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Biomedical subjects

A Madan

Publications and source records attributed to A Madan.

At least 19 recordsLinked to original sources
PubMed2006

Despite high satisfaction, majority of gastro-oesophageal reflux disease patients continue to use proton pump inhibitors after antireflux surgery.

BACKGROUND: While antireflux surgery is effective in controlling symptoms of gastro-oesophageal reflux, its role in eliminating the use of antireflux medicines after surgery and as such its long-term cost-effectiveness remains controversial. AIM: To assess the patient satisfaction and the continued medication use following laparoscopic Nissen fundoplication at a tertiary level community hospital. METHODS: Adult patients who underwent laparoscopic Nissen fundoplication at our institution over a period of over 3 years were asked to complete a questionnaire recording their demographic information, date and reason for the surgery, preprocedure and postprocedure symptoms, smoking and alcohol use, and medication use preoperatively and post-operatively. Patients were also asked about their satisfaction with surgery. RESULTS: One hundred patients participated in the study. Overall, 90% patients experienced satisfaction with their surgery. Eighty percentage patients were willing to undergo surgery again, if needed. Over two-thirds (67%) patients had decrease in the severity of their symptoms. None of the patients had worsening of symptoms post-operatively. However, 80% patients were still taking antireflux medications including proton pump inhibitors (53%). CONCLUSIONS: Most patients continue to use antireflux medications including after laparoscopic Nissen fundoplication despite high satisfaction with surgery.

Antacids↗
PubMed2006

Neurologic events in neonates treated surgically for congenital heart disease.

OBJECTIVE: The incidence of acute neurologic events prior to discharge in neonates with congenital heart disease (CHD) was determined and peri-operative characteristics predictive of a neurologic event were identified. STUDY DESIGN: A retrospective chart review over 1 year was conducted of infants <1 month of age with a diagnosis of CHD. Outcomes were measured by the occurrence of an acute neurologic event defined as electroencephalogram (EEG)-proven seizure activity, significant hypertonia or hypotonia, or choreoathetosis prior to hospital discharge. Stepwise logistic regression identified variables most likely to be associated with an acute neurologic event. RESULTS: Surgical intervention occurred in 95 infants who were admitted with a diagnosis of CHD. The survival rate was 92%. Of the survivors, 16 (17%) had an acute neurologic event, with 19% of events occurring preoperatively. Factors associated with neurologic events included an elevated nucleated red blood cell (NRBC) count, an abnormal preoperative brain imaging study, and a 5-min Apgar score <7 (P<0.05). CONCLUSIONS: Neonates with CHD have a significant risk of neurologic events. Preoperative brain imaging, the 5-min Apgar score, and initial serum NRBC counts may identify infants at highest risk for central nervous system injury.

Acute Disease↗
PubMed2004

Embolization for major lower gastrointestinal haemorrhage: five-year experience.

The management of major lower gastrointestinal haemorrhage has changed dramatically in the last 15 years. Innovations in coaxial catheter technology have allowed the interventional radiologist to reach the small peripheral mesenteric arteries and perform superselective embolization with a variety of agents. The present large series represents the 5-year experience of this technique at the Alfred Hospital, Melbourne, in a patient cohort with a high number of comorbidities. Technical success was achieved in 96% of cases. The clinical symptoms of mesenteric ischaemia developed in four patients after embolization and were managed conservatively in two. The procedure-related mortality was low when compared with the published complication rates for emergency surgery, in this clinical setting.

Adult↗
PubMed2001

Limb/pelvis hypoplasia/aplasia with skull defect (Schinzel phocomelia): distinctive features and prenatal detection.

Schinzel phocomelia syndrome is characterized by limb/pelvis hypoplasia/aplasia: specifically, intercalary limb deficiencies and absent or hypoplastic pelvic bones. The phenotype is similar to that described in a related multiple malformation syndrome known as Al-Awadi/Raas-Rothschild syndrome. The additional important feature of large parietooccipital skull defects without meningocele, encephalocele, or other brain malformation has thus far been reported only in children with Schinzel phocomelia syndrome. We recently evaluated a boy affected with Schinzel phocomelia born to nonconsanguineous healthy parents of Mexican origin. A third-trimester fetal ultrasound scan showed severe limb deficiencies and an absent pelvis. The infant died shortly after birth. Dysmorphology examination, radiographs, and autopsy revealed quadrilateral intercalary limb deficiencies with preaxial toe polydactyly; an absent pelvis and a 7 x 3-cm skull defect; and extraskeletal anomalies including microtia, telecanthus, micropenis with cryptorchidism, renal cysts, stenosis of the colon, and a cleft alveolar ridge. A normal 46,XY karyotype was demonstrated, and autosomal recessive inheritance was presumed on the basis of previously reported families. This case report emphasizes the importance of recognizing severe pelvic and skull deficiencies (either post- or prenatally) in differentiating infants with Schinzel phocomelia from other multiple malformation syndromes that feature intercalary limb defects, including thalidomide embryopathy and Roberts-SC phocomelia.

Abnormalities, Multiple↗
PubMed2001

A physical map of the human genome.

The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map.

Chromosomes, Artificial, Bacterial↗
PubMed2001

Subcutaneous epinephrine vs nebulized salbutamol in asthma.

OBJECTIVE: This study was conducted to compare the efficacy of the subcutaneous epinephrine with nebulized salbutamol. METHODS: Fifty asthmatic children in the age range of 6-14 years were divided into two equal groups. Group I children were given subcutaneous epinephrine and Group II were nebulized with salbutamol. Patients were observed at 15, 20, 30, 60, 120, 180 and 240 minute intervals. Both the groups had comparable mean increase in peak expiratory flow rate (PEFR %) (Group I 27.7 +/- 0.7; Group II 28.8 +/- 0.06, p >0.05). RESULT: In Group I there was significant increase in systolic blood pressure, 30 minutes after the start of treatment, however it settled on its own by 60 minutes. CONCLUSION: Both the groups had satisfactory improvement in clinical parameters which continued upto 4 hours after start of treatment. Subcutaneous epinephrine can be safely used if nebulizers are not available.

Acute Disease↗
PubMed2001

Imaging of frontal sinus disease: concepts, interpretation, and technology.

Imaging of the frontal sinus is an integral part of patient evaluation. High-resolution computed tomography (CT) imaging is the preferred modality for evaluation of sinus inflammatory disease. Magnetic resonance (MR) imaging plays an important role in differentiating tumors from inflammatory diseases and serves as a problem-solving tool.

Carcinoma, Squamous Cell↗
PubMed2001

Drugs, guns, and kids: the association between substance use and injury caused by interpersonal violence.

BACKGROUND: Drug and alcohol uses have been linked to the frequency of injury events, recurrent hospital admission for injury, and interpersonal violence. Data regarding the association of recent substance use and injury type and frequency in children and young adults are not available. Such data probably would be valuable in planning interventions to prevent substance use and reduce the risks of injuries. METHODS: Evidence of substance use was assessed in trauma patients presenting to the authors' level 1 trauma center over a 6-month interval. Demographic data, mechanisms of injury, revised trauma scores (RTS), injury severity scores (ISS), hospital days, and mortality rate were evaluated. Chi square analysis and 2-tailed, paired t tests were used for statistical analysis. Multivariate logistic regression was utilized to determine the influence of individual variables. RESULTS: From a total group of 743 patients with life-threatening injuries, trauma registry records of 186 patients less than 21 years old were eligible for evaluation, and 126 of these had complete blood and urine drug assessments completed on admission to the trauma center. Forty-two percent (53 of 126) patients tested positive for alcohol or drugs. No patients less than 14 years of age (n = 61) had positive drug screen results. However, in the cohort of patients aged 14 and 15 (n = 17), 71% tested positive. Also, 72% of adolescents (age < 18) who were victims of injuries from gunshot wounds had evidence of substance use. Multivariate analysis showed gunshot wounds (P <.003) to be associated independently with positive drug screens. No statistical differences were observed in ethnic distribution, ISS, RTS, hospital days, or mortality rate when patients with positive screen results were compared with those without evidence of substance use. CONCLUSIONS: Trauma victims had evidence of substance use in early teen age years especially in the 14 and 15-year-old age groups. Toxicology screening disclosed that substance use is associated strongly with gunshot wounds. Substance use, along with poverty, inadequate family support, and peer pressure are factors that influence injury risk. Interventions to prevent substance use in young children may reduce the risk of injury.

Adolescent↗
PubMed2001

Congenital hypomyelination neuropathy in a newborn infant: unusual cause of diaphragmatic and vocal cord paralyses.

We report a case of congenital hypomyelination neuropathy presenting at birth. The infant had generalized hypotonia and weakness. There was decreased respiratory effort along with a right phrenic nerve and left vocal cord paralyses. Tongue fasciculations were present. Deep tendon reflexes were absent in the upper extremities and hypoactive (1+) in the lower extremities. Magnetic resonance imaging of the head revealed no intracranial abnormalities, including normal cerebral myelination. Nerve conduction study showed absence of motor and sensory action potentials in the hands when the nerves in the upper limbs were stimulated. A motor response could be elicited only in the proximal leg muscles. Needle electromyography study was normal in the proximal limb muscles, but showed active denervation in the distal muscles of the arm and leg. These findings were thought to be consistent with a length-dependent sensorimotor peripheral polyneuropathy of axonal type with greater denervation of the distal muscles. A biopsy of the quadriceps muscle showed mild variability in fiber diameter, but no group typing or group atrophy. The muscle fibers showed no intrinsic abnormalities. Biopsy of the sural nerve showed scattered axons with very thin myelin sheaths. There was also a nearly complete loss of large diameter myelinated fibers. No onion bulb formations were noted. These findings were thought to be consistent with congenital hypomyelination neuropathy with a component of axonopathy. DNA analysis for identification of previously characterized mutations in the genes MPZ, PMP22, and EGR2 was negative. Several attempts at extubation failed and the infant became increasingly ventilator-dependent with increasing episodes of desaturation and hypercapnea. He also developed increasing weakness and decreased movement of all extremities. He underwent surgery at 2 months of age for placement of a gastrostomy tube and a tracheostomy. He was discharged from the hospital on a ventilator at 6 months of age. The infant was 13 months old at the time of submission of this report. Although he appears cognitively normal, he remains profoundly hypotonic and is on a home ventilator. There was no evidence of progressive weakness. Congenital hypomyelination neuropathy is a rare form of neonatal neuropathy that should be considered in the differential diagnosis of a newborn with profound hypotonia and weakness. It appears to be a heterogeneous disorder with some of the cases being caused by specific genetic mutations.

Demyelinating Diseases↗
PubMed2001

Coordinate regulation of xenobiotic and bile acid homeostasis by pregnane X receptor.

Identification and characterization of the pregnane X receptor (PXR) as a key regulator of cytochrome P450 3A (CYP3A) gene expression has led to an increased understanding of the molecular basis of many drug-drug interactions. Mice lacking PXR (PXR-KO) were used in the present study to delineate the role of PXR in regulating hepatomegaly and regulating the activity of CYP3A, organic anion transporting polypeptide-2 (Oatp2), and Cyp7a1 (cholesterol 7alpha-hydroxylase) gene products in vivo. Pregnenolone-16alpha-carbonitrile (PCN) produced hepatomegaly in the wild-type mice but not in the PXR-KO mice. PCN increased both the number of proliferating cell nuclear antigen immuno-positive nuclei and apparent cell size in the wild-type mice but not in the PXR-KO mice. To determine the role PXR plays in regulating CYP3A activity, 6beta-hydroxylation of testosterone and the duration of the loss of righting reflex following administration of the muscle-relaxant zoxazolamine were measured. PCN increased the level of testosterone 6beta-hydroxylation and decreased the duration of the loss of righting-reflex time following zoxazolamine administration in wild-type mice, but did not effect either of these parameters in PXR-KO mice. PCN increased the hepatic uptake of [(3)H]digoxin, an Oatp2 substrate, in wild-type mice but not in the PXR-KO mice. Similarly, PCN decreased bile acid excretion in wild-type mice but not in the PXR-KO mice. Taken together, these data demonstrate a pivotal role for PXR in the regulation of drug-induced hepatomegaly and in the metabolism (CYP3A), transport (Oatp2), biosynthesis (Cyp7a1), and excretion of xenobiotics and bile acids in vivo.

Animals↗
PubMed2000

Characterization, chromosomal localization, and the complete 30-kb DNA sequence of the human Jagged2 (JAG2) gene.

The genomic sequence of the human Jagged2 (JAG2) gene, which encodes a ligand for the Notch receptors, was determined. The 30-kb DNA sequence spanning the JAG2 gene contains 26 exons and a putative promoter region. Several potential binding sites for transcription factors, including NF-kappab, E47, E12, E2F, Ets-1, MyoD, and OCT-1, were found in the human JAG2 promoter region. The JAG2 gene was also mapped to the chromosomal region 14q32 using fluorescence in situ hybridization.

Base Sequence↗
PubMed2000

Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha.

The switch to an angiogenic phenotype is a fundamental determinant of neoplastic growth and tumor progression. We demonstrate that homozygous deletion of the p53 tumor suppressor gene via homologous recombination in a human cancer cell line promotes the neovascularization and growth of tumor xenografts in nude mice. We find that p53 promotes Mdm2-mediated ubiquitination and proteasomal degradation of the HIF-1alpha subunit of hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor that regulates cellular energy metabolism and angiogenesis in response to oxygen deprivation. Loss of p53 in tumor cells enhances HIF-1alpha levels and augments HIF-1-dependent transcriptional activation of the vascular endothelial growth factor (VEGF) gene in response to hypoxia. Forced expression of HIF-1alpha in p53-expressing tumor cells increases hypoxia-induced VEGF expression and augments neovascularization and growth of tumor xenografts. These results indicate that amplification of normal HIF-1-dependent responses to hypoxia via loss of p53 function contributes to the angiogenic switch during tumorigenesis.

Adenocarcinoma↗
PubMed2000

Expression and regulation of cytochrome P450 enzymes in primary cultures of human hepatocytes.

The aim of this study was to test suitable culture conditions for maintaining normal cellular cytoarchitecture and inducibility of P450 enzymes in primary cultures of human hepatocytes by prototypical inducers. The selectivity and sensitivity of a sandwich culture system were determined by treating cultures with a number of clinically relevant drugs that are known to be inducers of either rodent and/or human P450 enzymes. The results showed that considerable induction of CYP3A4 activity is observed at DMSO concentrations greater than 0.1% (v/v). No differences in P450 induction response were observed between cultures maintained under different matrix conditions. However, the matrix condition considered to be optimal for maintaining cellular integrity, protein yields, and P450 enzyme induction was a sandwich configuration in combination with modified Chee's medium containing insulin (6.25 microg/mL) and dexamethasone (< or =0.1 microM). Under these conditions, induction of CYP3A4 occurred at clinically relevant drug concentrations, and maximal activities were achieved after 3 days of exposure. Overall, the response of human hepatocyte cultures to treatment with both positive and negative modulators was found to reflect that observed in vivo with respect to both enzyme specificity and potency of enzyme induction, although considerable sample-to-sample variability was observed in the magnitude of induction.

Cells, Cultured↗
PubMed2000

Gentamicin effects on urinary electrolyte excretion in healthy subjects.

BACKGROUND: Symptomatic hypomagnesemia, hypocalcemia, and hypokalemia caused by renal electrolyte wasting occasionally develop in patients treated with aminoglycosides. This phenomenon has been attributed to aminoglycoside tubular injury. However, rats administered a single dose of gentamicin show immediate dose-related calcium and magnesium renal wasting without sodium or potassium wasting days before other evidence of tubular dysfunction or structural injury can be shown. The mechanism is undefined but transient and is not dependent on the presence of parathyroid hormone. OBJECTIVE: To determine whether gentamicin administration to humans causes renal electrolyte wasting. DESIGN: Five healthy volunteers ingested a 400-mg calcium, 100-mEq sodium diet for 1 week before the study. After a 90-minute baseline period, 5 mg/kg gentamicin was administered intravenously over 30 minutes. Urine and serum were collected for 5 hours after gentamicin administration. RESULTS: Peak serum gentamicin levels ranged from 12.8 to 20.6 microg/mL. There was no change in serum electrolytes. The urinary fractional calcium excretion rose from a baseline of 1.8% +/- 0.5% to 6.8% +/- 1.4% (P < .01), and the magnesium fractional excretion rose from 3.4% +/- 0.8% to 11.8% +/- 6.4% (P = .03). These effects were transient. Gentamicin caused no change in renal excretion of sodium, potassium, or phosphate. CONCLUSIONS: Gentamicin administered at the standard clinical dose causes immediate and transient renal calcium and magnesium wasting in normal humans. The mechanism of gentamicin-associated urinary magnesium wasting and calciuria is undefined. However, the pattern of electrolyte excretion after gentamicin administration suggests that the site of action of these gentamicin effects is the distal convoluted tubule.

Adult↗
PubMed2000

Integration of modeling and acoustic microscopy measurements for thin films

A model for measuring the V(z) curve by line-focus acoustic microscopy contains the reflectance function of the specimen as a principal component. In this paper the reflectance function has been analyzed for multilayered thin films on a substrate for both fast-on-slow and slow-on-fast systems. The phase velocities of modes of surface acoustic wave propagation and their associated mode reflection coefficients can be obtained from the reflectance function. This information can be used together with estimates of the elastic constants to determine suitable frequency ranges for measuring the V(z) curve. Minimization of the difference between phase velocities obtained from measured and calculated V(z) curves is used to determine the elastic constants. Results are presented for TiN films on M2 high-speed steel substrates.

Journal Article↗
PubMed2000

Testing the hypothesis of a recombinant origin of human immunodeficiency virus type 1 subtype E.

The human immunodeficiency virus type 1 (HIV-1) epidemic in Southeast Asia has been largely due to the emergence of clade E (HIV-1E). It has been suggested that HIV-1E is derived from a recombinant lineage of subtype A (HIV-1A) and subtype E, with multiple breakpoints along the E genome. We obtained complete genome sequences of clade E viruses from Thailand (93TH057 and 93TH065) and from the Central African Republic (90CF11697 and 90CF4071), increasing the total number of HIV-1E complete genome sequences available to seven. Phylogenetic analysis of complete genomes showed that subtypes A and E are themselves monophyletic, although together they also form a larger monophyletic group. The apparent phylogenetic incongruence at different regions of the genome that was previously taken as evidence of recombination is shown to be not statistically significant. Furthermore, simulations indicate that bootscanning and pairwise distance results, previously used as evidence for recombination, can be misleading, particularly when there are differences in substitution or evolutionary rates across the genomes of different subtypes. Taken jointly, our analyses suggest that there is inadequate support for the hypothesis that subtype E variants are derived from a recombinant lineage. In contrast, many other HIV strains claimed to have a recombinant origin, including viruses for which only a single parental strain was employed for analysis, do indeed satisfy the statistical criteria we propose. Thus, while intersubtype recombinant HIV strains are indeed circulating, the criteria for assigning a recombinant origin to viral structures should include statistical testing of alternative hypotheses to avoid inappropriate assignments that would obscure the true evolutionary properties of these viruses.

Evolution, Molecular↗
PubMed2000

Maturational differences in hyperoxic AP-1 activation in rat lung.

Immature organisms (neonates; <12 h old) have vastly differing responses to hyperoxic injury than adults. A common feature of hyperoxic gene regulation is involvement of activator protein (AP)-1. We evaluated lung AP-1 binding as well as that of the AP-1 subunit proteins c-Fos, c-Jun, phosphorylated c-Jun, Jun B, and Jun D after exposure to >95% O(2) for 3 days. Unlike adults, neonates showed no increased AP-1 binding in hyperoxia despite a high affinity of the AP-1 binding complexes for phosphorylated c-Jun and Jun D as demonstrated by supershift of these antibodies with the AP-1 complexes. Moreover, neonatal lungs exhibited two distinguishable AP-1 binding complexes, whereas adult lungs had one. In neonates, sequential immunoprecipitation revealed that the lower AP-1 complex was composed of proteins from both the Fos and Jun families, whereas the upper complex consisted of Jun family proteins, with predominance of Jun D. In adults, the single AP-1 complex appeared to involve other Fos or non-Fos or non-Jun family proteins as well. Neonatal lungs showed a higher level of Jun B and Jun D immunoreactive proteins in both air and hyperoxia compared with those in adult lungs. These results suggest that significant maturational differences in lung AP-1 complexes exist and that these may explain transcriptional differences in hyperoxic gene regulation.

Aging↗