Eight Days of Cyclosporine Overdose: A Case Report

A 25–year-old woman was admitted to the hospital because of rising trough cyclosporine concentrations thought to be due to self-administration of 4 times the normal dosage of the drug for 8 days. Her symptoms included colicky central abdominal pains and urinary retention; her serum creatinine concentrations were elevated. Whole blood cyclosporine and metabolite concentrations were measured by high-performance liquid chromatography and monoclonal radioimmunoassays. The highest reported trough cyclosporine concentration was 5877 ng/ml, and AM1 (M17) concentration was 3425 ng/ml. A cyclosporine half-life of 91 hours was calculated. Nine days after the agent was discontinued the patient's serum creatinine concentration had returned to normal and her symptoms resolved. Due to the availability of three sizes of cyclosporine capsules, and the need for frequent dosage changes, continued vigilance is necessary to ensure that patients understand their drug regimen.     

Age-related Changes in Excitability and Recurrent Inhibition in the Rat CA1 Hippocampal Region

In hippocampal slices from male Wistar rats aged 1–34 months, we recorded the synaptic field potential responses of the CA1 neurons to stimulation of Schaffer collaterals. Eight electrophysiological indexes were extracted from input/output curves and compared in 11 age groups from 1 to 30 months. Neuronal excitability presented a U-shaped curve of development with a minimum at ˜7–8 months of age. There was a significant continuous increase in neuronal excitability, i.e. a decrease in excitatory postsynaptic potential (EPSP) producing both the threshold and half-maximal population spike from middle age (8–10 months) to senescence (30 months). Synaptic efficiency also increased in old rats to reach a maximum during senescence, i.e. both the current for threshold EPSP and that for half-maximal EPSP reached a minimum in senescence, although the earlier developmental patterns of these two indexes were non-linear. The duration of the field EPSP elicited with maximal stimulation presented an abrupt decay after the first month. Aged animals presented a relatively small maximal population spike. Recurrent inhibition was most prominent on neuronal excitability rather than synaptic strength. Measured as the percentage change in the half-maximal EPSP and half-maximal population spike, recurrent inhibition was found to decrease during the first 7–10 months of life and remained small in later development.     

Transurethral evaporation of prostate (TUEP) with Nd:YAG laser using a contact free beam technique: Results in 61 patients with benign prostatic hyperplasia

Objective. This prospective study was undertaken to evaluate the safety and efficacy of neodymium:yttrium-aluminium-garnet (Nd:YAG) laser for treatment of symptomatic benign prostatic hyperplasia (BPH).Methods. A total of 61 patients at a mean age of 71.6 years with symptomatic bladder outlet obstruction due to BPH underwent transurethral evaporation of prostate (TUEP) using Nd:YAG laser. Twelve of the patients were experiencing acute retention. Pre- and postoperative evaluation consisted of American Urological Association (AUA) symptom questionnaire and a sexual function questionnaire, uroflowmetry, postvoid residual urine, electrolytes, blood urea nitrogen, creatinine, hematocrit, and prostate volume estimation by transrectal ultrasound. TUEP was achieved by employing a side-firing Nd:YAG laser fiber with a durable quartz reflector and high-power density (Ultraline, Heraeus LaserSonics, Milpitas, CA) that was used in a contact mode.Results. All patients have been evaluated for three months, 26 for six rnonths, and 7 for twelve months. Mean prostatic size was 41.1 g. The mean improvement in symptom scores at one, three, six, and twelve months was 69.8 percent, 70.9 percent, 76.0 percent, and 70.9 percent, respectively (P = < 0.0001). The mean increase in maximum uroflow at one, three, six, and twelve months was 63.4 percent, 66.7 percent, 41.94 percent, and 164.52 percent, respectively (P = < 0.0001). There was no instance of significant fluid absorption or bleeding. The duration of postoperative catheterization was two days in 43 patients, three to seven days in 16 patients, and two to three weeks in 2 patients. There were no deaths. All patients evaluated by TRUS at six months had open channeling defects. Videocystoscopy performed in 16 patients at two to three months postoperatively revealed tissue slough. At repeat cystoscopy in these patients at six months, the prostatic fossa was completely healed with no evidence of tissue slough.Conclusions. It is concluded that the technique of TUEP using Nd:YAG laser is safe and, in preliminary results, appears apparently effective in the management of BPH.     

In vitro stability of a novel compliant poly(carbonate-urea)urethane to oxidative and hydrolytic stress.

Poly(ester)urethane and poly(ether)urethane vascular grafts fail in vivo because of hydrolytic and oxidative degradative mechanisms. Studies have shown that poly(carbonate)urethanes have enhanced resistance. There is still a need for a viable, nonrigid, small-diameter, synthetic vascular graft. In this study, we sought to confirm this by exposing a novel formulation of compliant poly(carbonate-urea)urethane (CPU) manufactured by an innovative process, resulting in a stress-free. Small-diameter prosthesis, and a conventional poly(ether)urethane Pulse-Tec graft known to readily undergo oxidation in a variety of degradative solutions, and we assessed them for the development of oxidative and hydrolytic degradation, changes in elastic properties, and chemical stability. To simulate the in vivo environment, we used buffered solutions of phospholipase A(2) and cholesterol esterase; solutions of H(2)O(2)/CoCl(2), t-butyl peroxide/CoCl(2) (t-but/CoCl(2)), and glutathione/t-butyl peroxide/CoCl(2) (Glut/t-but/CoCl(2)); and plasma fractions I-IV, which were derived from fresh human plasma centrifuged in poly(ethylene glycol). To act as a negative control, both graft types were incubated in distilled water. Samples of both graft types (100 mm with a 5.0-mm inner diameter) were incubated in these solutions at 37 degrees C for 70 days before environmental scanning electron microscopy, radial tensile strength and quality control, gel permeation chromatography, and in vitro compliance assessments were performed. Oxidative degradation was ascertained from significant changes in molecular weight with respect to a control on all Pulse-Tec grafts treated with t-but/CoCl(2), Glut/t-but/CoCl(2), and plasma fractions I-III. Pulse-Tec grafts exposed to the H(2)O(2)/CoCl(2) mixture had significantly greater compliance than controls incubated in distilled water (p < 0.001 at 50 mmHg). No changes in molecular weight with respect to the control were observed for the CPU samples; only those immersed in t-but/CoCl(2) and Glut/t-but/CoCl(2) showed an 11% increase in molecular weight to 108,000. Only CPU grafts treated with the Glut/t-but/CoCl(2) mixture exhibited significantly greater compliance (p < 0.05 at 50 mmHg). Overall, results from this study indicate that CPU presents a far greater chemical stability than poly(ether)-urethane grafts do.     

A comment and a reply to the paper by Kristinn Tomasson et al.: “Failed and short seizures associated with prior electroconvulsive therapy”

Eur Arch Psychiatry Clin Neurosci: (1992) 241:307–313     

The Developmental Profile of Seizure Genesis in the Inferior Collicular Cortex of the Rat: Relevance to Human Neonatal Seizures

The ontogeny of seizure genesis within the inferior collicular cortex was characterized in rats ranging in age from 3 days old to adult. Brief electrical stimulation of the right inferior collicular cortex in 30-day-old rats evoked poststimulus wild running behavior that coincided with afterdischarge activity in the inferior collicular cortex but not in the adjacent occipital cortex. Similar electrical stimulation in 16-day-old rats produced poststimulus wild running and jumping behaviors, which also coincided with afterdischarge in the inferior collicular cortex. In 10- and 5-day-old rats, electrical stimulation of the inferior collicular cortex produced poststimulus locomotion and coincident afterdischarge activity, but unlike older rats the locomotor behaviors consisted of forelimb paddling, hindlimb treading, and rolling/curling movements of the torso. Identical behaviors can be electrically elicited in 3-day-old rats. Although many of the seizure characteristics appear to be similar among the different age groups, 5-day-old rats were more sensitive to low frequency stimulation than 16-day-old rats, who in turn were more sensitive than adult rats. Thus, the inferior collicular cortex is capable of generating seizure activity in rats as young as 3 days of age, providing a focal model of neonatal seizure genesis.     

A prospective study of the predictive value for in-hospital mortality of mandibulodiaphragmatic distance and mandibular dentition on portable anteroposterior chest radiographs

Conclusions Mandibulodiaphragmatic distance, measured on the portable anteroposterior chest radiograph and applied to the predictive equation developed in this study, is a strong tool for the prediction of in-hospital mortality that could find wide application in clinical practice and provide vital information for risk stratification and resource allocation in a wide variety of acutely ill patients.Over the years, I have been disconcerted by the volume of useless investigation that surfaces in some of our journals. Many of these are correlative studies that have little usefulness other than to pad the investigator's bibliography and to fill journal pages. To follow, you will find a tongue-in-cheek research paper written by Dr. George H. Lindbeck, a colleague of mine, which nicely illustrates this pseudoscientific phenomenon. I think you will enjoy the satire. Theodore E. Keats, M.D.     

Human ovarian-carcinoma cell lines and companion xenografts: a disease-oriented approach to new platinum anticancer drug discovery

Summary A disease-oriented approach to the discovery of novel platinum anticancer drugs has been established through the setting up of parallel human ovarian-carcinoma cell lines and xenografts. The correlation between in vitro and in vivo antitumour activity was determined for four reference platinum agents (cisplatin, carboplatin, iproplatin and tetraplatin) in eight companion lines. Two methods of assessing antitumour effect were used in vitro (tritiated thymidine incorporation and sulforhodamine B staining) and three were applied in vivo [28-day treated/control (T/C) ratio, growth delay and specific growth delay]. In vitro, large differences in cytotoxicity across the cell lines were observed for each drug. This was also reflected in the xenografts for cisplatin and carboplatin and, to a lesser extent, for iproplatin. A correlation analysis of in vitro vs in vivo data revealed a high, statistically significant positive correlation for cisplatin and a strong positive correlation for carboplatin. However, for the two platinum(IV) drugs, the correlation was less good. In particular, tetraplatin was markedly less active in vivo (showing a general lack of activity against all of the tumour lines) than its in vitro potency against the cell lines predieted, resulting in poor correlation coefficients. These human tumour panels may be valuable for the elucidation of both cellular/molecular and corresponding in vivo pharmacological mechanisms of platinum drug resistance. Moreover, the HX/62 and SKOV-3 tumour lines, which exhibit a level of intrinsic resistance to the four reference agents both in vitro and in vivo (and which were derived from patients who had not received prior platinum therapy), represent particularly useful evaluation models for the discovery of novel broad-spectrum platinum drugs.This study was supported by grants to the Institute of Cancer Research from the Cancer Research Campaign and the Medical Research Council, the Johnson Matthey Technology Centre and Bristol Myers Squibb Oncology