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Biomedical subjects

A Agrawal

Publications and source records attributed to A Agrawal.

At least 19 recordsLinked to original sources

The use of latissimus dorsi miniflap for reconstruction following breast-conserving surgery: experience of a small breast unit in a district hospital.

BACKGROUND: Immediate reconstruction with autogenous tissue is one of the options for reconstruction following breast-conservation surgery for breast cancers in major centres with ready availability of appropriate skills. Immediate correction of volume deficit by latissimus dorsi miniflap (LDMF) in addition has cosmetic appeal by filling the defect without extra skin incision. METHODS: Data was collected retrospectively from clinical records of 51 patients who underwent LDMF procedures in a district general hospital between June 2000 and December 2004, and the results were analysed. Postal questionnaire survey was done to assess the level of subjective satisfaction of the cosmetic outcome. RESULTS: Wide local excision and axillary-node sampling/clearance along with immediate reconstruction with a LDMF (involving a musculo-subcutaneous flap without skin) were performed in all patients. Patients' median age was 50 years. Sixty-five percent of the tumours were in the upper-outer quadrant, median weight of the specimen was 217.5 g (31-510 g), median clearance margin was 5 mm (0-15 mm) and median pathological size of the tumour was 20 mm (8-60 mm). Four patients required mastectomy later, whereas 1 patient had flap necrosis. At a median follow-up of 33 months, there has been no recurrence. Eighty-six percent of the patients who responded to the postal survey were satisfied with the cosmetic outcome. CONCLUSION: Immediate LDMF reconstruction is an acceptable way of correcting deformity after breast-conservation surgery. We demonstrate by our experience that it is a viable option for breast cancer in small district hospitals/ breast units.

Adult↗

Contrasting models of genetic co-morbidity for cannabis and other illicit drugs in adult Australian twins.

BACKGROUND: The use of cannabis and other illicit drugs (OIDs) and their co-morbid misuse are frequently reported in the literature. Correlated vulnerabilities and causal or gateway influences have been implicated in this association. We investigated the source of this co-morbidity between cannabis use (experimentation, early and repeated use, and problems) and OID experimentation and problems using genetic models proposed by Neale and Kendler (American Journal of Human Genetics 1995, 57, 935-953). METHOD: In a sample of 4152 same-sex male and female adult Australian twin individuals, we fit 13 genetically informative models of co-morbidity to data on experimentation, early use, repeated use of cannabis and co-morbid OID experimentation, and to abuse/dependence (A/D) problems with cannabis and OIDs. RESULTS: Model-fitting results suggest that common genetic, shared and unique environmental factors are responsible for the association between cannabis experimentation, early use, repeated use and A/D problems and OID experimentation or problems. The liability causation model, which is a reduced form of the correlated vulnerabilities model, also fit very well. In women, we found evidence for high-risk cannabis experimenters and repeated users to be at increased risk for OID experimentation, despite being below the risk threshold on the liability distribution for OID experimentation (extreme multiformity). CONCLUSIONS: Co-morbid cannabis and OID use and misuse are due partly to a common predisposition to substance use disorders. Putative causal effects could not be ruled out. These models warrant further research, so that features of the correlated vulnerabilities model and the gateway models can be studied jointly in a single series of adaptive nested models.

Adolescent↗

Male breast cancer: a review of clinical management.

AIMS: Male breast cancer incidence is 1% of all breast cancers and is increasing. We aim to present an overview of male breast cancer with particular emphasis on clinical management. METHODS: Studies were identified by an online search of literature in the MEDLINE database till June 2006 followed by an extensive review of bibliographies. RESULTS: Increased risk factors include genetic predisposition as in BRCA2 families; testicular dysfunction due to chromosomal abnormality such as Klinefelter's syndrome or environmental factors such as chronic heat exposure and radiation. Clinical assessment with biopsy is the hallmark of diagnosis. Earlier presentations are becoming commoner but there are wide geographical differences. Surgical treatment involves simple or modified radical mastectomy along with surgical assessment of the axilla, either via sentinel node biopsy in clinically node-negative disease or axillary sampling/clearance in node-positive disease. Reconstructions for restoring body image have been recently reported. Indications for adjuvant therapies are similar to that in women. For metastatic disease, tamoxifen is still the mainstay for oestrogen receptor positive disease. For oestrogen receptor negative disease, doxorubicin based chemotherapy regimens are used. In addition, the oft neglected psychological aspects of men having a "cancer of women" are increasingly being recognised. CONCLUSIONS: There is, thus, need for further increasing awareness among men to reduce stigma associated with presentation of symptoms related to breast. This should be in addition to stressing to clinicians the ways of earlier detection and tailor-made "gender oriented" treatment of breast cancer in men.

Breast Neoplasms, Male↗

Inhibition of mucin secretion with MARCKS-related peptide improves airway obstruction in a mouse model of asthma.

Allergic asthma is associated with airway epithelial cell mucous metaplasia and mucin hypersecretion, but the consequences of mucin hypersecretion on airway function are unclear. Recently, a peptide derived from the myristoylated alanine-rich C kinase substrate protein NH(2)-terminal sequence (MANS) was shown to inhibit methacholine (MCh)-induced mucin secretion from airway mucous cells by >90%. We studied the effect of intranasal pretreatment with this peptide on specific airway conductance (sGaw) during challenge with MCh in mice with allergen-induced mucous cell metaplasia. sGaw was noninvasively measured in spontaneously breathing restrained mice, using a double-chamber plethysmograph. Pretreatment with MANS peptide, but not a control peptide [random NH(2)-terminal sequence (RNS)], resulted in partial inhibition of the fall in sGaw induced by 60 mM MCh (mean +/- SE; baseline 1.15 +/- 0.06; MANS/MCh 0.82 +/- 0.05; RNS/MCh 0.55 +/- 0.05 cmH(2)O/s). The protective effect of MANS was also seen in mice challenged with allergen for 3 consecutive days to increase airway hyperresponsiveness, although the degree of protection was less (baseline 1.1 +/- 0.08; MANS/MCh, 0.65 +/- 0.06; RNS/MCh 0.47 +/- 0.03 cmH(2)O/s). Because routine sGaw measurement in mice includes nasal airways, the effectiveness of MANS was also confirmed in mice breathing through their mouths after nasal occlusion (baseline 0.92 +/- 0.05; MANS/MCh 0.83 +/- 0.06; RNS/MCh 0.61 +/- 0.03 cmH(2)O/s). In all instances, sGaw in the MANS-pretreated group was approximately 35% higher than in RNS-treated controls, and mucous obstruction accounted for approximately 50% of the MCh-induced fall in sGaw. In summary, mucin secretion has a significant role in airway obstruction in a mouse model of allergic asthma, and strategies to inhibit mucin secretion merit further investigation.

Airway Obstruction↗

Association of the kappa-opioid system with alcohol dependence.

Opioid receptors and their endogenous peptide ligands play important roles in the reward and reinforcement of drugs such as heroin, cocaine, and alcohol. The binding of dynorphins to the kappa-opioid receptor has been shown to produce aversive states, which may prevent the development of reinforcement. We genotyped SNPs throughout OPRK1, encoding the kappa-opioid receptor, and PDYN, which encodes its ligand prodynorphin, in a group of 1860 European American individuals from 219 multiplex alcohol dependent families. Family-based analyses demonstrated associations between alcohol dependence and multiple SNPs in the promoter and 3' end of PDYN, and in intron 2 of OPRK1. Haplotype analyses further supported the association of PDYN. Thus, variations in the genes encoding both the kappa-opioid receptor and its ligand, OPRK1 and PDYN, are associated with the risk for alcohol dependence; this makes biological sense as variations in either should affect signaling through the kappa-opioid system.

Alcoholism↗

Bran and irritable bowel syndrome: the primary-care perspective.

BACKGROUND: We have shown that bran exacerbates irritable bowel syndrome symptoms in a large proportion of secondary-care patients. However, it is unknown if this also happens in primary-care or whether a better response to bran occurs, leading to bran failures being selected for referral to the specialist. AIMS: To assess the response to bran in primary-care irritable bowel syndrome comparing it to that obtained in secondary-care. PATIENTS AND METHODS: One hundred consecutive primary-care irritable bowel syndrome patients were asked how bran or soluble fibre products affected their symptoms. RESULTS: Bran improved symptoms in 27% of primary-care and 10% of secondary-care patients (p<0.01) and exacerbated symptoms in 22% of primary-care and 55% of secondary-care patients (p<0.001). Fifty-one percent of primary-care and 33% of secondary-care patients reported no change with bran. In primary-care, proprietary fibre led to improvement in 25%, deterioration in 19% and no change in 56% which was not significantly different to secondary-care. CONCLUSION: Although not especially effective in primary-care irritable bowel syndrome patients, bran does not cause so many problems and is more helpful than in secondary-care. The effects of soluble fibre are similar in both primary-care and secondary-care. This study highlights the problem of extrapolating the response to treatment in irritable bowel syndrome from different care settings.

Adult↗

Effects of a 5-HT(4) receptor agonist on oesophageal function and gastro-oesophageal reflux: studies using combined impedance-manometry and combined impedance-pH.

BACKGROUND: 5-HT(4) receptor agonists are used as promotility agents of the stomach, small and large intestine. There is limited information on the influence of 5-HT(4) receptor agonists on oesophageal function and gastro-oesophageal reflux. AIM: To evaluate the effects of tegaserod, a 5-HT(4) agonist on oesophageal function using impedance-manometry and postprandial reflux using impedance-pH monitoring. METHODS: Twenty healthy volunteers were enrolled in a double-blind randomized three-period crossover placebo-controlled study. Impedance-manometry and impedance-pH monitoring after a refluxogenic meal were performed at baseline and after 2 days of dosing with tegaserod 6 mg b.d. or placebo. Multichannel intraluminal impedance-EM recorded pressure and bolus transit data during standardized swallows. Multichannel intraluminal impedance-pH monitoring recorded the number of 2-h postprandial acid and non-acid reflux episodes. RESULTS: We found no significant difference in distal oesophageal amplitude when subjects received placebo (median 94.5; range: 53-243 mmHg) or tegaserod (93.6; 43-216 mmHg). Bolus transit time was similar during dosing with placebo (7.1; 5.3-9.4 s) and tegaserod (7.2; 5.9-11.1 s). We observed similar numbers of acid and non-acid reflux episodes during dosing with placebo (5; 0-15 and 3; 0-18, respectively) and tegaserod (2; 0-11 and 4; 0-19, respectively). CONCLUSION: Tegaserod, a 5-HT(4) receptor agonist does not change oesophageal motility and gastro-oesophageal reflux parameters in healthy volunteers.

Adult↗

Power law of decaying homogeneous isotropic turbulence at low Reynolds number.

We focus on an estimate of the decay exponent (m) in the initial period of decay of homogeneous isotropic turbulence at low Taylor microscale Reynolds number R lambda (approximately equal to 20-50). Lattice Boltzmann simulations in a periodic box of 256(3) points are performed and compared with measurements in grid turbulence at similar R lambda. Good agreement is found between measured and calculated energy spectra. The exponent m is estimated in three different ways: from the decay of the turbulent kinetic energy, the decay of the mean energy dissipation rate, and the rate of growth of the Taylor microscale. Although all estimates are close, as prescribed by theory, that from the Taylor microscale has the largest variability. It is then suggested that the virtual origin for the decay rate be determined from the Taylor microscale, but the actual value of m be estimated from the decay rate of the kinetic energy. The dependence of m on R lambda(0) (the value of R lambda at the beginning of the simulation) is also analyzed, using the present data as well as data from the literature. The results confirmed that m approaches 1, as R lambda(0) increases.

Journal Article↗

Stability of Delta(9)-tetrahydrocannabinol (THC) in oral fluid using the Quantisal collection device.

This article details the stability of Delta(9)-tetrahydrocannabinol (THC) in oral fluid during collection, extraction and storage. Oral fluid is being increasingly used as the specimen of choice for the detection of drug use in various applications. Studies to determine the extraction efficiency of THC from the collection buffer and stability under various laboratory storage conditions were carried out. THC was extracted from the collection pad and buffer with an average efficiency over 80% and was stable in Quantisal oral fluid extraction buffer when stored at refrigerated temperatures. Fluorescent lighting caused THC losses of over 50%, however the presence of the pad reduced the loss. In the dark, the loss of THC at room temperature was approximately 20% over 14 days. When stored with the serum separators in place, THC losses were significant. After 3 days, THC concentration was reduced by almost 30%, and after 14 days, 60% of the drug was lost and the losses were not concentration dependent.

Buffers↗

Combined multichannel intraluminal impedance-pH monitoring to select patients with persistent gastro-oesophageal reflux for laparoscopic Nissen fundoplication.

BACKGROUND: Combined multichannel intraluminal impedance-pH (MII-pH) monitoring detects gastro-oesophageal reflux and identifies acid and non-acid reflux events. It can be used in patients with persistent symptoms on proton-pump inhibitor (PPI) therapy. The aim of this study was to assess laparoscopic Nissen fundoplication as a treatment for patients with persistent symptoms associated with reflux despite acid suppression documented by MII-pH monitoring. METHOD: A prospectively maintained database identified patients with persistent symptoms of gastro-oesophageal reflux disease despite PPI therapy who had undergone MII-pH monitoring and this was cross-referenced with patients who had undergone fundoplication at this institution. Follow-up after fundoplication was by periodic telephone interview and review of clinical records. RESULTS: Of 200 evaluated patients, 19 (14 female; mean age 40 (range 0.7-78) years) underwent laparoscopic Nissen fundoplication. Before surgery, 18 of 19 patients had a positive symptom index (at least half of symptoms associated with reflux) and one, a negative symptom index. After a mean follow-up of 14 (range 7-25) months, 16 of 17 (94 per cent) patients with a positive symptom index were asymptomatic or markedly improved (one patient was lost to follow-up). Persistent symptoms occurred in the patient with a negative symptom index, and one patient had recurrent symptoms after 9 months. CONCLUSION: Patients with a positive symptom index resistant to PPIs with non-acid or acid reflux demonstrated by MII-pH monitoring can be treated successfully by laparoscopic Nissen fundoplication.

Adolescent↗

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↗

Reduced bone mineral density and hyaloid vasculature remnants in a consanguineous recessive FEVR family with a mutation in LRP5.

BACKGROUND/AIMS: Familial exudative vitreoretinopathy (FEVR) is an inherited blinding condition characterised by abnormal development of the retinal vasculature. FEVR has multiple modes of inheritance, and homozygous mutations in LRP5 have recently been reported as underlying the recessive form of this disease. The aim of this study was to examine LRP5 in a consanguineous recessive FEVR family and to clarify the eye and bone phenotype associated with recessive FEVR. METHODS: All family members were examined by slit lamp biomicroscopy and indirect ophthalmoscopy. Linkage to LRP5 was determined by genotyping microsatellite markers, constructing haplotypes and calculating lod scores. Mutation screening of LRP5 was performed by polymerase chain reaction amplification of genomic DNA followed by direct sequencing. Bone mineral density (BMD) was evaluated in all family members using dual energy x ray absorptiometry (DEXA). RESULTS: The clinical features observed in this family were consistent with a diagnosis of recessive FEVR. A homozygous LRP5 missense mutation, G550R, was identified in all affected individuals and all unaffected family members screened were heterozygous carriers of this mutation. Reduced BMD, hyaloid vasculature remnants, and nystagmus were features of the phenotype. CONCLUSION: Recessive mutations in LRP5 can cause FEVR with reduced BMD and hyaloid vasculature remnants. Assessment of a patient with a provisional diagnosis of FEVR should therefore include investigation of BMD, with reduced levels suggestive of an underlying LRP5 mutation.

Adolescent↗

Alkyl succinate poisoning.

A case of alkyl succinate poisoning is being reported. Oral ingestion of this compound led to gastrointestinal tract involvement and central nervous system manifestatations suggestive of parkinsonism. The patient recovered completely following conservative management without any sequelae.

Diarrhea↗

Short course of prednisolone in patients with solitary cysticercus granuloma: a double blind placebo controlled study.

The study was conducted to confirm the role of a short course of oral corticosteroids in patients with solitary cysticercus granuloma with seizures by a double-blind placebo-controlled study. In an open-label trial we, in past, had demonstrated a beneficial role of prednisolone. A short course of prednisolone helped in early resolution of solitary cysticercus granuloma. In this double-blind placebo-controlled randomized study, 60 patients with new-onset seizures and a single enhancing computed tomography (CT)-detected lesion of cysticercosis were randomly divided in two groups to receive either anti-epileptic monotherapy with prednisolone (n=30) or anti-epileptic monotherapy along with placebo (n=30). The patients received prednisolone, 1mg/kg/day for 10 days, followed by tapering over next 4 days. None of the patients received albendazole therapy. The patients were followed up monthly, at least for 9 months. A repeat CT scan was performed after 6 months. The data were analysed by chi-square test. The majority of patients were young. Simple partial seizure, with or without secondary generalization, was the commonest seizure type encountered. Follow-up CT scans at 6 months demonstrated non-significantly better response for prednisolone treated patients. In prednisolone group the lesion disappeared in 52% of patients and in 48% patients who received placebo. However, a significantly lesser number of prednisolone treated patients (n=12%) than controls (n=48%), had seizure recurrence. Our study suggests that short-term prednisolone therapy may not help in rapid resolution of solitary cysticercus granuloma, however, prednisolone therapy improves seizure-related prognosis.

Adolescent↗

Mesh migration following repair of inguinal hernia: a case report and review of literature.

New surgical procedures in the aftermath of their benefits beget new complications as well. Laparoscopic repair of inguinal hernia is widely practised now. It involves reinforcement of hernial defect with a synthetic mesh. We report a rare case of migration of mesh into urinary bladder following this mode of hernial repair. We also present a review of literature involving migration of mesh following all inguinal hernial repairs.

Aged↗