Change from slowly rotating 8-hour shifts to rapidly rotating 8-hour and 12-hour shifts using participative shift roster design.

OBJECTIVES: The study examined the impact of change, from slowly rotating continuous 8-hour shifts to more rapidly rotating continuous 8-hour and 12-hour shifts, on the health and quality of life of shift workers. METHODS: Self-report survey data were collected from 72 shift workers at 3 sewage treatment plants before and several months after roster change. After the change 1 plant first worked a rapidly rotating, 8-hour shift roster and then worked a 12-hour shift roster, and the other 2 plants worked continuous 12-hour shift rosters. RESULTS: After the change the shift workers at each plant reported increased satisfaction with roster design, a decrease in physical and psychological circadian malaise associated with shift work, improved day sleep quality, less tiredness, and improvements in the quality of home, social and work life. A between-plant comparison of the rapidly rotating 8-hour and 12-hour shift rosters showed greater improvements had been obtained with the 12-hour shift roster, and no significant differences in tiredness or sleep quality between the redesigned 8- and 12-hour shift rosters. However, a within-plant matched-pairs comparison at the 1st plant of the rapidly rotating 8-hour shift roster and the 12-hour shift roster showed no significant differences. CONCLUSIONS: The results show that the prior level of support for change may best explain the impact of roster redesign on individual well-being. They lend further support to shift worker participation in roster design.

Startle disease, or hyperekplexia: response to clonazepam and assignment of the gene (STHE) to chromosome 5q by linkage analysis.

Familial startle disease (also known as hyperekplexia and congenital "stiff-man" syndrome) is an autosomal dominant disorder characterized by an exaggerated startle reaction of sudden, unexpected auditory or tactile stimuli; affected neonates also have severe and occasionally fatal hypertonia. We recently encountered a large, five-generation family with startle disease, and treated 16 patients (including 1 neonate) with clonazepam; all experienced dramatic and sustained improvement. We performed systematic linkage analysis in this family, and found tight linkage between the disease locus and a polymorphic genetic marker locus (colony-stimulating factor receptor, or CSF1R) that has been physically mapped to chromosome 5q33-q35. The maximum odds ratio favoring linkage over nonlinkage is greater than 10,000,000:1 (lod score, 7.10) at 3% recombination. Several genes encoding neurotransmitter receptor components have been physically mapped to the subtelomeric region of chromosome 5q, and are thus candidates for the startle disease gene. The availability of additional large pedigrees with startle disease should facilitate identification and characterization of the gene for this disorder.

Phenytoin dosage predictions in paediatric patients.

Phenytoin dosing in paediatric patients is complicated both by alterations in patient requirements due to growth and maturation changes and by the capacity-limited characteristics of phenytoin metabolism. This study examines 2 pharmacokinetic methods to adjust phenytoin dosage based on a single dosing-rate/steady-state serum phenytoin concentration pair. A Bayesian forecaster and a fixed parameter [rate of metabolism (Vmax)] method were examined with previously published sets of a priori parameter estimates. The fixed Vmax method was utilised with the parameter derived from native Japanese (method 1), US Caucasian (method 2) and European (method 3) patients. The Bayesian forecaster used a priori parameter estimates obtained from native Japanese (method 4) and European (method 5) patients. Each method was examined retrospectively in 34 paediatric patients with a total of 48 predictions possible. Measures of absolute predictability, bias (mean error, % dose) and precision (root mean squared error, % dose), were -3.58/12.2, -1.51/12.2, 4.06/9.96, -4.38/13.2, and -3.10/11.5, for methods 1, 2, 3, 4 and 5, respectively. There was no significant difference among the 5 methods. However, the Bayesian algorithm tended to be more robust over a broad range of situations, providing predictions in all cases. The fixed Vmax methods could not provide predictions in every case. Finally, all methods had a significant number of overpredictions of dosage. Poorer results were observed when prediction of steady-state serum concentrations were performed, partly due to the retrospective nature of the study. We conclude that close monitoring of patients, regardless of the method chosen to adjust dosage, is recommended.

Clinical neurologic disorders in children with special otorhinolaryngologic relationships.

The anatomic (and functional) relationship of otorhinologic structures to the CNS has a potential for altered vascular supply, penetration by bacterial agents, and impaired gas exchange. The pathophysiologic relationship at times may be subtle or occult as indicated by examples. An awareness of potential relationships is critical for proper diagnosis and management.

Urine and plasma free phenytoin concentration correlation.

In an attempt to find a simple, noninvasive method for estimating the plasma free concentration (CPf) of phenytoin (PHT), the relationship between urine PHT concentration (Cu) and CPf was studied in 40 epileptic patients who were 6 to 50 yr old. Cu was determined by gas-liquid chromatography and CPf by equilibrium dialysis at 37 degrees. Cu was generally greater than CPf, but correlation between the two was strong (r2 = 0.876) and in the same range as previously published results for saliva and CPf. Correlation of Cu with CPf was not influenced by patient age, urine pH, or urine flow rate. In 24 patients timed urine collections were obtained and calculated renal clearances of PHT were shown to increase in proportion to urine flow rates. Although it is not known if renal impairment and albuminuria will alter the relationship between Cu and CPf it appears that Cu may be useful in estimating the concentration of pharmacologically active PHT in plasma.

Phase I evaluation of tetrahydrouridine combined with cytosine arabinoside.

In conventional clinical use, cytosine arabinoside (ara-C) is rapidly deaminated by pyrimidine nucleoside deaminase to the nontoxic compound uracil arabinoside. Tetrahydrouridine (THU) effectively inhibits this enzymatic degradation but is by itself nontoxic. This study demonstrates that concomitant administration of THU markedly increases the myelosuppressive potency of ara-C. When 25 or 50 mg/kg of THU iv and 0.1--0.2 mg/kg of ara-C iv are given daily x 5 days, they produce moderate-to-severe leukopenia and mild-to-moderate thrombocytopenia. A dose of 25 mg/kg of THU with 0.1 mg/kg of ara-C iv daily x 5 days appears appropriate for phase II studies; it produces myelosuppression equivalent to that produced by 3 mg/kg/day x 5 days of ara-C alone. No toxicity occurred with this combination that would not have been expected from ara-C given alone in an equitoxic dose. Although THU and ara-C produced a reduction in peripheral blood and bone marrow blast cells in eight of nine patients with acute leukemia, bone marrow remission did not occur in any of these heavily pretreated patients.