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Biomedical subjects

S Jenkins

Publications and source records attributed to S Jenkins.

At least 19 recordsLinked to original sources

Plasma cholesterol esterase level is a determinant for an atherogenic lipoprotein profile in normolipidemic human subjects.

Plasma cholesterol level is controlled by various factors. In the present study, high plasma activity of cholesterol esterase was found to correlate with plasma total cholesterol and low density lipoprotein (LDL) cholesterol levels in normolipidemic human subjects. However, the cholesterol esterase is not elevated in plasma of patients with familial hypercholesterolemia. These observations suggest that cholesterol esterase level is not determined by plasma cholesterol level, but elevated cholesterol esterase may be causative in increasing plasma cholesterol and LDL. Additional experiments further demonstrated that cholesterol esterase can convert the larger and less-atherogenic LDL to the smaller and more atherogenic LDL subspecies in vitro. These results suggest that plasma cholesterol esterase contributes to the formation and accumulation of atherogenic lipoproteins, and thus is a major risk factor for premature atherosclerosis in normal human subjects.

Adult

Management of hypertension and the core services guidelines: results from interviews with 100 Auckland general practitioners.

AIM: To determine if the management of a hypothetical case of essential hypertension by general practitioners conforms with the Report to the National Advisory Committee on Core Health and Disability Services guidelines on the Management of Raised Blood Pressure in New Zealand (Core Services Report on Hypertension) sent to all general practitioners in November 1992. METHOD: A cross-sectional survey of a random sample of 100 Auckland general practitioners using a standard case of a 60 year old man with essential hypertension. Seventy interviews were conducted by a face-to-face interview and 30 by telephone interview. The main outcome measures were. Initial choice of medication and levels at which blood pressure would require treatment. RESULTS: Forty one percent of the interviewed doctors had read the Core Services report on hypertension. Fifty percent of the doctors indicated they would use the recommended first line antihypertensive medication (ie, diuretic or beta blocker). Doctors who prescribed beta blockers had been graduated a significantly longer time than those who did not. The majority of doctors indicated that they would initiate pharmacological treatment at lower blood pressures in younger patients than older patients contrary to the recommendation of the report. CONCLUSIONS: Current reported practice is only partially consistent with that suggested by the Core Services report on hypertension. Approximately half of the doctors interviewed were prescribing the recommended first line medication. Treatment was more likely to be initiated at lower levels in younger patients than in older patients in spite of the higher absolute risk and potential absolute benefit in the latter group. Adherence to the guidelines could see a shift from overtreatment of younger patients to an increase in treatment for older patients who are at higher risk of blood pressure related disease. More specific graduate educational measures will be needed if the Core Services report on hypertension are to be implemented.

Adult

Manipulation of substrate utilization with somatostatin in patients with secondary multiple organ dysfunction syndrome.

OBJECTIVES: To determine whether glucose utilization and metabolic substrate (glucose and fat) oxidation could be manipulated in patients with secondary multiple organ dysfunction syndrome. DESIGN: Prospective study. SETTING: Intensive care units (ICU) of two university hospitals. PATIENTS: Eight adults free of hepatic disease and hemodynamically stable at the time of study, but with failed respiratory and gastrointestinal systems, who thus required mechanical ventilation and intravenous nutrition. INTERVENTIONS: Patients were infused with 20% dextrose through central venous cannulas at rates that increased and maintained (clamped) their plasma glucose concentration at 216 mg/dL (12 mmol/L) for 3 hrs. Somatostatin was infused continuously during the second and third hours of the clamp to reduce plasma concentrations of endogenous insulin and glucagon. Exogenous insulin was administered together with somatostatin during the third hour to restore basal insulin concentrations. Energy expenditure was measured by indirect calorimetry throughout the study and blood samples were withdrawn regularly for determination of metabolite and hormone concentrations. Main statistical comparisons were made between the baseline data (first hour of the study) and data collected during the second and third hours of the clamp. MEASUREMENTS AND MAIN RESULTS: Plasma glucagon concentrations were reduced by nearly 50% (p < .05) toward the end of the study, whereas no significant changes in plasma concentrations of cortisol or growth hormone occurred. Energy expenditure did not change significantly at any time during the clamp procedure. Glucose utilization (6.1 mg/kg/min [34 mumol/kg/min]) during the first hour of the hyperglycemic clamp, decreased by 53% (p < .05) with the infusion of somatostatin during the second hour of the clamp. However, once exogenous insulin was infused during the third hour, glucose utilization increased by 55% (p < .05) when compared with the baseline (hour 1) rate. Glucose oxidation was nearly doubled during the third hour of the study when compared with oxidation rates during the first and second hours. Fat oxidation decreased steadily during the 3-hr clamp. CONCLUSIONS: Glucagon has a significant inhibitory effect on glucose utilization during intravenous glucose infusion in the multiple organ dysfunction syndrome patient. Pharmacologic intervention with somatostatin and insulin (physiologic dose) can facilitate glucose utilization and oxidation in these patients. Further investigations are needed to determine whether long-term alteration of glucose and fat metabolism would be beneficial in the patient with secondary multiple organ dysfunction syndrome.

Aged

Altered cytokine expression in T lymphocytes from human immunodeficiency virus Tat transgenic mice.

Examination of the interaction between human immunodeficiency virus (HIV) regulatory gene products and the host immune system is fundamental to understanding the pathogenesis of HIV and could reveal possible targets for therapeutic intervention in the treatment of AIDS. The HIV Tat gene is a potential candidate for this type of strategy. Transgenic mice can be used to investigate the in vivo effects of Tat on the developing and dynamic immune system and on cellular gene expression. Thus, we have generated transgenic mice that harbor the HIV type 1 Tat gene under the transcriptional control of the human CD2 gene regulatory elements. This expression cassette results in high-level, tissue-specific transcription of the transgene within the T-cell compartment. In this report, we demonstrate the effects of Tat on the in vivo immune system. CD2-Tat transgenic mice show no signs of aberrant thymic development and have normal levels of T-cell subsets in the thymus and peripheral lymphoid organs. However, activated T cells from transgenic mice contain increased levels of tumor necrosis factor beta mRNA as well as biologically active tumor necrosis factor protein and express elevated levels of transforming growth factor beta and interleukin-4 receptor mRNA. These increased cytokine levels do not appear to alter mitogen- or antigen-stimulated responses or induce the formation of dermal lesions in ageing mice. Such investigations should provide insight into the combination of host immune factors mediating pathogenesis in HIV infection.

Aging

Construction of a community height surveillance programme: the Hackney growth initiative.

OBJECTIVES: To determine why, in the London Borough of Hackney before 1990, fewer children than expected were identified with remedial causes of short stature. To construct a practical model for height surveillance of 5 and 11 year old school entrants to improve the quality of child growth surveillance. SETTING: City and Hackney Borough, London, United Kingdom. METHODS: School nurses were trained by a clinical auxologist to measure children's height at school entry accurately and reproducibly. New procedures for measurement technique, plotting of data, referral, and audit were established. A reference manual was provided and a continuing training programme was started. RESULTS: During the first year the percentage of the target group measured was low. Changes in work practice led to improvements from 77% measured in the first year to 91% in the second year and 87% in the third year for 5 year olds. Improvements for 11 year olds were from 36% to 86% to 87% over the three years. Only 1.2% of 5 year olds and 2.6% of 11 year olds measured had height less than the third centile (compared with Tanner's height standards). CONCLUSIONS: School nurses measured height reliably. New audit procedures led to rapid changes in working practice and improvements in the percentage of children measured. The low numbers of short children previously identified with unrecognised abnormality may indicate an upward trend in height in this inner city population.

Body Height

Borrelia burgdorferi in eastern Virginia: comparison between a coastal and inland locality.

In Virginia, Borrelia burgdorferi was more prevalent in a site along the Atlantic Ocean, near Maryland, than in an inland site near Williamsburg and Yorktown. At the coastal site on Assateague Island, B. burgdorferi was isolated from 4.2% of 475 animals sampled, including four species of small mammals. Serologic tests indicated that 25-37% of the small rodents assayed had been exposed to B. burgdorferi. Immunofluorescence antibody assays specific for B. burgdorferi showed spirochete infection in Ixodes scapularis and Dermacentor variabilis but not in other species of ticks also examined from this site. At another coastal site (Parramore Island), no evidence of Peromyscus leucopus was found, no immature specimens of I. scapularis were collected, and no isolations were made from numerous raccoons or small mammals sampled. Borrelia burgdorferi infection was found in one I. cookei nymph, but not in numerous specimens of I. scapularis or other tick species from this locality. At the inland site between Williamsburg and Yorktown, B. burgdorferi was isolated from two small mammal species and antibodies to B. burgdorferi were found in only 7-10% of the small mammals sampled. Ixodes scapularis were less abundant at this locality than at the Assateague Island site. Borrelia burgdorferi spirochetes were found in I. scapularis and a single nymph of Amblyomma americanum, but not in any of numerous specimens of four other species. Infection with B. burgdorferi was found in 20% of unfed adult I. scapularis from vegetation, but in only 0.2% of numerous adults from hunter-killed deer. Infection in immature ticks was much lower than at Assateague Island. Borrelia burgdorferi may be more prevalent along the Atlantic coast than in inland areas. Isolations, seroprevalence, immature I. scapularis densities, and spirochete infection rates in ticks were higher at the Assateague Island site than the Williamsburg/Yorktown site. Consequently, the risk of human exposure to Lyme disease may be higher in some parts of the coastal area than elsewhere in Virginia. Overall, B. burgdorferi is less intense in Virginia than in the northeastern United States.

Animals

Effects of canine donor heart preservation temperature on posttransplant left ventricular function and myocardial metabolism.

The generally accepted method of preserving donor heart integrity during transfer is to arrest it with cold cardioplegic solution, then store it in a plastic bag immersed in an iced electrolyte solution. Temperatures between 0 degree C and 4 degrees C are maintained by this method until the heart is transplanted. Although profound hyperthermia best inhibits metabolic processes, it may damage the myocardium. Higher myocardial temperatures may be more advantageous and may result in better preservation. The efficacy of this hypothesis has been investigated in a canine model. The hearts of 40 dogs were isolated, arrested with cold cardioplegia, removed from the animal, and stored at different temperature ranges from 0-3 degree C to 12-15 degrees C for 4 hr. After this time period, the hearts were transplanted into a recipient animal in the cervical heterotopic position. The degree and speed of myocardial functional recovery were monitored by measuring end-systolic elastance generated from pressure-diameter loops using sonomicrometry techniques. Myocardial metabolism was studied simultaneously by monitoring coronary flow, O2, glucose, lactate, pyruvate, and free fatty acid uptakes. The results were compared with those from a control group of hearts transplanted immediately after their removal. Our results indicate that donor heart function was significantly depressed 30 min after heterotopic transplantation, but returned to "control" levels after 2 hr when stored between 0 degrees C and 6 degrees C. Myocardial function remained significantly depressed throughout the 2-hr recovery period in hearts stored at higher (6-15 degrees C) temperatures. Hearts stored at all temperatures continued to extract glucose, lactate, and free fatty acids, but produced significantly higher levels of pyruvate at higher storage temperatures, which may be related to the favored use of free fatty acids. In conclusion, donor hearts stored at colder temperatures for 4 hr regain complete left ventricular function faster than hearts stored at higher temperatures. Our experiments support the presently applied methods of donor heart preservation for 4 hr.

Animals

Multicenter in vitro comparative study of fluoroquinolones after four years of widespread clinical use.

In vitro activities of ciprofloxacin, fleroxacin, lomefloxacin, ofloxacin, and seven other oral antimicrobials including amoxicillin-clavulanic acid (A/C), oxacillin, cefaclor, cefixime, cefuroxime, erythromycin, and trimethoprim-sulfamethoxazole (T/S) were evaluated against 1708 fresh bacterial isolates from four hospital laboratories approximately 4 years after the introduction of ciprofloxacin. T/S and ofloxacin had the lowest MIC90s and greatest percentage of susceptible strains overall, followed by the other three quinolones. Quinolones were the most active drugs tested against Gram-negative bacteria, with little variation in the activity among the four compounds against most species. Quinolone resistance was detected to some degree in the majority of Gram-negative species tested, with Pseudomonas, Acinetobacter, Xanthomonas, and Providencia demonstrating the highest percentage of resistant strains. Ofloxacin and ciprofloxacin were relatively more active against Gram-positive bacteria than were fleroxacin and lomefloxacin, but T/S and A/C had more susceptible strains than any of the quinolones. Oxacillin-resistant staphylococci, enterococci, and streptococci exhibited the least quinolone susceptibility. This study showed that while resistance is developing among several previously susceptible bacterial species, quinolones remain important alternatives for the oral treatment of many types of infections. Actions to prevent or limit resistance will be important to maintain the viability of the quinolones as therapeutic agents in both hospital and community environments.

Anti-Bacterial Agents

Dose response of chlorhexidine against plaque and comparison with triclosan.

The optimum dose of chlorhexidine delivered by mouthrinse, which balances efficacy against local side-effects, is generally considered to be in the region of 20 mg 2 x daily. Unfortunately, there have been few dose-response studies for chlorhexidine mouthrinses and for these, only limited details are published. The aims of this study were to determine the dose response of chlorhexidine to plaque inhibition and position a 0.1% triclosan rinse within this model. 28 subjects took part in this 7-treatment, double-blind, randomised cross-over 4-day plaque regrowth study. The rinses were 0.01%, 0.05%, 0.1% and 0.2% chlorhexidine, 0.1% triclosan and minus active controls for chlorhexidine and triclosan. On day 1 from a zero plaque baseline, volunteers suspended tooth-cleaning and commenced supervised 2 x daily rinsing with 10 ml volumes of the allocated rinses. On Day 5, plaque was scored by index and area. Treatment differences between the 7 rinses were highly significant. A clear dose-response pattern was seen for chlorhexidine with mean plaque scores decreasing with increasing dose. Even at 0.01%, chlorhexidine showed considerable and significant plaque inhibition compared to control. Triclosan at 0.1% showed limited plaque inhibition and less than 0.01% chlorhexidine. The findings of this study suggest that consideration could be given to low concentration chlorhexidine rinses as adjuncts to oral hygiene.

Adult

The magnitude and duration of the effects of some mouthrinse products on salivary bacterial counts.

The persistence of action or substantivity of an antimicrobial agent in the mouth relates to the plaque inhibitory action of that compound. Substantivity can be assessed by measuring the magnitude and duration of the fall in salivary bacteria following single rinses with antimicrobials. This was a randomised single-blind, cross-over study measuring the effects of single 60-s rinses of 5 mouthwash products on salivary bacterial counts in 14 healthy human volunteers. Effects over a 7-h period were compared with a chlorhexidine rinse product (positive control) and saline (negative control). All but one rinse, containing cetylpyridinium chloride (CPC), significantly reduced bacterial counts compared to saline up to 5-7 h. No rinse produced the magnitude or duration of effect noted for chlorhexidine and decrements from baseline, with one exception, were highly significantly lower than with the chlorhexidine product. Comparing the 2 CPC rinses, the findings suggest that the activity of one product was vitiated by some other ingredient. The triclosan/copolymer, the essential oil/phenolic and one CPC products exhibited similar persistence. In those cases where information is available, these data are consistent with comparative plaque inhibitory findings for the products or their active ingredients. Again, it is concluded that the method is a useful screening and comparison test for the potential plaque inhibitory activity of antimicrobial oral hygiene products.

Adult

A comparison of cetylpyridinium chloride, triclosan and chlorhexidine mouthrinse formulations for effects on plaque regrowth.

A relatively small number of agents are used in mouthrinse products, although the possible variability in the final formulations is enormous. The aim of this study was to compare equal concentrations of 3 antimicrobial agents, in simple formulations, for plaque inhibition. This 4-day plaque regrowth study was a 5-cell, randomised, double blind cross-over design, involving 20 healthy human volunteers. The mouthrinse formulations were aqueous 0.05% solutions of cetylpyridinium chloride (CPC), chlorhexidine and triclosan, together with a 0.1% CPC and a minus active control rinse. On Day 1, from a zero plaque baseline, volunteers ceased normal oral hygiene and rinsed 2x daily for 1 min. with 10-ml volumes of the allocated rinses. On Day 5, plaque was scored by index and area. All rinses produced lower mean plaque values compared to control, but unlike the CPC and chlorhexidine rinses, the differences with triclosan did not always reach significance. The CPC and chlorhexidine rinses were always significantly more effective than the triclosan rinse. The greatest plaque inhibition was with 0.1% CPC although rarely significantly greater than the 0.05% CPC and chlorhexidine rinses which were similar in efficacy. The results indicate that further studies on lower concentration chlorhexidine solutions are warranted.

Adult

Nutritional status of schoolchildren in an inner city area.

Data were collected on the seven day weighed food intakes of 65 schoolchildren, aged 12-13 years, living in an inner city, socially deprived area in east London. Blood samples were collected during the week and analysed for cholesterol, serum ferritin, vitamins A, E, B-12, beta carotene, and folic acid. Boys generally fared better than girls with almost a quarter of the girls having intakes of calcium, magnesium, iron, zinc, vitamin A, and riboflavin less than the lower reference nutrient intake, an amount which, by definition, is enough for only the few people in a group who have low needs. Although the mean energy intake was close to the estimated average requirement for both boys and girls, 74% did not meet the recommended intake for fibre and a high proportion of children consumed more than 11% of their energy from saturated fat (85%) and added sugar (88%). Thirty seven per cent of the children ate no fresh fruit during the week they kept a diary and only 19% had vegetables (fresh or frozen), other than potatoes, on a daily basis. Their main sources of energy were chips, bread, and confectionery. No association was found between fat intakes and plasma cholesterol concentrations. Girls had significantly lower blood concentrations of folic acid, ferritin, and beta carotene. The findings of this study confirm the anxieties often expressed that many schoolchildren, particularly in less affluent areas, are eating diets which are unhealthy according to government recommendations.

Adolescent

Efficacy of breathing and coughing exercises in the prevention of pulmonary complications after coronary artery surgery.

One hundred twenty patients undergoing coronary artery surgery completed a randomized controlled study designed to investigate whether prophylactic chest physiotherapy affected the incidence of postoperative pulmonary complications. Group 1 patients received no preoperative or postoperative chest physiotherapy. Group 2 patients received preoperative education and instruction in breathing and coughing exercises and postoperative supervision and assistance in performing the same. These exercises were supervised by a physiotherapist twice per day on the first 2 postoperative days and once per day on the 3rd and 4th postoperative days. Physiotherapy for group 3 patients was the same as for group 2 patients except that patients were seen by a physiotherapist 4 times per day on the first 2 postoperative days and twice per day on the 3rd and 4th postoperative days. Group 2 and 3 patients were instructed to practice breathing and coughing exercises every hour. Overall, an incidence of clinically significant postoperative pulmonary complications of 7.5 percent was demonstrated. In general, these patients demonstrated lower levels of preoperative pulmonary function and very low early postoperative oxygenation compared with those who did not develop pulmonary complications. There was no indication that the incidence or severity of fever, hypoxemia, chest roentgenologic abnormalities or clinically significant postoperative pulmonary complications was different between groups. These results suggest that the necessity for prophylactic chest physiotherapy after routine coronary artery surgery should be reviewed.

Breathing Exercises

Maternal and congenital syphilis in Brooklyn, NY. Epidemiology, transmission, and diagnosis.

OBJECTIVE: To define the epidemiology, to determine factors associated with transmission, and to describe the clinical and laboratory features of congenital syphilis. DESIGN: Retrospective chart review and prospective analysis. SETTING: Kings County Hospital Center, Brooklyn, NY. PATIENTS: A total of 403 pregnancies during a 23-month period associated with positive syphilis serological findings. RESULTS: Seventy-three pregnancies (18%) resulted in congenital syphilis (35 live-born and 40 stillborn neonates). Pregnancies associated with congenital syphilis were significantly associated with lack of prenatal care, lack of maternal therapy for syphilis, and a higher rapid plasma reagin titer, but not with a reported history of "crack" or cocaine use, although detection of cocaine in urine samples was more likely with positive syphilis serology. CONCLUSION: Most live-born infants with congenital syphilis (23 of 35) lacked rash, hepatosplenomegaly, or adenopathy but were identified by laboratory tests (roentgenograms, cerebrospinal fluid VDRL test, conjugated bilirubin determination, or aspartate aminotransferase levels in serum samples). Half of the infants with congenital syphilis were stillborn.

Delivery, Obstetric

A 6-month home usage trial of a 1% chlorhexidine toothpaste (1). Effects on plaque, gingivitis, calculus and toothstaining.

Research and development has been aimed towards the development of toothpastes for oral hygiene and gingival health benefits. The most effective antiplaque agent to date, chlorhexidine, is difficult to formulate into active toothpaste products. Despite some encouraging findings for experimental chlorhexidine toothpastes, there are to date no commercially available products. Based on positive findings from an experimental gingivitis study, this investigation evaluated 2 chlorhexidine toothpastes, one with fluoride, as adjuncts to oral hygiene. The study was a double-blind controlled, parallel, balanced group design, extending over 6 months. A total of 297 volunteers commenced the study after screening for a minimum acceptance level of gingivitis. At baseline, 6, 12 and 24 weeks, stain, gingival, bleeding and plaque indices were recorded, together with a calculus index at 6, 12 and 24 weeks. After a baseline prophylaxis, volunteers used the allocated product 2 x per day, with no other oral hygiene instructions given. Plaque, gingival and bleeding scores improved in all 3 groups, but to an overall significantly greater extent in the active groups. However, staining and calculus indices were significantly increased in the active compared to the control group. If the local side-effects of chlorhexidine are considered to be acceptable, these chlorhexidine toothpastes could be recommended for the same clinical applications as other chlorhexidine products. The apparent compatibility of fluoride with chlorhexidine in the one product may be pertinent to caries prevention.

Adolescent

A dose-response study of triclosan mouthrinses on plaque regrowth.

Triclosan is used in toothpastes and mouthrinses as a plaque inhibitory agent. The concentrations used and therefore the dose of triclosan varies between products and there is, as with most plaque inhibitory agents, little information on the dose response of this agent. The purpose of this investigation was to measure the plaque inhibitory properties of triclosan in a simple mouthrinse formulation over a range of concentrations and therefore doses. The study was a 5 treatment, double-blind, Latin-square randomised, minus-active controlled design balanced for residual effects. The formulations were 0.01%, 0.05%, 0.1% and 0.2% triclosan in 0.5% sodium carbonate and 5% alcohol aqueous solutions, used as 10 ml, 1-min rinses 2 x daily, without tooth-brushing. 2 groups each of 15 healthy volunteers rinsed during alternate 4-day treatment, 1-week washout periods with the allocated rinses. From a zero-plaque baseline on Day 1, plaque was scored by index and area on Day 5. A dose response pattern of decreasing plaque indices and particularly areas, with increasing triclosan dose was observed. However, by far the largest sequential drop in plaque scores occurred between 0.1% and 0.2% triclosan treatments. Extending the dose-response study to higher concentrations is considered impractical if not unjustifiable, because of potential harmful local side-effects and compliance difficulties. Dose-response studies to assess the agents thought to potentiate triclosan would seem warranted.

Adult

Evaluation of a mouthrinse containing chlorhexidine and fluoride as an adjunct to oral hygiene.

Chlorhexidine and fluoride have valuable preventive roles in dental and oral diseases. There is also evidence that in caries prevention, together, they provide additive benefits. However, combined chlorhexidine/fluoride formulations have rarely been evaluated. The aim of this study was to determine whether a 0.12% chlorhexidine, 100 ppm F- mouthrinse provided adjunctive oral hygiene benefits compared to a minus active control rinse. The study was a randomised double-blind parallel design involving 102 subjects of whom 99 completed the 6 week experimental period. Subjects rinsed 2x per day for 1 min with 15 ml of the allocated rinse. Normal toothbrushing procedures were maintained throughout the study. At 6 weeks, plaque and gingivitis scores were significantly lower and the incremental reduction significantly larger in the active rinse group. However, as expected, toothstaining was significantly increased with the active rinse. It is apparent that this chlorhexidine/fluoride rinse could be used in those regimens recommended for other chlorhexidine formulations. The value of the formulation in caries prevention would seem worthy of further investigation.

Adolescent