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BACKGROUND: Multiple endocrine neoplasia type 2 (MEN 2) and familial medullary thyroid carcinoma (FMTC) are autosomal dominantly inherited cancer syndromes that predispose to C-cell hyperplasia and MTC. MEN 2A and FMTC are caused by mutations in the RET proto-oncogene. METHODS: We used a multiplex polymerase chain reaction-based assay to screen exons 10, 11, 13, and 14 of RET for mutations in 2 families with FMTC. We correlated mutation status with calcitonin and pathologic studies to determine genotype-phenotype correlations. RESULTS: We identified a mutation in codon 804 in exon 14 (GTG-->ATG; V804M) in both families. An 86-year-old person who was a gene carrier and other individuals over age 70 who were suspected by pedigree analysis to be gene carriers had no overt clinical evidence of MTC. Four of 21 patients who underwent a thyroidectomy also had papillary thyroid cancer. One individual in each family had metastatic MTC at age 30 and 32 years, and all 26 people having thyroidectomies had either MTC or C-cell hyperplasia, leading us to continue to recommend prophylactic thyroidectomy for all identified patients who were gene carriers. CONCLUSIONS: Because of active MTC in younger members of these families, including metastases, we have continued to advocate thyroid surgery in mutation-positive individuals. While DNA diagnosis of gene carriers and subsequent genetic counseling was relatively straightforward, the acceptance of surgical recommendations was more difficult for some individuals. These families demonstrate that the search for RET mutations should include exons 13, 14, 15, and 16 in patients whose studies in exons 10 and 11 are negative.

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The Multiple Sleep Latency Test (MSLT) was used to assess the effects of ethanol at the peak and descending phases of the breath ethanol curve. Ethanol (0.75 g/kg) was administered (at 0900 hr) to 8 healthy, normal-sleeping men, aged 21 to 45 years old after 8 hr of sleep the previous night. MSLTs were conducted and breath ethanol concentrations (BrECs) were measured at 15, 45, 75, 105, 225, and 345 min after drinking was completed. Subjective measures were administered immediately before each sleep latency test. BrECs over the first 75 min (tests 1 to 3) peaked and differed from all subsequent tests (tests 4 to 6) over which BrECs declined. Sleep latency and subjective measures were averaged over tests 1 to 3 and 4 to 6. There was a significant increase in mean sleep latency relative to placebo for tests 1 to 3 and a significant reduction for tests 4 to 6. The subjective measure of stimulation sedation, the Biphasic Alcohol Effects Scale, showed lessened sedation after ethanol versus placebo on tests 1 to 3, compared with tests 4 to 6. This study confirmed the presence of a biphasic ethanol effect using an electrophysiological method (MSLT), showing increased physiological alertness on the peak phase of the BrEC curve and increased sedation on the descending phase. Relative to the effects observed on the MSLT with other low-dose stimulant drugs, the stimulatory effect of ethanol was mild.

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Parents who decide to continue a pregnancy diagnosed with a sex chromosome abnormality (SCA) experience a variety of emotions as they deal with complex medical and genetic information. To better understand these individuals' psychosocial, educational, and support needs, 26 parents who received prenatal diagnosis of an SCA after 1989 and who had decided to continue their pregnancy were interviewed by telephone. Twenty (77%) reported they initially had a "poor" understanding of the predicted syndrome. All parents later met with a genetics professional. Twenty-two (92%) parents considered sterility and underdevelopment of secondary sexual characteristics to be the most negative aspects of SCAs. Contact with other parents of children with SCAs and with support organizations were generally viewed as helpful experiences. Insight gained from this study should be useful for genetic counselors and other health care providers involved with patients who have received abnormal prenatal diagnosis results.

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Thirty-six healthy young men and women (age range 21-35 years) were studied in an experimental model of sleep fragmentation. On 2 nights sleep was disrupted by presenting tones to produce brief electroencephalogram (EEG) arousals (without shortening sleep time) and daytime function was assessed the following day with the Multiple Sleep Latency Test and a divided attention performance test. The fragmentation of sleep produced significant disruption of nocturnal sleep and reduced daytime alertness. Adaptation in EEG-defined arousals occurred from the 1st to the 2nd night of fragmentation. Threshold (measured indirectly) characteristics of EEG-defined arousals were somewhat different than those of previous studies requiring behavioral awakening. The percent of tone series producing arousal, number of tones necessary for arousal and duration of the arousal all reflected heightened thresholds in stage 3/4 and rapid eye movement (REM) sleep compared to stage 1 and stage 2 sleep. In the last 3 hours of sleep versus the first 3 hours, arousals occurred less frequently, required more tones to produce, resulted in shorter durations and in fewer sleep stage changes, except for REM sleep where the converse was the case.

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