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Biomedical subjects

A Phillips

Publications and source records attributed to A Phillips.

At least 145 records · Page 8Linked to original sources
PubMed1990

The selectivity of a new progestin.

Norgestimate is a new progestin developed for use with ethinyl estradiol as a combination oral contraceptive. It binds to rabbit uterine progestational receptors and in the oral form stimulates a progestational endometrial effect in rabbits. Norgestimate also exerts a direct effect on target organs, stimulating the endometrium in rabbits when injected directly into the uterine horn and inhibiting luteinizing hormone release from rat pituitary cells in culture. Like other progestins, norgestimate inhibits ovulation in several species and estrogen-induced vaginal cornification in ovariectomized rats, but it is not estrogenic. Unlike other progestins, including levonorgestrel and gestodene, norgestimate is relatively free of androgenic activity. Norgestimate's affinity for the androgen receptor is very poor (0.003 x dihydrotestosterone [DHT]), even poorer than that of progesterone (0.005 x DHT). In sharp contrast are the marked affinities of levonorgestrel (0.220 x DHT) and gestodene (0.154 x DHT) for that receptor. The selectivity of norgestimate at receptor level is demonstrated clearly by its highly favorable androgen-to-progestin binding ratio. Norgestimate is similar to progesterone in not significantly stimulating ventral prostate growth in immature rats, whereas levonorgestrel, gestodene, and desogestrel are significantly androgenic in this model. Further evidence of norgestimate's minimal androgenicity is its lack of affinity for human sex hormone binding globulin in vitro. In conclusion, these preclinical studies, consistent with clinical studies, demonstrate the progestational efficacy and selectivity of norgestimate.

Animals↗
PubMed1989

Association between serum albumin and mortality from cardiovascular disease, cancer, and other causes.

In a prospective study of 7735 middle-aged British men (British Regional Heart Study) 660 died during an average follow-up period of 9.2 years. There was a marked increase in mortality rate with decreasing serum albumin concentrations that persisted even after adjustment for age, social class, town of residence, cigarette smoking, serum total cholesterol, systolic blood pressure, serum total calcium, and forced expiratory volume in 1 s. When serum albumin concentration was less than 40 g/l, the mortality rate was 23/1000 per year compared with 4/1000 per year for a concentration equal to or above 48 g/l. A similar pattern was observed for cardiovascular, cancer, and other deaths. The associations persisted for cardiovascular disease and cancer even when deaths within the first five years of follow-up were excluded. These results must be interpreted with caution since there was no prior hypothesis concerning serum albumin. However, the strength of the association between serum albumin and mortality seems to be comparable with that for cigarette smoking.

Adult↗
PubMed1989

A comparison of sclerotherapy with staple transection of the esophagus for the emergency control of bleeding from esophageal varices.

We compared two procedures for the emergency treatment of bleeding esophageal varices in patients who did not respond to blood transfusion and vasoactive drugs. We randomly assigned 101 patients with cirrhosis of the liver and bleeding esophageal varices to undergo either emergency sclerotherapy (n = 50) or staple transection of the esophagus (n = 51). Four patients assigned to sclerotherapy and 12 assigned to staple transection did not actually undergo those procedures, but all analyses were made on an intention-to-treat basis. Total mortality did not differ significantly between the two groups; the relative risk of death for staple transection as compared with sclerotherapy was 0.88 (95 percent confidence interval, 0.51 to 1.54). Mortality at six weeks was 44 percent among those assigned to sclerotherapy and 35 percent among those assigned to staple transection. Complication rates were similar for the two groups. An interval of five days without bleeding was achieved in 88 percent of those assigned to staple transection and in 62 percent of those assigned to sclerotherapy after a single injection (P less than 0.01) and 82 percent after three injections. In only 2 of the 11 patients who received a third sclerotherapy injection was bleeding controlled for more than five days, and 9 died. We conclude that staple transection of the esophagus is as safe as sclerotherapy for the emergency treatment of bleeding esophageal varices and that it is more effective than a single sclerotherapy procedure. We currently recommend surgery after two injection treatments have failed.

Adolescent↗
PubMed1989

Cyclosporine-induced deterioration in patients with AIDS.

Eight patients with AIDS (acquired immune deficiency syndrome) but free of life-threatening infection were treated with the immunosuppressive drug cyclosporine for a mean of 53.9 days. The serum cyclosporine levels were maintained in the desired therapeutic range. All eight patients experienced severe toxic symptoms, which necessitated discontinuation of cyclosporine therapy in six. The serum levels of creatinine, urea and potassium rose during treatment and fell after therapy was stopped. The total leukocyte count, hemoglobin level, platelet count, total T-cell count, and T4- and T8-cell counts all fell markedly during treatment. The total leukocyte count, platelet count, and T4- and T8-cell counts rose after therapy was stopped, but the hemoglobin level remained low. No patient experienced resolution of symptoms during therapy, and the condition of all patients improved after treatment was stopped. The results of this pilot study indicate that cyclosporine does not alleviate, and may worsen, the symptoms and laboratory findings in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Relative weight and major ischaemic heart disease events in hypertensive men.

Some studies have suggested that lean hypertensive men may be at greater risk of major ischaemic heart disease (IHD) events than obese hypertensive men. The issue was examined on data from the British Regional Heart Study for 7735 middle-aged men followed up for an average of 7.5 years; during this time 443 men experienced a major IHD event. Hypertension was defined as systolic blood pressure of 160 mm Hg or above, diastolic blood pressure of 95 mm Hg or above, or receiving treatment for hypertension. For both hypertensive and normotensive men the rate of major IHD events, standardised for age and cigarette smoking, rose with increasing body mass index (BMI). The relative odds associated with a 5 kg/m2 difference in BMI (ie, a 15 kg difference in weight in men of average height [1.73 m]) were 1.30 (p = 0.02) and 1.43 (p = 0.0004) for hypertensive and normotensive men, respectively. A review of eleven prospective studies, including the British Regional Heart Study, presented in standard form for comparative purposes, suggests that lean hypertensive men are not at higher risk of major IHD events than overweight/obese hypertensive men. There seems to be no justification for the suggestion that a policy of weight reduction to lower blood pressure might be inappropriate.

Adult↗
PubMed1989

The possible dental effects of children's rusks: laboratory evaluation by two different methods.

In response to concern over the sugar content and possible dental effects of infants' rusks, a programme of research was undertaken to compare six different kinds of rusk with respect to (a) their cariogenicity in caries-active laboratory rats; (b) their capacity to serve as substrates for acid production by oral microorganisms, and the attack of this acid on dental mineral; (c) the adhesiveness of the rusks to the enamel surface. The caries scores in the animal experiments ranged from very high, with rampant dental destruction, for 31%-sucrose rusks, down to virtually non-cariogenic on a zero-sucrose variety. With only one anomaly, cariogenicity correlated well with sucrose content. The results of the studies in vitro showed good general agreement with the animal data. The sucrose in the rusks, rather than their content of other sugars such as glucose, maltose and lactose, etc, emerged as a major factor in determining their effect on teeth, but cereal components can also play a part in governing adhesiveness and fermentability.

Animals↗
PubMed1989

Cirrhotics with variceal hemorrhage: the importance of the time interval between admission and the start of analysis for survival and rebleeding rates.

The importance of variable time of entry for analysis of survival following variceal bleeding has recently been disputed. In a study of 194 cirrhotic patients with bleeding esophageal varices in whom 2-day mortality was 3%, statistically significant differences in both survival and rebleeding rates were obtained by shifting the starting point for analysis of survival by 2 weeks following admission to hospital or by 5 days for the analysis of rebleeding. In addition, the curve of hazard function for death or for failure to control bleeding following admission clearly showed that any change in entry time in a study of variceal bleeding would introduce bias and alter survival or rebleeding rates. Thus, the starting point for analysis following variceal hemorrhage is an important confounding variable when calculating both survival and rebleeding. It should always be taken into account, particularly in clinical trials, which are often performed in centers where patients are referred from other hospitals at different times following bleeding.

Epidemiologic Methods↗
PubMed1989

Laboratory studies of the dental properties of soft drinks.

The composition and dental properties of eight different soft drinks, representing some of the most popular types used in the UK, were examined. Demineralization experiments were conducted on hydroxylapatite, the basic component of dental enamel, determining calcium dissolving by atomic absorption spectroscopy and phosphorus by u.v. visual spectrophotometry. The titratable acid content of the drinks was found to give a better guide than their pH to their potential dental erosiveness. The sugar content, in their ready-to-drink form, varied from zero in a low-calorie product up to almost 14% in a blackcurrant drink, but using a technique with a relatively long contact time, and in the absence of intact dental plaque, the demineralizing action on hydroxylapatite of the acids already in the drinks eclipsed the effects of the acid generated by oral micro-organisms from the sugars in the drinks. The pure citrus juices showed potentially the worst dental properties, followed by the orange and blackcurrant concentrates after dilution to their ready-to-drink form, with least demineralization from the carbonated drinks, and a cola drink giving especially low values.

Beverages↗
PubMed1989

Dental and metabolic effects of lactitol in the diet of laboratory rats.

1. Because so little is known about the properties of lactitol as a possible alternative bulk sweetener to sucrose, it was tested in two large-scale experiments in laboratory rats. Matched groups of caries-active Osborne-Mendel rats were fed on uniform diets containing lactitol and compared with a sucrose control in both experiments, plus a xylitol control in the first experiment. 2. In the early stages of the experiments weight gains and food utilization were better on the sucrose than on the lactitol regimens. Body-fat storage was higher on the sucrose than on the polyol regimens. 3. At the end of 8 weeks the mandibular molars were examined for dental plaque accumulation and dental caries. The dental caries scores when 160 g sucrose/kg in the diet was replaced by lactitol were lower by a highly significant margin, bringing them down to the same low level as those on a 160 g xylitol/kg regimen. 4. Testing lactitol in a manufactured food product, shortbread biscuits, in comparison with ordinary sucrose biscuits, showed differences in plaque scores (significant) and caries levels (highly significant), with 60% fewer lesions on the lactitol regimen. 5. The results confirm the low cariogenic potential of lactitol, but show metabolic differences compared with sucrose.

Animals↗
PubMed1989

Prediction of progression to AIDS by analysis of CD4 lymphocyte counts in a haemophilic cohort.

Serial CD4 lymphocyte counts were recorded in 112 anti-HIV-positive haemophiliacs who were followed for up to 8 years after seroconversion. The patients remained at low risk of developing AIDS until their CD4 lymphocyte count fell to 0.25 X 10(9)/l. From this point, the risk increased as their count approached zero. Using this result and on the assumption (which is evaluated) that the underlying trend over time in CD4 lymphocyte counts is linear, the predicted rate of progression to AIDS was calculated for the cohort. It was estimated that 73% (95% confidence limits 60-86%) of the cohort will develop AIDS within 15 years of HIV-seropositivity. During 8 years of follow-up, this cohort had shown similar rates of progression to AIDS to other cohorts--haemophilic and otherwise--suggesting that this estimate may well have general applicability. The method described could be used to plan the provision of health-care resources for groups of anti-HIV-positive patients as it allows the number of new cases of AIDS to be predicted year by year, even when the patients' dates of seroconversion are unknown.

Acquired Immunodeficiency Syndrome↗
PubMed1989

The somatosensory evoked potential as a noninvasive method to determine flow rates for hyperosmotic disruption of the blood-brain barrier.

We have developed a noninvasive method to determine the flow rates necessary to produce hyperosmotic blood-brain barrier disruption in individual animals. The method uses the intracarotid infusion of 0.9% NaCl at increasing flow rates, while concurrently measuring the amplitude of the somatosensory evoked potential (SSEP). For these studies, dogs were prepared with craniotomies to visualize the duration of cortical blanching. Saline (0.9% NaCl) was infused into the internal carotid artery at flow rates of 0.9 to 2.1 ml/s for periods from 2 to 40 seconds while the SSEP was concurrently measured in six 30-second epochs before, during, and after the infusion. There was a linear relationship between the duration of cortical blanching (from 2 to 30 seconds) and amplitude suppression of the major negative deflection of the SSEP. This relationship allowed us to predict the intracarotid infusion rate necessary to achieve cortical blanching for periods of 20 seconds or more. Subsequent infusion of 1.4 or 1.6 osmolar mannitol at the predicted flow rate resulted in more pronounced suppression of the SSEP than did 0.9% NaCl and produced disruption of the blood-brain barrier as documented by computed tomographic scans with contrast enhancement. Intracarotid infusions of 0.9% NaCl that produced partial blanching (partial replacement of blood in cortical vessels) were associated with paradoxical enhancement of SSEP amplitude, thus providing an additional measure of the adequacy of the infusion rate. This technique provides a reliable method to determine intracarotid infusion rates for hyperosmotic disruption of the blood-brain barrier in individual animals, before the intracarotid infusion of hyperosmolar solutions.

Animals↗
PubMed1989

The temperature sensitivity of the Sabin type 3 vaccine strain of poliovirus: molecular and structural effects of a mutation in the capsid protein VP3.

The growth of the Sabin strain of type 3 poliovirus is reduced at high temperatures compared to that of its virulent precursor strain Leon. Recombinant viruses have been generated from infectious cDNA clones and demonstrate that the temperature-sensitive (ts) phenotype is mainly attributable to a difference in residue 91 of the virion protein VP3. Examination of non-ts mutants derived in vitro or in vivo reveals the existence of second site mutations some of which are clearly able to suppress the ts phenotype. The location of residue 91 of VP3, and of a number of candidate suppressor mutations, in the atomic structure of the virion suggests that the ts phenotype may result in destabilization of the particle and that the suppressors may function by stabilizing specific interfaces. It is not yet clear whether the ts phenotype is expressed at the level of the particle or in the form of defects in assembly or uncoating of the virion, or all three.

Amino Acid Sequence↗
PubMed1989

The natural history of human immunodeficiency virus infection in a haemophilic cohort.

112 haemophilic patients infected with HIV were followed up with clinical and laboratory assessment between 1 December 1979 and 30 November 1988. Sixty-six (59%) of the patients developed HIV-related clinical symptoms and 22 (20%) developed AIDS. Twenty (18%) of the patients developed p24 antigenaemia. Amongst the 59 patients whose date of seroconversion could be estimated the calculated 8-year cumulative incidence of AIDS was 40% (symptoms 73%). For the whole cohort of 112 patients, the median slope of linear regression of the absolute T4 lymphocyte count was steeper for those with AIDS (-0.113 x 10(9)/l per year) than for those without AIDS (-0.054 x 10(9)/l per year) (P less than 0.02). While 15 cases of AIDS developed during 58 patient-years of follow up after falling below a T4 lymphocyte count of 0.2 x 10(9)/l, only two cases occurred during 450 patient-years before reaching this count. Thus the decline of the T4 lymphocyte count to 0.2 x 10(9)/l may be an appropriate additional end-point for the assessment of new treatments for asymptomatic patients infected with HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Studies of the dental properties of lactitol compared with five other bulk sweeteners in vitro.

Standardized mixed cultures of dental plaque microorganisms were incubated for 24 h in media containing six different bulk sweeteners as energy source. The attack of the acid generated on tooth mineral was measured by calcium and phosphorus analyses. Demineralization was most severe with glucose and sucrose. Less acid was generated from sorbitol and mannitol, with much reduced demineralization. Fermentation of lactitol and xylitol was only very slight, leaving the final pH high and leading to extremely low enamel demineralization figures. The amounts of polysaccharide synthesized by the microorganisms in the incubations decreased in the order: glucose greater than sucrose greater than sorbitol greater than mannitol greater than lactitol greater than xylitol.

Bacteria↗
PubMed1989

Analgesia following inguinal herniotomy or orchidopexy in children: a comparison of caudal and regional blockade.

The effectiveness of postoperative analgesia was compared in 44 children undergoing inguinal surgery, 19 of whom received caudal analgesia (1 ml 0.2% bupivacaine/kg) and 25 ilioinguinal block (0.25 ml 0.5% bupivacaine/kg). The requirement for supplementary analgesia (intramuscular morphine) was less in the caudal group, although this did not reach statistical significance in the number studied. Ilioinguinal and caudal blockade both provide useful postoperative analgesia for children following ilioinguinal surgery.

Analgesia↗
PubMed1988

Inhibition of pregnancy before and after implantation in rats with monoclonal antibody against progesterone.

A monoclonal antibody against progesterone completely blocked pregnancy when rats were injected intraperitoneally at 0.53 mumol/kg/day on days 1 and 2, or on day 11 of a first pregnancy. The antibody was equally effective when injected again during a second pregnancy. There was no evidence for anti-idiotypic antibody production even when the injection of a heterologous (mouse) antibody was repeated in a second pregnancy.

Animals↗
PubMed1988

Evaluation of the anaphylactoid activity of a new LHRH antagonist.

ORF 23541 [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,Ser4,Nic-Lys5,D-Nic-Lys 6, Leu7, I-Lys8, Pro9,D-Ala10NH2; "Nal-Lys antagonist"] was identified as a potent LHRH antagonist without significant anaphylactoid activity. It blocked ovulation in proestrus rats when administered subcutaneously with an ED50 of 5.8 micrograms/kg. Much higher doses of ORF 23541 than of other antagonists were required to induce a cutaneous anaphylactoid-like reaction. Intradermal administration of ORF 23541 caused an 8.75 x 8.75 mm wheal response with estimated doses of 10.9 and 13.7 micrograms in rats and guinea pigs, respectively. These doses were at least 10 times greater than that required of other LHRH antagonists for the same response. ORF 23541 also did not alter pulmonary function in guinea pigs or dogs when administered intravenously at doses up to 10 mg. These results indicate that ORF 23541 represents a new generation of LHRH antagonists with an improved safety margin.

Anaphylaxis↗