FISH-based analysis of stable translocations in a Techa River population

Bone morphogenetic proteins (BMPs) and their receptors (BMPRs) are thought to play an important role in bone morphogenesis. The purpose of this study was to determine the locations of BMP-2/-4, osteogenic protein-1 (OP-1, also termed BMP-7), and BMP type II receptor (BMPR-II) during rat fracture healing by immunostaining, and thereby elucidate the possible roles of the BMPs and BMPR-II in intramembranous ossification and endochondral ossification. In the early stage of fracture repair, the expression of BMP-2/-4 and OP-1 was strongly induced in the thickened periosteum near the fracture ends, and coincided with an enhanced expression of BMPR-II. On day 7 after fracture, staining for BMP-2/-4 and OP-1 immunostaining was increased in various types of chondrocytes, and was strong in fibroblast-like spindle cells and proliferating chondrocytes in endochondral bone. On day 14 after fracture, staining with OP-1 antibody disappeared in proliferating and mature chondrocytes, while BMP-2/-4 staining continued in various types of chondrocytes until the late stage. In the newly formed trabecular bone, BMP-2/-4 and OP-1 were present at various levels. BMPR-II was actively expressed in both intramembranous ossification and endochondral ossification. Additionally, immunostaining for BMP-2/-4 and OP-1 was observed in multinucleated osteoclast-like cells on the newly formed trabecular bone, along with BMPR-II. In reference to our previous study of BMP type I receptors (BMPR-IA and BMPR-IB), BMPR-II was found to be co-localized with BMPR-IA and BMPR-IB. BMP-2/-4 and OP-1 antibodies exhibited distinct and overlapping immunostaining patterns during fracture repair. OP-1 may act predominantly in the initial phase of endochondral ossification, while BMP-2/-4 acts throughout this process. Thus, these findings suggested that BMPs acting through their BMP receptors may play major roles in modulating the sequential events leading to bone formation.     

Mechanism of ovalbumin proteolysis

Papain, thermitase and pepsin at pH 4.0 hydrolyze ovalbumin to low molecular weight peptides. Simultaneously a stepwise formation of several short fragments resulting in the appearance of a group of high molecular weight fragments and a subsequent splitting of the latter into two fragments of intermediate molecular mass takes place. The fragments are retained in the molecule by noncovalent bonds. The fragments formed under the action of different enzymes are similar in size, which is suggestive of splitting in the same narrow segments of the ovalbumin polypeptide chain. The results obtained indicate that during proteolysis of the native ovalbumin two extreme types of the proteolysis--the one-by-one and zipper types--occur in parallel, while the course of the latter is largely determined by the ovalbumin structure.     

Ketorolac tromethamine in the maintenance of intraoperative mydriasis

BACKGROUND AND OBJECTIVE: Mydriatics and antiprostaglandins are routinely applied preoperatively to facilitate the aspiration of cortical material during extracapsular cataract surgery and to prevent intraoperative miosis. Unfortunately, the ideal antiprostaglandin has yet to be introduced. This study represents the first prospective, case-controlled, randomized, masked, clinical trial comparing the efficacy of oral ketorolac tromethamine (KT) with the efficacy of topical flurbiprofen sodium (FS) and a placebo (normal saline) in maintaining intraoperative mydriasis without adrenaline in the irrigation solution. PATIENTS AND METHODS: Sixty-three patients, undergoing extracapsular cataract extraction with posterior chamber intraocular lens implantation, were randomly divided into three equal groups. Group 1 received 20 mg of oral KT 2 hours prior to surgery, group 2 received 0.03% FS topical solution at the recommended dosage, and group 3 received topical normal saline in a regimen identical to that of group 2. Identical mydriatics were used in both groups. The patients' pupils were measured at five stages of surgery. RESULTS: The mean pupillary diameters at each surgical stage were greater in group 1 than in group 2; however, the difference was not statistically significant. The pupils in group 3 were significantly smaller than those of group 1 or group 2 (P < .05). No systemic toxicity to KT was observed. Moreover, the need for additional postoperative analgesics was significantly greater in groups 2 and 3. CONCLUSIONS: Oral KT is safe, convenient, and as effective as topical FS, and has the added advantage of reducing postoperative pain.     

Myocardial revascularisation in elderly patients with refractory or unstable angina and advanced coronary disease

BACKGROUND: Elderly patients with ischaemic heart disease are often treated more conservatively and for longer than younger patients, but this strategy may result in subsequent invasive intervention of more advanced and higher risk coronary disease. METHODS: We performed a retrospective analysis of 109 patients aged > or = 70 years (mean age 74 years, 66% men), who presented with angina refractory to maximal medical treatment or unstable angina over a 2-year period (1988-1990), to compare the relative risks and benefits of myocardial revascularisation [coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA)] in this higher-risk age group. RESULTS: Sixty patients underwent CABG and 49 patients PTCA. There were eight periprocedural deaths in total (six in the CABG group, and two in the PTCA group, P = 0.29). Six patients in the CABG group suffered a cerebrovascular accident (two fatal). Acute Q-wave myocardial infarction occurred in one patient in the CABG group and in two patients in the PTCA group. The length of hospital stay was longer for the CABG group (CABG group 11.4 +/- 5.4 days, range 7-30 days, PTCA group 7.4 +/- 7.6 days, range 1-39 days, P = 0.01). Outcome was assessed using the major cardiac event rate (MACE; i.e. the rate of death, myocardial infarction, repeat CABG or PTCA). The cumulative event-free survival in the CABG group in 1, 2 and 3 years was 87, 85 and 85%, respectively. In contrast, in the PTCA group it was 55, 48 and 48% (P = 0.0001). Age, sex, number of diseased vessels, degree of revascularisation and left ventricular function were not predictive of the recurrence of angina in both groups. Actuarial survival (total mortality, including perioperative mortality) was lower at 1 year in the CABG group due to the higher perioperative mortality, but similar in both groups after the second year (P = 0.62). CONCLUSIONS: Elderly patients with refractory or unstable angina who are revascularised surgically have a better long-term outcome (less frequent event rate of the composite end-point--myocardial infarction, revascularisation procedures and death) compared with those who are revascularised with PTCA. This benefit is been realised after the second year. Total mortality is similar in both groups after the second year. Therefore elderly patients who are fit for surgery should not be denied the benefits of CABG. PTCA may be regarded as a complementary and satisfactory treatment, especially for those whose life expectancy is limited to less than 2 years. The use of stents may improve outcome in the PTCA group and this needs to be evaluated.     

Central nervous system cryptococcosis: parenchymal calcification and large gelatinous pseudocysts

In an 11-year-old immunocompetent girl with protracted cryptococcal infection of the central nervous system, CT showed multiple areas of parenchymal calcification. MR imaging showed large gelatinous pseudocysts around the brain stem. These imaging features and the child's age are unusual for intracranial cryptococcosis.     

Ceftriaxone in treatment of streptococcal endocarditis

The authors studied efficacy and safety of ceftriaxone given intravenously for 3-4 weeks in a dose 2-4 g/day to patients with streptococcal endocarditis (SE). Of them, 8, 8 and 1 patients were infected with Streptococcus viridans, Streptococcus pyogenes, Pneumococcus, respectively. Hospital trial and follow-up lasted up to 2 years. Cure without surgical correction occurred in 7 patients, valvular replacement was needed in 4 patients, 1 patient died, 4 patients developed recurrences 3 and more months after therapy with ceftriaxone. The drug was safe and well tolerated. 33% of the patients were discharged from hospital with obvious improvement after 2-3 week treatment to continue it outpatiently for 1-2 weeks.     

Prospects of riboflavin carrier protein (RCP) as an antifertility vaccine in male and female mammals

MDL 26479 is a new drug undergoing clinical evaluation for the treatment of depression and for memory loss associated with Alzheimer's disease. As part of a dose tolerance trial, the single- (SD) and multiple-dose (MD) pharmacokinetics of MDL 26479 were evaluated in healthy male volunteers. SDs ranging from 2 to 465 mg, and doses of 30, 60, and 120 mg administered twice daily for 28 d, were examined. Serial blood samples were collected for up to 48 h. Plasma MDL 26479 concentrations were determined by HPLC. Plasma MDL 26479 concentration versus time profiles increased rapidly, followed by multiexponential decline. Time to maximum plasma concentration increased over the 230-fold SD range from 0.5 to 3.8 h. Maximum concentrations and areas under the concentration versus time curves increased disproportionately with dose. Apparent oral clearance estimates decreased from 52.9 to 13.8 Lh-1. MD pharmacokinetic parameters for doses from 30 to 120 mg were consistent with those observed following SD, thus indicating that SD pharmacokinetics are predictive of MD. SD and MD terminal half-life estimates were similar and independent of dose.     

The muscarinic acetylcholine antagonist scopolamine impairs short-distance homing pigeon navigation

The present study employed intramuscular (i.m.) injections of the acetylcholine (ACh) receptor antagonist scopolamine hydrobromide (0.10 mg/kg) to investigate the possible involvement of ACh in naturally occurring spatial navigation in homing pigeons (Columba livia). Control pigeons receiving injections of saline or scopolamine methylbromide, an ACh antagonist that does not cross the blood-brain barrier, were oriented in a homeward direction when released from a location 8 km from home. In contrast, pigeons injected with scopolamine hydrobromide (0.10 mg/kg, i.m.) were less well oriented and took more time to return home from the same location. These results suggest that homing pigeon navigation is regulated, in part, by central cholinergic mechanisms.