The effect of lithium on amphetamine-induced locomotor stimulation

Rats were treated chronically with -methyl-p-tyrosine methyl-ester HCl (-MT) twice daily for 0–14 days. At 1 h after the (last) -MT injection, d-amphetamine sulphate was given and motor activity was measured in an ANIMEX activity meter for 4 h. Amphetamine-induced excitatory and stereotyped behaviour was scored according to a rating scale in a separate experiment. A single dose of -MT markedly reduced the activity response after amphetamine. After 1–3 days of -MT treatment, tolerance to its amphetamine-antagonistic affect started to develop, reaching a maximal degree after 7–14 days. The pattern of the amphetamine response, monophasic in control rats, became biphasic in the -MT tolerant rats with an early (at 0–1 h) and a late (2–4 h) peak of motor activity. The late peak appeared within 3 days, while the early peak appeared after 7 days of -MT treatment. The results on amphetamine-induced excitatory and stereotyped behaviour in essence agreed with the motor-activity data. It is concluded that tolerance to the amphetamine-antagonistic action of -MT is not complete. Its rate of development varies in a complex pattern, indicating the presence of more than one mechanism of tolerance.     

Interphase cell death as related to the cell cycle of melphalan-treated human myeloma cells

The effect of melphalan on cell loss, cell growth and cell-cycle traverse was studied on the human myeloma cell line RPMI 8226. Melphalan treatment resulted in arrest of cells in late S- and G₂-phases in a population of unsynchronized cells. At high concentrations of melphalan (e.g. 40 μm), cell loss was noticed duringthe first cell cycle after melphalan treatment in addition to the aforementioned arrest of cells in late S and G₂. The cell loss after melphalan treatment was further analysed in cells enriched for G₁-phase. Cell death in this population of cells occurred between 24 and 48 hr after treatment as the cells were in S and moving over to G₂.     

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.     

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.     

Timing of the sentinel lymph node biopsy in breast cancer patients receiving neoadjuvant therapy – Recommendations for clinical guidance

Neoadjuvant chemotherapy (NAC) is an increasingly important component in the treatment of both locally advanced and early-stage breast cancer. With this, a debate on the timing of the sentinel lymph node biopsy (SLNB) has emerged. At the end of the last century, the SLNB was introduced as an axillary staging modality, and this paper aims to further elucidate this issue in the context of NAC. We compiled available data on the SLNB after NAC and provide clinical guidance for timing the SLNB in this context. On the basis of our findings, we recommend that the SLNB can be performed after NAC in all cases. In patients with a clinically node-negative (cN0) status prior to NAC, the SLNB should be performed after NAC, and in case of a histologically confirmed negative SLNB, a completion axillary lymph node dissection (ALND) has no added value and can be omitted. In patients with clinically positive nodal involvement (cN+) prior to NAC, all axillary surgery can also be performed after NAC.