Prolongation of the ejaculation latency in the male rat by thioridazine and chlorimipramine

Thioridazine (3 mg/kg) and chlorimipramine (1.5–6.0 mg/kg) prolonged the ejaculation latency and increased the number of mounts but did not change the number of intromissions preceding ejaculation. Blockade of peripheral and central noradrenaline receptors by phentolamine and phenoxybenzamine respectively resulted in a suppression of all aspects of the sexual behavior with increasing doses. dl-5-HTP (25–100 mg/kg) in combination with an inhibitor of peripheral 5-HTP decarboxylase (benserazide, 25 mg/kg) produced, like chlorimipramine and thioridazine, a prolongation of ejaculation latency and an increase in the number of mounts preceding ejaculation. Selective inhibition of 5-HT reuptake however, by zimelidine (0–20 mg/kg) or alaproclate (0–20 mg/kg) did not affect the mating behavior. At higher doses of these drugs some animals failed to initiate sexual activities. There was an increase in the postejaculatory interval but no change in the ejaculatory latency.It is concluded that the prolonged ejaculation latencies observed following treatment with thioridazine or chlorimipramine is not due to a blockade of central or peripheral adrenergic -receptors.     

Steady-state kinetics of imipramine in patients

Steady-state plasma level kinetics were studied in 76 patients given imipramine (IP) 150 to 225 mg/day for 2–5 weeks. IP was given in three divided doses at 8.00 a.m., 1.00 p.m. and 5.00 p.m. Plasma concentrations of IP and its active metabolite desipramine (DMI) were determined by quantitative in situ thin-layer chromatography. The plasma levels of IP and DMI showed pronounced flucutations throughout the day with a ratio of about 2 between highest and lowest level. Patients with steady-state levels of IP and/or DMI below 50 g/l reached this within 1 week of treatment. Patients with higher steady-state levels reached steady-state concentrations within 2–3 weeks. There were some intraindividual fluctuations in plasma levels from week to week after steady state had been reached (coefficient of variation: 10–20%). Interindividually, the steady-state levels corrected to a dose of 3.5 mg/kg per day varied considerably: IP: 6–356 g/l, DMI: 24–659 g/l and IP+DMI: 58–809 g/l. The steady-state plasma levels showed a skew distribution that became normal by logarithmic transformation. The IP/DMI ratio ranged from 0.07 to 5.5 with a median value of 0.47. Compared to data from amitriptyline treated patients the IP/DMI ratios had significantly lower median value and larger variation than the corresponding plasma level ratios of amitriptyline/nortriptyline. Several statistically significant differences in steady-state levels between age groups were found. For IP: Women aged 30–39 had lower levels than women aged 20–29, 40–49, and 50–59, and men aged 50–59 and 60–65; men aged 30–39 had lower levels than men aged 60–65. For DMI: Women aged 30–39 had lower levels than women aged 50–59.     

Bipartite parietal bone: A rare cause of plagiocephaly

A case of an infant with an asymmetrical head is presented. On clinical assessment the patient displayed features of deformational plagiocephaly. With the aid of three‐dimensional CT imaging of the skull, a bipartite parietal bone was diagnosed. The prevalence and possible aetiology of a bipartite parietal bone is discussed as well as a brief overview of the common causes of plagiocephaly.     

System weaknesses as contributing causes of accidents in health care.

OBJECTIVE: Accidents in health care, resulting in injury or death to the patient, are a matter of considerable concern. The aim of this study is to examine whether system weaknesses can contribute to these accidents, and if so, how. DESIGN: Eight consecutive accidents reported to the Health Authority in Sweden were analysed using MTO (Man-Technique-Organization) analysis. SETTING: Emergency care hospitals in Sweden. RESULTS: All cases that involved the system supported the assumption that system weaknesses are a contributing factor to accidents. In this study two types of latent failure could be identified: process control latent failures and interactional latent failures. The time span from activation of process control latent failures to operator error was very short, and the study demonstrates the simple relationship between situational factors and operator errors. Interactional latent failures exert system influence in a more indistinct manner. Latent failures, as seen in this study, act not only by creating opportunities for operator errors but also by hindering error detection in the time window available. Safety barriers, which might have prevented the accidents, could be proposed in seven out of eight cases. CONCLUSION: System weaknesses seem to play an important role in accident evolution. Consequently, certain measures can be suggested in order to improve patient safety: (i) sufficient resources should be allocated for research and development at both medical schools and hospitals in order to establish competence and procedures for systematic analyses of processes; and (ii) authorities handling accident cases should have adequate competence in system analysis.     

Pseudophakic accommodation with translation lenses – dual optic vs mono optic

PURPOSE: To investigate the pseudophakic accommodation effect in dual and mono optic translation accommodative intraocular lenses (AIOL) using linear matrix methods in the paraxial space. METHODS: Dual (anterior optic of power +32 D linked to a compensatory posterior optic of negative power) and mono lens power was determined in the non-accommodated state using linear geometric optics based on the Gullstrand model eye. The position of the AIOL was calculated from a regression formula. Pseudophakic accommodation was assessed with three systems: (1) forward shift of the mono optic lens, (2) anterior translation of the anterior optic in the dual optic lens system with an unchanged position of the posterior minus lens and (3) symmetrical anterior and posterior translation of the anterior and posterior lens. The Gullstrand model eye was modified by changing the axial length (and proportionally changing the phakic anterior chamber depth) to investigate the accommodative effect in myopic and hyperopic eyes. RESULTS: The dual optic lens system (2) yields a nearly constant accommodation amplitude of 2.4-2.5 D mm(-1) movement over the total range of axial lengths. The mono optic lens (1) provides a higher accommodative effect only in extremely short eyes (high refractive power of the lens), whereas for normal eyes (1.4-1.5 D mm(-1) movement) and for long (myopic) eyes the accommodative effect is much less than the dual optic lens. The dual optic lens system under condition (3) yields less accommodation amplitude compared with the dual optic system under condition (2) over the total range of axial length but provides higher accommodation amplitude compared with the mono optic lens system (1) with axial lengths greater than 22.3 mm (lens power 25.5 D). In the accommodated state, with lens translation of 1 mm, the absolute value of the lateral magnification increases with the refractive power of the mono optic lens (1) and decreases in both dual optic lens systems (under conditions 2 and 3). CONCLUSIONS: A mathematical strategy is presented for calculation of the accommodative effect of mono-optic and dual optic AIOL. The dual optic lens yielded a nearly constant accommodation amplitude of about 2.4-2.5 D mm(-1) translation, whereas the mono optic lens yielded an accommodative response of <2 D mm(-1) translation in long myopic or normal eyes. Only in extremely short eyes is the accommodative amplitude of the mono-optic lens higher than the dual optic lens.     

sCR1sLe ameliorates ischemia/reperfusion injury in experimental lung transplantation

BACKGROUND: The nonspecific immune response with activation of the complement system and polymorphonuclear leukocytes is important for the mediation of reperfusion injury after lung transplantation. In this study, we investigated the combined blockade of the complement system and leukocyte adhesion by a novel drug combining soluble complement receptor type 1 (sCR1, CD35) with the selectin ligand sialyl Lewis X (sLe(X), CD15s) synthesized to sCR1sLe(X). Both sCR1 and sCR1sLe(X) were supplied by AVANT Immunotherapeutics, Inc, Needham, Massachusetts. METHODS: Orthotopic allogeneic single left lung transplantation was performed in male rats (Brown Norway to Fischer F344; n = 5 in all groups) after a total ischemic time of 20 hours. Recipients received either no specific treatment (control) or administration of sCR1 (10 mg/kg) or sCR1sLe(X) (10 mg/kg) 15 minutes before reperfusion by intracardiac injection. Twenty-four hours after reperfusion, the native contralateral lung was occluded to assess gas exchange of the graft only. In additional animals (5 per group), lung tissue was frozen 24 hours after reperfusion and assessed for myeloperoxidase activity as a measurement of neutrophil migration into the graft and thiobarbituric acid reactive substances to quantify lipid peroxidation. RESULTS: Graft function as assessed by arterial PO (2) in recipients treated with sCR1sLeX was superior not only to that of controls (383 +/- 53 vs 56 +/- 7 mm Hg, P =. 000095) but also to that of animals treated with sCR1 (243 +/- 45 mm Hg, P =.031). This improvement was confirmed by significant reduction of neutrophil migration (0.33 +/- 0.05 vs control, 1.0 +/- 0.09 DeltaOD/mg/min, P =.0000024) and lipid peroxidation (6.2 +/- 0. 38 vs control, 10.6 +/- 0.54 pmol/g, P =.00021). CONCLUSIONS: Our data indicate that combined inhibition of complement activation and leukocyte adhesion with sCR1sLe(X) reduces reperfusion injury significantly and that both mechanisms are effectively inhibited in this model.     

Fludarabine in combination with alemtuzumab is effective and feasible in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: results of a phase II trial.

PURPOSE: To determine the efficacy and safety of a newly developed concomitant administration of fludarabine and alemtuzumab (FluCam) in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL). PATIENTS AND METHODS: A total of 36 patients were treated in this phase II study (median age, 61.47 years; mean number of prior chemotherapies, 2.6; Binet stage C, n = 28). After an initial dose escalation of alemtuzumab over 3 days, alemtuzumab 30 mg and fludarabine 30 mg/m2 were administered on 3 consecutive days. Treatment was repeated after 28 days for up to six cycles. Restaging (following National Cancer Institute criteria) was carried out after cycles 2 and 4 and 1 month after the end of treatment. RESULTS: The overall response rate was 83% (11 complete responses, 19 partial responses, one stable disease, and five progressive diseases). Two patients with progressive disease developed fungal pneumonias, and one patient died as a result of Escherichia coli sepsis. Two subclinical cytomegalovirus reactivations occurred. CONCLUSION: The new FluCam regimen is effective and feasible in patients with relapsed and refractory B-CLL.     

Age of uptake of early cancer detection facilities by low-risk and high-risk patients with familial breast and ovarian cancer.

INTRODUCTION: Some 5-10% of all cases of breast cancer and ovarian cancer have a hereditary genesis. In the setting of an interdisciplinary cancer genetics clinic, a study of the age at which patients first take advantage of early cancer detection (ECD) facilities was conducted in order to assess the influence of familial risk on health issues. METHODS: The study included 556 women who fulfilled the inclusion criteria (IC) for genetic analysis of the BRCA1 and BRCA2 genes, as well as 205 who did not meet these criteria but attended the primary consultation. RESULTS: Consulters who met the inclusion criteria took advantage of nearly all methods of ECD at an earlier time than women who did not. A comparison of consulters with or without breast cancer showed that those without breast cancer participated in all methods of ECD at an earlier time. CONCLUSION: Methods of improving and increasing participation in ECD facilities, and of encouraging women who are at risk to start on such programs at a younger age, need to be discussed. In this study, familial risk already resulted in a younger age of uptake of ECD facilities.     

Exome sequencing in individuals with cardiovascular laterality defects identifies potential candidate genes

The birth prevalence of laterality defects is about 1.1/10,000 comprising different phenotypes ranging from situs inversus totalis to heterotaxy, mostly associated with complex congenital heart defects (CHD) and situs abnormalities such as intestinal malrotation, biliary atresia, asplenia, or polysplenia. A proportion of laterality defects arise in the context of primary ciliary dyskinesia (PCD) accompanied by respiratory symptoms or infertility. In this study, exome sequencing (ES) was performed in 14 case-parent trios/quattros with clinical exclusion of PCD prior to analysis. Moreover, all cases and parents underwent detailed clinical phenotyping including physical examination, echocardiography by a skilled paediatric cardiologist and abdominal ultrasound examinations not to miss mildly affected individuals. Subsequent survey of the exome data comprised filtering for monoallelic de novo, rare biallelic, and X-linked recessive variants. In two families, rare variants of uncertain significance (VUS) in PKD1L1 and ZIC3 were identified. Both genes have been associated with laterality defects. In two of the remaining families, biallelic variants in LMBRD1 and DNAH17, respectively, were prioritized. In another family, an ultra-rare de novo variant in WDR47 was found. Extensive exome survey of 2,109 single exomes of individuals with situs inversus totalis, heterotaxy, or isolated CHD identified two individuals with novel monoallelic variants in WDR47, but no further individuals with biallelic variants in DNAH17 or LMBRD1. Overall, ES of 14 case-parent trios/quattros with cardiovascular laterality defects identified rare VUS in two families in known disease-associated genes PKD1L1 and ZIC3 and suggests DNAH17, LMBRD1, and WDR47 as potential genes involved in laterality defects.Subject terms: Disease genetics, Genetic counselling, Biological sciences     

Software-Automated Implant Detection for Intraoperative 3D Imaging—First Clinical Evaluation on 214 Data Sets

Previous studies have demonstrated a frequent occurrence of screw/K-wire malpositioning during surgical fracture treatment under 2D fluoroscopy and a correspondingly high revision rate as a result of using intraoperative 3D imaging. In order to facilitate and accelerate the diagnosis of implant malpositioning in 3D data sets, this study investigates two versions of an implant detection software for mobile 3D C-arms in terms of their detection performance based on comparison with manual evaluation. The 3D data sets of patients who had received surgical fracture treatment at five anatomical regions were extracted from the research database. First, manual evaluation of the data sets was performed, and the number of implanted implants was assessed. For 25 data sets, the time required by four investigators to adjust each implant was monitored. Subsequently, the evaluation was performed using both software versions based on the following detection parameters: true-positive-rate, false-negative-rate, false-detection-rate and positive predictive value. Furthermore, the causes of false positive and false negative detected implants depending on the anatomical region were investigated. Two hundred fourteen data sets with overall 1767 implants were included. The detection parameters were significantly improved (p<.001) from version 1 to version 2 of the implant detection software. Automatic evaluation required an average of 4.1±0.4 s while manual evaluation was completed in 136.15±72.9 s (p<.001), with a statistically significant difference between experienced and inexperienced users (p=.005). In summary, version 2 of the implant detection software achieved significantly better results. The time saved by using the software could contribute to optimizing the intraoperative workflow.