Citations

The propensity for both arterial and venous thrombotic disorders involves a genetic predetermination that operates In concert with environmental factors or triggers. Appropriate clinical assessment and therapeutic recommendations for patients with thrombosis requires a thorough knowledge of genetic variables that influence this propensity. This review focuses on the pathophysiology, natural history, and molecular biology of defined thrombophilic risk factors relevant to the care of patients with thrombotic disorders.

Abstract The natural history of idiopathic pulmonary fibrosis (IPF) has been characterized as a steady, predictable decline in lung function over time. Recent evidence suggests that some patients may experience a more precipitous course, with periods of relative stability followed by acute deteriorations in respiratory status. Many of these acute deteriorations are of unknown etiology and have been termed acute exacerbations of IPF. This perspective is the result of an international effort to summarize the current state of knowledge regarding acute exacerbations of IPF. Acute exacerbations of IPF are defined as acute, clinically significant deteriorations of unidentifiable cause in patients with underlying IPF. Proposed diagnostic criteria include subjective worsening over 30 days or less, new bilateral radiographic opacities, and the absence of infection or another identifiable etiology. The potential pathobiological roles of infection, disordered cell biology, coagulation, and genetics are discussed, and future research directions are proposed.

The Cognitive Adaptive Test/ Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) was designed for use by primary pediatric health care providers to identify children with developmental delays. This study assesses the concurrent and predictive validity of CAT/CLAMS developmental quotient (DQ) scores and the Mental Developmental Index (MDI) of the Bayley Scales of Infant Development in healthy children without risk factors for developmental delay. Overall CAT/CLAMS DQ scores correlated significantly with Bayley MDI scores at both 12 (r=0.393; p=0.008) and 30 months (r=0.742; p=0.0001) of age. Overall CAT/CLAMS DQ scores at 12 months of age also correlated modestly with Bayley MDI scores at 30 months of age (r=0.181; p=0.036). Despite its modest predictive validity at 12 months, its satisfactory concurrent validity plus its ease and speed of administration make the CAT/CLAMS a reasonable choice for assessment of early development by primary pediatric health care providers.

Barriers to early identification of children with developmental delays include time constraints during well-child visits and lack of easily administered, quantitative measures that can be used by pediatricians. This study assesses the ease of administration of the Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) during well-child visits from 2 to 36 months of age. During a single visit 177 children were assessed by either a developmental pediatrician (n = 121) or a third-year pediatric resident (n = 56). The mean time required to complete the CAT/CLAMS for all subjects was 6 minutes and 10 seconds (SD 2 minutes 44 seconds); less than 10 minutes was required in 92% of children assessed. There were no significant differences in the time required by the 2 examiners at any age level. Its ease of administration and psychometric properties make the CAT/CLAMS an excellent choice for the assessment of early development by primary care pediatricians.

In this study we examine factors which are associated with nursing home placement in terms of both their frequency of occurrence and the degree to which caregivers perceive them to have influenced placement. We propose “Tolerance Weighted Frequency Indices “ (TWFIs) to rank symptoms in terms of their association with placement decisions. Given our method for calculating TWFIs we observe that basic activity of daily living impairments appear to have a comparatively stronger association with nursing home placement than many disruptive behaviors. These findings emphasize the importance of management of ADL impairments in strategies designed to delay or prevent nursing home placement.

All patients treated for a first-time anterior glenohumeral dislocation in Olmsted County, Minnesota, from 1970 through 1979 were identified. Of these 124 patients, 116 were available for study at a mean followup of 4.63 years (range 2 to 11). Of the 116 patients, 38 (33%) had recurrence of dislocation: 21 of the 32 (66%) pa tients less than 20 years old,17 of the 43 (40%) patients 20 through 40 years old, and none of the 41 patients older than 40 years. Symptomatic instability remained a problem in 24 patients. Twenty-seven of 33 (82%) young athletes had recurrence of dislocation as com pared with only 8 of 27 (30%) nonathletes of similar ages. Patients restricted from resuming sports partici pation for 6 weeks or more had significantly better results than those restricted for less than 6 weeks. The recurrence rate of dislocation is not as high as previously reported. However, the rate in athletes is much higher than that in nonathletes. Many patients continue to complain of symptomatic instability without actual redislocation. In our younger patients, we now advise immobilization for from 3 to 6 weeks, followed by extensive rehabilitation before return to athletic ac tivity.

To compare the validity of direct pediatric developmental evaluation with developmental screening by parent report, parents completed a developmental screen (the Child Development Review), a pediatrician performed a direct developmental evaluation (Capute Scales), and a psychologist administered the Bayley Scales of Infant Development to a group of 30-month-old children. The agreement between these instruments was tested. All developmental quotient scores derived from the Capute Scales were more highly correlated with concurrent Bayley Mental Development Index scores than developmental quotient scores derived from the Child Development Review. Differences between developmental quotient scores derived from the Capute Scales and corresponding Bayley Mental Development Index scores were significantly smaller than those derived from the Child Development Review. Thus, direct pediatric developmental evaluation more reliably predicted concurrent Mental Development Index scores at 30 months of age than developmental screening by parent report. Increased emphasis on training of pediatric health care providers in direct developmental evaluation should be considered.

Dihydropyrimidine dehydrogenase (DPD) is one of the factors that determine the efficacy and toxicity of 5-fluorouracil. Variations in DPD activity may result from alterations at the transcriptional level of the DPYD gene. Heterogeneity in DPYD expression has been reported, but the molecular mechanisms responsible for this remain unclear. We investigated methylation of the DPYD promoter as a mechanism for transcriptional regulation of DPYD in the RKO colorectal cancer cell line. We demonstrate that the active transcription machinery for DPYD is present in RKO cells, but promoter binding of Sp1, a transactivator of DPYD, was inhibited, which on subsequent examination was shown to be associated with dense promoter methylation. Treatment with 5-aza-2′-deoxycytidine alone or the combination of 5-aza-2′-deoxycytidine and trichostatin A induced demethylation of the promoter and markedly increased the DPYD mRNA level in RKO cells but not in unmethylated WiDr cells. Furthermore, in vitro methylation of the DPYD promoter decreased promoter activity. These data suggest an important role for methylation in DPYD suppression. The transcriptional suppression of DPYD by methylation may be responsible for the increased 5-fluorouracil sensitivity observed in some patients. This may also provide insight into the mechanism underlying the downregulation of DPYD in some colorectal cancers.