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PubMed2005

Histone deacetylase inhibitors: a review of their clinical status as antineoplastic agents.

The histone code refers to specific modifications in the biochemical composition of nucleosome-associated histone proteins involved in the regulation of gene transcription. These modifications include, among several, acetylation, methylation, and phosphorylation of several histone amino acid residues and are associated with different states of chromatin configuration and gene expression. In particular, acetylation of specific residues in histones H3 and H4 has been associated with an open chromatin configuration and a permissive gene transcription state. This particular modification is regulated by several enzymatic activities with the capacity to either transfer acetyl groups or to induce histone deacetylation. This last activity is associated with gene silencing. Several agents have been shown to have histone deacetylase inhibitory activity (HDACI). In vitro, experiments in multiple neoplastic cancer cell lines have demonstrated that treatment with HDACIs results in increased global and gene specific histone acetylation, and reactivation of aberrantly silenced genes. This phenomenon has been associated with cell differentiation and induction of apoptosis. Based on these observations, several of these agents are now in clinical development both for solid tumor and hematological malignancies. In this article, we provide a brief introduction to the field of histone deacetylation inhibition in cancer and review the most relevant clinical data so far published.

Acetylation↗

PubMed2004

The G2028R glycine substitution mutation in COL7A1 leads to marked inter-familiar clinical heterogeneity in dominant dystrophic epidermolysis bullosa.

BACKGROUND: Glycine substitution mutations in COL7A1 not only cause dominant dystrophic epidermolysis bullosa (DDEB), but can also be silent mutations which lead to recessive dystrophic epidermolysis bullosa (RDEB) in combination with additional mutations in the other allele. OBJECTIVE: In this study, we have examined a large American Caucasian pedigree in which 10 family members from four generations presented with simple toenail dystrophy without skin fragility in autosomal dominant manner. METHOD: We sequenced COL7A1 of this pedigree. RESULTS: Mutational analysis indeed detected a heterozygous G-to-A transition at nucleotide position 6082 leading to G2028R in all the affected members. Surprisingly, mutation database revealed that this G2028R mutation had been previously identified in two distinct Asian families with DDEB showing apparent skin fragility and blister formation. One case was a 17-month-old Chinese female with classical phenotype of DDEB and the other was a 27-year-old Japanese female with typical epidermolysis bullosa (EB) pruriginosa. To better understand the molecular mechanisms of this marked inter-familiar clinical heterogeneity, we examined the entire sequence of all the exons and exon-intron borders as well as the promoter region of COL7A1 in all the three families. Sequence results demonstrated no significant nucleotide difference in COL7A1 among the three pedigrees. CONCLUSION: This paper has demonstrated for the first time that identical COL7A1 glycine substitutions can cause remarkably heterogeneous clinical phenotypes extending from simple toe nail dystrophy without skin fragility to typical DDEB and EB pruriginosa. In addition, the fact of inter-familiar, not intra-familiar clinical heterogeneity associated with G2028R suggest that the other molecular mechanisms not controlled by COL7A1 coding sequence might be responsible for the clinical heterogeneity.

Adult↗

PubMed1985

Patient exposition and physician explanation in initial medical interviews and outcomes of clinic visits.

To replicate an earlier study and explore associations between verbal behaviors in patient-physician interactions and outcomes of care, 102 visits to a medicine walk-in clinic were tape-recorded, transcribed, and coded according to the Verbal Response Mode (VRM) system. Questionnaires given before and after the clinic visit and telephone interviews 1 week and 4 weeks after the visit were used to measure patient satisfaction, compliance, and change in symptoms. Data were collected on patients' sociodemographic characteristics, illness characteristics, and health beliefs. Two verbal exchanges were examined: in the medical history, the Patient Exposition exchange, which was measured as the frequency with which patients make statements about their illnesses in their own words; and in the conclusion, the Physician Explanation exchange, which was measured as the percentage of physician statements that are factual. These verbal indexes showed correlations with patient satisfaction, thus replicating the earlier study, but no significant correlations with compliance. Analysis of variance showed that the association between verbal exchanges and patient satisfaction remained after controlling for physician differences and for patient age, education, and belief in the controllability of the illness.

Adult↗

PubMed2005

Molecular evaluation of CFTR sequence variants in male infertility of testicular origin.

Although the involvement of the CFTR gene has been well established in congenital agenesia of vas deferens, its role in non-obstructive (NOb) infertility is still a matter of debate. In order to definitively define the involvement of the CFTR gene in spermatogenic impairment and a potential synergistic contribution to known genetic and clinical factors, genetic variants in the entire coding sequence and the immediately flanking regions of the CFTR gene, along with a thorough clinical evaluation, were analysed in 83 NOb infertile patients and 87 clinically well-defined fertile individuals as controls. The results of our study showed no statistical difference between CFTR carrier frequency in the infertile and fertile population. Specifically, the IVS8-6(5T) allele carrier frequency was similar in NOb infertile patients when compared with fertile men, but it is noteworthy that, when fertile men were classified into having optimal and suboptimal fertility, no 5T allele was found among the 35 men with optimal fertility parameters. In conclusion, extensive CFTR analysis in infertile individuals and fertile population as adequate control definitively excludes the involvement of the CFTR gene variants in sperm production and stresses the importance of carefully identifying those individuals with obstructive defects, in whom CFTR screening will be beneficial.

Base Sequence↗

PubMed1998

Epidemiology of carotid endarterectomy among Medicare beneficiaries: 1985-1996 update.

BACKGROUND AND PURPOSE: This article describes changes in the rate and outcome of carotid endarterectomies among Medicare beneficiaries. METHODS: We analyzed International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes as shown on Medicare bills to calculate carotid endarterectomy frequency, rate, and perioperative mortality by patient demography and hospital characteristics. RESULTS: After initially peaking at 61273 procedures (20.6 per 10000 beneficiaries) in 1985, the frequency of carotid endarterectomy among Medicare beneficiaries declined to 46571 (14.3 per 10000) in 1989 and then rose to 108275 (28.6 per 10000) in 1996. Patients were predominantly aged 65 to 74 years, male, and white; surgery occurred mainly in large, urban, nonprofit, and teaching hospitals. Perioperative mortality declined from 3.0% in 1985 to 1.6% in 1996. CONCLUSIONS: The frequency and rate of carotid endarterectomy showed prompt response to reports from clinical trials. Perioperative mortality both improved and converged over time but did not attain the rates reported by the trials. Patients aged 85+ years suffered twice the average perioperative mortality.

Black or African American↗

PubMed2005

Measuring medical complexity during inpatient rehabilitation after traumatic brain injury.

OBJECTIVE: To compare the performance of 3 severity of illness (SOI) indices--the Comprehensive Severity Index (CSI), All Patient Refined Diagnosis Related Groups Severity of Illness, case-mix group (CMG)--and 5 well-known neurologic parameters, as measures of medical complexity. DESIGN: Retrospective chart review. SETTING: Inpatient rehabilitation center within a level I trauma center. PARTICIPANTS: Consecutive traumatic brain injury (TBI) admissions (N=212). INTERVENTION: Acute inpatient TBI rehabilitation. CSI and neurologic parameters were scored by chart extraction. SOI was based on diagnosis codes by using 3M PC Grouper software, version 15. MAIN OUTCOME MEASURES: Adjusted R 2 was used to predict rehabilitation charges as a proxy of medical complexity. RESULTS: The highest adjusted R 2 values for single variables predicting charges were: CMG .349, CSI .293, duration of posttraumatic amnesia .260. Adjusted R 2 values for the CMG combined with the CSI, 5 neurologic parameters, and SOI to predict charges were .446, .431, and .365, respectively. CONCLUSIONS: The CMG was the best single predictor of rehabilitation charges for TBI. Predictive ability was better when the CMG was combined with the CSI or a combination of the 5 neurologic parameters. A severity index based on objective clinical findings rather than diagnostic codes may have distinct advantages for rehabilitation outcome studies and reimbursement methodology.

Adolescent↗

PubMed1995

Representing HIV clinical terminology with SNOMED.

1. RESEARCH OBJECTIVES AND METHODS. Because of a need for a standard classification and coding system to encode data for HIV infected patients in the AIDS Program clinic at San Francisco General Hospital, we have begun a subset of clinical terms commonly used in the care of patients with HIV disease, and we have sought to represent these terms using terminology from the SNOMED International classification system. We selected a sample of key findings for AIDS primary care for the AIDS Registry database. The areas of chest x-ray findings, psychological problems, and patient symptoms were chosen because they were representative of a number of SNOMED International axes, including diagnoses, morphology, topography, and function. They also included modifiers representing the concepts of laterality, time, severity, and certainty. 2. RESULTS. As shown by the sample terms in the table below, the findings suggest that SNOMED is a good starting point for a standard classification and coding system to support the clinical care of patients with HIV disease. The next phase of the research will focus on the evaluation of the adequacy and acceptability of the SNOMED representation to clinicians in the AIDS clinic.

HIV Infections↗

PubMed2005

The new apheresis and blood and marrow transplantation-related current procedural terminology codes for payment of apheresis and blood and marrow transplantation services.

To address deficiencies in Current Procedural Terminology (CPT) codes that describe many of the clinical services offered to patients, several physicians in the blood and marrow transplantation and apheresis field joined with a coalition including the American Society of Hematology, American Society for Blood and Marrow Transplantation, American Association of Blood Banks, American Society of Clinical Oncology, American Society for Apheresis, National Marrow Donor Program, and American Red Cross to collaborate in addressing these deficiencies by designing new CPT codes. The CPT editorial panel approved 18 new or revised codes. All these codes were given permanent or temporary value by the relative value unit update committee, but not all values were approved by the Centers for Medicare & Medicaid Services (CMS), in particular, the cell-processing codes and the unrelated donor search code. Further discussions addressing these concerns are under way with the CMS. Use of these new codes allows apheresis and transplant centers to charge appropriately for these services. This will help transplant center contracts with CPT codes, with payers more specifically describing services offered to these patients. In turn, this will give better justification for payment. This may allow certain payments for services to increase and help transplant centers better allocate revenue from fixed global case rate payments. Details about the individual codes and their approval process are reviewed in this article.

Blood Component Removal↗

PubMedDate not supplied