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Biomedical subjects

R Wilson

Publications and source records attributed to R Wilson.

At least 667 records · Page 37Linked to original sources

Effect of betamethasone and betamethasone with neomycin nasal drops on human nasal mucociliary clearance and ciliary beat frequency.

The effects of two topical nasal preparations on human nasal ciliary beat frequency in vitro and on nasal mucociliary clearance in vivo were investigated. Betamethasone and betamethasone with neomycin drops were found to be ciliotoxic when ciliated epithelium was exposed to them in vitro, mainly owing to the effects of the preservatives benzalkonium chloride and thiomersal. The nasal mucociliary clearance and in vitro ciliary beat frequency of nasal ciliated epithelium taken from healthy subjects were not adversely affected after topical application; neither did treatment with betamethasone, with or without neomycin, for four weeks affect these indices in two groups of patients with rhinitis. Thus, despite a ciliotoxic effect when ciliated epithelium is exposed to these preparations in vitro, they do not affect nasal clearance or ciliary beat frequency (as measured in vitro) adversely when administered topically to the nose.

Administration, Intranasal↗

Regulation of parathyroid hormone release and cytosolic calcium by extracellular calcium in dispersed and cultured bovine and pathological human parathyroid cells.

Alterations in parathyroid glandular sensitivity to calcium may contribute to the hypersecretion of PTH in hyperparathyroidism. Since the cytosolic calcium concentration may mediate the effects of extracellular calcium on PTH release, we have employed the calcium-sensitive intracellular dye QUIN-2 to examine the relationship between extracellular calcium, cytosolic calcium, and PTH secretion in adult, neonatal, and cultured bovine as well as pathological human parathyroid cells. PTH release was measured using C- and N-terminal radioimmunoassays. Neonatal bovine parathyroid cells showed a greater set-point for secretion (the Ca++ concentration causing half of the maximal inhibition of PTH release) than adult cells (1.27 +/- 0.11 vs. 1.06 +/- 0.11 mM extracellular calcium, P less than 0.01), and a slightly higher extracellular calcium was necessary to raise the cytosolic calcium concentration to a given level in neonatal than in adult bovine parathyroid cells. In individual neonatal and adult cell preparations, there was a close correlation between the set-point for secretion and the "set-point" for cytosolic calcium (r = 0.832, P less than 0.001). In cells from five human parathyroid adenomas, which had an increase in set-point for secretion, the extracellular calcium concentration necessary to raise the cytosolic calcium concentration to a given level was slightly greater than in the neonatal cells. In four preparations of human parathyroid cells there was a significant correlation between the set-points for secretion and cytosolic calcium (r = 0.856, P less than 0.01). Because neonatal bovine and pathological human parathyroid glands show cellular hyperplasia, we studied the temporal relationship between cellular proliferation and the regulation of PTH release and cytosolic calcium concentration in cultured bovine parathyroid cells. Cellular proliferation, estimated by 3H-thymidine incorporation, increased significantly in culture from 104 +/- 10.1 counts/well on day 1 (first 24 h in culture) to 588 +/- 188 and 6,156 +/- 649 counts/well on days 2 and 4, respectively. In cultured cells on day 1, highly Ca++ (2-3 mM) inhibited maximal PTH release by 58.8 +/- 3.2%, which decreased significantly (P less than 0.001) to 38.2 +/- 1.9 and 17.1 +/- 3.7% on days 2 and 4, respectively. The cytosolic calcium observed at 3 mM calcium on day 1 was 701 +/- 43 nM, which declined to 466 +/- 60 and 314 +/- 14 nM on days 2 and 4 (P less than 0.05). There was a close correlation between this progressive decrease in maximal inhibition of PTH release and the cytosolic calcium at high extracellular calcium in cultured cells (r = 0.99, P < 0.001). Thus, during active proliferation of cultured cells, there is an alteration in the regulation of cytosolic calcium at a given extracellular calcium concentration, and changes in the regulation of PTH release and cytosolic calcium by extracellular calcium may be related to enhanced cellular proliferation.

Animals↗

Management and outcome of necrotizing enterocolitis.

A survey of all cases of NEC in the State of Georgia during 1977 and 1978 identified 148 infants with NEC. Fifty-two of these infants were treated surgically, and the survival rate was 48 percent (26/54). The survival rate of medically treated patients was 68 percent (64/94) p less than 0.02. Survival was inversely associated with birthweight, although the survival rate following surgery was similar regardless of size. Age of presentation did not influence frequency of surgery or survival, but if perforation at surgery was present in smaller infants (less than or equal to 1500 g) the survival was less than if operation occurred prior to perforation (78% vs. 39%) p less than 0.05. The type of surgical procedure required also was associated with survival. The survival rate was greatest (90%) if only large bowel was removed and least (27%) if small bowel was resected. These results indicate the influence of birthweight, surgical procedure required, and presence or absence of perforation on survival and particularly surgical survival in NEC. They suggest that reviews of outcome in surgical management must take into account the extent of the surgical procedure that it was necessary to employ.

Birth Weight↗

Selection bias in clinical trials.

Of 90 patients with intermediate or high-grade sarcoma eligible for a randomized trial of adjuvant doxorubicin (Adriamycin, Adria Laboratories, Columbus, Ohio), 48 were not entered: 24 (27%) by physician's choice and 24 refused randomization. Sixty-five percent of lower stage patients were randomized compared with 37% of those with higher stage (P = .02). Patients with extremity lesions were more frequently offered participation in the study (P = .07). Patients with lower stage lesions accepted randomization more readily than those with higher stage lesions (P = .01). As predicted by the higher stage and percentage of central lesions, the disease-free survival of nonrandomized patients was inferior to that of randomized patients (P = .15). Thus, patients at high risk appeared to avoid randomization and adjuvant doxorubicin in this trial, resulting in an inferior disease-free survival for the nonrandomized control group. Important questions generally require randomized trials that reliably determine relative treatment differences. If, however, the patients in a clinical trial are not representative of the entire patient population because of patient and physician selection biases, the generalizability of the results to the entire patient population may be compromised. For example, the prognosis of the general population cannot necessarily be inferred from the selected group in the study. In this study, the randomized and nonrandomized series yielded differing conclusions regarding treatment efficacy, even when an adjustment was made for known prognostic facts.

Clinical Trials as Topic↗

Relapse of Graves' disease after medical therapy: predictive value of thyroidal technetium-99m uptake and serum thyroid stimulating hormone receptor antibody levels.

In 49 patients with Graves' disease, the 20-min thyroidal uptake of 99mTc and serum levels of thyroid stimulating hormone (TSH) receptor antibody were estimated at presentation and at intervals during a 1-yr course of carbimazole and triiodothyronine. In the 12 mo after cessation of therapy, 29 patients developed recurrent thyrotoxicosis. Thyroidal 99mTc uptake had a poor predictive value for recurrence of thyrotoxicosis, both at presentation and during therapy. A very high level of TSH receptor antibody was present in seven patients at presentation, all of whom relapsed on withdrawing therapy. An abnormal value of TSH receptor antibody at the end of the course of medical therapy was present in 24/29 (83%) patients who relapsed and in 1/20 (5%) patients who remained euthyroid 1 yr after stopping antithyroid drugs.

Adolescent↗

Successful management of Graves' disease in a patient undergoing regular dialysis therapy.

Classic Graves' disease associated with thyroid-stimulating hormone receptor antibodies developed in a woman undergoing regular hemodialysis for uremia from chronic pyelonephritis. Her condition responded well to treatment initially with carbimazole and then an ablative dose of sodium iodide I 131 therapy. To our knowledge this is only the second documented case of hyperthyroidism in a patient with chronic renal failure, and it demonstrates that conventional forms of therapy are efficacious and safe.

Adolescent↗

Effect of 8-(3-diethylaminopropyl)-6,6-dimethyl-(2-phenyl-1 H-imidazo(4,5 h))isoquinoline-7,9-(6H)-dione dihydrochloride (AR-LH31) on experimental cardiac arrhythmias in dogs.

The effects of intravenously administered 8-(3-diethylaminopropyl)-6,6-dimethyl-(2-phenyl-1H-imidazo (4,5H))-isoquinoline-7,9-(6H)-dione dihydrochloride (AR-LH31) on experimentally induced ventricular tachycardia were studied in dogs. Ventricular tachycardia was produced in 6 anaesthetised dogs by the intravenous injection of ouabain (66.7 +/- 4.9 mg/kg). AR-LH31 administered by increasing bolus injections every 5 min completely suppressed the ventricular tachycardia with a return to sinus rhythm in 1 out of 6 dogs, with a partial return of sinus beats in a second dog. There was no return to sinus rhythm in the 4 remaining dogs after doses ranging from 1.75 to 15.75 mg/kg. Observations were made in 9 conscious dogs 22-24 hours after ligation of the anterior descending branch of the left coronary artery when a ventricular tachycardia was present. The administration of AR-LH31 by bolus intravenous injection in 4 dogs did not abolish the arrhythmia in any dog but increased the number of sinus beats. In 3 out of 4 dogs after a cumulative dose of 7.75 mg/kg, 60% of ventricular beats were of sinus origin. The effects of larger doses could not be studied be cause of adverse effects. In 5 dogs the administration of AR-LH31 by constant intravenous infusion at 16 mg/kg/h restored sinus rhythm in all dogs after a mean dose of 9.9 +/- 0.9 mg/kg. These studies indicate that AR-LH31 has anti-arrhythmic activity in dogs and highlight the importance of the method of administration in determining the effects of a drug.

Animals↗

Potential for low-LET charged-particle radiation therapy in cancer.

The current and likely future status of low-LET charged-particle therapy of cancer is reviewed with regard to both physical and clinical aspects. We conclude that such therapy has reached the stage at which clinical implementation is practical and that a broader program is needed if the clinical advantages of improved dose distributions are to be determined.

Clinical Trials as Topic↗

Race as a risk factor for progressive glaucomatous damage.

Retrospective analysis of black and white men with glaucoma indicated that open-angle glaucoma may be a more severe disease in blacks than in whites. Disk damage and visual field loss at initial diagnosis appeared to be worse in the eyes of blacks. Progression of disease as evidenced by further disk damage and visual field loss was more marked in the eyes of blacks. Furthermore, at initial diagnosis blacks were younger than whites, suggesting an earlier onset of open-angle glaucoma among blacks.

Adult↗

Computer assisted management of warfarin treatment.

Maintenance of anticoagulation is laborious and costly, and the results are often indifferent. An automatic system which adjusts the dose of warfarin has been designed using a formula devised after a survey of prescribing habits. Programs running on a microcomputer maintain a file of the necessary information and deal with the bulk of the weekly clinic. Dosage is advised, the date of the next visit determined, and the file updated. A doctor uses the console to advise some 10% of patients reserved for special reasons. The system produces clinic and ambulance lists, copies of the advice sent to patients, and, as a protection against machine failure, a weekly copy of the updated file. The results after 16 months are at least as good as those achieved manually. Medical and secretarial time is saved, and statistics about the clinic and its efficacy are made available.

Appointments and Schedules↗

Effects of tumor growth on interleukins and circulating immune complexes. Mechanisms of immune unresponsiveness.

This study delineates the temporal relationship between immune complex formation and tumor growth, and provides one possible explanation for host immunosuppression during tumor growth. The authors have studied serial circulating immune complex (CIC) levels and interleukin (IL) elaboration by peripheral blood cells (IL-1 production by adherent mononuclear cells [AMC]; and IL-2 generation by peripheral blood mononuclear cells [PBMC]) during the growth of syngeneic tumor isografts in an inbred rat model. Male Wistar/Furth (W/Fu) rats were injected, subcutaneously (SC) with 2 X 10(6) W163 ( a dimethylhydrazine [DMH]-induced colon adenocarcinoma) cells into their hind limbs. Serial CIC levels, (measured by the antigen nonspecific polyethylene glycol turbidity assay) and IL-1 and IL-2 production were measured before isografting and weekly thereafter. Progressive local tumor growth occurred for 3 weeks followed by regional lymph node metastases during the fourth week. During local tumor growth, there was a progressive rise in CIC levels (123% rise compared with baseline value; P less than 0.05) which correlated with a fall in both IL-1 and IL-2 generation (r = -0.768). At the time of regional metastasis, the mean CIC levels declined, and there was a further significant decrease in IL production (IL-1 = 0.9% and IL-2 = 10% of controls in tumor bearers). These results show that progressive tumor growth results in decreased IL production by host PBC, and suggest that CIC may be involved in regulating IL generation.

Adenocarcinoma↗

Actin filaments in contracting preretinal membranes.

In 14 patients, preretinal membranes, causing retinal traction and severe visual impairment, were removed by vitrectomy and evaluated by light and electron microscopy using myosin subfragment-1 to stain actin filaments. Eight membranes were of vascular origin, six of nonvascular origin. All but one contained bundles of oriented actin filaments within a number of their nonvascular stroma cells, suggesting that the contractile protein action may have been involved in their clinically observed contraction.

Actins↗

Effects of low energy laser on wound healing in a porcine model.

Low energy helium neon laser has been suggested as an effective adjuvant in the healing of open wounds. To date, supportive studies have been performed in loose-skinned animals. For such data to be clinically meaningful, it was felt necessary to study this effect in an animal with a dermal structure more closely resembling that of man, the pig. After creating 62 partial thickness wounds on the dorsum of domestic swine, one-half of these were randomized to receive laser treatment. The remainder served as controls. Laser treated wounds received a daily treatment of 15 sec/cm2 at an irradiance of 64 mW/cm2 (energy fluence = .96 J/cm2/day). With these treatment parameters, we could not demonstrate any clinically significant laser induced acceleration of open wound healing.

Animals↗

Age-related changes in glucose metabolizing enzymes in spleen, thymus, and pulmonary lavage cells from F344 rats.

Healthy male Fischer 344 rats were sampled at 6, 12, 18, and 24 months of age. There was no gross pathological evidence or deviations in body weight, hematology, or clinical chemistry that were indicative of disease. Mixed populations of thymus, spleen, and pulmonary cells were obtained for enzymatic analyses. Key enzymes from the hexose monophosphate shunt, glycolysis and the tricarboxylic acid cycle were evaluated to determine if there were tissue-specific or pathway-specific changes that occurred during aging. The enzyme responses among the tissues were not consistent during the aging process. Generally the activities of the glucose metabolizing enzymes in thymus and pulmonary lavage cells decreased with age whereas they increased in the spleen cells. Between 18 and 24 months enzymes representative of all three glucose metabolic pathways decreased in pulmonary lavage cells, whereas the decreases in thymic cells were mainly restricted to glycolytic enzymes. By contrast there were two- to ten-fold increases during aging in all of the splenic enzymes measured except malate dehydrogenase. The alterations in tissue enzyme activities probably reflected the changing cellular populations during aging, and in the thymic and pulmonary lavage cellular environment resulted in a loss of energy production by glucose oxidation, compared to the vigorous activity maintained in spleen.

Aging↗

The impact of political violence on mild psychiatric morbidity in northern Ireland.

Evidence concerning the impact of the violence in Northern Ireland on psychiatric morbidity is limited to studies examining admission rates and psychotropic drug prescribing rates; their results varied from suggesting no effect to indicating that greater levels of violence are actually equated with higher levels of mental health. The present study is the first to use a community sample, in which respondents (797) from two towns, which have experienced contrasting levels of violence over the last ten years, completed the 30-item version of the General Health Questionnaire (GHQ), and also indicated their perception of the level of violence in their area and how safe they felt this was to live in. Those who lived in the more violent town scored higher on the GHQ, as did women compared to men and those who perceived that their area had experienced more violence. There was also a two-way interaction, such that the small number of people, who perceived much violence in their area and who also lived in the more violent town, scored more highly on the GHQ. It is possible that the majority of people in Northern Ireland deal effectively with stress generated by the political violence, but do so by denying the existence of this violence around them.

Adult↗