Variable waveforms in downbeat nystagmus imply short-term gain changes

A patient with downbeat nystagmus subsequent to ankylosing spondylitis was studied. His nystagmus was found to exhibit both increasing- and decreasing-velocity exponential slow phases as well as the linear form more often reported. Alternation between waveforms sometimes occurred on a beat-to-beat or even intrabeat basis. Possible explanations for all three waveforms are presented in terms of short-term gain changes in cerebellar compensation for leaky brainstem neural integrators. A computer model was developed and its results are discussed.     

Acute poisoning caused by the herbicide dichlorprop (preparation SYS 67 PROP)

We report on the acute poisoning of a 5-year-old boy by the herbicide "dichlorprop". This preparation is described as an effective means of plant protection. The effects of the intoxication were established by changes observed in almost all of the child's organs. The predominant effect was haemolytic anemia. All the pathological parameters regressed as a result of symptomatic therapy. General conclusions are drawn about intoxication, especially by means of plant protection agents.     

Radioactive seed embolization to the lung following prostate brachytherapy

Over the past decade, prostate brachytherapy has been increasingly utilized as definitive management for early stage carcinoma of the prostate gland. One risk of the procedure is pulmonary seed embolization. In this article we report the incidence and timing of seed migration. Pulmonary embolization of radioactive seeds occurs in approximately 20% of patients undergoing prostate brachytherapy. To date, no acute or delayed detrimental effects have been reported which are attributable to the pulmonary embolization of the seeds; nevertheless, it is imperative that patients and health care providers be cognizant of this possible event.     

Molecular and cellular biology of prostate cancer

Prostate cancer is an enigmatic disease. Although prostatic-intraepithelial neoplasia appears as early as the third decade and as many as 80% of 80 year old men have epithelial cells in their prostate that fit the morphological criteria for cancer, only about 10% of men will ever have the clinical disease and less than 3% will die from it. There have been no significant proven interventions which have altered the natural history of the disease since hormone down regulation was introduced in the 1940s and new research has been poorly supported. There is however an urgent need to develop new criteria to distinguish those patients with localised disease who will benefit from intervention from those that do not require it or who will have occult extra prostatic metastases. Similarly, there is an urgent need to develop new treatment for those in whom the disease is extra-prostatic and therefore incurable by conventional treatments. This review covers the latest developments in epidemiology, cellular and molecular biology including new areas such as ion channels in the field of prostate cancer.     

The effect of evening primrose oil on the radiation response and blood flow of mouse normal and tumour tissue

PURPOSE: To investigate the effect of the oral administration of evening primrose oil on the radiation response and the blood flow of normal tissue and a tumour in BALB/c mice. METHODS AND MATERIALS: Aliquots of evening primrose oil were fed to BALB/c mice daily and the radiation response of the skin was assessed by the determination of ED50 values for the incidence of moist desquamation, using probit analysis. Tumour radiosensitivity was investigated by determining the growth delay caused by irradiation of a transplantable rhabdomyosarcoma. The 86RbCl uptake technique was used to determine the blood flow in normal foot and tumour tissue. The fatty-acid content of red blood cells, plasma and tumour tissue was measured using gas chromatography. RESULTS: Daily evening primrose oil dietary supplementation reduced the sensitivity of skin to radiation-induced moist desquamation and prevented the radiation-associated increase in blood flow that was observed in this tissue. No modification of tumour blood flow or of tumour sensitivity to radiation resulted from evening primrose oil supplementation of mice. Evening primrose oil supplementation resulted in changes in plasma levels of linoleic acid (LA), gamma-linolenic acid (GLA), dihomo-gamma-linolenic acid (DGLA) and arachidonic acid (AA). These changes were contingent on whether the mice had been irradiated or not. In red blood cells evening primrose oil supplementation increased the GLA level of unirradiated mice and the LA level at 20 days after irradiation. There were no changes in tumour fatty-acid levels as a result of evening primrose oil treatment. CONCLUSIONS: Daily evening primrose oil supplementation reduced the sensitivity of skin to radiation-induced moist desquamation but did not alter tumour sensitivity to radiation.     

Species differences in the disposition of the CCR5 antagonist, UK-427,857, a new potential treatment for HIV.

UK-427,857 (4, 4-difluoro-N-[(1S)-3-[exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]oct-8-yl]-1-phenylpropyl]cyclohexanecarboxamide) is a novel CCR5 antagonist undergoing investigation for use in the treatment of human immunodeficiency virus (HIV) infection. Pharmacokinetic and metabolism studies have been performed in mouse, rat, dog, and human after single and multiple administration by oral and intravenous routes. The compound has physicochemical properties that are borderline for good pharmacokinetics, being moderately lipophilic (log D(7.4) 2.1) and basic (pK(a) 7.3), possessing a number of H-bonding functionalities, and with a molecular weight of 514. The compound was incompletely absorbed in rat (approximately 20-30%) but well absorbed in dog (>70%). Based on in vitro studies in Caco-2 cells, UK-427,857 has relatively poor membrane permeability, and transcellular flux is enhanced in the presence of inhibitors of P-glycoprotein. Further evidence for the involvement of P-glycoprotein in restricting the oral absorption of UK-427,857 was obtained in P-glycoprotein null mice (mdr1a/mdr1b knockout). In these animals, AUC after oral administration was 3-fold higher than in control animals. In oral dose escalation studies in humans, the compound demonstrated nonlinear pharmacokinetics, with increased dose-normalized exposure with increased dose size, consistent with saturation of P-glycoprotein. The oral dose-exposure relationship of UK-427,857 in humans was not reflected in either rat or dog. In animal species and humans, UK-427,857 undergoes some metabolism, with parent compound the major component present in the systemic circulation and excreta. Elimination of radioactive dose was primarily via the feces. In rat, parent compound was secreted via bile and directly into the gastrointestinal tract. Metabolites were products of oxidative metabolism and showed a high degree of structural consistency across species.     

Delayed effects of thallium in the rat brain: regional changes in lipid peroxidation and behavioral markers, but moderate alterations in antioxidants, after a single administration.

Thallium (Tl+) toxicity has been related with the generation of reactive oxygen species (ROS) and oxidative stress (OS) in the central nervous system. Since changes in endogenous antioxidant systems might contribute to acute Tl+-induced OS and neurotoxicity, in this study we measured the metal concentration and the levels of lipid peroxidation (LP) in different brain regions (hypothalamus (Ht); cerebellum (Ce); striatum (S); hippocampus (Hc) and frontal cortex (Cx)) in possible correlation with the content of reduced glutathione (GSH), the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD), and the animal performance in behavioral tests, all evaluated after a single administration of thallium acetate (8 or 16 mg/kg, i.p.) to rats. Seven days after Tl+ administration, the metal was homogeneously and dose-dependently accumulated in all regions evaluated. LP was increased in Ht, Ce and S, while GSH was depleted in S. Cu,Zn-SOD activity was also decreased in Ht and S. All these changes occurred with 16 mg/kg dose and at 7 days after treatment, but not at 1 or 3 days. In addition, Tl+-treated animals exhibited general hypokinesis, but no changes were observed in spatial learning. Our findings suggest that a delayed response of the brain to Tl+ may be the result of its residual levels. Also, despite the regional alterations produced by Tl+ in LP and the limited changes in endogenous antioxidants, there is a correlation between the Tl+-induced oxidative damage and the affected behavioral tasks, suggesting that, although still moderate, Tl+ evokes neurotoxic patterns under the experimental conditions tested.     

Children with neurological disorders do not always need fundoplication concomitant with percutaneous endoscopic gastrostomy

Whether antireflux surgery should be routinely performed at the time of gastrostomy in children with neurological disorders is debatable because of the risk of gastroesophageal reflux. Some argue that these children should be screened for occult gastroesophageal reflux as this will determine the need for fundoplication. This study retrospectively examines outcome in 29 children with neurological disorders who underwent percutaneous endoscopic gastrostomy (PEG) without concomitant fundoplication. Children were included if they had no clinical evidence of severe gastroesophageal reflux before PEG insertion. The median age of children at PEG insertion was 5.6 years (range 1.1 to 18.0). The children were followed for a median of 2.6 years (range 0.4 to 4.9). Insertion of PEG was technically impossible in two children; and an asymptomatic gastrocolic fistula in another child led to subsequent tube removal. Fourteen of the 26 remaining children developed symptomatic gastroesophageal reflux after PEG; five of these showed no reflux on pH monitoring prePEG. Control of symptoms was achieved by medical intervention in 12, but two required fundoplication. Our findings indicate that in the child with neurological disabilities without symptoms indicating severe gastroesophageal reflux, fundoplication is unlikely to be necessary as a consequence of PEG insertion. We conclude that routine investigation for gastroesophageal reflux in the child without severe vomiting can be avoided and the number of antireflux procedures reduced.     

Joint angular velocity in spastic gait and the influence of muscle-tendon lengthening

BACKGROUND: Joint angular velocity (the rate of flexion and extension of a joint) is related to the dynamics of muscle activation and force generation during walking. Therefore, the goal of this research was to examine the joint angular velocity in normal and spastic gait and changes resulting from muscle-tendon lengthening (recession and tenotomy) in patients who have spastic cerebral palsy. METHODS: The gait patterns of forty patients who had been diagnosed with spastic cerebral palsy (mean age, 8.3 years; range, 3.7 to 14.8 years) and of seventy-three age-matched, normally developing subjects were evaluated with three-dimensional motion analysis and electromyography. The patients who had cerebral palsy were evaluated before muscle-tendon lengthening and nine months after treatment. RESULTS: The gait patterns of the patients who had cerebral palsy were characterized by increased flexion of the knee in the stance phase, premature plantar flexion of the ankle, and reduced joint angular velocities compared with the patterns of the normally developing subjects. Even though muscle-tendon lengthening altered sagittal joint angles in gait, the joint angular velocities were generally unchanged at the hip and knee. Only the ankle demonstrated modified angular velocities, including reduced dorsiflexion velocity at foot-strike and improved dorsiflexion velocity through mid-stance, after treatment. Electromyographic changes included reduced amplitude of the gastrocnemius-soleus during the loading phase and decreased knee coactivity (the ratio of quadriceps and hamstring activation) at toe-off. Principal component analyses showed that, compared with joint-angle data, joint angular velocity was better able to discriminate between the gait patterns of the normal and cerebral palsy groups. CONCLUSIONS: This study showed that muscle-tendon lengthening corrects biomechanical alignment as reflected by changes in sagittal joint angles. However, joint angular velocity and electromyographic data suggest that the underlying neural input remains largely unchanged at the hip and knee. Conversely, electromyographic changes and changes in velocity in the ankle indicate that the activation pattern of the gastrocnemius-soleus complex in response to stretch was altered by recession of the complex.