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Biomedical subjects

C Norris

Publications and source records attributed to C Norris.

At least 55 records · Page 3Linked to original sources
PubMed1992

Comparison of SCH 39304, fluconazole, and ketoconazole for treatment of systemic infections in mice.

SCH 39304 was compared with fluconazole and ketoconazole in a systemic Candida albicans infection in mice (10(6) CFU per mouse). Results were based on survival rates and CFU in kidneys following once-daily oral treatment of 2, 5, or 10 days duration. In normal mice, SCH 39304 (dose to reduce kidney counts by 4 log units, 0.5 mg/kg of body weight) was 3 and 200 times more active than fluconazole and ketoconazole, respectively. In immunocompromised mice (gamma irradiation, 600 rads), SCH 39304 (dose to reduce kidney counts by 4 log units, 1.3 mg/kg) was 35 and greater than 100 times more active than fluconazole and ketoconazole, respectively. In normal mice, when the infecting inoculum varied from 10(5) to 10(7) CFU, only a fivefold increase in the dose to reduce kidney counts by 4 log units was observed with SCH 39304. Excellent protection was also seen when mice were treated with a single oral dose of SCH 39304 up to 24 h prior to infection with C. albicans. Studies in a systemic C. albicans infection model indicated that SCH 39304 is equally efficacious following either oral or intravenous administration. In a systemic Aspergillus flavus infection, mice treated with SCH 39304 (5 mg/kg) survived twice as long (16 days) as those treated with fluconazole (50 mg/kg) or controls did.

Administration, Oral↗
PubMed1992

In vitro and in vivo activities of SCH 42427, the active enantiomer of the antifungal agent SCH 39304.

SCH 39304, a new triazole antifungal agent, is a 50:50 racemic mixture of two enantiomers, SCH 42427 and SCH 42426. The activities of these three compounds were compared in a series of in vitro and in vivo experiments. SCH 42427 was twofold more active in vitro against a variety of yeasts and dermatophytes than SCH 39304, while SCH 42426 was inactive (MICs greater than 64 micrograms/ml). In a systemic Candida albicans infection in mice, SCH 42427 administered orally (p.o.) (50% protective dose [PD50], 0.17 mg/kg of body weight; 50% effective dose, [ED50], 0.47 mg/kg) had greater efficacy than SCH 39304 (PD50, 0.21 mg/kg; ED50, 0.62 mg/kg) and SCH 42426 (greater than 100 mg/kg for PD50 and ED50). In a pulmonary Aspergillus flavus infection in mice, SCH 42427 p.o. (PD50, 13 mg/kg) was also more effective than SCH 39304 (18 mg/kg) and SCH 42426 (greater than 250 mg/kg). In a C. albicans vaginal infection in hamsters, SCH 42427 p.o. (ED50, 3.5 mg/kg) was more active than SCH 39304 (8.5 mg/kg) and SCH 42426 (320 mg/kg). Following topical administration, against a Trichophyton mentagrophytes infection in guinea pigs, SCH 42427 was about 2-fold more active than SCH 39304 and about 100-fold more active than SCH 42426. These and other results indicated that SCH 42427 is the active enantiomer, responsible for all the antifungal activity observed with SCH 39304.

Animals↗
PubMed1992

A permanent transvenous lead system for an implantable pacemaker cardioverter-defibrillator. Nonthoracotomy approach to implantation.

A transvenous lead system for implantable defibrillators would obviate a surgical thoracotomy and reduce the morbidity and mortality associated with implantation. We evaluated the clinical performance of a new nonthoracotomy lead system that included a defibrillation lead in the coronary sinus. At the time of defibrillator implantation, transvenous defibrillation leads were inserted percutaneously through the left subclavian vein into the right ventricular apex (RVA), superior vena cava (SVC), and distal coronary sinus (CS) under fluoroscopic guidance. A subcutaneous patch electrode (SQ) was also available if required. The first single- or dual-pathway electrode configuration that successfully terminated three of four ventricular fibrillation episodes using 18 J or less was implanted. Eleven men and three women aged 39-77 years (60.0 +/- 10.1 years) with left ventricular ejection fraction ranging from 16% to 63% (33.4 +/- 13.1%) were evaluated. Nine presented with ventricular tachycardia, three had ventricular fibrillation, and two had both. A totally transvenous lead system (RVA/CS/SVC) was implanted in seven patients (50%) with a mean defibrillation threshold of 15.6 +/- 2.9 J (10-18 J). Four patients received a partial transvenous lead system (RVA/CS/SQ). An effective nonthoracotomy lead system was not found in three patients; they received epicardial electrodes. After cumulative follow-up of 73 patient-months, nine patients remain alive and free of problems related to the implanted nonthoracotomy leads. One patient died of respiratory failure 3 months after defibrillator implant, and the leads from another patient were removed at 9 months because of bacterial infection. A transvenous lead system that includes a defibrillation lead in the coronary sinus is a safe, reliable, and, at least in the short term, effective nonthoracotomy approach for automatic defibrillator implantation.

Adult↗
PubMed1991

Cyclic AMP modulates sensory-neural communication at the vestibular end organ.

Adenosine 3':5'-cyclic phosphate (cAMP) is a second messenger that plays an important role in mediating neuronal interactions in many systems. A possible role for cAMP in sensorineural communication at the vestibular end organ was studied. The putative roles for cAMP action investigated here were: the ability of cAMP to act as the second messenger for the efferent transmitter, acetylcholine, and the possible involvement of cAMP in modulating spontaneous or mechanically-evoked afferent nerve firing. Levels of cAMP were increased pharmacologically with forskolin, 3-isobutyl-1-methyl xanthine (IBMX) and dibutyryl cAMP. Changes in multiunit afferent nerve firing measured from the ampullar nerve of the semicircular canal, and the transepithelial potential measured across the neuroepithelium of the semicircular canal were recorded. At selected doses, all drugs produced a similar increase in spontaneous multiunit afferent nerve firing with a concomitant decrease in the transepithelial potential. Mechanically-evoked hair cell activity and the response to exogenously applied acetylcholine were unaffected by these drugs. We are suggesting that the excitatory aspects of the acetylcholine response are not mediated via a cAMP-dependent mechanism. However, cAMP does play an important role in modulating spontaneous afferent nerve firing in the semicircular canal. The finding that spontaneous afferent nerve firing can be biochemically modulated without altering mechanically-induced afferent firing is novel and deserves further investigation.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Effect of oat bran muffins on calcium absorption and calcium, phosphorus, magnesium and zinc balance in men.

Metabolic balance studies were conducted in adult human males to investigate the effect of oat bran on the nitrogen, calcium, phosphorus, magnesium and zinc balance, on the intestinal absorption of calcium and on the endogenous fecal calcium, using 47CaCl2 as the tracer. A 40-d control period preceded a 32-d experimental period in which subjects consumed four oat bran muffins daily as part of a constant metabolic diet. No significant changes in the calcium, magnesium or zinc balances were observed, but the nitrogen and phosphorus balances increased. The net or apparent absorption of nitrogen, magnesium and phosphorus expressed per milligram of intake increased significantly in the oat bran period due to the added content of these nutrients in the oat bran muffins. The intake of the oat bran muffins led to a significant increase in urinary phosphorus and significant decreases in urinary calcium and 47Ca excretions. The intestinal absorption of calcium, determined with 47Ca, did not change, whereas the endogenous fecal calcium increased slightly but significantly.

Adult↗
PubMed1990

Feasibility of long-term electrocardiographic monitoring with an implanted device for syncope diagnosis.

Patients with infrequent recurrent syncope undiagnosed after extensive noninvasive and invasive testing pose a diagnostic and therapeutic dilemma. The purpose of this pilot study was to assess the feasibility of using an implanted, long-term monitor as an aid to diagnosis in these patients. This was done using commercially available pacemakers with monitoring functions. Sixteen patients (eight males and eight females), aged 59.7 +/- 17 years who had unexplained syncope despite a 12-lead electrocardiogram, repeated Holter monitoring, exercise testing, echocardiography, an electrophysiological study, and a tilt test (n = 6), were entered into the study. Patients had experienced a mean of 3.1 +/- 1 episodes of syncope in the 12 months prior to the study. All provided a history suggestive of Stokes-Adams attacks and were referred for consideration of pacemaker implantation. Two patients had ischemic heart disease and one patient had a long QT interval. Patients had an Intermedics Nova II or Medtronic Quintech DPG pulse generator capable of recording sensed and paced events implanted with a single right ventricular lead. Syncope or presyncope occurred in ten patients (62%) 4.9 +/- 4.2 months after pacemaker implantation. Bradycardia was detected in six patients and four patients had no arrhythmia. In addition to bradycardia, one patient also had tachycardia detected. Pacing therapy resulted in symptom relief in all six patients with syncope or presyncope due to bradycardia. Complications of pacemaker implantation (lead insulation failure) occurred in two patients. One of these patients subsequently had an infection of the generator pocket with associated systemic sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1990

Evaluation of amino-oxyacetic acid as a palliative in tinnitus.

Amino-oxyacetic acid (AOAA) was evaluated as a palliative in tinnitus. Sixty-six patients with tinnitus presumed to be of cochlear origin were given either a placebo or 75 mg of AOAA four times a day for 1 week. Response was evaluated by both audiometric measurement of tinnitus loudness and subjective rating by patients of change or no change in tinnitus severity. Because loudness measurements and self-rating have not been shown to be independent, and since the aim of clinical treatment of tinnitus is the alleviation of subjective distress, greater weight was given to the patient's self-rating. A total of 21% of all patients reported a subjective decrease in tinnitus severity, usually within 3 to 4 days after the start of AOAA use. Patients with tinnitus caused by presbycusis or Meniere's disease were the most likely to respond to AOAA treatment with a reduction in tinnitus severity, whereas those with drug-induced tinnitus were the least likely to respond. Nausea and dysequilibrium were the most common side effects of AOAA use. Of the 21% of patients who responded to AOAA, 71% developed some type of side effect. Amino-oxyacetic acid produces a reduction in the severity of tinnitus in about 20% of patients; however, the incidence of side effects makes the drug unacceptable for clinical use.

Acetates↗
PubMed1990

Use of the Million Clinical Multiaxial Inventory in evaluating patients with severe tinnitus.

The Million Clinical Multiaxial Inventory (MCMI) was evaluated as a diagnostic tool for personality disorder among 41 patients with severe tinnitus. Nearly 70 percent of the subjects demonstrated a personality disorder. Nearly half of the patients fell into one of two categories; dependent/submissive or the narcissistic category. Other important features include a high incidence (24%) of severe anxiety. One-third of the patients had a complaint tendency but 50 percent had a denial problem. We have found the MCMI to be easy to administer and evaluate and it provides the clinician with useful information. We believe that more routine use of this or similar instruments would improve the treatment outcome of tinnitus sufferers by bringing into focus the important psychological factors found in each patient.

Auditory Perceptual Disorders↗
PubMed1990

Initial clinical experience with the pacemaker-cardioverter-defibrillator.

The implantation of a new multiprogrammable pacemaker-cardioverter-defibrillator is reported in four patients suffering from drug-refractory ventricular tachycardia or fibrillation. The generator (PCD 7215; Medtronic Inc) was interfaced to the epicardium by three countershock patch electrodes and one ventricular myocardial screw-in lead for sensing/pacing. The device employs separate rate detection criteria for ventricular tachycardia and ventricular fibrillation with automatic delivery of up to four therapies per episode. Therapeutic options include: antitachycardia burst or autodecremental pacing, synchronized cardioversion, defibrillation and ventricular demand pacing at 30 to 90 beats/min. Four men and one woman (ages 29 to 75 years) underwent intraoperative implant evaluation, and the device was implanted in the four men. Over a follow-up of 1.5 to 23 months, 161 spontaneous episodes of ventricular tachycardia and nine episodes meeting ventricular fibrillation criteria (cycle length less than 280 to 290 ms) were detected and treated by the device. Ramp pacing was initially employed to terminate 140 ventricular tachycardia episodes and was successful 88.5% of the time while 10 (7.2%) required low energy epicardial cardioversion (4 to 10 J). Six (4.3%) episodes terminated spontaneously prior to therapy delivery. All nine spontaneous episodes of ventricular fibrillation were defibrillated using 10 to 15 J. Two patients continue to do well with the device functioning reliably. The device was removed at the time of heart transplant in one patient, while another patient died suddenly from drug overdose. No other complications, device malfunctions or inappropriate therapy delivery have been observed. These early results demonstrate the potential usefulness of a programmable device which provides graded therapy for ventricular tachycardia with added defibrillation and bradycardia pacing capability.

Adult↗
PubMed1989

Effect of indomethacin, cycloheximide, and aminoglutethimide on ovarian steroid and prostanoid levels during ovulation in the gonadotropin-primed immature rat.

It has become popular to use the gonadotropin-primed immature rat to study ovulation. The ovarian content of progesterone, estradiol, PGE2, PGF2 alpha, and 6-keto-PGF1 alpha during the ovulatory process was determined in this model. Also, the effect of three anti-ovulatory agents on the ovarian levels of the above substances was determined. At 23 days of age, Wistar rats were primed with pregnant mares serum gonadotropin (PMSG) sc, and two days later the ovulatory process was initiated with human chorionic gonadotropin (hCG) sc. The ovarian follicles began rupturing 12 h later. Ovaries were assayed for the two steroids and prostanoids at 2-h intervals before and several 4-h intervals after ovulation. The ovarian estradiol level increased slightly between 0 and 2 h after hCG, while the progesterone level increased sharply between 2 and 4 h after hCG--at a time when the estradiol declined markedly. All three prostanoids increased concomitantly with progesterone. When the PG synthesis was blocked by indomethacin treatment at 1 h before hCG, ovarian progesterone levels still increased. In contrast, when steroidogenic activity was inhibited by aminoglutethimide, the ovarian prostanoid levels also decreased. Cycloheximide had little effect on the steroids and prostanoids. It is concluded that ovarian prostanoid synthesis might be influenced by ovarian steroid output.

Aminoglutethimide↗
PubMed1987

Cytochalasin D suppresses sound evoked potentials in the guinea pig cochlea.

Cytochalasin D (CD), an inhibitor of actin polymerization, was perfused through the guinea pig cochlea while monitoring various cochlear potentials. CD (10(-7)-10(-5) M) reduced the magnitude of the compound action potential of the cochlear nerve and the summating potential, and increased N1 latency. The cochlear microphonic potential was the least sensitive potential with only a slight effect being observed at 10(-5) M. The results are consistent with the hypothesis that actin has a role in cochlear function.

Actins↗
PubMed1987

Effect of zinc supplements on the intestinal absorption of calcium.

Pharmacologic doses of zinc are widely used as zinc supplements. As calcium and zinc may compete for common absorption sites, a study was carried out on the effect of a pharmacologic dose of zinc on the intestinal absorption of calcium in adult males. The analyzed dietary zinc intake in the control studies was normal, averaging 14.6 mg/day. During the high zinc study, 140 mg zinc as the sulfate was added daily for time periods ranging from 17 to 71 days. The studies were carried out during both a low calcium intake averaging 230 mg/day and during a normal calcium intake of 800 mg/day. Calcium absorption studies were carried out during the normal and high zinc intake by using an oral tracer dose of Ca47 and determining plasma levels and urinary and fecal excretions of Ca47. The study has shown that, during zinc supplementation, the intestinal absorption of calcium was significantly lower during a low calcium intake than in the control study, 39.3% vs 61% respectively, p less than 0.001. However, during a normal calcium intake of 800 mg/day, the high zinc intake had no significant effect on the intestinal absorption of calcium. These studies have shown that the high zinc intake decreased the intestinal absorption of calcium during a low calcium intake but not during a normal calcium intake.

Adult↗
PubMed1987

Effective long-term immunosuppression maintained by low cyclosporine levels in primary cadaveric renal transplant recipients.

Nephrotoxicity and cost are the major problems in the use of cyclosporine (CsA) in renal transplantation. Thus, maintenance of CsA levels at the lower limits of the therapeutic range is desirable. The lowest CsA level effective in preventing rejection while avoiding nephrotoxicity has not been defined. We report on 44 primary cadaveric renal transplant recipients treated with a protocol that involved a progressive reduction in the trough CsA levels. CsA was initiated at an oral dose of 15 mg/kg, and this dose was adjusted to achieve serum trough levels, as measured by radioimmunoassay, of 150-200 ng/ml during the first month, 100-150 ng/ml during the second month, 75-100 ng/ml during the third month, and 50-75 ng/ml thereafter. Patient and graft survival at 18 months were 94% and 83.6%, respectively. The mean daily CsA doses were 6.7 +/- 3.1 mg/kg at 6 months, 5.5 +/- 3.2 mg/kg at 12 months, and 4.7 +/- 2.4 mg/kg at 18 months. Corresponding trough serum CsA levels were 94 +/- 59 ng/ml, 64 +/- 22 ng/ml, and 44 +/- 21 ng/ml at 6, 12, and 18 months, respectively. Mean serum creatinine concentrations were 1.8 +/- 0.6 mg/dl at 6 months, 1.7 +/- 0.5 mg/dl at 12 months, and 1.6 +/- 0.5 mg/dl at 18 months. The mean serum creatinine concentration at 18 months was not significantly different from that of 18 conventionally treated primary cadaveric renal transplant recipients (1.6 +/- 0.5 vs. 1.4 +/- 0.4 mg/dl, P = .31). A total of 67% of patients did not have any rejection episodes under this protocol, while 71% of patients never developed CsA nephrotoxicity. No patient was taken off CsA for progressive nephrotoxicity. We conclude that trough serum CsA levels of 50-75 ng/ml, as measured by radioimmunoassay, are sufficient to maintain effective immunosuppression in the long-term management of primary cadaveric renal transplant recipients. These values are much lower than previously recommended, and this approach ameliorates chronic CsA nephrotoxicity.

Adult↗