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Biomedical subjects

D Gianola

Publications and source records attributed to D Gianola.

At least 19 recordsLinked to original sources
PubMed1992

Efficacy of a new long-acting injectable form of bromocriptine in hyperprolactinaemic patients.

OBJECTIVE: The objective of this study was to assess the relationship of different doses of a long-acting bromocriptine preparation (Parlodel LAR) to the degree and duration of PRL suppression. We also measured circulating bromocriptine levels and altered tolerability of the drug. DESIGN: A double-blind randomized study of three different doses 25, 50 and 100 mg of Parlodel LAR. PATIENTS: Twenty-one female patients (seven patients/dose) with both tumoral and non-tumoral hyperprolactinaemia. MEASUREMENTS: After a single injection of Parlodel LAR 25, 50 or 100 mg, serum PRL and plasma bromocriptine levels were assessed during a follow-up of 60 days together with changes in clinical symptoms and signs of hyperprolactinaemia. RESULTS: Serum PRL levels normalized in 19 of 21 patients. The suppression of PRL secretion lasted 28 days in four of seven patients treated with either 25 or 50 mg Parlodel LAR and in five of seven patients who received Parlodel LAR 100 mg. In five of seven patients treated with the 100 mg dose, serum PRL levels were still within the normal range on day 60. Plasma bromocriptine levels remained therapeutically active for 28 days in all three groups. On day 60 they were within the therapeutic range only in the 100 mg group. Clinical data show a rapid disappearance of symptoms and signs of hyperprolactinaemia. Adverse events were mostly mild and transient. CONCLUSIONS: These data support the excellent efficacy and good tolerability of Parlodel LAR in patients with hyperprolactinaemia.

Adult↗
PubMed1992

Estimation of heterogeneous variances using empirical Bayes methods: theoretical considerations.

Procedures are described to estimate variances when heterogeneity of genetic and residual dispersion parameters exists for some criterion. Genetic and residual variances are considered to follow distributions with either known or unknown parameters. The estimates of variances obtained are weighted averages of the corresponding parameter and of a data-based statistic. Although the techniques presented are largely inspired by Bayesian ideas, the procedures can be given a frequentist interpretation, and the parameters of the prior distributions can be estimated from the data at hand. Techniques are described and illustrated for situations in which animals are related or unrelated across herds. We conjecture that the proposed estimators have smaller mean squared error than those obtained by grouping observations in some way and then applying REML within each group.

Animals↗
PubMed1992

Estimation of heterogeneous within-herd variance components using empirical Bayes methods: a simulation study.

Genetic evaluation using BLUP can accommodate heterogeneous variances if the necessary variance components are known; this may require estimation of variance components within each heterogeneous subclass. Properties of sire and residual variance estimates obtained by an empirical Bayes approach, which combines within-herd and prior estimates, were examined via simulation. Prior estimates were obtained using REML across herds, as if variances were homogeneous. Convergence was improved by incorporation of prior information such that variance component estimates could be obtained in within-herd situations for which a REML algorithm failed to converge. Accuracy of sire variance estimates was greatest when both within-herd and prior information were used, but improvement in accuracy of residual variance estimates associated with incorporation of prior information was minimal. Correlations between sires' standardized true transmitting abilities and PTA that used empirical Bayes variance estimates were larger than those obtained when heterogeneity was ignored. Proportions of sires selected, based on standardized PTA, from environments with differing genetic and residual variances became more uniform as the relative weight placed on within-herd data in variance estimation increased. Thus, useful variance component estimates can be obtained within individual herds by using empirical Bayes methods with across-herd estimates as prior information; this may allow prediction of breeding values that are less influenced by heterogeneous variances.

Algorithms↗
PubMed1991

A new oral slow release form of bromocriptine, Parlodel SRO, in the chronic treatment of 26 hyperprolactinemic patients.

Parlodel SRO, a new slow release form of bromocriptine, was studied in 26 patients with tumoral and non-tumoral hyperprolactinemia. Prior to the treatment, serum prolactin (PRL) levels ranged from 45 ng/ml to 7000 ng/ml and they decreased to within the normal range in all but one patient after 7 days-1 year of treatment with this new formulation of bromocriptine. The clinical improvement paralleled the normalization of PRL secretion. Tolerability was rated good or very good in 24 patients, even in the three patients who had been intolerant of oral Parlodel. In conclusion, Parlodel SRO administered as a single daily dose resulted in very effective lowering of serum PRL in patients with hyperprolactinemic disorders.

Administration, Oral↗
PubMed1991

Hypocalcemic effects of rectal and intramuscular administration of synthetic salmon calcitonin.

To assess the acute biological activity of a new rectal form of synthetic salmon calcitonin (SMC), 10 healthy subjects were randomly assigned, according to a crossover design, to single doses of either 50 IU SMC intramuscularly or 100 IU SMC rectally. Ionized and total calcium were measured as SMC bioactivity indicators in blood samples collected during a 6-hour period after the administration of the drug. In all the subjects, rectal administration of 100 IU of SMC induced falls in both plasma total calcium and whole blood ionized calcium: similar levels were observed after intramuscular injection of 50 IU of SMC. The pharmacodynamic bioavailabilities for total and ionized calcium of the 100 IU suppository and the 50 IU intramuscularly were 106% and 60%. The total and ionized calcium AUCs were the same after i.m. injection and suppository. We conclude that, in normal subjects, synthetic salmon calcitonin administered by the rectal route at the dose of 100 IU is effective and has the same biological effects as 50 IU of SMC given intramuscularly. Therefore, this new rectal form may be a useful alternative to parenteral injection.

Administration, Rectal↗
PubMed1990

New perspectives in medical management of hyperprolactinemia.

We performed 113 new treatments in 98 patients (pts) (69 females and 27 males), 41 with macroprolactinoma, 26 with microprolactinoma, 5 with empty sella and 26 with idiopathic hyperprolactinemia. Parlodel LA was administered in 31/113, Parlodel LAR in 51/113, Parlodel SRO in 24/113 and Cabergoline in 8/113. In each pt the clinical effect, PRL plasma level CT-scan and visual field examination were monitored. PRL plasma levels normalized in 84/98 pts. In 13/41 macroadenoma pts a complete disappearance of the adenomatous mass was observed at CT-scan after 0.5-3 years' oral bromocriptine or Parlodel LAR therapy. The clinical features normalized in most of the pts. In conclusion, the new long acting dopamine agonists may represent the future of the management of hyperprolactinemic states because of their effectiveness, tolerability and good compliance.

Adenoma↗
PubMed1990

Medical management of acromegaly: effects of SMS 201-995 in 30 patients.

The effect of chronic administration of SMS 201-995, a long acting analogue of somatostatin, has been studied in 30 acromegalic patients (pts). CT-scan showed pituitary adenoma in 20/30 pts, empty sella in 9/30 pts and no sign of pituitary tumor in one case. SMS 201-995 was administered subcutaneously every 8 hours at the daily dose of 150-900 micrograms. Blood samples for GH, insulin and blood glucose were taken hourly from 04:00 to 20:00 h before treatment, after 15 days and then monthly or fortnightly. IGF-I plasma levels were assayed at 08:00 h in the same day as GH determinations. CT-scan controls were carried out after 12-24 months of treatment in 16/20 pts. GH plasma levels were normalized in 16/30 pts after 0.5-9 months of SMS treatment, whereas in 14/30 pts they were reduced by about 50%. In 10/16 pts the CT-scan examination showed a shrinkage of the tumor size of 20-55%, while no variation of the tumor mass was observed in the 2 pts. In conclusion our data show that SMS 201-995 is a very effective medical treatment in acromegalic patients.

Acromegaly↗
PubMed1989

Insulin secretion and glucose tolerance in non-insulin dependent diabetic patients after chronic nifedipine treatment.

The effect of nifedipine 40 mg.day-1 for 3 months on glucose tolerance, insulin and C-peptide secretion after an oral glucose tolerance test (OGTT), intra-venous glucose tolerance test (IVGTT) and glucagon stimulatory test, has been studied in 8 moderately hypertensive women suffering from non-insulin dependent diabetes mellitus (NIDDM). No significant variation in glucose metabolism was noted after nifedipine treatment, except for a slight improvement in insulin secretion after OGTT at the end of the study. There was an increase in cholesterol as a collateral effect.

Blood Glucose↗
PubMed1989

Likelihood estimation of quantitative genetic parameters when selection occurs: models and problems.

Conceptual aspects of estimation of genetic components of variance and covariance under selection are discussed, with special attention to likelihood methods. Certain selection processes are described and alternative likelihoods that can be used for analysis are specified. There is a mathematical relationship between the likelihoods that permits comparing the relative amount of information contained in them. Theoretical arguments and evidence indicate that point inferences made from likelihood functions are not affected by some forms of selection.

Animals↗
PubMed1989

Models for genetic analysis of dystocia and calf mortality.

Calvings of 106,750 Israeli Holstein heifers were analyzed for dystocia and calf mortality, which were scored dichotomously. Models fitted included herd-year-season, sex of calf, calving age, calving month, sire of cow, sire of calf, and groups of sire of cow and calf. Herd-year-season, sire of cow and of calf, and residuals were random with diagonal variance-covariance matrices. Traits were analyzed with and without a herd-year-season effect, and dystocia was analyzed separately for male and female calvings and with both sexes combined. Variance components were estimated by REML for linear models and by the counterpart of REML for threshold models. Heritability estimates were two to four times larger in threshold than in linear models, but correlations between corresponding sire evaluations were all greater than .9. Correlations between evaluations computed with and without herd-year-season effects were .9 for sire of calf evaluations for dystocia and greater than .97 for all other evaluations. Correlations between sire evaluations computed separately for male and female calvings were between .3 and .7. Thus, calving difficulty is expressed differently in male and female calvings. Genetic trends were unfavorable for dystocia but favorable for calf mortality. Phenotypic trends were curvilinear with maxima in 1982 and 1983 for calf mortality and dystocia.

Age Factors↗
PubMed1988

Genetic analysis of dystocia and calf mortality in Israeli-Holsteins by threshold and linear models.

Calvings of 106,751 Israeli Holstein heifers were analyzed for dystocia and calf mortality, scored dichotomously, and a composite trait, scored trichotomously. Dystocia was also studied with 146,973 second and third parity records. Models fitted included herd-year-season, sex of calf, calving age, calving month, sire of cow, sire of calf, and groups of sire of cow and of calf. Herd-year-season, sire of cow and calf, and residuals were random with diagonal variance-covariance matrices. Herd-year-season variance was assume to be 10% of the residual component. Other variance components were estimated by REML for linear models and by the counterpart of REML for threshold models. Heritability estimates were two to five times greater in threshold than in linear models, but correlations between corresponding sire evaluations were all greater than .9. Linear model sire evaluations were skewed positively, whereas threshold model evaluations had symmetrical distributions. Heritability for dystocia was greater in first than in later parities. Correlations between first and later parity sire evaluations were less than .5. Thus, the genetic control of dystocia seems to be different for heifers and cows. Correlations between sire of cow and calf evaluations were less than .3. Correlations between dystocia and calf mortality evaluations were about .7.

Animals↗
PubMed1987

Mixed-model analysis of a censored normal distribution with reference to animal breeding.

A mixed-model procedure for analysis of censored data assuming a multivariate normal distribution is described. A Bayesian framework is adopted which allows for estimation of fixed effects and variance components and prediction of random effects when records are left-censored. The procedure can be extended to right- and two-tailed censoring. The model employed is a generalized linear model, and the estimation equations resemble those arising in analysis of multivariate normal or categorical data with threshold models. Estimates of variance components are obtained using expressions similar to those employed in the EM algorithm for restricted maximum likelihood (REML) estimation under normality.

Analysis of Variance↗
PubMed1986

Long-lasting suppression of prolactin secretion and rapid shrinkage of prolactinomas after a long-acting, injectable form of bromocriptine.

Since Corenblum reported in 1975 the first documented reduction of tumor size in two patients with macroprolactinoma, evidence has accumulated that bromocriptine causes shrinkage of PRL-secreting adenomas in most patients. Recently a long-acting form of bromocriptine (bromocriptine LA) was developed. A single dose of 50 mg i.m. decreases basal and sleep-related PRL secretion in normal subjects for 28 days. We treated 13 patients (8 women, 5 men) with PRL secreting tumors (5 macroadenomas and 8 microadenomas) with a single dose (50 mg) of bromocriptine LA. In the 5 patients with macroprolactinomas plasma PRL levels decreased markedly within 12 hours, reaching normal levels in only one patient. In all patients the suppression of PRL secretion lasted at least 28 days and the tumor size was reduced by 20% to 59% within 21 days after the injection. Visual fields improved in all 3 patients with abnormal vision prior to the injection. In one patient with bitemporal hemianopsia an almost normalization of the visual field was noted 24 hours after bromocriptine LA administration. In 7/8 patients with microprolactinomas plasma PRL levels decreased to within the normal range within 12 hours after the administration of bromocriptine LA. The normalization of PRL secretion lasted for at least 28 days. Menses resumed in all 6 women 7 to 41 days after the injection, galactorrhea disappeared in all 4 patients, and libido and potency become normal in both men with microprolactinomas. Patients treated with bromocriptine LA reported only short-lasting (1 hour - 2 days) mild or moderate adverse effects, consisting of dizziness (4 patients) and nausea (4 patients). Long-acting bromocriptine should be considered as the initial management for patients with PRL-secreting tumors. The use of bromocriptine LA could also overcome the compliance problems that occur in many patients soon after the initiation of oral bromocriptine therapy.

Adolescent↗
PubMed1986

Sire evaluation for multiple binary responses when information is missing on some traits.

A procedure of sire evaluation for multiple binary responses when information is missing for some traits is described. The genetic model assumes a conceptual underlying multivariate normal distribution rendered discrete by abrupt thresholds. Statistical inferences are made from a posterior distribution consisting of several conditionally independent likelihood functions and a multivariate normal prior distribution. Each likelihood function corresponds to a particular class of information available. Point estimators and predictors of fixed and random effects are the values that maximize the posterior distribution conditionally on heritabilities and genetic correlations. The procedure involves nonlinear maximization. An example involving joint selection for calving ease and skeletal development illustrates the principles. Application of the methodology as a potential means of removing bias due to selection for categorical traits is discussed.

Animals↗
PubMed1985

Observations on sire evaluation with categorical data using heteroscedastic mixed linear models.

The ability of three mixed linear models to rank sires correctly for dichotomous and ordered tetrachotomous traits was studied using simulated half-sib progeny data. The models differed in the assumptions made regarding homogeneity of residual variance. Ranking ability was assessed by estimating the realized response to truncation selection (20% of the candidates selected) upon sire evaluations in populations consisting of 50 such sires. Results suggested that weighting for unequal residual variances, in spite of reducing apparent prediction error variance, impairs the ability of best linear unbiased prediction to identify superior sires. This is consistent with theoretical arguments stemming from threshold models.

Animals↗