Changes in calcium homeostasis in acromegaly treated by pituitary adenomectomy

Patients with acromegaly have alterations in mineral metabolism. To determine the effect of correction of excess GH secretion on calcium metabolism, we studied 12 acromegalic patients before and 3-4 weeks after pituitary adenomectomy. Treatment of acromegaly resulted in significant decreases in both serum calcium [from 9.3 +/- 0.2 to 8.7 +/- 0.1 mg/dl (mean +/- SEM); P less than 0.01] and urinary calcium excretion (from 200 +/- 24 to 88 +/- 12 mg/24 h; P less than 0.0002). Serum phosphate also decreased significantly (P less than 0.01) from 4.8 +/- 0.2 to 4.3 +/- 0.2 mg/dl. Both serum immunoreactive PTH and calcitonin levels were normal initially and did not change after surgery. The mean serum 25-hydroxyvitamin D (25OHD) level was significantly (P less than 0.01) lower and the 1,25-dihydroxyvitamin D [1,25-(OH)2D] level was significantly (P less than 0.0001) higher in acromegaly compared with measurements in 25 normal subjects. After surgery, the serum 25OHD level did not change; however, the serum 1,25-(OH)2D concentration fell significantly (P less than 0.0001) from 60 +/- 4 to 43 +/- 2 pg/ml. A positive correlation was found between the decrements in urinary calcium excretion and the serum 1,25-(OH)2D level when the comparison was made between the decrements as percentages of pretreatment values (r = 0.64; P less than 0.05). The accumulated data suggest that the hypercalciuria in acromegaly might be due to intestinal calcium hyperabsorption, which could be attributed to the elevated circulating 1,25-(OH)2D level. Excessive GH secretion might stimulate the production of 1,25-(OH)2D and might also directly stimulate calcium absorption.     

Traumatic paraplegia in snowboarders

STUDY DESIGN: Patients with traumatic paraplegia resulting from snowboarding accidents were reviewed. OBJECTIVE: To understand the clinical features and mechanisms of paraplegic snowboarding injuries. SUMMARY OF BACKGROUND DATA: The recent explosion in the popularity of snowboarding has resulted in dramatically increased numbers of snowboarding injuries. However, little information is available as to the types and mechanisms of snowboard-related spinal injuries and their neurologic involvement. METHODS: The subjects of this study were six male patients, with an average age of 23.7 years, referred to the authors' institution for neurologic deficits associated with spinal injuries between January 1996 and March 1999. The clinical features of these patients were reviewed with respect to the mechanism of the injury, fracture pattern, neurologic status, treatment, and clinical outcome. The mean follow-up period was 23.7 months. RESULTS: The six snowboarders with traumatic paraplegia constituted a very homogenous group with the following features: They were all young men between the ages of 23 and 25 years. All the injuries had occurred at the vertebral junctions. The primary mechanism of the fractures was a backward fall from an intentional jump. The fracture patterns were of the flexion-distraction type. These homologous features suggest that this snowboarding group is at high risk for severe spinal injury. CONCLUSION: The high risk of traumatic paraplegia for a group within the snowboarding population requires the development and provision of injury prevention strategies specific to this group.     

Improved survival and ammonia metabolism by intraperitoneal transplantation of microencapsulated hepatocytes in totally hepatectomized rats

BACKGROUND: We evaluated the effects of intraperitoneal transplantation of microencapsulated hepatocytes in a 3-stage total hepatectomy rat model. METHODS: A new model of total hepatectomy was created as follows. First, the infrahepatic inferior vena cava was ligated just above the right renal vein. Seven days later, the portal vein was ligated and a portacaval shunt was established using a Teflon catheter over a venipuncture needle. Another 7 days later, total hepatectomy was completed by ligating and dividing the suprahepatic inferior vena cava, the hepatic artery, and the bile duct. Next, 4 x 10(7) hepatocytes (4% of the normal liver hepatocyte mass) isolated from male Wistar rats were microencapsulated within a collagen matrix enveloped by a 3-layer membrane of sodium alginate-poly-L-lysine-sodium alginate copolymer. Capsules containing hepatocytes (diameter, 500-800 microm) and empty capsules (control) were transplanted intraperitoneally 4 days before the total hepatectomy. Survival time and selected blood chemistry concentrations after the total hepatectomy were measured. The capsules were also examined histologically with hematoxylin and eosin staining and modified Gmelin's stain for bile pigments. RESULTS: The survival time was greater in the rats given the microencapsulated hepatocytes than in the control rats (17.3 +/- 3 vs 3.7 +/- 0.1 hours; P <.01). The blood ammonia concentrations increased soon after total hepatectomy but remained significantly lower in the rats with microencapsulated hepatocytes (P <.05). The microcapsules contained numerous viable hepatocytes with abundant bile pigments and no lymphocytic infiltration. CONCLUSIONS: Microencapsulated hepatocytes with an ultrathin polymer layer that protects them from inflammatory and lymphocytic reactions may facilitate their ability to function. In this study, 4 x 10(7) hepatocytes significantly prolonged the survival of rats that underwent hepatectomy and supported ammonia metabolism. Further development of this technique may permit its use in patients with hepatic failure.     

A case of fulminant type 1 diabetes mellitus with exocrine pancreatic insufficiency and enhanced glucagon response to meal ingestion

Non-specific aggression to endocrine alpha and beta cells as well as exocrine pancreas has been suggested in fulminant type 1 diabetes (FT1DM), while its effect on glucagon secretion and exocrine function is unknown. Here, we report a FT1DM case with exocrine pancreatic insufficiency and enhanced glucagon response to meal ingestion.     

Kir6.2 is required for adaptation to stress

Reaction to stress requires feedback adaptation of cellular functions to secure a response without distress, but the molecular order of this process is only partially understood. Here, we report a previously unrecognized regulatory element in the general adaptation syndrome. Kir6.2, the ion-conducting subunit of the metabolically responsive ATP-sensitive potassium (K(ATP)) channel, was mandatory for optimal adaptation capacity under stress. Genetic deletion of Kir6.2 disrupted K(ATP) channel-dependent adjustment of membrane excitability and calcium handling, compromising the enhancement of cardiac performance driven by sympathetic stimulation, a key mediator of the adaptation response. In the absence of Kir6.2, vigorous sympathetic challenge caused arrhythmia and sudden death, preventable by calcium-channel blockade. Thus, this vital function identifies a physiological role for K(ATP) channels in the heart.     

Effect of 1,25-dihydroxyvitamin D3 on insulin secretion: direct or mediated?

In order to clarify the role of vitamin D (D) in regulating insulin secretion, we studied the effect of long term (10 days) and short term (3 days) supplementation with D and/or calcium (Ca) on insulin secretion from the isolated, perfused pancreas of D- and Ca-deficient rats. The influence of the nutritional state induced by D deficiency was also evaluated. The long term supplementation of either D, Ca, or both restored the body weight and improved insulin secretion induced by high glucose concentration to the same extent; thus, no significant difference in insulin secretion was found between the D-only-supplemented group and the Ca-only-supplemented group. When the insulin secretion was compared in D-deplete vs. D-replete rats given the same amount of Ca, insulin secretion was significantly higher in D-replete animals, although plasma Ca levels were also higher. In short term experiments, insulin release was significantly augmented to a similar extent in D- or Ca-replete rats as compared with D- and Ca-deficient rats, despite no significant change in body weight. In a separate experiment, the pancreas from D-deficient rats was perfused with or without 1,25-dihydroxyvitamin D3 [1,25-OH)2D3] to observe its acute effect on insulin release. The perfusion with 1,25-(OH)2D3 did not affect insulin release. This result suggests that impaired insulin secretion in D-deficient rats is caused by a decrease in Ca in the body fluid and possibly by the lack of D effect on the pancreas.     

The polymorphism linked to the human insulin gene: its lack of association with either IDDM or NIDDM in Japanese

Polymorphism of 5' portion of the human insulin gene was examined in 188 unrelated Japanese subjects (49 normal, 71 with IDDM, and 68 with NIDDM) using restriction endonuclease analysis. Restriction fragments were classified according to the insertion size: Class 1 (600 base pairs), Class 2 (1300 base pairs), and Class 3 (2000 base pairs). We found a very high frequency of Class 1 alleles (96.8%) and a low frequency of both Class 2 (0.8%) and Class 3 alleles (2.4%) and that approximately 94% of the genotypes were Class 1/Class 1 homozygote. In addition, there was no correlation of allelic or genotypic frequency with NIDDM or IDDM. We conclude that length polymorphism of the human insulin gene cannot be a useful marker for diabetes in Japanese.