Deregulation of c-myc gene expression in human colon carcinoma is not accompanied by amplification or rearrangement of the gene.

The structure and expression of the c-myc oncogene were examined in 29 primary human colon adenocarcinomas. Dot blot hybridization of total RNA showed that 21 tumors (72%) had considerably elevated expression of c-myc (5- to 40-fold) relative to normal colonic mucosa. These data were corroborated by Northern blots of polyadenylated RNA, which showed a 2.3-kilobase transcript. Southern analysis of the c-myc locus in these tumors indicated the absence of amplification or DNA rearrangement in a 35-kilobase region encompassing the gene. In a parallel study, elevated expression of c-myc without amplification or DNA rearrangement was also observed in three of six colon carcinoma cell lines examined; in addition, unlike a normal colon cell line control, these three cell lines exhibited constitutive, high-level expression of the gene during their growth in cultures. These results indicate that elevated expression of the c-myc oncogene occurs frequently in primary human colon carcinomas and that the mechanism involved in the regulation of c-myc expression is altered in tumor-derived cell lines.

Clinical outcomes with unfractionated heparin or low-molecular-weight heparin as bridging therapy in patients on long-term oral anticoagulants: the REGIMEN registry.

BACKGROUND: Patients who receive long-term oral anticoagulant (OAC) therapy often require interruption of OAC for an elective surgical or an invasive procedure. Heparin bridging therapy has been used in these situations, although the optimal method has not been established. No large prospective studies have compared unfractionated heparin (UFH) with low-molecular-weight heparin (LMWH) for the perioperative management of patients at risk of thromboembolism requiring temporary interruption of long-term OAC therapy. PATIENTS/METHODS: This multicenter, observational, prospective registry conducted in North America enrolled 901 eligible patients on long-term OAC who required heparin bridging therapy for an elective surgical or invasive procedure. Practice patterns and clinical outcomes were compared between patients who received either UFH alone (n = 180) or LMWH alone (n = 721). RESULTS: Overall, the majority of patients (74.5%) requiring heparin bridging therapy had arterial indications for OAC. LMWH, in mostly twice-daily treatment doses, represented approximately 80% of the study population. LMWH-bridged patients had significantly fewer arterial indications for OAC, a lower mean Charlson comorbidity score, and were less likely to undergo major or cardiothoracic surgery, receive intraprocedural anticoagulants or thrombolytics, or receive general anesthesia than UFH-bridged patients (all P < 0.05). The LMWH group had significantly more bridging therapy completed in an outpatient setting or with a < 24-h hospital stay vs. the UFH group (63.6% vs. 6.1%, P < 0.001). In the LMWH and UFH groups, similar rates of overall adverse events (16.2% vs. 17.1%, respectively, P = 0.81), major composite adverse events (arterial/venous thromboembolism, major bleed, and death; 4.2% vs. 7.9%, respectively, P = 0.07) and major bleeds (3.3% vs. 5.5%, respectively, P = 0.25) were observed. The thromboembolic event rates were 2.4% for UFH and 0.9% for LMWH. Logistic regression analysis revealed that for postoperative heparin use a Charlson comorbidity score > 1 was an independent predictor of a major bleed and that vascular, general, and major surgery were associated with non-significant trends towards an increased risk of major bleed. CONCLUSIONS: Treatment-dose LMWH, mostly in the outpatient setting, is used substantially more often than UFH as bridging therapy in patients with predominately arterial indications for OAC. Overall adverse events, including thromboembolism and bleeding, are similar for patients treated with LMWH or UFH. Postoperative heparin bridging should be used with caution in patients with multiple comorbidities and those undergoing vascular, general, and major surgery. These findings need to be confirmed using large randomized trials for specific patient groups undergoing specific procedures.

Use of enoxaparin for the chronically anticoagulated patient before and after procedures.

Patients who require chronic anticoagulation and a procedure have been traditionally managed either by stopping warfarin and starting intravenous standard heparin or by adjusted dose subcutaneous standard heparin or taken off all anticoagulation for a week before the procedure. Enoxaparin may be useful as an alternative method of anticoagulation, avoiding hospitalization and the need for frequent monitoring.

The management of anticoagulation before and after procedures.

Patients maintained on warfarin for atrial fibrillation, mechanical heart valves, or deep venous thrombosis may occasionally need to stop their anticoagulation during invasive procedures. This article reviews the literature on bleeding risks of certain procedures, thrombosis risks of stopping anticoagulation, and heparin and warfarin pharmacokinetics. Recommendations regarding how to manage anticoagulated patients are discussed.

The outpatient with unilateral leg swelling.

Approaching the patient with unilateral leg swelling presents a challenge to the physician in ambulatory practice. Contributing to the difficulty is the lack of studies that have assessed a population of patients presenting with unilateral leg swelling. The purpose of this article is to discuss unilateral leg swelling with respect to the chronicity of the presentation and the most common differential diagnoses based on a review of the current literature and personal clinical experience.

Outpatient anticoagulation issues for the primary care physician.

Increasingly, primary care providers are caring for patients who require anticoagulation. In this article the indications for, complications of, and methods of dosing and monitoring warfarin in the outpatient setting are reviewed. Heparin use among ambulatory patients also is discussed.

Epidemiology of venous thromboembolic disease.

From the information presented in this article, it can be concluded that clinical suspicion of VTE should be increased in patients with a history of VTE, recent surgery, spinal cord injury, trauma, or malignancy. A variety of medical illnesses also increase the risk of venous thrombosis, including congestive heart failure, myocardial infarction, stroke with paresis, nephrotic syndrome, cigarette smoking, and obesity. Hypercoagulable states, such as antithrombin III deficiency, protein C deficiency, protein S deficiency, or factor V Leiden mutation should be considered in those patients who develop VTE in the absence of known risk factors. Additionally, the presence of vena caval filters does not exclude the possibility of PE or recurrent DVT. With a careful assessment of risk, physicians can hope to increase the diagnostic yield of VTE and decrease the significant morbidity and mortality of caused by this disease.

Primary care physicians' views on screening and management of alcohol abuse: inconsistencies with national guidelines.

BACKGROUND: The effects of patients' abuse of and dependence on alcohol are well known, but screening for problem drinking by primary care physicians has been limited. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) recommends that all patients be screened for alcohol use, all users be screened with the CAGE questionnaire, and all nondependent problem drinkers be counseled. We evaluated primary care physicians' screening methods for alcohol use and their management of problem drinkers to determine if they were following the NIAAA guidelines. METHODS: We mailed a questionnaire to 210 internists and family physicians to assess their alcohol screening and management methods. RESULTS: Only 64.9% of the respondents reported screening 80% to 100% of their patients for alcohol abuse or dependence during the initial visit; even less (34.4%) screened that many patients during an annual visit. Nearly all respondents (95%) reported "frequently" or "always" using quantity-frequency questions to screen for alcohol abuse, but only 35% "frequently" or "always" used the CAGE questionnaire. Only 20% of the respondents rated treatment resources as adequate for early problem drinkers, and 72% preferred not to counsel these patients themselves. A belief that a primary care physician could have a positive impact on an alcohol abuser was less likely to be held by respondents who were older, in a nonurban setting, or had more years in practice (P = .05). CONCLUSIONS: A substantial proportion of the physicians in our survey sample were not following NIAAA recommendations. Most physicians preferred not to do the counseling of nondependent problem drinkers themselves, but to refer those patients to a nurse trained in behavioral interventions.

Comprehension of discharge instructions by patients in an urban emergency department.

STUDY OBJECTIVE: To assess patients' comprehension of their emergency department discharge instructions and to determine if inner-city patients' literacy levels are adequate to comprehend written discharge instructions. DESIGN: Prospective, observational study. SETTING: The ED of an inner-city university hospital. PARTICIPANTS: Two hundred seventeen patients consecutively discharged from the ED during 12 separate time slots. INTERVENTIONS: Patients were interviewed after discharge from the ED and asked to state their diagnosis, medication instructions, and follow-up instructions. Comparisons between patient recall and instructions as written in the chart were assessed by independent raters and scored from poor to excellent. Patients were administered a standardized test of reading ability. RESULTS: Overall comprehension rates were judged to be good, although 23% of patients exhibited no understanding of at least one component of their discharge instructions. Mean reading ability of the patients was at the sixth-grade level. The ED's printed discharge instructions were written at an 11th-grade reading level. Patients with low literacy scores were more likely to have poor comprehension of instructions. CONCLUSION: Overall comprehension rates in this population were good despite the fact that ED instruction sheets were written at an inappropriately high reading level. Verbal instructions given by the discharging physician likely have a significant effect on patients' comprehension of instructions.

Insertional mutagenesis of the myc locus by a LINE-1 sequence in a human breast carcinoma.

The proto-oncogene c-myc is the cellular homologue of the transforming sequence carried by the avian myelocytomastosis virus MC29. A growing body of evidence implicates structural and functional alterations in and around proto-oncogenes such as c-myc in tumorogenesis. Here we report that comparison of the structure of myc from a ductal adenocarcinoma of the breast and from normal breast tissue of the same patient (Sc) revealed a tumour-specific rearrangement of one myc locus and amplification of the other myc locus. (For myc reviews see refs 1-4; for myc involvement in breast neoplasia see refs 5-7.) Within the second intron of the rearranged locus was a non-myc sequence with nearly complete homology to a long interspersed repetitive element (a LINE-1 sequence or L1). In this case, the L1 sequence has functioned as a mobile genetic element to produce a somatic mutation.