Human recombinant insulin and amyloidosis: an unexpected association.

A 48-year-old patient with diabetes mellitus was treated with human (recombinant) insulin. He developed cutaneous amyloidosis twice at different locations where subcutaneous insulin had been injected. There were no signs of systemic amyloidosis. Additional pathological-anatomical investigations demonstrated insulin in one (the most recent) amyloid tumour. A limited number of similar cases have been reported in the literature, although mostly associated with porcine insulin. Cutaneous amyloidosis may be associated with local injections of human (recombinant) insulin. One should therefore also consider this diagnosis when finding tumours at sites where insulin has been injected.

Treatment of severe psychosis due to ectopic Cushing's syndrome.

Severe psychosis in patients with Cushing's syndrome is rare and generally difficult to treat. We report a 46-yr-old woman suffering from Cushing's syndrome caused by an inoperable ACTH-producing lung carcinoma. She was initially treated with chemotherapy and radiotherapy. Six months later she presented with severe psychosis. Laboratory findings revealed a severe hypokalemia and metabolic alkalosis, which was caused by extremely high serum ACTH (788 ng/l) and cortisol (4.2 micromol/l). She was unresponsive to treatment with conventional antipsychotic drugs; she was therefore sedated and intubated. Treatment was started i.v. with etomidate, which blocks the cortisol synthesis, and orally by nasogastric tube with mifepristone, which competes with cortisol for binding to their receptors. To counteract adrenal insufficiency, she received corticosteroids. After 5 days there was a normalization of the ACTH, cortisol levels, and the metabolic disorders. After discontinuing etomidate she was extubated; there were no signs of psychosis observed. Computed tomography (CT) scan of the brain showed no metastasis, however CT scan of the abdomen showed liver metastasis and bilateral adrenal enlargement. Unfortunately, the clinical situation worsened and the patient died due to progression of the metastasis. This case report demonstrates the efficacy of a treatment of mifepristone with etomidate in a patient with an ectopic ACTH-producing Cushing's syndrome.

Asystole during combination chemotherapy for non-Hodgkin's lymphoma: the acute tumor lysis syndrome.

The acute tumor lysis syndrome is a rare condition that has most frequently been documented in patients with rapidly dividing myeloproliferative and lymphoproliferative malignancies. It is characterized by the development of hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, acute renal failure and metabolic acidosis, as a result of massive tumor cell destruction, usually secondary to effective cytotoxic treatment. We want to present the case history of a 62-year-old woman who died from cardiorespiratory arrest during combination chemotherapy for non-Hodgkin's lymphoma due to acute tumor lysis syndrome. Despite general preventive measures, severe electrolyte abnormalities developed within 18 h of the start of chemotherapy. The general guidelines for the management of this potentially fatal oncologic emergency are discussed, with special emphasis on the pathogenetic mechanisms and risk factors in our patient.

Primary aortoduodenal fistula.

The aortoenteric fistula is a well-known but uncommon cause of gastrointestinal haemorrhage. It is usually secondary to previous reconstructive surgery of an abdominal aortic aneurysm. Primary aortoenteric fistula is a rare disorder which predominantly occurs in the duodenum. We report the case of a 76-year-old patient who presented with melaena and hypovolaemic shock due to a primary aortoduodenal fistula. Pathogenesis, diagnostic procedures and postmortem pathologic examination of this condition are discussed. The value of computed tomography in establishing the diagnosis is emphasized.

A patient with gastric fundal varices and colonic varices due to splenic vein thrombosis.

We report a patient presenting with melena. Endoscopic examination showed gastric fundal varices as well as colonic varices. The latter is rarely encountered and is usually associated with portal hypertension. On angiography there appeared to be a splenic vein thrombosis which is only reported once earlier as a cause of colonic varices. A short review of the literature concerning colonic varices is added.

Additional weight-bearing during exercise is more important than duration of exercise for anabolic stimulus of bone: a study of running exercise in female rats.

Mechanical loading is necessary for maintenance of skeletal integrity, but the most effective type, intensity, and duration of exercise are not known. In vivo experiments have indicated that the strain generated by the stimulus is more important than the duration of the stimulus. To elucidate this question, we studied 5-month-old female Wistar rats exercised on a motor-driven exercise belt for 17 weeks, 5 days per week (average velocity 20 m/min). Group 1 served as controls, group 2 was trained for 30 min, group 3 was trained for 30 min with a 50-g backpack, and group 4 was trained for 15 min with a 50-g backpack. Total body bone mineral content (BMC), bone mass of the lower extremities (LEBMC), total body lean soft-tissue mass (LSTM), and total body fat-tissue mass (FTM) were measured by dual-energy absorptiometry (DXA) at 0, 6, and 17 weeks. The BMC increased more in group 4 than in controls (15% vs. 8%, p < 0.03). In the other two intervention groups, no significant increases of total body BMC occurred compared with controls, although a trend was observed (12%). The LEBMC increased significantly in all exercising groups after 17 weeks, being 16% in group 2, 15% in group 3, and 20% in group 4, compared with 6% in controls (p < 0.05). The increase in LSTM after 6 weeks was most pronounced in group 3, at 20%, compared with 10% in the control group (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Loss of bone in the proximal part of the femur following unstable fractures of the leg.

We evaluated the subsequent loss of bone from the proximal part of the ipsilateral and contralateral femora and from the lumbar spine of seven men and nine women who had a fracture of the tibia. The average age was sixty years. All of the fractures were unstable, and the involved leg bore no weight for an average of eight weeks. The bone mineral density was measured with dual-energy x-ray absorptiometry of the lumbar spine and of the femoral neck and the trochanteric region of both hips immediately after the fracture, after the period of immobilization, and at approximately three, six, and twelve months after the fracture. During the period of immobilization, the bone mineral density of the trochanteric region decreased an average of 9 +/- 7 per cent on the side of the fracture, compared with the value immediately after the fracture, but there was no change on the contralateral side (p < 0.01). At twelve months, the average decrease in the trochanteric area was 15 +/- 10 per cent on the side of the fracture, compared with the value immediately after the fracture, but again there had been no change on the uninjured side (p < 0.01). The bone mineral density of the femoral neck on the side of the fracture had decreased 6 +/- 6 per cent at twelve months, compared with a decrease of 2 +/- 4 per cent on the uninjured side (p < 0.05). The bone mineral density of the lumbar spine decreased only during the period of unloading of the fractured leg (1 +/- 2 per cent, p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Intranasal calcitonin suppresses increased bone resorption during short-term immobilization: a double-blind study of the effects of intranasal calcitonin on biochemical parameters of bone turnover.

Immobilization is associated with increased bone resorption and decreased bone formation. We evaluated in a double-blind trial the effect of intranasal administration of salmon calcitonin on biochemical parameters of bone turnover in 32 patients immobilized for a prolapsed intervertebral disk. Calcitonin in a dose of two times 200 IU/day partially inhibited the increase in the fasting 2 h urinary hydroxyproline/creatinine ratio (OHPr/Cr) and calcium/creatinine ratio (Ca/Cr). The increase in OHPr/Cr was 40% less in the calcitonin group compared to the placebo group (P = 0.01), and the increase in Ca/Cr was 80% less in the calcitonin group (P = 0.04). Calcitonin also partially inhibited the increase in serum cross-linked carboxyl-terminal telopeptide of collagen type I (P < 0.05). The decrease in serum 1,25-dihydroxyvitamin D after 10 days of immobilization was significantly less in the calcitonin-treated group than in the placebo group (14 versus 29%, respectively; P < 0.05). Intranasal calcitonin did not influence the pain scores as measured with a visual analog scale (VAS). The tolerability of the nasal calcitonin preparation was excellent. We conclude that nasal salmon calcitonin counteracts the early increase in bone resorption induced by immobilization.

Human pharmacokinetics of orally administered (24 R)-hydroxycalcidiol.

To gain an insight in the regulation of (24R)-hydroxycalcidiol, we studied the pharmacokinetics of orally administered (24R)-hydroxycalcidiol in 6 healthy subjects without calcium supplementation, in 4 healthy subjects with calcium supplementation and in 6 patients with primary hyperparathyroidism. Various quantities related to calcium and vitamin D metabolism were also monitored. In the healthy subjects without calcium supplementation, the basal (24R)-hydroxycalcidiol concentration (Cb) in serum was 2.4 +/- 0.8 nmol/l (mean +/- SD, n = 5), the terminal serum half-time (t 1/2) 7.2 +/- 1.4 days, the production rate 0.05 +/- 0.01 nmol/kg.day, and the production rate/[calcidiol] ratio (1.5 +/- 0.4 x 10(-3) l/kg.day). In the healthy subjects studied, the serum concentration vs time curves exhibited a second maximum after administration, possibly due to binding by intestinal cells or (partial) uptake by the lymph system. In the calcium-supplemented healthy subjects, the pharmacokinetic quantities were not significantly different while the area under the serum concentration-time curve and the estimated bioavailability were significantly decreased. Basal concentration (Cb), production rate and the production rate/[calcidiol] ratio were significantly lower in patients with primary hyperparathyroidism but t 1/2 was unchanged. Exogenous (24R)-hydroxycalcidiol had no clear effect on calcium and vitamin D metabolism. In conclusion, a) exogenous (24R)-hydroxycalcidiol has no clear effect on calcium and vitamin D metabolism, b) clearance and production rate of (24R)-hydroxycalcidiol are not affected by calcium supplementation, c) bioavailability is lower in the calcium-supplemented state, d) basal concentration (Cb) and production rate are significantly decreased in patients with hyperparathyroidism.

Effects of short-term low-dose heparin administration on biochemical parameters of bone turnover.

Heparin therapy may cause osteoporosis. The effects of short-term low-dose heparin are not known. We have studied the effects of short-term heparin administration, twice daily 5000 IU s.c., for 10 days on the biochemical parameters of bone turnover in six healthy male volunteers. No effects were observed on the urinary excretion of hydroxyproline and calcium. Serum levels of cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), a new marker of bone resorption, did not change significantly. A slight but significant decrease in serum alkaline phosphatase was observed. TmP/GFR increased significantly during heparin administration. In all volunteers a uniform increase in serum transaminases appeared which completely reversed after discontinuation of heparin administration. We conclude that short-term low-dose heparin administration does not change biochemical parameters of bone resorption, but has a small significant suppressing effect on serum alkaline phosphatase levels. Heparin administration resulted in a significant but transient increase of serum transaminase levels.

Progressive hypercalcemia during continuous arterio-venous ultrafiltration (SCUF).

A case report is described of a patient who developed severe hypercalcemia during slow continuous arterio-venous ultrafiltration (SCUF). Which was instituted because of refractory congestive heart failure with pulmonary edema. The hypercalcemia was due to a preexisting mild hyperparathyroidism and aggressive fluid removal by SCUF. The differential diagnosis of hypercalcemia in the intensive care ward is discussed.

Biochemical parameters of bone turnover during ten days of bed rest and subsequent mobilization.

Immobilization is associated with increased bone resorption. To investigate the early onset of increased bone resorption, we evaluated 14 patients who were immobilized for 10 days because of lumbar disc protrusion. The fasting urinary hydroxyproline/creatinine ratio increased significantly after four days (P less than 0.01), reached a peak after 10 days (16.4 +/- 3.3 mumol/mmol, 27.6 +/- 8.8 mumol mmol, P less than 0.01) and returned slowly to baseline values after mobilization. The fasting urinary calcium creatinine ratio followed a similar pattern. Serum calcium and phosphate increased during immobilization (P less than 0.01). Serum 1,25-dihydroxyvitamin D decreased significantly during immobilization (98 +/- 33 pmol/l vs. 79 +/- 36 pmol/l, P less than 0.05), and reached a nadir one week after mobilization (P less than 0.01). We conclude that there is an early significant increment in resorption parameters, with a slow return during the mobilization period. Serum 1,25-dihydroxyvitamin D is suppressed as a result of the increased serum calcium and serum phosphate levels.