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Biomedical subjects

R Patel

Publications and source records attributed to R Patel.

At least 289 records · Page 16Linked to original sources

Implications of an audible third heart sound in evaluating cardiac function.

We prospectively compared auscultatory findings of third heart sounds with radionuclide ventriculographic analysis of systolic and diastolic function. Cardiac auscultation was done to detect an S3 in patients referred for radionuclide ventriculographic analysis of ventricular function. Of 49 adult men with the diagnosis of chronic, nonvalvular heart failure who were referred for the evaluation of heart failure, 22 (45%) at the time of the ventriculography had an S3 present on examination. For the entire study group, the radionuclide ventriculography-derived ejection fraction was 33% +/- 19.5 (mean +/- SD) with a range of 6% to 74%. The peak ejection rate was 2.05 +/- 1.09 end-diastolic volume per second with a range of 0.30 to 4.56. The peak filling rate was 1.97 +/- 1.07 end-diastolic volume per second with a range of 0.44 to 3.94, and the time to peak filling rate was 0.18 +/- 0.11 per second with a range of 0.05 to 0.61. The presence of an S3 was associated with a reduced ejection fraction and also with impaired diastolic function as determined by the peak filling rate. The sensitivity and specificity for the S3 in detecting abnormal systolic function (ejection fraction < 50%) were 51% and 90%, respectively, with a positive predictive value of 95% and a negative predictive value of only 32%. For an ejection fraction of less than 30%, the S3 had a sensitivity and specificity of 78% and 88%. The presence of an S3 was highly predictive of an abnormal ejection fraction. The absence of an S3, however, is not uncommon in patients with a mildly impaired ejection fraction.

Aged↗

Enzyme-linked immunosorbent assay for the detection of antibodies to exocellular proteins of Staphylococcus aureus in bone infection.

An enzyme-linked immunosorbent assay (ELISA) was developed for measurement of the antibody response to exocellular protein antigens of Staphylococcus aureus. The wells of a microtitre plate were coated with the exocellular proteins present in the tryptic soya broth growth medium from a stationary phase culture of a bone infection strain of S. aureus. The wells were then reacted sequentially with patient sera, protein A-peroxidase conjugate and chromogenic substrate. Serum from patients with S. aureus bone infection gave a significantly higher IgG titre than sera from patients with Staphylococcus epidermidis or Streptococcus sanguis bone infection or healthy uninfected individuals. The assay therefore appears to have potential in the serodiagnosis of S. aureus bone infection.

Antibodies, Bacterial↗

Generation of Minute phenotypes by a transformed antisense ribosomal protein gene.

Antisense RNAs have been used for gene interference experiments in many cell types and organisms. However, relatively few experiments have been conducted with antisense genes integrated into the germ line. In Drosophila reduced ribosomal protein (r-protein) gene function has been hypothesized to result in a Minute phenotype. In this report we examine the effects of antisense r-protein 49 expression, a gene known to correspond to a Minute mutation An antisense rp49 gene driven by a strong and inducible promoter was transformed into the Drosophila germ line. Induction of this gene led to the development of flies with weak Minute phenotypes and to the transient arrest of oogenesis. Parameters that may affect the success of antisense gene inactivation are discussed.

Animals↗

Human recombinant interferon alpha inhibits naloxone binding to rat brain membranes.

Regulation of certain central nervous system (CNS) functions by the immune system may involve interferons (IFNs) acting through opioid receptors. Human recombinant interferon alpha (hrIFN alpha), as well as natural IFN alpha, have been reported to modulate a variety of physiological CNS functions both in vivo and in vitro. If the mechanism is via opioid receptors then IFN alpha should inhibit the binding of certain opioid radioligands to brain membranes. This study reports the inhibitory effect of hrIFN alpha on the binding of 3H-naloxone to rat brain membranes in vitro. The inhibitory effect at 37 degrees C is hrIFN alpha concentration dependent over the range of 500 to 6000 antiviral units per ml (U/ml) with 500 micrograms of membrane protein. The presence of NaCl (100mM) increases specific binding of naloxone and attenuates the inhibitory effect of hrIFN alpha. The inhibitory effect of hrIFN alpha is sensitive to temperature with maximum inhibition observed at 37 degrees C, and less as incubation temperature is reduced. These data suggest that IFN alpha may modulate certain physiologic functions via opioid pathways in the brain.

Animals↗

An unusual case of myxedema megacolon with features of ischemic and pseudomembranous colitis.

Myxedema megacolon is rare; usually, it manifests with abdominal distention, flatulence, and constipation. Herein we describe a 72-year-old man who had intermittent diarrhea, bloating, and abdominal pain for more than a year. Cultures of stool specimens for Clostridium difficile enterotoxin were variably positive and negative. Colonoscopic biopsy specimens were thought to be consistent with chronic ischemia. Thyroid function tests showed severe hypothyroidism; the patient's symptoms resolved with thyroid hormone replacement. We hypothesize that gross dilatation of the colon, attributed to myxedema, was followed by intestinal ischemia and complicated by recurrent episodes of pseudomembranous colitis. A review of the relevant literature is provided. This unusual manifestation of myxedema should be considered in the differential diagnosis when a patient has diarrhea, bloating, and abdominal pain.

Aged↗

Thyroid involvement in multiple myeloma.

Involvement of the thyroid gland by plasma cell neoplasms is a rare occurrence. Two modes of presentation are described; firstly as part of disseminated myeloma and secondly, as an isolated plasma cell neoplasm of the thyroid as the only evidence of disease. We wish to describe two cases of thyroid involvement as part of disseminated disease.

Aged↗

Venous occlusion secondary to subluxation of the shoulder--a case report.

This is the case report of an eighty-seven-year-old woman who was seen because of swelling of her left upper extremity and breast of one week's duration. She had a history of severe arthritis of the knees and had been wheelchair-bound for seven years. Venography showed compression of the cephalic vein and thrombosis of the distal basilic vein with extension into the axillary and subclavian veins. To the author's knowledge, this is the first case report of venous thrombosis in association with subluxation of the shoulder.

Aged↗

Methemoglobinemia in a patient undergoing gastrointestinal endoscopy.

OBJECTIVE: To report a case of methemoglobinemia induced by benzocaine in a patient undergoing gastrointestinal endoscopy. CASE SUMMARY: Before undergoing an upper gastrointestinal endoscopy, a 15-year-old girl received 20% benzocaine as a spray, to locally anesthetize the pharyngeal mucosa. Thirty minutes after the endoscopy, the patient suddenly became cyanotic, short of breath, and comatose. She was intubated and transferred to the intensive care unit. Her blood methemoglobin concentration was 54 percent. The patient was treated with intravenous methylene blue. Four hours later she was extubated. She was alert, awake, and asymptomatic. DISCUSSION: This is the fourth reported case of methemoglobinemia induced by benzocaine spray in patients undergoing gastrointestinal endoscopy. Pathways for the formation of methemoglobin in the body are reviewed. Intravenous methylene blue is the drug of choice for this condition, and produces rapid and dramatic reversal of methemoglobinemia. CONCLUSIONS: It is common to use benzocaine spray prior to upper gastrointestinal endoscopy. Benzocaine rarely induces methemoglobinemia in these patients. Prompt diagnosis and treatment with intravenous methylene blue is warranted in such cases.

Adolescent↗

Inhibition by amiloride and quinacrine of specific [3H]nitrendipine binding to rat cardiac membranes.

Binding studies were designed to test if and how amiloride and quinacrine affected the specific binding of [3H]nitrendipine (NIT) to rat cardiac membranes. Specific binding of NIT was inhibited in a dose-dependent manner by amiloride [Hill coefficient (nH), 1.46; concentration of inhibitor producing 50% inhibition (K0.5) = 9.2 x 10(-4) M] and quinacrine (nH = 0.54, K0.5 = 7.7 x 10(-6) M). The inhibitions were incomplete in the presence of 10(-3) M Ca ions. The Hofstee plot was convex upwards for amiloride and concave upwards for quinacrine. Amiloride increased the Kd, decreased the maximum specific binding and increased the k-1. Quinacrine increased the Kd without changing the maximum specific binding and increased the k-1. The effects of amiloride and quinacrine on k-1 were nonadditive. We conclude that amiloride and quinacrine bind to or close to the L-type Ca channel, and inhibit the specific binding of NIT by allosteric, complex interactions influenced by the free concentration of Ca++. The nonadditive allosteric effects suggest a shared mechanism of interaction for amiloride and quinacrine with the site(s) of NIT. Several mechanisms are discussed to explain how amiloride and quinacrine can produce such inhibition of NIT binding.

Allosteric Regulation↗

Blood pressure effects of tranylcypromine when prescribed singly and in combination with amitriptyline.

Data on blood pressure was extracted from the findings of a 6-week double-blind study that was carried out to evaluate the efficacy and safety of prescribing tranylcypromine (TCP) singly and in combination with amitriptyline (AMI). The effect of TCP on blood pressure was one of the methods used to evaluate its safety. Target daily doses of medication for the final 2 weeks of the study were: TCP 30 mg, AMI 150 mg, or the two in combination. Because of side effects, mean daily doses actually achieved were lower: single TCP 18.5 mg; single AMI 114.3 mg; combined TCP/AMI: TCP 19.7 mg, AMI 108.7 mg. When TCP alone was prescribed, a significant fall in diastolic blood pressure in the standing position was noted and orthostatic hypotension was more frequently observed. Dizziness was complained of on at least one occasion in over three quarters of patients on TCP/AMI. No correlation between blood pressure effects and dizziness was detected and there were no other troublesome side effects from this antidepressant combination. The study concluded that although TCP's overall effect on mean blood pressure readings when prescribed alone or in combination was small, its orthostatic effect is noteworthy and should be borne in mind by the prescribing clinician.

Adult↗

Transmembrane signalling by insulin via an insulin receptor mutated at tyrosines 1158, 1162, and 1163.

In order to study the role of tyrosine autophosphorylation in insulin receptor signalling, we investigated a mutant human insulin receptor whereby the three major tyrosine autophosphorylation sites at positions 1158, 1162, and 1163 in the receptor beta-subunit were mutated to phenylalanines. When these mutant receptors were expressed in HTC rat hepatoma cells, there was no enhanced beta-subunit autophosphorylation and tyrosine kinase activity. In these cells there was enhanced insulin stimulation of [3H]AIB uptake and [3H]thymidine incorporation when compared to wild type HTC cells. The present study suggests therefore that the presence of the major insulin autophosphorylation sites is not a requirement for insulin stimulation of amino acid transport and mitogenesis.

Aminoisobutyric Acids↗

Pharmacology and phase I trial of high-dose oral leucovorin plus 5-fluorouracil in children with refractory cancer: a report from the Children's Cancer Study Group.

Because of the synergy seen in adult trials when 5-fluorouracil is combined with leucovorin, we initiated a Phase I trial of this combination in children's refractory cancer. Leucovorin, an equal mixture of the (6R,S)-diastereoisomers, was administered p.o. for 6 consecutive days as 4 equal doses at 0, 1, 2, and 3 h totaling 500 mg/m2/day. 5-Fluorouracil was given daily on days 2 to 6 as an i.v. bolus immediately following the last dose of leucovorin. The leucovorin dose was held constant while the 5-fluorouracil dose was escalated in cohorts of patients from 300 mg/m2/day to its maximally tolerated dose. Thirty-five patients (19 with acute leukemia and 16 with solid tumors) were evaluable for toxicity. The maximally tolerated dose of FUra was 450 mg/m2/day for 5 treatments for patients with solid tumors and 650 mg/m2/day for 5 treatments for the children with leukemia. The dose-limiting toxicities were myelosuppression and stomatitis. Other side effects included transient, mild elevations of serum transaminases, mild nausea, vomiting, and diarrhea. The pharmacokinetics of high-dose p.o. leucovorin was studied in 23 children. There was considerable interpatient variability in the plasma concentrations of total bioactive folates (TBAF), (6S)-leucovorin, and (6S)-5-methyltetrahydrofolic acid. The maximum plasma concentration (Cmax) of TBAF was 821 +/- 97 (SE) nM, occurring at a median of 8 h; the Cmax of (6S)-leucovorin was 77 +/- 11 nM, occurring at 4 h. The TBAF concentration fell to 146 +/- 42 nM by 24 h. (6S)-5-Methyltetrahydrofolic acid accounted for 90 +/- 7% of the TBAF at the Cmax. The plasma concentration of (6R)-leucovorin, the unnatural isomer, was equal to that of TBAF. Thus, p.o. leucovorin reduced the 5-fold excess of (6R)-leucovorin over TBAF seen after i.v. doses. The relative amounts of the three major plasma species were approximately the same as in adults, even though the Cmax of each compound was lower.

Administration, Oral↗