Long-term results of surgery for lithium-associated hyperparathyroidism.

BACKGROUND: Lithium therapy for affective bipolar disease is frequently associated with hyperparathyroidism (HPT), but the results of surgical treatment are virtually unknown. The aim of this retrospective review was to analyse the long-term outcome after surgery for lithium-induced HPT in a large series of patients. METHODS: Seventy-one patients on chronic lithium therapy who underwent surgery in three university and three district hospitals in Sweden were followed for a median of 6.3 years. Histopathology, complications of surgery and normocalcaemia at 6 months after surgery and last follow-up were analysed. RESULTS: The primary histopathological diagnoses were adenoma (45 per cent), double adenomas (3 per cent) and hyperplasia (52 per cent). No permanent paresis of the recurrent laryngeal nerve was recorded but 13 per cent of the patients suffered from permanent hypoparathyroidism. At follow-up, the rate of persistent and recurrent HPT was 42 per cent regardless of the histopathological diagnosis. CONCLUSION: The results of conventional surgery for lithium-associated HPT are poor. The surgical approach should be adjusted for the multiglandular disease that is usually the cause of HPT in patients on chronic lithium therapy.

Parafibromin immunoreactivity: its use as an additional diagnostic marker for parathyroid tumor classification.

Parafibromin is a protein product derived from the hyperparathyroidism 2(HRPT2) tumor suppressor geneand its inactivation has been coupled to familial and sporadic forms of parathyroid malignancy. In this study, we have conducted immunohistochemistry on 33 parathyroid carcinomas (22 unequivocal and 11 equivocal) using four parafibromin antibodies directed to different parts of the protein. Furthermore, for a fraction of cases, the immunohistochemical results were compared with known HRPT2 mutational status. Our findings show that 68% (15 out of 22) of the unequivocal carcinomas exhibited reduced expression of parafibromin while the 25 sporadic adenomas used as controls were entirely positive for parafibromin expression. Additionally, three out of the six carcinomas with known HRPT2 mutations showed reduced expression of parafibromin. Using all four antibodies, comparable results were obtained on the cellular level in individual tumors suggesting that there exists no epitope of choice in parafibromin immunohistochemistry. The results agree with the demonstration of a approximately 60 kDa product preferentially in the nuclear fraction by western blot analysis. We conclude that parafibromin immunohistochemistry could be used as an additional marker for parathyroid tumor classification, where positive samples have low risk of malignancy, whereas samples with reduced expression could be either carcinomas or rare cases of adenomas likely carrying an HRPT2 mutation.

Role of vascular alpha-2 adrenoceptors in regulating lipid mobilization from human adipose tissue.

The role of alpha-2 adrenoceptors in lipid mobilization and blood flow was investigated in situ using microdialysis of subcutaneous adipose tissue in nonobese healthy subjects. The alpha-2 agonist clonidine caused dose-dependent biphasic response with increased glycerol levels at low clonidine concentrations and decreased glycerol levels at concentrations > 10(-7) mol/liter. Similar results were observed with epinephrine plus propranolol. Clonidine action was unaffected in the presence of labetalol (beta-/alpha-1 antagonist) but completely blunted by the presence of yohimbine (alpha-2 antagonist). The pseudolipolytic effect of clonidine was significantly more pronounced in gluteal as compared with abdominal adipose tissue. When clonidine was added together with the vasodilating agents nitroprusside or hydralazine, the pseudolipolytic effect was abolished and a dose-dependent decrease in dialysate glycerol was observed at all clonidine concentrations (10(-10)-10(-4) mol/liter). When ethanol was added to the perfusate to monitor blood flow, the escape of alcohol from the dialysate was accelerated by 30% with hydralazine or nitroprusside (P < 0.01) and 30% retarded (P < 0.05) by clonidine (10(-10) mol/liter). Thus, the results demonstrate an important role of blood flow for regulating lipid mobilization from adipose tissue in vivo. Alpha-2 adrenoceptor activation causes marked retention of lipids in adipose tissue due to vasoconstriction in combination with antilipoiysis.

Demonstration of an in vivo functional beta 3-adrenoceptor in man.

Although it is well established in several mammalian species that beta 3-adrenoceptors play a major role in regulating lipolysis and thermogenesis in adipose tissue, the functional existence and role of this receptor subtype in man has been controversial. We investigated whether the beta 3-adrenoceptor functionally co-exists with beta 1- and beta 2-adrenoceptors in vivo in human adipose tissue. Subcutaneous abdominal adipose tissue of healthy non-obese subjects was microdialyzed with equimolar concentrations of dobutamine (selective beta 1-adrenoceptor agonist), terbutaline (selective beta 2-adrenoceptor agonist), or CGP 12177 (selective beta 3-adrenoceptor agonist). All three agents caused a rapid, sustained, concentration-dependent and significant elevation of the glycerol level in the microdialysate (lipolysis index). However, only terbutaline stimulated the nutritive blood flow in adipose tissue, as measured by an ethanol escape technique. Dobutamine and CGP 12177 was equally effective in elevating the glycerol level (maximum effect 150% above baseline). Terbutaline was significantly more effective than the other two beta-agonists (maximum effect 200% above baseline). When adipose tissue was pretreated with the beta 1/beta 2-selective adrenoceptor blocker propranolol the glycerol increasing effect of dobutamine or terbutaline was inhibited by 80-85% but the glycerol response to CGP 12177 was not influenced. It is concluded that a functional beta 3-adrenoceptor is present in vivo in man. It co-exists with beta 1- and beta 2-adrenoceptors in adipose tissue and may therefore play a role in lipolysis regulation. It appears, however, that the beta 2-adrenoceptor is the most important beta-adrenoceptor subtype for the mobilization of lipids from abdominal subcutaneous adipose tissue because of its concomitant stimulatory effect on lipolysis and blood flow.

Operation for primary hyperparathyroidism: the new versus the old order. A randomised controlled trial of preoperative localisation.

BACKGROUND AND AIMS: In patients with primary hyperparathyroidism (PHPT), parathyroid imaging is nowadays routinely used for the purpose to perform a focused unilateral minimally invasive operation. The outcome of this new strategy has, however, not been established in randomised trials. MATERIAL AND METHODS: Patients were randomised to either preoperative localisation with sestamibi scintigraphy and ultrasonography (group I) or no preoperative localisation (group II). In group I, a minimally invasive parathyroidectomy was performed in patients in whom both localisation studies were consistent with a single pathological gland, whereas a conventional bilateral neck exploration was performed in cases with negative localisation findings. In group II all patients underwent conventional bilateral neck exploration. Primary outcome measure was normocalcaemia at 6 months postoperatively. RESULTS: In the preoperative localisation group (group I) 23/50 (46%) of the patients could be operated on with the focused operation whereas 26/50 (52%) were operated on by bilateral neck exploration. All patients in the no localisation group (group II; n = 50) were operated on with the intended bilateral neck operation. Normocalcaemia was obtained in 96% and 94% in group I and II, respectively. Total (localisation and operative) costs were 21% higher in group I. CONCLUSIONS: Routine preoperative localisation, with the intention to perform minimally invasive parathyroidectomy, is not cost effective if concordant results of scintigraphy and ultrasonography are a prerequisite for the focused operation. Less than half of the patients were successfully managed with this strategy, at a higher cost and without obtaining a more favourable clinical outcome.

The Swedish Infant High-grade Reflux Trial - Bladder function.

INTRODUCTION: It has been suggested that infants with high-grade vesicoureteral reflux (VUR) have lower urinary tract dysfunction (LUTD) that is characterised by large bladder capacity (BC) and increased post-void residual (PVR). However, most of these infants have normal or small BC in early infancy and develop large capacity during the first year of life. OBJECTIVE: This study aimed to see whether LUTD development during the infant years in children with high-grade VUR could be prevented by early reflux resolution. MATERIALS AND METHODS: For early VUR intervention, endoscopic treatment (ET) was used in a randomised trial comprising 77 infants (55 boys) aged <8 months with VUR grade 4-5 (n = 30/n = 47); 39 were randomised to antibiotic prophylaxis and 38 to ET. Voiding cystourethrogram, free voiding observation (FVO) and renal scintigraphy were performed at baseline and after 1 year. Bladder capacity and PVR were obtained from FVO. LUTD was defined as a BC of ≥150% of expected and a PVR of ≥20 ml. RESULTS: There were no differences in bladder function variables seen between the treatment groups, despite significant differences in VUR resolution. Analysing bladder function related to VUR outcome (VUR grade ≤2 vs grade >2), independent of treatment, showed that VUR grade ≤2 was associated with a smaller BC at 1 year (P = 0.050) (a tendency already seen at baseline) and a lower PVR at baseline (P = 0.010). PVR increased from baseline to 1 year (P = 0.037) in children with grade ≤2 VUR (Summary Table). The group with persistent bilateral grade 5 VUR at 1 year had more abnormal bladder variables compared with other study subjects, with a tendency of larger BC (P = 0.057), higher PVR (P = 0.0073) and more LUTD (P = 0.029) at baseline and a larger BC at 1 year (P = 0.016). In explanatory analyses, using logistic regression, a high PVR at baseline was identified as a predictor of VUR grade >2 (P = 0.046), persistent bilateral grade 5 VUR (P = 0.022), recurrent urinary tract infection (P = 0.034), and only a tendency was seen regarding new renal damage (P = 0.053). CONCLUSION: There was no between-group difference seen in bladder function. In children with VUR resolution at follow-up, independent of treatment, BC decreased, whereas PVR increased. High PVR at baseline was a predictive factor for both non-resolution of high-grade VUR and recurrent urinary tract infection. The results suggest that LUTD cannot be prevented by early VUR resolution, but rather is an important prognostic factor for VUR outcome in both endoscopic and prophylactic treatment.

Influence of trauma on plasma elimination of exogenous fat and on lipoprotein lipase activity and mass.

BACKGROUND: Trauma is followed by an increased plasma clearance and oxidation of exogenous fat but the underlying mechanism is not fully understood. AIM: To examine the influence of a surgical trauma on the plasma elimination of exogenous triglycerides (TG) and its relationship with lipoprotein lipase (LPL) activity and LPL mass. METHODS: Nine patients underwent a hypertriglyceridaemic clamp and a lipolytic capacity test before and after open abdominal surgery. The infusion rate was adjusted to maintain a stable TG concentration of 4 mmol x l(-1) during 180 min. The lipolytic capacity was determined as the change in LPL activity and mass following a bolus dose of 100 IU x kg BW(-1) heparin sodium. RESULTS: Postoperatively, the plasma elimination rate of fat was 2.6 times higher (P<0.001). Infusion of lipids in the postoperative state was followed by a smaller rise in free fatty acids (P<0.05) in comparison with the preoperative situation. The postoperative basal fasting LPL activity was half of that in the preoperative state and the LPL activity rose almost two-fold during the clamp. The heparin-induced rises in LPL activity and LPL mass were similar (n.s.) before and after surgery. CONCLUSIONS: A moderate surgical trauma is accompanied by a greater than two-fold rise in plasma elimination rate of exogenous fat despite a lower basal LPL activity and a virtually unchanged LPL pattern during infusion of lipids. Our study demonstrates that although trauma may substantially enhance the fat elimination capacity a significant proportion of the infused fat is not utilized for metabolic purposes.

Bone mineral recovery after parathyroidectomy in patients with primary and renal hyperparathyroidism.

Patients with hyperparathyroidism (HPT) generally display reduced bone mass due to excessive PTH activity. The effect of parathyroidectomy on bone mass changes in different types of HPT, however, is not well understood. Bone mineral density (BMD) was measured in the distal radius, total body, femoral neck, and lumbar spine by dual energy x-ray absorptiometry in four groups of patients with different hyperparathyroid conditions: primary symptomatic HPT (n = 54), primary asymptomatic (mild) HPT (n = 24), HPT associated with hemodialysis (n = 20), and HPT associated with renal transplant (n = 30). Subsets of patients with primary symptomatic HPT (n = 52), HPT associated with hemodialysis (n = 19), and HPT associated with renal transplant (n = 15) underwent parathyroidectomy, and bone density was measured longitudinally for 3 yr. Patients with primary asymptomatic (mild) HPT did not undergo surgery and were followed prospectively. Before surgery, all groups showed a greater reduction of bone mineral density in cortical bone (distal radius) than in predominantly trabecular bone (lumbar spine). In primary symptomatic HPT, the BMD z-score of the distal radius was -1.80 +/- 0.21 (+/-SEM), and the corresponding figures for the total body, femoral neck, and lumbar spine were -0.60 +/- 0.15, -0.54 +/- 0.14, and -0.53 +/- 0.18 compared with those of an age- and sex-matched reference group. In renal HPT BMD z-scores were -2.51 +/- 0.38 (hemodialysis patients) and -2.83 +/- 0.43 (renal transplant patients) for the distal radius and between -0.81 and -1.46 for the other measured sites. After parathyroidectomy, BMD increased by 1-8% at all sites in patients with primary symptomatic HPT and HPT associated with renal transplant. The largest increase in bone mass was observed in patients with HPT associated with hemodialysis, in whom the improvement amounted to 7-23%. In patients with primary HPT and HPT associated with hemodialysis, this increase in bone density resulted in virtual recovery from their preoperative bone loss. The majority of patients with asymptomatic primary HPT disease (n = 21) maintained their bone density during the follow-up period and have not shown evidence of increases in serum calcium or PTH levels, but three patients followed conservatively underwent parathyroidectomy due to progressive deterioration of BMD. We conclude that, regardless of the etiology, a large proportion of HPT patients show reduced bone density. In patients with primary symptomatic HPT and patients with HPT associated with hemodialysis, bone density increases after parathyroidectomy to an extent that largely restores the preoperative bone loss. However, no anabolic effect of parathyroidectomy on bone mass was observed in patients with HPT associated with renal transplant, probably because of their immunosuppressive therapy.

Bone mineral density in patients with chronic hypoparathyroidism.

Photon absorptiometry was used to measure skeletal mass in the proximal femur, lumbar spine, and distal radius in 19 females with hypoparathyroidism after operation for either thyroid carcinoma or hyperparathyroidism. Healthy subjects as well as normocalcemic patients who had undergone the same surgical procedure without developing hypoparathyroidism were used as controls. Skeletal mass was measured after a mean postoperative time of 13 and 10 yr in patients operated on for thyroid carcinoma and hyperparathyroidism, respectively. Bone mass was 10-32% greater in hypoparathyroid patients than in controls. In patients with retained parathyroid function after total thyroidectomy and surgical treatment of hyperparathyroidism, bone mass did not differ from that in age-matched healthy controls. Long term T4 medication in doses that suppressed endogenous TSH production was not associated with a decreased bone mass. Reduced PTH production, vitamin D treatment, and calcium supplementation may all have contributed to the increased bone mass found in the patients with postsurgical hypoparathyroidism.

Microdialysis of adipose tissue during surgery: effect of local alpha- and beta-adrenoceptor blockade on blood flow and lipolysis.

The adrenergic regulation of adipose tissue lipolysis and blood flow was investigated in nonobese patients (10 men and 23 women) undergoing cholecystectomy. Two microdialysis probes were inserted into the scadipose tissue and microdialyzed in the absence or presence of 10(-4) mol/L of either nonselective beta-adrenoceptor blocker propranolol or nonselective alpha-adrenoceptor blocker phentolamine. The catecholamines increased rapidly after intubation and subsequent surgery and extubation (P = 0.0001; F = 11-13). In the middle of surgery, the elevations of the noradrenaline and adrenaline levels were almost 3 times the basal value. At the end of surgery, they dropped in parallel, but increased again, only to reach their absolute maximum in connection with extubation (10- and 3-fold elevation, respectively). Plasma glycerol and free fatty acids started to increase about 30 min after plasma catecholamines. These increases in catecholamines were paralleled by an increase in the dialysate glycerol level (lipolysis index). Propranolol inhibited by two thirds (P = 0.003) and phentolamine further stimulated by 25% (P = 0.04) the increase in glycerol in the tissue dialysate induced by the operation. There was a transient decrease in tissue blood flow (ethanol escape from the microdialysis probe; P < 0.001) at the beginning of the surgical procedure. This was not affected by propranolol or phentolamine. In conclusion, during anesthesia and surgical trauma, endogenous catecholamines modulate adipose tissue lipolysis via alpha- and beta-adrenoceptors. However, the vasoconstriction induced by these procedures seems to be independent of the adrenergic system.

Lipolysis during abdominal surgery.

Subcutaneous adipose tissue lipolysis has been monitored with microdialysis during elective cholecystectomy by laparotomy in otherwise healthy nonobese subjects. Eight of the subjects received saline and seven received glucose iv during the operation. In both groups the glycerol level in the microdialysate (lipolysis index) started to increase steadily from the start of the general anesthesia until the abdominal wall was closed. Thereafter it leveled off and remained elevated until after extubation. Plasma glycerol started to rise after the surgical incision. The levels of noradrenaline and adrenaline, but not of insulin, glucagon, and cortisol in plasma, changed in parallel with that of glycerol in the microdialysate. The glycerol response in adipose tissue in the group receiving iv glucose was three times more marked than in the saline group (P = 0.01) in spite of marked hyperinsulinemia, but there was no difference between the groups in plasma glycerol response. The plasma noradrenaline response was 50% higher (P = 0.03) in the glucose group than in the saline group, but there was no difference between the groups in the plasma adrenaline, glucagon, or cortisol responses. Adipose tissue blood flow was measured by the escape of ethanol from the dialysis solvent into the extracellular space. It was constant throughout the experimental period in both groups. In conclusion, the lipolysis rate is accelerated during general anesthesia and abdominal surgery because of increased catecholamine production. Perioperative glucose infusion is associated with a further acceleration of the lipolytic rate in subcutaneous adipose tissue due to an additional activation of the sympathetic nervous activity that overrides the antilipolytic effect of the glucose-induced hyperinsulinemia. Other adipose regions may be less sensitive to glucose infusions and anesthesia.

Familial isolated hyperparathyroidism maps to the hyperparathyroidism-jaw tumor locus in 1q21-q32 in a subset of families.

Approximately 70 families with familial isolated hyperparathyroidism (FIHP) have been reported. Whether it is a separate entity or a variant of multiple endocrine neoplasia type 1 (MEN1 at 11q13) or hyperparathyroidism-jaw tumor (HPT-JT or HRPT2 at 1q21-32) syndrome is not known. We describe here 3 unreported families with familial primary hyperparathyroidism and evaluate their clinical, pathological, and genetic profiles. Biochemical and radiological screenings for MEN1 were negative for all families. In 2 families with a total of 10 affected cases and 3 female obligate carriers, there is no evidence of jaw or renal lesions despite careful radiological investigations. In both families the disease was linked to the 1q21-q32 region with the maximum logarithm of the odds (lod) scores of 3.10 and 3.43 for markers D1S222 and D1S249 respectively, at recombination fraction of 0. In 1 family 2 types of parathyroid pathology were found: 3 of chief cell type and 1 of oxyphil/oncocytic cell type. Two chief cell tumors and 1 oxyphil tumor were found to have loss of heterozygosity (LOH) involving loss of the wild-type alleles for chromosome 1q markers. In the third family, with 4 affected siblings, a parathyroid carcinoma and 2 cases of polycystic kidney disease were found. The parathyroid carcinoma also showed loss of heterozygosity in the 1q region. In conclusion, we found that the hyperparathyroidism traits in a subset of FIHP families are linked to the 1q21-32 markers in the HRPT2 region. We describe the spectrum of parathyroid disease in 1q-linked families involving 3 different types of pathology and demonstrate for the first time loss of wild-type alleles in these parathyroid tumors. Taken together, the results suggest that some of the FIHP are a variant of HPT-JT and that the gene involved is a tumor suppressor gene.

Decreased chemotactic and random migration of leukocytes during Intralipid infusion.

The soybean oil emulsion Intralipid was given intravenously to 12 healthy subjects for 2 hr. During the infusion an impairment of the chemotactic and random migration of leukocytes was noted. It was correlated to the dose given and to the degree of hypertriglyceridemia induced. Migration was fully restituted 22 hr after the infusion. Also when added in vitro Intralipid caused an impairment of leukocyte motility that followed a dose response pattern.

Characterization of insulin resistance after surgery.

The effects of insulin on glucose utilization were investigated in seven nonobese patients before and 24 hours after elective cholecystectomy. Surgery was followed by a significant increase in the circulating levels of glucose and insulin. The hypoglycemic action of insulin was reduced by one third (p less than 0.01) after surgery. In isolated fat cells after surgery there was a significant overall reduction of 35% to 50% of the effects of insulin on 3-0-methylglucose transport and lipogenesis at 1 mumol/L of glucose (where hexose transport is rate-limiting for insulin action). However, there was no change in insulin sensitivity in these cells. The effects of insulin on lipogenesis in adipocytes incubated with 100 mumol/L of glucose (where glucose metabolism is rate-limiting for insulin action) and adipocyte insulin receptor binding were not influenced by surgery. Insulin action in vivo and in vitro was not altered in five nonoperated control subjects 24 hours after they were given the same type of nutritional support as the cholecystectomy patients postoperatively. It was concluded that an elective moderate surgical trauma induces a rapid and marked insulin resistance that is not the result of postoperative nutritional restriction and involves a postreceptor binding alteration of glucose transport.

Skeletal remineralization after surgery for primary and secondary hyperparathyroidism.

Bone mineral was measured by photon absorptiometry before and after parathyroid surgery in patients with primary or secondary hyperparathyroidism (HPT). The mean bone mineral density of lumbar vertebrae was 0.82 +/- 0.04 (SEM) gm/cm2 in primary HPT (n = 7) and 0.86 +/- 0.05 gm/cm2 in secondary HPT (n = 11). These values are significantly lower than for age-matched normal subjects. After successful parathyroid surgery, the bone mass of the distal radius and lumbar vertebrae increased by approximately 10% within 3 months after operation and then remained stable during the first postoperative year. In conclusion, parathyroid surgery is followed by a significant increase of bone mass in primary and secondary HPT. The substantial increase in bone mass in parts of the skeleton consisting predominantly of trabecular bone, as well as in sites with predominantly cortical bone, indicates that remineralization after operation involves a generalized increase in bone mass.

Influence of parenteral carbohydrate on fat oxidation in surgical patients.

The administration of parenteral carbohydrate to nutritionally depleted patients in amounts approximating energy expenditure will markedly suppress fat oxidation. If the amount of carbohydrate is increased, net lipogenesis will occur. In contrast, it has been reported that in acutely ill, hypermetabolic patients net fat oxidation continued during the administration of glucose in quantities that exceeded energy requirements. This investigation was undertaken in an attempt to determine to what extent the latter response is due to persistent oxidation of endogenous plasma free fatty acids (FFAs) or stores of lipid in tissue. In this study, carbohydrate intake above energy equilibrium resulted in a 29% increase in CO2 production, a 2% increase in O2 consumption, and an increase in respiratory quotient (RQ) from 0.77 to 0.97 in nutritionally depleted patients. Injured and infected patients displayed a 44% increase in CO2 production and a 15% increase in O2 consumption, while the RQ increased only to 0.9. An isotopic palmitate infusion was used to measure FFA oxidation during parenteral nutrition with variable amounts of carbohydrate. Simultaneous estimates of net fat oxidation were made by indirect calorimetry. At low carbohydrate intakes, oxidation of plasma FFAs accounted for 50% of net fat oxidation in both groups of patients. Suppression of FFA oxidation was greater in the nutritionally depleted patients than in the acutely ill group at intermediate and at high carbohydrate intakes. We conclude that the continued net fat oxidation seen in acutely ill patients receiving high carbohydrate intakes is at least partially due to continuing plasma FFA oxidation. Tissue fat stores that are not in rapid equilibrium with plasma FFAs make a substantial contribution to net fat oxidation.

Biochemical hyperparathyroidism and bone mineral status in patients treated long-term with lithium.

Lithium is known to interfere with normal calcium homeostasis, but the long-term effects and possible clinical significance are uncertain. Thus, we measured indices of parathyroid function including intact parathyroid hormone (PTH) and ionized and total calcium levels in 26 patients treated for manic-depressive psychosis with lithium for 10 years or longer (mean +/- SD duration, 15 +/- 6 years). Increased ionized calcium levels were found in 11 patients and increased PTH concentrations in five patients. Altogether, 54% of the patients (14 of 26) had ionized calcium and/or PTH levels above the laboratory reference range. The PTH/ionized calcium relationship of the lithium-treated patients was compared with that of a group of normal subjects (n = 23) and with those of three different groups of patients with abnormal parathyroid function (chronic hypoparathyroidism, n = 21; primary hyperparathyroidism [HPT], n = 50; and tertiary HPT, n = 21). Lithium-treated patients had significantly higher ionized calcium levels (P < .0001) but not significantly higher PTH concentrations (P = .08) than the normal subjects. In comparison to the normal controls, lithium-treated patients had a right-sided shift in their PTH/ionized calcium relationship that was in the same direction but less prominent than in primary or tertiary HPT. Dual-energy x-ray absorptiometry disclosed similar bone mineral densities (BMDs) of lithium-treated patients and age-, sex-, and body mass-matched normal controls in the whole body, lumbar spine, and femoral neck (Z scores: +1.20, +1.22, and +1.02, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of carbohydrate intake on the lipolytic rate in depleted patients.

The effect of intravenous carbohydrate intake on glycerol turnover and fat metabolism was estimated in six nutritionally depleted surgical patients requiring total parenteral nutrition. Two diets were given. Nitrogen intake was the same in both diets. The calorie intake, adjusted by varying glucose intake, provided either 72% or 128% of the measured resting energy expenditure. Glycerol turnover was measured during administration of 5% dextrose solutions before starting total parenteral nutrition, and again after 4 days on each diet. Turnover rates of glycerol were closely correlated with plasma concentrations. However, fractional turnover rates were only two-thirds of normal values, indicating decreased clearance possibly due to decreased hepatic blood flow. Glycerol turnover, plasma free fatty acid concentrations, and rate of fat oxidation declined progressively with increased glucose intake. When compared with these results, previous studies of injured and septic patients showed: higher values for glycerol turnover, FFA concentrations, and fat oxidation; poor corrlation between glycerol turnover and concentration; inhibition of lipogenesis at high glucose intake; and high rates of norepinephrine excretion. The data suggest that in severe injury, counter regulatory hormones may almost completely block the effects of insulin on hormone sensitive lipase but have less influence on insulin stimulation of FFA esterification and inhibition of ketone body synthesis.

Survival of macroencapsulated allogeneic parathyroid tissue one year after transplantation in nonimmunosuppressed humans.

The use of immunoisolation devices may allow transplantation without need for immunosuppression and could widen the indications for cell transplantation. In this study, we evaluated the survival of encapsulated parathyroid tissue in nonimmunosuppressed humans. Autologous parathyroid implants: Seven patients undergoing parathyroidectomy had devices containing small pieces of their own parathyroid tissue implanted SC. These devices were explanted after 2-4 weeks for histological evaluation. Allogeneic parathyroid implants: Four patients with chronic hypoparathyroidism were transplanted with one to three large (40 microl) and one small (4.5 microl) device filled with meshed parathyroid tissue and implanted SC. The small devices were explanted at 4 weeks, while the large ones were explanted 8.5 to 14 months after implantation. In both studies, control implants were placed in nude mice. Autologous study results: At explantation, the grafts consisted of 22 +/- 6% endocrine tissue and 63 +/- 7% fibrosis, while 15 +/- 5% of the grafts were necrotic. Allogeneic study results: In devices explanted from the patients at 4 weeks, fibrosis dominated and only 1%, 5%, and 23% of the grafts consisted of endocrine tissue. A similar histological appearance was found in grafts from nude mice. In devices explanted at 8.5-14 months, histologically intact endocrine tissue was found in all patients. However, nearly all the tissue consisted of fibrosis. There was no detectable increase in the parathormone (PTH) level in all patients. Macroencapsulated human allogeneic parathyroid tissue can survive up to 1 year after transplantation into nonimmunosuppressed patients. However, marked fibroblast overgrowth occurred, especially in the allogeneic implant study, using meshed parathyroid tissue. This was probably not related to the allo-response, because similar findings were observed in the nude mouse implants. In future studies, better tissue preparation and improvements in the physiological milieu inside the device may help to reduce fibroblast overgrowth and increase survival of the parathyroid cells.

Plasma lipolytic activity after subcutaneous administration of heparin and a low molecular weight heparin fragment.

The effect of heparin and a low molecular weight heparin fragment (LMWH, mean molecular weight 4000-6000) on plasma anticoagulation and lipolysis was studied in eight healthy men. The activities of antifactor Xa (antiFXa), lipoprotein lipase (LPL), hepatic lipase (HL) and plasma levels of free fatty acids (FFA) were analysed after the injection of 5000 antiFXa units of heparin or LMWH subcutaneously. In comparison with heparin, the administration of LMWH resulted in a significantly higher antiFXa activity (p less than 0.001) but a lower release of LPL and HL (p less than 0.001), which did not increase plasma FFA. It is concluded that subcutaneous injection of LMWH in men elicits an adequate anticoagulant effect measured as antiFXa activity but has a negligible effect on plasma lipolytic activity.