The effect of cimetidine on ethanol concentrations in fasting women and men after two different doses of alcohol.

BACKGROUND: Serum ethanol concentrations may become higher when alcohol is consumed during treatment with histamine receptor antagonists, especially if ethanol is ingested postprandially. Only a few studies have investigated fasting subjects, and women have only been investigated sporadically. METHODS: The present study compared serum ethanol concentrations after a 4-h fast followed by a low (0.15 g/kg) and a high (0.45 g/kg) dose of ethanol, on two separate occasions in six women and six men. The study was carried out before and after treatment with 400 mg cimetidine twice daily. RESULTS: Cimetidine administration did not change the area under the concentration-time curve or the maximal serum ethanol concentration in either women or men, irrespective of ethanol dose. Ethanol elimination rate was unchanged by cimetidine. CONCLUSION: Cimetidine does not influence the ethanol concentration-time curve when ethanol is ingested on an empty stomach.

Working capacity and expression of myosin heavy chain isoforms in skeletal muscle of chronic alcoholic men without liver disease after 1 day and 4 weeks of alcohol abstinence.

1. The aim of this study was to examine the effect of chronic alcohol ingestion on working capacity and on the expression of myosin heavy chain isoforms in fibre types of human skeletal muscle. 2. Six alcoholic men having drunk more than 240 g of alcohol/day for more than 10 years underwent a test for working capacity and a muscle biopsy on the first day of alcohol abstinence (test 1) and again after 4 weeks of abstinence (test 2). The biopsies were analysed using histochemical, immunochemical and gel-electrophoretic techniques, and the results were compared with those from eight age-matched non-alcoholic control subjects. 3. The area of type IIB muscle fibres was decreased by 33% in the alcoholic patients compared with normal control subjects at both test 1 and test 2. The area of type IIA fibres was lower (13%) in alcoholic patients at test 1 than in the control group, and increased to the normal level at test 2. 4. The relative proportion of fibres expressing only myosin heavy chain type IIB isoforms was one-third of normal in the alcoholic patients at both tests 1 and 2. The relative proportion of fibres expressing only myosin heavy chain type IIA isoforms was the same in alcoholic patients at test 1 and in normal control subjects, but increased by 25% between test 1 and 2 in the alcoholic group.(ABSTRACT TRUNCATED AT 250 WORDS)

[Adrenal cortex function in patients with AIDS and healthy HIV-positive persons]. / Binyrebarkfunktionen hos AIDS-patienter og raske HIV1-positive personer.

Adrenal function was estimated by synthetic ACTH test in 18 men with AIDS (or AIDS-related complex) and compared with that of 10 HIV positive but otherwise healthy men. According to this test none fulfilled the criteria for adrenal insufficiency defined as plasma cortisol concentration less than 500 nmol/l 30 minutes after ACTH stimulation. Seven of eighteen AIDS patients had baseline cortisol concentrations above 0.5 mumol/l compared to none in the HIV-positive group. Three of eighteen AIDS patients had a limited response to synthetic ACTH injection compared to none in the HIV-positive group. Two of these three AIDS patients had lowered serum Na+ concentration; they survived for two and three weeks, respectively. Otherwise the basal cortisol level and response to synthetic ACTH was uncorrelated with survival time, other signs of adrenal insufficiency, treatment with ketokonazole, CMV-infection, T-helper cell count or Th/Ts-ratio. The pituitary-adrenal axis was estimated by measuring the diurnal rhythm of serum ACTH and cortisol in eight patients and was found intact and normal in all of them. Thus, absolute adrenal insufficiency is uncommon in AIDS-patients. Relative adrenal insufficiency may occur in severely ill preterminal patients as a result of primary target organ failure, but the pituitary-adrenal axis generally appears to be undisturbed.

Responses of glucose and glucoregulatory hormones to exercise in thyrotoxic and myxoedematous patients before and after 3 months of treatment.

1. The effect of moderate endurance exercise on blood glucose concentration and on glucoregulatory hormones was studied in nine thyrotoxic and five myxoedematous humans before and 3 months after anti-thyroid and substitution therapy, respectively. 2. At rest, the fasting concentrations of insulin and pro-insulin correlated positively with the prevailing total tri-iodothyronine concentration, whereas the concentrations of noradrenaline and cortisol correlated inversely with the tri-iodothyronine concentration. 3. During exercise the plasma insulin, pro-insulin and C-peptide concentrations decreased. The plasma glucagon concentration increased slightly in thyrotoxic patients before and after treatment and was largely unchanged in myxoedematous patients in either state. 4. The plasma noradrenaline concentration increased before and after treatment in both groups, with concentrations two times higher in the myxoedematous than in the thyrotoxic patients. Treatment for 3 months did not change this pattern. The plasma adrenaline concentration increased in both groups, but in the untreated thyrotoxic patients the increase was two to three times greater than that after treatment or that in the myxoedematous group. 5. The blood glucose concentration decreased in eight of nine untreated thyrotoxic patients, but was largely unchanged after treatment or in the myxoedematous patients. A strong negative correlation was found between the decline in blood glucose concentration and the increase in plasma adrenaline concentration in the thyrotoxic group. 6. Thus, during exercise untreated thyrotoxic patients are prone to hypoglycaemia, show an inadequate glucagon response, and exhibit a large counter-regulatory increase in plasma adrenaline concentration.

Thyroid function tests in patients with acquired immune deficiency syndrome and healthy HIV1-positive out-patients.

The thyroid function tests as well as evidence of thyroiditis were studied in 18 male patients with acquired immune deficiency syndrome (AIDS) and 12 healthy HIV1-positive persons compared with an age-matched control group. Serum total thyroxine was not significantly different between the groups, but both serum total triiodothyronine, triiodothyronine uptake test, and free thyroid hormone indices showed significantly decreasing values from HIV1-positive healthy persons to AIDS patients compared with controls (P value from less than 0.05 to less 0.001). Serum TBG was elevated in HIV1-positive subjects and in patients with AIDS, with a significant inverse correlation with the T3-uptake test (Spearman's rho = 0.657, P less than 0.01). There was no correlation between thyroxine binding globulin and the other measured variables. The serum level of thyrotropine was not significantly different in the groups, whereas serum thyroglobulin was significantly lowered in the AIDS group. There was no correlation between thyroid function variables and survival time, hepatic function and ratio of T-helper to T-suppressor cells. No evidence of thyroiditis was observed. In conclusion thyroid tests showed an atypical outcome in HIV1-positive patients with or without AIDS compared with the pattern normally seen in non-thyroid illness, and should, therefore, caution the interpretation of the biochemical changes when diagnosing abnormal thyroid function in these patients.

Lactate balance in perfused rat liver: effects of glucose concentration, flow and low pH on glucose to lactate flux.

The effects of medium glucose concentration (0-20 mmol l-1), pH (7.4 and 6.8) and flow (100 to 33% normal) on lactate uptake and glycolytic flux from 6-3H glucose were studied in perfused livers from 48-h starved rats. At both pH values, the glycolytic flux increased proportionally with the medium glucose concentration. Maximum glycolytic flux at 20 mmol l-1 glucose in the medium was 0.5 mumol min-1 g-1 liver (C6-units) at pH 7.4. At pH 7.4 and 20 mmol l-1 glucose the glycolytic flux decreased approximately proportional with flow. At pH 6.8 the glycolytic flux was extremely low and independent of flow. At flow 33% normal and pH 7.4 a net lactate production was accounted for by glycolysis from medium glucose concentration, indicating virtually no simultaneous lactate uptake. In contrast, at pH 6.8 net lactate production accounted for only half the glycolytic rate, indicating that lactate uptake occurred simultaneously with glycolysis. Thus, glucose-to-lactate flux in liver (as in muscle and brain) is subject to inhibition by low pH, and lactate uptake is enhanced by low pH.

Mechanisms of changes in K+ balance on reduction and reestablishment of flow in isolated rat liver.

The effects of low flow and reestablished normal flow on K+ balance and carboxylic acid balance was studied in perfused liver of 48-h starved rats at perfusate pH 7.4 and 6.8. The rate of net K+ release induced by ouabain was 1.8 mumol.min-1.g-1 at pH 7.4 and 1.4 mumol.min-1.g-1 at pH 6.8. Lowering of flow to 30% normal was accompanied by a transient, diphasic loss of K+ (max 0.15 mumol.min-1.g-1). Reestablished normal flow was immediately accompanied by a monophasic K+ uptake (max 0.35 mumol.min-1.g-1). These changes in potassium balance were independent of perfusate pH. Reduction of flow caused an almost immediate depolarization of 4 mV followed by a steady tendency to repolarization. Reestablished normal flow induced a transient hyperpolarization. Production of carboxylic acids during the low flow period did not correlate with the diphasic time course of K+ loss, and carboxylic acid uptake after reestablishment of flow did not correlate with the transient uptake of K+. The data show that the initial phase of K+ loss during low flow is due to inhibition of the Na(+)-K(+)-pump; the second phase may be reasonably explained by increased K+ permeability concomitant to cellular volume regulation.

Regulation of lactate uptake and lactate production in liver from 48-h-starved rats: effects of pH, flow and glucose concentration.

1. The effects of medium glucose concentration (0-20 mmol/l) and flow (100-33% of normal) on lactate uptake at low lactate concentration were studied in perfused livers from 48-h-starved rats with perfusate pH values of 7.4 and 6.8. 2. Lactate uptake was independent of glucose concentration in the range 5-10 mmol/l, but was slightly inhibited with time at 20 mmol/l glucose. This pattern was independent of perfusate pH. 3. At both pH values lactate uptake decreased proportionally with flow, and at low flow lactate was produced by the livers. The effect of flow was greatest at pH 7.4 where a net lactate production was found at 48% of normal flow, whereas at pH 6.8 lactate production was not seen until the flow was reduced to 33% of normal. 4. When glucose was omitted from the perfusate lactate production ceased at both pH values. 5. The effect of low pH on lactate uptake and production in liver probably reflects inhibition of glycolysis by low pH.

The low physical working capacity of thyrotoxic patients is not normalized by oral antithyroid treatment.

The low working capacity in thyrotoxic patients has not been quantified and its causes have not been clarified. We studied the working capacity in nine thyrotoxic patients at diagnosis (test 1), after 3 months of oral antithyroid medication (test 2), and in four of them again after 1 year (test 3). The maximum power output was low in thyrotoxic patients (1.65 +/- 0.15 W/kg-1) and was not significantly higher after 3 months of treatment (1.84 +/- 0.15), although plasma thyroid hormone concentrations had been normalized for approximately 3 months. After 1 year's treatment the maximum power output was still somewhat low in the four tested patients (2.75 +/- 0.34). The rate of oxygen uptake under maximum exercise was low (26 ml/min-1/kg-1) and was not significantly increased at test 2 and 3. The net mechanical efficiency was low at test 1 and 2 (18.9 +/- 2.1% and 20.1 +/- 1.8%, respectively), but was normal at test 3 (25.2%). At all three tests the blood lactate response upon maximum exercise attained only about 50% of normal concentration. Thus, low work capacity in thyrotoxic patients remained for a long period of time after euthyroid conditions had been attained. The low capacity was due to low aerobic and anaerobic capacities and initially also to a low mechanical efficiency.

Blood-retinal barrier permeability versus diabetes duration and retinal morphology in insulin dependent diabetic patients.

The blood-retinal barrier permeability to fluorescein was quantitated in 54 patients (22 females and 32 males) with insulin dependent diabetes mellitus (IDDM) of different duration. Correlation was demonstrated between permeability and diabetes duration. A normal permeability was measured in patients with up to ten years diabetes duration. A pathologically increased permeability was measured with ten to 15 years diabetes duration and during the next decade the permeability increased rapidly to 5-10 times the normal value. Onset of diabetes in the decade before and after puberty did not change the pattern. However, the pathologically increased permeability after ten years duration of the disease could not be demonstrated in diabetics with onset of the disease after the age of 30 years. The permeability of the blood-retinal barrier correlated well with changes in retinal morphology as seen by ophthalmoscopy and fluorescein angiography. However, there was an overlap in permeability between groups with different retinal appearance. A significant factor was the presence of macular edema, which also apparently indicated a preproliferative state.

Heart rate response to breathing: dependency upon breathing pattern.

Heart rate responses to stepwise and periodic changes in lung volume were studied in seven young healthy males. Stepwise inspiration and expiration both resulted in an increase in heart rate followed by a rapid decrease in heart rate. The fastest heart rate was reached in 1.6 +/- 0.5 s and in 3.6 +/- 1.4 s in response to inspiration and expiration, respectively (P less than 0.01). The slowest heart rate was reached in 4.8 +/- 1.0 s and in 7.6 +/- 1.9 s in response to inspiration and expiration, respectively (P less than 0.01). Following this biphasic change the heart rate returned to a steady level. The difference between the fastest and the slowest heart rates was significantly larger in response to inspiration (21.7 +/- 7.3 beats per minute) than in response to expiration (12.0 +/- 7.3 beats per minute; P less than 0.01). Periodic changes in lung volume were performed with frequencies from 3.0 to 12.0 respirations per minute (r.p.m.). The changes in heart rate showed a constant amplitude in the frequency range below 5.5 r.p.m. Maximal heart rate changes were found at frequencies of 5.5 to 7.0 r.p.m. Changes in heart rate decreased in a linear manner on a log-log scale in the frequency range above 7.0 r.p.m. The relation between frequency and changes in heart rate is explained by interference between the transient changes in heart rate induced both by inspiration and by expiration. It is concluded that if heart rate changes in response to periodic changes in lung volume are to be used as a measure of vagal function a number of factors have to be taken into consideration and to simplify the analysis of heart rate responses to breathing we recommend, instead, the use of the transient changes in heart rate induced by stepwise changes in lung volume.

Combined adrenal myelolipoma and adenoma associated with Cushing's syndrome.

A case of Cushing's syndrome in a 31-year-old woman is presented. The resected left adrenal gland revealed a tumor consisting of cortical cells intermingled with myelolipomatous tissue comparable to that of normal bone marrow. The adjacent cortex was atrophic. Postoperative plasma cortisol concentrations have remained quite low. Previously, 28 cases of surgically removed adrenocortical tumors with a main diagnosis of myelolipoma have been published. Of these, three cases (two pituitary Cushing's disease, one steroid 21-hydroxylase deficiency) were associated with endocrine dysfunction. The combination of a myelolipoma and a true adenoma has only been described once before (in a case of virilization) and never in connection with Cushing's syndrome. The etiology of myelolipoma is discussed, and a local trigger mechanism related to adrenocortical growth disturbances is suggested.

Illness-behaviour, attitude, and knowledge in newly diagnosed diabetics.

Sixty-five consecutive patients with newly diagnosed type I diabetes, aged 15-52, were exposed to a systematic educational programme and followed up by three-monthly controls for two to four years. In order to identify psychic, social and behavioural factors associated with good metabolic control and appropriate adaptation to illness, they were clinically tested and filled in a questionnaire. The study shows that the illness and the therapeutic regime created few problems regarding practical circumstances of daily living, but there were a vast number of psychological problems: perceived disability, fatigue, fear, anger, strain, bad conscience, and perceived discrimination. The patients assessed the treatment regimen they had been taught as fair, but still the majority reported inadequate compliance and problems in relation to compliance, especially regarding dietary restrictions. The educational programme was evaluated by the patients as useful and satisfying. Actual illness-related knowledge, skills and compliance were not closely associated, suggesting that knowledge itself is an insufficient precondition to appropriate management of the illness. Social class and other social environment factors were not associated with illness-related behaviour and attitudes and neither was metabolic control. There were no psychological or social differences between the patients with good and those with poor control. A possible interpretation of these findings is that an increase of quality of life in diabetic patients requires separate efforts to increase metabolic control and to create appropriate psycho-social adjustment to the change in life situation.

The blood-retinal barrier permeability to fluorescein in normal subjects and in juvenile diabetics without retinopathy.

The blood-retinal barrier permeability to fluorescein was determined in 20 eyes from 17 normal volunteers (mean age 31 years) and in 20 eyes from 19 juvenile diabetics without apparent retinopathy (mean age 35 years - mean duration of diabetes 6 years). The permeability was in normal subjects (1.1 +/- 0.4) X 10(-7) cm/sec (mean +/- 2 X SD) and in juvenile diabetics (1.1 +/- 0.7) X 10(-7) cm/sec (mean +/- 2 X SD). Thus a break-down of the blood-retinal barrier cannot be demonstrated as a very early and general phenomenon in the early course of the diabetic disease. The fluorescein diffusion coefficient in the vitreous body was determined and juvenile diabetics without apparent retinopathy showed a diffusion coefficient of (0.80 +/- 0.25) X 10(-5) cm2/sec (mean +/- 2 X SD), which was the same as in normals where the diffusion coefficient was (0.69 +/- 0.46) X 10(-5) cm2/sec (mean +/- 2 X SD).

Hepatic lactate uptake is enhanced by low pH at low lactate concentrations in perfused rat liver.

The effect of pH on lactate uptake was studied in perfused liver of rats starved for 48 h. At both low pH (6.8) and normal pH (7.4) lactate uptake was a linear function of lactate concentration in input medium in the range 0.4-1.5 mmol/l. In the lower concentration range (0.4-0.8 mmol/l) the rate of lactate uptake was 30% higher at pH 6.8 than at pH 7.4. At pH 6.8 lactate uptake was independent of whether PCO2 was 2.7 or 5.3 kPa. We suggest the increased rate of lactate uptake at low pH and concentrations lower than 0.8 mmol/l was due to the stimulatory effect of H+ on the lactate carrier.

Diffusion and polymerization determines the insulin absorption from subcutaneous tissue in diabetic patients.

In 23 diabetic patients, the disappearance from subcutaneous tissue of 125I-labelled short-acting insulin and of 133Xe (measuring subcutaneous blood flow (SBF] were registered simultaneously. Alterations in the SBF were produced either by orthostatic changes or by application of local heat or cold. The insulin absorption rate was related to the SBF in a curvilinear way with an almost linear relation at SBF below 2-3 ml . (min . 100 g)-1, whereas at SBFs above the value the insulin absorption rate increased less than proportional to SBF. Capillary diffusion capacity of the injected insulin was 0.0145-0.0874 ml . (min . 100 g)-1; indicating that insulin is absorbed in a polymeric form. This was supported by studies of insulin diffusion in agar gel at 37 degrees C, showing that insulin in the normal pharmacological concentration diffuses as a molecule of about 46,000 MW. In conclusion, the absorption of short-acting soluble insulin is curvilinearly related to the SBF. This can be explained by a diffusion-limited transport of insulin in the interstitial space, and increasing transcapillary transport of insulin at increasing blood flow rates caused by recruitment of capillaries, thus increasing exchange surface area and decreasing diffusion distance.

Mild mental stress in diabetes: changes in heart rate and subcutaneous blood-flow.

A TV-game of tennis of 20 min duration was used to study the influence of mild mental stress on subcutaneous blood-flow (SBF), blood-pressure and heart rate in nine insulin-dependent diabetics and nine healthy subjects. SBF was measured on the thigh by local clearance of xenon-133. Measurements were made before, during and after the period of stress. During stress, SBF increased significantly by 26% in the healthy subjects, while SBF remained unchanged in the diabetics. The difference between the two groups was significant (P less than 0.05). Following stress, SBF returned to pre-stress level in the healthy subjects, while a significant decrease of 33% was observed in the diabetics. The pre-stress heart rate level was higher and the stress-induced increase in heart rate was less in the diabetics compared with the healthy subjects (P less than 0.05). During the stress a slight--but insignificant--increase in blood-pressure was observed in both groups. In conclusion, we found that even mild mental strain influences SBF in both normal subjects and in diabetics. The induced alterations in the two groups are different, probably because of a slight parasympathetic dysfunction in the diabetics.