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PubMed2003

Genetics and susceptibility to toxic chemicals: do you (or should you) know your genetic profile?

This review is based on a symposium/roundtable session, sponsored by the Division of Toxicology of the American Society for Pharmacology and Experimental Therapeutics, that was held at the 2002 Experimental Biology meeting in New Orleans, LA. The focus is on the role of pharmacogenomics in determining individual susceptibility to chemically induced toxicity. An individual's risk of disease from exposure to toxic chemicals is determined by a complex interplay between genetics, physiology, and concurrent or prior exposures to drugs and other chemicals. The first section of the review defines the basics of pharmacogenetics and pharmacogenomics and assesses the current state of the science. Selected applications to specific enzyme systems are summarized by way of example. New, state-of-the-art approaches to studying genetic determinants of susceptibility, including analytical methods and transgenic technology, are then discussed. Finally, ethical and legal concerns with the application of this knowledge and methodology to human health will be discussed.

Animals↗
PubMed1999

Sarcoidosis presenting as a tumorlike muscular lesion. Case report and review of the literature.

Sarcoid myopathy presenting as a tumorlike lesion is an exceedingly rare presentation of sarcoidosis. Concurrent extramuscular involvement is common. Chest radiographs, if abnormal, may suggest the diagnosis. Magnetic resonance imaging is the preferred study for diagnosis and follow-up of tumorous sarcoid myopathy. Optimal therapy is not clear. Favorable responses have been cited with surgery or corticosteroids (alone or in combination). Azathioprine or alternative immunosuppressive agents (for example, antimalarials or methotrexate) may have a role in corticosteroid-recalcitrant patients. The role of local radiotherapy is controversial and should be reserved for severe localized disease refractory to aggressive medical therapy.

Female↗
PubMed2004

Psychological interactions with infertility among women.

Despite the fact that various studies have demonstrated the importance of the mind-body connection and fertility, the psychosocial aspects of infertility have not been adequately addressed. Fertility treatments, ranging from medical monitoring, to hormonal remedies and in vitro fertilization (IVF), are both a physical and emotional burden on women and their partners. Psychological factors such as depression, state-anxiety, and stress-induced changes in heart rate and cortisol are predictive of a decreased probability of achieving a viable pregnancy. A couple that is trying to conceive will undoubtedly experience feelings of frustration and disappointment if a pregnancy is not easily achieved. However, if the difficulties progress and the man and or woman are labelled as having fertility problems, then this may result in a severe insult to self-esteem, body image, and self-assessed masculinity or femininity. Three types of relationships have been hypothesized between psychological factors and infertility. These include: (1) psychological factors are risk factors of subsequent infertility; (2) the experience of the diagnosis and treatment of infertility causes subsequent psychological distress; (3) a reciprocal relationship exists between psychological factors and infertility. The evidence for these three relationships is reviewed and an alternative approach to the treatment of infertility including stress evaluation that precedes or is concurrent to fertility treatment is suggested.

Cost of Illness↗
PubMed1979

Effects of concurrent sepsis with clinically significant pulmonary embolic disease.

Forty-one patients with significant pulmonary emboli were reviewed. The presence of heart disease and obesity was found with relatively constant frequency throughout the groups presented. Postoperative infections (wounds or abscess) were frequently associated with fatal or significant pulmonary embolism, particularly after abdominal and pelvic operations. The infection rate (65 per cent) in patients in whom significant pulmonary embolism developed after abdominal and pelvic operations is particularly striking when compared to the overall infection rate of 7 per cent for major operations in our hospital. Recent studies of prophylactic minidose heparinization reveal an increased number of complications due to the heparin [24], and thus the proper selection of cases for prophylactic minidose heparin is mandatory. The data suggest that patients at high risk for the development of postoperative complications of infection are also at high risk for the development of significant pulmonary emboli and should be considered candidates for prophylactic minidose heparinization.

Adult↗
PubMedDate not supplied

Longitudinal analysis of the use of etanercept versus infliximab determined from medical chart audit.

OBJECTIVE: To describe the dosing of etanercept and infliximab for the treatment of rheumatoid arthritis (RA). METHODS: Adult patients with a diagnosis of RA who were treated with either etanercept or infliximab between 1999 and 2002 were selected from 16 rheumatology practices in the western and southeastern United States. Patients with a terminal illness or those receiving a tumor necrosis factor (TNF)-alpha inhibitor for an indication other than RA were excluded. Data were collected through a review of the patient medical records. Data collected on each patient included demographics, concurrent disease-modifying antirheumatic drug therapy, TNF-alpha inhibitor dose, frequency, duration of TNF-alpha inhibitor therapy, and discontinuation of TNF-alpha inhibitor therapy. RESULTS: A total of 244 patients were included in the evaluation (etanercept only [n=128; 52%], infliximab only [n=89; 36%], both [n=27; 11%]). The mean age of these patients was 55.1+/-13.3 years, 54.9+/-13.5 years, and 52.8+/-14.0 years, respectively; the mean duration of RA was 13.3 +/- 8.8 years, 13.4+/-8.0 years, and 14.0 +/- 9.9 years, respectively. Female patients constituted 70% of the sample. Health maintenance organization insurance was the most common form of medical insurance (45.8%), followed by Medicare (22.3%). The mean duration of follow-up for etanercept and infliximab treatment was 29.3+/-14.1 months and 14.8+/-6.9 months, respectively. Among patients who were still receiving therapy at the time of review, the mean initial and last etanercept doses were 25.0 mg versus 25.8 mg (P=0.16); the mean initial and last infliximab doses were 3.38 mg/kg versus 4.51 mg/kg (P<0.001). CONCLUSION: The dosing of etanercept and infliximab therapy was consistent with the approved labeling of both medications.

Antibodies, Monoclonal↗
PubMed2006

Finding the missing link between ictal bradyarrhythmia, ictal asystole, and sudden unexpected death in epilepsy.

Basic science studies of the human brain have supported the cortical representation of cardiovascular responses, including heart rate variability. Clinical observations of ictal bradyarrhythmia may be mechanistically explained by the influence of the central autonomic network, although the localization and lateralization issues need to be considered in the light of patterns of seizure spread, hand dominance, and presence of lesions. Ictal bradyarrhythmia also offers a mechanistic explanation of sudden unexpected death in epilepsy (SUDEP), though it may explain only some but not all cases of SUDEP. The missing links are (1) clinical evidence of common factors shared by patients with ictal bradyarrhythmia and patients who die from SUDEP, (2) evidence of arrhythmia as a risk factor for SUDEP from epidemiological studies, and, (3) determination of the importance of ictal bradyarrhythmia in SUDEP with respect to other proposed mechanisms including apnea and intrinsic cardiac abnormalities. There remains a need to review the seizure mechanisms in cases of SUDEP and to step up the amount of concurrent ECG/intracranial EEG analysis in both ictal bradyarrhythmia and SUDEP cases.

Autonomic Nervous System↗
PubMed2006

Composite EBV negative peripheral T-cell lymphoma and diffuse large B-cell lymphoma involving the ileum: a case report and a systematic review of the literature.

We report a case of an intestinal peripheral T-cell lymphoma (PTCL) with a concurrent diffuse large B-cell lymphoma (DLBL) involving the ileum and a regional lymph node. The patient presented with an abdominal mass. The terminal ileum showed a diffuse and monotonous population of small CD3-positive T cells. The T-cell receptor gamma (TCRgamma) gene was rearranged by PCR while the immunoglobulin heavy chain (IgH) gene was not. A separate section of the ileum showed a colliding large B-cell proliferation. The regional lymph node showed a diffuse proliferation of large centroblasts positive for CD20 and CD79a admixed with small T cells and showed a rearranged IgH receptor gene without evidence of a clonally rearranged TCRgamma gene. Both the PTCL and DLBL components were negative for EBV. A review and analysis of the pertinent literature describing composite T- and B-cell lymphomas is performed and reported.

Adolescent↗
PubMed1994

Aldicarb poisoning. A case report with prolonged cholinesterase inhibition and improvement after pralidoxime therapy.

Aldicarb is the most potent of the commercially available carbamate pesticides and is an unusual source of acute human poisonings. We present the case of a 43-year-old man exposed to aldicarb who developed severe cholinergic symptoms and progressive weakness requiring intubation for 5 days. Both his red blood cell cholinesterase and plasma pseudocholinesterase levels were depressed for a minimum of 44 hours. He demonstrated neuromuscular improvement concurrent with pralidoxime administration. The pertinent medical literature on aldicarb poisoning is reviewed.

Adult↗
PubMed1998

Assessing outcomes, costs, and benefits of emerging technology for minimally invasive saphenous vein in situ distal arterial bypasses.

BACKGROUND: Instrumentation for a minimally invasive angioscopic in situ peripheral arterial bypass (MIAB) with catheter-directed side-branch occlusion has recently been approved for use. Despite the attractiveness of this approach (2 short incisions), benefits such as lower morbidity and shorter hospitalizations remain undocumented. To justify wide acceptance, minimally invasive surgical techniques must match conventional procedures in durability and cost while enhancing patient comfort. Often such comparisons are difficult during the implementation phase of a new procedure. OBJECTIVE: To compare the outcomes of the MIAB procedures with a concurrent group of patients undergoing conventional in situ bypass procedures. DESIGN: Retrospective review. SETTING: University medical center. PATIENT: The first 20 consecutive MIAB procedures in 19 patients performed between August 1, 1995, and July 31, 1997, were compared with 19 contemporaneous consecutive conventional in situ bypass procedures performed at the same institution. MAIN OUTCOME MEASURES: Operative time, postoperative length of stay, hospital costs, complications, primary assisted and secondary patency, limb salvage, and survival. RESULTS: The patient groups were comparable with respect to age, sex, incidence of smoking, coronary artery disease, hypertension, diabetes, renal failure, cerebrovascular disease, indication, and distal anastomosis level. The median operative time was significantly greater for the MIAB group (6.6 hours vs 5.7 hours; P=.009), and intraoperative completion arteriography more frequently showed retained arteriovenous fistulas in the MIAB group (55% vs 21%; P=.05). The median postoperative length of stay and total cost were 6.5 days and $18,000 for the MIAB group and 8 days and $27,800 for the conventional group (P > or = .05). There were no significant differences in major complications (10% in the MIAB group vs 11% in the conventional group), wound complications (10% vs 11%, respectively), primary assisted patency at 1 year (68%+/-11% vs 78%+/-10%, respectively), secondary patency at 1 year (79%+/-10% vs 88%+/-8%, respectively), limb salvage at 1 year (85%+/-10% vs 94%+/-6%, respectively), or patient survival at 1 year (89%+/-8% vs 61%+/-13%, respectively). CONCLUSION: Patients undergoing the MIAB procedure avoided lengthy vein exposure incisions without sacrificing short-term results. There was a trend toward decreased hospital stay and cost, which may be further realized as the clinical experience broadens. Although longer follow-up and larger cohorts will always be required to define durability, immediate access to outcomes and costs on small numbers of patients facilitates the early assessment of emerging technology.

Adult↗
PubMed1992

The quality of mercy. Caring for patients with 'do not resuscitate' orders.

OBJECTIVE: To assess (1) the effect of an ethics education intervention for medical house officers on practices surrounding "Do Not Resuscitate" (DNR) orders and (2) the association of DNR care with patient diagnosis and demographic variables. DESIGN: A 1-year randomized, controlled trial. SETTING: An urban, university teaching hospital. PARTICIPANTS: Eighty-eight internal medicine house officers. INTERVENTION: House officers were arbitrarily assigned to four "firms." One firm was randomized to an extensive ethics education intervention (EI), one to a limited intervention, and two served as controls. MAIN OUTCOME MEASURES: Charts of patients with DNR orders were reviewed for compliance with the hospital's DNR policy, which instructs that when DNR orders are written there should be (1) an attending signature, (2) documentation of reasons, (3) appropriate consent, and (4) attention to 11 concurrent care concerns (CCCs) (eg, the appropriateness of intubation, tube feedings, hospice). RESULTS: Thirty-nine charts were reviewed before the intervention and 57 after. The number of CCCs per DNR order fell among patients cared for by controls (1.9 to 1.0, P less than .05) and rose among patients cared for by the EI group (0.9 to 3.8, P less than .05). Compliance with the DNR policy varied among patients with differing diagnoses. "Do Not Resuscitate" orders were signed less frequently (P = .01) for patients with the acquired immunodeficiency syndrome (AIDS) (65%) compared with patients who had other diagnoses (85%) or malignancy (91%). Similarly, appropriate consent was recorded for 59% of patients with AIDS, 83% of others, and 85% of those with malignancy (P less than .05). The number of CCCs per DNR was 0.7 for AIDS, 1.4 for others, and 2.4 for malignancy (P less than .05). In multivariate regression analysis, house officer ethics education and patient diagnosis, but not patient gender, age, race, or insurance status, were predictors of the number of CCCs per DNR. CONCLUSIONS: (1) An extensive ethics education intervention can improve care for DNR patients, especially with respect to CCCs. (2) In this setting, quality of care for DNR patients varied systematically with diagnosis. These results have implications for the design and implementation of ethics education programs.

Baltimore↗
PubMed1988

The implication of tobacco use in the young adult with head and neck cancer.

To define the biologic characteristics of head and neck cancer in the young adult, the clinical course of 83 previously untreated patients less than or equal to 40 years of age with head and neck cancer was reviewed retrospectively. Their course was compared to that in a randomly chosen, concurrently treated, site-matched and stage-matched older head and neck cancer population (matched control). Patterns of recurrence as well as overall disease-free survival in each of the two populations were not significantly different. An important stratification factor, however, was related to tobacco usage. Thirty percent of the young patients denied using tobacco compared with only 9% of the controls (P less than 0.05). The 5-year disease-free survival rate of the young adults who did not use tobacco was 66% compared with 86% for their matched control group with a history of smoking. These differences were most significant in young adults with Stage II disease (P less than 0.05 by log-rank testing). The growth and progression of head and neck cancer in the young adults is characterized by tobacco use patterns; a family history of head and neck cancer in five of 17 nontobacco using young adults raises the issue of an inherent genetic determinant.

Actuarial Analysis↗
PubMed1991

Prophylactic antiparkinson drug use: I. Initial prophylaxis and prevention of extrapyramidal side effects.

The use of prophylactic antiparkinson medications during neuroleptic treatment is controversial. Although the efficacy of these agents in the treatment of extrapyramidal side effects is well established, the questions of when to initiate therapy and for how long remain unanswered. There are only a few double-blind, placebo-controlled studies on the value of concurrent antiparkinson drug use at the beginning of neuroleptic treatment. The authors reviewed all studies on initial prophylaxis, and found most to be methodologically deficient. There is evidence to support the use of these agents to prevent acute dystonic reactions. Further work needs to focus on other types of extrapyramidal symptoms. In light of the inability to predict who will experience these side effects, the authors conclude that initial prophylaxis is beneficial for most patients who are starting neuroleptic medications.

Antiparkinson Agents↗
PubMed1986

Special aspects of human alcohol withdrawal.

There are still surprising gaps in our knowledge of alcohol withdrawal. While quantitative alcohol consumption accounts for about one third of the variability in severity of acute withdrawal, there is little systematic knowledge about the other factors involved. Thus, we cannot precisely predict the severity of withdrawal in individual patients. Controversy exists as to the role of medical vs. social detoxification approaches to acute withdrawal, the influence of acute withdrawal and its treatment on the long-term outcome of alcoholism, and the importance (or even existence) of chronic withdrawal. There is little systematic data to guide withdrawal treatment in special clinical settings, e.g., with concurrent medical or psychiatric illness or with mixed substance dependence. This chapter reviews the published literature, tries to point out methodological and conceptual problems, and suggests areas for future research.

Alcoholism↗
PubMed1987

Oocyte pickup by laparoscopy replaced by transvaginal aspiration in an in vitro fertilization program.

The results of laparoscopic (lap) and transvaginal (TV) oocyte pickups (OPUs) performed concurrently for in vitro fertilization in 232 consecutive treatment cycles have been reviewed. The patients were compared for age, preoperative estradiol concentration, luteal-phase support, and number of follicles aspirated and were found to be similar but were not matched for cause of infertility. The lap OPU group had more oocytes recovered per follicle aspirated (P less than 0.001), but because of a lower fertilization rate (P less than 0.01), the number of embryos transferred was similar. Nevertheless, more (P less than 0.05) pregnancies occurred in the TV OPU group. Patients were subgrouped so that comparisons of patients with the same cause of infertility, tubal disease alone, were considered. This showed that the pregnancy rate was still higher in the TV OPU group (P less than 0.05). TV OPU was less painful and not associated with increased morbidity, and since the data suggest that TV OPU was at least as successful as lap OPU, it is recommended that all oocyte pickups in the future be performed transvaginally.

Adult↗
PubMed1992

Treatment of rectal prolapse in the elderly by perineal rectosigmoidectomy.

The results and complications of perineal rectosigmoidectomy for complete rectal prolapse in 114 patients have been reviewed. Most patients were elderly and high risk by virtue of other concurrent medical conditions. Fourteen patients (12 percent) developed significant postoperative complications. Hospital stay was short (median, four days). Ten patients were lost to follow-up. The remaining 104 patients were followed for 3 to 90 months. Eleven patients (10 percent) developed recurrent full-thickness rectal prolapse, six of them underwent repeat perineal rectosigmoidectomy. Sixty-seven patients had fecal incontinence prior to surgery. Eleven patients underwent concomitant levatoroplasty; 10 of them either improved or regained full continence of feces postoperatively. Twenty-six of the 56 patients who underwent perineal rectosigmoidectomy alone improved or regained full continence. Rectal prolapse can be successfully treated by perineal rectosigmoidectomy in elderly, high-risk patients with minimal morbidity. Levatoroplasty dramatically improves fecal incontinence occurring in association with rectal prolapse.

Adult↗
PubMedDate not supplied

Right ventricular dilatation in the fetus: a study of associated features and outcome.

Right ventricular dilatation is an infrequent finding at fetal echocardiography. Previous studies have documented an association with aortic coarctation. However, there are associations with other congenital abnormalities. We reviewed our experience of fetal right heart dilatation in order to recognize concurrent anomalies and to assess the outcome of the affected fetuses. We studied all fetuses with right ventricular dilatation over a 5-year period. We documented associated cardiac and noncardiac lesions, and outcome data were assessed in terms of the number of fetuses that were born live and the number surviving to 2 months of age. Forty-three fetuses with right heart dilatation were seen. Fifteen had associated cardiac abnormalities: most commonly coarctation (n = 4) and VSD (n = 4). Seven had associated noncardiac abnormalities. There were seven fetuses who also had chromosomal abnormalities. In total, there were three terminations of pregnancy, four intrauterine deaths, one stillbirth and 35 live-births. Twenty-eight were alive at 2 months of age (70% of the nonterminated pregnancies). Fetal right heart dilatation is frequently associated with both cardiac and noncardiac congenital abnormalities. Our outcome figures suggest a guarded prognosis be given during counseling of parents of fetuses with right heart dilatation.

Adult↗
PubMed1993

Intraperitoneal cisplatin and regional hyperthermia for ovarian carcinoma.

PURPOSE: To review the theoretical basis and results of a Phase I study of concurrent intraperitoneal cisplatin and hyperthermia in the treatment of ovarian carcinoma. METHODS AND MATERIALS: Previously treated patients with epithelial ovarian carcinoma received intraperitoneal instillation of cisplatin and 60 minutes of regional hyperthermia, with a goal temperature of 41.5 degrees C. Cisplatin dose started at 20 mg/m2 with escalation to the maximally tolerated dose. Six such cycles given every 3 weeks were planned. Pharmacokinetic studies with and without hyperthermia were performed. RESULTS: Fifteen patients receiving 17 courses of treatment were evaluable. The maximally tolerated dose of cisplatin was between 80 and 120 mg/m2. The dose limiting toxicity was nephrotoxicity in all but one course. The median intraperitoneal temperature was 40.7 degrees C; the majority of treatments in which the goal temperature was not reached had power limited by patient discomfort. No major toxicities attributable to hyperthermia were noted. Pharmacokinetic studies noted no significant differences between treatments with vs. without hyperthermia, with intraperitoneal to plasma area under the curve ratios being 30-35. Ten patients had a decline in their CA-125 count during treatment, although in only two patients did this response persist beyond their course of treatment. CONCLUSION: Intraperitoneal cisplatin and regional hyperthermia can be performed with reasonable toxicity. The maximally tolerated dose of 80-120 mg/m2 in pretreated patients (which is similar to those reported with cisplatin alone) and median intraperitoneal temperatures of 40.7 degrees C, however, are felt to be too low to be efficacious in a significant percentage of women with bulky recurrent disease. Further study using intravenous thiosulfate and controlled analgesia is being performed.

Antigens, Tumor-Associated, Carbohydrate↗