Real-world data on efficacy and safety of pembrolizumab in the first-line treatment of metastatic lung cancer in patients with PD-L1 expression >0% - a single center experience.

OBJECTIVE: With the advent of immunotherapy, there has been a significant improvement in the outcomes of non-small cell lung cancer treatment. Several clinical trials have confirmed the efficacy and safety of pembrolizumab, but research with real-world data is needed to confirm the findings from clinical trials. PATIENTS AND METHODS: In this retrospective study, data on the treatment of lung cancer with pembrolizumab were analyzed in 78 patients who started pembrolizumab therapy as first-line treatment for metastatic disease at University Hospital Centre Osijek, from May 15, 2018, until December 31, 2021. November 30, 2022, was set as the last date of data monitoring. Patients who had received less than 3 cycles of pembrolizumab were excluded from the study. The main objectives of the study were OS (overall survival) and PFS (progression-free survival). The differences in the incidence and type of adverse events between the two groups of patients were also compared. RESULTS: Kaplan-Meier analysis of the survival determined that the median OS was 20 months and PFS was 13 months. Although OS and PFS are longer in patients with PD-L1 (programmed death-ligand 1) ≥ 50%, the differences are not statistically significant. The most commonly reported adverse events related to pembrolizumab treatment were gastrointestinal adverse events. No significant differences were found in the frequency of occurrence of certain adverse events between the two groups of patients. CONCLUSIONS: This study demonstrates that real-world data for pembrolizumab treatment of non-small cell lung cancer confirm the efficacy and safety indicated by clinical trials. Nevertheless, it is necessary to assess the patient's general condition more objectively before starting the treatment.

Antioxidative effects of supplementing linseed oil-enriched diets with α-tocopherol, ascorbic acid, selenium, or their combination on carcass and meat quality in broilers.

In a previous study, we examined the synergistic effects of the dietary supranutritional supplementation with vitamin E, vitamin C, and Se on the in vivo antioxidative status of broilers under conditions of dietary oxidative stress induced by feeding a diet high in n-3 PUFA. In this study, we examined the effect of their inclusion on the quality characteristics and oxidative stability of raw or cooked meat, both fresh or after a long-term frozen storage. Four hundred 21-day-old Ross 308 male broilers were allocated to 5 experimental groups fed 5% linseed oil-enriched finisher diets (days 21 to 40): Cont (recommended levels of vitamin E, C, and selenium), +E (200 IU vitamin E/kg feed), +C (250 mg vitamin C/kg feed), +Se (0.2 mg selenium/kg feed), or +ECSe (concentrations as in the sole supplementation, combined). Animal performance and carcass characteristics were monitored at the age of 40 D. Breast meat samples of 12 chickens per group were analysed fresh, fresh after frozen storage, cooked fresh, and cooked after frozen storage (2 × 2 factorial design) for parameters of meat quality (water-holding capacity-WHC, pH, and color) and oxidative stability (concentrations of vitamin E, malondialdehyde-MDA, antioxidant capacity of the water-soluble compounds-ACW, and fatty acid composition). Vitamin E alone (+E) and combined with Se and vitamin C (+ECSe) increased the α-tocopherol concentration in breast muscle, and showed similar protective effects against lipid peroxidation measured as MDA regardless of the frozen storage or cooking. The sole supplementation of vitamin C or selenium showed no effects on the meat quality parameters. In conclusion, the dietary supranutritional inclusion of vitamin E inhibited the lipid peroxidation in fresh, frozen stored, cooked fresh, and frozen stored meat in broilers fed with diets rich in n-3 PUFAs. Even though no clear synergistic effects of the supranutritional supplementation of vitamin C and Se with vitamin E were detected, their dietary inclusion did not negatively affect broilers carcass and meat quality parameters.

Effects of supplementation with α-tocopherol, ascorbic acid, selenium, or their combination in linseed oil-enriched diets on the oxidative status in broilers.

A trial was conducted to investigate whether, and if so to what extent, the combined supplementation of vitamin E, vitamin C, and selenium was superior to their sole supplementation concerning the oxidative stress induced by a high n-3 dietary polyunsaturated fatty acids (PUFA) intake in broilers. Four hundred 21-day-old Ross 308 male broilers were allocated to 5 experimental groups fed the following linseed oil (5%)-enriched finisher diets: Cont (no supplement), +E (200 IU vitamin E/kg feed), +C (250 mg vitamin C/kg feed), +Se (0.2 mg selenium/kg feed), or +ECSe (concentrations as in the sole supplementation, combined). Analyses of malondialdehyde (MDA), vitamin C, and α- and γ-tocopherols in plasma, antioxidant capacity of water- (ACW) and lipid- (ACL) soluble compounds in serum, and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities in whole blood were performed. In breast muscle, analyses of MDA, α- and γ-tocopherols, ACW, selenium, and fatty acid (FA) composition were carried out. Birds fed the combination of antioxidants showed reduced average daily gain (ADG) and average daily feed intake (ADFI) and, as +E, lower MDA and γ-tocopherol, together with raised α- tocopherol levels in plasma and lower MDA and raised α- tocopherol levels in breast muscle compared to the control. The combination of antioxidants in the +ECSe group raised GPx activity in whole blood compared to the control. In conclusion, results indicated that vitamin E is the most effective antioxidant to alleviate oxidative stress caused by high dietary PUFA and that the supplementation with additional vitamin C and selenium did not have clear synergistic effect.

Intracranial infection as a common complication following war missile skull base injury.

The purpose of this paper is to stress the importance of clinical observation, the appropriate antimicrobial therapy, and early surgery in the management of intracranial infection following war missile penetrating skull base injury. There were 21 skull base missile injuries treated surgically in a 4-year period. Careful removal of devitalised brain tissue with dural closure was performed with all patients to prevent the development of intracranial infection. Subsequent clinical and radiological surveillance was performed to detect evidence of infection and abscess formation if fragments were left in place. Broad range antibiotic coverage, and the antioedematous agents were applied in the early postoperative period. Infection about the brain was seen in four cases. We recorded three cases of brain abscess formation, while one patient developed bacterial meningitis. The incidence of infectious complications was relatively high in our series. After the organisms causing infection were known, treatment was modified to be as specific as possible. It was not necessary to reoperate on intracranially retained foreign bodies and fragments since they did not increase the infection rate. However, repeated surgery is necessary for a brain abscess.

[Cholinesterase in the differential diagnosis of parenchymal and obstructive icterus and in the differentiation between malignant and benign obstruction]. / Cholinesterase in der Differentialdiagnostik des parenchymatischen und obstruktiven Ikterus und bei der Differenzierung maligner und benigner Obstruktion.

Determination of CHE has already been proven as a useful test in the diagnosis of liver diseases. Our investigation included 2 groups of patients: a group suffering from parenchym hepatitis caused by virus infection A and B, and a second group of patients suffering from etiologically different obstructive hepatitis (malign and benign obstruction). Our tests show that there is lower CHE activity in patients with hepatitis B. There is a remarkable difference of CHE activity in benign and malign obstructive hepatitis.

[Isoenzymes of gammaglutamyltransferase in patients with obstructive and hepatocellular icterus]. / Die Isoenzyme der Gammaglutamyltransferase bei Patienten mit obstruktivem und hepatozellulärem Ikterus.

We have been determining the GGT IE isoenzyme in patients with hepatitis A and B with decomposed liver cirrhosis, with obstructive hepatitis caused by the gall stones. In patients with hepatitis A and B the IE is located between albumin and betaglobulin, as well as in patients with obstructive hepatitis caused by the gall stones; in the latter partly between Alpha 1 and Alpha 2 globulin. In patients with decompensated liver cirrhosis (37.7% of the patients) there was IE activity 100% in Alpha 2 globulin area; in 6.25% of patients the activity was in the prealbumin area. In patients with secondary liver tumors we got a rather high increase of the GGT IE activity in Alpha 1 globulin area, in 77.7% of the patients even 80 to 100%. In some patients with disease progression we noticed the GGT IE activity in Beta globulin area. The results in primary liver malignomas were different. In 68.5% of the patients the GGT IE activity dominated in Alpha 1 globulin area.

Metabolic effects of tibolone in postmenopausal women with non-insulin dependent diabetes mellitus.

OBJECTIVE: Postmenopausal women with non-insulin dependent diabetes (NIDDM) are frequently obese, hypertensive and hyperlipidaemic and hence at particular risk of coronary heart disease (CHD). They might therefore benefit from menopausal therapy. In view of the improvement in insulin sensitivity and the reduction in triglyceride levels induced by tibolone in healthy postmenopausal women we evaluated the effects of 12 months of tibolone on glycaemic control, serum insulin and lipid levels in postmenopausal women with NIDDM. DESIGN: A prospective 12 months before/after intervention study. PATIENTS: Fourteen postmenopausal women (mean age 58.14 +/- 1.25 years; mean duration of menopause 121.21 +/- 13.42 months; mean BMI: 26.55 +/- 0.97) with NIDDM (mean duration of diabetes 113.79 +/- 13.89 months). MEASUREMENTS: Fasting and postprandial blood glucose levels were assessed monthly, serum fructosamine, fasting and postprandial insulin every 3 months and serum lipids (total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol) every 6 months. RESULTS: Changes in blood glucose, both fasting and postprandial, were not statistically significant during the treatment period. Serum fructosamine concentration increased significantly after 9 months. A significant decrease in fasting and postprandial insulin concentrations was observed after 9 months. A non-significant decrease was observed in total cholesterol, LDL cholesterol and triglyceride but no change in HDL cholesterol. Body weight did not change during the period of observation. CONCLUSION: A slight deterioration in glycaemic control, a fall in insulin concentration and no change in serum lipids were observed in women with NIDDM during 12 months treatment with tibolone.

Thyroid C cells of middle-aged rats treated with estradiol or calcium.

The structure and function of C cells of middle-aged female rats (14-months old) treated with estradiol dipropionate (EDP), calcium (Ca) or a combination of EDP+Ca were studied. A stereological method was used to determine the volume of calcitonin (CT)-immunoreactive C cells and their nuclei, and the relative volume density and mean number of the C cells per section were calculated. Serum levels of CT, osteocalcin, parathyroid hormone (PTH), and beta-estradiol were also measured. A significant decrease in body weight of the rats treated with EDP or EDP+Ca was observed. These treatments led to a significant decrease in cellular and nuclear volumes, relative volume density, and mean number of C cells per section, in comparison with the corresponding controls. A reduction of the serum level of CT, PTH, and osteocalcin was also recorded in EDP- and EDP+Ca-treated animals. No statistically significant differences between Ca- and vehicle-injected rats, with regard to all morphometric C cell parameters and biochemical values determined, were seen. However, a conspicuous degranulation of the C cells and decreased immunoreactivity for CT in the Ca-receiving group, which could be interpreted as the signs of increased activity of these cells, were noticed. This effect of Ca was also observed in rats injected with EDP and Ca in combination, when the inhibitory effect of EDP on C cell function was less noticeable than in the group treated with EDP alone.

Tick-borne encephalitis in eastern Croatia.

92 patients treated for tick-borne encephalitis (TBE) in the Department for Infectious Diseases, University Hospital Osijek, over a 22-year period (1973-1995) were analysed. The patients were mostly forestry workers. The appearance of the disease followed the biological activity of the tick, with the largest number of affected individuals recorded between April and August. TBE in eastern Croatia is a relatively frequent infectious disease, appearing almost every year. In a smaller number (9.8%) of cases the clinical picture was aseptic meningitis, while in the majority of patients (90.2%) it presented as an acute meningoencephalomyelitic form. The course was relatively severe in the majority of the patients analysed, with disturbances of consciousness (32.6%) and transitory neurological signs (61.9%). Three patients died (3.3%) in the early phase of the disease. A monophasic course dominated. The clinical and epidemiological data were compared with the cases described in other parts of Croatia and regional differences were seen in the severity of illness. These variations could be due to the previously hypothesized different virus subtypes, or to some other unknown factors.

Changes in prolactin levels with the menopause: the effects of estrogen/androgen and calcitonin treatment.

Prolactin levels were evaluated over a 2-year period in three groups of postmenopausal women: group A consisted of 35 untreated women distributed according to time since the menopause; group B consisted of 17 women on a combined estrogen/androgen preparation (Gynodian depot) intramuscularly at monthly intervals; and group C consisted of 12 women on 100 units of salmon calcitonin intranasally on alternate days and 1500 mg calcium daily. The control group (group D) consisted of 11 healthy premenopausal women. Serum prolactin, estradiol, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured at the onset and at 6-month intervals over 24 months. Mean serum prolactin concentrations decreased significantly during the second postmenopausal year in untreated women p = 0.0001 and p = 0.0000 after 18 and 24 months, respectively) when compared to either the levels in premenopausal women or those at the beginning of the menopause (p = 0.0007). Neither combined estrogen/androgen nor calcitonin therapy significantly influenced prolactin levels which were similar throughout the observed period. In the group on a combined estrogen/androgen preparation, physiological estradiol concentrations together with a suppression of gonadotropins during the first 6 months of therapy were achieved. In women treated with intranasal salmon calcitonin, estradiol, FSH and LH levels were unchanged. Our results show that prolactin levels decrease significantly during the second year of the menopause. Neither combined estrogen/androgen, nor salmon calcitonin therapy had any effect on serum prolactin concentrations in postmenopausal women.

Oral hygiene and root caries occurrence in Slovenian adults.

This study investigated root caries related findings made in connection with basic clinical dental routines. A total of 410 adults, mean age 42.8 years, seeking dental care in two Slovenian communities, rural Ravne and urban Ljubljana, during a three-month period, were clinically examined for root caries. Primary root caries was defined as a softened yellowish-brown lesion gently penetrable by an explorer and situated principally on a root surface. Past root caries was defined as fillings at a similar location. A subject's oral hygiene was judged clinically as good, fair or poor, based on presence of dental plaque and subgingival calculus. Subjects' background variables included age, gender, and number of teeth. Subjects had on average 23.1 teeth, from which 0.8 teeth had primary root caries and 0.4 had fillings on root surfaces. Primary root caries occurred in 42 per cent of subjects, in 38 per cent of men and 45 per cent of women (P = 0.21), but fillings on root surfaces in only 19 per cent of the subjects, 11 per cent of men and 25 per cent of women (P = 0.001). The strongest factors explaining the presence of root caries, with control for other factors, were poor oral hygiene (odds ratio 3.1), smaller number of teeth (odds ratio 2.3 to 2.7), and older age (odds ratio 2.1). In conclusion, in everyday clinical dental practice, more emphasis should be placed on patients' proper oral hygiene and their encouragement and motivation to achieve it.

Cardiac flow velocity in women with the polycystic ovary syndrome.

OBJECTIVE: Women with the polycystic ovary syndrome (PCOS) often have several of the known risk factors for cardiovascular disease, including hyperinsulinaemia. We have therefore investigated variables of cardiac flow in young women with PCOS and related them to blood levels of reproductive hormones (LH, FSH, oestradiol and testosterone) and also of insulin. DESIGN: A prospective study. PATIENTS: Twenty-six young women with PCOS (mean age 22.8 +/- 0.9 years; mean BMI 23.0 +/- 0.8) and 11 healthy age matched women with regular ovulatory cycles (mean age 26.3 +/- 1.7 years; mean BMI 22.9 +/- 0.9). MEASUREMENTS: Cardiac flow was measured by pulsed wave Doppler echocardiography in the follicular phase of the cycle in controls and oligomenorrhoeic women; there was no special timing for amenorrhoeic women. The indicators assessed were: ejection fraction (EF), pre-ejection time (PEP), ejection time (ET), peak systolic flow velocity (PFV), acceleration time (AT), flow velocity integral (FVI), mean acceleration (MA), diastolic time (DT), early diastolic filling time (Ei), atrial filling time interval (Ai), peak velocity of the early diastolic filling (PE) and peak velocity of the atrial filling (PA). Serum LH, FSH, oestradiol, testosterone, SHBG and insulin concentrations were analysed by standard RIA. RESULTS: Significantly lower PFV (1.055 +/- 0.025 vs 1.242 +/- 0.054, P = 0.0006) and MA (17.06 +/- 0.57 vs 23.00 +/- 1.49, P = 0.0001) and longer AT (0.063 +/- 0.001 vs 0.056 +/- 0.004, P = 0.026) were found in women with PCOS as compared to age matched controls. Significant negative correlation between serum fasting insulin concentration and EF (r = -0.725, P = 0.002), PFV (r = -0.719, P = 0.0025), FVI (r = -0.654, P = 0.008) and MA (r = -0.757, P = 0.001) was observed in the 15 women with PCOS in whom insulin was measured. CONCLUSION: An inverse relation between serum fasting insulin level and left ventricular systolic outflow parameters suggests that insulin is associated with the decreased systolic flow velocity observed in women with PCOS.

Effect of recombinant human growth hormone treatment on insulin-like growth factor (IGF-I) levels in insulin-dependent diabetic patients.

Basal and recombinant human growth hormone (rhGH)-stimulated insulin-like growth factor (IGF-I) levels were studied in 19 insulin-dependent diabetic patients and 4 healthy subjects. Diabetic patients were divided according to glucagon test result into CpN (10 patients without residual beta cell activity) and CpP (9 patients with preserved beta-cell activity) and CpP (9 patients with preserved beta-cell activity) groups, and according to age into three groups (A = 21-30 years; B = 31-40 years; C = 41-50 years). All control subjects belonged to group B. Blood glucose and growth hormone were measured at hourly intervals and IGF-I every 6 h during 24 h before and after 7 days treatment with 4 IU of rhGH given subcutaneously at 8 p.m. The age-related decrease in basal IGF-I levels was evident in both CpN and CpP groups of diabetic patients. IGF-I net increase with rhGH treatment was variable and insignificant in comparison with basal value without age-related differences in CpN diabetics. Progressively larger, age-related increases in IGF-I concentrations were observed in CpP diabetic patients. This study indicates impairment of hepatic IGF-I generation capacity in diabetic patients without residual beta-cell activity and the importance of simultaneous actions of portal insulin and GH on hepatic IGF-I production.

The effects of the somatostatin analogue octreotide on ovulatory performance in women with polycystic ovaries.

The elevated luteinizing hormone (LH) and androgen concentrations characteristic of women with polycystic ovaries (PCO) are considered crucial factors in their infertility. The somatostatin analogue octreotide lowers LH and androgen concentrations in women with PCO. The effects of octreotide given concurrently with human menopausal gonadotrophin (HMG) were therefore compared with that of HMG alone in 28 infertile women with PCO resistant to clomiphene. In 56 cycles of combined HMG and octreotide therapy there was more orderly follicular growth compared with the multiple follicular development observed in 29 cycles in which HMG was given alone (mean number of follicles > 15 mm diameter on the day of human chorionic gonadotrophin (HCG) administration: 2.5 +/- 0.2 and 3.6 +/- 0.4 respectively; P = 0.026). There was a significantly reduced number of cycles abandoned (> 4 follicles > 15 mm diameter on day of HCG) in patients treated with octreotide+HMG, so that HCG had to be withheld in only 5.4% of cycles compared to 24.1% with HMG alone (P < 0.05). The incidence of hyperstimulation was also lower on combined treatment. Octreotide therapy resulted in a more 'appropriate' hormonal milieu at the time of HCG injection, with lower LH, oestradiol, androstenedione and insulin concentrations. Although growth hormone concentration was similar on both regimens, significantly higher insulin growth factor-I concentrations were observed on the day of HCG in women on combined therapy than on HMG alone.

The effect of intranasal salmon calcitonin on biochemical parameters of bone turnover in postmenopausal women.

This study aims to evaluate the effect of intranasal salmon calcitonin on variables of bone metabolism in 12 postmenopausal women during 24 months of treatment. A treatment regime of 100 U of intranasal salmon calcitonin on alternate days and 1500 mg daily of oral elementary calcium was applied. The control group consisted of 35 postmenopausal women distributed according to time since menopause. Biochemical and hormonal evaluations of calcium metabolism were performed at the start of treatment and after 6, 12, 18 and 24 months of treatment. Mean serum osteocalcin concentration was unchanged during the 1st year of treatment but was significantly elevated during the 2nd year (p = 0.03 and p = 0.005 after 18 and 24 months, respectively) when compared to levels at 12 months. Similar elevation of osteocalcin levels was observed in untreated women during the first 12 postmenopausal months. Mean 24-h hydroxyproline excretion decreased during the first 12 months of therapy but increased in the subsequent 6 months. The observed rise in serum osteocalcin concentration and urinary hydroxyproline excretion during the 2nd year of treatment with calcitonin was accompanied by a significant rise in serum calcitonin level. No significant differences in serum calcium, phosphorus, alkaline phosphatase or parathormone concentration, or urinary calcium excretion, were observed between treated and untreated women during the 24-month period. This study shows that 12 months' treatment with intranasal salmon calcitonin decreases bone resorption in early postmenopausal women, while bone formation remains unchanged. Longer treatment with intranasal salmon calcitonin, however, seems to be ineffective, most probably due to secondary resistance to calcitonin.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of two different progestins (cyproterone acetate and norgestrel), administered in a cyclical estradiol valerate regimen, on markers of bone turnover.

It has been suggested that some progestogens could have a stimulating effect on bone formation. This study was therefore undertaken in order to compare the influence of cyproterone acetate and norgestrel on bone metabolism when administered in a discontinuous, sequentially combined regimen with estradiol valerate. Twenty healthy early postmenopausal women were randomly assigned to treatment with either Cyclo-Progynova, containing 0.5 mg of norgestrel, or Climen, containing 1 mg of cyproterone acetate (CPA), over two 28-day cycles. Markers of bone resorption-fasting urinary hydroxyproline/creatinine and calcium/creatinine ratios - and of bone formation-serum alkaline phosphatase and osteocalcin-were determined initially, before the start of treatment and thereafter twice weekly (a total of 17 assessments for each women) during the 8-week treatment period. Serum osteocalcin concentrations were slightly but not significantly higher throughout the study period in women receiving Climen, compared to those taking Cyclo-Progynova. Cyclical fluctuation of serum osteocalcin levels were more pronounced in women with a high baseline level of osteocalcin. During the period of progestogen administration, osteocalcin concentrations were either similar to or even lower than those in the phase of administration of estradiol valerate alone. Serum calcium and alkaline phosphatase concentrations were relatively stable during the study period with both treatment regimens. Urinary excretion of calcium and hydroxyproline varied during the cycle but the variation was unrelated to either type or time of progestogen administration. Mean urinary hydroxyproline excretion during the 8-week study period was similar for both preparations, although the mean decrease in the urinary hydroxyproline/creatinine ratio was insignificantly higher for the CPA-containing preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

24-hour serum cortisol profiles in women with polycystic ovary syndrome.

We studied the 24-h blood profiles of cortisol in obese and non-obese women with polycystic ovary syndrome (PCOS), for comparison with the levels in healthy women (controls). The levels of other hormones, such as androgens, which are known to be disturbed in PCOS, were also compared. Luteinizing hormone (LH) and androgen (testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS)) concentrations were significantly (p < 0.005) raised in patients with PCOS, compared to those in control women. Sex hormone binding globulin (SHBG) concentration was significantly lower in women with PCOS, particularly in those who were overweight. There was a significant negative correlation between body mass index (BMI) and SHBG concentrations (r = -0.59; p = 0.006). Mean 24-h cortisol concentrations were similar in women with PCOS and controls, as well as in the obese and non-obese PCOS patients. However, the 24-h blood cortisol profile pattern was significantly different in women with PCOS as compared to the controls (p = 0.0039). Significantly lower cortisol levels were observed during the night (levels were determined between 20.00 and 04.00 and are expressed as the area under the curve) in subjects with PCOS, compared to the control women (p = 0.02). These changes were most marked in the non-obese women with PCOS who had lower blood cortisol levels during the night than either the controls or the obese PCOS subjects. Our finding of significantly lower cortisol concentrations during the night could reflect a subtle abnormality of adrenal steroid secretion in women with PCOS.

The effect of recombinant human growth hormone on regulation of growth hormone secretion and blood glucose in insulin-dependent diabetes.

GH hypersecretion in insulin-dependent diabetes (IDDM) is well documented. Although it has recently been shown that residual insulin secretion determines the magnitude of this GH hypersecretion, the underlying mechanisms of the disorder have not yet been clarified. The 24-h GH and blood glucose profiles, insulin-like growth factor I (IGF-I) concentrations and GH responses to GRF were analyzed in 21 insulin-dependent diabetics and 4 healthy subjects before and after 7 days treatment with recombinant human GH (rhGH) (4 IU given sc at 0800 h). According to C-peptide response to glucagon IDDM patients were subdivided into C-peptide negative (CpN, n = 12) patients without endogenous pancreatic beta-cell activity and C-peptide positive (CpP, (n = 9) patients with endogenous insulin secretion. No significant difference could be observed between the mean 24-h blood glucose profile before and after rhGH treatment in any treated group. Before and on rhGH treatment the highest 24-h GH values were observed in CpN patients when compared to CpP and controls. The rhGH treatment induced a similar increase in the mean 24-h GH concentrations in all groups studied which was statistically significant only in CpP diabetics. Mean pretreatment serum IGF-I concentrations were not significantly different between CpN, CpP patients and controls. The net increase in IGF-I concentrations after rhGH treatment was however, significantly lower in CpN patients than in CpP and control subjects. GRF-induced GH response before and after rhGH treatment was significantly greater in diabetics than in controls. The response of GH to GRF in CpN diabetics was however, almost unchanged after treatment whereas it became lower in CpP diabetics and controls. The dose of 4 IU of rhGH increased significantly GH levels in diabetics with preserved beta-cell function with consequent increase in IGF-I levels and attenuation of GRF induced GH response. In contrast, the same dose of rhGH failed to induce significant increase in GH levels in diabetics without residual beta-cell activity, most probably due to already high pretreatment levels. In addition, neither increase in IGF-I levels nor suppression of GH response to GRF on rhGH treatment was observed in CpN diabetics. The results are in keeping with an important role of portal insulin in GH-induced hepatic IGF-I secretion.

Growth hormone levels in patients with type 1 diabetes are age related.

Possible effects of age on the growth hormone (GH) levels in Type 1 diabetes were examined. The study was performed in 71 patients with Type 1 diabetes (40 C-peptide negative (CpN), without residual beta cell activity; 31 C-peptide positive (CpP), with preserved beta cell activity) and 11 healthy subjects. The patients and controls were divided into three age groups (A = 21-30; B = 31-40; C = 41-50 years). Blood glucose and growth hormone (GH) were measured at hourly intervals during 24 h in all subjects in hospital conditions. GH levels decreased significantly with age in patients with Type 1 diabetes (mean 24-h GH group A: 7.3 +/- 1.0, group B:5.3 +/- 0.6, group C: 3.7 +/- 0.4 mU 1(-1); A vs C: p = 0.0007; B vs C: p = 0.03). In all age groups GH levels were significantly higher in CpN than either in CpP diabetic patients or controls (group A CpN: 8.3 +/- 1.2, CpP: 4.7 +/- 1.0, controls: 2.2 +/- 0.3 mU 1(-1); p < 0.001; group B CpN: 7.3 +/- 0.8, CpP: 3.2 +/- 0.5, controls: 1.6 +/- 1.0 mU 1(-1); p < 0.0002; group C CpN: 5.2 +/- 0.5, CpP: 2.5 +/- 0.4, controls: 1.4 +/- 0.4 mU 1(-1); p < 0.001). Mean GH levels were significantly higher in C-peptide positive patients than in controls in all age groups (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)