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Biomedical subjects

E Christiansen

Publications and source records attributed to E Christiansen.

At least 37 records · Page 2Linked to original sources

Day-to-day and within-day variation in urinary iodine excretion.

OBJECTIVE: To examine the day-to-day and within-day variation in urinary iodine excretion and the day-to-day variation in iodine intake. DESIGN: Collection of consecutive 24-h urine samples and casual urine samples over 24h. SETTING: The study population consisted of highly motivated subjects from our Institute. SUBJECTS: Study 1: Ten healthy subjects (seven females and three males) aged 30-46 y. Study 2: Twenty-two healthy subjects (9 males and 13 females) aged 30-55 y. METHODS: Study 1: 24-h urine samples were collected for four consecutive days. Study 2: Each urine voided over 24 h was collected into separate containers. In both studies dietary records were kept. MAIN OUTCOME MEASURES: Twenty-four-hour urinary iodine excretion, 24-h urinary iodine excretion estimated as I/Cr*24 h Cr and as a concentration in casual urine samples. RESULTS: Study 1: Both iodine excreted in 24-h urine and iodine intake varied from day-to-day. Iodine excretion correlated with iodine intake (=-0.46, P=0.01). Iodine intake (mean 89 +/- 6.5 microg/d) was not significantly different from iodine excretion (mean 95 +/- 5.3 microg/d). Study 2: Twenty-four hour iodine excretion estimated as I/Cr*24 h Cr from the morning urine sample was significantly lower than actual 24-h iodine excretion, whereas 24-h iodine excretion estimated as I/Cr*24 h Cr from the first sample after the morning sample and the last sample before the subjects went to bed was not significantly different from actual 24-h iodine excretion. Twenty-four-hour urine excretion estimated as a concentration was lower than actual 24-h iodine excretion in casual urine taken at any time of the day. CONCLUSIONS: For determination of iodine status in an individual, more than one 24-h urine sample must be used. The use of the I/Cr ratio in casual urine samples is a usable measure of iodine status if corrected for the age- and sex-adjusted 24-h creatinine excretion. Further, the study suggests that fasting morning urine samples would underestimate iodine status in this population.

Adult↗

Intracavernosal therapy for erectile failure--impact of treatment and reasons for drop-out and dissatisfaction.

OBJECTIVES: To examine the impact of intracavernosal therapy on libido, ejaculatory control, quality of life and treatment dependency in men with erectile failure. Furthermore to assess the drop-out rate and reasons for dissatisfaction with the technique. SUBJECTS AND METHODS: Questionnaires were sent to 1116 subjects with erectile failure who had previously elected to use intracavernosal therapy in the period 1995-1997. RESULTS: The response rate was 72.5%. The majority of erections lasted 30-60 min, 10-20% of the erections were considered unsatisfactory for intercourse and 15% of subjects reported erections lasting longer than 5 h on at least 10% of the occasions. Bleeding at the injection site occurred in 60% on at least 10% of the occasions and various degrees of deformation of the penis shaft were reported by 10%. The latter was related to the age of the subject and not the type of medication employed. Forty percent experienced at least partially improved control over ejaculation and almost 50% experienced some degree of increase in libido. One quarter retained penile rigidity after ejaculation but this was age-dependent. In those satisfied with intracavernosal treatment, 80% admitted that it had improved the quality of their lives. Sixty percent did not feel that their dependency on intracavernosal treatment had lessened during the treatment period. Approximately 40% of subjects admitted to dropping out of the programme, the majority within the first six months. The age of the subject did not influence the decision and the type of medication or the mode of injection had only a minor impact on drop-out rate. Of those currently using IC therapy, 87% were either fully or partly satisfied with this form of treatment. The corresponding figure for those discontinuing treatment was 58%. Dissatisfaction was higher in the younger age groups and could not be clearly related to the mode of injection. The major reasons for drop out or dissatisfaction were inadequate penile rigidity, the expense of the treatment, penile discomfort and the lack of spontaneity it necessitated. Penile discomfort was more associated with younger age groups, whilst an inadequate response to medication was more often experienced by men over 60 y. Deformation of the penile shaft was observed in 5% of those dissatisfied with IC therapy and was four times more often reported by those over 70 compared to subjects younger than 40 y. In 6% of cases, a return of spontaneous erections was given as reason for drop-out. This was more often associated with younger subjects. In 16% of the subjects, the partner had expressed dissatisfaction with the technique primarily because of inadequate rigidity, lack of spontaneity or the complicated nature of the treatment. CONCLUSIONS: Intracavernosal treatment for erection failure is associated with side-effects such as penile fibrosis and bleeding at the injection site but has advantages including increased libido, an increase in the quality of life and ejaculatory control. Only a small proportion of men reduce their dependency on the technique with time. The therapy has a relatively high attrition rate. In many cases, the reasons for subject and partner dissatisfaction are potentially correctable e.g. by altering the medication used, by the use of injector devices or by obtaining financial support for IC medication from medical welfare.

Adult↗

The prevalence of thyroid dysfunction in a population with borderline iodine deficiency.

OBJECTIVE: We lack information on the influence of borderline iodine deficiency on the occurrence of thyroid dysfunction. Iodine deficiency has been reported to facilitate the development of toxic nodular goitre, whereas a high iodine intake may increase the prevalence of autoimmune hypothyroidism. SUBJECTS AND METHODS: In a cross-sectional study of a random sample of the general population in our region with borderline iodine deficiency 2656 (65%) of 4073 men and women aged 41 to 71 years participated. Records were made of previous thyroidal illness. Blood samples were drawn for thyroid parameters and TPO Ab values. Iodine and creatinine was assessed in casual urine samples. RESULTS: Previous or present hyperthyroidism was reported by 1.4% of the participants whereas 0.6% had unknown biochemical hyperthyroidism. All cases of undiagnosed hyperthyroidism were among women. Previously diagnosed and treated hypothyroidism was reported by 1.0% and undiagnosed hypothyroidism was found in 0.4%. Subclinical hyperthyroidism was found in 1.3% and subclinical hypothyroidism in 0.7%. TPO Ab titres >200 kU/l were found in 16.9% of the women and 6.6% of the men, and 83% of participants with TSH >5 mU/l had TPO Ab titres >200 kU/l. Participants with TPO Ab titres between 100 and 200 kU/l had no increased frequency of thyroid dysfunction. The median iodine excretion rate was estimated as 103 microg/day. Serum TSH values were higher in women than in men and showed higher dispersion in women as well as in old age. Serum free T3 was found to be higher in women than in men and increased with age. Serum free T4 showed no sex difference but values increased with increasing age. CONCLUSION: In our region with borderline iodine deficiency more than 5% of the general population has clinical or subclinical thyroid dysfunction. We found a relatively high prevalence of hyperthyroidism, especially previously undiagnosed disease, but a low prevalence of hypothyroidism as would be expected in an area of iodine deficiency. Hypothyroidism was related to TPO Ab titres of >200 kU/l. Thyroid hormone levels varied with age and sex.

Adult↗

Induced resistance to pathogenic fungi in norway spruce

Norway spruce (Picea abies) trees (approximately 16 m high) of a single clone were used to study the effects of fungal infection and wounding on induction of resistance to the bark beetle-associated bluestain fungus Ceratocystis polonica. A dose-response experiment was designed involving three different dosages of fungal (fungus and wound) and sterile agar (wound) pretreatment inoculations (10, 50, or 100 inoculations/m(2) on the stem between 0.8 and 2.0 m high). Three weeks after pretreatment, trees were challenged with a massive C. polonica inoculation (400 inoculations/m(2)). Control trees that received no pretreatment were heavily colonized and killed by the challenge inoculation. The high and medium fungal pretreatments reduced subsequent fungal colonization success by 76% to 97% relative to the control, and fungal pretreatments protected the trees much more efficiently than sterile agar pretreatments. The protection was demonstrated to be local and not systemic in a subsequent experiment, where trees were pretreated with the medium fungal dosage on the lower bole and challenge inoculated further up the stem. Protection was also demonstrated to be pathogen nonspecific, as trees that had been pretreated with a medium dosage of the root rot fungus Heterobasidion annosum showed enhanced resistance to challenge inoculation with C. polonica.

Journal Article↗

Effect of pancreas transplantation and immunosuppression on proinsulin secretion.

Insulin resistance and increased demand for insulin secretion occur after successful pancreas transplantation. To investigate the potential effects of immunosuppression and pancreas transplantation on fasting beta-cell function, we studied fasting proinsulin and 32,33 split proinsulin secretion cross-sectionally and longitudinally in segmental pancreatic graft recipients (SPx, n = 18); in whole-pancreas graft recipients (WPx, n = 13); in nondiabetic kidney transplant recipients (Kx, n = 14) and in normal subjects (Ns, n = 14). Basal insulin secretion rates were significantly increased in SPx 15.8 (1.7), WPx 24.4 (4.5) and Kx 22.1 (2.1) vs Ns 9.7 (1.6) pmol min(-1) l(-1), p < 0.05, mean (SEM). Total proinsulin, intact proinsulin and 32,33 split proinsulin concentrations were significantly higher in all the transplanted groups than in normal subjects (p < 0.05), whereas the total proinsulin to C-peptide ratio and the 32,33 split proinsulin ratio were higher in SPx than in WPx, Kx and Ns (< 0.05). In the longitudinal study, beta-cell function in terms of proinsulin secretion remained stable for 1 year. In conclusion, fasting glucose homeostasis in pancreas-kidney transplant recipients is obtained at the expense of increased proinsulin secretion and increased insulin secretion rates, primarily induced by immunosuppression. In segmental pancreas graft recipients, increased fasting proinsulin and 32,33 split proinsulin relative to the number of beta-cells transplanted indicate more stress on the residual beta-cell and therefore higher secretory demand than in whole pancreas transplant recipients.

Adult↗

Insulin secretion rates estimated by two mathematical methods in pancreas-kidney transplant recipients.

After pancreas-kidney transplantation, it is difficult to obtain an accurate estimate of the insulin secretion of the pancreas graft, since several pitfalls are involved using peripheral C-peptide and/or insulin measurements in this determination. In this study, the individual kinetic parameters of C-peptide and then the rates of insulin secretion were estimated by two mathematical methods, the deconvolution method and the "combined model" during slow (oral glucose) and fast (intravenous glucagon) changes in insulin secretion in six successful pancreas-kidney transplant recipients with systemic delivery of insulin (Px), six nondiabetic kidney-transplant recipients with portal insulin secretion (Kx), six nondiabetic controls (NS), and six C-peptide-negative insulin-dependent diabetes mellitus patients (IDDM). Decreased C-peptide clearance and basal and poststimulatory hyperinsulinemia were found in both Px and Kx compared with NS (P < 0.05). Similar glucose responses were observed after intravenous glucagon in all groups, whereas the responses after oral glucose were 30% higher in Px and Kx than in NS (P < 0.05). During oral glucose and after intravenous glucagon, both mathematical methods resulted in significantly lower maximal and incremental insulin secretion rates (ISR) in Px than in Kx (P < 0.05). In contrast, calculations of incremental ISR in NS and Px induced by the two beta-cell stimuli were about the same but significantly higher in Kx than in NS (P < 0.05). These results differed markedly from those obtained using peripheral measurements of insulin and C-peptide alone. In conclusion, when C-peptide clearance and insulin metabolism change, such as in pancreas-kidney transplant recipients, accurate evaluation of insulin secretion from the graft can be obtained only by using individual kinetics of the peptides before calculating the ISR. This study also clearly demonstrates that insulin secretion after pancreas transplantation is still defective.

Adult↗

Glucose metabolism, lipid metabolism, and cardiovascular risk factors in adult Turner's syndrome. The impact of sex hormone replacement.

OBJECTIVE: To examine glucose metabolism, blood pressure, physical fitness, and lipid metabolism in adult untreated women with Turner's syndrome compared with a group of normal women and to examine the effects of female sex hormone substitution on these factors. RESEARCH DESIGN AND METHODS: A total of 26 patients with Turner's syndrome were examined before and during sex hormone replacement with 17 beta-estradiol and norethisterone, and an age-matched control group (n = 24) was examined once. A frequently sampled intravenous glucose tolerance test was applied with minimal model assessment. We also performed an oral glucose tolerance test, measurement of 24-h ambulatory blood pressure, and assessment of physical fitness and lipid metabolism. RESULTS: Insulin sensitivity (SI) and glucose effectiveness (SG) were similar in Turner's syndrome patients and control subjects, whereas the acute insulin response (P = 0.03) was lower in Turner's syndrome patients, and no change was seen during sex hormone treatment. Abnormal glucose tolerance was found in 50% of Turner's syndrome patients before and 78% during treatment with sex hormones. Fat-free mass (FFM; P = 0.0005) and physical fitness (P = 0.002) were lower in Turner's syndrome subjects compared with control subjects. During treatment, an increase in FFM (P = 0.001) and physical fitness (P = 0.02) was seen in Turner's syndrome patients. Blood pressure was increased in Turner's syndrome, and a decrease was seen in diastolic blood pressure during treatment with sex hormones. CONCLUSIONS: Turner's syndrome is associated with glucose intolerance, diminished first-phase insulin response, elevated blood pressure, reduced FFM, and physical fitness. Sex hormone administration causes a deterioration in glucose tolerance, increases FFM and physical fitness, and has beneficial effects on blood pressure. The deleterious effect on glucose tolerance may be mediated by norethisterone, a gestagen known to have androgenic effects.

Administration, Oral↗

Discrepancies between thyrotropin (TSH) measurement by four sensitive immunometric assays.

A comparison of four different commercial immunometric thyrotropin (TSH) assays (Amerlite R TSH-30 Ultrasensitive assay from Kodak, BeriLux R hTSH from Behring Werke, Delfia R hTSH Ultra from Wallac and IMX R Ultrasensitive hTSH from Abbott) was made by measuring serum TSH in 81 consecutive patients referred to hospital for various reasons with a serum TSH less than 0.8 mlU/l in the IMX assay. The analytical and functional assay sensitivities of each of the assays were analysed. Even though three of the methods had a sensitivity corresponding to third generation assays, we could only demonstrate an overall agreement of serum TSH when comparing two of the kits. The measurements in Delfia Ultra and Berilux showed good agreement (P = 0.7, paired t-test and bias = 0.003 mIU/l), while the comparisons between the other assays showed different measurements (P < 0.00001, paired t-test and bias more than 0.07 mIU/l). Differences in the calibrators used in the assays might explain some of the discrepancy, although all methods were calibrated according to the same international standard. Also, differences in the specificity of the TSH monoclonal antibodies used in the assays might be an evident explanation and further studies of the specificity of the monoclonal antibodies are needed. An international collaborative study to clarify reasons for the differences between the TSH assays and to standardize the measurements is recommended.

Adolescent↗

Insulin resistance in cardiac syndrome X and variant angina: influence of physical capacity and circulating lipids.

Insulin resistance has been demonstrated in patients with angina pectoris irrespective of detectable atherosclerosis at coronary angiograms. We compared insulin sensitivity, lipid profiles, and exercise capacity in 20 patients with syndrome X, 15 patients with variant angina, and 20 healthy controls to investigate whether the presentation of the insulin resistance syndrome differs between the two patient groups with disparate vascular abnormalities. All patients had angiographically normal coronary arteries. Maximal oxygen uptake (VO2 max) was determined at bicycle exercise testing. Insulin sensitivity (SI) was assessed by the minimal model analysis of the intravenous glucose tolerance test. Patients with variant angina had significantly lower VO2 max than controls (mean +/- SE, 25.6 +/- 1.5 vs 30.6 +/- 1.4 ml x kg-1 x min-1, p < 0.05), whereas VO2 max in patients with syndrome X was intermediate (27.1 +/- 1.3 ml x kg-1 x min-1). Compared with controls, patients with syndrome X and variant angina had reduced insulin sensitivity (controls, 1.47 +/- 0.16 10(-4) x min-1/per pmol/L vs syndrome X, 0.86 +/- 0.11 10(-4) x min-1 per pmol/L and variant angina, 0.96 +/- 0.15 x 10(-4) x min-1 per pmol/L; analysis of variance, p < 0.05). Only patients with syndrome X exhibited fasting hyperinsulinemia. Patients with syndrome X also had higher fasting concentrations of triglycerides and total cholesterol and lower concentrations of high-density lipoprotein cholesterol than controls. When adjusting SI for variances of VO2 max, differences in SI vanished between controls and patients with variant angina but not between controls and patients with syndrome X. Thus syndrome X and variant angina are both associated with insulin resistance, but lipid abnormalities are only prominent in patients with syndrome X. A variable expression in terms of concomitant disturbances of lipid profiles and disparate influences of physical capacity suggests different underlying mechanisms.

Angina Pectoris, Variant↗

Increased risk of stress fractures of the ribs in elite rowers.

In rowing, stress fractures are rare. However, the intensity of training has increased in terms of more specific rowing movements throughout the year. Simultaneously, new equipment has been developed resulting in faster rowing over the racing distance with increased risk of injuries on bones, muscles and ligaments. We report five cases of chest pain and one case of pain in the shoulder in national elite rowers, diagnosed as stress fractures of the ribs employing 99mTechnetium-MDP bone scan. In all cases, an increase or alteration in physical activity in the weeks prior to the injury and an increase in specific rowing movements with special emphasis on the new equipment, combined with increased biomechanical stress applied to the thoratic skeleton in the catch and the early part of the drive phase of the stroke, most probably caused the injuries.

Adult↗

Metabolism of oral glucose in pancreas transplant recipients with normal and impaired glucose tolerance.

To gain insight into the pathophysiology of impaired glucose tolerance in pancreas transplantation, glucose kinetics and insulin secretion were assessed after an oral glucose load in four combined pancreas-kidney recipients with impaired glucose tolerance (IPx), in five combined pancreas-kidney recipients with normal glucose tolerance, in six nondiabetic kidney transplant recipients, and in eight normal subjects employing a dual isotope technique, beta-Cell function was evaluated by calculating prehepatic insulin secretion rates, which subsequently were correlated to the ambient glucose concentrations to obtain an index of beta-cell responsiveness. Oxidative and nonoxidative glucose metabolism were assessed by indirect calorimetry. Basal insulin secretion rates, the glucose-stimulated early insulin secretion rates, as well as beta-cell responsiveness were markedly reduced in IPx than in the glucose-tolerant transplant subjects. Total systemic glucose appearance was similar in the groups with apparently comparable inhibition of systemic glucose release and increase in exogenous glucose appearance. The hyperglycemic response in IPx was due to a significant reduction in the glucose disappearance rates during the first 2 h after glucose ingestion. Nonoxidative glucose metabolism increased significantly less in IPx than in glucose-tolerant groups. Glucagon secretion was less suppressed in the early part of the study in IPx, which may have contributed to the excessive hyperglycemia. In conclusion, IPx after pancreas transplantation was characterized by 1) impaired early insulin secretion, 2) reduced beta-cell responsiveness, 3) reduced glucose uptake, 4) impaired nonoxidative glucose metabolism, and 5) impaired early inhibition of glucagon secretion.

Adult↗

Intake of a diet high in trans monounsaturated fatty acids or saturated fatty acids. Effects on postprandial insulinemia and glycemia in obese patients with NIDDM.

OBJECTIVE: High intake of trans fatty acids and saturated fatty acids (SFAs) is known to increase the risk of coronary heart disease. We studied the effects of diets enriched in various fatty acids on postprandial insulinemia and fasting serum levels of lipids and lipoproteins in obese patients with NIDDM. RESEARCH DESIGN AND METHODS: Sixteen obese NIDDM patients were studied in a free-living outpatient regimen. After a run-in period, the patients received three different isocaloric diets for 6 weeks using a randomized crossover design. The patients were instructed to keep the energy intake from carbohydrate and protein constant at 50 and 20 E% (percent of energy intake), respectively, on all three diets. The fat composition of the diets differed: saturated fat (SAT) diet (20 E% SFAs, 5 E% polyunsaturated fatty acids [PUFAs], and 5 E% monounsaturated fatty acids [MUFAs]) versus cis monounsaturated fatty acid (CMUFA) diet (20 E% cis-MUFAs, 5 E% PUFAs, and 5 E% SFAs) versus trans monounsaturated fatty acid (TMUFA) diet (20 E% trans-MUFAs, 5 E% PUFAs, and 5 E% SFAs). Fasting serum levels of lipids and lipoproteins were measured at baseline and in the fasting state before meal tolerance tests at the end of each study period. Insulin secretion was assessed from incremental serum insulin and C-peptide responses during the meal tests. RESULTS: BMI, waist-to-hip ratio, and glycemic control remained stable throughout the study. After meal stimulation, postprandial glycemic responses were similar on all diets; however, serum insulin and C-peptide responses were greater following the TMUFA and SAT diets than following the baseline or CMUFA diets (P < 0.05). No statistical difference was found in fasting levels of serum lipids (total cholesterol, triglyceride, phospholipid, and nonesterified fatty acids) or lipoproteins of HDL cholesterol, VLDL cholesterol, LDL cholesterol, and apolipoprotein B between diets. CONCLUSIONS: In the presence of unchanged glycemia, both dietary trans fatty acids and SFAs induce an increase in postprandial insulinemia in obese patients with NIDDM.

Blood Glucose↗

Purification and 1H NMR spectroscopic characterization of phase II metabolites of tolfenamic acid.

Tolfenamic acid, an anti-inflammatory drug (NSAID), is metabolized in vivo to form several oxidative metabolites which are all conjugated with beta-D-glucuronic acid. In this study, the metabolites of tolfenamic acid were identified by 1H nuclear magnetic resonance (NMR) spectroscopy in urine samples obtained on days 7 to 10 from a human volunteer after oral administration of 200 mg of the drug three times per day (steady-state plasma concentration). The metabolites of tolfenamic acid were initially concentrated by preparative solid phase extraction (PSPE) chromatography, thereby removing the endogenous polar compounds that are present in the urine. The individual metabolites were purified by preparative high performance liquid chromatography (HPLC) and then identified using 1H NMR. Both one- and two-dimensional NMR experiments were performed to identify the phase II metabolites of tolfenamic acid; the study shows the applicability of 1H NMR for the identification of drug metabolites in biological fluids. In addition to NMR analysis, two metabolites were also identified by mass spectrometry (MS). The glucuronides of the following parent compounds, N-(2-methyl-3-chlorophenyl)-anthranilic acid (T), N-(2-hydroxymethyl-3-chlorophenyl)-anthranilic acid (1), N-(2-hydroxymethyl-3-chloro-4-hydroxyphenyl)-anthranilic acid (2), N-(2-formyl-3-chlorophenyl) anthranilic acid (3), N-(2-methyl-3-chloro-4-hydroxyphenyl)-anthranilic acid (4), N-(2-methyl-3-chloro-5-hydroxyphenyl)-anthranilic acid (5), N-(2-carboxy-3-chlorophenyl)-anthranilic acid (6), N-(2-hydroxymethyl-3-chlorophenyl)-4-hydroxy-anthranilic acid (7), N-(2-methyl-3-chlorophenyl)-5-hydroxy-anthranilic acid (8), N-(2-methyl-3-chloro-4-metoxyphenyl)-anthranilic acid (9), N-(2-methyl-3-chlorophenyl)-4-hydroxy-anthranilic acid (10), and N-(2-methyl-4-hydroxyphenyl)-anthranilic acid (11) were identified. The phase II metabolites (5-11) had not previously been identified in urine from humans administered tolfenamic acid. The phase I metabolites of the glucuronides 7, 8, 10, and 11 were identified here for the first time. An HPLC method was developed that simultaneously separates all the phase II metabolites identified as well as some phase I metabolites in urine samples obtained after intake of tolfenamic acid.

Anti-Inflammatory Agents, Non-Steroidal↗

Hepatitis B core antibody screening in a high prevalence group: comparison of three enzyme immunoassays using receiver operating characteristic analysis.

Selected sera from 296 homosexual men were screened by 3 commercially available anti-HBc enzyme immunoassays (EIA). All patients could be classified either as non-immune to hepatitis B, or with current or previous hepatitis B infection. Using the cut-off optical density values (O.D. values) recommended by the respective manufacturers, the results from these three assays were identical for 83% of the serum samples. For anti-HBc reactivity, the ratio (percentage) was calculated using O.D. sample x 100 divided by the O.D. cut-off value. Employing these ratios, sensitivities and specificities for the three assays were compared. All assays performed well when analyzed by receiver operating characteristic curves with area under the curves of 96-97%. A higher specificity, with only a marginal loss of sensitivity could be achieved by lowering the cut-off to 55% for the Enzygost EIA, to 85% for the Enzygost-monoclonal EIA and to 60% for the Corzyme EIA. Using the modified cut-off values, the results with the three assays agreed for 93% of the serum samples.

Hepatitis Antibodies↗

Pancreatic endocrine function in recipients of segmental and whole pancreas transplantation.

To determine potential abnormalities in beta-cell function after pancreas transplantation, the secretory capacity of the pancreatic grafts was assessed by measuring the glucose-potentiating effect on arginine-induced insulin secretion in recipients of cadaveric segmental (SPx; n = 8) and whole organ pancreas grafts (WPx; n = 6) and compared to that in nondiabetic kidney transplant recipients (Kx; n = 6) and normal controls (Ns; n = 7). alpha-Cell adaptation to increasing hyperglycemia and the glucagon response to arginine stimulation were also studied. The secretory capacity of the beta-cell to arginine-induced (5 g L-arginine) insulin secretion was measured at fasting plasma glucose and 15 and 30 mmol/L glucose. Insulin secretion was evaluated by the calculation of insulin secretion rates. Insulin sensitivity was markedly reduced in all three transplanted groups compared to that in normal subjects (P < 0.05). The prestimulation insulin secretion rate and maximal insulin secretion rate in response to hyperglycemia and arginine were significantly lower in SPx than in WPx, Kx, or Ns (P < 0.05). The incremental amount of insulin secreted in response to arginine was reduced by 40-70% in SPx depending on glycemia compared to that in all other groups (P < 0.05), among which there were no statistical differences. Both SPx and WPx demonstrated suppression of glucagon release in response to graded hyperglycemia, but failure to adequately suppress arginine-induced glucagon release. In conclusion, recipients of cadaveric segmental pancreas grafts display a markedly reduced maximal insulin secretory reserve capacity. This impairment was primarily due to an insufficient beta-cell mass. Taking the concomitant insulin resistance into account, recipients of a cadaver whole organ pancreas graft had an impaired insulin secretory reserve capacity as well.

Adult↗

Impaired insulin-stimulated nonoxidative glucose metabolism in pancreas-kidney transplant recipients. Dose-response effects of insulin on glucose turnover.

Insulin resistance is a characteristic feature in recipients of a pancreas transplant, but the relative contribution of the liver and peripheral tissues to this abnormality within a spanning range of insulin concentrations is unknown. To assess the impact of insulin action on glucose metabolism after pancreas transplantation, a euglycemic-hyperinsulinemic clamp with sequential insulin infusions (5, 40, and 200 mU.m-2.min-1 for 120 min each), combined with isotopic determinations of the rates of hepatic glucose production and extrahepatic glucose uptake, indirect calorimetry, and measurements of glycogen synthase and hexokinase activities in vastus lateralis muscle, were performed in six pancreas-kidney transplant recipients (Px group) and compared with those performed in six nondiabetic kidney transplant recipients with similar immunosuppression (Kx group) and six nondiabetic control subjects. The overall effects of insulin on whole-body glucose metabolism, determined as the glucose infusion rates versus the corresponding steady-state serum insulin concentrations, demonstrated a rightward shift in the dose-response curves of the transplanted groups compared with those of normal subjects. The dose-response curve for glucose disposal rates (Rd) was shifted to the right in the Px and Kx groups, and the maximal glucose disposal rate was reduced by 40% in the Px group (11.7 +/- 1.1 mg.kg-1 fat-free mass.min-1) and 30% in the Kx group (13.9 +/- 1.2 mg.kg-1 fat-free mass.min-1) compared with that in control subjects (19.1 +/- 2.2 mg.kg-1 fat-free mass.min-1) (P < 0.05). The dose-response curve for suppression of hepatic glucose output rates was similar at increasing hepatic sinusoidal insulin concentrations. Glucose oxidation rates were similar in all groups, whereas nonoxidative glucose rates were reduced by 50% in the Px group and by 30% in the Kx group compared with those in the control group (P < 0.05). In the Px group, an impaired activation of the fractional velocity and absent decrease in the half-maximal stimulation of muscle glycogen synthase occurred during the insulin infusion. However, this finding could only explain in part the degree of impairment in nonoxidative glucose metabolism. No differences were found in total hexokinase activity in muscle between normal subjects and the transplant groups at basal insulinemia or after insulin stimulation. During hyperinsulinemia, glucagon and nonesterified fatty acids were not suppressed as much in the transplanted groups as they were in normal control subjects (P < 0.05). In conclusion, pancreas transplantation causes impaired peripheral action of insulin as compared with that in normal subjects and kidney transplant recipients. The main course of insulin resistance in the two transplant groups is explained by the immunosuppressive treatment, but the augmented insulin resistance in pancreas transplant recipients could partly be explained by the chronic peripheral hyperinsulinemia. The principal site of insulin resistance was a reduced insulin-stimulated nonoxidative glucose metabolism of peripheral tissues, which resulted in decreased capacity to store glucose as glycogen. The impaired peripheral insulin action could only partly be explained by a reduced activation of the glycogen synthase enzyme in skeletal muscle.

Adult↗

Determinants of satisfactory rigidity after intracavernosal injection with prostaglandin E1 in men with erectile failure.

The study examines the erectile response of intracavernosal injection with increasing doses of prostaglandin E1 (PGE) and papaverine/phentolamine (PP) in 516 men with erectile failure. The response was correlated to age, the duration of erectile failure, the quality of spontaneous erections, tobacco consumption and medicine use. In addition, the erectile response was related to penile brachial index (PBI) the free testosterone index and various hormonal parameters. Over 60% of the subjects obtained satisfactory rigidity of at least 30 min duration with 7-15 micrograms PGE. A further 15% (PGE non-responders at the doses tested) obtained rigidity with PP. The average dose necessary to achieve rigidity was 8.8 micrograms for PGE and 0.94 ml (papaverine: 15 mg/ml; phentolamine 0.5 mg/ml) for PP. The average duration of rigidity was 2.2 h and 2.3 h for PGE and PP, respectively. Tobacco consumption, the duration of erectile failure and the age of the subject did not influence the response to intracavernosal injection. Moreover the PBI, the free testosterone index or libido of the subject, did not appear to be generally important for obtaining satisfactory rigidity. In contrast, chronic medication, especially antihypertensive drugs, was associated with significantly higher numbers of poor responders, a shorter duration of erection in the responders and higher doses of PGE necessary to achieve a satisfactory response. The combination of increasing age and antihypertensive medication was predictive for a poor intracavernosal response. In general, a reduced incidence of morning erections was predictive of a weaker response to PGE. The proportion of men with a PBI lower than 0.75 increased with age. These subjects more often took chronic medication, had a lower frequency of morning erections and exhibited a significantly weaker reaction to PGE than subjects with higher PBI. In summary, a large number of men with erectile failure can obtain satisfactory rigidity with intracavernosal injection. In men taking antihypertensive medication, especially in higher age groups, the dose of the intracavernosal medication had to be increased. A reduced sensitivity to intracavernosal medication could be predicted from a lower PBI and a reduced frequency of spontaneous erections.

Adrenergic alpha-Antagonists↗