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Biomedical subjects

D Johnson

Publications and source records attributed to D Johnson.

At least 325 records · Page 18Linked to original sources
PubMed1995

Trimethylaminuria, fish odour syndrome: a new method of detection and response to treatment with metronidazole.

Trimethylaminuria is an autosomal recessive disorder involving deficient N-oxidation of the dietary-derived amine trimethylamine (TMA). TMA, a volatile tertiary amine, accumulates and is excreted in urine of patients with deficient TMA oxidase activity. Treatment strategies for this condition are limited. We report a new stable-isotope dilution method for rapid sequential analysis of TMA concentrations and the clinical and biochemical response to treatment with metronidazole.

Adult↗
PubMed1995

The effect of lipid peroxides on isolated human umbilical artery contraction.

OBJECTIVE: Our purpose was to determine the effect of oxidized lipids on the contractile activity of isolated human umbilical arteries. STUDY DESIGN: Umbilical artery rings were prepared for isometric tension recording and exposed to cumulative concentrations of oxidized and nonoxidized lipid and control solutions. Rings were also incubated with the lipid or control solutions and then contracted with cumulative concentrations of U46619. A final set of rings in Ca(++)-free depolarized solution was incubated with the agents above, and then the Ca++ concentration was increased cumulatively. RESULTS: The lipids had no direct contractile effect. Both lipids inhibited the response to U46619 and Ca++, with the oxidized lipids having the most significant effect. CONCLUSION: Oxidized lipids lack a direct contractile effect on isolated human umbilical arteries and inhibit the contractile response to thromboxane and calcium.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Human umbilical vessels: responses to agents frequently used in obstetric patients.

OBJECTIVE: Our purpose was to study the effects of some drugs frequently used in pregnant women on isolated human umbilical artery and vein segments. STUDY DESIGN: Umbilical artery and vein rings from normal term pregnancies were mounted in Krebs-bicarbonate solution in organ baths for isometric tension recording. Rings were contracted with potassium chloride (60 mmol/L) or U46619 (10(-8) mol/L) and then exposed to cumulative concentrations of nimodipine, nifedipine, nicardipine, phenytoin, magnesium sulfate, and hydralazine. Concentration-response curves were constructed by means of the difference in the percent relaxation between test and control vessels. Data analysis was by repeated measures analysis of variance, Newman-Keuls test, and the unpaired Student t test as appropriate. A value of p < 0.05 was considered statistically significant. RESULTS: All the agents studied were effective umbilical vasodilators, except for hydralazine, which had minimal effect. The dihydropyridine calcium antagonists were more potent vasodilators than were the other agents studied. Nifedipine was the most potent calcium blocker and was the only dihydropyridine that relaxed the umbilical vein to a greater extent than the umbilical artery. CONCLUSION: The most commonly used drugs in preeclampsia have variable effects on the umbilical vessels.

Analysis of Variance↗
PubMed1995

Evaluation of the Hybrid Capture human papillomavirus deoxyribonucleic acid detection test.

OBJECTIVE: Our purpose was to evaluate the sensitivity and accuracy of a new, nonradioactive human papillomavirus deoxyribonucleic acid detection method. STUDY DESIGN: Cervical samples from 520 women were assayed for human papillomavirus deoxyribonucleic acid with both the Hybrid Capture test and polymerase chain reaction. RESULTS: Human papillomavirus deoxyribonucleic acid was detected with Hybrid Capture in 106 (42%) of 254 samples from women with no evidence of cervical intraepithelial neoplasia and 211 (79%) of 266 with cervical intraepithelial lesions or cervical cancer. There was a good correlation between Hybrid Capture and polymerase chain reaction. Hybrid Capture correctly identified 92% of samples found to contain a human papillomavirus type with a high or intermediate oncogenic risk with polymerase chain reaction. Although Hybrid Capture can quantify the amount of human papillomavirus deoxyribonucleic acid present in a sample, no correlation was observed between the relative amount of human papillomavirus deoxyribonucleic acid detected with Hybrid Capture and the grade of cervical lesion. CONCLUSION: The Hybrid Capture test is a sensitive and accurate method for identifying human papillomavirus types of high and intermediate oncogenic risk in clinical specimens.

Cervix Uteri↗
PubMed1995

Delivery of a foreign gene to sympathetic preganglionic neurons using recombinant herpes simplex virus.

Two recombinant herpes simplex type 1 viruses expressing beta-galactosidase (encoded by the Escherichia coli lacZ gene) inserted into the unique long 41 (encoding virus host shutoff) or unique short 5 (encoding glycoprotein J) open reading frames were generated. Purified recombinants or wild-type herpes simplex type 1 were injected into the left adrenal gland of hamsters. Three days later, virus-infected neurons were detected in spinal cord sections from all infected hamsters. Neurons were visualized with beta-galactosidase histochemistry in spinal cord sections from hamsters infected with either of the recombinants but not with the wild-type virus. Wild-type virus could only be detected with immunocytochemistry. Insertional mutagenesis into the unique long 41 or unique short 5 regions of the herpes simplex genome by lacZ did not disrupt the neurotropic properties of the virus. Both recombinant viruses labelled the central nervous system sympathoadrenal preganglionic neurons as well as brainstem neurons. Because the virus host shutoff recombinant more readily crossed synapses to reach the brainstem compared to the glycoprotein J recombinant, the presence of glycoprotein J may facilitate cell to cell transmission in vivo. Both recombinants may be useful for the study of synaptic organization of neural circuits. Our recombinant viruses were less lytic yet neurovirulent after mutation of either glycoprotein J or virus host shutoff of herpes simplex virus type 1 wild-type. These recombinant viruses express the bacterial beta-galactosidase which is readily detectable using simple histochemistry. Inoculation of the adrenal gland or kidney with these viruses led to clear labelling of spinal cord cells. These viruses may be useful markers of specific neural circuits.

Animals↗
PubMed1995

Peripheral blood flow responses to exercise after successful correction of coarctation of the aorta.

OBJECTIVES: The purpose of this study was to characterize peripheral flow kinetics in response to progressive discontinuous maximal exercise in 10 patients who underwent repair of coarctation of the aorta and 11 age-matched healthy adolescents. BACKGROUND: An impairment of leg blood flow has been suggested on the basis of exaggerated femoral muscle lactate accumulation in patients with successful repair of coarctation. Few data are available describing blood flow kinetics of the exercising leg in such patients. METHODS: Duplex ultrasound provided transcutaneous measurements of peak systolic and end-diastolic flow velocities of the femoral, humeral and renal arteries at rest and immediately after mild, moderate and maximal exercise intensities for computation of mean velocity, resistance index and femoral blood flow. RESULTS: Femoral mean velocity and femoral blood flow increased linearly with exercise intensity in both groups, but the slope of this increase was significantly lower in patients. Similarly, humeral mean velocity increased significantly less in patients than in control subjects. Femoral resistance index sharply decreased from that at rest (patients [mean +/- SE] 1.4 +/- 0.04; control subjects 1.4 +/- 0.03) to mild exercise intensity in both groups (patients 0.69 +/- 0.03; control subjects 0.72 +/- 0.03). A further decrease was observed at maximal exercise in patients (0.60 +/- 0.04, p = 0.08) but not in control subjects (0.69 +/- 0.02). CONCLUSIONS: These observations suggest that despite a greater exercise-induced femoral vasodilation, patients with successful correction of coarctation of the aorta demonstrate an impaired lower limb blood flow in response to strenuous dynamic exercise. In the absence of stenosis at rest, this alteration could result from exaggerated flow turbulence in the descending aorta distal to the site of correction because of loss of elasticity at the site of the resection of the coarcted segment.

Adolescent↗
PubMed1995

Isoniazid-associated rhabdomyolysis.

We report the occurrence of rhabdomyolysis and hepatitis in a 17-year-old girl after the ingestion of up to 10.8 g of isoniazid. The initial isoniazid concentration in the blood was 1,230 mmol/L. There were no findings indicating the ingestion of other substances known to be associated with rhabdomyolysis. In addition to rhabdomyolysis (peak creatine phosphokinase 88,000 U/L), the patient had a significant elevation of her liver enzymes (peak aspartate aminotransferase 1,980 U/L). She recovered completely without evidence of liver or renal damage. Rhabdomyolysis and isoniazid-induced hepatitis are complications that should be considered when caring for patients with acute isoniazid ingestion.

Adolescent↗
PubMed1995

Use of peptide combinatorial libraries in drug design: the identification of a potent serotonin reuptake inhibitor derived from a tripeptide cassette library.

BACKGROUND: Medicinal chemistry traditionally requires the identification of biologically active molecules by synthesizing and screening each purified substrate. Further progress in drug discovery then requires definition of the structure-activity relationship of the lead compound. More recently, combinatorial chemistry has emerged as a way to examine structure-activity relationships by screening a large mixture of compounds synthesized in a predictably random manner, without the labor-intensive costs of molecular isolation and purification. We set out to use this approach to examine the structural requirements for peptide binding to serotonin and dopamine transporters. RESULTS: We screened a tripeptide cassette library for serotonin and dopamine reuptake inhibition using cloned transporter assay systems. The method has afforded a number of tripeptide pharmacophores with inhibitory IC50 values ranging from 10 microM to < 1 microM in the dopamine and serotonin reuptake systems. The conformation of one of these tripeptides, N-acetyl-D-Trp-L-Phe-D-Lys-CONH2 (which inhibits serotonin uptake with an IC50 of 10 microM) was compared to that of the serotonin uptake inhibitor s-fluoxetine, and was shown to be more similar in conformation to fluoxetine than was an analogous tripeptide containing L-Lys (IC50 > 50 microM). CONCLUSIONS: We have identified five tripeptides with inhibitory IC50 values of < 10 microM in the serotonin reuptake system. One tripeptide was predicted to have pharmacophore features similar to that of fluoxetine, a selective and potent non-peptide serotonin reuptake inhibitor. Our results suggest that tripeptides derived from combinatorial libraries will help to define the important structural elements of pharmacophores.

Animals↗
PubMed1995

Effect of multiple-dose activated charcoal on the clearance of high-dose intravenous aspirin in a porcine model.

STUDY OBJECTIVE: To study the effect of multiple-dose activated charcoal (MDAC) on salicylate clearance in pigs given high-dose i.v. aspirin. DESIGN: In a crossover design, six fasted pigs received 300 mg/kg i.v. aspirin followed by no treatment or MDAC (1 g/kg hourly for 6 doses by gastrostomy). Serum salicylate samples were obtained every 30 minutes for 6 hours. RESULTS: The mean peak salicylate concentrations were 47.4 +/- 6.2 mg/dL and 48.4 +/- 3.9 mg/dL (P = .74), and the areas under the time-serum salicylate concentration curve over 6 hours were 171,000 +/- 24,000 mg.minute/L and 188,000 +/- 18,000 mg.minute/L for the control and treatment arms, respectively (P = .22). This study had a 90% power to detect a 30% difference between arms. CONCLUSION: MDAC does not enhance the clearance of salicylate after administration of high-dose i.v. aspirin.

Animals↗
PubMed1995

Differential effects of 4'-chlorodiazepam on expressed human GABAA receptors.

The interactions of the atypical benzodiazepine 4'-chlorodiazepam (Ro 5-4864) with functionally expressed human GABAA receptor cDNAs were determined. Cotransfection of human alpha 2, beta 1, and gamma 2 subunits was capable of reconstituting a 4'-chlorodiazepam recognition site as revealed by a dose-dependent potentiation of t-[35S]butylbicyclophosphorothionate ([35S]-TBPS) binding to the GABA-activated chloride channel. This site is found on GABAA receptor complexes containing sites for GABA agonist-like benzodiazepines and neuroactive steroids. The importance of the alpha subunit was further demonstrated as substitution of either alpha 1 or alpha 3 for the alpha 2 subunit did not reconstitute a 4'-chlorodiazepam recognition site that was capable of modulating [35S]TBPS binding under the same experimental conditions. The 4'-chlorodiazepam modulatory site was shown to be distinct from the benzodiazepine site, but the phenylquinolines PK 8165 and PK 9084 produced effects similar to 4'-chlorodiazepam, consistent with the previous analysis of the 4'-chlorodiazepam site in brain homogenates. Further analysis of the subunit requirements revealed that coexpression of alpha 2 and beta 1 alone reconstituted a 4'-chlorodiazepam recognition site. It is interesting, however, that the 4'-chlorodiazepam site was found to inhibit [35S]TBPS binding to the GABA-activated chloride channel. Thus, the 4'-chlorodiazepam site may be reconstituted with only the alpha and beta polypeptides.

Benzodiazepinones↗
PubMed1995

The "revolution" in outpatient care.

Although the concept of outpatient care is not a new one, the growth in ambulatory facilities has revolutionized medical care in the United States. The growth in ambulatory surgery centers, imaging centers, and cancer centers in Florida is explored in detail. With the many changes forthcoming in health care, ambulatory care will play an increasing role in delivering good health care at a reasonable cost.

Ambulatory Care↗
PubMed1995

Assessment of the terminal 40-millisecond QRS vector in children with a history of tricyclic antidepressant ingestion.

Tricyclic antidepressant (TCA) ingestions remain a serious and not uncommon overdose in children. In adults, a terminal 40 millisecond QRS vector (T40-ms) between 120 and 270 degrees has been proposed as a marker for TCA overdose; however, the normal rightward deviation and high incidence of incomplete right bundle branch block noted in the electrocardiograms (ECGs) of young children may limit the usefulness of this criterion in this population. A retrospective chart review of pediatric patients less than 11 years of age admitted to the Hospital for Sick Children with birth dates after 1971 identified by International Classification of Diseases, Ninth Edition, coding for TCA ingestion was undertaken, and data related to complications were collected and reviewed. The ECGs of 35 children presenting with TCA ingestion were examined by two blinded cardiologists and the T40-ms as well as QRS, QTc, and PR intervals were calculated and compared to those of 35 healthy age-matched controls undergoing routine ECGs. In the 35 children (aged 48 +/- 39 months [mean +/- SD]) with a history of TCA ingestion, symptoms were categorized as significant in 18 (51%), mild in 12 (34%), and none in five (14%). Seizures were present in 13 (37%), hypotension in three (9%), and arrhythmias in five (14%). The mean T40-ms axes in the TCA and control groups were 111 +/- 66 degrees and 97 +/- 71 degrees, respectively. A T40-ms between 120 and 270 degrees had a sensitivity of 38% and a specificity of 74%. A marked variability in the T40-ms was noted in both the exposed and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Antidepressive Agents, Tricyclic↗
PubMed1995

Acute renal insufficiency in ibuprofen overdose.

Since the introduction of ibuprofen as a nonprescription drug in the US, there have been reports of significant toxicity associated with large ingestions (> 400 mg/kg) in both children and adults. Acute renal insufficiency is a rare, reversible effect of ibuprofen overdose documented in adults, but we could find no published pediatric cases. We report a case of a healthy two-year-old boy, without a previous history of renal problems, who developed reversible acute renal insufficiency after a toxic ingestion of approximately 640 mg/kg ibuprofen. By 11 hours, his initially normal creatinine began to rise, reaching a peak value of 181 mmol/L (2.1 mg/dl) by 27 hours. His urinalysis showed moderate microscopic hematuria without the presence of casts or proteinuria. No problems arose with fluid management. Normalization of his renal function occurred by 72 hours. A serum ibuprofen concentration obtained by high-performance liquid chromatography and drawn approximately four hours after ingestion was 1724 mumol (therapeutic serum concentration, 50-250 mumol). This case demonstrates that acute, reversible renal insufficiency can occur in healthy children after a severe overdose of ibuprofen; hence, renal function should be monitored in such instances.

Acute Kidney Injury↗
PubMed1995

Pacemaker inhibition due to anodal ring electrode contact.

A 79-year-old patient with a permanent DDD pacemaker due to a complete AV block and severe bradycardia was seen with complaints of syncope. A surface ECG rhythm strip verified the loss of ventricular output with 6-second periods of asystole. Subsequent investigation using the pacemaker's annotated event markers and multiple polarity intracardiac electrograms indicated spurious signals arising from the anodal ring. On fluoroscopic examination intermittent contact was observed between the anodal ring of the pacing lead and the ring electrode of an abandoned lead. Reprogramming of the pulse generator's ventricular channel to the unipolar sensing configuration corrected the problem.

Aged↗
PubMed1995

Postoperative physical therapy after coronary artery bypass surgery.

Coronary artery bypass surgery is frequently complicated by postoperative atelectasis. Although routinely prescribed, the efficacy of any specific chest physical therapy is not well established. We studied patients at a university center undergoing elective coronary artery bypass surgery. Based upon chest X-ray criteria at extubation, patients (n = 228) were classified as demonstrating greater or lesser degrees of atelectasis. Those with a lesser degree of atelectasis were randomized to receive either early mobilization or sustained maximal inflations (SMI). Those with greater a degree of atelectasis were separately randomized to receive either SMI or single-handed percussions (SSP). We found the extent of atelectasis at extubation did not predict the risk of developing pneumonia. Hospital stays and intensive care unit stays were similar regardless of treatment. Physical therapy costs were highest in the most labor-intensive therapy group (SSP). We conclude that postoperative respiratory dysfunction is common but does not commonly cause significant morbidity or prolong hospital stay. Adding SMI to patients with minimal atelectasis at extubation does not improve clinical outcomes. Similarly, adding SSP to patients with marked atelectasis does not improve outcomes over those obtained with SMI and early ambulation.

Aged↗