Obesity and preeclampsia: the potential role of inflammation.

OBJECTIVE: Systemic inflammation might contribute to the pathogenesis of preeclampsia. In addition, the association between obesity and inflammation in preeclampsia has not been examined in detail. We determined whether first-trimester elevation of serum C-reactive protein, an index of systemic inflammation, was associated with preeclampsia. METHODS: We conducted a prospective, nested case-control study among women enrolled in the Massachusetts General Hospital Obstetrical Maternal Study cohort. High-resolution C-reactive protein assays were performed on first-trimester (11 +/- 2 weeks' gestation) serum samples in 40 women in whom preeclampsia developed (blood pressure [BP] greater than 140/90 mmHg, and proteinuria, either 2+ or more by dipstick or greater than 300 mg per 24 hours), and in 80 matched controls. This sample size had greater than 80% power to detect a difference in C-reactive protein levels between cases and controls. We used nonparametric tests to compare C-reactive protein levels and conditional logistic regression to control for confounding variables. RESULTS: First-trimester C-reactive protein levels were significantly higher among women in whom preeclampsia subsequently developed compared with controls (4.6 compared with 2.3 mg/L, P =.04). When women were subdivided into C-reactive protein quartiles, the odds ratio (OR) of being in the highest quartile of C-reactive protein was 3.2 (95% confidence interval [CI] 1.1, 9.3, P =.02) among cases of preeclampsia compared with controls. When body mass index (BMI) was added to the multivariable model, the highest quartile of C-reactive protein was no longer associated with increased risk of preeclampsia (OR 1.1, 95% CI.3, 4.3, P =.94). In the same model without BMI, the highest quartile of C-reactive protein was associated with increased risk of preeclampsia (OR 3.5, 95% CI 1.3, 9.5, P =.01). CONCLUSION: In women with preeclampsia, there was evidence of increased systemic inflammation in the first trimester. Inflammation might be part of a causal pathway through which obesity predisposes to preeclampsia.

Pulse pressure and risk of preeclampsia: a prospective study.

OBJECTIVE: To find whether pulse pressure, a measure of arterial compliance, is associated early in pregnancy with increased risk of developing preeclampsia. METHODS: In a prospective cohort of 576 nulliparas, we examined blood pressures throughout pregnancy and at 6-8 weeks postpartum. Measurements during weeks 7-15, 16-24, and 25-38 of gestation were pooled to find averages for each period. Outcomes assessed were gestational hypertension and preeclampsia. Logistic regression analysis was used to develop relative risks and 95% confidence intervals. RESULTS: We confirmed 34 (5.9%) cases of preeclampsia, 32 (5.6%) cases of gestational hypertension, and 510 normotensive women. Mean systolic and diastolic blood pressures and mean arterial pressures were elevated throughout pregnancy in women who developed hypertensive disorders of pregnancy compared with normotensive women. Pulse pressure at 7-15 weeks was significantly higher in women who developed preeclampsia (45 +/- 6 mmHg) than in those who developed gestational hypertension (41 +/- 7 mmHg, P =.03) and normotensive women (41 +/- 8 mmHg, P =.01). Examined in tertiles, increasing pulse pressure was associated with increasing risk of developing preeclampsia (P for trend =.01) but not gestational hypertension (P for trend =.95). After adjustment for potential confounders, a 1-mmHg rise in early pregnancy pulse pressure was associated with a 6% (95% confidence interval: 1, 10) increase in risk for developing preeclampsia but not gestational hypertension (relative risk: 1%; 95% confidence interval: -1, 6). Beyond 15 weeks' gestation, differences between groups diminished, but women with any hypertensive disorder had higher pulse pressures than women with uncomplicated pregnancies. CONCLUSION: Elevated pulse pressure, indicating poor arterial compliance, was evident early in pregnancies of women who subsequently developed preeclampsia.

Behaviour problems in Angelman syndrome.

Angelman syndrome (AS) is a genetic disorder that is associated with a deletion on chromosome 15, and is characterized by abnormalities or impairments in neurological, motor and intellectual functioning. While behaviour problems have been reported in clients with AS, relatively little is known about their developmental course and outcome. In this study, data on the nature and prevalence of behaviour problems among clients with AS were gathered from two sources: (1) a review of published case reports; and (2) parent responses to a survey of behaviour problems in a small (n = 11) sample of children with AS. Data from both sources showed that behaviour problems were present in males and females of all ages, and included language deficits, excessive laughter, hyperactivity, short attention span, problems with eating and sleeping, aggression, noncompliance, mouthing of objects, tantrums, and repetitive and stereotyped behaviour. Identification and treatment of severe behaviour problems in clients with AS may improve their adaptive functioning.

Subjective symptoms and cardiac reactivity to brief hyperventilation in individuals with high anxiety sensitivity.

Cognitive models maintain that panic attacks may be initiated by fear resulting from the interpretation of somatic sensations as personally threatening or harmful. Similarly, several researchers have proposed that the enhanced response of panickers to biological challenge may result from the fear of induced anxiety sensations rather than from direct stimulation of aberrant biochemical systems. The present study examined the effects of both panic history and fear of anxiety sensations on subjective and cardiac responses to biological challenge. Eighty nonclinical subjects were chosen on the basis of level of anxiety sensitivity and history of previous panic attacks. High and low anxiety-sensitive panickers and nonpanickers (four groups of 20 subjects) were subjected to a 90 sec period of voluntary hyperventilation, during which heart rate was assessed. Regardless of panic history, total symptom scores did not differ between high and low anxiety-sensitive subjects at baseline or pre-hyperventilation, but did differ at post-hyperventilation. There were, however, no significant differences in post-hyperventilation measures of heart rate. The apparent mismatch of subjective and physiological responsivity to the challenge in high anxiety-sensitive individuals (i.e. more severe symptom self-reports in the absence of increased cardiac activation) provides support for the hypothesis that high anxiety sensitivity is associated with an enhanced tendency to panic in response to biological challenge.

Fearful and non-fearful panic attacks in a student population.

The phenomenon of non-fearful panic was investigated in a sample of 83 university students who reported histories of unexpected panic attacks. Based on severity ratings of individual panic symptoms, Ss were classified as having panic attacks characterized by No Fear (N = 22), Low Fear (N = 30) or High Fear (N = 31). The three groups were similar with respect to the age-of-onset of panic attacks, the frequency with which they experienced panic and the severity of panic symptoms unrelated to fear. However, Ss reporting fear during panic attacks were more likely to engage in avoidance behaviour and to use alcohol or drugs as ways of coping with panic. Only High Fear subjects showed significant elevations on self-report measures of depression and global psychopathology. These results indicate that the experience of fear during panic attacks may be important in the transition from non-clinical panic to panic disorder, in a manner proportional to the amount of reported fear.

Panic attacks and interoceptive acuity for cardiac sensations.

It has been suggested that perception of visceral changes, and cognitive reactions to such changes, may be important for triggering panic attacks. It remains to be determined, however, whether people with panic attacks are actually characterized by enhanced perceptual acuity for interoceptive stimuli. The purpose of this study was to explore the relationship between panic attacks and awareness for cardiac sensations using an objective heartbeat discrimination procedure. Twenty panickers and 20 nonpanickers were given 60 trials of the Whitehead heartbeat discrimination procedure. Thirty trials were given during rest and 30 following hyperventilation. Results indicated that panic attacks were not related to enhanced interoceptive acuity for cardiac sensations, either at rest or following hyperventilation. These results are discussed in terms of their relevance to cognitive models of panic.

A combined behavioral/pharmacological treatment of sleep-wake schedule disorder in Angelman syndrome.

Angelman syndrome (AS) is a genetic disorder associated with a deletion on chromosome 15. Behavior problems among children with AS include sleep difficulties. Data are presented on the successful treatment of a sleep-wake schedule disorder (SWSD) in a 9-year-old boy with AS. The treatment program included behavioral and pharmacological components. During baseline, the child slept a mean of 1.9 hours per night and 1.3 hours during the day; night sleep was increased to a mean of 8.3 hours and day sleep was reduced to a mean of .08 hours after introduction of the full-treatment program. Medication was discontinued subsequently, and the child slept a mean of 7.8 hours during the night and .07 hours during the day. At 45-day follow-up, night sleep was maintained at 7.1 hours and day sleep remained stable at .29 hours. This is the first known report of an effective treatment of a SWSD in a child with AS.

Panic attacks in the nonclinical population: an empirical approach to case identification.

Although self-reports of panic attacks are common among student populations, it is not clear that their panic experiences are actually comparable to those of patients with clinical anxiety disorders. An empirical approach was taken to this problem by using a cluster analysis procedure to identify subjects within two samples of university students who reported panic attack symptom profiles that resembled those of patients with panic disorder. Such empirically defined "clinical" panic attacks were reported by 7.0% and 8.1% of the two samples. This predominantly female group accounted for most of the increased psychopathology that has been reported in previous studies of nonclinical panic.

Rescue from the abnormal oocyte maternal-effect lethality by ABO heterochromatin in Drosophila melanogaster.

The euchromatic maternal-effect mutation abnormal oocyte (abo), of Drosophila melanogaster interacts with regions of heterochromatin known as ABO, which reside on the X, Y and second chromosomes. Here, we show that survival of progeny from abo females depends in part upon the maternal dosage of ABO heterochromatin. A comparison was made of the recovery of genotypically identical progeny from abo mothers bearing sex chromosomes of various ABO contents. The results show that the recovery of daughters was decreased if mothers were ABO-/ABO-. However, no decrease was observed if mothers were ABO+/ABO-. In addition, the survival of daughters was greater when they received an ABO-X chromosome from an ABO-/ABO+ mother rather than the father. We suggest that these results reflect a complementation or interaction between the ABO-deficient X and the ABO heterochromatin in the maternal genome. This proposed interaction could occur early in oogenesis in the mother or prior to completion of meiosis I in the fertilized egg. To determine if zygotic dosage of ABO heterochromatin might also be important at very early stages of embryogenesis, we examined the timing of zygotic rescue by paternally donated ABO heterochromatin using a second mutation, paternal loss (pal). Homozygous pal males produce progeny which lose paternally derived chromosomes during the early zygotic divisions. Zygotes that have lost a paternal sex chromosome in a fraction of their nuclei will be mosaic for the amount of ABO heterochromatin. By monitoring the recovery of pal-induced mosaics from abo and abo+ females, we could determine the temporal and spatial requirements for ABO function. Results show that the survival of progeny from the abo maternal-effect lethality was increased if ABO heterochromatin was present prior to the pal-induced loss event. Analysis of mosaic patterns did not reveal a specific lethal focus. We conclude from these results that ABO heterochromatin serves its vital function prior to completion of the early cleavage divisions in progeny of abo mothers.

An evaluation of the distinction of ectopic and pituitary ACTH dependent Cushing's syndrome by clinical features, biochemical tests and radiological findings.

The efficiency of various laboratory and radiological investigations in the differentiation of ectopic from pituitary dependent Cushing's syndrome was studied, based on findings in 23 patients with verified Cushing's disease and seven patients with the ectopic ACTH syndrome. Clinical features strongly favouring the ectopic type were male sex and history for less than 18 months. Basal biochemical features strongly indicating the ectopic syndrome included plasma K+ less than 3.0 mmol/l and HCO3 greater than 30 mmol/l; serum cortisol at 9 a.m. or midnight of greater than 800 nmol/l; urine free cortisol greater than 1300 nmol/24 hours; plasma ACTH greater than 100 ng/l. In the high-dose dexamethasone suppression test, suppression by less than 50 per cent of 9 a.m. serum cortisol, urine free cortisol or 17-oxogenic steroids was usually indicative of an ectopic source of ACTH. A mean suppressed value of greater than 450 nmol/l for the 9 a.m. and midnight cortisol combined occurred in all of those with the ectopic syndrome, but in none of the 23 patients with Cushing's disease. For urine free cortisol, a mean suppressed value of less than 1000 nmol/24 hours was found in all patients with Cushing's disease, but in none of those in the ectopic group. In the metyrapone test, there was an increase of less than or equal to 3-fold in 11-deoxycortisol at 24 hours in patients with ectopic ACTH; the increase was greater than 3-fold in all but one of the patients with Cushing's disease. Failure to respond to either dexamethasone or metyrapone was found in only one of the patients with Cushing's disease (Patient 16); in the ectopic group, all patients except Patient D failed to respond to either test. It is concluded that patients presenting with clinically obvious Cushing's syndrome along with measurable plasma ACTH can be reliably divided by conventional tests into those that are driven from the pituitary and those driven by ectopic ACTH.

Pharmacokinetics of the long-acting somatostatin analogue octreotide (SMS 201-995) in acromegaly.

A single-dose study was performed to examine the pharmacokinetics of subcutaneous octreotide in acromegalic patients and to investigate the relationship between growth hormone and the elimination half-life of the drug. Fourteen acromegalic patients (six men and eight women; age range 35-59 years) who had previously received conventional treatment were studied. Two subjects were on long-term octreotide which had been discontinued 72 h before the study. Octreotide 100 micrograms was administered subcutaneously and plasma samples taken every 10 min for 1 h and then hourly for up to 8 h. Growth hormone was measured at 0, 2 and 8 h. Octreotide was rapidly absorbed with a mean (+/- SEM) t1/2abs of 5.4 min (+/- 0.8) peaking at a mean plasma concentration of 3.4 nmol/l (+/- 0.2) in 27.4 min (+/- 3.7). The monoexponential elimination phase had a mean half-life of 110 min (+/- 9.6). The apparent volume of distribution was 29.4 1 (+/- 1.9) and total clearance was 172 ml/min (+/- 10.4). These results were similar to those obtained in normal volunteers. There was no simple relationship between the level of growth hormone and the half-life of octreotide. Growth hormone levels ranged from 2.5 to 34.0 mIU/l but were only greater than 10 mIU/l in three subjects. Further studies of octreotide pharmacokinetics are needed in untreated patients with acromegaly with raised growth hormone levels.

Factors involved in nurses' teaching breast self-examination.

It has been demonstrated that breast self-examination (BSE) is a reliable method for early detection of breast abnormalities when practiced regularly and correctly. In addition, it has been found that a woman is likely to be more proficient if she has been taught BSE by a physician or nurse. In a hospital-based study, nurses were surveyed regarding both their personal practice and their teaching of BSE to patients. Although the nurses revealed themselves to be highly compliant in terms of performing the procedure themselves, only 40% included BSE in their patient teaching. The nurses' teaching of BSE was found to be unrelated to their age, BSE practice, or personal risk for breast cancer. Nurses agreed that BSE was a valuable tool in the prevention of deaths from breast cancer. They also believed themselves to be susceptible to breast cancer despite good health and low-to-medium risk sources. We suggest that nurses' ambivalent attitudes towards breast cancer and BSE may influence their teaching behavior.

Long term follow-up of patients with Cushing's disease treated by interstitial irradiation.

The first 86 patients with Cushing's disease treated with interstitial irradiation (by needle implantation) as the sole therapy were reviewed. In the 82 patients who were reassessed 1 yr after treatment 63 (77%) achieved remission. This study comprises the outcome and complications in the 54 patients who had a remission and whom we were able to follow. The follow-up period ranged from 3-26 yr (mean, 10.5) from the time of remission. No instance of clinical or radiological relapse has occurred. Of these 54 patients, yttrium-90 alone was used in 32, of whom 12 (37%) required corticosteroid or T4 replacement therapy in a mean time of 3.5 months; in 7 of these 12 we elected to give an ablative dose. Gold-198 alone was used in 15 patients, of whom 7 (47%) developed hypopituitarism in a mean time of 76 months. Both isotopes were used in 7 patients. A diurnal serum cortisol rhythm was found in 28 of the 31 patients who were not receiving corticosteroid therapy. In 5 of the 7 patients with an initially abnormal pituitary fossa, serial radiological studies revealed remodelling in 3. There have been no complications in the last 17 years. Pituitary implantation with yttrium-90 is an effective alternative to transsphenoidal hypophysectomy, with a high remission rate, no recurrence (as yet), no operative complications, and avoidance of hormone replacement in the majority.

Long-term follow-up of patients who underwent yttrium-90 pituitary implantation for treatment of proliferative diabetic retinopathy.

Between 1960 and 1976 117 patients underwent pituitary implantation with yttrium-90 (90Y) for treatment of proliferative retinopathy at the Hammersmith Hospital, London. Mean age at operation was 35 +/- 11 years (mean +/- SD), and mean duration of diabetes 18.6 +/- 10.0 years. Mean insulin dosage prior to implant was 67.2 +/- 24 units, falling to 30.4 +/- 14.9 units post-implant. Thirty-two per cent of patients are still living, 60% are deceased and 8% are lost to follow-up. The 5-year survival rate was 82%. Of the causes of death, 21% died of infection, adrenal insufficiency or hypoglycaemia, 12% of renal failure, and 47% of myocardial or cerebral vascular disease. Ophthalmological follow-up was carried out on the 100 patients operated on between 1965 and 1976. The mean age of this group at implant was 35 +/- 10.5 years, and mean duration of diabetes 17.2 +/- 8.7 years. Visual acuity in the better eye at operation was 6/12 or better in 84% of patients, and this percentage remained similar at the time of the 5 and 10 year follow-up. Blindness (6/60 or worse) in both eyes was present in 12% of patients at the time of 5 and 10 year assessments. By 5 years new vessels on the disc had improved from a mean grading of 2.7 +/- 1.6 to 0.8 +/- 1.2 (p less than 0.001), and by 10 years there was no disc neovascularisation in any eye. There was a similar improvement in the grading of hard exudates, microaneurysms and haemorrhages, but there was an increase in fibrous retinitis proliferans.(ABSTRACT TRUNCATED AT 250 WORDS)