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Biomedical subjects

D J Donovan

Publications and source records attributed to D J Donovan.

14 recordsLinked to original sources

Effects of intracoronary nicardipine, diltiazem and verapamil on coronary blood flow.

BACKGROUND: Intracoronary (IC) calcium channel blockers (CCB) such as diltiazem and verapamil are frequently utilized during percutaneous coronary interventions to maximize coronary blood flow. Their use, however, may be limited by systemic side effects such as hypotension and bradyarrhythmias. The vasoselective dihydropyridines, such as nicardipine, may be more effective at increasing coronary blood flow with fewer systemic side effects. This study compares the effects of nicardipine, diltiazem and verapamil on coronary blood flow, heart rate and blood pressure. METHODS: IC nicardipine (200 mcg), diltiazem (1 mg) and verapamil (200 mcg) were serially administered in a randomized, double-blinded fashion in minimally diseased (< 30% stenosis) left anterior descending or left circumflex arteries in nine patients. Epicardial coronary artery diameter (ECAD) was determined by quantitative coronary angiography and coronary blood flow velocity (CBFV) was measured by Doppler Flowire in each patient before and after each medication. RESULTS: Nicardipine significantly increased CBFV (p < 0.05) and had a longer duration of effect (p < 0.05), but had no difference in ECAD compared with diltiazem and verapamil. No differences were noted between CCB in changes in heart rate or mean arterial blood pressure. However, two patients had transient episodes of Type I second degree AV block after receiving diltiazem. CONCLUSION: When compared with diltiazem and verapamil, nicardipine appears to offer more potent and more prolonged vasodilatation with less risk of serious systemic side effects. Future studies are needed to assess the efficacy of IC nicardipine in patients with no-reflow.

Aged↗

Intravenous versus subcutaneous vitamin K1 in reversing excessive oral anticoagulation.

Our data suggest that compared with the subcutaneous route of administration, intravenous vitamin K1 results in a more prompt reduction in the international normalized ration. However, for most patients, subcutaneous vitamin K1 is an effective and safe alternative when used in conjunction with modification of subsequent warfarin dosing, because virtually all patients achieved a safe level of anticoagulation within 72 hours with this route of administration.

Adult↗

The removal of a transdural pedicle screw placed for thoracolumbar spine fracture.

STUDY DESIGN: This report describes the method of removal of a pedicle screw that had been misplaced through the thecal sac and the cauda equina instead of its proper location within the pedicle. OBJECTIVES: A patient who previously had undergone placement of pedicle screws and Roy-Camille plates for fixation of L1 burst fracture presented to the authors with neurologic deficits and a cerebrospinal fluid leak. Computed tomography myelogram and surgical findings demonstrated misplacement of three of the screws, one of which was placed through the dura with resulting impingement of nerve roots within the thecal sac. SUMMARY OF BACKGROUND DATA: Removal of the screws was required for neural decompression and resolution of the cerebrospinal fluid leak. METHODS: The patient underwent laminectomy to expose the screw and primary durotomy to include the entry point of the screw. This technique allowed safe removal under direct vision, with direct protection of the nerve roots. A subsequent anterior fusion procedure was performed. RESULTS: The patient regained full neurologic function, and his cerebrospinal fluid leak ceased. At 2-year follow-up evaluation, he describes only mild, occasional back pain. CONCLUSIONS: Penetration of the dura and injury to the neural elements can occur when pedicle screw instrumentation is used. Removal of the screw under these circumstances may cause additional neurologic injury. Durotomy and direct visualization of the neural elements in this case was a valuable adjunct to safe removal of the screw.

Adult↗

Delayed-type hypersensitivity skin testing predicts progression to AIDS in HIV-infected patients.

OBJECTIVE: To evaluate the prognostic significance of cutaneous delayed-type hypersensitivity (DTH) skin testing in persons infected with HIV. DESIGN: Cohort study. SETTING: United States Air Force (USAF) Medical Center. PATIENTS: Consecutive sample of 889 HIV-infected USAF personnel or dependents undergoing their first staging evaluation from 1985 through August 1990 in the USAF HIV Natural History Study. MEASUREMENTS: All patients were evaluated with DTH skin testing including purified protein derivative and four control skin test antigens: mumps, candida, tetanus toxoid, and trichophyton. In addition, all patients underwent CD4+ T-cell surface marker determinations. The relation between DTH skin test response at first evaluation and progression to Walter Reed stage 6 (presence of an AIDS-defining opportunistic infection) was evaluated using Kaplan-Meier survival analysis. RESULTS: Patients with more than 400 CD4+ T cells/mm3 are more likely than those having fewer than 400 CD4+ T cells per mm3 to respond to at least one (94% compared with 67%, P < 0.001) or at least two (86% compared with 45%, P < 0.001) DTH skin tests. Mean CD4 counts are lower for anergic compared with nonanergic patients and for patients responding to a single control skin test compared with those responding to two or more skin tests (P < 0.05). The DTH skin test response at first evaluation was also found to predict progression to AIDS; the relative risk at 5 years of follow-up was 2.5 (95% CI, 1.2 to 5.2) for anergy compared with a single positive skin test and 3.0 (CI, 1.4 to 6.2) for a single compared with two or more skin test responses. The DTH skin test response at first evaluation was a predictor of progression (P < 0.001) when controlling for initial CD4 count and Walter Reed stage in a Cox proportional hazards regression analysis. CONCLUSIONS: The DTH skin test response, a functional measure of cellular immunity, is an independent predictor of progression to AIDS in persons with HIV.

Acquired Immunodeficiency Syndrome↗

Anticoccidial effect of monensin against Eimeria mitis and Eimeria dispersa.

Four chick and five poult trials were conducted in order to investigate the anticoccidial efficacy of monensin against Eimeria mitis in chickens and Eimeria dispersa in turkeys. The chicks were fed a basal diet with either 0 or 100 ppm of monensin. The poults were fed a basal diet with either 0 or 60 ppm of monensin. Two days after the initiation of each experiment, the chicks and poults were crop-intubated with oocysts of E. mitis and E. dispersa, respectively. A group was also included that was not infected and not medicated. Growth and feed intake were recorded. At 6 or 7 days postinoculation, the birds were killed by cervical dislocation and were scored for the incidence and severity of intestinal abnormalities. The Eimeria mitis infection reduced (P less than .01) gain and the feed:gain ratio, compared with uninfected birds; the E. dispersa infection only reduced (P less than .05) gain. Although well-defined, discrete lesions were not observed, marked intestinal abnormalities were noted in birds infected with either E. mitis or E. dispersa. Also, the infected, unmedicated birds had increased (P less than .01) intestinal scores compared with uninfected birds or those with infection but treated with monensin. Monensin eliminated the reduction in gain and feed efficiency seen in the infected birds. The infected birds fed monensin had intestinal scores, gain, and feed:gain ratios similar (P greater than .10) to those for the birds that were not infected and that did not receive medication.

Animals↗

Effect of narasin and roxarsone combinations on Eimeria tenella infections in floor pen-raised broilers.

A series of four floor pen trials was conducted to evaluate the effects of narasin and roxarsone, both alone and in combination, on their capacity to control severe Eimeria tenella infections in broilers. Three levels of narasin (0, 60, and 80 ppm) were fed to chickens receiving either 0, 25, or 50 ppm roxarsone in a factorial design. Cecal coccidiosis was induced by seeding the litter with ionophore-tolerant and ionophore-sensitive strains of E. tenella. After 8 days, 10 birds/pen were killed and their cecal lesions scored. Performance (body weight and feed consumption) and mortality were measured at the termination of the trials. Narasin reduced the severity of cecal coccidiosis as measured by a reduction in cecal lesions and an improvement in bird performance. Roxarsone also reduced cecal lesion scores. The highest level of roxarsone (50 ppm) in combination with 60 or 80 ppm narasin produced additive responses in the control of E. tenella infections. Maximum performance was obtained when narasin alone was fed at 80 ppm; drug combinations improved performance when compared with that of nontreated or roxarsone only-medicated groups.

Animals↗

Randomized surgical adjuvant trial of interferon alfa-n1 in recurrent papillomatosis.

Sixty-six patients with recurrent respiratory papillomatosis of juvenile onset were treated for six months with interferon alfa-n1 (Wellferon) in a randomized crossover trial. Half received interferon alfa-n1 intramuscularly at a dosage of 5 megaunits per square meter daily for 28 days and then thrice weekly for five months, followed by six months of observation. The other half were observed for six months and then treated. Operations were performed every two months to assess disease extent by a scale developed for this purpose. The score for the patients during the first observation period was stable. There was a statistically significant lowering of score in patients receiving interferon alfa-n1 during both periods of drug administration. Eight of 57 patients with assessable airway disease achieved complete remission, as did one additional patient with disease limited to the nasopharynx. No patients achieved complete remission during six months of observation alone. This difference was statistically significant. Patients without tracheostomy were significantly more likely to achieve remission than those with a tracheostomy. The patients who were observed after discontinuation of the drug therapy showed a significant rise in score within four months. Symptoms of toxicity included transient fever, fatigue, nausea, and headache. Elevations in serum aspartate aminotransferase levels occurred in 64% of the patients. There was an inverse correlation between age and the ability to tolerate the medication. The dose studied may be close to the maximum tolerated dose. It appears that interferon alfa-n1 as an adjuvant to routine surgical management is effective in slowing the growth of respiratory papillomas.

Clinical Trials as Topic↗

Comparative hemodynamic consequences of inflation hold, PEEP, and interrupted PEEP: an experimental study in normal dogs.

Cardiac output and airway, intrathoracic, arterial, pulmonary artery, left atrial, and central venous pressures were studied in 8 mongrel dogs. They were anesthetized and ventilated with (1) inflation hold of various duration, (2) continuous positive end-expiratory pressure and one breath off). The results indicate a minimal decrease in cardiac output (of approximately 5 per cent) with inflation hold. Diminished cardiac output was noted with increasing levels of continuous PEEP. The severity of the decrease in cardiac output wasproportional to the airway pressure. The higher levels (20 cm H2O) OF PEEP were associated with profound decreases. Utilization of a technique of interrupted PEEP substantially reduced the adverse hemodynamic effects in the dog.

Animals↗

Carcinogen chemistry. I. Reactions of protonated dialkylnitrosamines leading to alkylating and aminoalkylating agents of potential metabolic significance.

Three distinct modes of protolytic dialkylnitrosamine fragmentation were observed when we followed the time dependence of the nuclear magnetic resonance (NMR) spectra of seven nitrosamines in superacid solution: 1) In equimolar HSO3F: SbF5 ("magic acid"), dimethylnitrosamine was cleaved to the protonated Schiff base of formaldehyde and methylamine, and diethylnitrosamine was similarly converted to the protonated acetaldehydeethylamine Schiff base.2) By contrast, of the five dipropyl-and dibutylnitrosamines were studied, all cleaved nonoxidatively under these conditions (with loss of nitrogen gas) to the corresponding propyl or butyl cations. The carbocations thus produced underwent condensation and fragmentation to form the tert-butyl cation as the principal product ultimately observable by NMR. 3) Thethird fragmentation mechanism, which involved denitrosation to the dialkylammonium ion, was observed only as a minor pathway in the sulfuric or fluorosulfuric acid protolysis of dimethylnitrosamine. The mechanisms that are postulated for these cleavage reactions, if functioning in vivo, could account for several metabolic observations that have proved difficult to reconcile with previous conceptions of nitrosamine metabolism.

Alkylating Agents↗