Vestibular perception in patients with acquired ophthalmoplegia

Using a perceptual technique it is shown that patients with chronic external ophthalmoplegia have shortened vestibular responses. It is postulated that this is secondary to the retinal image slip experienced by these patients during head movements and a useful compensatory mechanism to suppress motion-induced sickness and spatial disorientation.     

Human DNA topoisomerase I: An anticancer drug target present in human sarcomas

New anticancer drugs targeting DNA topoisomerase I (topo I) are showing activity against human sarcomas. Laboratory studies have indicated that cells responsive to topo I-targeted drugs have elevated levels of topo I, require active DNA replication, and may require a functional apoptotic pathway. In this study, we evaluated these potential markers of topo I-targeted drug sensitivity in 55 cases of human sarcoma (42 high grade, 4 intermediate grade, and 9 low grade). By immunohistochemical staining, we observed elevated topo I expression in 20 of 55 neoplasms (36%). Immunohistochemical staining for the proliferation marker DNA topoisomerase II-alpha (topo II-alpha), showed that 15 of 55 neoplasms (27%) had topo II-alpha indices >50, indicating a large number of actively cycling tumor cells. Abnormal p53 expression was observed in 19 of the 55 cases (35%). None of the cases were interpreted as positive for ALK-1. To complement our immunohistochemical staining of topo I, we isolated functionally active topo I from extracts of a human sarcoma. These isolates demonstrated that sarcoma topo I is sensitive to topo I-targeted anticancer drugs. Of the 55 cases of human sarcoma, 7 (13%) had high levels of topo I, a large number of cycling tumor cells, and normal p53 expression. These are the molecular parameters that might suggest responsiveness to drugs targeting topo I.     

Long-lasting decreases of type II calmodulin kinase expression in kindled rat brains.

The kindling model of epilepsy is associated with long-lasting changes in type II calmodulin kinase (CaM kinase) activity and immunoreactivity. In order to determine the mechanism of these alterations, we measured gene expression of CaM kinase using in situ hybridization in septally kindled rat brains and paired controls using a 35S-labeled riboprobe for the beta subunit of the enzyme. We found CaM kinase mRNA concentrated in the hippocampus and other limbic structures. Kindling decreased hippocampal CaM kinase mRNA by 30% in CA1, 34% in CA2, 35% in CA3 41% in CA4, and 29% in the dentate gyrus. Hybridization was also decreased by 21% in the cerebral cortex but not in the lateral septum. These changes are similar in distribution and direction to those previously measured by immunohistochemistry. These data suggest that altered CaM kinase activity and immunoreactivity associated with kindling reflect long-lasting alterations in gene expression of this important synaptic protein, and provide further evidence for its possible importance in the kindling phenomenon.     

Entrance and Exit of Obstetrics Providers in Rural Alabama

In Alabama between 1985 and 1989, a total of 94 physicians outside of the four largest cities in the state dropped the obstetrics portion of their practices or left practice in their communities altogether. During the same period 82 physicians entered obstetrics practice in this area. The study presented here used survey and archival data to compare practice characteristics of generalists and specialists in rural and town counties who made different decisions about providing obstetrics care. More generalists left and more specialists entered practice both in town and in rural counties. Rural counties lost more obstetrics providers because more generalists provided the obstetrics care in these areas. Across both specialty and county categories, physicians in group practice who accepted Medicaid and had local access to larger numbers of patients were more likely to remain or begin new obstetric practices. During this period, some obstetrics specialists moved into rural communities that had previously supported only generalist physicians. These findings suggest that the options for organizing successful obstetrics practices have narrowed, putting solo and generalist physicians who operate small-scale obstetrics practices at a disadvantage. These physicians also face competition from obstetrics specialists who are beginning to enter practice in the rural areas of the state. Designing policies that effectively improve geographic access to care requires a realistic understanding of the practice constraints faced by obstetrics providers. For example, as centralized specialist group practices serve residents from surrounding rural areas, programs that facilitate linkages, such as satellite clinics and use of mid-level practitioners, can be promoted.(ABSTRACT TRUNCATED AT 250 WORDS)     

Failure of rectal ornithine decarboxylase to identify adenomatous polyp status.

Rectal mucosal ornithine decarboxylase (ODC) activity has been reported to distinguish between patients with and without adenomatous polyps (AP). In the present investigation, ODC activity has been measured in 28 patients with AP and 34 patients without AP. To assess the intraindividual variation in ODC activity, repeat biopsies were performed on 11 patients. In addition, the effect of postbiopsy sample handling was investigated by storage of samples on either dry or wet ice during transport to the laboratory. The mean rectal mucosal ODC activity in patients with AP was 196.0 +/- 195.5, whereas that in AP negative patients was 182.2 +/- 320.5. The rectal mucosal ODC activity in patients with colorectal cancer was 388.2 +/- 581. Repeat samples in individuals were generally within the same range as the original samples. The method of sample transport did not significantly affect the level of ODC measured in a particular biopsy. Because of high variability in rectal mucosal ODC activity within the population, there was wide overlap in ODC values between those patients with and without AP in an unselected general population. Thus, the measurement of flat rectal mucosal ODC activity is not a good predictor of the presence or absence of AP. Additional studies of the factors affecting mucosal ODC activity are necessary before the potential clinical utility of the method can be realized in the general population.     

Improvement of cervical dystonia: possible role of transcranial magnetic stimulation simulating sensory tricks effect

Idiopathic cervical dystonia (ICD) is the most common form of focal dystonia. A characteristic and unique diagnostic feature is the presence of "sensory tricks", for example, a finger placed on the chin to neutralize the spasm. Although approximately 70% of patients with ICD experience effective sensory tricks, the exact mechanism of these tricks is still unknown. However, recent evidence suggests that higher sensorimotor integration processes are involved. A study using H2(15)O positron emission tomography demonstrated that the application of sensory trick stimulus, resulting in a near-neutral head position, led to an increased activation mainly of the superior and inferior parietal lobules (ipsilateral to head turn) and bilateral occipital cortex and to a decreased activity of the supplementary motor area and the primary sensorimotor cortex (contralateral to head turn). Since transcranial magnetic stimulation (TMS) is an experimental device with the ability to excite or depress the neural circuits, we hypothesize that the use of TMS of specific parameters to specific brain areas (as above) may produce an effect similar to sensory tricks resulting in the relief of spasms and the improvement of cervical dystonia.     

Dissecting the twin-arginine translocation pathway using genome-wide analysis

A recently discovered route for protein export, known as the twin-arginine translocation (Tat) pathway, has received much attention owing to several atypical characteristics that distinguish it from other transport mechanisms. For instance, recent evidence has clearly established that this pathway only transports folded polypeptides. Moreover, several studies have demonstrated a vital role for the Tat pathway in bacterial pathogenesis. In this review, we discuss genomic approaches that have been employed to determine the prevalence and capacity of the Tat system and how the information generated from these approaches is helping to connect Tat transport to bacterial physiology and virulence.     

Oscillopsia of peripheral vestibular origin. Central and cervical compensatory mechanisms

Eight patients with absent vestibular function categorized into four grades according to the disability they suffered from oscillopsia have been studied with a view to correlating its severity with the development of gaze stabilizing compensatory mechanisms. Eye movements were recorded while the following sinusoidal rotational stimuli were delivered: 1) trunk on head oscillation in the dark (COR); 2) head on trunk oscillation in the dark; 3) head on trunk and whole body (head and trunk) oscillation in the light in the presence of optic fixation. The COR was potentiated in all the patients regardless of their clinical status. Velocity gains (peak slow phase eye velocity/peak head velocity) during whole body rotation were significantly lower than head on trunk gains in the light in the better compensated patients. Since in the absence of vestibular function whole body rotation involves only the otokinetic system (OKN), this finding implies a depression of the OKN in these patients which can be corrected during head on trunk movements by virtue of a dynamic input from the neck. The results suggest that the processes of recovery from oscillopsia are dependent, in the main, upon the development of central mechanisms by means of which undesirable image movement across the retina is perceptually suppressed. Depression of OKN may be secondary to this perceptual rearrangement.