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J Blanks

Publications and source records attributed to J Blanks.

9 recordsLinked to original sources

The Onchocerciasis Elimination Program for the Americas: a history of partnership.

The decision in 1987 by the pharmaceutical firm Merck & Co. to provide Mectizan (ivermectin) free of charge to river blindness control programs has challenged the international public health community to find effective ways to distribute the drug to rural populations most affected by onchocerciasis. In the Americas, PAHO responded to that challenge by calling for the elimination of all morbidity from onchocerciasis from the Region by the year 2007 through mass distribution of ivermectin. Since 1991, a multinational, multiagency partnership (consisting of PAHO, the endemic countries, nongovernmental development organizations, the Centers for Disease Control and Prevention in Atlanta, Georgia, as well as academic institutions and funding agencies) has developed the political, financial, and technical support needed to move toward the realization of that goal. This partnership is embodied in the Onchocerciasis Elimination Program for the Americas (OEPA), which is supported by the River Blindness Foundation (RBF) and now by the Carter Center. OEPA was conceived as a means of maintaining a regional initiative to eliminate what is otherwise a low priority disease. Since its inception in 1993, the OEPA has provided more than US$ 2 million in financial, managerial, and technical assistance to stimulate and/or support programs in Brazil, Colombia, Ecuador, Guatemala, Mexico, and Venezuela, so as to take full advantage of the Merck donation. Now halfway into a five-year, US$ 4 million grant provided through the Inter-American Development Bank, the OEPA's capacity to support the regional initiative is assured through 1999.

Americas↗

Lens tropomodulin: developmental expression during differentiation.

Lens epithelial cells undergo a dramatic transformation during the process of differentiation into elongated fiber cells. The membrane-associated actin cytoskeleton is likely to play a critical role in the stabilization and maintenance of the highly elongated fiber cell shape. Tropomodulin is a tropomyosin-binding protein associated with actin filaments in a variety of terminally differentiated cell types where stable actin filament organization is required for cell function. We now present results of studies to determine the temporal expression of tropomodulin in the developing lens. In situ hybridization experiments detected expression of tropomodulin mRNA in the developing mouse lens in elongating cells with a pattern similar to that of the fiber specific beta- and gamma-crystallins. Tropomodulin mRNA expression first appeared around 11.5 days post-coitum in elongating cells in the posterior part of the lens vesicle. At later stages the signal for tropomodulin was present in the elongating cells at the lens equator and in cortical fiber cells; signal was absent from the epithelium. To investigate the possible link between tropomodulin expression and fiber differentiation we used a well-established lens epithelial explant culture system in which fiber differentiation is induced by fibroblast growth factor (FGF). Tropomodulin expression was only observed in FGF-treated explants in conjunction with morphologic changes characteristic of lens fiber cell differentiation. The appearance of tropomodulin during the process of fiber cell differentiation suggests that tropomodulin may be important for stabilization and/or determination of actin filament length.

Animals↗

Light-induced acceleration of photoreceptor degeneration in transgenic mice expressing mutant rhodopsin.

PURPOSE: Mutations at various loci on the rhodopsin gene have been shown to cause autosomal dominant retinitis pigmentosa (ADRP). One of the most common is a point mutation (P23H) near the N-terminus of the protein. The authors have studied the effects of light deprivation on the rate of degeneration in pigmented transgenic mice expressing the P23H mutation as well as two additional mutations near the N-terminus of opsin (V20G, P27L). METHODS: Transgenic and normal littermates were reared in darkness or in cyclic light (approximately 7 foot-candle) for periods of 2, 4, or 6 months. Retinal structure and function were evaluated by electroretinography, retinal densitometry, light microscopy, and TUNEL labeling. RESULTS: Retinas of normal animals, whether reared in darkness or in cyclic light, had no structural or functional abnormalities. The rate of photoreceptor degeneration in dark-reared transgenic mice was significantly slower than in transgenic mice raised under cyclic light conditions. Differences between the two groups of animals were evident in the retinal histology, the electroretinographically determined sensitivity to photic stimulation, and the rhodopsin levels in the retina. TUNEL labeling of retinal wholemounts showed that cyclic light-reared animals had a threefold higher incidence of photoreceptor cell death than their dark-reared counterparts; the density of apoptotic cells was greatest in the inferior retina, the region most severely affected in patients with the P23H mutation. In comparison, photoreceptor cell death was more uniformly distributed across the retina in dark-reared transgenic mice. CONCLUSIONS: These findings suggest that light activation of rhodopsin contributes to the severity of the degenerative disease resulting from the P23H opsin mutation, and they raise the possibility that minimizing exposure to light may help to prolong useful vision of patients with this form of retinitis pigmentosa.

Animals↗

Hydrocephalus: the zero ICP ventricle shunt (ZIPS) to control gravity shunt flow. A clinical study in 56 patients.

Significant morbidity from ventricle shunt overdrainage at 6-7 years after initial shunt placement for hydrocephalus is increasingly recognized as due to excessive gravity-flow of shunted CSF when upright. Shunts are designed primarily to control high ICP. Shunts should also mimic normal upright ICP. Normal upright ICP is -65 mm of water (vertex reference), indicating that a level of zero ICP exists at 65 mm below the brain vertex, with negative ICP above and positive ICP below that level. This normal zero ICP level must be maintained by CSF shunts to mimic normal upright ICP. This will prevent and correct CSF shunt overdrainage. The zero ICP shunt (ZIPS) by design controls this zero level with a zero pressure device (ZPD; siphon control device) installed at the normal vertical level of zero ICP (cm/mm) below the vertex (65 mm). The shunt thus prevents excessive gravity-induced CSF shunt flow. Successful use of ZIPS in 56 patients is reported (low ICP group: n = 42; high ICP group: n = 14). Follow-up is up to 4.5 years. Results show that: (1) adjustability of ZPD level can achieve the desired clinical results; (2) the level of ZPD installed correlates within 4 mm of upright ICP attained; (3) the optimal level of ZPD installation to produce normal upright ICP is 65 mm below the vertex; (4) CT ventricle size, both slit ventricles and large ventricles, may or may not normalize when normal upright ICP is attained in this group of complex, previously shunted patients.

Cerebral Ventricles↗

Shunted hydrocephalus: normal upright ICP by CSF gravity-flow control. A clinical study in young adults.

Hydrocephalic patients with years of ventricle shunts may be disabled by shunt overdrainage. Gravity-induced upright CSF shunt flow produces this overdrainage with abnormally low, upright ICP. Consequently, the concept of a normal level of zero ICP, which ventricle shunts must mimic, was developed. For 4.5 years, this concept has been applied in hydrocephalus patients by using a Siphon Control Device as a Zero Pressure Device in ventricle shunts. The results in 56 patients, including 42 overdrainage problems, were assessed by clinical grading, ICP record analyses, and computed tomographic (CT) ventricle size comparisons. All patients ultimately achieved satisfactory clinical results. This occurred in 80% of the patients on the first insertion. Adjustment of the vertical level of the Zero Pressure Device was necessary in 20%. The optimum clinical result correlated with an upright ICP of -66 mm of H2O. This postoperative ICP correlated within 4 mm of the Zero Pressure Device placement below vertex. Ventricle size correlated poorly with clinical grade and normal ICP. Only 73% of slit ventricles enlarged by 16.5 months. The need to mimic normal upright ICP by maintaining a normal level of zero upright ICP in shunted patients is supported by these results.

Adolescent↗

Intracranial pressure effects on auditory evoked responses in the rabbit: preliminary report.

Acute elevated intracranial pressure (ICP) effects on the auditory evoked response (AER) were studied in the rabbit. Simultaneous CSF infusions to increase ICP and contralateral ICP pressure recordings were done through bilateral ventriculostomies. During rarefaction auditory stimulation, a minicomputer obtained a time-locked AER from ongoing electroencephalographic activity at base line ICP mean pressure and at three levels of increased ICP (250, 500, and 700 mm CSF) above base line. The results showed a statistically significant increased latency of the N3-P3 portion of the AER as well as of the P1-P3 central conduction time. The amplitude of AERs appeared unchanged. The effect is reversible and presumably is a neuropraxic type pressure effect on brain stem auditory pathways. Its clinical relevance is discussed.

Acoustic Stimulation↗

Experimental transcerebral fistula. Perineural olfactory CSF flow in the normal, hydrocephalic, and postoperative hydrocephalic dog shown by radionuclide ventriculography.

Cerebrospinal fluid dynamics were studied in eight dogs during normal, hydrocephalic, and postoperative phases. Radionuclide-labeled substances introduced into the normal ventricular system flow out of the exits from the fourth ventricle to the convexity subarachnoid spaces superiorly to be absorbed in the sagittal sinus, and basorostrally to the exits from the perineural olfactory sheath into the nose to produce physiological cerebrospinal fluid (CSF) rhinorrhea. Serial radionuclide ventriculography of the head following intraventricular isotope injection of labeled proteins and chelate into the kaolin-induced hydrocephalic system shows a high degree of ventricular stasis with no perineural olfactory nerve flow (rhinorrhea). An operative transcerebral fistula, fashioned from a dilated lateral ventricle to the convexity subarachnoid space, reestablishes perineural olfactory flow of CSF into the nose, as demonstrated by the radionuclide ventriculography studies. This suggests a potential method for treatment of hydrocephalus. Serial imaging studies in this surgically modified system clearly demonstrate radionuclide flow through the patent fistula to distal absorption sites, thereby bypassing the basal obstruction. Moreover, augmented CSF pressures associated with obstructive hydrocephalus can be controlled by such treatment. The application of this method in treating clinical hydrocephalus is discussed with emphasis on fistula arachnoid closure to assure fistula patency.

Animals↗