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Biomedical subjects

J Patel

Publications and source records attributed to J Patel.

At least 73 records · Page 4Linked to original sources

Size distribution of recruited alveolar volumes in airway reopening.

In 11 isolated dog lung lobes, we studied the size distribution of recruited alveolar volumes that become available for gas exchange during inflation from the collapsed state. Three catheters were wedged into 2-mm-diameter airways at total lung capacity. Small-amplitude pseudorandom pressure oscillations between 1 and 47 Hz were led into the catheters, and the input impedances of the regions subtended by the catheters were continuously recorded using a wave tube technique during inflation from -5 cm H(2)O transpulmonary pressure to total lung capacity. The impedance data were fit with a model to obtain regional tissue elastance (Eti) as a function of inflation. First, Eti was high and decreased in discrete jumps as more groups of alveoli were recruited. By assuming that the number of opened alveoli is inversely proportional to Eti, we calculated from the jumps in Eti the distribution of the discrete increments in the number of opened alveoli. This distribution was in good agreement with model simulations in which airways open in cascade or avalanches. Implications for mechanical ventilation may be found in these results.

Animals↗

Randomized double-blind controlled trial comparing the effects of ibuprofen with indomethacin on cerebral hemodynamics in preterm infants with patent ductus arteriosus.

A prospective randomized controlled trial was performed to compare the effects of ibuprofen with indomethacin on cerebral hemodynamics measured using near infrared spectroscopy in preterm infants during treatment for patent ductus arteriosus. Infants were randomly assigned to three intravenous doses of either indomethacin (0.20-0.25 mg/kg, 12 hourly) or ibuprofen (5-10 mg/kg, 24 hourly) and also received a dose of saline. The primary end points of the study were the effects of the first dose on cerebral blood flow (CBF) and cerebral blood volume. Fifteen infants received indomethacin and 18 received ibuprofen. The group mean (SD) values for CBF (mL x 100 g(-1) x min(-1)) before and after the first dose of indomethacin were 13.6 (4.1) and 8.3 (3.1), respectively, the change being significant (p<0.001). In contrast, no significant changes in CBF were observed with the first dose of ibuprofen, the respective before and after values being 13.3 (3.2) and 14.9 (4.7) mL x 100 g(-1) x min(-1). The median (interquartile range) value for change in cerebral blood volume (mL/100 g) after the first dose in the indomethacin group was -0.4 (-0.3 to -0.6) and in the ibuprofen group was 0.0 (0.1 to -0.1), the difference between the two groups being significant (p<0.001). Cerebral oxygen delivery changed significantly after the first dose in the indomethacin group but not in the ibuprofen group. Significant reductions in CBF, cerebral blood volume, and cerebral oxygen delivery also occurred after the 24-h dose of indomethacin, but there were no significant changes after the 48-h dose of saline in the indomethacin group or after the 24- and 48-h doses of ibuprofen. The patent ductus arteriosus closure rates after indomethacin and ibuprofen were 93 and 78%, respectively. We conclude that ibuprofen, unlike indomethacin, has no adverse effects on cerebral hemodynamics and appears to mediate patent ductus arteriosus closure.

Brain↗

Nerve conduction impairment in experimental diabetes-proximodistal gradient of severity.

We compared a conventional method of measurement of sciatic motor and sensory nerve conduction velocity, with a novel procedure that measures conduction in an 8-mm segment of the rat sural nerve. Conventional procedures gave reductions in velocity of 20% and 14% for motor and sensory fibers, respectively, whereas sural sensory fibers showed a 40% reduction (P <0.05). Changes were attenuated by treatment with either an aldose reductase inhibitor or a gamma-linolenic acid-alpha-lipoic acid conjugate, such that values from conventional procedures were not significantly different from controls and the sural sensory deficit halved. Putative motor fibers of the sural nerve showed no conduction velocity deficit in diabetic rats. Measurement of chronaxie and rheobase in sural sensory fibers revealed mild reductions in excitability in diabetics, with prevention of the chronaxie change by the treatments. Thus, measurement of sensory conduction in distal nerve segments show more profound defects in diabetic rats and may give a truer picture of preventive drug efficacy.

Animals↗

Is blastocyst transfer useful as an alternative treatment for patients with multiple in vitro fertilization failures?

OBJECTIVE: To determine whether blastocyst transfer is of benefit to patients with multiple IVF failures. DESIGN: Retrospective cohort study. SETTING: The George Washington University Medical Center. PATIENT(S): Patients undergoing IVF between October 1, 1997, and November 30, 1998, who had previously undergone three or more unsuccessful IVF cycles. Patients who had at least three embryos at the 8- to 12-cell stage available on day 3 were eligible for the study. INTERVENTION(S): Patients were given the option of day 3 ET (group A) or blastocyst transfer (group B). MAIN OUTCOME MEASURE(S): Blastocyst-formation rate, clinical pregnancy rate (PR) per transfer, and implantation rate per transfer. RESULT(S): Groups A and B were similar in terms of age, the number of previous failed IVF cycles, fertilization rate, and the number of fertilized oocytes per cycle. The blastocyst-formation rate was 51.0%. Clinical pregnancy and implantation rates per transfer were statistically significantly higher in the blastocyst-transfer group. There were no multiple pregnancies after blastocyst transfer. CONCLUSION: Blastocyst transfer increases implantation rates and PRs in patients with multiple failed IVF cycles, without increasing the risk of multiple pregnancy.

Adult↗

Severe polyethylene wear in uncemented acetabular cup system components: a report of 5 cases.

We report 5 cases of severe failure of the polyethylene liner at 4 to 7.4 years after uncemented anatomic medullary locking (AML) total hip arthroplasty, using the acetabular cup system (ACS). The mode of failure was by a combination of wear-through to the metal backing and liner fracture. Four of the 5 cases were associated with a 32-mm head. The ACS design is flawed because of a lack of hemispherical geometry resulting in rim loading on a region of the liner that has the thinnest polyethylene. All patients with this type of implant should be monitored for evidence of excessive polyethylene wear.

Acetabulum↗

Rosiglitazone monotherapy improves glycaemic control in patients with type 2 diabetes: a twelve-week, randomized, placebo-controlled study.

AIM: Rosiglitazone is the most potent of the thiazolidinediones, a novel class of oral antidiabetic agents that reduce blood glucose levels by sensitizing peripheral tissues to insulin. This study was designed to identify doses of rosiglitazone that would lower fasting plasma glucose (FPG) in patients with type 2 diabetes. METHODS: In this 12-week, double-blind, multicentre study, 380 patients with FPG values > or =7.8 mmol/L (140 mg/dL) and < or =13.3 mmol/L (240 mg/dL) were randomly assigned to receive treatment with placebo or rosiglitazone, 0.05, 0.25, 1.0, or 2.0 mg twice daily. The primary efficacy parameter was changed in FPG from baseline after 12 weeks of treatment. Secondary endpoints were changes in HbA1c, fructosamine, C peptide, insulin, lipid levels, and body weight (b.w.). Safety monitoring included clinical laboratory evaluations, electrocardiography, and echocardiography. RESULTS: Rosiglitazone 1.0 and 2.0 mg b.i.d. produced significant decreases in FPG (p=0.0001). Fructosamine also decreased in patients treated with these two dosages (p=0.003 in the 2.0 mg b.i.d. group). Rosiglitazone 2.0 mg b.i.d. significantly reduced plasma insulin levels (p=0.0044) and free fatty acids (p=0.0014) compared with placebo. Total cholesterol (p=0.0001), HDL (p=0.0009), and LDL (p=0.0001) increased in the rosiglitazone 2.0 mg b.i.d. group, but there was no significant change in the total cholesterol/HDL ratio or triglyceride levels in any rosiglitazone treatment group. Clinically insignificant dose-dependent increases in b.w. were observed in the rosiglitazone 1.0 and 2.0 mg b.i.d. treatment groups. CONCLUSIONS: Twelve weeks of treatment with rosiglitazone 2.0 mg b.i.d. significantly decreases fasting plasma glucose, fructosamine, plasma insulin, and free fatty acids in patients with type 2 diabetes. Longer studies using higher doses will be needed to assess the efficacy and safety of rosiglitazone in patients with type 2 diabetes mellitus.

Adult↗

The impact on accuracy and cost of ligase chain reaction testing by pooling urine specimens for the diagnosis of Chlamydia trachomatis infections.

BACKGROUND AND OBJECTIVES: Nucleic acid amplification testing is the most accurate approach to diagnosing Chlamydia trachomatis infections. Our objective was to compare the accuracy and cost savings of pooling urines as opposed to individual testing. STUDY DESIGN: Strategies of pooling urine specimens into groups of four (4x pool) or eight (8x pool) followed by testing the positive pools individually were compared to individual specimen testing to determine if significant cost savingS could be realized without compromising the sensitivity and specificity of the LCx C. trachomatis Assay (Abbott Laboratories, Abbott Park, Chicago, IL) performed in a busy private medical laboratory. RESULTS: A total of 1,220 patient urine samples, 1,187 male (97%) and 33 female (3%), were tested using the normal LCx specimen to cutoff ratio (S/CO) of 1.0 and a decreased S/CO value of 0.2. Individual testing identified 98.2% (109/111) of positive urines. The 4x pooling maneuver identified 92.8% (103/111) of positive patients with the regular cutoff and 96.4% (107/111) when the cutoff was decreased. These values were 95.9% (47/49) and 97.9% (48/49), respectively, when eight urines were pooled. Both pooling and individual testing strategies identified all the negative samples accurately. Cost savings of pooling were calculated to be 44.5% for pools of four and 37.5% for pools of eight, applying the lowered cutoff. CONCLUSIONS: Pooling urine specimens for testing with the C. trachomatis LCx system is a simple, accurate, and cost-saving approach that can significantly reduce the cost of amplified nucleic acid testing with minimal sacrifice of testing accuracy.

Adolescent↗

Covalent interactions are not required to permit or stabilize the non-covalent association of hepatitis C virus glycoproteins E1 and E2.

Hepatitis C virus (HCV) encodes two glycoproteins, E1 and E2, which are thought to locate to the envelope of virus particles. These proteins form two complexes in tissue culture systems, a high molecular mass aggregate that contains intermolecular covalent bonds and a native complex in which E1 and E2 associate by non-covalent interactions. The contribution of either complex to the structures of the proteins on virus particles is not known. Using dithiothreitol to reduce inter- and intramolecular disulphide bonds in situ, we have studied the nature of the interactions within the aggregate and the role of covalent bonds in the early stages of E1-E2 association. Results with two HCV type 1a strains, Glasgow and H77, showed that the aggregate contains not only covalent interactions but also non-covalent associations between E1 and E2. These non-covalent associations are complex since deletion mutant analysis failed to identify any single region which was required for non-covalent interaction. Complex formation by de novo synthesized proteins was not arrested under reducing conditions which prevented the production of inter- and intramolecular disulphide bonds. Moreover, a conformation-specific antibody continued to recognize the E2 protein in reduced complexes, indicating that covalent bonds do not stabilize certain structures of E2 that can interact with E1. These data suggest that disulphide bonds are not required either to allow association between the proteins or to stabilize E1-E2 complexes.

Hepacivirus↗

Serum paraoxonase after myocardial infarction.

HDL has been shown to prevent the oxidative modification of LDL. The antioxidant activity of HDL is believed to reside in its enzymes, particularly paraoxonase. Human serum paraoxonase (PON1) is closely associated with a specific HDL subfraction also containing apoA1 and clusterin. Recently PON1 has been implicated in the pathogenesis of atherosclerosis. We have examined the activity, concentration, and specific activity of PON1 in 50 patients on admission to hospital immediately after acute myocardial infarction (MI) and in 48 age- and gender-matched controls. Serum PON1 activity and concentration were significantly lower in patients with MI than in controls (activity, 221.5 [99.3 to 303.2] nmol. min-1. mL-1 in controls and 130.1 [78.9 to 230.3] nmol. min-1. mL-1 in MI patients [P<0.05]; concentration, 95.7 [73.2 to 135.5] microg/mL in controls and 35.4 [21.6 to 51.3] microg/mL in MI patients [P<0.001]). PON1-specific activity was significantly higher in patients with MI than in controls (1.5 [0.9 to 2.9] versus 3.4 [2.0 to 8.5] nmol. min-1. microg-1 [P<0.001]) due to the much lower PON1 concentration. PON1 activity had risen significantly (P<0.05) to 158.1 (85.4 to 282.0) nmol. min-1. mL-1 at day 42 but was still significantly less than that of controls. No significant variation in PON1 concentration occured in the days after MI or at 6 weeks. Also, no significant variation in specific activity was seen after MI. When the patients were divided into subgroups based on whether or not they received thrombolytic therapy on admission to hospital, no significant difference in PON1 levels was observed. Serum HDL cholesterol in patients with MI on admission was not significantly different than in controls, and the decrease that occurred by the fifth day after MI did not explain the lower PON1 levels. We conclude that low serum PON1 activity in patients with MI may be a consequence of the coronary event itself or could have been present before MI. The low PON1 activity was also not explicable on the basis of PON1 genotypes because the prevalence of genotypes associated with low activity was not sufficient to explain fully the difference in activity levels between patients and controls. The explanation for the low PON1 activity was most likely a decrease in serum PON1 concentration. The importance of PON1 as a predictive risk factor for MI should be assessed in future studies.

Aryldialkylphosphatase↗

Anaesthesia for LSCS in a morbidly obese patient.

The management of a morbidly obese parturient with a body mass index of 88 is reported. She developed asthma during the pregnancy. Lumbar epidural anaesthesia was successfully used for an elective caesarean section and tubal ligation.

Adult↗

Phase I clinical and pharmacologic study of 13-cis-retinoic acid, interferon alfa, and paclitaxel in patients with prostate cancer and other advanced malignancies.

PURPOSE: Recent studies demonstrate that retinoids decrease expression of the anti-apoptotic protein bcl-2, enhance the effect of chemotherapy, and act synergistically with interferon alfa (IFNalpha) to inhibit tumor cell growth in vitro. A phase I trial of 13-cis-retinoic acid (CRA), IFNalpha, and paclitaxel (TAX) was conducted to determine the toxicity and recommended phase II dose of this combination. Pharmacodynamic studies were performed to determine whether CRA and IFNalpha could modulate bcl-2 expression in vitro and in patients. PATIENTS AND METHODS: Twenty-two patients with prostate cancer or other advanced malignancies were treated with CRA/IFNalpha and escalating doses of TAX. The effect of CRA/IFNalpha on TAX pharmacokinetics was analyzed in both patients and human liver microsomes. The effect of CRA/IFNalpha on bcl-2 expression was assessed in vitro and in peripheral-blood mononuclear cells (PBMCs) by immunoblotting. RESULTS: CRA 1 mg/kg on days 1 to 4, IFNalpha 6 MU/m(2) subcutaneously on days 1 to 4, and TAX 175 mg/m(2) on day 3 was well tolerated. Pharmacokinetic studies demonstrated that CRA/IFNalpha caused a 33% decrease in TAX clearance and a 23% decrease in the area under the concentration-time curve values of the TAX metabolite 6-alfa-hydroxytaxol (6-HT). CRA alone reduced conversion of TAX to 6-HT by 41% in human liver microsomes. CRA/IFNalpha decreased bcl-2 expression in vitro and in PBMCs. CONCLUSION: CRA/IFNalpha and TAX is a well-tolerated regimen. CRA/IFNalpha increases TAX area under the concentration-time curve through an inhibitory effect of CRA on the metabolism of TAX to 6-HT. CRA/IFNalpha can modulate bcl-2 expression in vitro and demonstrates similar biologic activity in patients. Further studies will determine the activity of CRA/IFNalpha/TAX and validate the assessment of bcl-2 in PBMCs as a marker of tumor response.

Adult↗

Aberrant neurofilament phosphorylation in sensory neurons of rats with diabetic neuropathy.

Aberrant neurofilament phosphorylation occurs in many neurodegenerative diseases, and in this study, two animal models of type 1 diabetes--the spontaneously diabetic BB rat and the streptozocin-induced diabetic rat--have been used to determine whether such a phenomenon is involved in the etiology of the symmetrical sensory polyneuropathy commonly associated with diabetes. There was a two- to threefold (P < 0.05) elevation of neurofilament phosphorylation in lumbar dorsal root ganglia (DRG) of diabetic rats that was localized to perikarya of medium to large neurons using immunocytochemistry. Additionally, diabetes enhanced neurofilament M phosphorylation by 2.5-fold (P < 0.001) in sural nerve of BB rats. Neurofilaments are substrates of the mitogen-activated protein kinase (MAPK) family, which includes c-jun NH2-terminal kinase (JNK) or stress-activated protein kinase (SAPK1) and extracellular signal-regulated kinases (ERKs) 1 and 2. Diabetes induced a significant three- to fourfold (P < 0.05) increase in phosphorylation of a 54-kDa isoform of JNK in DRG and sural nerve, and this correlated with elevated c-Jun and neurofilament phosphorylation. In diabetes, ERK phosphorylation was also increased in the DRG, but not in sural nerve. Immunocytochemistry showed that JNK was present in sensory neuron perikarya and axons. Motoneuron perikarya and peroneal nerve of diabetic rats showed no evidence of increased neurofilament phosphorylation and failed to exhibit phosphorylation of JNK. It is hypothesized that in sensory neurons of diabetic rats, aberrant phosphorylation of neurofilament may contribute to the distal sensory axonopathy observed in diabetes.

Animals↗

Association analysis of sequence variants of GABA(A) alpha6, beta2, and gamma2 gene cluster and alcohol dependence.

Quantitative trait analyses in mice suggest a vulnerability locus for physiological alcohol withdrawal severity on a chromosomal segment that harbors the genes encoding the alpha1, alpha6, beta2, and gamma2 subunits of the gamma-aminobutyric acid type-A receptor (GABR). We tested whether genetic variation at the human GABA(A) alpha6, beta2, and gamma2 gene cluster on chromosome 5q33 confers vulnerability to alcohol dependence. The genotypes of three nucleotide substitution polymorphisms of the GABRA6, GABRB2, and GABRG2 genes were assessed in 349 German alcohol-dependent subjects and in 182 ethnically matched controls. To eliminate some of the genetic variance, three more homogeneous subgroups of alcoholics were formed by: (1) a history of alcohol withdrawal seizure or delirium (n = 106); (2) a history of parental alcoholism (n = 120); and (3) a comorbidity of dissocial personality disorder (n = 57). We found no evidence that any of the investigated allelic variants confers vulnerability to either alcohol dependence or severe physiological alcohol withdrawal symptoms or familial alcoholism (p > 0.05). The frequency of the T allele of the GABRA6 polymorphism was significantly increased in dissocial alcoholics [f(T) = 0.799] compared with the controls [f(T) = 0.658; p = 0.002; OR(T+) = 7.26]. Taking into account the high a priori risk of false-positive association findings due to multiple testing, further replication studies are necessary to examine the tentative phenotype-genotype relationship of GABRA6 gene variants and dissocial alcoholism.

Adult↗

Measuring the noise attenuation of shotblasting helmets.

Air-fed blasting helmets are used in abrasive blasting operations to provide essential face, eye and respiratory protection. BS EN 271: 1995 (equivalent to the European Standard EN 271: 1997), the standard that deals with the construction of blasting helmets, addresses the above matters and also the problem of noise generated by the breathing air supply. However it has no requirements for manufacturers to measure or report the helmet's ability to attenuate the very high levels of noise generated by the blasting process. The aim of the project was to develop a test method to measure the noise attenuation of shotblasting helmets. The method developed is an objective measurement, using a head and torso simulator (HATS), which provides a suitable means for helmet manufacturers to report their product's ability to attenuate blasting noise. The results from this project showed that the HATS currently prescribed by BS EN 271: 1995 can be used for measuring the noise attenuation of helmets against typical shotblasting noise. Using such a HATS in the proposed test method will give attenuation values that correlate well with those measured using human subjects. Therefore the HATS already used by manufacturers to show compliance of their product with BS EN 271: 1995 could also be used to provide information on the helmet's noise attenuation. Results from this project also showed that the same HATS can be used, in place of human subjects, to measure the air supply noise according to the method defined in BS EN 271: 1995. BS EN 271: 1995 is due for revision in 2000. The results from this work should be used to influence future revisions of the standard so that requirements to measure and report noise attenuation of shotblasting helmets are considered, a major omission in the present standard.

Equipment Design↗