Stig Engkjær Christensen

Low cerebrospinal fluid somatostatin in Parkinson disease An irreversible abnormality

In 39 parkinsonian patients, CSF somatostatin content was 88.0 ± 4.1 pg per milliliter, which was about 40% less than in controls (147.3 ± 5.1 pg per milliliter). Somatostatin values were unrelated to age, sex, body weight, total CSF protein, immunoglobulin, or cell count in either group. Parkinsonian values were not related to duration of disease, severity, specific signs, or treatment. In contrast to multiple sclerosis, in which CSF somatostatin is low only during relapses, the low somatostatin content of CSF in Parkinson disease seems to be irreversible, to be present at the onset of symptoms, and to imply an irreparable functional or structural alteration of somatostatin-secreting neurons.

CONTINUOUS SUBCUTANEOUS PUMP INFUSION OF SOMATOSTATIN ANALOGUE SMS 201‐995 VERSUS SUBCUTANEOUS INJECTION SCHEDULE IN ACROMEGALIC PATIENTS

Diurnal serum GH patterns were determined in 10 acromegalic patients before treatment, after 3 d continuous s.c. pump infusion and then after 3 d with three equal daily s.c. injections in both instances totalling 100 μg/24 h. Subcutaneous injections (33 μg) induced impressive suppression of serum GH lasting 3‐6 h in eight patients followed by escape to pretreatment values before the next injection. In contrast, continuous infusion resulted in greater and more stable 24 h suppression to the levels reached at the nadir between injections. Suppression of mean 24 h serum GH below 5 ng/ml was achieved by pump treatment in four patients, while two patients had mean values between 5 rig/ml and 10 ng/ml. In four patients occasional or all levels were above 10 ng/ml (24 h average 12.4‐102 ng/ml) implying either that adequate suppression by the SMS 201‐995, was impossible during the 3 d pump infusion period, or that the dose administered was inadequate. Carbohydrate tolerance was unaffected in either regimen, indicating that reduction in insulin antagonistic hormones balanced inhibition of insulin release. Interestingly, and in contrast to somatostatin, SMS 201‐995 did not inhibit TSH release. No untoward effects were observed at the moderate dosage and blood clinical chemistry was unchanged. Fairly constant diurnal serum SMS 201‐995 values were obtained during pump infusion, while levels undulated inversely with serum GH during injection treatment. Average diurnal serum somatostatin‐C immunoreactivity (all patients) decreased from 496 ± 129 (mean ± SD) to 385 ± 100 ng/ml (P < 0 003) during pump treatment and did not decrease further during the following 3 d injection treatment (363 ± 76 ng/ml).

Low somatostatin content in cerebrospinal fluid in multiple sclerosis: AN INDICATOR OF DISEASE ACTIVITY?

In 27 patients with multiple sclerosis (MS), and in 10 control subjects of comparable age, percent ideal body weight and sex ratio, the cerebrospinal fluid (CSF) content of somatostatin was measured by radioimmunoassay.

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 μg/ day in 4 divided s.c. injections (50 + 50 + 50 +100 μg) for 1 month, 250 μg/24 h as continuous s.c. infusions for another month and thereafter 200 μg 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 after 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> 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> 0.0007) and 71 ± 7 mmHg (P> 0.0001) respectively at month 12. The left ventricular wall thickness was reduced from 26 ± 3 mm before treatment to 24 ± 3 mm (P> 0.05) at month 6 and to 24 ± 4 mm (P> 0.04) at month 12. The left ventricular wall mass was 168 ± 48 g/m2 before octreotide treatment, 156 ± 46 g/m2 (NS) after 6 months and 157 ± 52 g/m2 after 12 months (P> 0.08) of octreotide treatment. In age and sex‐matched normal control subjects the left ventricular wall thickness was 20 ± 2 mm, and the left ventricular wall mass was 122 ± 26 g/m2. The wall thickness and the wall mass were increased in the acromegalic patients as compared to the controls before and following the octreotide treatment periods. We suggest that reduction of serum growth hormone levels by octreotide in acromegalic patients is associated with a decrease of the left ventricular wall thickness, but the wall thickness is not reduced to levels of normal control subjects.

Characterization of somatostatin release from the pancreas: the role of potassium

The effect of potassium on somatostatin secretion from the isolated perfused canine pancreas was studied. Potassium stimulated dose-dependent somatostatin release in a monophasic response pattern. The effect of potassium was abolished in the absence of calcium. Perfusion of 1 micronmol/l atropine and 1 micronmol/l propranolol was without effect on the potassium induced somatostatin release. The results suggest that the stimulatory effect of potassium on somatostatin release is secondary to increases in calcium influx into the D cell. The sympathetic and parasympathetic nerve endings in the pancreas are apparently not involved in the potassium mediated secretory processes.

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.

A double-blind study of the efficacy of neutral human and porcine insulin in type I diabetes using a glucose-controlled insulin infusion system

The comparative potency of equimolar amounts of soluble porcine and semisynthetic human insulin were studied in ten patients with type 1 diabetes in acute experimental situations. In both situations residual subcutaneous insulin depots were eliminated by intramuscular treatment exclusively with soluble insulin four days before the experiments. Then, practically identical metabolic states were achieved by connecting the patients to a glucose-controlled insulin infusion system (Biostator) 12 hours before the study. In one study, 0.5 g/kg body weight of glucose was administered intravenously as a bolus, and thereafter insulin was infused at a rate of 1.0 mU/kg/min. The decline in blood glucose was rectilinear and identical for the two insulins: y = -1.18x + 206 and y = -1.17x + 205. The insulin effect is well below maximum, and a 10% increase in the infusion rate of insulin was easily detected. Although changes in blood glucose and pancreatic glucagon were identical, a significantly lower plasma growth hormone level was noted after human insulin infusion. In the second study, 24 hours of near-normoglycemia was attained by the glucose-controlled insulin infusion system, the patients being supine and having identical meals at identical intervals. The diurnal blood glucose, plasma growth hormone, and pancreatic glucagon patterns were identical and the total 24 hour insulin consumption was 47.7 +/- 3.5 units and 47.7 +/- 3.7 units for the two insulins.

Circadian Variation of Plasma Growth Hormone in Normal Subjects and Diabetic Patients. Effects of Somatostatin Infusion, Age and Body Weight

When these studies were initiated late in 1968 the 24-h plasma growth hormone pattern in normal subjects was just discovered. Hunter and Rigal (1) had reported raised plasma growth hormone values during night in children. Quabbe and coworkers (2) had found in adults low day time plasma growth hormone values, intermittent bursts during night with high peaks occurring during times of deeper sleep. Glick and Goldsmith (3) had shown an effect of various feeding procedures on the 24-h plasma growth hormone level. Takahashi et al. (4) and Honda et al. (5) had demonstrated that the release of growth hormone during night coincides with the onset of electroencephalographically determined deep sleep. Experiments in which they had delayed or interrupted sleep provided evidence that the nocturnal growth hormone secretion was related to the onset of sleep and did not reflect a true endogenous circadian rhythm in growth hormone secretion. Extensive studies by Parker and coworkers (6, 7) have amply confirmed and extended these findings