Lack of amyloid in abdominal fat aspirates from patients undergoing long-term hemodialysis

Recent reports describe the carpal tunnel syndrome (CTS) due to amyloid infiltration of the beta 2 microglobulin protein as a frequent complication of long-term hemodialysis. Carpal synovial and cystic bone lesion amyloid deposits have been reported; however, the extent of systemic amyloid deposition has not been determined. We examined 30 patients undergoing long-term hemodialysis for CTS and performed abdominal fat tissue aspiration for amyloid staining to evaluate the presence of systemic amyloid disease. In this group, CTS was frequent (37%) and its prevalence correlated with the duration of hemodialysis. In all patients, the abdominal fat tissue, stained with Congo red, was negative for amyloid deposits. These results confirm that CTS is a frequent complication of long-term hemodialysis; however, in this study, no detectable amyloid deposits were found in abdominal subcutaneous fat tissue. Thus, abdominal fat aspiration may not be a reliable screening test for hemodialysis-associated amyloidosis.     

Depressed monocyte production of interleukin-1 and tumor necrosis factor-alpha in patients with alcoholic liver cirrhosis

Interleukin-1 and tumor necrosis factor-alpha activity by E. coli lipopolysaccharide-triggered monocytes were studied in patients with chronic alcoholic liver disease. Monocytes from cirrhotic patients were shown to have a significant reduction in IL-1 and TNF-a activity, compared with that from age- and sex-matched healthy controls. These findings indicate further immunoregulatory disturbances concerning alcoholic liver cirrhosis.     

Inhibition of pancreatic secretory and trophic response to caerulein by the H2-receptor antagonist ranitidine in the rat

The effect of ranitidine (20 mg . kg-1) and cimetidine (50 mg . kg-1) on pancreatic secretory and trophic responses to caerulein (1 microgram . kg-1) was studied in the rat. Ranitidine or cimetidine were administered alone or combined with caerulein twice a day for 7 days. Saline-treated rats were used as controls. At the end of treatment animals were anesthetized and pancreatic juice was collected for 1 h after intravenous secretin plus CCK-PZ (8 U . kg-1). Afterwards rats were sacrificed and growth and composition of pancreatic tissue were determined. Compared with control (saline) values, volume of pancreatic juice and output of trypsin and amylase were increased by treatment with caerulein. Ranitidine, when given combined with caerulein, completely abolished the secretory response induced by the peptide, whereas it was totally ineffective when given alone. Cimetidine (alone or combined with caerulein) was always ineffective. Caerulein increased pancreatic weight, total pancreatic trypsin, amylase and RNA content. Here again ranitidine, combined with caerulein, abolished almost completely the trophic effect of caerulein on the pancreas, but when given alone it did not influence pancreatic growth and composition. Also in this case, cimetidine was completely inactive. These results suggest that ranitidine affects exocrine pancreas with an action independent of the H2-receptor blockade.     

Experiences with PMMA cement as a stand-alone intervertebral spacer

Background

The treatment of symptomatic degenerative disc disease of the lumbar spine in elderly patients by standard surgical methods is often limited due to severe comorbidities (e.g., cardiopulmonary disease, hypertonia, diabetes). Minimally invasive procedures are more acceptable in this population, since they reduce surgical morbidity and the risk of complications. The percutaneous cement discoplasty (PCD) technique was introduced by the authors to treat dynamic (and angular) instability of the symptomatic lumbar segment by injecting bone cement (polymethylmethacrylate, PMMA) into the disc spaces showing vacuum phenomena via a posterolaterally positioned Jamshidi needle. The aim of this article is to describe the indication, method, and clinical results of PCD.

Method

A total of 81 patients were treated with PCD in a tertiary care referral center over a 6-year period. The current study includes the first group of 47 consecutive patients to complete a pre- and postoperative questionnaire booklet regarding leg and back pain using the visual analog scale (VAS) and the Oswestry disability index (ODI) questionnaire.

Results

A total of 130 discs in these 47 patients were treated with PCD. The majority of patients reported a reduction in their lower back and leg pain (69?% and 66?%, respectively; p?p?

Conclusion

Elderly patients with symptomatic dynamic foraminal stenosis and vacuum phenomenon in the intervertebral disc are suitable candidates for PCD, particularly if they represent high-risk patients for open surgery.

     

Antagonist of growth hormone-releasing hormone induces apoptosis in LNCaP human prostate cancer cells through a Ca2+-dependent pathway

Antagonists of growth hormone-releasing hormone (GHRH) exert antiproliferative effects directly on cancer cells, which are mediated by the tumoral GHRH receptors. However, the signal transduction pathways involved in antiproliferative effect of GHRH antagonists have not yet been elucidated. We used flow cytometry to investigate whether GHRH antagonist JV-1-38 can induce changes in the cytosolic free Ca2+ concentration leading to apoptosis in LNCaP human prostate cancer cells. JV-1-38 evoked prompt Ca2+ signal in a dose-dependent way (1-10 microM) and induced early stage of apoptosis in LNCaP human prostate cancer cells at a concentration effective in suppression of cell proliferation (10 microM) peaking after 3 h. Unexpectedly, agonist GHRH(1-29)NH2, which elevates cytosolic free Ca2+ concentration in pituitary somatotrophs at nanomolar concentrations, failed to induce Ca2+ signal or apoptosis even at a 10-fold higher concentration (100 microM). However, agonist GHRH(1-29)NH2 inhibited JV-1-38-induced Ca2+ signals in a dose-dependent way without affecting the antagonist-induced apoptosis. Peptides unrelated to GHRH did not induce Ca2+ signals in LNCaP human prostate cancer cells. EDTA (10 mM) or nifedipine (10 microM) significantly reduced the Ca2+ signal and early stage of apoptosis induced by JV-1-38, supporting the view that the increase in intracellular Ca2+ in response to JV-1-38 occurs primarily through extracellular Ca2+ entry through voltage-operated Ca2+ channels. In conclusion, GHRH antagonists activate tumoral GHRH receptors and are able to induce apoptosis in LNCaP human prostate cancer cells through a Ca2+-dependent pathway. Treatment with GHRH antagonists may offer a new approach to the therapy of prostate and other hormone-sensitive cancers.     

Effect of single doses of dexamethasone and adrenocorticotrop hormone on serum bone markers in healthy subjects and in patients with adrenal incidentalomas and Cushing's syndrome

The aim of the present study was to explore whether short-term changes in glucocorticoid activity which occur during dynamic testing of the pituitary adrenal axis with dexamethasone, ACTH, or metyrapone could have an effect on serum osteocalcin (OC) and beta-crosslaps (beta-CTx) concentrations in healthy subjects, in patients with adrenal incidentalomas and in those with Cushing's syndrome. The study included 40 healthy subjects (35 women and 5 men, age range 18-69 yr), 49 patients with adrenal incidentalomas (34 women and 15 men, age range 19-77 yr) and 8 patients with Cushing's syndrome (5 cortisol-producing adenomas and 3 pituitary-dependent Cushing's syndrome, 3 women and 5 men, age range 19-70 yr). Serum OC and beta-CTx concentrations were determined with electrochemoluminescent immunoassays at midnight, after an overnight fast between 08:00 and 09:00 h, after an overnight dexamethasone test (1 mg, orally) and after a single dose of metyrapone (30 mg/kg, orally). In healthy subjects and in patients with adrenal incidentalomas, serum bone marker concentrations were also measured after a single dose of ACTH injection (Cortrosyn depot, 1 mg im). Patients with Cushing's syndrome, but not those with adrenal incidentalomas, showed significantly lower serum OC at midnight (18.5+/-12 ng/ml, mean+/-SD) and between 08:00 and 09:00 h (17.7+/-9.6 ng/ml) compared to corresponding values obtained in healthy subjects (24.5+/-7.0 and 28.3+/-12.2 ng/ml, respectively). Serum OC concentrations were significantly decreased after a single dose of 1-mg dexamethasone in healthy subjects (from 28.3+/-12.2 to 21.8+/-9.5 ng/ml) and in patients with adrenal incidentalomas (from 29.8+/-15.9 to 24.1+/-14.1 ng/ml), whereas serum OC concentrations remained unchanged in patients with Cushing's syndrome. In addition, serum OC concentrations were even more markedly decreased after a single dose of ACTH injection in both healthy subjects (12.5+/-4.6 ng/ml) and in patients with adrenal incidentalomas (12.2+/-6.5 ng/ml). By contrast, metyrapone administration failed to induce significant changes in OC levels. There were no significant differences in beta-CTx concentrations between the three groups or after drug treatments. Thus, serum OC levels should be interpreted with caution when obtained during testing of the pituitary-adrenal axis with dexamethasone or ACTH.