Clinical course of pain in acute osteoporotic vertebral compression fractures.

PURPOSE: The authors prospectively determined the natural course of pain in patients with conservatively treated acute osteoporotic vertebral compression fractures (VCF). In addition, the type of conservative therapy that these patients received was assessed. MATERIALS AND METHODS: Patients older than 50 years, referred for spine radiography for acute back pain, were asked to complete a baseline clinical questionnaire. Patients with an acute VCF were followed up at 6 and 23 months with a questionnaire that included a Visual Analog Score (VAS) and type of pain medication and other conservative treatment. Significant pain relief was defined as a decrease in VAS of 50% or more. RESULTS: Forty-nine patients (mean age, 78 years; range, 51-95) with acute VCF were followed up for almost 2 years. Significant pain relief was noted in 22 of 35 patients (63%) at 6 months and in 25 of 36 (69%) at 23 months. In patients with persisting pain at 23 months (mean VAS 6.4), some decrease in VAS was apparent at 6 months but not in the 6-23 months interval. No predictors for significant pain relief could be identified. Patients with significant pain relief used less pain medication and had less physical therapy. CONCLUSIONS: In most patients with an acute VCF, pain decreases significantly with conservative therapy, predominantly in the first 6 months. However, almost 2 years after an acute VCF, a third of patients still had severe pain necessitating pain medication and physical therapy in the majority. No predictors for transition from acute to chronic pain could be identified.

Sodium appetite in sheep induced by cerebral ventricular infusion of angiotensin: comparison with sodium deficiency.

Intraventricular administration of supraphysiological amounts of renin, nerve growth factor preparation, or angiotensin II greatly increased the consumption of water and hypertonic sodium bicarbonate solution by sheep. These effects were antagonized by intraventricular administration of drugs that prevent the formation of angiotensin II or block its receptors. The fact that these angiotensin-blocking drugs did not change the sodium intake of sodium-deficient sheep challenges the idea that central angiotensin action is involved in sodium appetite due to a deficiency.

Postpartum thyroiditis and autoimmune thyroiditis in women of childbearing age: recent insights and consequences for antenatal and postnatal care.

Postpartum thyroiditis is a syndrome of transient or permanent thyroid dysfunction occurring in the first year after delivery and based on an autoimmune inflammation of the thyroid. The prevalence ranges from 5-7%. We discuss the role of antibodies (especially thyroid peroxidase antibodies), complement, activated T cells, and apoptosis in the outbreak of postpartum thyroiditis. Postpartum thyroiditis is conceptualized as an acute phase of autoimmune thyroid destruction in the context of an existing and ongoing process of thyroid autosensitization. From pregnancy an enhanced state of immune tolerance ensues. A rebound reaction to this pregnancy-associated immune suppression after delivery explains the aggravation of autoimmune syndromes in the puerperal period, e.g., the occurrence of clinically overt postpartum thyroiditis. Low thyroid reserve due to autoimmune thyroiditis is increasingly recognized as a serious health problem. 1) Thyroid autoimmunity increases the probability of spontaneous fetal loss. 2) Thyroid failure due to autoimmune thyroiditis-often mild and subclinical-can lead to permanent and significant impairment in neuropsychological performance of the offspring. 3) Evidence is emerging that as women age subclinical hypothyroidism-as a sequel of postpartum thyroiditis-predisposes them to cardiovascular disease. Hence, postpartum thyroiditis is no longer considered a mild and transient disorder. Screening is considered.

Thyroid function disorders--Guidelines of the Netherlands Association of Internal Medicine.

Thyroid function disorders are common with a female to male ratio of 4 to 1. In adult women primary hypothyroidism and thyrotoxicosis have a prevalence of 3.5/1000 and 0.8/1000, respectively. This guideline is aimed at secondary care providers especially internists, but also contains relevant information for interested general practitioners and gynaecologists. A multidisciplinary working group, containing delegates of professional and patient organisations, prepared the guideline. According to principles of 'evidence-based medicine' available literature was studied and discussed. Considering the availability and quality of published studies a practical advice was formulated. For a full overview of the literature and considerations the reader is referred to the original version of the guideline (accessible through NIV-net). In this manuscript we have aimed to provide the practicing internist with practical and 'as evidence-based as possible' treatment guidelines with respect to thyroid function disorders.

[The surgical treatment of Graves' disease]. / Chirurgische behandeling van de ziekte van Graves.

A man aged 80 and three women aged 66, 26, and 39 years respectively, underwent surgery for Graves' disease. The first woman had pneumonia and experienced thyrotoxic storm. Euthyroidism was restored with antithyroid drugs (ATD) and thyroidectomy was performed as ablative treatment for hyperthyroidism. The man presented with thyrotoxicosis and had severe Graves' ophthalmopathy. After euthyroidism was restored with ATD, he underwent subtotal thyroidectomy. The second woman presented with severe thyrotoxicosis but was allergic to ATD. She was treated with iodine and beta-blockers after which subtotal thyroidectomy was done as an ablative procedure. Medical treatment for hyperthyroidism failed in the last patient and, as she had experienced severe psychological disturbances during a previous relapse, she too chose surgery as a definitive treatment option. In two patients the postoperative course was complicated by early hypocalcaemia and one of these patients experienced temporary recurrent laryngeal nerve paralysis. Surgery has a limited role in the treatment of Graves' disease. In pregnant women with severe ATD-resistant thyrotoxicosis, surgery is the only treatment option, while in patients with Graves' orbitopathy surgery may be preferable because of its neutral and perhaps even beneficial effects on eye symptoms. Large goitre size and thyroid nodules are concomitant reasons for choosing surgery, as are allergy to ATD and patients' preference. Lastly, in patients who have suffered from severe thyrotoxicosis, surgery provides rapid and definitive treatment. Early morbidity following surgery is common and should be discussed with the patient.

Experience of 5-aminosalicylate nephrotoxicity in the United Kingdom.

AIM: To study 5-aminosalicylate nephrotoxicity in patients with inflammatory bowel disease in the UK. METHODS: A detailed postal questionnaire was sent to all 1298 names in the British Society of Gastroenterology database and 290 consultant members of the Renal Association. The British Society of Gastroenterology reported new cases monthly, the Renal Association 6 monthly. Results were expressed as estimated glomerular filtration rate. RESULTS: Retrospective study: cases--British Society of Gastroenterology:Renal Association 202:87, aged 15-76 years. Median peak (range) creatinine (British Society of Gastroenterology:Renal Association) - 300:301 (78-1200) micromol/L. Prospective study - 59 cases, median age 52 years (M:F ratio: 47:12). Median pre-treatment estimated glomerular filtration rate: 76.9 (123.9-39), at diagnosis 28.4 (80.5-3.6, creatinine range: 92-1361 micromol/L), recovery 46.8 [111.2-end stage renal failure] mL/min/1.73 m2. Recovery of renal function was significantly improved for patients treated for < 12 months [n = 10, median recovery estimated glomerular filtration rate 70.5 (92-26.9) vs. > 12 months 38.4 (111.2-end stage renal failure) mL/min/1.73 m2, P = 0.028]. CONCLUSIONS: Regular monitoring of renal function may allow earlier detection of nephrotoxicity, particularly during the first year of therapy. Based on an inflammatory bowel disease prevalence in the United Kingdom of 412 x 10(5) with about 50% on treatment, we estimate that the incidence of clinical nephrotoxicity in patients taking 5-aminosalicylate therapy is approximately one in 4000 patients/year.

Renal tubular proteinuria in patients with irritable bowel syndrome.

OBJECTIVE: Irritable bowel syndrome (IBS) is a common condition that is poorly understood. We have previously demonstrated tubular protinuria in patients with inflammatory bowel disease. This study examined whether tubular proteinuria was a feature of IBS. METHODS: Eighty control subjects (male:female, 28:52; age range 20-65 years) and 21 patients with IBS (male:female, 9:12; age range 16-64 years) (not significant) were recruited. Patients with known renal disease, hypertension, diabetes or microbiological evidence of urinary infection were excluded. The IBS patients all fulfilled the ROME II criteria. None had preceding gastroenteritis. Urinary alpha1-microglobulin (alpha1-M) was measured in a second-voided morning urine sample and corrected for urinary concentration by measurement of creatine. Blood samples were analysed for haematochemical indices including C-reactive protein. Statistical analysis was by unpaired t test. RESULTS: None of the IBS patients were reclassified with inflammatory bowel disease over a 5-year follow up period. All had normal haematochemical parameters. Mean +/- standard deviation urinary alpha1-M concentrations were significantly higher in IBS patients than controls (IBS patients, 1.17 +/- 0.65 mg/mmol; controls, 0.75 +/- 0.36 mg/mmol; P < 0.01) and exceeded 1.5 mg/mmol (the upper reference limit) in seven patients. There was no difference in urinary alpha1-M concentrations in the diarrhoea-predominant and constipation-predominant groups (mean +/- standard deviation, 1.342 +/- 0.65 versus 0.76 +/- 0.48 mg/mmol; P = 0.062). CONCLUSIONS: Urinary alpha1-M concentration is commonly increased in IBS, suggesting the presence of renal proximal tubular injury.

[Minimally-invasive parathyroidectomy: a good operative procedure for primary hyperparathyroidism even without the use of intraoperative parathyroid-hormone assessment or a gamma probe]. / Minimaal invasieve parathyreoïdectomie: ook zonder het gebruik van intraoperatieve parathormoonmeting of gammaprobe een goede behandeling voor primaire hyperparathyreoïdie.

OBJECTIVE: To evaluate the results of minimally-invasive parathyroidectomy without the use of intraoperative parathyroid-hormone assessment or a gamma probe. DESIGN: Retrospective. METHODS: In 2 community hospitals in the Netherlands, 49 patients with primary hyperparathyroidism in whom preoperative investigations had shown a solitary adenoma underwent minimally-invasive surgery by the lateral neck approach. In total 9 men and 40 women with an average age of 58 years (limits: 25-84) underwent this procedure. More extensive preoperative investigations were carried out at the Mesos Medisch Centrum (n = 29) including neck CT in 76% of patients as well as ultrasonography, and scintigraphy. At the Diakonessenhuis (n = 20) scintigraphy was the preferred method of adenoma localisation. Intraoperative parathyroidhormone assessment and a gamma probe were not used in the operative procedure. At the Diakonessenhuis intraoperative frozen-section investigations were done. RESULTS: In 44 of the 49 patients (90%) minimally-invasive parathyroidectomy resulted in normocalcaemia. In the remaining 5 patients a second procedure was necessary--a conventional neck exploration and also resulted in normocalcaemia. In 2 of these patients the adenomas had been missed during first procedure by the surgeon, while in 3 other patients preoperative examinations were falsely positive in the sense that the adenoma proved to be present but in an area other than that indicated by preoperative imaging. Permanent recurrent laryngeal-nerve paralysis complicated the postoperative course in 2 patients. The success rate of the minimally-invasive operation was the same for both groups. CONCLUSION: Without the use of intraoperative parathyroid-hormone assessment or a gamma probe minimally-invasive parathyroidectomy was successful in 90% of patients.

Do gastroenterologists monitor their patients taking 5-amino-salicylates following initiation of treatment.

BACKGROUND: 5-Amino salicylate (5-ASA) medications may rarely be associated with a significant decline in renal function and interstitial nephritis. British Society of Gastroenterology guidelines advise regular renal function monitoring for patients taking these drugs. AIM: To assess whether gastroenterologists in Kent were following best practice guidelines regarding the monitoring of their patients on 5-ASA therapy. METHODS: Using longitudinal community and regional pathology databases for the Kent population, our renal unit regularly screens a total population of 300 000 for evidence of renal disease. The data extracted are analysed using an automated computerised system to identify patients requiring intervention for kidney disease. All patients taking 5-ASA medication were identified from a population of 300 000. The pathology database was studied to identify the patients on 5-ASA treatment and whether they had had renal function tests. RESULTS: 800 adult patients were identified taking 5-ASA therapy. 612 patients received 5-ASAs for 3 months or more, and these were included in the final analysis. 293 patients had no renal function checks while on treatment. 79 patients had renal function tests less than once every 4 years and 36 patients once every 2-4 years. 204 patients had renal function measurements in 50% or more of years of treatment, of whom 116 were checked every year. Some patients were started on treatment with abnormal results at baseline and some with identified kidney disease continued on their 5-ASAs. CONCLUSIONS: The majority of patients receiving 5-ASA compounds do not have regular renal function monitoring. Clinicians are failing to follow best practice guidelines.

Tumor necrosis factor alpha inhibits the hormonal response of the pituitary gland to hypothalamic releasing factors.

Tumor necrosis factor alpha (TNF alpha), a monokine produced by activated macrophages and monocytes, may be an essential mediator of the pathogenesis and of the hormonal response to endotoxic shock. It has been suggested that an elevated level of TNF alpha is a marker for morbidity and mortality during septic shock, and that treatment with antibodies against TNF alpha decreases mortality. Because monokines have been shown to interact at the hypothalamic-pituitary level, we have studied the effect of TNF alpha on basal and stimulated hormone release from normal rat anterior pituitary cells. After 3 days of incubation, primary cultures of rat anterior pituitary cells were stimulated with either 0.5 ng/ml CRF, 3 ng/ml AVP, 10 ng/ml angiotensin II (AII), 10(-6) M TRF, 10(-8) M LHRH, or 10(-8) M GHRH, alone or in the presence of 20 or 50 ng/ml human or murine recombinant TNF alpha. The culture media were analyzed for ACTH, GH, LH, and PRL content. Each experiment was performed in triplicate and was repeated 3 to 8 times. Time-course experiments (n = 3) demonstrated that TNF alpha inhibited CRF-stimulated ACTH production over a period of 8, 16, and 24 h, but had no effect before a period of 4 h. At doses ranging from 1 to 100 ng/ml, TNF alpha did not affect basal ACTH secretion but inhibited CRF-stimulated ACTH release in a dose-dependent manner (ED50 approximately 10 ng/ml). At a dose of 50 ng/ml, TNF alpha inhibited AVP-stimulated ACTH release by 30% and blocked the effect of AII. TNF alpha (20 and 50 ng/ml) completely prevented the CRF-AVP potentiation of ACTH release. Similarly, TNF alpha inhibited the stimulated release of GH (100% inhibition), LH (35% inhibition), and PRL (100% inhibition). TNF alpha had no effect on the basal secretion of GH or LH but inhibited basal PRL in a dose-dependent manner. The administration of the monokine did not cause any cellular damage because 48 h after removal of the TNF alpha treatment the cells showed normal basal and stimulated hormone levels in response to their specific stimuli. Incubation of TNF alpha solutions with antibody to TNF alpha reversed all TNF alpha actions. These data suggest that TNF alpha inhibits the secretion of pituitary hormones and particularly suppresses the response of the corticotroph cells. This inhibitory effect may contribute to the increased mortality observed in cases of severe septic shock with high circulating TNF alpha levels.

Binding and activation properties of angiotensin II in dispersed rat anterior pituitary cells.

The properties of angiotensin II receptors were studied in isolated rat anterior pituitary cells prepared by trypsin digestion. Angiotensin II bound in a time- and temperature-dependent manner to pituitary cells, with Kd of 4.1 x 10(-9) M. The heptapeptide, des-Asp1-angiotensin II, had only one-tenth of the affinity of the octapeptide (Ki = 5.5 x 10(-8) M). These two peptides displayed a similar potency ratio in their ability to stimulate ACTH release from pituitary cells. These results indicate that angiotensin II may play a regulatory role in controlling ACTH secretion from the pituitary gland.

Specific effect of CV 205-502, a potent nonergot dopamine agonist, during a combined anterior pituitary function test.

CV 205-502, an octahydrobenzo[g]quinoline, is a dopamine agonist compound that is not an ergot or ergoline derivative. To investigate the site of action of CV 205-502, three groups of five men were given single daily doses of CV 205-502 (0.04, 0.06, or 0.08 mg/day, doses that suppress plasma PRL by 60-80% for 24 h) for 5 days; on day 6 a combined anterior pituitary function test using iv administration of four hypothalamic releasing hormones (TRH, 200 micrograms; GHRH, 100 micrograms; CRH, 100 micrograms; LHRH, 100 micrograms) was performed. One month later the challenge tests were repeated to obtain control values. The following hormones were measured by RIA in plasma: TSH, ACTH, cortisol, PRL, GH, LH, FSH, and testosterone. With the exception of plasma PRL levels, basal and releasing hormone-stimulated values were similar after CV 205-502 administration and after the 1-month washout period. Basal plasma PRL was lower after CV 205-502 administration, and the response to TRH was attenuated by all three doses of CV 205-502 (the mean percent inhibition values were 76%, 93%, and 94%, respectively). All three doses of CV 205-502 were well tolerated, and another group of men well tolerated 0.1 mg daily. The results confirm that CV 205-502 is a potent dopamine agonist, which directly inhibits lactotropic cells but has no effect on other pituitary cell types.

Decrease of free thyroxine levels after controlled ovarian hyperstimulation.

Controlled ovarian hyperstimulation could lead to opposing effects on thyroid function. Therefore, in a prospective study of 65 women undergoing controlled ovarian hyperstimulation, thyroid hormones, T4-binding globulin, TPO antibodies, gonadotropins, estradiol, and PRL were measured before and after controlled ovarian hyperstimulation. After ovarian stimulation (mean +/- SE of mean): free T4 decreased, 14.4 +/- 0.2 vs. 12.9 +/- 0.2 pmol/L (P < 0.0001); thyroid-stimulating hormone increased, 2.3 +/- 0.3 vs. 3.0 +/- 0.4 mU/L (P < 0.0001); T4-binding globulin increased, 25.2 +/- 0.7 vs. 33.9 +/- 0.9 mg/L (P < 0.0001); total T4 increased, 98.1 +/- 2.3 vs. 114.6 +/- 2.5 nmol/L (P < 0.0001); total T3 increased, 2.0 +/- 0.04 vs. 2.3 +/- 0.07 nmol/L (P < 0.0001); TPO antibodies decreased, 370 +/- 233 U/mL vs. 355 +/- 224 U/mL (P < 0.0001); LH decreased, 8.1 +/- 1.1 vs. 0.4 +/-0.1 U/L (P < 0.0001); FSH did not change, 6.5 +/- 0.6 vs. 7.9 +/- 0.9 U/L (P = 0.08); human CG increased, <2 +/- 0.0 vs. 195 +/- 16 U/L (P < 0.0001); estradiol increased, 359.3 +/- 25.9 pmol/L vs. 3491.8 +/-298.3 pmol/L (P < 0.0001); and PRL increased, 0.23 +/- 0.02 vs. 0.95 +/- 0.06 U/L (P < 0.0001). Because low maternal free T4 and elevated maternal thyroid-stimulating hormone levels during early gestation have been reported to be associated with impaired psychomotor development in the offspring, our findings indicate the need for additional studies in the children of women who where exposed to high levels of estrogens around the time of conception.

Blockade of the growth hormone (GH) receptor unmasks rapid GH-releasing peptide-6-mediated tissue-specific insulin resistance.

The roles of GH and its receptor (GHR) in metabolic control are not yet fully understood. We studied the roles of GH and the GHR using the GHR antagonist pegvisomant for metabolic control of healthy nonobese men in fasting and nonfasting conditions. Ten healthy subjects were enrolled in a double blind, placebo-controlled study on the effects of pegvisomant on GHRH and GH-releasing peptide-6 (GHRP-6)-induced GH secretion before and after 3 days of fasting and under nonfasting conditions (n = 5). Under the condition of GHR blockade by pegvisomant in the nonfasting state, GHRP-6 (1 microg/kg) caused a increase in serum insulin (10.3 +/- 2.1 vs. 81.3 +/- 25.4 mU/L; P < 0.001) and glucose (4.2 +/- 0.3 vs. 6.0 +/- 0.6 mmol/L; P < 0.05) concentrations. In this group, a rapid decrease in serum free fatty acids levels was also observed. These changes were not observed under GHR blockade during fasting or in the absence of pegvisomant. We conclude that although these results were obtained from an acute study, and long-term administration of pegvisomant could render different results, blockade of the GHR in the nonfasting state induces tissue-specific changes in insulin sensitivity, resulting in an increase in glucose and insulin levels (indicating insulin resistance of liver/muscle), but probably also in an increase in lipogenesis (indicating normal insulin sensitivity of adipose tissue). These GHRP-6-mediated changes indicate that low GH bioactivity on the tissue level can induce changes in metabolic control, which are characterized by an increase in fat mass and a decrease in lean body mass. As a mechanism of these GHRP-6-mediated metabolic changes in the nonfasting state, direct nonpituitary-mediated GHRP-6 effects on the gastroentero-hepatic axis seem probable.

Acute effect of pegvisomant on cardiovascular risk markers in healthy men: implications for the pathogenesis of atherosclerosis in GH deficiency.

Cardiovascular risk is increased in GH deficiency (GHD). GHD adults are frequently abdominally obese and display features of the metabolic syndrome. Otherwise healthy abdominally obese subjects have low GH levels and show features of the metabolic syndrome as well. We investigated in healthy nonobese males the effect of the GH receptor antagonist pegvisomant in different metabolic conditions. This is a model for acute GHD without the alterations in body composition associated with GHD. We compared the effect of pegvisomant with that of placebo before and after 3 d of fasting. In addition, we investigated the effect of pegvisomant under normal, i.e. fed, conditions. Three days of fasting as well as pegvisomant alone decreased serum free IGF-I levels (1.0 +/- 0.15 vs. 0.31 +/- 0.05 ng/ml and 0.86 +/- 0.23 vs. 0.46 +/- 0.23 ng/ml, respectively). Fasting in combination with pegvisomant also decreased serum free IGF-I levels (1.0 +/- 0.15 vs. 0.31 +/- 0.07 ng/ml). Treatment with pegvisomant had no additional influence on the decline of free IGF-I induced by fasting. Pegvisomant alone had no influence on insulin sensitivity. The increase in insulin sensitivity induced by fasting was comparable to the increase in insulin sensitivity induced by fasting combined with pegvisomant. Among serum lipid concentrations, only serum triglycerides increased significantly as a result of pegvisomant alone (1.0 +/- 0.2 vs. 1.6 +/- 0.4 mmol/liter). The changes in lipid concentrations induced by fasting alone or pegvisomant were not different from those induced by pegvisomant alone. von Willebrand factor antigen levels declined significantly under the influence of pegvisomant alone (1.1 +/- 0.07 vs. 0.8 +/- 0.06 U/ml). In conclusion, in different metabolic conditions the GH receptor antagonist pegvisomant induces no significant acute changes in the major risk markers for cardiovascular disease. These data suggest that the secondary metabolic changes, e.g. abdominal obesity or inflammatory factors, that develop as a result of long-standing GHD are of primary importance in the pathogenesis of atherosclerosis in patients with GHD.

Renal tubular injury is present in acute inflammatory bowel disease prior to the introduction of drug therapy.

BACKGROUND: 5-aminosalicylic acid (5-ASA) has been associated with renal complications in inflammatory bowel disease. Renal function is typically monitored using serum creatinine; however, significant disease may predate increases in creatinine. AIMS: To identify whether markers of early renal disease (urinary albumin, alpha-1-microglobulin [alpha-1-M] and N-acetyl-beta-D-glucosaminidase [NAG], and serum cystatin C) are useful in the assessment of renal function in inflammatory bowel disease patients receiving 5-ASA. METHODS: Twenty-one patients with a new diagnosis of inflammatory bowel disease were investigated. Samples were taken at diagnosis, and at 3-monthly intervals after the commencement of 5-ASA, for 1 year. RESULTS: Mean creatinine clearance was 100 mL/min and did not change following treatment. Inflammatory bowel disease was not associated with albuminuria. Urinary N-acetyl-beta-D-glucosaminidase and alpha-1-microglobulin at diagnosis were increased in 10 (48%) and 11 (52%) patients, respectively: treatment was not associated with consistent changes in urinary protein excretion. There was a significant correlation between cystatin C and creatinine clearance both at diagnosis (r=-0.533, P=0.0275) and combining the initial and follow-up data (r=-0.601, P < 0.01), but not between creatinine and creatinine clearance (P > 0.05). CONCLUSIONS: Tubular proteinuria is an extra-intestinal manifestation of inflammatory bowel disease irrespective of 5-ASA treatment. Tubular proteins are not useful predictors of an adverse renal response to 5-ASA. Serum cystatin C may be an improved marker of glomerular filtration rate in this setting.

Metabolic bone disease is present at diagnosis in patients with inflammatory bowel disease.

AIM: To establish whether bone disease is present at diagnosis in inflammatory bowel disease and to identify contributory metabolic abnormalities. METHODS: Newly diagnosed patients with inflammatory bowel disease (19 males, 15 females; mean age, 44 years; range, 17-79 years; 23 ulcerative colitis, 11 Crohn's disease) were compared against standard reference ranges and a control group with irritable bowel syndrome (eight males, 10 females; mean age, 40 years; range, 19-64 years). Bone mineral density (g/cm2, dual-energy X-ray absorptiometry: lumbar spine and femoral neck) and biochemical bone markers were measured. RESULTS: Femoral neck bone mineral density, T- and Z-scores (mean +/- s.d., respectively) were lower in inflammatory bowel disease patients than in irritable bowel syndrome controls (0.78 +/- 0.12 vs. 0.90 +/- 0.16, P = 0.0046; - 0.88 +/- 0.92 vs. 0.12 +/- 1.17, P = 0.0018; - 0.30 +/- 0.89 vs. 0.61 +/- 1.10, P = 0.0030). Lumbar spine bone mineral density and T-scores were also significantly lower in patients than controls (0.98 +/- 0.15 vs. 1.08 +/- 0.13, P = 0.0342; - 1.05 +/- 1.39 vs. - 0.14 +/- 1.19, P = 0.0304). Compared with controls, the urinary deoxypyridinoline : creatinine ratio was increased (7.66 vs. 5.70 nmol/mmol, P = 0.0163) and serum 25-hydroxy vitamin D was decreased (18.7 vs. 28.5 micro g/L, P = 0.0016); plasma osteocalcin and serum parathyroid hormone did not differ (P > 0.05). CONCLUSIONS: The bone mineral density is reduced at diagnosis, prior to corticosteroid treatment, in both Crohn's disease and ulcerative colitis. Our data suggest that this is attributable to increased resorption rather than decreased bone formation.

Pneumoblastoma in neurofibromatosis.

Pneumoblastoma is a rare tumor composed of two histologic cell types, arising from epithelium and stroma. Patients with von Recklinghausen's disease are known to develop certain types of tumors. A rare, and possibly first case of pneumoblastoma arising in a patient with neurofibromatosis is described.

Very severe self-poisoning lithium carbonate intoxication causing a myocardial infarction.

A case of severe lithium carbonate self-poisoning is described, presenting with a very high serum lithium level (14.6 mmol/L) on admission. Lengthy and repeated hemodialyses were required to lower lithemia to nontoxic ranges. As is usually reported, our patient had prolonged neurologic manifestations (coma, hyperreflexia, fluctuating focal signs) and developed hypotension, cardiovascular collapse, nephrogenic diabetes insipidus, and diarrhea. Other less common features were the occurrence of acute myocardial infarction without coronary artery lesions and thrombocytopenia. The possible pathogenic mechanisms are discussed. Hemodialysis and supportive intensive care treatment are commented upon. The final outcome was favorable, and the patient recovered completely.

Anatomical Localization of Corticotropin-Releasing Factor and Arginine Vasopressin in the Human Hypothalamus; the Effect of Corticosteroids on their Concentrations in Human and Rat Hypothalami.

Abstract In this study, we have determined the distribution of corticotropin-releasing factor and vasopressin in the human hypothalamus, and investigated the effect of glucocorticoid administration on the concentrations of both peptides. Corticotropin-releasing factor and vasopressin were measured by a two-site immunoradiometric assay and/or radioimmunoassay. The presence of both peptides was studied in extracts of eleven areas of the human hypothalamus as well as in the pituitary stalk from autopsied patients who had been free of chronic steroid administration (n = 14) or had received Corticosteroids (n = 5). Unlike vasopressin, corticotropin-releasing factor was detected in all extracts: the highest concentration was found in the pituitary stalk, whilst the lowest detectable amounts occurred in the supraoptic and lateral areas and in the mammillary bodies. This pattern of distribution is similar to that reported for the rat hypothalamus. The excellent correlation (R = 0.994) between corticotropin-releasing factor data obtained by immunoradiometric assay and by radioimmunoassay renders the presence of a corticotropin-releasing factor precursor molecule in the extracts highly unlikely. In the human brain extracts, glucocorticoid treatment affected neither the content, nor the distribution of corticotropin-releasing factor and vasopressin. In the rats, dexamethasone administration produced a 50% decrease in the vasopressin content (P < 0.05) of the basomedial and dorsal parts of the hypothalamus and had no effect on the corticotropin-releasing factor content of these areas. These results show that the distribution of corticotropin-releasing factor is similar in both human and rat hypothalami. The rat data suggest that negative feedback effects of glucocorticoids involve changes in hypothalamic vasopressin content.