Quality of life in adults with growth hormone (GH) deficiency: response to treatment with recombinant human GH in a placebo-controlled 21-month trial.

We examined the effect of GH supplementation on the psychological capacity and sense of well-being in 36 patients with adult-onset GH deficiency (GHD). Recombinant human GH was given in a 21-month cross-over, double blind trial, and quality of life was assessed by using three self-rating questionnaires: the Hopkins Symptom Check List (HSCL), the Nottingham Health Profile (NHP), and the Psychological General Well-Being index. In addition, at the final examination the spouses completed a short questionnaire concerning their partner. Before treatment, the patients had lowered quality of life as determined by the HSCL and NHP inventories, and a correlation between the duration of GHD and the reported symptoms was observed. Upon treatment, the HSCL score was lower (better) after placebo administration (mean +/- SD, 84 +/- 21.3) than at baseline (89 +/- 18.9; P = NS) and fell to 80.2 +/- 18.5 (P < 0.001) when active drug was given. The subscales regarding anxiety, fearfulness, and cognition were the most sensitive. It was apparent that the effect determined after GH therapy in part was due to a placebo effect. With NHP, the dimensions of energy and emotions responded most to treatment. Further, the spouses observed their partners to be improved in several aspects of mood and behavior (P < 0.05 to P < 0.0001) when active drug was given. The data thus demonstrate that GH, which is known to have multiple somatic effects, produces an improvement in the quality of life of adults with GHD.

Psychiatric symptoms and cerebrospinal fluid monoamine metabolites in primary hyperparathyroidism.

This prospective study included 32 patients with primary hyperparathyroidism (HPT). As compared with a healthy reference group, the patients had pronounced psychiatric symptomatology [CPRS score 17.2 +/- 9.0 (SD) versus 4.4 +/- 2.0], which was mainly affective in character. The severity of symptoms was not related to the serum calcium or parathyroid hormone concentrations. The majority of the patients had low CSF concentrations of monoamine metabolites (5-HIAA, HVA, and MHPG) and, in particular, those with the most severe psychiatric symptoms had low values for 5-HIAA. At follow-up, 1 year after parathyroid surgery, the patients displayed a clear improvement in mental health (CPRS score 4.4 +/- 3.0) together with an increase in CSF concentrations of 5-HIAA and HVA. The study demonstrates that significant psychiatric disturbances, which can be improved/normalized by surgery, are common in patients with HPT and are possibly related to changes in the central nervous system turnover of monoamines.

Brain networks affected by synchronized sleep visualized by positron emission tomography.

Nineteen lightly sleep-deprived healthy volunteers were examined with H2(15)O and positron emission tomography (PET). Scanning was performed during wakefulness and after the subjects had fallen asleep. Sleep stage was graded retrospectively from electroencephalogram (EEG) recordings, and scans were divided into two groups: wakefulness or synchronized sleep. Global flow was quantified, revealing no difference between sleep and wakefulness. A pixel-by-pixel-blocked one-way analysis of variance (ANOVA) was performed after correcting for differences in anatomy and global flow. The sum of squares of the z-score distribution showed a highly significant (P < 0.00001) omnibus difference between sleep and wakefulness. The z-score images indicated decreased flow in the thalamus and the frontal and parietal association cortices and increased flow in the cerebellum during sleep. A principal component (PC) analysis was performed on data after correction for global flow and block effects, and a multivariate analysis of variance (MANOVA) on all PC scores revealed significant (P = 0.00004) differences between sleep and wakefulness. Principal component's 2 and 5 correlated to sleep and revealed distinct networks consisting of PC 2, cerebellum and frontal and parietal association cortices, and PC 5, thalamus.

Neuroimaging study in autosomal dominant cerebellar ataxia, deafness, and narcolepsy.

Four patients affected with autosomal dominant cerebellar ataxia, deafness, and narcolepsy underwent brain CT and MRI. Radiologic findings were supratentorial atrophy (more pronounced than infratentorial atrophy), pronounced dilatation of the third ventricle, low T2 signal intensity in the basal ganglia, loss of cerebral cortex-white matter differentiation, and periventricular high-signal rims. 2-[18F]Fluoro-2-deoxy-D-glucose PET was done with one patient, without specific findings. Genetic analyses excluded SCA-1, SCA-2, SCA-3, SCA-6, SCA-7, DRPLA, and huntingtin gene mutations.

Sleep of children with enuresis: a polysomnographic study.

OBJECTIVE: To evaluate relationships between bladder voiding and sleep in children with enuresis. METHODS: Polysomnographic recordings were obtained from 25 children, aged 7 to 17 years, with monosymptomatic nocturnal enuresis. During 52 recorded nights, 37 enuretic events were detected. Responders (n = 7) and nonresponders (n = 16) to desmopressin treatment were compared. RESULTS: The mean latency between sleep onset and the first bladder voiding was 3 hours 20 minutes (SD = 2 hours 5 minutes). The number of voidings were 19, 7, 10, and 1 occurring during stages 2, 3, and 4, and rapid-eye movement sleep, respectively. Desmopressin responders were found to void during the early or late part of the night, whereas the voidings of the nonresponders were dispersed evenly throughout the night (chi2 = 8.09). CONCLUSIONS: The enuretic event is a predominantly non-rapid eye movement sleep phenomenon. Responders and nonresponders to desmopressin treatment void during different parts of the night.

Sleep disturbances in a young adult population: can gender differences be explained by differences in psychological status?

To study the prevalence of reported sleep disturbances and the association between these complaints and psychological status, 529 randomly selected subjects aged 20-45 years were questioned about their sleep symptoms and psychological status by means of questionnaires. In this young population, feeling refreshed in the morning almost every day was reported by only 15.3%. Females reported a significantly longer mean total sleep time (TST) than males (F: 425 +/- 58 minutes, M: 403 +/- 50 minutes; p < 0.01). Despite this, the difference compared with the reported need of sleep was greater in females (56 +/- 62 minutes) than in males (40 +/- 51 minutes) (p < 0.05). Difficulties maintaining sleep (DMS, > or = 3/week) (F: 20.1%, M: 10.4%; p < 0.01), the absence of feeling refreshed in the morning (F: 36.2%, M: 26.8%; p < 0.05), and excessive daytime sleepiness (EDS) (F: 23.3%, M: 15.9%; p < 0.05) were significantly more common among females. According to the Hospital Anxiety and Depression scale, females suffered from anxiety more frequently than males (F: 32.8%, M: 18.9%; p < 0.001). An association was found between anxiety and many sleep disturbances. After making adjustments for age, smoking, snoring, gender and psychological status by means of multiple regression, the gender differences mentioned above remained significant. We conclude that despite a longer TST, females report insufficient sleep, EDS, DMS, and the absence of feeling refreshed in the morning more frequently than males. The higher prevalence of anxiety among females alone cannot explain the gender differences in sleep disturbances seen in this population.

Prevalence of sleep disturbances among young adults in three European countries.

The aim of this investigation was to study the geographic variation in sleep complaints and to identify risk factors for sleep disturbances in three European countries: Iceland (Reykjavik), Sweden (Uppsala and Göteborg) and Belgium (Antwerp). The study involved a random population of 2,202 subjects (age 20-45 years) who participated in the European Community Respiratory Health Survey. The subjects answered a questionnaire on sleep disturbances. Participants in Iceland and Sweden also estimated their sleep habits and sleep times during a period of 1 week in a sleep diary. Habitual (> or = 3/week) difficulties inducing sleep (DIS) were reported by 6-9% and early morning awakenings by 5-6% of the subjects. The estimated number of awakenings and the prevalence of nightmares was significantly lower in Reykjavik. Participants in Reykjavik went to bed at night and woke in the morning approximately 1 hour later than participants at the Swedish centers (p < 0.001). Symptoms of gastroesophageal reflux (GER) were associated with DIS (odds ratio [OR] = 2.7), nightmares (OR = 4.4), longer sleep latency and frequent nocturnal awakenings. Smoking correlated positively to DIS (OR = 1.8) and estimated sleep latency. We conclude that the prevalence of DIS was fairly similar at these four European centers but that there was a variation in the prevalence of nightmares and nocturnal awakenings. The significant correlation between reported GER and subjective quality of sleep should be followed up in studies using objective measurements.

Cerebrospinal fluid calcium, parathyroid hormone, and monoamine and purine metabolites and the blood-brain barrier function in primary hyperparathyroidism.

Psychiatric disturbances are common in primary hyperparathyroidism (HPT), but their pathogenesis is essentially unknown. This study deals with cerebrospinal fluid (CSF) calcium homeostasis and its connection with parathyroid hormone (PTH), blood-brain barrier (BBB) function, and central monoamine and purine metabolites in patients with primary HPT. In 22 patients with primary HPT (serum calcium 2.85 +/- 0.21 mmol/l), the CSF concentrations of total and ionized calcium were higher (1.21 +/- 0.08 mmol/l, p less than 0.01, and 1.09 +/- 0.05 mmol/l, p less than 0.001, respectively) than in 11 normocalcemic reference subjects. The values correlated with serum calcium concentration (p less than 0.001) and CSF/serum albumin ratio, a measure of BBB permeability. The latter ratio was elevated in one-third of the patients with HPT, indicating BBB damage. CSF immunoreactive intact PTH was higher in the HPT patients than in the reference group (p less than 0.05), and serum and CSF PTH were positively correlated (p less than 0.05). The CSF levels of the monoamine metabolites 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) were lower, and the level of urate in CSF was higher, in the HPT patients than in the reference subjects, while there were no consistent differences in CSF hypoxanthine or xanthine. CSF 5HIAA correlated inversely with CSF ionized calcium (r = -0.42, p = 0.02). After parathyroid surgery, CSF calcium and urate decreased significantly and CSF monoamine metabolites increased slightly. The decrease in CSF ionized calcium correlated with the alleviation of psychiatric symptoms. The results indicate the importance of increased CSF calcium concentrations in patients with primary HPT and suggest a relation between central calcium regulation and central turnover of monoamines.

A double-blind, controlled trial in primary care patients with generalized anxiety: a comparison between buspirone and oxazepam.

Two hundred thirty patients with generalized anxiety and Hamilton Rating Scale for Anxiety (HAM-A) scores greater than or equal to 18 were subdivided at random, according to a double-blind design, into one group treated with 5-10 mg of oral buspirone t.i.d. or one group treated with 10-20 mg of oral oxazepam t.i.d. for 6 weeks. No anxiolytic treatment was allowed 3 months prior to trial entry. Analysis of demographic variables revealed no significant imbalance between the two treatment groups. Twenty patients were excluded from efficacy analysis because of treatment withdrawal before the first efficacy evaluation on Day 7. Another 4 patients were excluded because they were taking concomitant psychotropic medication. The remaining 206 patients displayed a decrease in HAM-A scores (mean +/- SD) from 23.9 +/- 4.1 to 10.6 +/- 7.7 in the buspirone group and from 23.9 +/- 4.2 to 11.5 +/- 8.0 in the oxazepam group. The two treatment groups were also found to be virtually identical in an "intent to treat" analysis of all 230 patients as well as in other ratings (Hamilton Rating Scale for Depression, Raskin Depression Scale, Covi Anxiety Scale, Physicians Questionnaire, global ratings, and Hopkins Symptom Checklist [HSCL]-56). However, oxazepam was never superior to buspirone in any of the efficacy analyses. Of the 230 patients, 127 spontaneously reported adverse events, including drowsiness, dizziness, headache, nausea, and nervousness. Adverse events were relatively similar in the two groups. In conclusion, buspirone and oxazepam appear to be equally effective in the treatment of generalized anxiety encountered by general practitioners. This outcome, in addition to a previously documented absence of any dependency liability, makes buspirone a clinically important anxiolytic drug.

Case-control study on symptoms and signs of "asymptomatic" primary hyperparathyroidism.

BACKGROUND: Symptoms, signs, and treatment of mild primary hyperparathyroidism (HPT) are controversial. METHODS: One hundred two patients with HPT and matched controls were recruited from 5202 females attending population-based mammography screening at age 55 to 75 years. Patients' total serum calcium averaged 10.40 +/- 0.564 mg/dL and intact serum parathyroid hormone 58 +/- 33 ng/L. All patients lacked knowledge of their disease. Questions revealed traditional symptoms of HPT in 24% of cases and 43% of controls (P = .01). All individuals underwent the same biochemical analyses, bone mass determination, and questionnaires on symptoms, illnesses, medications, and background variables. RESULTS: Patients with HPT had more psychic complaints (P = .03 to .007) of lassitude, fatigue, irritability, and lack of sexual and emotional interests. They had lower bone density in total body, spine, and hip (P = .008 to .0004) and higher serum alkaline phosphatase, cholesterol (very-low-density lipoprotein), triglycerides (total, very-low-density lipoprotein), glucose, urate, and hemoglobin values (P = .02 to .0001). Patients visited physicians more often (P = .008) and had more antihypertensive therapy (P = .02). CONCLUSIONS: Mild, "asymptomatic" HPT in patients unaware of their disorder displays significant psychic symptoms, bone loss, and risk factors of cardiovascular disease.