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Biomedical subjects

M Mahadevan

Publications and source records attributed to M Mahadevan.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of forearm and conventional Bier's blocks for manipulation and reduction of distal radius fractures.

Forearm-based Bier's block has been advocated as a useful anaesthesic technique in hand surgery. However, there is limited data comparing forearm blocks with the conventional Bier's block. We conducted a randomised controlled trial (n=30) comparing the two techniques of anaesthesia for manipulation and reduction of closed distal radius fractures in an emergency room setting. Pain scores measured using the Visual Analogue Scale during the procedure were used as the primary outcome assessment. There was no significant difference in pain scores between the forearm and conventional Bier's block (mean VAS 18.4 SD 22.10 versus 33.7 SD 29.6). No major complications were observed in either group. The forearm-based Bier block is an effective alternative to the conventional block.

Adult↗
PubMed2002

Emergency department asthma: compliance with an evidence-based management algorithm.

BACKGROUND: Recent surveys in emergency medicine departments show inadequacies in many aspects of acute asthma management. OBJECTIVE: The objective of this study was to evaluate the adherence to management algorithm for acute asthma in the emergency department which focused on evidence-based treatment steps rather than documentation and patient classification. METHODS: A retrospective audit of consecutive adult patients with acute exacerbations of asthma in the emergency medicine department of a university hospital managed in the context of a clinical algorithm. RESULTS: We collated information from 344 episodes of acute asthma (94% of total) over a 4-month period. The first-line treatment was nebulised bronchodilators in 97%, combination of salbutamol and ipratropium bromide in 93% and the combination in recommended dosages in 87%. Systemic corticosteroid treatment was administered to 82% of patients. A further course of systemic corticosteroid was prescribed at discharge for 94% of patients. Overall, 93% of patients received some form of systemic corticosteroid treatment. The admission rate was 35.2%, and was significantly higher in women and the elderly. Of those who were admitted, 46.2% received > or = 3 nebulised treatments and 69% received intravenous hydrocortisone. CONCLUSIONS: In the management of acute asthma, we found excellent compliance with specific treatment steps based upon clinical evidence. However, adherence to second-line treatment was less satisfactory. Nevertheless, whenever second-line treatment was complied with, reasonable outcomes were achieved. It may be more appropriate to emphasise evidence-based treatment rather than extensive documentation.

Acute Disease↗
PubMed2000

Cervical lymphadenitis due to non-tuberculous mycobacteria: surgical treatment and review.

A retrospective study was carried out on 57 children, presenting with non-tuberculous mycobacterial (NTM) lymphadenitis of the head and neck, over a 12 year period. Cultures recovered 56 Mycobacterium avium-intracellulare (MAI), and one Mycobacterium kansasaii. Anti-mycobacterial agents were used in seven patients only. On the basis of the initial operation there were two groups. Group 1 (11 patients) had an excision, and Group 2 (46 patients) had incision and drainage (30 patients), incision and curettage (13 patients), or aspiration (three patients). There was no significant difference in the makeup of these two groups. However, Group 1 had significantly lower number of re-operations than Group 2, P<0.01, and achieved a significantly greater healing rate than Group 2, P<0.001. In Group 2 those who had an excision following failure of the first operation were significantly more likely to heal than those who did not, P<0. 005. Operative excision gives a lower rate of re-operation, and a higher rate of healing than other procedures. The treatment, natural history, clinical presentation, pathogenesis, and diagnosis of NTM cervical lymphadenitis are discussed.

Adult↗
PubMed2000

Prospective randomized study of analgesic use for ED patients with right lower quadrant abdominal pain.

Giving an analgesic to patients with right lower quadrant (RLQ) pain causes greater alteration of abdominal signs predictive of appendicitis than placebo. A randomized double-blinded controlled trial of 68 patients who received either tramadol or placebo. Absence or presence of seven abdominal signs (tenderness on light and deep palpation, tenderness in the RLQ and elsewhere, rebound, cough, and percussion tenderness) and pain (100 mm Visual Analog Scale [VAS]) at 0 and 30 minutes were recorded. The predictive value of each physical finding (PF) was measured using an 11-point PF score weighted by likelihood ratios. There was significant reduction in mean VAS of 14.2 mm (95% CI 5.6 to 22.8) in analgesic group versus 6.5 mm (95% CI 1.6 to 11.4) in placebo group. The analgesic group had less normalization of signs as measured by the PF score in all patients [32 of 154 (20.8%) versus 40 of 121 (33.1 %) (P = .031)] and in those with proven appendicitis [4 of 33 (12.1%) versus 10/22 (45.5%) (P = .014)]. Parenteral use of tramadol in emergency department patients with RLQ pain resulted in significant levels of pain reduction without concurrent normalisation of abdominal examination findings indicative of acute appendicitis.

Abdominal Pain↗
PubMed2000

Investigation and treatment of thyroglossal cysts in children.

Thyroglossal cysts are the commonest midline neck masses in children. To evaluate current practice questionnaires were sent to all ear, nose and throat (ENT) and paediatric surgeons in the UK and 72% responded. The commonest investigation requested was an ultrasound scan (54%) and the commonest operation was a variant of Sistrunk's procedure (78%). Paediatric surgeons did fewer investigations than ENT surgeons and tended to excise more of the thyroglossal tract. Review of the published work suggests that ultrasound scanning and Sistrunk's procedure are the best management policy. The scan can avoid inadvertent excision of an ectopic thyroid gland. Extensive thyroglossal tract excisions give lower recurrence rates.

Child↗
PubMed1999

Perioperative pharmacodynamics of acetaminophen analgesia in children.

BACKGROUND: There are no adequate pharmacodynamic data relating concentrations of acetaminophen in serum to analgesia. METHODS: Children undergoing outpatient tonsillectomy were administered acetaminophen either orally, 0.5-1.0 h preoperatively (n = 20), or per rectum at induction of anesthesia (n = 100). No other analgesic agents were administered. Individual concentrations of acetaminophen in serum and pain scores (0-10) measured over a 4-h postoperative period were analyzed using a nonlinear mixed-effects model (NONMEM). RESULTS: Mean (% CV) estimates of population pharmacokinetic parameters with percent coefficient of variation, standardized to a 70-kg person, for a one-compartment model with first-order input, lag time, and first order-elimination were a volume of distribution of 60 (21) 1 and a clearance of 13.5 (46) 1/h. Rectally administered acetaminophen had an absorption half-life of 35 (63) min with a lag time of 40 min. The absorption half-life for the oral preparation was 4.5 (63) min without a detectable lag time. The relative bioavailability of the rectal compared with the oral formulation was 0.54. The equilibration half-time of an effect compartment was 1.6 (131) h. Pharmacodynamic population parameter estimates (percent coefficient of variation) for a fractional sigmoidal Emax model, in which the greatest possible pain relief equates to an Emax of 1, were Emax = 1, EC50 (the concentration producing 50% of Emax) = 3.4 (94) mg/l, and Hill coefficient = 0.54 (42). CONCLUSIONS: The pharmacodynamics of acetaminophen can be described using a sigmoidal Emax model with a low Hill coefficient. To achieve a mean posttonsillectomy pain score of 3.6 of 10, an effect compartment concentration of 10 mg/l is necessary.

Acetaminophen↗
PubMed1999

Unilateral tonsillar enlargement and tonsillar lymphoma in children.

The clinical presentation and surgical and pathological findings of 46 children with unilateral tonsillar enlargement (UTE; age range 2 to 13 years, mean age 6.5) who underwent tonsillectomy for biopsy purposes between 1975 and 1995 were compared with those of 7 children who received treatment for tonsillar lymphoma (TL; age range 2 to 9 years, mean age 4.8) during the same period. There was no history of rapid tonsillar enlargement in children in the UTE group, and only 20 (43%) were symptomatic. Symptoms included recurrent sore throats in 10 patients (22%), snoring in 5 (11%), nasal obstruction in 4 (9%), and dysphagia in 1 (2%). No children had systemic symptoms or significant cervical lymphadenopathy. In contrast, tonsillar enlargement was observed to occur within a 6-week period in all children with TL, and 6 (86%) children had symptoms at presentation that included dysphagia in 5 (71%), snoring in 3 (43%), night sweats in 2 (29%), and fever and rigors in 2 (29%). Cervical lymphadenopathy greater than 3 cm was present in 6 (86%) children, while 1 child (14%) had hepatosplenomegaly. There was no histopathologic evidence of neoplasia in the UTE group, and a true discrepancy in size between the two tonsils was confirmed in only 21 of 44 (48%) cases. All 7 patients in the TL group had non-Hodgkin's lymphoma. All received chemotherapy, with 5 of the 7 cured and 2 dying of disease. The data suggest that tonsillectomy should be performed for biopsy purposes in UTE where there is a history of progressive enlargement, significant upper aerodigestive tract symptoms, systemic symptoms, suspicious appearance of the tonsil, cervical lymphadenopathy, or hepatosplenomegaly. The diagnosis of TL should also be considered when UTE is present in an immunocompromised child or one with a previous malignancy, when acute tonsillitis is asymmetric and unresponsive to medical treatment, or when rapid bilateral tonsil enlargement occurs. Observation is appropriate management for other cases of UTE.

Adolescent↗
PubMed1998

Sequence of a 131-kb region of 5q13.1 containing the spinal muscular atrophy candidate genes SMN and NAIP.

The spinal muscular atrophies (SMA), which are characterized by motor neuron loss and progressive paralysis, are among the most common autosomal recessive disorders. The SMA region of chromosome 5q13.1 is distinguished by variable amplification of genomic sequence incorporating a number of genes and pseudogenes. Recently, two SMA candidate genes mapping to this area were identified: survival motor neuron (SMN) and neuronal apoptosis inhibitory protein (NAIP). The telomeric copy of SMN (SMNtel) is deleted in over 95% of cases of SMA, with NAIP deletions primarily seen in type I SMA. We present here 131 kb of genomic sequence from 5q13.1 incorporating both NAIP and SMNtel in addition to revisions of the original NAIP cDNA sequence. The Alu-rich NAIP-SMNtel interval contains the microsatellite polymorphisms that are deleted in as many as 80% of type I SMA chromosomes, focusing attention on this region in the pathogenesis of type I SMA.

Amino Acid Sequence↗
PubMed1992

Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene.

Myotonic dystrophy (DM) is the most common inherited neuromuscular disease in adults, with a global incidence of 1 in 8000 individuals. DM is an autosomal dominant, multisystemic disorder characterized primarily by myotonia and progressive muscle weakness. Genomic and complementary DNA probes that map to a 10-kilobase Eco RI genomic fragment from human chromosome 19q13.3 have been used to detect a variable length polymorphism in individuals with DM. Increases in the size of the allele in patients with DM are now shown to be due to an increased number of trinucleotide CTG repeats in the 3' untranslated region of a DM candidate gene. An increase in the severity of the disease in successive generations (genetic anticipation) is accompanied by an increase in the number of trinucleotide repeats. Nearly all cases of DM (98 percent or 253 of 258 individuals) displayed expansion of the CTG repeat region. These results suggest that DM is primarily caused by mutations that generate an amplification of a specific CTG repeat.

Base Sequence↗
PubMed1992

Cloning of the essential myotonic dystrophy region and mapping of the putative defect.

Myotonic dystrophy is a common dominant disorder (global incidence of 1:8,000) with variable onset and a protean nature of symptoms mainly involving progressive muscle wasting, myotonia and cataracts. To define the molecular defect, we have cloned the essential region of chromosome 19q13.3, including proximal and distal markers in a 700-kilobase contig formed by overlapping cosmids and yeast artificial chromosomes (YACs). The central part of the contig bridges an area of about 350 kilobases between two new flanking crossover borders. This segment has been extensively characterized through the isolation of five YAC clones and the subsequent subcloning in cosmids from which a detailed EcoRI, HindIII, MluI and NotI restriction map has been derived. Two genomic probes and two homologous complementary DNA probes were isolated using the cosmids. These probes are all situated within approximately 10 kilobases of genomic DNA and detect an unstable genomic segment in myotonic dystrophy patients. The length variation in this segment shows similarities to the instability seen at the fragile X locus. The physical map location and the genetic characteristics of the length polymorphism is compatible with a direct role in the pathogenesis of myotonic dystrophy.

Blotting, Southern↗
PubMed1992

Physical mapping and cloning of the proximal segment of the myotonic dystrophy gene region.

The myotonic dystrophy (DM) region has been recently shown to be bracketed by two key recombinant events. One recombinant occurs in a Dutch DM family, which maps the DM locus distal to the ERCC1 gene and D19S115 (pE0.8). The other recombinant event is in a French Canadian DM family, which maps DM proximal to D19S51 (p134c). To further resolve this region, we initiated a chromosome walk in a telomeric direction from pE0.8, a proximal marker tightly linked to DM, toward the genetic locus. An Alu-PCR approach to chromosome walking in a cosmid library from flow-sorted chromosome 19 was used to isolate DM region cosmids. This effort has resulted in the cloning of a 350-kb genomic contig of human chromosome 19q13.3. New genetic and physical mapping information has been generated using the newly cloned markers from this study. As a result of this new mapping information, the minimal area that is to contain the DM gene has been redefined. Approximately 200 kb of sequence between pE0.8 and the closest proximal marker to DM, pKEX0.8, that would have otherwise been screened for DM candidate genes, has been eliminated as containing the DM gene.

Base Sequence↗
PubMed1992

Characterization of the myotonic dystrophy region predicts multiple protein isoform-encoding mRNAs.

The mutation underlying myotonic dystrophy (DM) has been identified as an expansion of a polymorphic CTG-repeat in a gene encoding protein kinase activity. Brain and heart transcripts of the DM-kinase (DMR-B15) gene are subject to alternative RNA splicing in both human and mouse. The unstable [CTG]5-30 motif is found uniquely in humans, although the flanking nucleotides are also present in mouse. Characterization of the DM region of both species reveals another active gene (DMR-N9) in close proximity to the kinase gene. DMR-N9 transcripts, mainly expressed in brain and testis, possess a single, large open reading frame, but the function of its protein product is unknown. Clinical manifestation of DM may be caused by the expanded CTG-repeat compromising the (alternative) expression of DM-kinase or DMR-N9 proteins.

Alternative Splicing↗
PubMed1992

The correlation of age of onset with CTG trinucleotide repeat amplification in myotonic dystrophy.

The gene for myotonic dystrophy (DM) has recently been isolated and amplification of an unstable CTG trinucleotide repeat, located within the DM gene, has been identified in virtually all patients studied to date. A high proportion of DM families who are studied show a progressively earlier age of onset with succeeding generations and, in the few pedigrees reported so far, an increasing degree of amplification of the CTG repeat has been noted to parallel this trend. It has been implicit in several of the original reports on the nature of the changes in the DM gene that knowledge of CTG amplification status at the DM locus of a person will provide useful information concerning prognosis. However, no studies of genotype-phenotype correlation have been reported and there are no specific data on which to base such counsel. In this paper we report the correlation between the degree of CTG amplification and age of onset in 109 DM gene carriers from 17 families. Included are parent-child and sib-sib comparisons which provide a framework in which to incorporate DNA diagnostic studies when counselling subjects and families at risk for DM.

Adolescent↗
PubMed1989

Immunosuppressive activity in human in vitro fertilization (IVF) culture supernatants and prediction of the outcome of embryo transfer: a multicenter trial.

The supernatants from cultured human oocytes fertilized in vitro contain low molecular weight factors that can suppress or stimulate the proliferative response of lymphocytes in vitro. The inhibitory and stimulatory effects are nonspecific and may be detected using cultured human or murine tumor cell lines. Using such a bioassay, we previously tested fetal cord serum-supplemented culture supernatant and found that an absence of suppression was correlated with an absence of subsequent pregnancy. To test this association further, additional samples were obtained from four different in vitro fertilization (IVF) units and studied blindly without knowledge of the pregnancy outcome. In this series, samples were obtained after the first 12-24 hr of sperm-oocyte incubation and all of the supernatants were from individual embryo cultures. The average number of preembryos transferred to those achieving pregnancy did not differ significantly from the number transferred to those not achieving pregnancy but the level of suppression was greater (8.7 +/- 1.9%) in those becoming pregnant compared to those not achieving pregnancy (0.8 +/- 1.5%). Twenty-two of 61 patients who received at least one embryo with a suppressive supernatant achieved pregnancy, whereas 0 of 19 patients received embryos lacking suppressive supernatants became pregnant. Two patients who received a single embryo from cultures with suppression became pregnant. Several problems with the bioassay method were defined. The culture medium in this series was always supplemented with adult serum, usually from the patient herself, and this serum could be suppressive.(ABSTRACT TRUNCATED AT 250 WORDS)

Blastocyst↗