A prospective, randomized, cross-over comparison of two methods of artificial insemination by donor on the incidence of conception: intracervical insemination by straw versus cervical cap

In a prospective, randomized study of insemination with donor semen, intracervical insemination by straw was compared with insemination using a cervical cap with an intracervical reservoir. A total of 91 patients completed 486 treatment cycles. There were no significant differences in age, parity, indication for insemination by donor, or method of cycle monitoring between women who became pregnant and those who did not conceive with either insemination method. In 236 standard intracervical insemination cycles, 14 patients became pregnant (5.9% per cycle), whereas 38 patients conceived in 250 cervical cap cycles (15.2% per cycle). Both the crude pregnancy rates and the cumulative pregnancy rates calculated by the Kaplan-Meier life-table method were significantly different (chi(2)-test, P < 0.001, and log-rank test, P < 0.005 respectively). Pregnancy rates in artificial insemination with cryopreserved donor semen may be improved by the use of a cervical cap when compared to cervical insemination by straw. The use of the cervical cap may prolong the exposure of the spermatozoa to the cervical mucus and prevent the backflow of semen into the vagina.      

Reversal of multidrug resistance by two novel indole derivatives.

Two new fused indoles were found to overcome multidrug resistance in P388/Adr cells in vitro. These agents potentiated the cytotoxicity of the antitumor drugs Adriamycin, vinblastine, and vincristine in multidrug-resistant cells with no effect on drug-sensitive parent P388 cells. They significantly increased the ATP-dependent accumulation of [3H]-vinblastine and inhibited efflux of the labeled drug from resistant cells. These compounds also inhibited photoaffinity labeling of P-glycoprotein by [3H]azidopine in P388/Adr cells and membranes isolated from these cells. In addition, the calcium antagonist activity of these compounds was very weak compared with that of verapamil. These data suggest that the compounds reported here may specifically overcome multidrug resistance without the serious hypotensive effects associated with calcium antagonists and that this activity may be independent of their ability to block calcium transport.     

Intra-observer and inter-observer agreement of the manual examination of the lumbar spine in chronic low-back pain

Examination is a cornerstone in the manual procedures leading to mobilisation/manipulation of the low back. The observer variation of the more specific segmental tests remains to be investigated. Two skilled specialists in manual medicine examined the segmental changes in the lumbar spine. The patients were unknown to the examiners and no information of the case history was given. All test results were recorded by an observer present in the room who ensured that no conversation was allowed during the examination. The primary outcome measures were the kappa values for each test. The matching was defined as acceptable (acc) within two neighbouring levels and perfect (per) on the same level. Intra-observer variation (tested in 33 patients and 10 subjects without low-back pain): The agreement between first and second segmental diagnosis examination was 70% (per) and 82% (per + acc). Kappa values were: segmental diagnosis 0.60 (per) and 0.70 (per + acc), multifidus test 0.51 (per) and 0.60 (per + acc), sideflexion 0.57 (per) and 0.69 (per + acc), and ventral flexion 0.31 (per) and 0.45 (per + acc). Inter-observer variation (tested in 60 patients): The agreement for segmental diagnosis between the examiner A and B was 42% (per) and 75% (per + acc). Kappa values were: segmental diagnosis 0.21 (per) and 0.57 (acc), multifidus test 0.12 (per) and 0.48 (acc), sideflexion 0.22 (per) and 0.45 (acc), and ventralflexion 0.22 (per) and 0.44 (acc). By manual tests, skilled examiners seem to be able to diagnose segmental dysfunctions in the low back. The clinical implication of these dysfunctions remains to be clarified.     

Temporomandibular joint arthrography following surgical treatment of internal derangements

Arthrograms of the temporomandibular joint were obtained in 20 symptomatic joints that had previous reconstructive arthroplasty with disk repositioning because of internal derangements. Preoperative arthrograms were available for comparison in 18 joints. Symptoms resulting in a postoperative arthrogram included pain, limited ability to open the mouth, and clicking of the joints. Postoperative arthrographic findings included limited anterior translation of the condyle (90%), irregularity in outline of the intraarticular contrast agent (60%), a conical configuration of the posterior recess (25%), decreased size of the joint (28%), anterior displacement of the meniscus (25%), and perforated meniscus (15%). Many of these findings may have resulted from fibrosis and scarring, which may be a response to intraarticular bleeding. The mechanism by which the fibrosis causes the postsurgical arthrographic features is discussed.     

Phenytoin prodrug 3-phosphoryloxymethyl phenytoin (ACC-9653): pharmacokinetics in patients following intravenous and intramuscular administration

A phenytoin prodrug, 3-phosphoryloxymethyl phenytoin (ACC-9653; 1), has been developed with more favorable physicochemical properties than phenytoin for parenteral administration. The purpose of this study was to evaluate the pharmacokinetic profile of 1 following iv and im administration in adult patients receiving chronic oral phenytoin monotherapy. Each patient (9 males, 1 female) received a single iv dose of undiluted 1 equivalent to their twice daily phenytoin dose (100-200 mg). An equivalent dose of im 1 was administered in the gluteus maximus muscle one week later. Serial blood samples were obtained after each dose. Phenytoin and 1 concentrations were measured using HPLC. Compartmental analysis using weighted nonlinear least squares, and noncompartmental pharmacokinetic analysis were performed on each patient's concentration-time data. Data following iv 1 in eight of ten patients were best described using a two-compartment model. Mean pharmacokinetic parameter estimates for iv 1 in these patients were central volume of distribution (Vdc) of 0.040 +/- 0.0084 L/kg and plasma disappearance half-life (t1/2 alpha) of 8.0 +/- 2.9 min ("conversion" t1/2). Overall mean clearance (CL) was 0.24 +/- 0.080 L/kg/h in the 10 patients. Mean pharmacokinetic parameter estimates for im 1 were a rate constant (ka) of 2.47 +/- 1.41 h-1 and an absolute bioavailability (F) of 100.5 +/- 20.3%. Mean observed tmax values for phenytoin were 0.57 +/- 0.26 and 1.46 +/- 0.76 h following iv and im 1, respectively. Model-independent estimates of clearance agreed well with the compartmental analyses. Steady-state predose phenytoin concentrations did not significantly vary from the comparable concentrations following iv 1 administration (p = 0.22).(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of particulate trap oxidizers on emission of mutagenic compounds by diesel automobiles

Diesel exhaust particles are known to contain mutagenic and carcinogenic chemicals. The aim of this study was to determine whether, and to what extent, catalytic particulate trap oxidizers on light-duty diesel engines may reduce the emission of particle-associated mutagenic chemicals into the environment. Exhaust particles were collected from Mercedes Benz and Volkswagen diesel automobiles, equipped with or without the manufacturer's exhaust traps, while running on a chassis dynamometer under specified load conditions. Exhaust particles were collected from a dilution tunnel onto 20" X 20" Teflon-coated fiberglass filters. Mutagenesis tests of dichloromethane (DCM) extracts of the particles were conducted using the Ames Salmonella bacterial test system. The mutation rate was calculated in terms of histidine revertants per mile of travel during a set of standard test cycles. With both vehicles the traps produced an 87-92% reduction in the total amount of particulate material collected by the filters. There was no significant change in the specific mutagenic activity (revertants per microgram of DCM particle extract) with or without the traps. These studies support the notion that installation of exhaust traps which reduce particulate emission on diesel-powered vehicles will also reduce the emission of particle-associated mutagenic and carcinogenic materials into the environment.