Biomedical subjects
Publications and source records attributed to R Gunnarsson.
Diaphragmatic weakness in patients with systemic lupus erythematosus (SLE) is a controversial issue and is claimed to have a neuropathic, myopathic or unknown pathogenesis. In this patient a predominantly motor neuropathy with diaphragmatic paralysis due to axonal involvement of the phrenic nerve was discovered and successfully treated with immunosuppressive drugs.
STUDY DESIGN: A prospective randomized trial in 97 patients with a whiplash injury caused by a motor vehicle collision. OBJECTIVES: The study evaluates early active mobilization versus a standard treatment protocol and the importance of early versus delayed onset of treatment. SUMMARY OF BACKGROUND DATA: There is no compelling evidence to date on the management of acute whiplash-associated disorders. The few studies describing treatment, however, provide evidence to support the recommendation that an active treatment in the acute stage is preferable to rest and a soft collar in most patients. METHODS: Patients were randomized to four groups. Active versus standard treatment and early (within 96 hours) versus delayed (after 2 weeks) treatment. Measures of range of motion and pain were registered initially and at 6 months. RESULTS: Eighty-eight patients (91%) could be followed up at 6 months. Active treatment reduced pain more than standard treatment (P < 0.001). When type and onset of treatment were analyzed, a combined effect was seen. When active treatment was provided, it was better when administered early, and if standard treatment was provided, it was better when administered late for reduction of pain (P = 0.04) and increasing cervical flexion (P = 0.01). CONCLUSIONS: In patients with whiplash-associated disorders caused by a motor vehicle collision treatment with frequently repeated active submaximal movements combined with mechanical diagnosis and therapy is more effective in reducing pain than a standard program of initial rest, recommended use of a soft collar, and gradual self-mobilization. This therapy could be performed as home exercises initiated and supported by a physiotherapist.
Much effort has been devoted to finding methods for detecting individuals with low bone mass and risk of osteoporotic fractures. The aim of the present study was to investigate whether there is a relationship between the thickness of the alveolar process and the bone mineral density (BMD) of the distal forearm. In 24 women (38-65 years), the BMD of the distal forearm, obtained by dual X-ray absorptiometry, was correlated to the difference between two measures of the thickness of the mandibular alveolar process in the region of the first premolar. A highly significant correlation (r = 0.95, P< 0.001) was found. The method was cross-validated by using the equation obtained from the linear regression analysis above to predict BMD in two other groups. In both groups, the correlation between the measured BMD of the forearm and the predicted BMD was highly significant (r = 0.91, P< 0.001). The interdental thickness between the canine and the second incisor was also correlated to BMD, but with lower predictive value (r = 0.67, P<0.001). Measurements of the mandibular alveolar process can be used as one of several parameters to predict skeletal bone density.
The growth hormone-releasing hormone analogue GHRH(1-29)-NH2 was administered intravenously or intranasally to 30 healthy men aged 19-43 years. Intravenous injection of the lowest dose tested, 0.25 microgram/kg body weight, elicited significant release of growth hormone (GH). Maximal release (mean GH peaks of about 90 mU/l) was obtained with a dose of 1-2 micrograms/kg. Although GHRH(1-29)-NH2 was rapidly eliminated after intravenous injection, GH levels were elevated for about 3 hours. Absorption of GHRH(1-29)-NH2 through the nasal mucosa was found to be low, and the bioavailability was only 3-5%. There was a dose-dependent release of GH after intranasal administration of GHRH(1-29)-NH2, with the maximal response obtained with about 50 micrograms/kg; this dose was approximately as potent as 1 microgram/kg injected intravenously. The GH response after repeated intranasal administration of GHRH(1-29)-NH2 was sustained; there was no suppression of GH secretion during the night following a day when GHRH(1-29)-NH2 had been given three times intranasally. Based on these findings and the obvious convenience of intranasal administration compared with injections, it would be justified to test intranasal therapy for treatment of short stature in children with GH deficiency caused by hypothalamic damage.
In this study, 60 patients with proven growth hormone deficiency (GHD) of hypothalamic origin were randomized into three equal groups, and received growth hormone-releasing hormone(1-29)-NH2 (GHRH(1-29)-NH2), 30 or 60 micrograms/kg/day, or growth hormone (GH), 0.1 IU/kg/day, for 6 months. There were no significant differences in growth between the two groups given GHRH(1-29)-NH2, but growth in the GH group was significantly better than in the other two groups (p < 0.01). Mean height velocities at 6 months were 9.2, 9.3 and 14.6 cm/year for the three groups, respectively. Plasma GHRH concentrations increased steadily over the 6-month treatment period, with higher levels in the group on the higher dose. During GHRH(1-29)-NH2 treatment, serum concentrations of insulin-like growth factor I rose initially, but then fell to values similar to those before treatment. No GH antibodies were detected, but all 20 patients on high-dose GHRH(1-29)-NH2 and 19 of 20 patients on low-dose GHRH(1-29)-NH2 developed GHRH antibodies. These had almost disappeared by 9 months after stopping treatment. There was no correlation between antibody titres and increase in height. No serious side-effects were seen, but three patients receiving GHRH(1-29)-NH2 reported mild irritation at the injection site. These results from the continuous infusion of GHRH(1-29)-NH2 over 6 months suggest that this treatment, or the related use of a depot preparation, is unlikely to be as effective as GH for the promotion of growth in GHD.
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Subjective, neuroendocrine and cardiovascular functions were studied in high- and low-anxious musicians performing privately and publicly. Musicians were designated as "high-anxious" if they reported at least one episode of performance-related tremor and as "low-anxious" if they never had experienced tremor while performing in public. All musicians performed privately and publicly while measurements of subjective, neuroendocrine and cardiovascular functions were made. Ratings of effort and distress were made prior to performance. Heart rate was monitored telemetrically before, during and after performance. Urinary epinephrine, norepinephrine and cortisol were sampled after public and private performance, respectively. Situational factors influenced most measures. Epinephrine, norepinephrine, cortisol, heart rate and ratings of distress but not effort increased from private to public performance. Heart rate was higher in high- than in low-anxious musicians during public performance but similar during private performance. The increase in neuroendocrine activation from private to public performance was similar in the high- and low-anxious groups. It is concluded that heart rate is a sensitive measure of both situational and individual determinants of performance-related distress.
With current surgical techniques for pancreatic transplantation, the graft is anastomosed to the iliac vessels, resulting in delivery of insulin to the systemic circulation rather than to the portal vein as in healthy man. The possible influence of the altered route of insulin delivery on the regulation of splanchnic glucose metabolism was studied in four patients with Type 1 (insulin-dependent) diabetes mellitus at 6-19 months after combined pancreatic and kidney transplantation. Four non-diabetic, age-matched renal transplant recipients and two groups of age-matched healthy subjects served as controls. The studies were carried out in the basal state and during two rates of intravenous glucose infusion (2 and 4 mg.kg-1.min-1). Fasting arterial glucose and splanchnic glucose output was similar in all groups. Basal hyperinsulinaemia was present in pancreatic graft recipients compared to healthy subjects. During low rate intravenous glucose infusion splanchnic glucose output decreased to a similar extent in all groups. With the higher glucose infusion rate (4 mg.kg-1.min-1) a net glucose uptake was observed which was similar in all three groups. Peripheral glucose uptake was unchanged at the lower glucose infusion rate but increased by 45-55% at the higher rate. It is concluded that despite systemic insulin delivery from a heterotopic pancreatic graft, hepatic glucose metabolism appears normal both in the post-absorptive state and in response to glucose-stimulated endogenous insulin secretion. Portal insulin delivery is thus not necessary for normal hepatic glucose metabolism in the Type 1 diabetic patient.
The pharmacokinetic profile of recombinant human insulin-like growth factor I (IGF-I) was studied in healthy volunteers. Following a single subcutaneous injection of 40 micrograms/kg or 80 micrograms/kg, mean serum IGF-I concentrations increased by 150 ng/ml and 245 ng/ml, respectively. During repeated daily injections of 40 micrograms/kg, a steady-state IGF-I level of 150 ng/ml above baseline was reached. Of the pharmacokinetic indices measured, only Tmax varied between single and multiple dose regimens (6.9 hours versus 3.5 hours). No hypoglycaemic symptoms were observed, and after injection of IGF-I no depression of endogenous IGF-I production was observed. Fasting insulin levels were unaltered, but postprandial insulin was lowered by IGF-I with respect to placebo.
Out of a total of 8136 children registered in the Kabi Pharmacia International Growth Study, 12 have been reported to have diabetes either before or during treatment with growth hormone (GH). Two of these have non-insulin-dependent diabetes mellitus (NIDDM), of whom one had risk factors for the development of his condition, namely gross obesity and familial occurrence of NIDDM. One is a rare case of McCune-Albright's syndrome with insulin-dependent diabetes mellitus (IDDM), and 9 other patients have IDDM. Of these 9, 6 have idiopathic GH deficiency. In 8 of the 9 patients with IDDM, the condition was diagnosed before GH therapy was commenced, at ages ranging from less than 2 years to 16 years. The association is probably fortuitous, however, as the onset of IDDM in 7 patients was immediately before or during puberty, as often occurs in IDDM in general.
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This article reports the efficacy and safety of treatment with Somatonorm in 9 children with idiopathic growth hormone (GH) deficiency in China. The growth velocity increased from 2.6 +/- 0.2 cm/year before treatment to 10.7 +/- 0.5 cm/year at the end of 1-year treatment. The increment of human growth hormone (hGH) level and area under the response curve above the baseline level were larger after one injection of Somatonorm at the dose of 0.1 IU/kg sc than that of 0.17 IU/kg im. Increments of delayed bone age were not significant. There was no correlation between the increase of height growth velocities and the serum Somatomedin-C (SMC) levels during hGH therapy (r = -0.055). Blood sugar levels and blood alkaline phosphatase concentrations increased significantly after therapy. There were no significant side effects. Serum T4 levels of 3 patients dropped below normal after treatment. Serum anti-hGH antibody appeared at 3-12 month in 2 patients, but it did not attenuate the growth velocity.
Six short children with low 24-hour growth hormone (GH) secretion were treated with continuous subcutaneous infusion of GHRH (1-29)NH2 for 3 weeks using a portable infusion pump. Restoration of pulsatile GH secretion was observed in all three children treated with 40 micrograms/kg/day of GHRH, but in only one of the three children treated with 20 micrograms/kg/day. All parameters of 24-hour GH secretion increased, but in five children the magnitude of the GH response was greater on day 1 than on day 21 of GHRH treatment. This decrease was not observed in the single child who responded to a low dose of GHRH (20 micrograms/kg/day); on the contrary, the response in this patient was greater after 21 days of GHRH treatment. Plasma levels of GHRH (1-29)NH2 were significantly higher on day 21 than on day 1 of treatment, suggesting altered pharmacokinetics over time. The effect of GHRH treatment on growth could not be determined because of the short duration of the study, but the data obtained on 24-hour GH secretion and GHRH metabolism suggest that a long-acting analogue of GHRH could be useful for the treatment of GH deficient or insufficient children.
Fructose raises blood glucose and lactate levels in normal as well as diabetic man, but the tissue origin (liver and/or kidney) of these responses and the role of insulin in determining the end products of fructose metabolism have not been fully established. Splanchnic and renal substrate exchange was therefore examined during intravenous infusion of fructose or saline in six insulin-deficient type I diabetics who fasted overnight and in five healthy controls. Fructose infusion resulted in similar arterial concentrations and regional uptake of fructose in the two groups. Splanchnic glucose output increased threefold in the diabetics but remained unchanged in controls in response to fructose infusion, and the arterial glucose concentration rose more in diabetics (+5.5 mmol/liter) than in controls (+0.5 mmol/liter). Splanchnic uptake of both lactate and pyruvate increased twofold in response to fructose infusion in the diabetics. In contrast, a consistent splanchnic release of both lactate and pyruvate was seen during fructose infusion in controls. In diabetics fructose-induced hyperglycemia was associated with no net renal glucose exchange, while there was a significant renal glucose production during fructose infusion in the controls. In both groups fructose infusion resulted in renal output of lactate and pyruvate. In the diabetics this release corresponded to the augmented uptake by splanchnic tissues. In two diabetic patients given insulin infusion, all responses to fructose infusion were normalized. Fructose infusion in diabetics did not influence either splanchnic ketone body production or its relationship to splanchnic FFA inflow. We conclude that in insulin-deficient, mildly ketotic type I diabetes, (a) both the liver, by virtue of lactate, pyruvate, and fructose-derived gluconeogenesis, and the kidneys , by virtue of fructose-derived lactate and pyruvate production, contribute to fructose-induced hyperglycemia; (b) outcome of hepatic fructose metabolism; and (c) fructose does not exert an antiketogenic effect. These data suggest that while total fructose metabolism is not altered in diabetics, intermediary hepatic fructose metabolism is dependent on the presence of insulin.
The diurnal patterns of relevant metabolites and hormones in five pancreas-kidney-transplanted patients (aged 36 +/- 2 yr, mean +/- SD) with insulin-dependent diabetes mellitus (IDDM) were compared with those in five kidney-transplanted nondiabetic patients (aged 28 +/- 2 yr). The groups were matched for body mass and current dose and type of immunosuppressive treatment. The serum creatinine levels did not differ between the two study groups, but the serum urea level in the nondiabetic patients was slightly but significantly higher than in the diabetic patients. In the pancreas-kidney-transplanted group the investigation was performed 8-47 mo posttransplantation; in the kidney-transplanted nondiabetic patients, 12-18 mo posttransplantation. The mean 24-h levels and rhythms of blood glucose, free fatty acid, 3-hydroxybutyrate, and alanine did not differ between the groups. The mean 24-h levels of blood lactate and glycerol were moderately but significantly higher in the pancreas-kidney-transplanted diabetic patients. At fasting, the level of serum immunoreactive insulin was more than twice as high in the pancreas-kidney-transplanted patients, whereas the plasma C-peptide levels did not differ significantly between the two groups. The meal-induced increases in serum insulin as well as in the plasma C-peptide levels were more marked in the pancreas-kidney-transplanted patients. The findings suggest that the hyperinsulinemia in these patients was due to both the systemic delivery of insulin and an increase in insulin resistance, the latter being particularly apparent in the postprandial phase.(ABSTRACT TRUNCATED AT 250 WORDS)
The efficacy of Genotropin (recombinant somatropin, KabiVitrum AB, Sweden) was analysed in 194 children with GH deficiency, comprising a combined series of four multicentre trials. The linear height velocity increased from 3.3 +/- 1.4 to 9.3 +/- 2.6 cm/year in 149 prepubertal children with 12 months' data available. In 18 pubertal children the pretreatment height velocity was 4.0 +/- 1.2, and increased to 8.4 +/- 1.7 cm/year during 12 months of treatment. There was a positive correlation between the gain in height velocity and the weekly dose of Genotropin. Covariance analysis revealed significantly greater height velocity with 6-7 injections/week compared to 2-3 injections/week; corrections for chronological age, bone age, height SD score and dose were made. On average, a regimen of 6-7 injections/week was 25% more effective than one of 2-3 injections/week corresponding to an extra gain in height velocity of 1.8 +/- 0.6 cm/year. At 12 months, only 0.9% of the children had developed anti-GH antibodies. Very few side-effects have been reported from more than 1000 children on Genotropin.
We studied the effects of insulin-induced hypoglycemia on the absorption of 10 U 125I-labeled soluble human insulin injected sc in the thigh in 10 normal subjects. The disappearance of 125I from the injection site was followed by external gamma-counting. Subcutaneous blood flow (ATBF) was measured concomitantly with the 133Xe washout technique. The plasma glucose nadir [mean, 2.0 +/- 0.1 (+/- SE) mmol/L] occurred at 33 +/- 3 min and resulted in maximal arterial plasma epinephrine concentrations of approximately 6 nmol/L. From 30 min before to 60 min after the glucose nadir the [125I]insulin absorption rate was depressed compared to that during normoglycemia. The first order disappearance rate constants were reduced by approximately 50% (P less than 0.01) during the first 30-min interval after the glucose nadir. During the same period ATBF increased by 100% (P less than 0.05). The results suggest that in normal subjects the absorption of soluble insulin from a sc depot is depressed in connection with hypoglycemia, despite considerably elevated ATBF.
Effects of epinephrine (Epi) infusion on the absorption of subcutaneously injected 125I-labeled soluble human insulin (10 U) from the thigh or the abdomen were studied in 16 healthy subjects and from the thigh in 10 insulin-dependent diabetic (IDDM) patients. Epi was infused at 0.3 (high dose) or 0.1 (low dose; healthy subjects) nmol.kg-1.min-1 i.v., resulting in arterial plasma Epi levels of approximately 6 and 2 nM, respectively. Saline was infused on a control day. Insulin absorption was measured as disappearance of radioactivity from the injection site and as appearance of plasma immunoreactive insulin (IRI). Adipose tissue blood flow was measured with the 133Xe clearance technique. First-order disappearance rate constants of 125I from the thigh depot decreased approximately 40-50% during the high dose of Epi compared with control (P less than .001). The corresponding decrease from the abdominal depot was approximately 40% (P less than .001), whereas no significant change was found during the low Epi dose. IRI fell compared with control in all groups at the high Epi dose. The Epi-induced depression of insulin absorption occurred despite unaltered or even slightly increased subcutaneous blood flow. The results indicate that circulating Epi at levels seen during moderate physical stress depresses the absorption of soluble insulin from subcutaneous injection sites to an extent that might be important for glycemic control in IDDM patients. Furthermore, dissociation is found between changes in insulin absorption and subcutaneous blood flow during Epi infusion, suggesting that factors other than blood flow may also influence the absorption of subcutaneously injected insulin.