Bone metabolism in patients with primary hyperparathyroidism before and after surgery.

Primary hyperparathyroidism (PHPT) is accompanied with a reduced bone mineral density (BMD) and an increased risk of fracture. Surgery is the only option for cure. It is hypothesized that in patients with PHPT bone metabolism normalizes after parathyroidectomy (PTX) and that BMD gradually increases. Fifty-two patients with PHPT who underwent surgery were prospectively followed for 1 year. Biochemical analyses were performed at baseline and 1, 4, 7 days; 6 weeks; and 3, 6, and 12 months, and BMD before and one year after surgery. Parathyroid hormone (PTH), calcium, and the bone resorption marker dropped immediately, but transiently after PTX, bone formation decreased more slowly. Osteoprotegerin (OPG) as well as cathepsin K did not show significant changes. BMD of the lumbar spine, but not of the femoral neck, increased significantly within one year after surgery. Moderate correlations existed between the changes of total calcium, ionized calcium, as well as bone-specific alkaline phosphatase and changes of the lumbar BMD. Patients who needed postoperative supplementation with calcium and vitamin D had significantly higher PTH levels. Some gender-specific differences in patients with PHPT were observed. In patients with PHPT, males appear to be more severely affected than females. Within the first year after PTX, bone metabolism normalized, and BMD of the lumbar spine increased. Patients who needed a supplementation with calcium and vitamin D after PTX preoperatively had higher serum levels of PTH.

Sporadic hypercalcitoninemia: clinical and therapeutic consequences.

'Calcitonin screening' is not accepted as the standard of care in daily practice. The clinical and surgical consequences of 'calcitonin screening' in a series of patients with mildly elevated basal calcitonin and pentagastrin stimulated calcitonin levels are presented. 260 patients with elevated basal (>10 pg/ml) and stimulated calcitonin levels (>100 pg/ml) were enrolled in this prospective study. None of the patients was member of a known medullary thyroid carcinoma family. Thyroidectomy and bilateral central and lateral neck dissections were performed. Testing for the presence of germ-line mutations was performed in all patients. Histological and immunohistochemical findings were compared with basal and stimulated calcitonin levels. All patients were subsequently followed biochemically. C-cell hyperplasia (CCH) was found in 126 (49%) and medullary thyroid cancer was found in 134 (51%) patients. RET proto-oncogen mutations were documented in 22 (8%) patients (medullary thyroid cancer:18, CCH:4). In 56 (46%) of 122 patients, sporadic CCH was classified neoplastic ('carcinoma in situ'). Of 97 (72%; 10 with hereditary medullary thyroid cancer) had pT1 (International Union against Cancer recommendations 2002) and 33 (25%) had pT2 or pT3 and 4 (3%) pT4 tumors. Of 39 (29.1%) had lymph node metastases. 106 (79.1%; 15 (38.5%) with lymph node metastases) patients were cured. Evaluation of basal and stimulated calcitonin levels enables the prediction of medullary thyroid cancer. All patients with basal calcitonin >64 pg/ml and stimulated calcitonin >560 pg/ml have medullary thyroid cancer. Medullary thyroid cancer was documented in 20% of patients with basal calcitonin >10 pg/ml but <64 pg/ml and stimulated calcitonin >100 pg/ml but <560 pg/ml.

The bone marker plot: an innovative method to assess bone turnover in women.

BACKGROUND: Biochemical markers of bone turnover reflect the resorptive and reconstructive effects that act on the skeleton. Although elevated markers are commonly interpreted as a sign of an increased turnover rate, the balance between bone resorption and formation is mostly neglected. We introduce a graphic report combining both complementary processes. MATERIALS AND METHODS: Bone turnover markers were measured in 599 women (aged 25-74 years). To set up reference ranges, 269 from 599 women were selected because of having T-scores > -1 and inconspicuous basic laboratory data. Concentrations of resorption and formation markers were mathematically transformed to build up plots with four fields, symbolizing fast and slow resorption and fast and slow formation processes. The reference data of bone turnover were represented by a 95% confidence ellipse. For individual marker plots, we converted data of bone turnover markers from therapy follow-up profiles of patients in a similar manner. RESULTS: In pre-, peri- and postmenopausal women (n= 190, 39 +/- 6 years; n= 35, 51 +/- 6 years; n= 44, 55 +/- 5 years, respectively), the medians of the bone resorption marker CrossLaps and of the bone formation markers osteocalcin and aminoterminal propeptide of type I procollagen were 0.13/0.16/0.22 ng mL(-1), 21/21/25 ng mL(-1) and 36/35/45 ng mL(-1), respectively. In postmenopausal women, the marker plots revealed a shift towards accelerated bone resorption. A discrimination from osteopenic women (n= 138) failed. CONCLUSION: The proposed marker plot facilitates the intuitive perception of bone turnover in individual patients as well as in patient groups by a synopsis of the balance between bone formation and resorption with the rate of these processes.

Persistent arterial stiffness and endothelial dysfunction following successful pancreas-kidney transplantation in Type 1 diabetes.

OBJECTIVE: Successful simultaneous pancreas-kidney transplantation (SPK) in Type 1 diabetic (T1DM) patients results in improved cardiovascular outcome and survival. However, it is doubtful whether the impairment of cardiovascular and endothelial function in T1DM can be completely reversed. METHODS: Pulse-wave velocity, stroke volume, heart rate, serological markers of endothelial dysfunction (soluble intercellular, vascular cell-adhesion molecules, E-selectin, and plasminogen-activator-inhibitor-1) were measured in 10 T1DM patients after SPK with non-diabetic glucose levels, 10 T1DM patients with poor [T1DM>8; glycated haemoglobin (HbA1c)>8%], and 10 with good glucose control (T1DM<7, HbA1c<7%), in 6 non-diabetic patients after kidney transplantation (KT) and 9 non-diabetic control subjects (CON), matching for major anthropometric characteristics. RESULTS: Pulse-wave velocity was increased in SPK (P < 0.02 vs. CON, KT, T1DM<7) and in T1DM>8 (P < 0.02 vs. T1DM<7). Systolic blood pressure was increased in SPK (P < 0.05 vs. CON). Stroke volume was reduced in SPK, T1DM>8 and T1DM<7 and KT (P < 0.01 vs. CON). Heart rate was elevated in SPK and in T1DM>8 (P < 0.0003 vs. CON and T1DM<7). In SPK, soluble intercellular and vascular cell-adhesion molecules were 100% and 44% higher (P < 0.03 vs. CON), respectively, while plasminogen-activator-inhibitor-1 was decreased in SPK (P < 0.02 vs. CON). CONCLUSION: T1DM patients after SPK experience arterial stiffness, a higher heart-rate and blood pressure, reduced stroke volume and serological signs of endothelial dysfunction. Thus, functional and structural cardiovascular alterations as a result of glucotoxicity, uraemia and hypertension in T1DM might not be completely resolved by SPK.

Effect of acute citrate load on markers of bone metabolism in healthy volunteers.

BACKGROUND AND OBJECTIVES: This study aims to investigate the possible effects of acute citrate administration on bone metabolism in healthy men. MATERIALS AND METHODS: A placebo-controlled, crossover trial was conducted on 10 male volunteers. The volunteers received either a standardized infusion of citrate at 1.5 mg/kg body weight/min or the equal volume of placebo, separated by a washout period of 14 days. Serial blood and urine samples were collected and analysed for bone biochemical markers and electrolytes. RESULTS: Infusion of citrate resulted in increased serum levels of the bone formation marker osteocalcin (OC) and bone resorption marker C-telopeptide of type 1 collagen (CTX). Increases in CTX and OC were positively correlated to the surge in the serum concentration of intact parathyroid hormone (iPTH) but only OC showed correlation to changes in ionized calcium. Citrate infusion showed no effect on serum concentrations of bone alkaline phosphatase, osteoprotegerin, and bone tartrate-resistant acid phosphatase 5b, or the expression of receptor activator of nuclear factor kappa B ligand. Variations in OC and CTX were short-term as both bone markers gradually declined within 90 min following citrate exposure. CONCLUSION: Acute citrate load resulted in profound alterations of the bone markers OC and CTX. The short-term increase of CTX suggests a temporary shift to a higher bone turnover rate, although the clinical consequence of the observed changes in bone markers remains open.

Estrogen interaction with the anterior pituitary of female rats: Differential cytosol binding, nuclear translocation and stimulation of RNA synthesis by 17 beta-estradiol and tamoxifen.

The interaction of tamoxifen (trans-1-(rho-beta-dimethylaminoethoxyphenyl)-1,2-diphenylbut-1-ene) with the cytosol estrogen receptor of the anterior pituitary of female rats was studied. No differences were recorded between incubations of cytosol samples with 17 beta-[3H]estradiol performed in the presence of absence of unlabeled 17 beta-estradiol and tamoxifen, respectively, thus suggesting that these interactions were at common receptor sites and excluding possible cooperative interactions. Competition experiments and Scatchard plot analysis of saturation experiments add further evidence for common receptor sites. A dissociation constant for tamoxifen of Kd - 2 nM was recorded. Tamoxifen was found to be bound to a moiety sedimenting the 4-5 S region, on a 6-24% linear sucrose density gradient at low salt concentrations, whereas 17 beta-estradiol sedimented in the 8-9 S area. These data suggest possible conformational changes of the receptor in the presence of tamoxifen. Furthermore, nuclear estrogen receptor levels remained elevated for at least 80 h after the application of tamoxifen alone or in a combination with 17 beta-estradiol, and a concomitant inhibition of cytosol receptor replenishment was noted. Tamoxifen and 17 beta-estradiol, respectively, were found to stimulate progesterone receptor levels when applied through 5 days. Tamoxifen plus 17 beta-estradiol administration elevated progesterone receptor contents above those found for each of the two compounds alone. On the other hand, tamoxifen enchanced the 17 beta-estradiol-induced prolactin serum levels, but did not stimulate prolactin serum levels by itself. These data combine to suggest that tamoxifen interacts with common estrogen receptor sites at the rat anterior pituitary.

Nuclear translocation of estrogen-receptor complex and stimulation of RNA synthesis by estrogens of different biological potencies in the female rat pituitary.

Stimulation of RNA synthesis and of nuclear translocation of estrogen-receptor complexes was investigated in isolated nuclei of anterior pituitaries of castrated female rats after injection with estrogens of different biological potencies. The assay system for the estimation of total RNA synthesis was validated and data suggest that incorporation of [3H]UMP into acid-precipitable material is consistent with RNA synthesis. An increase in RNA synthesis was seen 30 min after application of either 17 beta-estradiol, estriol or 1,3-diacetyl-17 alpha-ethinyl-7 alpha-methyl-1,3,5,(10)estratriene-17,3-ol (DMEE). RNA synthesis was maximal 90 min after estrogen application. Thereafter, RNA synthesis decreased slowly and reached pretreatment levels 3, 8 and 30 h after application of estriol, 17 beta-estradiol and the diacetyl derivative of ethinyl-estradiol, respectively. All estrogens were found to stimulate rapidly nuclear translocation of estrogen-receptor complexes. Peak levels of nuclear receptor contents were reached 30 min after administration of estrogens. A concomitant depletion of cytosol receptor levels was noted. Nuclear retention of estrogen-receptor complexes paralelled duration of enhanced RNA synthesis and correlated with biological potencies of the steroids. Data of present experiments combine to suggest that long-term nuclear retention is a requisite for expression of biological activity of estrogens at the anterior pituitary. Furthermore, the degree of biological activity seems to be associated with duration of stimulation of RNA synthesis, amount of estrogen-receptor complexes translocated to the nucleus, and duration of nuclear retention.

Mutant and immunochemical studies on the involvement of cytochrome b5 in fatty acid desaturation by yeast microsomes.

The involvement of cytochrome b5 in palmitoyl-CoA desaturation by yeast microsomes was studied by using yeast mutants requiring unsaturated fatty acids and an antibody to yeast cytochrome b5. The mutants used were an unsaturated fatty acid auxotroph (strain E5) and a pleiotropic mutant (strain Ole 3) which requires either Tween 80 and ergosterol or delta-aminolevulinic acid for growth. Microsomes from the wild-type strain possessed both the desaturase activity and cytochrome b5, whereas those from mutant E5 contained the cytochrome but lacked the desaturase activity. Microsomes from mutant Ole 3 grown with Tween 80 plus ergosterol were devoid of both the desaturase activity and cytochrome b5, but those from delta-aminolevulinic acid-grown mutant Ole 3 contained cytochrome b5 and catalyzed the desaturation. The cytochrome b5 content in microsomes from mutant Ole 3 could be varied by changing the delta-aminolevulinic acid concentration in the growth medium, and the desaturase activity of the microsomes increased as their cytochrome b5 content was increased. The antibody to yeast cytochrome b5, but not the control gamma-globulin fraction, inhibited the NADH-cytochrome c reductase and NADH-dependent desaturase activities of the wild-type microsomes. It is concluded that cytochrome b5 is actually involved in the desaturase system of yeast microsomes. The lack of desaturase activity in mutant Ole 3 grown with Tween 80 plus ergosterol seems to be due to the absence of cytochrome b5 in microsomes, whereas the genetic lesion in mutant E5 appears to be located at ther terminal desaturase.

Early diagnosis and curative therapy of medullary thyroid carcinoma by routine measurement of serum calcitonin in patients with thyroid disorders.

To identify patients with medullary thyroid carcinoma (MTC) at a potentially curable stage of the disease, serum concentrations of calcitonin (hCT) were determined in 14,000 patients (including 10,158 patients with thyroid nodules) referred to a thyroid outpatient clinic. Excluding patients in whom elevated basal hCT concentrations had already been known at the time of their referral, 507 patients with thyroid nodules presented basal concentrations of hCT of more than 10 pg/ml. Following stimulation by IV pentagastrin (0.5 microg/kg BW), hCT concentrations of more than 100 pg/ml were seen in 103 patients. This group included 32 new cases of MTC (29 patients with sporadic MTC and 3 new index cases of the familial form) and 43 patients with C cell hyperplasia (CCH). Among the 3,843 patients without thyroid nodules, 2 were found to harbor sporadic MTC while 4 had CCH. As compared to 1.1 cases of MTC per 1,000 patients with nodular thyroid diseases diagnosed in our institution before hCT screening was begun, 3.2 cases of MTC per 1,000 patients were identified when hCT was determined in all patients with thyroid nodules. The determination of hCT in all patients with thyroid nodular disease facilitates the timely diagnosis of MTC, thus providing the chance of curative surgery.

Primary hyperparathyroidism as the leading symptom in a patient with a Y791F RET mutation.

Primary hyperparathyroidism (PHP; serum calcium 2.75 mmol/L, PTH 226 pg/ml) had been the first clinical manifestation of MEN-2A in a female patient (aged 55 years) with a mutation (Y791F, TAT-->TTT) in exon 13 of the RET proto-oncogene. The patient has a pentagastrin-induced rise in serum calcitonin (up to 57 pg/ml) considered normal for noncarriers but abnormal in family members of MEN-2 patients. This is the first case of MEN-2 due to this specific mutation with primary hyperparathyroidism as the first manifestation of the disease. In addition, the patient harbored, within the Menin gene, a polymorphism (D418D) reportedly associated with sporadic primary hyperparathyroidism. This case report indicates that molecular biological tests in MEN- 2 may only suggest a certain phenotype but cannot predict it with certainty. It may also suggest that genetic screening for MEN-2 may be advisable in patients with primary hyperparathyroidism and a borderline-high pentagastrin stimulation test, even in the absence of a positive family history.

Routine measurement of plasma calcitonin in nodular thyroid diseases.

In a prospective study, plasma concentrations of human calcitonin (hCT) were determined in 1062 consecutive patients with thyroid nodular disease. Basal plasma hCT was above the normal range (>6 pg/mL) in 55 patients and was elevated up to more than 100 pg/mL (range, 127-5459) in 3 of these 55 patients. A pentagastrin-induced rise in hCT up to more than 100 pg/mL was observed in only 1 of 38 patients with a basal concentration of hCT between 5-10 pg/mL, but was found in 10 of 31 patients with basal hCT ranging from 10-100 pg/mL. Histologically, 7 of the 14 patients with either basal or stimulated plasma concentrations of hCT above 100 pg/mL presented C cell hyperplasia, which in one case showed histological transition into a small (diameter, 3 mm) medullary thyroid carcinoma (MTC). Including this patient, MTC was found in 6 of the 12 patients. We conclude that the routine determination of hCT in all patients with thyroid nodular disease should be supplemented by pentagastrin-stimulation when the basal hCT concentration exceeds 10 pg/mL. Patients with basal and/or stimulated plasma CT concentrations of more than 100 pg/mL should be operated on because they run a substantial risk to suffer either MTC or C cell hyperplasia, a potentially precancerous condition. This will increase the chance of a timely diagnosis of MTC and provide the chance of curative surgery.

Acetaminophen has greater antipyretic efficacy than aspirin in endotoxemia: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To compare the antipyretic efficacy of aspirin and acetaminophen (INN, paracetamol) in 30 male volunteers with the use of endotoxin (lipopolysaccharide) to elicit a standardized febrile response. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in parallel groups. Subjects received an intravenous endotoxin bolus of 4 ng/kg after premedication with either placebo, 1000 mg aspirin, or 1000 mg acetaminophen by mouth. RESULTS: Peak body temperatures were 38.5 degrees C +/- 0.2 degrees C in the placebo group, 37.6 degrees C +/- 0.2 degrees C in the acetaminophen group (P = .001 versus placebo), and 38.6 degrees C +/- 0.2 degrees C in the subjects treated with aspirin (P = .001 versus acetaminophen; P = .570 versus placebo) at 4 hours after lipopolysaccharide infusion. Subjective symptom scores for chills and perception of fever were higher in the placebo group than in the acetaminophen group (chills, 2.5 +/- 0.3 versus 1.0 +/- 0.2, P = .009 and fever, 2.5 +/- 0.2 versus 2.0 +/- 0.2, P = .021). Tumor necrosis factor-alpha, interleukin-6, and interleukin-8 levels rose by several orders of magnitude (P < .001 versus baseline in all groups), without significant intergroup differences. CONCLUSIONS: Acetaminophen was the superior antipyretic drug in endotoxemia compared with aspirin. Treatment with acetaminophen ameliorates subjective symptoms induced by endotoxemia without compromising the humoral response of a subject to endotoxin. This observation has clinical interest and may also help to improve the lipopolysaccharide model, which can be used to test anti-inflammatory and anticoagulatory drugs.

Effects of parathyroidectomy on lead mobilization from bone in patients with primary hyperparathyroidism.

Since lead (Pb) accrued from environmental exposure accumulates in bone with a half life time between 6 and 10 years, a release of bone Pb into the circulation and/or urine (PbU) should be expected in diseases with increased bone metabolism such as hyperparathyroidism. We studied 60 patients with primary hyperparathyroidism (pHPT, 50 women, 10 men, aged 61.4 +/- 10.6 and 64.1 +/- 9.9 years, respectively) (a) before, (b) 1-6 months, and (c) 6-12 months after parathyroidectomy. Besides lead in blood (PbB) and lead in 24-h urine samples (PbU), parathyroid hormone (PTH), serum Ca2+, osteocalcin (OC), phosphate (PO4), and serum pyridinoline cross-linked telopeptide (cTP) were determined. Control data were determined in 20 healthy age-matched subjects. As expected, Ca2+ decreased after parathyroidectomy. Mean PbB in patients with pHPT was in the same range as in controls. A decrease of PbB after parathyroidectomy was found in the interval beyond 6 months. In contrast, mean PbU initially increased after surgery (3.05 +/- 1.94 vs. 4.25 +/- 2.65 microg/l, P = 0.004) and was not different beyond 6 months in comparison with preoperative values at (c). Investigating only patients with PTH < 150 ng/l, no significant PbB or PbU alterations were detected before and after parathyroidectomy. In patients with PTH > 150 ng/l, the decrease of PbB at (c) was more pronounced as was the increase of PbU at (b). In these patients, PbB and OC as well as PbB and cTP were correlated preoperatively. In conclusion, our data show that in environmentally lead-exposed (by food or by pollution) hyperparathyroid individuals, there is no hazardous PbB release from bone. The preoperative correlation between PbB and OC in pHPT patients with PTH > 150 ng/l provides evidence that in fact there is a Pb release from bone into the blood-pool by bone remodeling. The increase of PbU after parathyroidectomy is suspected to be caused by PTH-dependent Pb accumulation in the kidney, which seems to be restored with decreasing PTH. Moreover, our data confirm prior findings that bone remodeling seems to be normalized 6 months after parathyroidectomy.

Follow-up of metastatic breast cancer patients with a mucin-like carcinoma-associated antigen: comparison to CA 15.3 and carcinoembryonic antigen.

During a follow-up program, breast cancer patients were monitored with serum analyses of mucin-like carcinoma-associated antigen (MCA), CA 15.3 and carcinoembryonic antigen (CEA). Minimum as well as maximum marker values of the individual patterns were selected for further evaluation. Marker levels of risk patients differed significantly from those of patients with metastases. In several risk patients, elevated marker levels (especially of MCA) preceded clinical diagnosis of metastases for several months. In cases with already diagnosed metastases, sensitivity of MCA was comparable to CA 15.3 or CEA. The type of metastases determined marker sensitivity, concentration and the difference between maximum and minimum values.

Adrenal function in patients with chronic renal failure.

Previous studies have reported divergent findings on the function of the hypothalamic-pituitary-adrenal axis in patients with chronic renal failure (CRF). The low-dose adrenocorticotropin (ACTH) test offers the possibility of unmasking adrenal dysfunction, which might remain undiscovered using the ACTH test with the standard 250-microg dose. Furthermore, the choice of renal replacement therapy (either hemodialysis or continuous ambulatory peritoneal dialysis [CAPD]) might have an impact on adrenal function. To investigate these possibilities, ACTH tests were performed with three different doses (ie, 1, 5, and 250 microg) in 14 CRF patients and in seven healthy controls. Seven of the CRF patients were receiving chronic hemodialysis and seven were receiving CAPD. Basal plasma concentrations of cortisol were comparable in the three groups tested (5.3+/-0.4 microg/dL in the controls, 6.6+/-0.7 microg/dL in the hemodialysis patients, and 7.9+/-1.0 microg/dL in the CAPD patients), whereas basal ACTH concentrations were significantly elevated in the CRF patients (28.5+/-3.8 pg/mL in the hemodialysis patients and 33.0+/-6.0 pg/mL in the CAPD patients) when compared with normal controls (17.0+/-1.4 pg/mL; P < 0.05). All three doses of ACTH resulted in a rapid increase of plasma cortisol concentrations that was comparable in all three groups. In the hemodialysis patients, a trend toward a diminished response to the lowest dose of 1 microg was noticed. We conclude, therefore, that adrenal response to ACTH in various doses is unaffected in CRF independent of whether hemodialysis or CAPD is chosen for renal replacement therapy.

Efficacy of folinic versus folic acid for the correction of hyperhomocysteinemia in hemodialysis patients.

The effectiveness of intravenous folinic acid or intravenous folic acid for the treatment of hyperhomocysteinemia of hemodialysis patients is unknown. In a randomized, controlled, double-blind trial, 66 hemodialysis patients were administered either 15 mg of folic acid or an equimolar amount (16.1 mg) of folinic acid intravenously three times weekly. Normalization of total homocysteine (tHcy) plasma levels after 4 weeks of treatment was achieved in 10 patients (30.3%) in the folic-acid group and 6 patients (18.2%; P: = 0.389) in the folinic-acid group (normalization at any time during the study period in 39.4% and 33.3% of the patients; P: = 0.798). The relative reduction in tHcy plasma levels at week 4 was 32.2% in the folic-acid group and 34.1% in the folinic-acid group. A high baseline tHcy plasma concentration (P: = 0.00001), methylenetetrahydrofolate reductase (MTHFR) 677TT/1298AA genotype (P: = 0.03540), and low red blood cell folate concentrations (P: = 0.02285) were associated with a better relative response to treatment. Normalization of tHcy plasma levels was dependent on a lower baseline tHcy level (P: = 0.01976), younger age (P: = 0.00896), and MTHFR 677TT/1298AA or 677CT/1298AC genotypes (P: = 0.00208 and P: = 0.02320, respectively). A 4-week course of intravenous folinic acid is not superior to intravenous folic acid in reducing elevated tHcy plasma levels in hemodialysis patients. The response to treatment is predicted by tHcy plasma level, red blood cell folate content, and MTHFR genotype.

Early postoperative stress: video-assisted wedge resection/lobectomy vs conventional axillary thoracotomy.

Postoperative pain is a major cause of ineffective breathing after lung surgery, predisposing patients to hypoxemia. Because potent analgesics like opioids depress ventilation and other analgesic techniques are time-consuming, efficient postoperative pain therapy is difficult. Therefore, a less painful surgical approach could be beneficial. Forty-seven patients with diagnosis of a pulmonary nodule were prospectively studied. Patients were assigned to a video-assisted thoracic surgery (VATS) group (n=22) or a group undergoing axillary thoracotomy (n=25). Visual analogue scale (VAS) scores, plasma glucose levels, plasma epinephrine and plasma norepinephrine levels, as well as arterial oxygen (PaO2) and carbon dioxide (PaCO2) tension were determined the day before surgery, and 3, 15, 24, 48, and 72 h after surgery. Postoperative piritramide (a synthetic morphine compound) demand was recorded. VAS values were significantly lower (p<0.05) during the whole observation period in the VATS group. Significantly higher epinephrine levels were observed 3 and 15 h after surgery (267.4 +/- 28 vs 111.8 +/- 13 ng/L; p<0.01; and 176.6 +/- 46.5 vs 96 +/- 14.5 ng/L; p<0.05) in the thoracotomy group, whereas there was no significant difference in norepinephrine (correction of norephinephrine) levels. Piritramide demand was significantly (p<0.05) reduced in the VATS group throughout the whole observation period. There was no difference in PaCO2 values but PaO2 Values were higher in the VATS group over 72 h, with maximum differences occurring at 15 h after operation: 60.9 +/- 1.9 vs 49.2 +/- 2.4 mm Hg (p<0.01). In conclusion, the videoendoscopic approach is associated with less postoperative pain and better oxygenation than traditional surgical approaches.

Bone metabolism in patients more than five years after bone marrow transplantation.

We investigated the bone metabolism of 22 patients (median age 38 years) over 6 years after allogeneic bone marrow transplantation (BMT). Biplanar roentgenograms of the thoracic and lumbar spine were used to diagnose vertebral deformities caused by fractures. The actual bone mineral density (BMD) of the lumbar spine and the femoral neck were measured. Laboratory tests included calcium, phosphate, parathyroid hormone, a marker of bone resorption (beta-crosslaps, CTX), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase), osteoprotegerin (OPG)--antagonist of the osteoclast differentiation factor RANKL, and sex hormone status. One patient had a vertebral fracture. Seven patients (28%) had osteopenia in the lumbar spine while 12 patients (48%) had osteopenia in the femoral neck. Bone resorption was increased in nine patients (43%) and bone formation was increased in four patients (20%). BMT recipients had significantly increased serum levels of OPG (P=0.029). Three women (75%) and four men (25%) were hypogonadal. The data showed that BMD is reduced and bone metabolism is still disturbed more than 6 years after BMT. The RANKL/osteoprotegerin system appears to play an important role in the pathophysiology of late post transplantation osteoporosis.

The significance of determining CA 15-3 in the cytosol of breast cancer.

The identification of tumor markers in patients who had undergone operation for breast cancer provides important information in the follow-up in addition to evaluation by clinical and visual methods. The aim of our study was to determine the clinical prospective value of CA 15-3, mucin-like carcinoma-associated antigen and carcinoembryonic antigen in preoperative measurement of serum samples in patients with primary breast cancer, and to determine CA 15-3 and steroid receptors in the cytosol of the tumor. The results show that the most exact correlation occurred between serum CA 15-3 and the different stages of the tumor. However, there is no conclusive evidence for the prognosis and the course of the disease from preoperative findings of tumor markers in serum samples or in the cytosol of the tumor in patients with breast cancer.

The use of the pyridostigmine growth hormone-releasing hormone stimulation test to detect growth hormone deficiency in patients with pituitary adenomas.

The pyridostigmine (PD)/growth hormone-releasing hormone (GHRH) stimulation test was used to determine growth hormone (GH) secretion in patients with pituitary adenomas prior to (n = 55) and after (n = 72) transsphenoidal adenomectomy, as well as in 98 controls. In controls, maximum concentrations of GH showed a strong negative relationship both with body mass index (BMI) and age. Having calculated the 95% confidence intervals for maximum GH concentrations to be expected for any given age and BMI according to a statistical model, we compared these individually predicted ranges to GH concentrations actually observed in patients with pituitary disease during PD/GHRH stimulation. Preoperatively and postoperatively, a maximum GH concentration below the calculated confidence intervals was seen in 29 of 55 (52%) and in 57 of 72 (79%) of these patients, respectively. In the remaining patients, maximum GH concentrations were in or above the range defined by these confidence intervals. Our results indicate that maximum concentrations of GH during the PD/GHRH test depend to a large extent on the individuals' age and BMI. The results obtained with the PD/GHRH stimulation must, in each individual patient, be compared with a large control group taking into account both age and BMI. In individuals older then 55 years and with a BMI greater than 35 kg/(2), the diagnosis of GH deficiency cannot safely be made, at least not with this test.