with CH. Hematocrit rose in all hypoxic groups (up to 79% in CHLN). There was no significant pulmonary hypertension in IHLN versus NLN rats, although there was asymmetric wall thickening in pulmonary arterioles. Cerebral GLUT1 immunoreactivity increased with L-NAME, with or without hypoxia, especially in CHLN rats, but conspicuously there was no evidence of angiogenesis in brains of IHLN compared with NLN rats. NOS blockade may attenuate the cerebral and pulmonary vascular changes of IH while augmenting cerebral angiogenesis in continuous hypoxia. However, whether cerebral effects are due to systemic hypertension or changes in cerebral nitric oxide production needs to be evaluated.

Animals↗

Single-nucleotide polymorphisms in the RB1 gene and association with breast cancer in the British population.

A substantial proportion of the familial risk of breast cancer may be attributable to genetic variants each contributing a small effect. pRb controls the cell cycle and polymorphisms within it are candidates for such low penetrance susceptibility alleles, since the gene has been implicated in several human tumours, particularly breast cancer. The purpose of this study was to determine whether common variants in the RB1 gene are associated with breast cancer risk. We assessed 15 tagging single-nucleotide polymorphisms (SNPs) using a case-control study design (n< or = 4474 cases and n < or = 4560 controls). A difference in genotype frequencies was found between cases and controls for rs2854344 in intron 17 (P-trend = 0.007) and rs198580 in intron 19 (P-trend = 0.018). Carrying the minor allele of these SNPs appears to confer a protective effect on breast cancer risk (odd ratio (OR) = 0.86 (0.76-0.96) for rs2854344 and OR = 0.80 (0.66-0.96) for rs198580). However, after adjusting for multiple testing these associations were borderline with an adjusted P-trend = 0.068 for the most significant SNP (rs2854344). The RB1 gene is not known to contain any coding SNPs with allele frequencies > or = 5% but several intronic variants are in perfect linkage disequilibrium with the associated SNPs. Replication studies are needed to confirm the associations with breast cancer.

Aged↗

A comparison of infero-nasal and infero-temporal sub-Tenon's block.

BACKGROUND AND OBJECTIVE: Sub-Tenon's block is usually delivered by the infero-nasal (IN) approach, but occasionally this may not be possible. The infero-temporal (IT) approach has been described, but data is not available on its efficacy. METHODS: One hundred patients undergoing cataract extraction were randomized to receive an IN or IT sub-Tenon's injection of lidocaine 2% with hyaluronidase 15 IU mL-1. Akinesia was assessed using the Brahma scale at 0, 2, 4, 6 and 8 min. Injection, intraoperative and postoperative pain scores (verbal analogue score, 0-10) were noted, along with the incidence of sub-conjunctival haemorrhage and chemosis. RESULTS: There were no differences in patient characteristics data, or mean volume of administered local anaesthetic solution (3.3 (SD = 0.4) mL). There were no significant differences between groups in terms of onset of akinesia. Mean akinesia scores at 2, 4, 6 and 8 min were 2.7, 1.1, 0.4 and 0.2 for Group IN, compared to 2.2, 0.9, 0.8 and 0.3 for Group IT. Chemosis occurred in 14 patients in Group IN, compared to 22 in Group IT (P = 0.21).A sub-conjunctival haemorrhage was noted in 14 patients in Group IN and 19 patients in Group IT (P = 0.52). No patients required supplementary injections. Mean pain scores for the injection, intraoperatively and postoperatively were 0.9, 0 and 0 for Group IN, compared to 1.1, 0 and 0 for group IT. The surgeons scored all the blocks as 'good' except for one patient in each group. CONCLUSIONS: The IT approach provides an equally rapid onset of block, without a significant increase in complications.

Administration, Intranasal↗

Neuroblastoma with orbital metastasis: ophthalmic presentation and role of ophthalmologists.

INTRODUCTION: Neuroblastoma is predominantly a tumour of early childhood, which metastasises to the orbits. In such cases, ophthalmologists are involved in the multidisciplinary management. This unique series from a tertiary referral centre is used to elaborate the ophthalmic associations and the ophthalmologist's role in this rare condition. METHODS: A review of case notes was performed on six patients who presented to the paediatric ophthalmology - oncology liaison service at the Leeds teaching hospitals between 1998 and 2003. The ophthalmic outcome and role of the ophthalmologist were assessed. RESULTS: Average age of presentation was 29.8 months (range 15-69 months). Average duration of follow-up was 19.5 months (range 2-58 months). One child died during treatment. Two have completed treatment and are under follow-up. Presenting features of the six children were proptosis in four, periorbital ecchymosis in two, ocular motility restriction in two, and subconjunctival haemorrhage in one. Only one case developed blindness. CONCLUSIONS: The role of the ophthalmologist in patients with metastatic orbital neuroblastoma can vary from a supportive role to one of active intervention and management of ophthalmic complications. The ophthalmologist is involved in diagnosis and staging as well as monitoring response to treatment of both the primary disease and secondary ophthalmic complications.

Child↗

Angiomatoid variant of fibrous histiocytoma: a case report and review of literature.

Fibrous histiocytomas by themselves are not very common in the head and neck region. Apart from considering the above fact, this report describes a unique and relatively rare variant of the neoplasm - the angiomatoid fibrous histiocytoma (AFH) which has a characteristic appearance and predilection for young individuals that occurred in the left lower border of the mandible in a 13-year-old girl. Angiomatoid fibrous histiocytoma is a distinct fibrohistiocytic tumour of children and young adults that combines features of both fibrohistiocytic and vascular neoplasm. It is considered to be a tumour of intermediate malignancy because of its less aggressive course in contrast to the conventional malignant fibrous histiocytoma. The authors would like to stress upon the fact that clinicians should not overlook swellings that may not appear distinct visually and therefore consider it to be a part of normal anatomy, dismiss it as an anomaly with no significance, or treat it injudiciously, for ultimately it may prove to be a tumour that would require appropriate treatment and follow-up.

Adolescent↗

Vertebral artery origin stent placement with distal protection: technical and clinical results.

OBJECTIVE: To report the feasibility, safety, and 1-month results of performing stent placement for vertebral origin stenosis with the use of a distal protection device. Distal protection devices have been shown to reduce the number of cerebral emboli and subsequent ischemic events when used as adjuncts to percutaneous carotid intervention; however, one case of the use of a distal protection device for vertebral artery has been reported in the literature. METHODS: We retrospectively determined rates of technical success and 1-month stroke or death associated with stent placement by using distal protection (Filter EX; Boston Scientific, Natick, Mass) in patients with symptomatic vertebral artery origin stenosis. Technical success was defined as successful deployment of distal protection device and stent at target lesion followed by successful retrieval of the device and a final residual stenosis of less than 30%. Other outcomes ascertained included any stroke, death, and semiquantitative assessment of particulate material retained by the filter device. RESULTS: The mean age of the 12 treated patients was 68 years (range, 52-88 years) and the group included 9 men and 3 women. The mean percentage of vertebral artery origin stenosis was 71 +/- 6%. Femoral and radial approaches were used in 9 and 3 cases, respectively. Technical success was achieved in 11 of the 12 patients in whom distal protection device placement was attempted. Postprocedure residual stenosis was 5 +/- 4%. Eight devices held macroscopically visible embolic debris (large and small amounts in 3 and 5 devices, respectively). No stroke or death was observed in the 1-month follow-up. CONCLUSION: The present study demonstrates the feasibility of performing stent placement for vertebral artery origin stenosis by using a distal protection device. Further studies are required to determine the effectiveness of this approach for vertebral artery origin atherosclerosis.

Aged↗

Costs of running a universal adolescent hepatitis B vaccination programme.

In the first UK study to examine feasibility and acceptability of universal adolescent hepatitis B vaccination, the costs associated with the administration and uptake (80.2 and 89.3% for three doses and at least two doses, respectively), of a three-dose regimen in pupils in Glasgow schools (2001/2002) were measured. These data were used to estimate the economic outlay for the delivery of a routine, ongoing three-dose and two-dose hepatitis B vaccine programme in schools. Vaccine, accounting for almost 70% of the overall costs, was the largest cost item for both the pilot and routine programmes, using either regimen. However, the ongoing, two-dose regimen was the cheapest option in this analysis, irrespective of vaccine price. Cost data from this study may be useful for other countries wishing to implement a similar programme.

Adolescent↗

Time to hospital arrival, use of thrombolytics, and in-hospital outcomes in ischemic stroke.

OBJECTIVE: To determine the interval between symptom onset and hospital arrival and its relationship to baseline clinical characteristics, use of thrombolysis, and in-hospital outcomes in patients with acute ischemic stroke admitted to the 11 hospitals in the Buffalo metropolitan area and Erie County. METHODS: The medical records of 1,590 patients were reviewed to determine the severity of the neurologic deficits (NIH Stroke Scale [NIHSS]), in-hospital mortality, favorable outcome (modified Rankin Scale score of < or = 2 at discharge), and strata of time interval between symptom onset and hospital arrival. RESULTS: The time interval between symptom onset and hospital arrival was 0 to 3 hours in 337 (21%) patients, 3 to 6 hours in 177 (11%) patients, 6 to 24 hours in 301 (19%) patients, > 24 hours in 420 (26%) patients, and undetermined in 355 (22%) patients. IV (n = 23) and intra-arterial (n = 4) thrombolysis was used in 27 (8%) of the 337 patients that presented within 3 hours of symptom onset. In 1,235 patients with known time interval between symptom onset and hospital arrival, an association (p = 0.008) was observed between strata of increasing time interval and higher proportion of favorable outcomes at discharge. The initial NIHSS score was higher with decreasing interval between symptom onset and hospital arrival (p < 0.0001). CONCLUSIONS: A small proportion of patients who present within 3 hours of symptom onset receive thrombolytic therapy. The observation that patients with more severe neurologic deficits and subsequently worse in-hospital outcomes appear to present early after symptom onset to the hospital may have implications for clinical studies.

Acute Disease↗

The role of aromatization in testosterone supplementation: effects on cognition in older men.

OBJECTIVE: To determine the contribution of conversion of testosterone (T) to estradiol on cognitive processing in a population of healthy older men who received T supplementation. METHODS: Sixty healthy, community-dwelling volunteers aged 50 to 90 years completed a randomized, double-blind, placebo-controlled study. Participants were randomized to receive weekly IM injections of 100 mg T enanthate plus daily oral placebo pill (T group, n = 20), 100 mg testosterone enanthate plus 1 mg daily of anastrozole, an aromatase inhibitor (oral pill), to block the conversion of T to estradiol (AT group, n = 19), or saline injection and placebo pill (placebo group, n = 21) for 6 weeks. Cognitive evaluations using a battery of neuropsychological tests were conducted at baseline, week 3 and week 6 of treatment, and after 6 weeks of washout. RESULTS: Circulating total T was increased from baseline an average of 238% in the T and AT treatment groups. Estradiol increased an average of 81% in the T group and decreased 50% in the AT group during treatment. Significant improvements in spatial memory were evident in the AT and T treatment groups. However, only the group with elevated estradiol levels (T group) demonstrated significant verbal memory improvement. CONCLUSION: In healthy older men, improvement in verbal memory induced by testosterone administration depends on aromatization of testosterone to estradiol, whereas improvement in spatial memory occurs in the absence of increases in estradiol.

Aged↗

Lower gastrointestinal symptoms are not predictive of colorectal neoplasia in a faecal occult blood screen-positive population.

BACKGROUND: The aim of this study was to evaluate the incidence of lower gastrointestinal symptoms in faecal occult blood (FOB) test-positive participants in a colorectal screening programme, and to compare the colonoscopic findings in symptomatic and asymptomatic individuals. METHODS: Five hundred and sixty-three consecutive individuals with a positive FOB test in the Scottish arm of the national colorectal cancer screening pilot were studied. All were aged between 50 and 69 years and underwent colonoscopy. Before the procedure the participants were given a standard questionnaire to elicit gastrointestinal symptoms; these were correlated with the colonoscopic findings. RESULTS: Of the 563 participants, 439 (78.0 per cent) had one or more lower gastrointestinal symptoms and 124 (22.0 per cent) were symptom free. Taking adenoma and carcinoma together, 322 (57.2 per cent) of the subjects were found to have colorectal neoplasia, and 128 (22.7 per cent) had a completely normal colon. Rectal bleeding was the most common symptom, followed by change in bowel habit, abdominal pain, tenesmus, unexplained weight loss, rectal pain and unexplained anaemia. No significant associations were found between any of these symptoms and the findings at colonoscopy. CONCLUSION: In a FOB test-positive screened population, lower gastrointestinal symptoms are common, but are not predictive of colorectal neoplasia.

Abdominal Pain↗

Intrapartum oxytocin use for labor acceleration in rural India.

OBJECTIVE: To examine factors associated with the use of oxytocin for acceleration of labor in women delivered at home in rural India. METHOD: Quantitative data were collected from 527 women who were delivered at home and qualitative interviews were carried out with 21 mothers and 9 birth attendants. RESULTS: Oxytocin use was associated with higher education and socioeconomic status, primigravidity, and delivery by a traditional birth attendant. CONCLUSION: Labor acceleration with oxytocin occurs indiscriminately In India. Oxytocin use should be regulated, and training for birth attendants should be provided as well as health education for pregnant women.

Adolescent↗