The effects of phosphodiesterase inhibition on cyclic GMP and cyclic AMP accumulation in the hippocampus of the rat

The effects of selective and non-selective 3',5'-cyclic nucleotide phosphodiesterase (PDE) inhibitors on cGMP and cAMP accumulation were studied in rat hippocampal slices incubated in vitro. The following PDE inhibitors were used: vinpocetine and calmidazolium (PDE1 selective), erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA, PDE2 selective), SK&F 95654 (PDE3 selective), rolipram (PDE4 selective), SK&F 96231 (PDE5 selective), the mixed type inhibitors zaprinast and dipyridamole, and the non-selective inhibitors 3-isobutyl-1-metylxanthine (IBMX) and caffeine. cGMP levels were increased in the presence of different concentrations of IBMX, EHNA, dipyridamole, vinpocetine and rolipram. cGMP immunocytochemistry showed that incubation with different inhibitors in the presence and/or absence of sodium nitroprusside resulted in pronounced differences in the extent and regional localization of the cGMP response and indicate that PDE activity in the hippocampus is high and diverse in nature. The results suggest an interaction between cGMP and cAMP signalling pathways in astrocytes of the rat hippocampus.     

Generalized skull vault thickening in association with a large arteriovenous malformation

Generalized thickening of the skull is unusual but has a number of recognized associations such as chronic severe anaemia, Paget disease and phenytoin therapy. We report a case of generalized skull vault thickening seen in association with a large arteriovenous malformation of the brain.     

Heparin therapy in the Chinese--lower doses are required

Warfarin requirements are lower in the Chinese, but it is not known if this applies to heparin. We investigated the optimal dose for heparin therapy in Chinese patients, and to assess relationship between i.v. heparin dosage and anticoagulation efficacy. One hundred Chinese patients requiring intravenous heparin therapy were given an initial bolus followed by continuous intravenous infusion. The main outcome measures were: (i) Efficacy of anticoagulation assessed by blood coagulation studies (APTT) compared to heparin dosage, (ii) Determinants of dosage variation-age, gender, body weight, height, indication for heparin therapy and number of medications, other disease, and serum albumin level. It was found that the mean therapeutic infusion dose requirement of heparin was 848.7 +/- 274.7 units/h, 79% required a dose of 1000 units/h or less. Heparin dose correlated negatively with age (r = -0.40; p < 0.001) and positively with weight (r = 0.44 p < 0.001) and height (r = 0.49; p < 0.001). Chinese subjects require lower heparin doses (about 800 units/h) than usually recommended for Caucasians (usual dose 1000-1500 units/h). This can be partly explained by the lower body weight in Chinese patients.      

Safety of bazedoxifene in a randomized,double-blind,placebo- and active-controlled phase 3 study of postmenopausal women with osteoporosis

Background  

We report the safety findings from a 3-year phase 3 study (NCT00205777) of bazedoxifene, a novel selective estrogen receptor modulator under development for the prevention and treatment of postmenopausal osteoporosis.     

Critical Appraisal on the Role and Outcome of Emergency Colectomy for Uncomplicated Right-sided Colonic Diverticulitis

Background Emergency colectomy is well accepted for treating complicated right-sided colonic diverticulitis. However, the role of colectomy for uncomplicated diverticulitis is not well defined. The aim of this study was to evaluate the short-term and long-term surgical outcome of uncomplicated right-sided diverticulitis in our locality. Patients and Methods Retrospective chart review of patients operated for right-sided diverticulitis over a 20-year period was conducted. Recurrent attacks of right-sided diverticulitis, re-operation rate and re-hospitalisation rate were the long-term parameters of interest. An updated telephone interview was carried out for all surviving patients. Results Seventy-four patients (35 males and 39 females), median age 35.5 (range 16–70) years, were operated for uncomplicated diverticulitis. Thirty patients underwent colectomy, whereas the others underwent appendectomy with diverticulectomy (n = 8) or appendectomy alone (n = 36). All short-term parameters were less favourable for the colectomy group, including higher complication rate, slower return of gastrointestinal function, higher requirement of parenteral analgesic and longer hospital stay. Without colectomy, only 2 patients developed recurrent diverticulitis necessitating hospitalisation, both of whom resolved on conservative treatment. On the other hand, 1 patient required re-operation after colectomy because of intestinal obstruction. The overall re-hospitalisation rate was comparable between the colectomy and the non-colectomy group (16.7% vs. 13.6%). Conclusions Emergency colectomy can eradicate suspicious lesions and eliminate risk of recurrent diverticulitis but at the expense of higher morbidity rates. As the natural course of uncomplicated right-sided colonic diverticulitis is usually benign, conservative treatment with minimal surgery may be a better therapeutic option.