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Biomedical subjects

S E Christensen

Publications and source records attributed to S E Christensen.

At least 19 recordsLinked to original sources

[Patients' activity and length of stay after hip arthroplasty with balanced analgesia and early mobilization].

Thirteen consecutive patients were submitted to hip-replacement by Müller's method under epidural analgesia and were treated for postoperative pain with balanced analgesia by means of continuous epidural infusion of a mixture of bupivaine (0.625 mg/ml) and morphine (0.05 mg/ml) 4 ml hourly for 96 hours and supplemented by 600 mg ibuprofen every eight hour orally. The analgesic treatment was combined with intensive mobilization regime and altered postoperative care as regards early normalization of daily activities and reduced duration of hospitalization. The patients were found to be effectively relieved of pain during rest and also during mobilization and, together with suitable care and rehabilitation, this had the result that more than half of the patients were mobilized from bed for more than eight hours from the second postoperative day and that all of the patients were able to carry out ordinary everyday functions after the fourth postoperative day, with the assistance of the aids which the hip regimen required. Eleven of the patients were ready for discharge on the sixth postoperative day while two patients were not discharged until the eighth and ninth postoperative days on account of slight surgical complications. All of the patients were discharged to their homes and to outpatient rehabilitation for three weeks. Compared with the usual duration of hospitalization of approximately 13 days in corresponding patients, this pilot investigation appears to show that the analgesic regime employed was extremely effective but that traditional attitudes and routines in the postoperative care and mobilization must be revised if this is to be utilized for more rapid restitution and reduced duration of hospitalization.

Aged

Long-term efficacy and tolerability of octreotide treatment in acromegaly.

Twenty-five acromegalic patients were studied during 6 years of treatment with octreotide, with a particular focus on the following parameters: (1) Administration schedule: in 10 patients, continuous subcutaneous (SC) octreotide infusion was compared with injections of octreotide at three dose levels (100, 250, and 1,500 micrograms/24 h) and was found to induce a greater and less-fluctuating 24-hour growth hormone (GH) suppression. (2) Carbohydrate tolerance: average 24-hour blood glucose levels were unaffected by octreotide, regardless of administration schedule. Oral carbohydrate tolerance and intravenous (IV) glucose tolerance were unaffected by continuous octreotide infusion. However, octreotide injection given shortly before the tests reduced carbohydrate tolerance. (3) Thyroid function: octreotide and somatostatin acutely reduce the response of thyroid-stimulating hormone (TSH) to thyrotropin-releasing hormone (TRH). After a few days of treatment, it was demonstrated that octreotide slightly inhibits iodothyronine deiodination and induces a transient reduction in serum triiodothyronine (T3), rapidly compensated for by a persistent slight elevation of serum TSH. (4) Fat absorption was estimated as 24-hour fecal fat content and found to be in the same high-normal range before and after octreotide treatment. Vitamin K and D absorption were unaffected by octreotide. The incidence of gallstone formation was not greater than in the general Danish population, possibly due to the schedule used for octreotide injections. (5) Foot volume was regularly estimated and found to decrease with time, on average by 12% during the first 18 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly

Octreotide and diabetes: theoretical and experimental aspects.

Diabetes is characterized by paradoxical hypersomatotropinemia and hyperglucagonemia. The latter appears to enhance the tendency in imperfect metabolic control to reduce nitrogen balance, and the former appears to accelerate the deterioration of carbohydrate and lipid metabolism, and also to induce peripheral insulin resistance and hyperinsulinemia. In addition to direct metabolic effects, increasing evidence points to an association between hypersomatotropinemia and a number of metabolically dependent, characteristic functional abnormalities linked to the development of late diabetic manifestations. These include increased capillary fragility, lipid and hemostatic aberrations, tissue hyperperfusion, including increased cardiac output and renal plasma flow, and kidney hypertrophy. In theory, octreotide's actions could reduce these aberrations, and, in fact, this has been confirmed in recent experimental trials.

Animals

Preliminary results with Sandostatin nasal powder in acromegalic patients.

This report details the first half of a double-blind, crossover sequence (Latin square) study of local and hormonal effects of nasally insufflated Sandostatin compared with those of subcutaneously injected Sandostatin. Nine of the planned 16 patients have been studied. They received a single application of 0.5, 1.0, and 2.0 mg Sandostatin as nasal powder and 0.1 mg by subcutaneous (SC) injection. The results indicate that absorption from the nasal epithelium occurs after approximately 10 minutes and comprises approximately 20% of the dose administered. This indicates that peak serum Sandostatin values occur very rapidly, ie, 10 minutes after application. After approximately 2 hours, the serum disappearance rates are similar to those obtained after SC injection. The suppressive effect on serum growth hormone (GH) levels is equal with the two forms of application and suggests that future clinical treatment with an intranasal application of 0.5 mg thrice daily is feasible. No side effects were noted apart from an immediate swelling of nasal mucosa, which receded gradually over the following 2 hours. This was either unnoticed or considered insignificant by the patients and will probably be deemed harmless by the rhinologist in eventual long-term clinical trials.

Absorption

SMS 201-995 and thyroid function in acromegaly: acute, intermediate and long-term effects.

The acute (TRH-stimulation test), intermediate (0-6 days administration), and long-term (0-30 months administration) effects of SMS 201-995 (octreotide) treatment on thyroid function were studied. Subcutaneous injection of 100 micrograms SMS 201-995 one hour before 200 micrograms TRH intravenously reduced serum TSH response area by more than 50% in 8 healthy volunteers. After 3 days of continuous subcutaneous infusion (CSI) of SMS 201-995 in 9 acromegalic patients (100 micrograms/24 h) a slight but significant decrease in serum total triiodothyronine (TT3) and a concomitant increase in serum TSH were demonstrated, indicating an initial inhibitory effect on peripheral deiodination of thyroxine. After a further 3 days treatment serum T3 and TSH had returned to prevalues. Six of the nine acromegalics were treated with SMS 201-995 (100-1500 micrograms/24 h) and admitted for diurnal hormone profiles on 13 occasions over 30 months. Apart from a barely significant increase in serum TSH, no changes in thyroid function were noted. The study was especially designed to detect minute changes over time in thyroid hormones. The only long-term effect of SMS 201-995 was the barely significant clinically irrelevant increase in serum TSH, possibly caused by a slight inhibition of peripheral deiodination of thyroxine.

Acromegaly

Basal- and insulin-stimulated substrate metabolism in patients with active acromegaly before and after adenomectomy.

Active acromegaly is characterized by inappropriate tissue growth, increased mortality, and perturbations of intermediary metabolism. It is, in general, not well described to which extent these disturbances are normalized after treatment of the disease. To further assess basal and insulin stimulated fuel metabolism in acromegaly six patients with monotropic GH excess were each studied approximately 1 month prior to and 2 months after successful selective pituitary adenomectomy and compared to a control population of seven subjects. The studies consisted of a 3-h basal postabsorptive period and a 2-h hyperinsulinaemic (0.4 mU/kg/min) euglycemic clamp and the methods employed included isotopical measurement of glucose turnover, indirect calorimetry, and the forearm technique. When compared to the control subjects the patients with acromegaly were preoperatively and in the basal state characterized by: 1) increased circulating concentrations of GH, insulin, and C-peptide (P less than 0.05); 2) increased plasma glucose (5.9 +/- 0.2 vs. 5.2 +/- 0.2 mmol/L), blood lactate (710 +/- 90 vs. 580 +/- 70 mumol/L), glucose turnover (2.34 +/- 0.12 vs. 1.93 +/- 0.12 mg/kg/min), and plasma lipid intermediates and a decreased forearm glucose uptake (0.06 +/- 0.02 vs. 0.19 +/- 0.04 mmol/L) (P less than 0.05); and 3) a 20% increase in energy expenditure, a 50% elevation of lipid oxidation rates, and a 130% elevation of nonoxidative glucose turnover (P less than 0.05). During the clamp the patients with active acromegaly were substantially resistant to the actions of insulin on both glucose and lipid metabolism. Following pituitary surgery all of these metabolic abnormalities were abolished. We conclude that active acromegaly is characterized by profound disturbances of not only glucose but also lipid metabolism, which in theory may precipitate the increased mortality in this disease. By showing that these abnormalities and the concomitant overall insulin resistance can be completely reversed our results may also have important implications for other insulin-resistant states and for the potential therapeutic use of GH.

Acromegaly

A randomized comparison of intranasal and injectable octreotide administration in patients with acromegaly.

Fifteen acromegalic patients received four single doses of octreotide in random order (500 micrograms, 1000 micrograms, and 2000 micrograms applied intranasally and 100 micrograms given sc). Serum octreotide and GH data were subjected to pharmacokinetic analyses, and local nasal effects were evaluated by acoustic rhinometry. Average areas (+/- SEM) under the serum octreotide curves were: 2000 micrograms: 4597 +/- 536; 1000 micrograms: 1923 +/- 439; 500 micrograms: 957 +/- 168; and 100 micrograms sc: 896 +/- 81 micrograms.L-1.min (n = 13). The calculated relative availability was 27% +/- 0.03; 22% +/- 0.05; 22% +/- 0.03, respectively, for the three nasal doses. The rate of absorption after intranasally administered octreotide was greater than after sc application: t1/2 ka: 7.1 +/- 1.6; 7.9 +/- 1.6; 11.3 +/- 1.9, respectively, vs. 24.1 +/- 2.5 min, whereas the rates of disappearance were similar. GH suppression started immediately after application and reached minimum levels 1-2 h later. The average intervals during which serum GH was below 50% of preadministration values were: 2000 micrograms: 544 +/- 47; 1000 micrograms: 423 +/- 56; 500 micrograms: 289 +/- 52 vs. 351 +/- 34 min after sc injection of 100 micrograms. With 2000 micrograms intranasally all but one of the 15 patients attained constant suppression of serum GH below 5 micrograms/L for 273 to 680 min. Pharmacokinetic analysis demonstrated that 100 micrograms sc and 1000 micrograms intranasally induced the same GH suppressive effect and that 2000 micrograms intranasally approximately doubled the duration of action. Acoustic rhinometry was performed after nasal application of the largest dose of 2000 micrograms and after carrier (n = 9). A highly significant tumescence of the nasal mucosa was maximal after 10 min and gradually receded over the next 2 h. However, this was felt by the patients to be acceptable. The effect was caused by octreotide per se and was probably due to vasodilation.

Acromegaly

Effect of different test designs of immunoassays on "hook effect" of CA 19-9 measurement.

Determining serum CA 19-9 using regular Centocor kit frequently requires numerous repeats when specimens contain highly elevated levels of CA 19-9. We found that the number of repeats could be reduced if the Centocor kit with an extended concentration range was used. Using an extended Centocor kit could also eliminate falsely low CA 19-9 results. However, when a Biomira RIA kit, based on a competitive binding principle, was used, falsely low CA 19-9 values could be completely avoided and, in most cases, only a single repeat was usually required to arrive at the true result. This is because the level of CA 19-9 in the specimen can be approximated from the radioactivity count. Therefore, when designing an immunoassay for tumor markers, one needs to take into consideration the concentration range of the tumor marker in the specimens if one would like to avoid repeats and falsely low values.

Antigens, Tumor-Associated, Carbohydrate

Reduction in sella turcica volume. An effect of long-term treatment with the somatostatin analogue, SMS 201-995, in acromegalic patients.

Ten patients with acromegaly were treated with the long-acting somatostatin analogue, Sandostatin (SMS 201-995, octreotide) for more than one year. Computerized tomography was performed before and on 4 different occasions during the treatment. Sella turcica volumes were calculated in nine patients and showed a gradual decrease in all, averaging 32% +/- 14.6%, P less than 0.001 at the end of the study, which is probably indicative of a simultaneous reduction in adenoma size.

Acromegaly

Diurnal rhythm in serum osteocalcin: relation with sleep, growth hormone, and PTH(1-84).

We examined the role of sleep, growth hormone (GH), and parathyroid hormone [PTH(1-84)] as regulators of the diurnal rhythm of the osteoblastic bone marker, serum osteocalcin (OC). Nine normal subjects were followed with hourly blood sampling during one 24-hour period with normal sleep pattern, and one 24-hour period with absolute sleep deprivation. We found that the rhythm in serum OC did not exhibit significant changes (P greater than 0.50). Serum OC (mean +/- SE) was 30.9 +/- 2.5 micrograms/liter during sleep (2330-0730 hours) versus 29.9 +/- 4.9 micrograms/liter during sleep deprivation (not significantly different). The serum GH rhythm was significantly different on the two occasions (P less than 0.01). A maximum GH peak (mean +/- SE) of 10.3 +/- 2.4 micrograms/liter occurred at 0136 hours +/- 6 minutes during sleep compared with a maximal peak of 7.6 +/- 1.2 micrograms/liter (P less than 0.01) at 0245 hours +/- 20 minutes (P less than 0.01) during sleep deprivation. During sleep (2330-0730 hours), mean serum GH was 3.61 +/- 0.60 micrograms/liter compared with 2.39 +/- 0.40 micrograms/liter during sleep deprivation (P less than 0.005). Small insignificant changes occurred in serum PTH (1-84) and serum ionized calcium during the two occasions. We conclude that sleep and GH are not acute controlling factors of the diurnal rhythm in serum OC and the role of serum PTH(1-84) remains unsettled.

Adult

Effects of antibodies against octreotide in two patients with acromegaly.

Two patients developed specific IgG antibodies against octreotide after 2-3 years' treatment for acromegaly with this long acting somatostatin analogue. The presence of these antibodies reduced the plasma disappearance rate of total extractable octreotide by 60 and 80% respectively. When compared to that of non-immune acromegalic patients, the plasma half-life of octreotide in these two patients was 300 and 450 vs 110 min in those with no detectable octreotide antibodies. The sole observed consequence of the immunization was a marked prolongation of the interval of maximum GH inhibition from a mean of 5 to 8 and 10 h in the two patients described after octreotide injection.

Acromegaly

Acute effects of a somatostatin analogue on kidney function in type 1 diabetic patients.

Suppression of growth hormone by means of somatostatin has been suggested as a possible adjunct therapy in Type 1 diabetes. To assess the acute effect of the somatostatin analogue SMS 201-995 on kidney function in uncomplicated Type 1 diabetes, 13 normoalbuminuric, normotensive diabetic patients were investigated before and during IV infusion of SMS 201-995 (8 micrograms h-1). A control experiment with infusion of carrier only was also performed. The SMS infusion induced a reduction in the glomerular filtration rate (clearance of 125I-iothalamate) and renal plasma flow (131I-hippuran) from 140 +/- 15 (mean +/- SD) and 550 +/- 69 to 131 +/- 14 (2p less than 0.005) and 492 +/- 73 ml min-1 1.73-m-2 (2p less than 0.001), while filtration fraction and total renal resistance rose (both 2p less than 0.001). Urinary albumin excretion rate, blood pressure, and blood glucose concentration were unchanged. Plasma growth hormone and glucagon were significantly suppressed. The reduction in glomerular filtration rate and renal plasma flow correlated with the fall in glucagon concentration (r = 0.57, 2p = 0.04, and r = 0.63, 2p = 0.02). The urinary flow rate was markedly reduced, urine osmolality increased, and fractional excretion of sodium, calcium, and phosphate were reduced. Arginine vasopressin, atrial natriuretic peptide, angiotensin II, and aldosterone were unchanged by the SMS infusion. Thus SMS 201-995 acutely reduces glomerular filtration rate and renal plasma flow in uncomplicated Type 1 diabetes and has an antidiuretic effect. The effects may be related to suppression of glucagon secretion.

Adult

The anatomical fat pad and the radiological "scaphoid fat stripe".

The diagnostic value of the "scaphoid fat stripe" seen on X-rays in association with fractures of the scaphoid bone in the wrist is reviewed. The anatomical basis for these soft tissue radiological changes was investigated by dissection of the anatomical snuff-box and by injection studies. It is concluded that the snuffbox fat is part of a major fat-pad located in a recess radio-dorsally on the wrist. However the radiological structure named the "scaphoid fat stripe" was found to be the highly radiolucent common tendon sheath of the extensor pollicis brevis and the abductor pollicis longus muscles. Limitations in diagnostic sensitivity and specificity are discussed.

Adipose Tissue

The cardiovascular effects of octreotide treatment in acromegaly: an echocardiographic study.

Nine acromegalic patients were treated by the somatostatin analogue SMS 201-995 octreotide (Sandostatin (octreotide), Sandoz, Basle, Switzerland] 250 micrograms/day in 4 divided s.c. injections (50 + 50 + 50 + 100 micrograms) for 1 month, 250 micrograms/24 has continuous s.c. infusions for another month and thereafter 200 micrograms three times daily as s.c. injections. Echocardiography was performed before the treatment, following 1 month of octreotide s.c. infusion/injection and after 6 and 12 months of octreotide treatment. No differences in serum growth hormone, heart rate, blood pressure, cardiac contractility or left ventricular wall mass or wall thickness were found between the infusion and the injection periods. As compared to the pretreatment levels serum growth hormone decreased by 62 and 66% respectively following 6 and 12 months octreotide treatment. The heart rate per minute (+/- SD) decreased from the pretreatment level of 75 +/- 12 to 63 +/- 13 (P less than 0.007) at month 12. The systolic and the diastolic blood pressure decreased from the pretreatment level of 121 +/- 8 and 79 +/- 5 mmHg respectively to 108 +/- 7 (P less than 0.0007) and 71 +/- 7 mmHg (P less than 0.0001) respectively at month 12.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly

Enzyme immunoassay of hemoglobin A1c: analytical characteristics and clinical performance for patients with diabetes mellitus, with and without uremia.

We evaluated an enzyme immunoassay (Novo BioLabs) for determination of hemoglobin A1c and measured the contribution of carbamylated hemoglobin to the hemoglobin A1c results obtained by HPLC for patients with chronic renal failure. The reference interval, determined for blood donors, was 0.035-0.050 (i.e., 3.5% to 5% of the total hemoglobin). For non-diabetic patients with chronic renal failure, on hemodialysis, the mean proportion of hemoglobin A1c was 0.038 (SD 0.0045); for umbilical cord blood it was 0.006-0.009. For diabetic patients with normal or near-normal renal function, results by enzyme immunoassay (y) and HPLC (x) correlated well (r = 0.83): y = 0.99x - 0.005. Added fetal hemoglobin or carbamylated hemoglobin did not interfere with enzyme immunoassay, but added carbamylated hemoglobin co-chromatographed with hemoglobin A1c. Measurements for patients with chronic renal failure, with or without diabetes, by enzyme immunoassay and by HPLC, were compared with measurements for patients with diabetes mellitus but no renal failure. Carbamylated hemoglobin contributed 0.019 to the hemoglobin A1c results obtained by HPLC for patients with chronic renal failure.

Adult