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Biomedical subjects

J Vincent

Publications and source records attributed to J Vincent.

At least 19 recordsLinked to original sources

Vascular reactivity to phenylephrine and angiotensin II: comparison of direct venous and systemic vascular responses.

The objective of this study was to determine the relationship between peripheral venous responsiveness (use of the dorsal hand vein compliance technique) and systemic vascular responsiveness (measurement of blood pressure changes) to phenylephrine and angiotensin II in humans. There was a significant correlation (r = 0.70, p less than 0.02) between the dose causing a 20 mm increase in mean arterial pressure and the dose producing half-maximal response in the hand vein (log ED50) for phenylephrine but not for angiotensin II. There was no correlation between the systemic responses to angiotensin II and phenylephrine, but there was a significant correlation (r = 0.70, p less than 0.02) between the log ED50 measurements for phenylephrine and angiotensin II in the hand vein experiments. These findings suggest that systemic and hand vein responsiveness to phenylephrine are similar. Consequently, in evaluating alpha-adrenergic receptor mediated responses, the dorsal hand vein compliance approach offers a satisfactory alternative to the use of systemic hemodynamic changes.

Adult

Desensitization of beta-adrenoceptor- and prostaglandin E1 receptor-mediated human vascular smooth muscle relaxation.

Regulation of beta-adrenoceptors in animal tissues and human cell cultures has been extensively described; on the other hand, relatively little is known about regulation of beta-adrenoceptors in human tissues in vivo. Both beta-adrenoceptors and the prostaglandin E1 (PGE1) receptors stimulate vasodilation. We wondered if prolonged infusion of isoproterenol or PGE1 would cause desensitization of smooth muscle relaxation and used the dorsal hand-vein compliance technique to investigate this question. After constructing a dose-response curve to either the beta-agonist isoproterenol or to PGE1 in a phenylephrine preconstricted vein, isoproterenol (271 ng/min), PGE1 (956 pg/min), or saline was infused for 4 h in separate experiments. There was no change in the ED50 or Emax for either isoproterenol or PGE1 after saline infusion. After a 4-h infusion of isoproterenol, the maximal vasodilator response to isoproterenol was significantly (p less than 0.01) attenuated from 61 +/- 33% to 19 +/- 10%, while the ED50 significantly increased (p less than 0.01) from a geometric mean of 37 to 197 ng/min. After infusion of isoproterenol, the mean maximum PGE1-induced venorelaxation of 129 +/- 29% was modestly but significantly (p less than 0.05) blunted to 96 +/- 35%, while the ED50 of PGE1 increased significantly (p less than 0.01) from a geometric mean of 81 to 398 pg/min. A 4-h infusion of PGE1 significantly (p less than 0.01) attenuated the maximum response to PGE1 from 73 +/- 35 to 28 +/- 16%. The maximal vasodilatory response to isoproterenol was also significantly blunted (p less than 0.05) from 62 +/- 35 to 42 +/- 41%, with no change in ED50.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil

Desensitization of nitrate-induced venodilation: reversal with oral N-acetylcysteine in humans.

The objective of this study was to determine whether the dorsal hand vein could be used as a model to study tolerance to oral nitrates, and whether oral N-acetylcysteine (NAC) could reverse tolerance if present. Dose-response curves to nitroglycerin were constructed for 11 normotensive volunteers before and during treatment with a sustained-release formulation of isosorbide dinitrate, 80 mg, three times daily for 7 days and followed by concurrent treatment with NAC at a mean dose of 150 mg/kg/day, in divided doses, for 2 days. In separate studies, dose-response curves were constructed for seven normotensive volunteers before and after treatment with oral NAC at the same dose for 2 days. Nitroglycerin's Emax was significantly attenuated from 115 +/- 36 to 77 +/- 22% after treatment with isosorbide dinitrate alone (p < 0.009). Concurrent treatment with NAC reversed this decrease, as nitroglycerin's Emax of 108 +/- 26% during coadministration of isosorbide dinitrate and NAC was not different from its Emax in the control period. There was also no difference in the dose of phenylephrine required to cause 80% of maximal venoconstriction throughout the study. These studies demonstrate that smooth muscle tolerance to nitrates can be demonstrated in medium-sized veins in humans. In addition, high-dose oral NAC can reverse existing tolerance to oral nitrates in human veins. These results indicate that the dorsal hand vein compliance technique is a good model for the clinical investigation of tolerance to nitrates in humans.

Acetylcysteine

Pharmacological tolerance to alpha 1-adrenergic receptor antagonism mediated by terazosin in humans.

Chronic administration of alpha 1-receptor antagonists is associated with loss of clinical efficacy, especially in congestive heart failure, although the mechanism is uncertain. To evaluate changes in venous alpha 1-adrenoceptor responsiveness during chronic alpha 1-adrenoceptor blockade, dose-response curves to phenylephrine and angiotensin II were constructed in 10 healthy subjects before, during, and after administration of terazosin 1 mg orally for 28 d. Terazosin initially shifted the dose-response curve of phenylephrine to the right, with a significant increase in ED50 for phenylephrine from a control value of 102 to 759 ng/min on day 1 of terazosin (P < 0.001). However, by day 28, the dose-response curve had shifted back towards baseline with an ED50 of 112 ng/min. After discontinuing terazosin, the ED50 for phenylephrine remained near the baseline value, indicating no evidence of supersensitivity to phenylephrine. There was no change in responsiveness to angiotensin II during the course of treatment with terazosin. Plasma terazosin concentrations were stable throughout the period of drug administration. The mean Kd of terazosin was estimated as 11 +/- 15 nM in the first few days of treatment. This study demonstrates that pharmacological tolerance to the alpha 1-adrenoceptor blocking action of terazosin occurs in man and may be responsible for loss in efficacy with chronic therapy.

Adrenergic alpha-Antagonists

Efficacy of preprocedural rinsing with an antiseptic in reducing viable bacteria in dental aerosols.

This double-blind, controlled, cross-over, clinical study evaluated the effect of preprocedural rinsing with an antiseptic mouthrinse on the level of recoverable viable bacteria in an aerosol generated during a typical dental procedure. Eighteen subjects participated. Following 24 hours of abstention from all oral hygiene procedures, subjects received a 10-minute ultrasonic scaling of a randomly selected one-half of their mouth which served as the unrinsed control. They were then randomly assigned either antiseptic mouthwash or a control rinse and rinsed with 20 ml for 30 seconds, after which the remaining half mouth (experimental side) was scaled ultrasonically for 10 minutes. During each 10-minute scaling period aerosolized bacteria were collected on a sterile filter using a modified vacuum air-sampling device. Microbes captured on the sterile filter were quantitated by overlaying the filters onto trypticase soy agar, incubating the filters aerobically at 37 degrees C for 24 to 72 hours, and counting the resulting colony forming units (CFU). Preliminary experiments had confirmed that neither the collection method nor residual antiseptic mouthwash in the aerosol adversely affected the number of viable bacteria recovered from the filter. Rinsing with the antiseptic mouthwash produced a 94.1% reduction in recoverable CFUs compared to the non-rinsed control, while the control rinse produced a 33.9% reduction. The difference between the mouthwash and control was statistically significant (P < .001). This study indicates that preprocedural rinsing with an antiseptic mouthwash can significantly reduce the microbial content of aerosols generated during ultrasonic scaling and may have potential in-office use as part of an infection control regimen.

Adult

A simple purification method of squeezed krill for obtaining high levels of hydrolytic enzymes.

The raw material originating from freshly caught Antarctic krill (E. superba) was processed by centrifugation and then immediately frozen. This squeezed fluid adjusted to pH 7 was subjected to spontaneous autolysis by storing at different temperatures (20-45 degrees C) and times (10-48 h). The autolyzed material resulted in 3 distinct phases after high speed centrifugation. The intermediate phase (water-phase) was collected and concentrated by membrane filtration. The high-molecular-weight substances (greater than 10,000 Daltons) were further purified by ion-exchange chromatography and eluted by a salt gradient. In this matter a bulk enzymatic material from krill can be efficiently obtained for further purification of different hydrolytic enzymes (peptide hydrolases/carbohydrases).

Animals

Phototherapy of seasonal affective disorder in an adolescent female.

Seasonal affective disorder and its response to phototherapy has not been extensively studied in children and adolescents. In this case study, a 16-year-old girl with a 3-year history of seasonal affective disorder sought treatment. An A-B-A'-B study design demonstrates the remission of symptoms with phototherapy.

Adolescent

Proposal of Afipia gen. nov., with Afipia felis sp. nov. (formerly the cat scratch disease bacillus), Afipia clevelandensis sp. nov. (formerly the Cleveland Clinic Foundation strain), Afipia broomeae sp. nov., and three unnamed genospecies.

On the basis of phenotypic characterization and DNA relatedness determinations, the genus Afipia gen. nov., which contains six species, is described. The type species is Afipia felis sp. nov. (the cat scratch disease bacillus). Afipia clevelandensis sp. nov., Afipia broomeae sp. nov., and three unnamed not associated with cat-borne disease. All but one strain (Afipia genospecies 3) were isolated from human wound and respiratory sources. All Afipia species are gram-negative, oxidase-positive, nonfermentative rods in the alpha-2 subgroup of the class Proteobacteria. They are motile by means of a single flagellum. They grow on buffered charcoal-yeast extract agar and nutrient broth, but rarely on MacConkey agar, at 25 and 30 degrees C. They are urease positive; but they are negative in reactions for hemolysis, indole production, H2S production (triple sugar iron agar), gelatin hydrolysis, esculin hydrolysis, and peptonization of litmus milk. They do not produce acid oxidatively from D-glucose, lactose, maltose, or sucrose. The major cell wall fatty acids are 11-methyloctadec-12-enoic (CBr19:1), cis-octadec-11-enoic (C18:1omega7c), and generally, 9,10-methylenehexadecanote and 11,12-methyleneoctadecanoate; and there are only trace amounts of hydroxy acids. The guanineplus-cytosine content is 61.5 to 69 mol%. A. felis is positive for nitrate reduction and is delayed positive for acid production from D-xylose, but it is catalase negative. A. clevelandensis is negative in all of these tests. A. broomeae is weakly positive for catalase production and acid production from D-xylose, but it is negative for nitrate reduction.

Bacterial Typing Techniques

Use of red blood cells older than five days for neonatal transfusion.

Sick neonates often require periodic small volume transfusions (10 mL/kg) to replace blood drawn for laboratory monitoring during their hospital stay. We use red blood cells (RBCs), stored as CPDA-1 whole blood, up to their expiration date, and are unaware of any clinical problems with this practice. We proceeded to confirm our clinical impression by reviewing the hospital records of 22 transfused neonates who received a median of 2.5 RBC transfusions (range 1 to 11) with a volume of 16 mL (range 5 to 38) each, and total volume of 60 mL (range 16 to 152). The RBCs were stored a median of 7 days (range 2 to 27). Following transfusion, there was an increase (P less than .05) in hemoglobin (mean 2.8 +/- 1.6 gm/dL [SD]) and hematocrit (9.0% +/- 4.7%). The bilirubin also rose (0.6 +/- 1.5 mg/dL, P less than .05), but this was not considered clinically significant. No significant change occurred in pH or bicarbonate. Paradoxically, RBCs over 10 days of age resulted in a fall in potassium (-0.9 +/- 0.8 mEq/L, P less than .01), but not below 3.4 mEq/L. We could find no evidence by clinical observation or laboratory indexes that small volume transfusion of RBCs more than 5 days old was deleterious to the newborns studied. By using RBCs up to their expiration date, the number of donor exposures and the potential risk of transfusion-transmitted diseases can be decreased.

Blood Preservation

Familial defective apolipoprotein B-100: detection in the United Kingdom and Scandinavia, and clinical characteristics of ten cases.

Familial defective apolipoprotein B-100 (FDB) is a recently identified, dominantly inherited genetic disorder, which leads to increased serum concentration of low density lipoprotein (LDL) cholesterol with reduced affinity for the LDL receptor. This disorder is associated with a G to A mutation in exon 26 of the apolipoprotein B (apo B) gene which creates a substitution of glutamine for arginine in the codon for amino acid 3500. We have searched for this mutation in 374 unrelated individuals with hyperlipidaemia from the United Kingdom, and in 371 unrelated individuals with a primary clinical diagnosis of atherosclerosis from the United Kingdom and Scandinavia. Ten individuals, 9 from the U.K. and 1 from Denmark, were identified. The frequency of the mutation was 3% in individuals classified clinically as having familial hypercholesterolaemia (FH) and 3% in individuals with type IIa hyperlipidaemia without FH, and was not found in patients with types IIb and III hyperlipidaemia. The mutation was rare in individuals with a primary clinical diagnosis of atherosclerosis. Plasma lipid levels and clinical characteristics of the ten patients identified in the present study are similar to those reported for heterozygous FH. Thus, in our study, FDB is associated with moderate to severe hypercholesterolaemia, and appears to be a serious disorder causing premature cardiovascular disease. Individuals with this mutation can be identified unambiguously using routine molecular screening techniques.

Adult

Effects of methylphenidate on early adolescent growth.

Thirty-one hyperactive adolescents treated with methylphenidate for at least 6 months demonstrated no significant deviation from expected height and weight growth velocities. In contrast to findings in prepubertal children, these results suggest that early adolescent growth is insensitive to methylphenidate.

Adolescent

Protection against membrane-mediated cytotoxicity by calcium and zinc.

Injection of S. aureus alpha toxin or ultraviolet-inactivated Sendai virus into the mammary gland of lactating mice leads to cytopathic changes in the alveolar cells compatible with a breakdown of their permeability barrier. Simultaneous administration of Ca2+ or Zn2+ prevents such changes, as it does when added to alveolar cells in vitro. It is concluded that increased levels of Zn2+ (and under certain conditions of Ca2+) may exert a protective role that is clinically significant.

Animals

Biochemical and biological profile of a new enzyme preparation from Antarctic krill (E. superba) suitable for debridement of ulcerative lesions.

A protease extract from Antarctic krill (E. superba) intended as a new enzymatic debrider for necrotic ulcers has been characterized by sodium dodecyl sulphate polyacrylamide gradient gel electrophoresis and fast protein liquid chromatography. The predominant enzymes in the preparation represent trypsin-like activity associated with three serine proteinases. In addition two carboxypeptidases A and B are present as cooperative enzymes for a more complete breakdown of complex proteinaceous substrates. Biological studies on a well-defined substrate (fibrin) originating from leg ulcers, demonstrated more effective degradation by krill enzymes than bovine trypsin, a common component in marketed enzymatic debriders. These findings support previously in vitro/in vivo studies in an animal model (rat) using excised rat skin as "necrotic" tissue.

Animals

Comparative field evaluation of the fluorescent-antibody test, virus isolation from tissue culture, and enzyme immunodiagnosis for rapid laboratory diagnosis of rabies.

The rabies tissue culture infection test (RTCIT) and rapid rabies enzyme immunodiagnosis (RREID) were compared to the fluorescent-antibody test (FAT) with field specimens. At the French National Reference Center for Rabies, 15,248 specimens were analyzed by FAT and RTCIT, and 2,290 of those specimens were also tested by RREID; 818 other specimens were tested by FAT and RREID in 12 laboratories located in Africa, Asia, and Latin America. The sensitivities and specificities of RREID and RTCIT were comparable. This study showed that both tests can be used as backup procedures to confirm FAT. RREID is also strongly recommended for epidemiological studies and for laboratories which are not equipped for performing FAT.

Africa

Privatising residential care for elderly people: the geography of developments in Devon, England.

The growth in numbers of very elderly people is becoming a trend in many Western societies. Often, these people may come to require some kind of assisted living environment. In Britain during the 1980s the overwhelming growth of residential accommodation has been in the private rather than the public sector. This has links with a number of other trends in health care and other sectors of the economy which are moving towards privatisation. The reasons for this are discussed and a case study of the county of Devon introduced. A survey of about one-quarter of all 450 homes in the county in mid-1984 revealed that they had important characteristics as small businesses. Countywide, a marked concentration of private residential homes has developed in some coastal 'holiday' locations. However, there have recently been changes in this pattern and growth of numbers of homes in some main towns also. There have been certain adverse reactions to the growth of homes and in a few areas, planning authorities have attempted to prevent the development of local concentrations of homes. This has been related to other policies elsewhere to prevent the concentration and ghettoisation of service-dependent groups. The nature and results of such planning policies are briefly considered. The paper addresses the overall questions of the type of care we wish to provide for our elderly people and whether privatisation of this aspect of health and welfare services is justified. This poses an important area of research for medical geographers interested in service delivery and aspects of equity in health care provision.

Aged