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Biomedical subjects

H Patel

Publications and source records attributed to H Patel.

At least 199 records · Page 11Linked to original sources

Indomethacin therapy in premature infants with patent ductus arteriosus--determination of therapeutic plasma levels.

To determine the therapeutic range of plasma indomethacin levels for ductus closure, we evaluated the ductus response and renal side effects on two therapeutic regimens using different dosage; regimen I received 0.3 mg/kg q 24 h for a maximum of 3 doses, and regimen II received 0.1, 0.2 and 0.3 mg/kg at 24-hour intervals, for a maximum of 3 doses if needed. Infants in regimen I had significantly higher plasma indomethacin and higher ductus response rate than infants in regimen II. Urine output (U/O) was comparable between the regimens, but serum sodium was lower in regimen I than in regimen II. In both regimens, U/O and serum sodium return to normal by 72 h. The plasma indomethacin levels at 12 h after 1 dose correlated significantly with ductus response and hyponatremia. There appeared to be a minimal level of plasma indomethacin above which U/O decreased; with a plasma level greater than 170 ng/ml the majority (greater than 97%) of infants showed a decrease in U/O. While there was a 50% or greater chance that ductus would close when the plasma levels reached 600 ng/ml or more, a great proportion of infants would also develop renal side effects. Thus, a safe therapeutic range of plasma indomethacin appeared to be very narrow. However, when the dose of indomethacin is increased to optimize constrictive response, there is no significant increase in incidence and severity of renal adverse effects. In view of the transient nature of renal side effects, they should not hinder indomethacin therapy if ductus closure is indicated.

Ductus Arteriosus, Patent↗

Acute staphylococcal septic arthritis: the effect of cloxacillin therapy in an avian model.

An experimental model of acute staphylococcal septic arthritis in chickens was used to study the effect of different therapeutic regimens of the antibiotic cloxacillin on the natural history of the disease. Three different therapeutic regimens were used in order to assess the effect of increasing the frequency and of delaying the commencement of administration. The results were assessed by measurement of animal growth rate, clinical condition, bacterial and leukocyte counts in synovial fluid, and histological appearance. An inadequate dosage regimen (a single daily dose) prevented spread of bacteria but did not control abscesses. Delay in commencing treatment permitted persistence and spread of abscesses with destruction of the secondary (epiphyseal) ossification center and even transphyseal spread into metaphyseal bone. Repair by fibroblasts was mainly seen in articular and epiphyseal cartilage but was not seen in the epiphyseal ossification center during the duration of the experiments (up to 18 days). Synovial fluid sampling with measurement of leukocyte and bacterial concentrations appears to be a useful guide to the effectiveness of treatment, because the numbers of cells correlate with the pathological process.

Acute Disease↗

Use of lacZ expression to monitor transcription.

For use in monitoring transcription in operon fusion, we have constructed a lacZ sequence with the initiation codon ATG and the Escherichia coli consensus Shine-Dalgarno site. There are unique restriction endonuclease sites flanking the sequence to allow easy isolation of the lacZ sequence with or without the Shine-Dalgarno site. We have placed this lacZ sequence behind the bovine growth hormone (BGH) gene and found that the lacZ product beta-galactosidase synthesized reflects the level of BGH-specific mRNA.

Animals↗

Sources of error in neonatal blood sampling.

Significant underestimation of blood electrolyte concentrations may occur if less than 1 ml of blood is withdrawn from an indwelling arterial line before taking the sample for analysis. Compared with arterial samples capillary samples give significant overestimations of potassium concentration and carbon dioxide tension, and significant underestimation of oxygen tension.

Arteries↗

Temporal relationships in the effects of protein-free diet on the activities of rat liver branched-chain ketoacid dehydrogenase complex and kinase.

Feeding rats 0% casein diet decreased liver activities of branched-chain ketoacid dehydrogenase complex (active form) and of activator protein (complete within 4 days), and increased activity of branched-chain ketoacid dehydrogenase kinase (complete within 9-10 days). Refeeding normal diet to rats fed 0% casein diet for 10 days resulted in a rapid and partial (approx. 50%) reversal of the above effects within 24 h; complete reversal required 20-30 days of refeeding.

Animals↗

Induction of a cationic shift in IgG anti-DNA autoantibodies. Role of T helper cells with classical and novel phenotypes in three murine models of lupus nephritis.

We investigated the underlying mechanisms of systemic autoimmune disease in MRL-+/+, (NZB X NZW)F1, and (NZB X SWR)F1 mice, since these strains develop glomerulonephritis without the superimposition of any secondary lupus-accelerating genes. All three strains manifested a common immunoregulatory defect specific for the production of pathogenic anti-DNA autoantibodies that are of IgG class and cationic in charge. At or just before the age they began to develop lupus nephritis, spleen cells of the mice contained a subpopulation of Th cells that selectively induced their B cells in vitro to produce highly cationic IgG autoantibodies to both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). By contrast, T cells from younger preautoimmune mice were incapable of providing this help. Moreover, only B cells of the older lupus mice could be induced to secrete cationic anti-DNA antibodies of IgG class. B cells of young lupus mice could not produce the cationic autoantibodies even with the help of T cells from the older mice, nor upon stimulation with mitogens. In the older lupus mice we found two sets of Th cells that spontaneously induced the cationic shift in autoantibodies; one set belonged to the classical Th category with L3T4+,Lyt-2- phenotype, whereas the other surprisingly belonged to a double-negative (L3T4-,Lyt-2-), Lyt-1+ subpopulation. The latter set of unusual Th cells were unexpected in these lupus mice since they lacked the lpr (lympho-proliferation) gene. Thus three apparently different murine models of systemic lupus erythematosus possess a common underlying mechanism specific for the spontaneous production of pathogenic anti-DNA autoantibodies.

Animals↗

Effects of low-protein diet and starvation on the activity of branched-chain 2-oxo acid dehydrogenase kinase in rat liver and heart.

The activity of branched-chain 2-oxo acid dehydrogenase kinase was 3-fold greater in extracts of heart mitochondria than in extracts of liver mitochondria from rats fed on normal diet. Feeding rats on a 0%-casein diet for 10 days increased the activity of branched-chain kinase 4-fold in extracts of liver mitochondria and in branched-chain dehydrogenase complex purified from such extracts; starvation (48 h) was without effect. In extract of heart mitochondria, kinase activity was increased 2-fold by feeding on 0%-casein diet and 1.5-fold by 48 h of starvation.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

Infections in patients with non-small-cell lung cancer treated with intensive induction chemotherapy.

The records of 65 consecutive patients with non-small-cell lung cancer (NSCLC) treated with intensive induction chemotherapy were reviewed to study the infectious complications during therapy and to analyze the relationship of the frequency of infections to various predisposing factors. A total of 44 infectious episodes were observed among 30 of the 65 patients. Of the 44 infections, 18 were microbiologically documented and 19 clinically. Seven (16%) infections were without microbiological or clinical documentation and were categorized as "possible" infections. Among the 18 microbiologically documented infections, fifteen (83%) were caused by bacteria and three by fungi. The most frequent bacteria identified in 11 (61%) of the 18 infections were gram-negative organisms, Escherichia coli and Klebsiella pneumoniae being the most frequent. Eight of the 44 infections were associated with bacteremia and three with microbiologically documented pneumonias. There were three drug-related infectious deaths, two associated with bacteremia and one with possible infections. All 44 infectious episodes presented with WBC counts of less than 1,000/microliter, and 34 (79%) had WBC counts of less than 500/microliter. We observed that during therapy, patients with poor performance status (less than 80%) are at a much higher risk to develop infectious complications than those with good performance status (greater than 80%; p less than .001). Although encouraging responses with intensive chemotherapy have been reported for NSCLC in several studies, a major impact of chemotherapy on the survival of patients with this disease has yet not been established. Thus, intensive chemotherapy for NSCLC should remain an experimental treatment modality and should be offered only to patients with good prognostic factors such as those defined by pretreatment performance status.

Adult↗

Pulmonary and renal responses to furosemide in infants with stage III-IV bronchopulmonary dysplasia.

Pulmonary and renal responses to furosemide were evaluated in ten infants with stage III-IV bronchopulmonary dysplasia. Furosemide was given intravenously for two doses, 1 and 2 mg/kg, at approximately 24-hour intervals. The following indices were evaluated in series before and after entry into study: clinical respiratory distress syndrome score; blood pH; partial pressure of arterial carbon dioxide; alveolar-arterial oxygen gradient; urine output; glomerular filtration rate; fractional excretion of filtered sodium, chloride, potassium, and calcium; osmolar clearance; water clearance; and concentrations of serum electrolytes and calcium. A significant decrease in the respiratory distress syndrome score and in the partial pressure of arterial carbon dioxide was seen only transiently at two hours following each dose. There was no significant improvement in the alveolar-arterial oxygen gradient during the study. Furosemide induced diuresis and urinary excretion of sodium, chloride, potassium, and calcium. A significant decrease in serum chloride and potassium concentrations was seen at 48 hours after entry into study; serum sodium and calcium concentrations remained unchanged. This study has demonstrated that furosemide administration has only a short-term effect in the lung but has a potential for long-term complication on electrolytes and calcium balance in infants with well-established stage III-IV bronchopulmonary dysplasia.

Bronchopulmonary Dysplasia↗

Vindesine and high-dose cisplatin in the treatment of advanced non-small-cell lung cancer.

Seventeen patients with advanced non-small-cell lung cancer (NSCLC) were entered on a combination chemotherapy protocol including vindesine and high-dose cisplatin. All patients had measurable disease and had not previously received chemotherapy. All patients entered were evaluable for toxicity and response. Tumor regression was limited to one complete and one partial response (response rate, 11.7%; 95% confidence limits, 0 to 27%). The complete and partial response lasted 260 + and 82 days, respectively. For the 15 nonresponding patients, the median time to disease progression was 76 days. Median survival was 141 days for the whole group. Significant toxic effects were vindesine-related peripheral neuropathy and cisplatin-induced emesis. Myelosuppression was mild and manageable. The response for the vindesine-cisplatin combination observed in our study is inferior to that seen in a previous vindesine-cisplatin trial reported by others. Thus, the true value of this two-drug regimen in the treatment of NSCLC remains to be established.

Adenocarcinoma↗

Finite element method modeling of craniofacial growth.

The application of the concepts of continuum mechanics and of the numerical techniques of the finite element method permits the development of a new and potentially clinically useful method of describing craniofacial skeletal growth. This new method differs from those associated with customary roentgenographic cephalometry in that its descriptions and analyses are invariant; that is, they are independent of any method of registration and superimposition. Such invariance avoids the principal geometric constraint explicit in all analytical methods associated with conventional roentgenographic cephalometry. The conceptual and mathematical bases of the finite element method (FEM) are presented and illustrated by the numerical and graphic descriptions of the two-dimensional growth of the rat skull, for which two sets of longitudinal growth data are used. In practice, the FEM permits analysis of the skull at a scale significantly finer than previously possible, by considering cranial structure as consisting of a relatively large number of contiguous finite elements. For each such element, independently, it is then possible to describe and depict both the magnitude and the direction of temporal size and shape changes occurring in that element relative to itself at some initial time. It is emphasized that such descriptions are completely independent of any local reference frame.

Aging↗

Multiple system atrophy with neuronal intranuclear hyaline inclusions. Report of a case and review of the literature.

A 31/2-year-old girl presented with frequent falls. She had an unsteady gait, delayed behavioural development absent tendon reflexes and in the legs decreased strength tone and equivocal plantar responses. She then developed ataxia, nystagmus, choreoathetosis, cranial nerve palsies, diminished strength and tone in the arms, sensory deficit in the limbs and autonomic nervous system dysfunction. She became progressively less responsive and succumbed at the age of 63/4 years. Examination of the central, peripheral and autonomic nervous system showed ubiquitous neuronal intranuclear hyaline inclusions and neuronal loss in several sites.

Amino Acids↗

An acquired form of epidermolysis bullosa without immunoreactants. Report of a case.

A patient with a 10-year history of an acquired, scarring bullous eruption localized to the anterior surfaces of the lower extremities is described. Clinical, histologic, and electron microscopic features of an acquired form of epidermolysis bullosa are shown to occur in the absence of immune deposits, a finding not previously documented.

Aged↗

Brazilian pemphigus foliaceus autoantibodies are pathogenic to BALB/c mice by passive transfer.

Brazilian pemphigus foliaceus (fogo selvagem) is a cutaneous blistering disease endemic to certain areas of South America that has distinctive epidemiologic features suggestive of an infectious disease transmitted by an insect vector. Patients with the disease have antiepithelial autoantibodies, both circulating in the serum and bound to lesional epidermis. In order to examine the possible pathogenic role of these autoantibodies, IgG from the sera of these patients was purified and injected into the peritoneum of neonatal BALB/c mice. Thirty-four of 46 mice (74%) receiving parenteral IgG fractions from these patients developed cutaneous lesions that were identical to the human disease by clinical, histologic, immunologic, and ultrastructural criteria. High-titer Brazilian pemphigus foliaceus sera produced lesions more consistently and rapidly than low-titer sera. When injections were discontinued, new lesions ceased to appear and old lesions resolved. The extent of disease correlated with the titer of human antiepithelial antibodies detected in the mouse serum (z less than 0.01). Similar concentrations of IgG fractions obtained from sera of unaffected Brazilians living in endemic areas and from American donors did not induce disease when injected into littermates. These results establish that the antiepithelial autoantibodies play an important role in the pathogenesis of the cutaneous lesions in Brazilian pemphigus foliaceus.

Animals↗