Neuronal migration disorders increase susceptibility to hyperthermia-induced seizures in developing rats

PURPOSE: Retrospective studies suggest that adult patients with intractable epilepsy may have a history of febrile seizures in childhood. Risk factors for a febrile seizure may include the rate of increase in the core temperature (T-core), its peak (Tmax), the duration of the temperature increase, or an underlying brain pathology. Recently, neuronal migration disorders (NMD) have been diagnosed with increasing frequency in patients with epilepsy, but the link between NMD, febrile seizures, and epilepsy is unclear. We studied rat pups rendered hyperthermic to ascertain the incidence of seizures, mortality, and extent of hippocampal cell loss in each group. METHODS: We exposed 14-day-old rat pups with experimentally induced NMD (n = 39) and age-matched controls (n = 30) to hyperthermia (core body temperature > 42 degrees C). RESULTS: The incidence of hyperthermia-induced behavioral seizures and mortality rate were significantly higher in rats with NMD than in controls (p < 0.05). The longer duration of hyperthermia resulted in a higher incidence of behavioral seizures and higher mortality rate (p < 0.05). In rats with NMD, hyperthermia resulted in hippocampal pyramidal cell loss independent of seizure activity; the extent of neuronal damage correlated positively with the duration of hyperthermia. In control rats, occasional neuronal loss and astrocytosis occurred only after prolonged hyperthermia. CONCLUSIONS: In immature rats, NMD lower the threshold to hyperthermia-induced behavioral seizures and hyperthermia in the presence of NMD may cause irreversible hippocampal neuronal damage.     

Detection rates for abnormal cervical smears: what are we screening for?

We analysed rates of detection for smear abnormalities in 255,000 women served by the Bristol screening programme. The programme began in 1966 with the aim of eradicating the 30-40 deaths each year in Bristol from cervical cancer. Organisation has been good and population uptake has been high for the past 15 years. Records were computerised in 1977. During the 1988 to 1993 screening round, 225,974 women were tested. New smear abnormalities were found in 15,551, of whom nearly 6000 were referred for colposcopy. These numbers are excessively high in comparison with the incidence of the malignancy we are trying to prevent. The effect of screening on death rates in Bristol is too small to detect. Our conclusion is that despite good organisation of the service, much of our effort in Bristol is devoted to limiting the harm done to healthy women and to protecting our staff from litigation as cases of serious disease continue to occur. The real lesson from 30 years' cervical screening is that no matter how obvious the predicted benefit may seem for any screening test, introduction should never take place without adequate prior evaluation of both positive and negative effects in controlled trials.     

A morphofunctional validation of the use of electrostimulation by paired impulses combined with vibromassage for the treatment of patients with trauma to the peripheral nerves of the extremities

The exposure to paired electric impulses and vibromassage promotes completeness of repair in the treatment of injured peripheral nerves of the limb. The effect is achieved due to marked stimulation of myelinization and differentiation of the nerve fibers, regeneration of the nerve system in the denervated muscle.     

Is the chest radiograph a reliable tool in the assessment of tumor response after radiotherapy in nonsmall cell lung carcinoma?

BACKGROUND: The purpose of this study was to evaluate whether the chest radiograph is a reliable tool to assess response to radiotherapy. MATERIALS AND METHODS: Pre- and post-treatment chest radiographs and computed tomographs (CT) of 63 patients with nonsmall cell lung cancer (NSCLC) treated by radiotherapy were reviewed by four observers with regard to suitability for tumor measurement, and response. Suitability for tumor measurement was expressed as the number of measurable diameters. In addition, the consequences to clinical outcome were studied by survival analysis. RESULTS: The CT turned out to be more suited for tumor measurement before as well as after radiotherapy, resulting in an increase of the number of measurable cases. The number of measurable cases with CT was 52 (83%) as compared to 28 (44%) with chest radiography. Especially in case of centrally localized tumors, the presence of an atelectasis, or squamous cell carcinoma, CT contributed to a higher rate of measurable cases. The interobserver agreement with regard to response using chest radiograph was good (mean kappa = 0.74). In 25 of 28 cases (89%) measurable with CT as well as with chest radiograph, response was equally classified. When CT was used, the median survival of the responders was 14.2 months as compared to 6.8 months of the nonresponders. When chest radiograph was used, the median survival of these groups was 12.0 and 6.6 months respectively, which was not significantly different when response was assessed by CT. CONCLUSION: We conclude that CT is more suited for tumor measurement because more measurable lesions can be found and more evaluable lesions on chest radiograph become measurable on CT. The chest radiograph does have a valuable role to play in those lesions that are measurable because of the good interobserver agreement with regard to the response classification, the high overall agreement between CT and chest radiograph in case of measurable cases, and the lack of important differences with regard to survival.     

Predicting neurologic deterioration in patients with cerebellar hematomas

BACKGROUND: Patients with cerebellar hematomas may appear stable but may worsen suddenly. Whether certain clinical or CT scan findings predict worsening is not known. METHODS: We reviewed clinical and neuroimaging data in 72 patients with cerebellar hematomas at the Mayo Clinic from 1973 through 1993 to identify predictive features for neurologic deterioration. Patients presenting in coma and patients with vascular malformations or malignancies were excluded. Data were analyzed using chi-square or Fisher's exact test, with calculation of odds ratios with 95% confidence intervals. Multivariate logistic regression analysis was performed on appropriate variables. RESULTS: Thirty-three patients (46%) deteriorated, with a decrease in level of consciousness, new brainstem signs, or worsened motor response on the Glasgow Coma Scale. Clinical and neuroradiologic predictors for neurologic deterioration at p < 0.05 were admission systolic blood pressure greater than 200 mm Hg, pinpoint pupils and abnormal corneal or oculocephalic reflexes, hemorrhage extending into the vermis, hematoma size more than 3 cm in diameter, brainstem distortion, intraventricular hemorrhage, upward herniation, and acute hydrocephalus. Multivariate analysis demonstrated that hemorrhage located in the vermis (p = 0.03) and acute hydrocephalus (p = 0.0006) on admission CT scanning independently predicted deterioration. CONCLUSION: Patients with a cerebellar vermian hematoma or acute hydrocephalus are at high risk for neurologic deterioration. These patients should be carefully monitored and are more likely to require consideration for neurosurgical intervention.     

Autoimmunity, immunodeficiency and mucosal infections: chronic intestinal inflammation as a sensitive indicator of immunoregulatory defects in response to normal luminal microflora

Despite the fact that target antigens and the genetic basis of several autoimmune diseases are now better understood, the initial events leading to a loss of tolerance towards self-components remain unknown. One of the most attractive explanations for autoimmune phenomena involves various infections as possible natural events capable of initiating the process in genetically predisposed individuals. The most accepted explanation of how infection causes autoimmunity is based on the concept of "molecular mimicry" (similarity between the epitopes of an autoantigen and the epitopes in the environmental antigen). Infectious stimuli may also participate in the development of autoimmunity by inducing an increased expression of stress proteins (hsp), chaperones and transplantation antigens, which leads to abnormal processing and presentation of self antigens. Superantigens are considered to be one of the most effective bacterial components to induce inflammatory reactions and to take part in the development and course of autoimmune mechanisms. It has long been known that defects in the host defense mechanism render the individual susceptible to infections caused by certain microorganisms. Impaired exclusion of microbial antigens can lead to chronic immunological activation which can affect the tolerance to self components. Defects in certain components of the immune system are associated with a higher risk of a development of autoimmune disease. The use of animal models for the studies of human diseases with immunological pathogenesis has provided new insights into the influence of immunoregulatory factors and the lymphocyte subsets involved in the development of disease. One of the most striking conclusion arising from work with genetically engineered immunodeficient mouse models is the existence of a high level of redundancy of the components of the immune system. However, when genes encoding molecules involved in T cell immunoregulatory functions are deleted, spontaneous chronic inflammation of the gut mucosa (similar to human inflammatory bowel disease) develops. Surprisingly, when such immunocompromised animals were placed into germfree environment, intestinal inflammation did not develop. Impairment of the mucosal immune response to the normal bacterial flora has been proposed to play a crucial role in the pathogenesis of chronic intestinal inflammation. The use of immunodeficient models colonized with defined microflora for the analysis of immune reactivity will shed light on the mode of action of different immunologically important molecules responsible for the delicate balance between luminal commensals, nonspecific and specific components of the mucosal immune system.     

Carbohydrate chromatography: towards yoctomole sensitivity

Ward atmosphere was assessed with the help of the Ward Atmosphere Scale (WAS) by patients, nurses and physicians on 8 admission units before and after the introduction of the partial open door system. On average, on 45% of the days on which the units could have been potentially open, they were indeed at least temporarily open. Several significant changes in the WAS scores, mostly in desirable direction, were registered. However, close relationship with the partial opening of the units could be substantiated only with regard to the scale "praxis orientation"; still a positive result. No unequivocal relationships could be demonstrated between the introduction of the partial open door system and the changes in the frequency of "special events".