Relationships with serum parathyroid hormone in old institutionalized subjects.

OBJECTIVE AND BACKGROUND: Old people in residential care are at the highest risk of any group for hip fracture. This may relate to their high prevalence of hyperparathyroidism. There are few data, however, on relationships with serum parathyroid hormone (PTH) in these individuals. This study therefore examined complex associations with serum PTH in nursing home and hostel residents. DESIGN: Cross-sectional analysis. PATIENTS: One hundred and forty-three nursing home and hostel residents of median age 84 years. MEASUREMENTS: Serum PTH, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25-(OH)2D), plasma creatinine, phosphate, calcium, albumin, Bsm-1 vitamin D receptor genotype, age, weight and use of frusemide or thiazide. RESULTS: The statistical models determined accounted for half the interindividual variation in serum PTH. Heavier weight was associated with both the prevalence of secondary hyperparathyroidism and the serum concentration of PTH. Novel interactions with serum PTH were identified between: weight and 25OHD; 25OHD and phosphate; and phosphate and thiazide diuretic use. Plasma phosphate was associated with PTH independently of calcium and 1,25-(OH)2D. There was no independent association between PTH and nuclear vitamin D receptor genotype. CONCLUSIONS: Heavier weight is associated with both the prevalence and severity of secondary hyperparathyroidism and consistent with animal models of secondary hyperparathyroidism, phosphate may relate to serum PTH independently of 1,25-(OH)2D or calcium.

Urine calcium and urine sodium concentrations are not related, after adjustment for urine magnesium.

BACKGROUND AND OBJECTIVES: Urine calcium correlates with urine sodium. The aims of this study were to investigate whether the urine sodium-calcium relationship persists into old age and whether it holds after adjustment for urine magnesium. DESIGN: Cross-sectional descriptive analysis. PATIENTS: Residents of two aged care institutions (median age 84 years) who were not taking diuretics, calcium or vitamin D supplements. MEASUREMENTS: Early morning urine calcium, sodium and magnesium, plasma creatinine and serum 25-hydroxyvitamin D and parathyroid hormone. RESULTS: Urine calcium correlated with urine sodium (r = 0.29, P < 0.01) and with urine magnesium (r = 0.56, P < 0.001). After adjustment for urine magnesium, the relationship between urine sodium and urine calcium was no longer significant. Forty-five percent of the interindividual variation in urine calcium was explained by a linear model on the basis of urine magnesium and plasma creatinine. CONCLUSION: The data indicate that a correlation between urine sodium and calcium persists in very old age. However, this correlation no longer holds after adjustment for urine magnesium. Further studies examining urine calcium excretion should also consider urine magnesium.

Falls relate to vitamin D and parathyroid hormone in an Australian nursing home and hostel.

OBJECTIVES: To determine whether falling relates to serum levels of vitamin D and parathyroid hormone. DESIGN: A cross-sectional study with retrospective analysis. SETTING: An aged-care institution in Melbourne Australia. PARTICIPANTS: Ambulant nursing home and hostel residents (n = 83). MEASUREMENTS: Frequency of falling, frequency of going outdoors, use of cane or walker, age, sex, weight, type of accommodation, and duration of residence. Serum concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and parathyroid hormone (PTH). Plasma concentrations of albumin, calcium, phosphate, and creatinine. Use of furosemide or non-benzodiazepine anticonvulsants. RESULTS: Median age of residents was 84 years. The cohort was vitamin D deficient with a median (interquartile range) 25-hydroxyvitamin D level of 27 (18-37) nmol/L (one-third the reference range median), P < .001. The median (interquartile range) PTH of 5.2 (3.8-7.7) pmol/L exceeded the reference range median, P < .001. Residents who fell (n = 33) had lower serum 25-hydroxyvitamin D levels than other residents (medians 22 vs 29 nmol/L, P = .02) and higher serum PTH levels (medians 6.2 vs 4.8 pmol/L, P < .01). Sixty residents lived in the hostel (72%), and 41 (49%) walked without any walking aid. In a multiple logistic regression for falling, higher serum PTH remained independently associated with falling, with an odds ratio (95% confidence interval) for falling of 5.6 (1.7-18.5) per unit of the natural logarithm of serum PTH. Other terms in the regression were hostel accommodation, odds ratio .04 (.01-.25), and ability to walk without aids, odds ratio .07 (.01-.37). CONCLUSIONS: In ambulant nursing home and hostel residents, residents who fall have lower serum 25-hydroxyvitamin D and higher serum parathyroid hormone levels than other residents. The association between falling and serum PTH persists after adjustment for other variables.

Ontogeny of gastrin, somatostatin, and the H+/K(+)-ATPase in the ovine fetus.

In the term human and ovine fetus, plasma gastrin is elevated, but gastric acid secretion is below adult levels, suggesting a developmentally related immaturity in gastrin and gastric acid regulation. This study investigated a number of elements of the gastric acid regulatory system: gastrin and its glycine-extended precursor, somatostatin, and the H+/K(+)-ATPase. Measurements were made in blood, antrum, and fundus of the ovine fetus during the last half of gestation, of 15-day-old lambs, and of adult sheep at the level of mRNA synthesis, tissue storage, and secretion. Plasma amidated gastrin (gastrin-amide) was elevated at or above adult values from 125 days (term is 145 days) and steadily increased with development, peaking in the lamb. Similar changes occurred with plasma glycine-extended gastrin (gastrin-gly). The peak concentration of antral gastrin-amide was present in the lamb, while the maximum antral gastrin-gly level occurred 1 week before birth. Gastrin mRNA paralleled the changes in antral gastrin-gly. The proportion of higher mol wt species of gastrin decreased during gestation in both plasma and antrum. Low amounts of mRNA for the H+/K(+)-ATPase was present from at least 120 days of gestation and antedated gastric acid secretion. However, there was a 3-fold increase in H+/K(+)-ATPase mRNA from the 140-day-old fetus to the lamb, the period when the greatest reduction in gastric pH occurred (pH 5 to 2). Antral and fundic somatostatin increased rapidly in the fetus at 120 days gestation and were above adult values at term and in the lamb. Somatostatin mRNA changed in parallel to somatostatin peptide. Somatostatin-14 was the major species in antrum and fundus throughout development. The increase in circulating and antral gastrin-amide after birth may be the result of increased amidation of gastrin-gly as well as increased expression of gastrin mRNA. Amidation of gastrin may be a regulatory step in the production of biologically active gastrin during development. The major increase in gastrin and the H+/K(+)-ATPase that occurs in the week before and after gestation correlated with the onset of increased gastric acidity.

Sex steroid hormones and breast cancer: is there a link with oral contraceptives and hormone replacement therapy?

OBJECTIVE: To determine whether use of sex steroid hormones for contraception and hormone replacement therapy alters the risk of breast cancer, and whether the risk varies with their composition, duration of use, the period of a woman's life when the hormones are used, and after successful treatment for breast cancer. DATA SOURCES: The results of important epidemiological reports, readily available from the English literature and published since 1981, were evaluated, using reports of basic scientific work as a background to the problem. STUDY SELECTION: An attempt was made to obtain most of the relevant reports. Twenty case-control and seven cohort studies were available on the oral contraceptive pill (OCP) and eleven case-control and five cohort studies on hormone replacement therapy (HRT). DATA EXTRACTION: The relative risk estimates for breast cancer (and their 95% confidence intervals) determined by each report were tabulated according to the specific conditions of analysis, for example users under age 25, duration of use. Results by meta-analysis from previous studies were also used to determine risk. A significant positive association was present when the risk estimate exceeded 1.0 and the 95% confidence interval did not cross 1.0. DATA SYNTHESIS: Among OCP users, the vast majority of reports showed no significant risk of breast cancer--overall, longest duration of use, and use before first full-term pregnancy. However, a positive association between breast cancer and users under age 25 was found in three of eight reports. Similarly, the majority of reports showed no significant risk of breast cancer among HRT users, overall as well as in relation to duration of use and interval since first use. There was no increased risk with additional progestogen; it may be protective. An improved prognosis was found in users who developed breast cancer. On the limited data, use of hormones for postmenopausal symptoms did not appear to be harmful to women who had been successfully treated for breast cancer. CONCLUSIONS: The review revealed good evidence that use of sex steroid hormones had no significant effect on the risk of breast cancer, whether given for contraception or hormone replacement. There was some concern about increased risk with prolonged use of the OCP, especially in younger women. At present, use of these hormones is a matter of informed choice, with individual considerations of the risk-benefit ratio.

PIP: An attempt to determine whether use of sex steroid hormones for contraception and hormone replacement therapy (HRT) alters the risk of breast cancer, and whether the risk varies with their composition, duration of use, period of a woman's life when the hormones are used, and after successful treatment for breast cancer is reported. The results of important epidemiological reports, readily available from the English literature and published sine 1981, were evaluated, using reports of basic scientific work as a background to the problem. 20 case control and 7 cohort studies were available on oral contraceptive (OC) use and 11 case control and 5 cohort studies on HRT use. THe relative risk estimates for breast cancer (and their 95% confidence intervals) determined by each report were tabulated according to the specific conditions of analysis, e.g., users under age 25 and duration of use. Results by meta-analysis from previous studies were also used to determine risk. A significant positive association was present when the risk estimate exceed 1.0 and the 95% confidence interval did not cross 1.0. Among OC users, the vast majority of report showed no significant risk of breast cancer--overall, longest duration of sue and use prior to 1st full-term pregnancy. However, there was a positive association between breast cancer and users under age 25 in 3 of 8 reports. Similarly, the majority of reports showed no significant risk of breast cancer among HRT users, overall as well as in relation to duration of use and interval since 1st use. There was no increased risk with additional progestogen; it may be protective. An improved prognosis was found in users who developed breast cancer. On the limited data, use of hormones for postmenopausal symptoms did not appear to be harmful to women who had been successfully treated for breast cancer. This review revealed good evidence that use of sex steroid hormones had no significant effect on breast cancer risk, whether given for contraception or HRT. There was some concern about increased risk with prolonged OC use, especially in younger women. At the present time, use of these hormones is a matter of informed choice, with individual considerations of the risk-benefit ration.

Hormone replacement therapy at the menopause. The risks and benefits.

This review has been prepared as a practical guide for clinicians who see women in the perimenopause. The risks and benefits of hormone replacement therapy (HRT) are described. We recommend that HRT be prescribed for those women in whom the benefits outweigh the potential risks.

Inadvertent pregnancies in oral contraceptive users.

Two hundred and nine inadvertent pregnancies in oral contraceptive users were studied to determine the associated factors. The percentage of Pill types also were compared with the market usage over the same period. We found that the classically-suggested cofactors, such as missed pills, late pills, drug ingestion, and gastrointestinal upsets were reported commonly. The triphasic Pills also were represented more frequently than would have been expected from their share of the market.

PIP: Although oral contraceptives (OCs) are the most effective form of reversible fertility control, inadvertent pregnancies do occur in OC users. The most common causes of these pregnancies seem to be missed pills, drug interactions, and malabsorption resulting from vomiting or diarrhea. To assess the relative importance of these causes, a pilot study was conducted at family planning centers in Australia. In response to a questionnaire, 12 centers reported 209 cases of OC-associated inadvertent pregnancy occurring between December 1985 and July 1986. Triphasic OCs were used by 52% of these women, while only 42% of Australian women overall use this type of formulation. 35% of women with inadvertent pregnancies reported they had missed taking pills; another 25% had taken a pill late (at least 36 hours after the previous tablet). 34% of these women had used drugs believed to interact with OCs in their last 2 cycles before conception. In the majority of these cases (67%), these were antibiotic agents--most often amoxicillin. 27% reported vomiting or diarrhea in association with OC failure. Finally, 22% of the women had suffered some form of illness (various respiratory, urinary, and gastrointestinal infections) since the last menstrual cycle. 16% of the women experienced breakthrough bleeding in the cycle in which conception occurred. No predisposing factors could be identified in 14% of the women with unintended pregnancies. The most significant finding of this study is the higher rate of inadvertent pregnancies among users of triphasic as opposed to monophasic OCs. Also confirmed were the well-recognized risks of missed pills, late pills, drug interactions, and diarrhea and vomiting. OC users should be advised to take additional contraceptive precautions until at least 7 consecutive tablets have been taken after an episode that may impair the efficacy of the pill.

Nature of the gastric acid-gastrin feedback loop in the fetal sheep.

1. The neonates of sheep and other species have a decreased gastric acid secretion but an elevated plasma gastrin concentration. 2. Since low gastric acid secretion is a stimulus for gastrin release in mature animals the present study examined whether the relative hypochlorhydria in the sheep fetus was sustaining the hypergastrinaemia. 3. Fetal plasma gastrin was measured following fetal gastric acidification (pentagastrin infusion) and gastric neutralization (parietal cell blockade with the proton pump inhibitor omeprazole) in chronically cannulated fetal sheep from 101 days until term (145 days). 4. Acutely raising gastric pH with omeprazole increased plasma gastrin in the mature sheep. However, in the fetus increasing the pH with omeprazole or decreasing pH with pentagastrin had no effect on fetal plasma gastrin. This was true for fetuses from all age groups. 5. The results indicate that the gastric acid-gastrin feedback loop is not functional in the fetus and that the hypergastrinaemia at birth is therefore not the result of the relative hypochlorhydria. 6. The time after birth when the gastric acid-gastrin feedback loop matures remains to be determined.

Ontogeny of gastric acidity in the ovine fetus.

Hypoacidity and hypergastrinaemia have been reported in the newborn human. However, little is known about in utero gastric acid secretion, and the relationship to fetal plasma gastrin levels. The longitudinal pattern of development of basal and stimulated gastric acid secretion in the non-anaesthetized fetal sheep has been studied during the last 45 days of gestation. Fetuses had cannulae inserted into the jugular vein, carotid artery and stomach. Gastric juice and blood was sampled daily from 101 days gestation until birth (145 days). Intermittent basal acid secretion began between 120 and 133 days of gestation. These fluctuations in gastric juice pH continued until birth. Overall there was a decline in gastric pH from 7.5 +/- 0.2 (SEM), for fetuses 101-105 days to 4.3 +/- 0.5 by 131-135 days. Mean fetal plasma gastrin was higher than maternal levels after 111-115 days but no correlation between fetal plasma gastrin levels and gastric pH could be demonstrated. Pentagastrin and histamine infusion did not stimulate acid secretion in fetuses younger than 115 days. After this age the fetuses became responsive to both pentagastrin and histamine. In contrast, cholinergic stimulation, using bethanechol, did not stimulate acid production until 10 to 15 days later, suggesting a hierarchy in the development of the control of acid secretion in the fetus. The lack of response to endogenous gastrin and the hierarchy in the control of acid secretion suggest either a lack of receptors on the parietal cell or the presence of an inhibitor of acid secretion. These studies are relevant to human physiology since the present findings show that the sheep and human have a similar gastrin/acid profile at birth.

A comprehensive review of female sterilisation--tubal occlusion methods.

Female sterilisation using tubal occlusive methods are reviewed. The various techniques, failure rates, mortality, short and long-term morbidity, psychosexual effects and reversibility are discussed. Tubal occlusion is an effective method of female sterilisation but if failure should occur ectopic pregnancies are more likely if tubal diathermy, and less likely if Fallope rings or Filshie clips have been used for the original sterilisation procedure. Mortality rates are low and occur as a once-only risk when compared to ongoing contraception. Short-term morbidity rates are low when sterilisation is performed via the laparoscope, with single portal entry being more likely to result in complications. Mini-laparotomy and laparotomy also have low morbidity levels but complication rates are much higher when a transvaginal approach is used. There is no increase in morbidity when tubal sterilisation is performed at the time of pregnancy termination, providing uterine evacuation is not performed by hysterotomy. In the majority of cases no menstrual disturbance is noted; however, a small increase in menstrual disorders as a direct result of tubal sterilisation cannot be excluded absolutely. Sterilisation does not affect sexual satisfaction. Regret is more likely if the sterilisation is performed (i) post-termination or in the puerperium, (ii) when there is marital disharmony and (iii) for medical rather than social reasons. Low parity is not associated with regret except in cultures where high parity is prized. Microsurgical methods of reversal have higher pregnancy and lower ectopic rates than macrosurgical techniques. Successful reversal is inversely related to the degree of tubal destruction at the initial operation.

Who attends family planning clinics?

Data were obtained from 1,810 consecutive women who attended a central metropolitan (Brisbane) Family Planning Clinic during a 5 week period in 1982. Young women in particular formed the major client group with 32% being under 20 years of age. The client population was skewed towards women of upper socioeconomic status (SES). There was no SES disproportion in the use of oral contraceptives or IUD's. However, diaphragm use occurred disproportionately in women of upper SES groups; postcoital contraception was sought by and limited to, women of SES classes A and B only. The clinic satisfied a need for women with a history of failed or absent contraception and 15% had already had a termination of pregnancy by the time they first presented at the clinic.

PIP: Data were obtained from 1810 consecutive women who attended a central metropolitan (Brisbane) Family Clinic during a 5-week period in 1982 to define the clinic profile of family planning users. The purpose was to aid decisions concerning future allocation and to plan for the provision of services for that demographic subpopulation for whom contraceptive advice is still not easily accessible. The clinic sees approximately 5% of all Brisbane women of childbearing age, annually. Data were collected on the women's age, occupation, marital status, obstetric history, contraceptive use, and socioeconomic data. The age range of the women attending the clinic was 13-62 years. The age distribution showed a marked skew to women under age 25 when compared with the Brisbane female population. 73% of the women attending had never been married; 23% were married at the time of consultation. The remainder were widowed, divorced, or separated. 84% of the women were nulliparous. Of those with children, the median family size was 1 with a range of 1-7 children. 15% of those women attending for the 1st time had already had an abortion before attending the clinic. 3% had had more than 1 abortion with the maximum number of abortions recorded being 5 for 1 women. 10% of all teenagers attending the clinic had had an abortion at some time. 70.7% of the women first came to the clinic on the recommendation of a friend or a parent. 2% were referred by a family doctor and 2% by social welfare agencies. 9% indicated that they came because of advertising seen on public transport or had heard of the clinic through interviews on radio or television programs. 10% had come via another family planning clinic or had been referred from staff at a public hospital. Virtually all women attending were sexually active. 54% of all new patients were not adopting any form of contraception. 32% of new patients were taking oral contraceptives (OCs), 5% were IUDs and 6% barrier methods. 11% of the patients attending were students and 9% were umemployed. 3% were in receipt of social security pensioner benefits. The distribution of diaphragm users was shifted towards upper socioeconomic status groups; there were no significant socioeconomic status differences for OC and IUD use. An obvious need exists for better and more extensive education concerning the advantage of contraceptives for modern teenagers.

Presence and stability of gastrin in the gastric juice of the fetal sheep.

Although gastrin is found in adult gastric juice, rapid enzymatic destruction by pepsin in the acid environment makes a physiological role in the adult unlikely. Gastric pH in the fetal sheep is neutral so that gastric juice gastrin could be present, and if present, have a physiological function. The aim of this study was to determine the presence, molecular forms and metabolism of gastrin in gastric juice. Gastrin was present in fetal gastric juice at significantly higher concentrations than in fetal plasma. The majority of gastric juice gastrin was present as the biologically active gastrin-17. Gastrin was stable in normal fetal gastric juice, but was rapidly metabolized to smaller C-terminal fragments when the gastric juice was acidified. With the known growth promoting effect of gastrin on gastrointestinal mucosa, gastrin in fetal juice could have a unique role in the in utero development of the gastrointestinal tract.

A radioimmunoassay for neurotensin in human plasma.

A specific radioimmunoassay for neurotensin in plasma has been developed with a sensitivity of 2 pmol/l of plasma. The antiserum was directed towards the amino terminal region of neurotensin and did not cross-react with other gastrointestinal peptides. Non-specific interference was eliminated and the sensitivity increased by extracting the plasma samples with ethanol prior to assay. Within- and between-assay coefficients of variation were 7.8% and .12% respectively. The mean plasma concentration of neurotensin in 30 fasting subjects was 29 +/- 4 pmol/l. A mixed meal increased plasma neurotensin from 16 +/- 2 to 53 +/- 6 pmol/l at 2 h.

Fetal and maternal production and metabolism of gastrin in sheep.

In the sheep fetus, plasma levels of gastrin are raised above adult levels from 2 weeks before birth. This observation initiated the present study on the maternal and fetal secretion rate, metabolism and placental transfer of gastrin. The experiments were performed on conscious pregnant ewes with chronically cannulated fetuses and on newborn lambs. Metabolic clearance rate (MCR), production rate (PR) and placental transfer of gastrin were measured by alternate steady-state infusion of gastrin into the mother and fetus. Plasma levels of gastrin were measured by radioimmunoassay. Metabolic clearance rate was similar in the pregnant and non-pregnant ewe (8.4 +/- 1.1 (S.E.M.) and 9.0 +/- 1.4 ml/min per kg) respectively. However, fetal MCR was significantly increased. Term was 145 days. Metabolic clearance rate was 15.5 +/- 1.7 at 110-125 days of gestation, 25.6 +/- 2.9 at 126-135 days, 29.7 +/- 4.9 at 136-145 days and remained raised in the first 2 weeks post partum. Gastrin did not cross the placenta in either direction. Placental destruction of gastrin was not responsible for the increased fetal MCR as umbilical artery and umbilical vein levels were not significantly different during fetal gastrin infusion. Furthermore, MCR remained raised in the newborn lambs. Gastrin PR was significantly increased at all ages. The results showed that the previously reported fetal hypergastrinaemia is from fetal sources and is not a result of immaturity of clearance mechanisms. In fact, fetal MCR was significantly increased. The increased fetal plasma gastrin levels are due to an increased rate of production from the fetus.

Mood changes as reported by women taking the oral contraceptive pill.

PIP: In an effort to clarify the nature of emotional side effects frequently reported by women using oral contraceptives (OCs), an exploratory study was undertaken of the verbal descriptions of side effects provided by a sample of young, healthy, sexually active women attending the Family Planning Association of Queensland clinics in Brisbane; they had been using OCs for at least 6 months. The adjectives used in unstructured interviews by 20 women happy with pills and 20 complaining of side effects formed the basis for a questionnaire comparing occurrence of emotions before and after pill use. 3 consecutive sets of adjectives were tested using Principle Factor Analysis and orthogonal rotation. The final questionnaire along with questions concerning social variables were given to 100 women and the scores from different subgroups were compared using the t test. 4 distinct, specific, and uncorrelated factors containing 53 adjectives were identified, of which "annoyed" and "tiredness" suggest negative emotional effects and "passionate" and "reassured" suggest positive effects. The distribution of factor scores in subgroups with statistically significant differences indicate that increases in "annoyed" and "tiredness" scores are found mainly in women who complain of emotional side effects, who were bothered by remembering to take the pill, worried about pill-related dangers, and gained excessive weight. Increases in "passionate" scores were found in noncohabiting women with steady sexual relationships, and increases in "reassured" were universal. The results demonstrate the multidimensional nature of reported emotional side effects from the pill and indicate that highly specific and unique mood changes which do not fit into existing notions of depression or anxiety are reported by women taking the pill.^ieng

Prescribing an oral contraceptive for the individual woman.

It is possible to find a formulation suitable to almost any woman requesting oral contraception. Low dosage and strong affinity for target cell receptors are important in the selection of the appropriate agent. Details are given of an extensive clinical trial of a biphasic formulation containing ethinyloestradiol and levonorgestrel.