Prevention of early postmenopausal bone loss using low doses of conjugated estrogens and the non-hormonal,bone-active drug ipriflavone

Hormone replacement therapy is the optimal therapeutic choice for postmenopausal syndrome. While low doses of estrogens (0.3 mg/day of conjugated estrogens) can counteract neurovegetative menopausal symptoms, higher doses (0.625 mg/day of conjugated estrogens) are required to prevent bone loss in postmenopausal women. Experimental and clinical studies have shown that ipriflavone, a non-hormonal isoflavone derivative, is effective in the prevention and treatment of postmenopausal osteoporosis. The aim of the present investigation was to evaluate the efficacy and toler-ability of ipriflavone and very low doses of equine conjugated estrogens on bone loss in early postmenopausal women. Eighty-three healthy postmenopausal women (50.3±0.7 years) were enrolled for this 1-year multicenter study. All subjects were randomly allocated to receive: double placebo (n=24; group A), placebo plus conjugated equine estrogens 0.30 mg/day (n=31; group B) or conjugated equine estrogens 0.30 mg/day plus oral ipriflavone 200 mg tris in die at meals (n=28; group C), according to a double-masked design. Among women who completed the treatment period (valid completers), those of group A showed a progressive decrease in forearm bone density (FBD; measured by dual photon absorptiometry) that reached 1.7% after 12 months. The women in group B maintained their FBD in the first 6 months of treatment but, at the end of the study, showed a bone loss of 1.4% compared with basal values. By contrast, women in group C showed a significant increase in FBD after 1 year of treatment (+5.6%;p<0.01). Bothvalid completers andintention to treat analyses revealed a significant difference (p<0.05) between group A and group C over the study period. None of the treatments produced significant changes of biochemical markers of bone turnover, while hot flushes and other climacteric symptoms were significantly reduced after the sixth month of treatment in women receiving estrogens. Adverse events were generally mild, and did not differ among the groups. The results of this study suggest that low doses of estrogens combined with ipriflavone could represent a new therapeutic approach to the treatment of the postmenopausal syndrome.     

Differential inhibition of cyclooxygenase-1 (COX-1) and-2 (COX-2) by NSAIDS: Consequences on anti-inflammatory activity versus gastric and renal safety

The discovery of an inducible isoform of cyclooxygenase (COX-2) requires a refinement of the theory that inhibition of cyclooxygenase activity is responsible for both therapeutic and side-effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Pharmacological results with developmental compounds suggest that COX-2 is the relevant target for the therapeutic (i.e. anti-inflammatory) effects of NSAIDs, whereas gastric and renal side-effects are related to inhibition of constitutive COX-1. However a role of COX-1 in inflammation cannot be excluded. Furthermore, more research effort is needed to investigate the functional relevance of COX-2 in normal tissue.     

Management of hypothalamic gliomas in children: an analysis of 33 cases

The cases of 33 children with hypothalamic-chiasmatic gliomas are reviewed. Radiation therapy produced clinical or radiographic improvement in 11 (46%) of 24 patients. Progression was documented in 18 patients (54%). Overall, the median time to tumor progression was 60 months; it was 70 months in patients who received radiation therapy and 30 months in those who did not (P less than 0.05). Chemotherapy, either given initially or at the time of progression, caused the tumor to respond or to stabilize in 10 patients. Partial resection of the tumor led to improvement in 3 of 12 patients, obviating the need for a shunt in 2 of them; there were no deaths and postoperative morbidity was transient and minimal (diabetes insipidus, intraventricular hemorrhage, and left hemiparesis in one patient each). The 5- and 10-year survival probabilities were 93 and 74%, respectively. Patients with neurofibromatosis had a better prognosis.     

The use of bone scan to evaluate total hip prostheses. A preliminary study

The authors conducted a clinical and radiographic study on a group of 43 patients with hip arthroprostheses selected from the three-year period from 1984 to 1987, characterized by no immediate postoperative complications, no positional defects on X-ray examination, and with a Renther test greater than 1. Prostheses were cemented, cementless and combined. Scintigraphy was evaluated for areas of subdivision in the proximal end of the femur and acetabulum, making a semi-quantitative comparison of the intensity of captation of each area with that of the skull and sacroiliac synchondrosis. The authors emphasize that this procedure is both reliable and easy for the early determination (pre-clinical and pre-radiographic) of any complications. A scintigraphic examination of the single areas was also capable of revealing the site and entity of prosthetic bone-to-implant interactions. According to the results reported, PCA prostheses seem to be characterized by better biocompatibility.     

Electrolyte and humoral responses of renal transplant patients to head-out water immersion

Eighteen renal transplant recipients and sixteen volunteers were subjected to the physiological manoeuvre of head-out water immersion, in order to compare changes in electrolyte and humoral responses known to occur in healthy individuals with those arising as a result of renal denervation in the transplant recipients. Although the tubular sodium response to water immersion was normal, tubular potassium excretion was markedly different in the transplant patients. Plasma values of atrial natriuretic factor increased in both groups and showed a close temporal relationship to urinary excretion of cyclic GMP. The attenuation in transplant recipients of the well-documented suppression of plasma renin activity during water immersion was probably due to a combination of factors, namely lack of renal innervation and an increase in circulating ANF. The small but significant increase in the excretion of enzymically active urinary kallikrein observed only in the transplant recipients during immersion still requires explanation.     

The influence of central haemodynamics on transcutaneous oxygen (TcpO2) measurements

Transcutaneous oxygen measurements (TcpO2) have been shown to be an index of tissue perfusion and it has been suggested that the main haemodynamic variable influencing tissue perfusion is cardiac output, assuming that inspired oxygen remains constant. To investigate this hypothesis we studied 23 consecutive patients in order to identify if changes in cardiac output correlated with similar changes in TcpO2 measurements. No correlation was found to suggest that cardiac output was the main haemodynamic determinant of TcpO2 measurements.     

Analysis of serum free amino acid profiles in patients dying from major burns

An analysis of serum free amino acid profiles in 8 patients dying from major burns revealed that free amino acid began to decrease in shock period, decrease 31.12% in infection period and 41.3% before death in comparison with the control group. The amount of BCAA-also decrease 36.27% in infection period and 56.83% before death. If the serum free amino acid in major burn drops steadily, the prognosis will be worse.     

The importance of intraoperative cholangiography during laparoscopic cholecystectomy

Laparoscopic cholecystectomy (LC) using electrocoagulation was successfully performed in 56 out of 58 selected patients. Cholangiography was performed in 53 patients. Six patients had common duct stones; five were unsuspected preoperatively. After the gallbladder was removed, three patients underwent open common duct exploration. In another five cases, anatomical anomalies were discovered. Cholangiography performed via the cystic duct before any structures are divided can prevent the most serious complication--common duct injury. Cholangiography should be attempted on all patients undergoing LC.     

Decrease in mean platelet survival time in acute poststreptococcal glomerulonephritis (APSGN)

In an attempt to study further the possible participation of platelets in the pathogenesis of acute poststreptococcal glomerulonephritis (APSGN), we studied the platelet survival time, as an index of platelet activation, in 22 patients with APSGN. Mean platelet survival time was computed from the disappearance of radioactivity from blood, sampled serially after injection of autologous 51Cr-labelled platelets. C1q solid phase ELISA and conglutinin (K) solid phase ELISA were used to measure the serum levels of immune complexes. The platelet survival time in APSGN patients was 113 +/- 10 h vs 197 +/- 10 h in the control group (p less than 0.001); 68% of the patients had a shortened platelet survival, lower than 95% confidence limit. There was a significant increase in the platelet survival in the six patients that were studied after recovery from acute nephritic syndrome. There was no significant association between the mean platelet times survival and CICs (circulating immune complexes). Similarly, no significant correlation was found between the mean platelet lifespan and the severity of the glomerular disease, as assessed by the serum creatinine level and the proteinuria. These results support evidence of platelet activation and consumption in APSGN and we suggest that this activation occurs in the glomeruli capillary wall, due to platelet-vascular wall interaction.