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Biomedical subjects

W Webster

Publications and source records attributed to W Webster.

At least 19 recordsLinked to original sources

Disruption of Ini1 leads to peri-implantation lethality and tumorigenesis in mice.

SNF5/INI1 is a component of the ATP-dependent chromatin remodeling enzyme family SWI/SNF. Germ line mutations of INI1 have been identified in children with brain and renal rhabdoid tumors, indicating that INI1 is a tumor suppressor. Here we report that disruption of Ini1 expression in mice results in early embryonic lethality. Ini1-null embryos die between 3.5 and 5.5 days postcoitum, and Ini1-null blastocysts fail to hatch, form the trophectoderm, or expand the inner cell mass when cultured in vitro. Furthermore, we report that approximately 15% of Ini1-heterozygous mice present with tumors, mostly undifferentiated or poorly differentiated sarcomas. Tumor formation is associated with a loss of heterozygocity at the Ini1 locus, characterizing Ini1 as a tumor suppressor in mice. Thus, Ini1 is essential for embryo viability and for repression of oncogenesis in the adult organism.

Animals↗

Pharmacokinetic data support pharmacologically induced embryonic dysrhythmia as explanation to Fetal Hydantoin Syndrome in rats.

New studies suggest that the teratogenicity of phenytoin (PHT) is linked to its membrane-stabilizing pharmacological action via the rapid component of the delayed rectified potassium channel (lkr), resulting in embryonic cardiac dysrhythmia during a restricted sensitive period. In order to further elucidate this theory, PHT was administered to Sprague-Dawley rats on gestation day (GD) 11 with either a single dose of 150 or 100 mg/kg ip or 150 mg/kg po and developmental toxicity at term (GD 21) was studied. In satellite animals blood samples were withdrawn (0.5-24 h after dose) and total and free maternal plasma concentrations of PHT were measured. Pharmacokinetic data correlated well with pregnancy outcome data. At 150 mg/kg ip high concentrations of long duration (C(max) 240 microM and AUC 5300 microMhl(-1) - total) and marked developmental toxicity (embryonic death, decreased fetal weights, and orofacial clefts) were observed. After 100 mg/kg ip (C(max) 150 microM, AUC 2600 microMhl(-1) - total) only slight developmental toxicity (decreased fetal weights) was recorded and after 150 mg/kg po the plasma concentrations were even lower (C(max) 63 microM and AUC 1100 microMhl(-1) - total) and no adverse effects at all were observed. In separate experiments the effect of different concentrations of PHT on the embryonic heart was studied by adding PHT to GD 11 rat embryos cultured in vitro or by culturing GD 11 embryos from exposed dams. The decrease in heart rates was 3, 16, and 32% after culture with 50, 100, and 200 microM of PHT, respectively. After maternal administration of 150 mg/kg ip or po, the embryonic heart rate in vitro decreased by 25 and 7%, respectively, compared to controls. Altogether the results suggest that the development toxicity of PHT is caused by concentration-dependent induction of embryonic dysrhythmia and hypoxia related damage.

Abnormalities, Drug-Induced↗

Electromyographic (EMG) biofeedback in the comprehensive treatment of central pain and ataxic tremor following thalamic stroke.

Peripheral pain and ataxic tremor can appear suddenly following thalamic stroke and can significantly alter a patient's psychological, social, and physical functioning. The present paper reports the case of a 70-year-old Caucasian female who sustained an acute left posterior cerebral artery infarction involving the thalamus and left mesiotemporal regions. She subsequently developed Central Poststroke Pain and ataxic movement of her right arm and hand in addition to a significant right-side claudication. She was treated over 16 weeks (6 weeks of EMG biofeedback and 10 weeks of psychotherapy) with a combination of EMG biofeedback, progressive muscle relaxation, behavioral pain coping skills training, Forced Use Therapy, and Cognitive Behavioral Therapy 7 years after her initial cerebral accident. The case demonstrates the utility of biofeedback when combined as part of a comprehensive treatment program to address the multiple complications associated with thalamic stroke.

Aged↗

The pursuit of PET.

Explore the source record for details and available documents.

Cost-Benefit Analysis↗

Management of limb length inequality during total hip replacement.

Significant limb length inequality is not an uncommon problem after total hip replacement. Preoperative measurement of limb length inequality, preoperative planning with radiographic templates, and intraoperative correction with measurements of limb lengths before and after the insertion of the trial components using special calipers can reduce the incidence and magnitude of this problem. A review of 85 consecutive patients who had primary total hip arthroplasty in which these techniques were used by a single surgeon, showed that 43 had limb inequality preoperatively ranging from 0.5 to 7.25 cm, but only 14 (16%) had limb length inequality after surgery. Eleven limbs (13%) had been lengthened 0.5 to 1 cm compared with the contralateral limb. Of the 42 patients with equal limb lengths preoperatively, 3 had a lengthened limb postoperatively compared with their contralateral limb. Four patients were using lifts on the same side because the limb was too short, and 2 were using lifts on the other side because the limb was too long. None of the other patients complained about limb length inequality. The techniques described above are helpful in minimizing limb length inequality during total hip replacements.

Hip Prosthesis↗

Positron emission tomography; making an informed decision.

Research, planning and careful thought on the part of the radiology manager must precede the acquisition of a PET system. Mr. Webster's article discusses the strengths of positron emission tomography, offers questions designed to help the manager decide if it is applicable to his organization, and includes an anatomy of a PET center. All this valuable information will facilitate making a sound decision on this possible "new venture."

Capital Expenditures↗

Maternal hyperphenylalaninemia fetal effects.

Thirty-four children of 11 mothers with untreated hyperphenylalaninemia had a pattern of malformation consisting of prenatal and postnatal growth retardation, microcephaly and central nervous system dysfunction, increased incidence of malformations, and a peculiar facial appearance. Maternal hyperphenylalaninemia appears to be teratogenic, with a variability related to the blood phenylalanine concentration.

Adolescent↗

Intra-abdominal sepsis--ultrasound evaluation.

The advent of grey-scale ultrasound has made this facility an irreplaceable tool for diagnostic imaging techniques. Although well established in obstetric management, its application to abdominal "body" scanning is not yet fully realized and accepted. These case presentations demonstrate the role of ultrasound in the diagnosis, localization and clinical management of patients with intra-abdominal sepsis. It is emphasized that ultrasound should be used early in the work-up of such problems and is rapidly becoming the investigation of choice. The diagnostic information provided facilitates management, reduces the need for complex investigations and occasionally makes surgery unnecessary.

Abdomen↗

Interference with proliferative activity in the CNS and its relation to facial abnormalities.

In considering craniofacial abnormalities, possible caused by factors interfering with cell proliferation, it is important to keep in mind the central nervous system. The CNS produces specific cell types throughout gestation and interference with cell proliferation may cause permanent cell loss. In this study it is shown that brief insults may damage some brain structures and spare others. Which structures sustain damage depends on which cells are proliferating at the time of insult. The varied lesions produced by interference at different stages of development were found to be accompanied by different syndromes of behavioral abnormalities.

Abnormalities, Drug-Induced↗