Incidence of a second tumor in hypopituitary patients operated for pituitary tumors.

Recently, an association between increased blood levels of insulin-like growth factor I (IGF-I) and increased risks of prostate, breast, lung, and colorectal cancers has been suggested. As today adults with GH deficiency are subjected to GH substitution, there is a pressing need for baseline tumor incidence data. The aim of the study was to assess the risk for a second tumor in a cohort of 328 patients with hypopituitarism treated for a pituitary tumor from 1958--1992. The patients were receiving conventional hormone treatment, but without GH substitution. The overall tumor incidence [standardized incidence ratio (SIR)] was lower than expected (0.85), but the 95% confidence interval (CI) did not exclude unity (0.59--1.21). Only two prostate cancers occurred (SIR, 0.34; 95% CI, 0.04--1.24). Two brain tumors (SIR, 1.96; 95% CI, 0.24--7.08) and two endocrine tumors (part of multiple endocrine neoplasm syndromes; SIR, 4.00; 95% CI, 0.48--14.5) had occurred. When excluding brain and endocrine tumors, the overall SIR decreased to 0.77, but did still not differ significantly from unity (0.52--1.13). Thus, a tendency for a decreased overall tumor risk, although not statistically significant, was noted, especially when excluding brain and endocrine tumors. This tendency was more emphasized for prostate cancer, but low numbers hamper a firm conclusion. These results may serve as a baseline for tumor risk among adult patients with pituitary insufficiency supplemented with GH.

Hypopituitary females have a high incidence of cardiovascular morbidity and an increased prevalence of cardiovascular risk factors.

We recently reported that female patients with hypopituitarism receiving controlled thyroid and steroid hormone substitution, but without GH replacement, had a more than 2-fold increase in cardiovascular mortality compared to the general population. In the present study we investigated the incidence of cardiovascular disease as well as the prevalence of cardiovascular risk factors in 33 females with hypopituitarism for 6-46 yr (median, 18) compared to those in 33 control subjects recruited from the general population in the same geographical area and matched for sex, age, smoking habits, educational level, and residence location. The patients were with a very high probability GH deficient, as 29 had subnormal serum insulin-like growth factor I levels, and the other 4 were GH deficient, as assessed by an insulin tolerance test. The incidence of cardiovascular disease was significantly higher among the hypopituitary patients (incidence ratio, 3.7; 95% confidence interval, 1.2-11.3), and the consumption of cardioactive drugs was also significantly higher (P = 0.002). Hypopituitary patients had a lower degree of physical exercise during their spare time (P = 0.02), a higher waist/hip ratio (P = 0.01), lower high density lipoprotein cholesterol (P = 0.002), and higher low density/high density lipoprotein ratio (P = 0.009). Furthermore, the patients had a significantly increased left atrium size (P = 0.05), but no difference was observed for other cardiac measures. In the patients, serum insulin-like growth factor I levels significantly correlated with left ventricular mass index (r = 0.48; P = 0.006), suggesting that GH has a strong impact on cardiac size. More episodes of bradycardia (P = 0.05), but no increased occurrence of extrasystolies, were encountered in the patients during 24-h continuous electrocardiogram monitoring. Carotid artery intima-media thickness and plaque numbers did not differ between patients and controls. In conclusion, hypopituitary females exhibit an increased incidence of cardiovascular disease, higher cardioactive drug consumption, and an increased prevalence of cardiovascular risk factors. The increased cardiovascular morbidity could not be ascribed to inadequate estrogen or thyroid hormone treatment, and unsubstituted GH deficiency is probably an important contributing factor.

Postoperative prognosis in craniopharyngioma with respect to cardiovascular mortality, survival, and tumor recurrence.

Specific causes of death, survival, and recurrence rates were assessed in a cohort of 60 patients who had undergone surgery for craniopharyngioma between 1951 and 1988. Compared to the general population, the standardized mortality ratio (SMR) was increased [5.55; 95% confidence interval (CI), 3.68-8.22], and it was higher among females (SMR, 11.4) than males (SMR, 4.79). The risk of cardio- and cerebrovascular mortality (SMR, 3.21; 95% CI, 1.29-6.61) was also enhanced. The cumulative survival rates 10 and 15 yr after the initial operation were 68% (95% CI 54-78) and 59% (95% CI 30-63), respectively. A multivariate survival analysis adjusting for age showed a protective effect of radiotherapy (hazard ratio, 0.3; 95% CI, 0.1-0.8) and an increased risk of death after recurrence (hazard ratio, 4.4; 95% CI, 1.4-14), but no obvious effect of radicality at surgery. However, when patients who had died within 6 months after surgery were excluded, no significant protective effect of radiotherapy remained. The cumulative frequency of recurrence after 10 yr was 33% (95% CI, 22-48%), and that after 15 yr was 40% (95% CI, 28-56%). The incidence of recurrence did not differ significantly with respect to age, radicality at surgery, or postoperative radiotherapy. The determinants for long term outcome in patients with craniopharyngioma are interrelated in a complex way, which calls for strict selection criteria in follow-up studies and the use of multivariate statistical models.

Factors limiting exercise performance in progressive systemic sclerosis.

In order to evaluate to which extent various organs limit physical performance in PSS, maximal working capacity was studied in 22 patients. Special attention was given to cardiac and pulmonary function, joint mobility, and muscular strength. A model for scoring these parameters is given. Working capacity was on the average 51% of the predicted normal value. Ventilation at maximal workload was high despite normal arterial blood gases and presumably normal physiologic dead space. This can be explained by an increased demand on ventilation from an increased muscle metabolism. This may be due to impeded mobility of respiratory and locomotive organs. The maximal heart rate was low and patients with low physical capacity had only a small decrease in base excess. One third of the patients developed arrhythmia during exercise, which contributed to a low performance. Other myocardial involvement was common, seen in the Q-waves, low voltage, left axis deviation, and increased heart volume. In PSS, these ECG changes probably reflect myocardial fibrosis that has developed without clinically manifest infarction. Special attention must be given to arrhythmias at work, which are overlooked in a resting ECG. Ventricular tachycardia plays an important role in sudden death, which, when it occurs, almost always does so within the first years after the onset of PSS. There was no close linkage between cardiac dysfunction and pulmonary fibrosis or joint-muscle impairment. The scoring system showed an equal distribution in reduction of working capacity as to circulation, pulmonary function, and locomotive function.+2

Increased leptin and tumour necrosis factor alpha per unit fat mass in hypopituitary women without growth hormone treatment.

BACKGROUND: The adipocyte products, leptin and tumour necrosis factor (TNF)alpha, are associated with atherosclerotic diseases and may be factors contributing to the enhanced cardiovascular risk in hypopituitary patients with growth hormone (GH) deficiency. OBJECTIVE: To investigate whether leptin and TNFalpha are increased in a group of hypopituitary women previously found to have increased cardiovascular morbidity, and to compare them with matched individuals of the same sex and age and with similar body composition. DESIGN AND PATIENTS: Thirty-three GH-deficient women with a median age of 64 years (range 39-77 years) were investigated cross-sectionally. The patients were compared with 33 controls matched for sex, age, smoking habits, educational level and residence. METHODS: Body composition was measured by bioimpedance analysis. Fasting concentrations of leptin, TNFalpha and insulin were analysed in patients and controls. RESULTS: There was no significant difference in body mass index or fat mass between patients and controls (both P > or =0.4). Serum leptin did not differ significantly between patients and controls. However, when serum leptin concentrations were expressed per kilogram fat mass, the patients had significantly greater concentrations (P=0.01). Serum TNFalpha and TNFalpha per kilogram fat mass were also significantly greater in the patients (both P=0.001). In contrast, serum insulin did not differ significantly between patients and controls. In the patients, serum leptin concentrations correlated positively with kilogram fat mass (r=0.54, P=0.002). Leptin concentration per kilogram fat mass was positively correlated with insulin (r=0.40, P=0.03). CONCLUSIONS: In contrast to serum concentrations of TNFalpha, serum leptin did not differ from that in controls, implying that leptin is not a major contributor to the previously found increase in cardiovascular morbidity in the hypopituitary women investigated. However, the patients had increased leptin concentrations per unit fat mass, indicating an altered adipocyte secretory function in this group.

Lung mechanics and gas exchange during exercise in pulmonary sarcoidosis.

To clarify how lung function at exercise is affected in sarcoidosis, and to analyze how exercise studies compare to testing measurements, 63 patients with pulmonary sarcoidosis were examined with lung mechanics and arterial blood gases during exercise. These findings were compared with simultaneously obtained, but previously reported results of the static lung pressure/volume curve and the lung resistance/static lung pressure curve. While mechanical variables at maximal exercise were as sensitive as those determined by measuring the PstL/V and RL/PstL curves, mechanics during spontaneous breathing at rest was less sensitive. The derangement of mechanics was more evident than that of arterial blood gases. No measurement at rest was a good predictor of working capacity or of arterial PaO2. A comprehensive exercise examination may be an alternative to resting investigations, which are either more elaborate or less sensitive.

Individualized low-dose growth hormone (GH) treatment in GH-deficient adults with childhood-onset disease: metabolic effects during fasting and hypoglycemia.

Growth hormone (GH) has insulin-antagonistic effects, and GH secretion is augmented during fasting and hypoglycemia. In the present study, 10 patients aged 21 to 28 years with childhood-onset GH deficiency (GHD) were studied during a 24-hour fast and a hypoglycemic glucose clamp before and after 9 months of GH replacement. During the 24-hour fast, blood glucose, serum insulin, and serum free fatty acid (FFA) levels were measured. In the hypoglycemic clamp, the counterregulatory hormones (plasma catecholamines, serum glucagon, and serum cortisol), serum insulin-like growth factor (IGF) binding protein-1 (IGFBP-1), serum FFA, and glucose uptake were measured. The GH dose was adjusted to the response of serum IGF-I, and the median GH dose was 0.14 IU/kg/wk (range, 0.08 to 0.19). At the end of the study, serum IGF-I levels were normalized in all but one patient, in whom serum IGF-I was above the normal range. Nine months of GH treatment did not cause any significant changes in the blood glucose level, insulin to glucose ratio, or serum FFA level during the 24-hour fast, and none of the patients experienced hypoglycemia either before or after GH treatment. However, GH therapy resulted in increased insulin resistance during hypoglycemia, without changes in the counterregulatory hormonal responses, serum IGFBP-1, or serum FFA.

High incidence of cardiovascular disease and increased prevalence of cardiovascular risk factors in women with hypopituitarism not receiving growth hormone treatment: preliminary results.

Recently, epidemiological evidence has suggested that hypopituitarism with untreated growth hormone deficiency (GHD) is associated with a high incidence of cardiovascular mortality and that women are particularly at risk. In the present study, the incidence of cardiovascular disease and prevalence of cardiovascular risk factors in 33 such women was assessed and compared with matched controls. A significantly higher number of diagnosed circulatory disorders occurred in the women with hypopituitarism compared with controls, and drug consumption for cardiovascular disorders was also significantly higher in this group. Furthermore, patients with hypopituitarism had a significantly higher waist:hip ratio and a higher ratio of low-density lipoprotein to high-density lipoprotein than controls. Electrocardiogram data showed that hypopituitarism was associated with more episodes of bradycardia. In summary, women with hypopituitarism had an increased incidence of cardiovascular disease and a less favourable risk factor profile compared with matched controls. The data add support to previous studies that have shown increased risks of cardiovascular mortality associated with hypopituitarism with untreated GHD. We conclude that adequate cardiovascular surveillance programmes are required for patients with pituitary insufficiency.

One year follow-up of lung clearance of 99mTc-diethylene triamine penta-acetic acid and disease activity in sarcoidosis.

BACKGROUND AND AIM OF THE WORK: In interstitial lung disease lung clearance of 99mTc-diethylenetriaminepentaacetic acid (DTPA) reflects alterations in the alveolar capillary barrier. Our objective was to describe changes in lung clearance during one year in sarcoidosis, and to relate clearance to other data of lung function and disease activity. METHODS: Twenty-three newly diagnosed patients were studied with respect to lung DTPA clearance, spirometry, 67Ga scintigraphy and serum angiotensin converting enzyme (SACE). Lung mechanics and arterial PO2 at rest and exercise were studied in patients with radiological parenchymal changes. Six of these patients were prescribed peroral steroids. RESULTS: At inclusion lung DTPA clearance measured over 30 minutes was 53 +/- 16 minutes and at follow-up 59 +/- 20 minutes (p > 0.05). The number of pathological clearance curves at inclusion was 10 and at follow-up 6. In treated patients lung DTPA clearance improved as did lung 67Ga score and SACE. However, lung clearance did not correlate significantly with changes in lung function or other activity parameters. CONCLUSIONS: Lung DTPA clearance reflects lung function from an aspect different from that of other methods. It seems sensitive to pathology reversed by steroids and may, in some cases, help in the evaluation of disease activity.

Kinetics of lung clearance of 99mTc-DTPA in smoking patients with sarcoidosis compared to healthy smokers.

Investigation of lung clearance of 99mTc-labelled diethylene triamine penta-acetic acid (DTPA) in smoking sarcoid patients has been impeded by difficulties to differ between pathology of clearance kinetics caused by sarcoidosis and by smoking. This study explores the kinetics of lung clearance of 99mTc-DTPA in 15 current smokers with intrathoracic sarcoidosis. The results are compared with findings from 16 healthy smokers. Measurements of lung clearance over 180 min, i.e. longer than usual, revealed in II of the sarcoid patients a bi-exponential lung clearance course, which is pathologic. All healthy smokers also showed a bi-exponential lung clearance. In the analysis of the bi-exponential curve an initial fast, and a slow clearance component could be separated. The smokers with sarcoidosis had a significantly higher elimination rate of the slow component than the healthy smokers. Thus, analysis of the late part of the lung clearance curve may be rewarding in smoking sarcoid patients. The study shows that lung clearance of 99mTc-DTPA may be a method useful also in smoking patients with sarcoidosis.

Improvement of lung function in a scleroderma patient treated for 12 months with cyclofenil.

A 48 year old male scleroderma patient with typical impairment of respiratory function, including low vital capacity, low static lung compliance and low diffusing capacity for carbon monoxide, was treated with cyclofenil for one year. Assessment of lung function after 3, 6 and 12 months treatment showed marked improvement of vital capacity, increased physical working capacity, less hypoxia at maximum work, increase of static lung compliance and decreases of maximal transpulmonary pressure. Closing capacity decreased, and an increase in difussing capacity for carbon monoxide was seen.

[Comparative studies on preoperative skin disinfection]. / Vergleichende Untersuchungen über präoperative Hautdesinfektion

The antibacterial effects of Sepso-tincture, Kodan, Dibromol, and 70% ethanol as disinfectants were compared on the skin of 34 patients of the first surgical department of the general hospital in Hamburg-Barmbek. Special attention was paid to the regeneration of microorganisms in relation to time. The result was that the tested substances showed an almost equal effect after 2 min. However, after 10, and 60 min the tests showed considerable divergencies. In comparison, therefore, with the other substances, it could be proved that the least regeneration of microorganisms was observed after application of Sepso-tincture (significance after 10 min: P less than 0.01, after 60 min: P less than 0.05).

[Shortages in Swedish tuberculosis care. Good results only in 71 percent of cases after 12-month treatment as shown in a current study]. / Det finns brister inom den svenska tuberkulosvården. Fullgott resultat efter tolv månader hos endast 71 procent visar aktuell studie.

During the period August 1994-December 1995 783 cases of active tuberculos (TB) were notified to the health authorities in Sweden. By means of questionnaires sent to the consulting physicians (92 per cent response rate) the treatment outcome was studied twelve months after the diagnosis. Out of 676 patients only 71 per cent were reported to have completed the treatment and be cured of TB. This indicates that there is room for improvement as regards monitoring patients, if necessary by Directly Observed Therapy (DOT), in order to make sure that prescribed treatment is adhered to.

[Policy program to minimize spread of infection. Prolonged cough may be a sign of tuberculosis]. / Policyprogram för minskad smittspridning. Långdragen hosta kan vara tuberkulos.

In a worldwide epidemiological perspective, Sweden is well favoured with an annual tuberculosis incidence of approximately six cases per 100,000 of the population. Neither the impact of the HIV pandemic nor the occurrence of multiresistant strains of Mycobacterium tuberculosis has yet become a major problem in the care of tuberculosis patients in Sweden. Only a few per cent of HIV patients have developed tuberculosis, and during the period, 1991-94, only one per cent of M. tuberculosis isolates in Sweden were resistant to such antimycobacterials as isoniazid and rifampicin. However, the epidemiological situation in the neighbouring Baltic states is a matter for concern. Bovine tuberculosis has been eradicated in Sweden, the last case having been diagnosed in 1978. Although the reported efficacy of BCG (bacillus Calmette-Guérin) tuberculosis vaccine varies according to the population studied, protective rates of 70-85 per cent have been reported for Sweden and other west European countries. Re-vaccination of tuberculin-negative individuals has not been shown to yield added protection. The aim of a national programme for protection against tuberculosis is to preserve our favourable epidemiological situation by early detection of new cases, effective contact tracing, and BCG vaccination of children in population groups at risk. The primary means of achieving this is the education of health care personnel to retain tuberculosis as a differential diagnosis. Moreover, national guidelines for contact tracing must be duly observed, and immigrants from high prevalence areas need to be screened for tuberculosis. Registration of all cases of tuberculosis should be maintained at regional and national levels, and follow-up must be meticulous until a successful outcome of treatment is accomplished. Recommendations for dealing with tuberculosis should be made available and duly implemented at all hospitals caring for tuberculosis patients, in order to avoid nosocomial transmission. Although BCG vaccination at birth was formerly general in Sweden, since 1975 only children considered to be at risk have been vaccinated. Thus, non-vaccinated young adults are now entering the health care sector as students or employees, and should be offered BCG vaccination. Moreover, the epidemiological situation both in Sweden and in neighbouring countries needs to be monitored carefully in order that recommendations concerning BCG vaccination and other preventive measures can be modified if necessary.

[Psychological consequences of breast cancer screening among healthy women]. / Psykologiske følger af screening for brystkraeft blandt raske kvinder.

The number of healthy women undergoing screening for cancer is very large. It is therefore important to know about the psychological consequences of screening. The literature for this review was found by searching in national and international databases and reading lists of references. This review finds that both women with negative test results and women with false positive test results report on psychological consequences such as fear and raised anxiety, depression, impaired working capacity, reduced self-esteem and self-confidence, as well as effects on their relationship to other people. They also report on physical symptoms such as impaired sleep or appetite. This review suggests that methods other than psychometric questionnaires would offer more knowledge on the subject and that future research should concentrate on those women experiencing serious psychological effects of screening.

[Physicians' tasks in the Occupational Health Services]. / Laegernes arbejdsopgaver i bedriftssundhedstjenesten.

The aim of this study was to describe the kind of present and future tasks doctors employed in the Occupational Health Service (OHS) in Denmark carried out and to shed light on the reasons why only a moderate number of doctors are employed in the OHS. Additional aims were to map out the number of engaged part-time and full-time doctors in the OHS in Denmark compared with the number of other professionals engaged in the OHS. The study was based on questionnaires sent out to all 109 OHS units in Denmark and to all the doctors employed in the OHS. Ten persons in the OHS were strategically selected for an open interview. There were still only a very few doctors (9%) employed in the OHS in comparison to the other professionals employed in OHS, (nurses, various therapists and technicians) and the doctors were mostly engaged part-time; most of them for less than 10 hours a week. The moderate number of doctors was amongst other things explained by the relatively high cost of the doctors' salaries and the doctors having a reputation for being arrogant and dominating. The doctors were in general very experienced in occupational health matters and solved many problems which required a doctors education. A great deal of the problems they solved were in finding the causality between the workers' symptoms and the working-place conditions. The doctors suggested several future tasks for OHS, e.g. to evaluate its preventive results and to participate in a higher degree when planning working environments.

[Labor complications and interventions in immigrant and Danish women during the period 1983-1987]. / Fødselskomplikationer og indgreb blandt indvandrerkvinder og danske kvinder i perioden 1983-1987.

Based on data retrieved from the Danish Medical Birth Register, deliveries among Danish and immigrant women were compared in the years 1983-1987. The women were divided into two groups, primiparous and multiparous, and then compared by frequency and type of complications and interventions during labour. Five hospitals in the Copenhagen area were selected and more than 40,000 women were included in the survey. About 3,500 were from Yugoslavia, Turkey, Pakistan and Morocco and the remainder were from Denmark. An increased frequency of complications and interventions during labour was recorded among primiparous in comparison to multiparous during the period. This observation was not related to nationality. Stimulation of labour by intravenous drugs was more frequent among immigrant women than Danish women and was particular frequent among Moroccan and Pakistani women. Among these nationalities higher frequencies of complications were not recorded and the use of intravenous drugs did not imply more instrumental deliveries. It is presumed that one of the reasons why the use of intravenous drugs is more frequent among immigrant women is due to a feeling of insecurity during labour. This might be caused by defective communication between the woman in labour and the midwife. The subject calls for closer investigations based on case records and the women's own experiences. The necessities for special training of immigrant women and staff members in maternity wards are pointed out.

[The use of free maternal preventive services among immigrant pregnant women in Denmark during 1983-1987]. / Gravide indvandrerkvinders brug af det svangreprofylaktiske tilbud i Danmark 1983-1987.

As part of an investigation of immigrants' living conditions in Denmark, we have investigated how pregnant immigrant women utilize the possibility of free examinations during pregnancy. The study is based on data on all deliveries in Denmark in the years 1983-1987, retrieved from the Danish Medical Birth Registry concerning parturient women with permanent address in Denmark and who were born in either one of the Scandinavian countries, Yugoslavia, Turkey, Pakistan, Marocco, Iran of Vietnam. The women born outside Scandinavia gave birth to about 6,500 infants during the study period; roughly half of these were borne by Turkish women. The largest percentage of young parturients were found among women from Turkey and Yugoslavia. Pakistani and Maroccan mothers had higher parity. These two groups were especially concentrated in the municipality of Copenhagen, where half of the parturient women lived. A few lived in the remainder of the country while a total of 85% lived in the metropolitan area. Four out of ten pregnant Turkish or Pakistani women had been examined by a midwife less than the five times recommended. Among those living in the metropolitan area. Danish women have an average total of almost 11 examinations compared to 8.2-8.9 among immigrants. The conclusion of the study is that the immigrant women have less contact with the free antenatal care system during their pregnancies than the Scandinavian women and that the differences are greatest when examinations by the midwife were concerned. Further discussion on antenatal care in Denmark, is required.