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Biomedical subjects

D Johnson

Publications and source records attributed to D Johnson.

At least 505 records · Page 28Linked to original sources
PubMed1990

Sperm bound to zona pellucida in hemizona assay demonstrate acrosome reaction when stained with T-6 antibody.

A monoclonal antibody, T-6, useful for detecting acrosome-reacted sperm based on an immunofluorescent assay, was employed to evaluate acrosomal status of human sperm that were tightly bound to hemisected human zonae pellucidae (hemizona assay). Over 90% of the bound sperm evaluated exhibited immunofluorescent patterns indicative of acrosome reaction. This staining method for evaluating the acrosomal status of sperm bound to the zona pellucida may enable definition of a group of male infertility patients heretofore not recognized.

Acrosome↗
PubMed1989

Treatment of pulmonary manifestations of gastroesophageal reflux in children two years of age or less.

Apnea and worsening bronchopulmonary dysplasia as well as recurrent aspiration pneumonia have been found to be consequences of gastroesophageal reflux in infants and young children. Antireflux procedures are effective in preventing gastroesophageal reflux; however, the effect of this operation on the course of these respiratory problems in very young patients is not known. We reviewed the results in 51 patients 2 years of age or less who underwent an antireflux fundoplication for pulmonary problems attributable to severe gastroesophageal reflux unresponsive to medical treatment. Twenty-eight patients had recurrent episodes of aspiration pneumonia, 14 had nonimproving or worsening bronchopulmonary dysplasia, and 9 had unexplained apneic episodes. Seventy-three percent of these patients had coexisting congenital anomalies or acquired problems. No operative deaths and no major surgical complications occurred. There were eight late deaths occurring between 1 and 25 months postoperatively: three were due to associated congenital anomalies or acquired problems, three to sepsis, and two to sudden infant death syndrome. Of the 43 surviving children, 91 percent with preoperative recurrent aspiration pneumonia had no additional episodes after Nissen procedure. Eighty-eight percent of the infants with unexplained apneic episodes showed marked benefit and 83 percent of those with bronchopulmonary dysplasia had clinical improvement. There were no late problems attributed to the operation even when it was performed in preterm infants. Therefore, we recommend fundoplication for patients 2 years of age or less who have a persistent pulmonary problem attributed to gastroesophageal reflux that does not respond to medical therapy.

Apnea↗
PubMed1989

Augmentation of natural cytotoxicity by leucine enkephalin in cultured peripheral blood mononuclear cells from patients infected with human immunodeficiency virus.

Natural Killer (NK) activity of lymphocytes from acquired immunodeficiency syndrome (AIDS) patients is frequently below normal and declines as disease progresses. We studied the potential of leucine enkephalin (leu-enkephalin) to restore this immune parameter by incubating nylon wool nonadherent mononuclear cells from 14 patients in the presence or absence of leu-enkephalin, and measuring NK cytolysis in a standard 51Cr release assay. The NK activity of human immunodeficiency virus antibody positive (HIV+) individuals with some remaining NK lytic ability was significantly augmented by leu-enkephalin concentrations of 10(-10) and 10(-8) M (n = 7). HIV+ patients with no measurable basal level of NK activity (n = 3) were not responsive to stimulation with leu-enkephalin. Human immunodeficiency virus antibody negative (HIV-) individuals (n = 4) responded in a pattern similar to normals. In addition, naloxone, an antagonist of alkaloid and peptide opiates including leu-enkephalin, displayed the properties of an antagonist/agonist, reflecting the immunoregulatory capacities of the endogenous opiate system.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Antibodies to myelin-associated glycoprotein (MAG) in the cerebrospinal fluid of multiple sclerosis patients.

Cerebrospinal fluids (CSF) and sera from patients with multiple sclerosis (MS), other neurological diseases (ONDs) and healthy controls were tested for antibodies to myelin-associated glycoprotein (MAG) by several different assays. Using a very sensitive, solid-phase radioimmunoassay with radioiodinated protein A, a statistically significant elevation of anti-MAG antibodies was detected in MS CSFs in comparison to those from ONDs and healthy controls. The antibodies reacted with human MAG, but not with rat MAG, and appeared to be directed towards carbohydrate determinants in the glycoprotein. The CSFs from high IgG producers had significantly greater anti-MAG antibody levels than those from low IgG producers, even though the assays were done on CSF samples that had been normalized to the same IgG concentration. The elevated antibodies were not detected when the same samples were tested with a liquid-phase radioimmunoassay or an enzyme-linked immunosorbent assay, and the antibodies in the MS CSF also could not be detected by Western blotting. An elevated level of antibodies was not found in sera from MS patients by any of the assays, possibly because these samples gave higher and more variable background. The results suggest that there is a low level of humoral immunity to MAG in MS patients that can only be detected by the most sensitive assays. This weak immune response to MAG may be secondary to the demyelinating process, but could play a role in the progression of the disease.

Antibodies↗
PubMed1989

Treatment of experimental allergic neuritis with nedocromil sodium.

Peripheral nervous system mast cells degranulate early in the development of experimental allergic neuritis (EAN). This degranulation is associated with the release of vasoactive amines, chemoattractants and myelinolytic proteases which could provide a focus for inflammatory demyelination. To further assess the importance of mast cell degranulation in the development of EAN, we have treated Lewis rats inoculated with peripheral nervous system myelin and complete Freund's adjuvant, with nedocromil sodium, an anti-inflammatory drug with mast cell stabilizing properties. Treatment with nedocromil sodium (100-150 mg/kg), 3 times daily, starting on day 7 post-inoculation, significantly decreases the incidence and the severity of the disease. Histological examination of sciatic nerves confirms the absence of subclinical disease in successfully treated animals. The possible mode of action of the drug is discussed.

Animals↗
PubMed1989

Chromatographic methods for determining the identity, strength and purity of ranitidine hydrochloride both in the drug substance and its dosage forms--an exercise in method selection, development, definition and validation.

The selection, development, definition and validation of selective stability-indicating procedures for high-performance liquid chromatographic and thin-layer chromatographic analyses of ranitidine hydrochloride are described. The procedures used in conjunction can be applied to the quality assurance and stability assessments of both the drug substance and its dosage forms and serve to establish the identity, strength and purity of this drug used in the treatment of peptic ulcer and related conditions.

Chromatography↗
PubMed1989

Lorazepam pharmacodynamics and pharmacokinetics in children.

We evaluated the effects of low doses of lorazepam on episodic versus long-term memory, attention, and somatic and affective symptoms, as well as its pharmacokinetics, in a group of 16 children aged 2.8 to 14.2 years. Psychologic assessments of each child were performed twice before intravenous administration of lorazepam (0.03 mg/kg), and 1 1/2 hours and 24 hours after lorazepam; there were no significant changes in long-term memory, attention, or somatic symptoms. There was a significant decrease in affective symptoms at 1 1/2 hours (p = 0.011), with a trend toward decreased anxiety at 1 1/2 and 24 hours after lorazepam (p = 0.026 and 0.028, respectively). There was also a selective anterograde amnestic effect in 5 of 16 children after lorazepam (p = 0.06). Mean (+/- SD) lorazepam systemic clearance was 1.3 +/- 0.4 ml/min/kg, with a terminal half-life of 10.5 +/- 2.9 hours and an unbound clearance of 15.9 +/- 5.2 ml/min/kg. A group of healthy adult volunteers who were given lorazepam had a mean systemic clearance of 1.0 +/- 0.4 ml/min/kg, somewhat less than that of the children (p = 0.069). There were no significant differences in any lorazepam pharmacokinetic parameter between those children who did versus those who did not have changes in affective symptoms or amnesia. These data should be helpful in establishing the dose of lorazepam in children, as the drug becomes more widely used as an antiemetic, premedicant, and anticonvulsant agent.

Adolescent↗
PubMed1989

Development of phosphonate derivatives of gadolinium chelates for NMR imaging of calcified soft tissues.

We have synthesized several classes of gadolinium (Gd) complexes for use as NMR contrast agents in the detection of soft-tissue calcification. Class I was made up of strongly chelated GdDTPA complexes with one carboxylate arm coupled to a phosphonate-containing molecule through an amide link. Class II complexes were formed by Gd with several aminophosphonates and phosphono carboxylic acids. Class III were Gd complexes of weak chelates containing no phosphonate. The calcium-seeking ability of each complex was assessed by in vivo bone uptake. Tissue distribution in normal rats showed that only the complexes of GdDTPA modified with a diphosphonate group and GdEDTMP (EDTMP is ethylenediaminetetrakis(methylenephosponate] showed adequate bone localization at the concentrations required for NMR contrast enhancement (approximately 20% of a 100 mumol/kg dose).

Animals↗
PubMed1989

Synthesis and biological evaluation of omega-(N,N,N-trialkylammonium)alkyl esters and thioesters of carboxylic acid nonsteroidal antiinflammatory agents.

A series of novel omega-(N,N,N-trialkylammonium)alkyl ester and thioester derivatives [RCOM(CH2)nNR3+ X-, M = O or S. n = 2-6, X = I or Cl] of 11 nonsteroidal antiinflammatory carboxylic acid agents (naproxen, ketorolac, indomethacin, ibuprofen, sulindac, ketoprofen, flufenamic acid, mefenamic acid, zomepirac, etodolac, and tifurac) was prepared and evaluated for their antiinflammatory, analgesic, and gastrointestinal erosive properties. In general, each prodrug retained the antiinflammatory activity characteristic of the corresponding parent drug but exhibited moderately to greatly reduced gastrointestinal erosive properties and significantly reduced analgetic potencies. This profile is likely due to a combination of factors including the rate of hydrolysis of the esters in the stomach, gut, and plasma, changes in the locus of absorption of the prodrug or nonsteroidal antiinflammatory drug (NSAID), and altered metabolic disposition patterns resulting from these changes. The results obtained from the compounds of this series indicate that esters of this general class may offer a means to modulate both the aqueous/lipid solubility and the hydrolytic/enzymatic cleavage indices of NSAID prodrugs which potentially possess a more favorable therapeutic ratio of antiinflammatory to gastrointestinal erosive activities.

Animals↗
PubMed1989

Isoflurane for refractory status epilepticus: a clinical series.

General anesthesia has been recommended to control convulsive status epilepticus that is refractory to conventional anticonvulsant therapy. Halothane has been the recommended agent, but without experimental justification. Isoflurane, which has no reported organ toxicity and produces electrographic suppression at clinically useful concentrations in normal humans, should be a better volatile anesthetic for this purpose. The efficacy and safety of isoflurane administered to control convulsive status epilepticus were assessed on 11 occasions in nine patients in seven North American hospitals. Isoflurane, administered for 1-55 h, stopped seizures in all patients and was able to be titrated to produce burst-suppression patterns on electroencephalograms. Blood pressure support with iv fluids and/or pressor infusions was required in all of the patients. Seizures resumed upon discontinuation of isoflurane on eight of 11 occasions. Six of the nine patients died. The three survivors sustained cognitive deficits. In one patient urine fluoride concentrations were elevated, although not to nephrotoxic levels. These cases suggest that isoflurane 1) is an effective, rapidly titratable anticonvulsant; 2) does not reverse underlying causes of the refractory seizures; and 3) usually necessitates hemodynamic support with fluids and/or pressors. Isoflurane may be administered for seizures, but only when iv agents in anesthetic doses are ineffective or produce unacceptable side effects.

Adolescent↗