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Biomedical subjects

A Birnbaum

Publications and source records attributed to A Birnbaum.

At least 19 recordsLinked to original sources
PubMed2005

Pharmacological and clinical aspects of antiepileptic drug use in the elderly.

In this article, epidemiological and clinical aspects related to the use of antiepileptic drugs (AEDs) in the elderly are highlighted. Studies have shown that people with epilepsy receiving AED treatment show important deficits in physical and social functioning compared with age-matched people without epilepsy. To what extent these deficits can be ascribed to epilepsy per se or to the consequences of AED treatment remains to be clarified. The importance of characterizing the effects of AEDs in an elderly population is highlighted by epidemiological surveys indicating that the prevalence of AED use is increased in elderly people, particularly in those living in nursing homes. Both the pharmacokinetics and the pharmacodynamics of AEDs may be altered in old age, which may contribute to the observation that AEDs are among the drug classes most commonly implicated as causing adverse drug reactions in an aged population. Age alone is one of several contributors to alterations in AED response in the elderly; other factors include physical frailty, co-morbidities, dietary influences, and drug interactions. Individualization of dosage, avoidance of unnecessary polypharmacy, and careful observation of clinical response are essential for an effective and safe utilization of AEDs in an elderly population.

Aged↗
PubMed2003

Variability of total phenytoin serum concentrations within elderly nursing home residents.

BACKGROUND: Approximately 6% of all elderly nursing home residents receive phenytoin. Phenytoin concentrations are often measured to guide therapy. OBJECTIVE: To evaluate the intraresident variability among multiple measurements of total phenytoin serum concentrations in nursing home residents. METHODS: This was an observational study of 56 elderly (>or=65 years) nursing home residents from 32 nursing homes who had at least 3 phenytoin concentrations measured while on the same dose of phenytoin for at least 4 weeks and who were not taking any interfering concomitant medications. These were a subset of 387 elderly nursing home residents from 112 nursing homes across the United States who had total phenytoin concentration measurements between June 1998 and December 2000. RESULTS: The mean age was 80.1 years (range, 65 to 100 years) and 58.9% were women. The mean daily dose of phenytoin per resident was 4.9 +/- 1.5 mg/kg. Total phenytoin concentrations within an elderly nursing home resident varied as much as two- to threefold, even though there was no change in dose. The person with the smallest variability had a minimum concentration of 10.0 micro g/mL and a maximum of 10.4 micro g/mL. The person with the largest variability had a minimum concentration of 9.7 micro g/mL and a maximum of 28.8 micro g/mL. CONCLUSIONS: There is considerable variability in the total phenytoin concentrations in the elderly nursing home resident and measurement of a single total phenytoin concentration should not be used to guide treatment.

Age Distribution↗
PubMed2002

Cytochrome P450 isozymes 3A4 and 2B6 are involved in the in vitro human metabolism of thiotepa to TEPA.

PURPOSE: To establish the cytochrome P450 (CYP) isozymes involved in the metabolism of the alkylating agent, thiotepa, to the pharmacologically active metabolite, TEPA. METHODS: In vitro chemical inhibition studies were conducted by incubating thiotepa and pooled human hepatic microsomes in the presence of known inhibitors to CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4. Studies were also performed with cloned, expressed CYP3A4, CYP2A6, CYP2E1 and CYP2B6 microsomes, and anti-CYP2B6 monoclonal antibody. RESULTS: Known CYP3A4 inhibitors reduced TEPA production. Inhibition with CYP2E1 inhibitors was inconsistent. All other inhibitors produced little or no change in TEPA formation. Cloned, expressed CYP2B6 and CYP3A4 microsomes catalyzed TEPA formation, whereas CYP2A6 and CYP2E1 did not. Incubation of thiotepa with anti-CYP2B6 antibody and cloned, expressed CYP2B6 microsomes resulted in reductions in the formation of TEPA, but no change in TEPA formation occurred in human liver microsomes. CONCLUSIONS: Thiotepa is metabolized in human liver microsomes by CYP3A4 (major) and CYP2B6 (minor). There is a potential for CYP-mediated drug interactions with thiotepa. Pharmacokinetic variability of thiotepa may be related to expression of hepatic CYP isozymes.

Antibodies↗
PubMed2000

Liver transplantation in a patient with acute liver failure due to sickle cell intrahepatic cholestasis.

BACKGROUND: Sickle cell intrahepatic cholestasis is a potentially catastrophic complication of sickle cell anemia Once acute liver failure develops, transplantation is the only option. We describe a patient with sickle cell intrahepatic cholestasis who underwent liver transplantation. METHODS: Data were obtained from the chart. Serial hemoglobin S levels were monitored, and measures were taken to maintain hemoglobin S <20% to prevent sickle cell crisis. RESULTS: Although the allograft functioned well initially, the patient developed veno-occlusive disease and required repeat transplantation at 5 months after transplant. Histologic examination of the explant revealed occlusion of the terminal hepatic venules due to fibrosis and packed red cells. Repeat transplant was complicated by thrombosis of the intrahepatic portion of the hepatic artery, and sepsis. The patient died of sepsis after a third transplant. CONCLUSION: Liver transplantation for sickle cell disease involving the liver may carry a high risk of graft loss due to vascular problems. Repeat transplantation may not be feasible if disease recurs.

Anemia, Sickle Cell↗
PubMed1999

Unsuspected bile duct paucity in donors for living-related liver transplantation: two case reports.

Alagille's syndrome is a common cause of liver disease in children and may lead to the need for orthotopic liver transplantation. Alagille's syndrome is inherited in an autosomal dominant manner, with variable penetration, and may also be present in patients' parents, who may be considered potential donors for living-related transplantation. We report here on two cases in which the living-related donors for children with Alagille's syndrome had no liver function abnormalities or characteristic features of Alagille's syndrome. In both cases, the operation for living-related donation had to be aborted because of a paucity of bile ducts discovered intraoperatively. Given the variable presentation of Alagille's syndrome, we believe that it is necessary preoperatively to evaluate the biliary system of family members who are potential living-related donors for patients with this condition.

Adult↗
PubMed1999

Living related liver transplantation for acute liver failure in children.

The mortality rate among children with acute liver failure (ALF) on the waiting list for liver transplantation is high. We present our experience with living related donor liver transplantation (LRD-LT) in children who required urgent transplantation for ALF. Between December 1995 and July 1997, 6 children underwent LRD-LT for ALF. Cause of liver failure, recipient and donor demographics, clinical and laboratory data, surgical details, complications, and 6-month and 2-year graft and patient survival were recorded. Five boys and 1 girl received left lateral segment grafts from their parents. The mean age was 4 +/- 2.8 years (range, 1 to 9 years). ALF was caused by Wilson's disease in 1 patient and sickle cell intrahepatic cholestasis syndrome in 1 patient; in 4 patients, the cause was unknown. All patients had mental status changes; 2 were on life support. Mean pretransplantation liver function test values were: alanine aminotransferase, 972 +/- 565 U/L (normal, 1 to 53 U/L), total bilirubin, 31.3 +/- 12.4 mg/dL (normal, 0.1 to 1.2 mg/dL), prothrombin time, 34.3 +/- 12.4 seconds (normal, 10.8 to 13.3 seconds), international normalized ratio, 8.46 +/- 5.4 (normal < 2), and fibrinogen, 109 +/- 23.9 mg/dL (normal, 175 to 400 mg/dL). The donors were 5 mothers and 1 father. The mean donor age was 32.5 +/- 7.6 years (range, 19 to 40 years). No donor required blood transfusion, and no donor had any early or late postoperative complications. The donors' mean hospital length of stay was 5 days. In five cases, grafts were blood group-compatible; 1 child received a blood group-incompatible graft. All grafts functioned immediately. No patient had hepatic artery or portal vein thrombosis or biliary complications. The child who received a mismatched graft died of infection of the brain caused by Aspergillus spp at 22 days posttransplantation with a functioning graft. The child with ALF caused by sickle cell intrahepatic cholestasis syndrome developed outflow obstruction 3 months posttransplantation and required retransplantation; he eventually died of vascular complications related to his primary disease. Four children are alive at a mean follow-up of 27 months (range, 14 to 36 months). LRD-LT for children with ALF facilitates timely transplantation without drawing on cadaveric donor resources. The established safety record of LRD-LT made this option appealing to both physicians and parental donors.

Adult↗
PubMed1998

The intrahepatic cholangiopathies.

The intrahepatic biliary epithelial cells or cholangiocytes are the primary focus of injury in many congenital and acquired liver diseases of childhood. Although cholangiocytes account for only 3 to 5% of the liver cell population, injury and progressive loss of intrahepatic bile ducts can result in considerable morbidity and mortality. Table 1 provides an overview of the various disorders that affect the intrahepatic biliary tree. The more common disorders are discussed in detail below. One of the most important cholangiopathies, biliary atresia, characterized by complete destruction of the extrahepatic biliary tree, with variable involvement of the intrahepatic bile ducts, is discussed elsewhere in this series of articles. There has been considerable progress in our understanding of the embryology and physiology of the intrahepatic biliary system. These topics are also selectively reviewed, with an emphasis on advances that aid in the understanding of the pathophysiology of the disorders which affect the biliary tract in children.

Alagille Syndrome↗
PubMed1997

Low-dose aspirin therapy is associated with few side effects but does not prevent hepatic artery thrombosis in liver transplant recipients.

Hepatic artery thrombosis occurs in 4% to 10% of adult patients and in up to 26% of children undergoing liver transplantation. Aspirin has been used to prevent this complication but may increase procedure-related and gastrointestinal bleeding. The aim of this study was to assess the efficacy and safety of low-dose aspirin in the prophylaxis of hepatic artery thrombosis. The histories of 529 patients who survived liver transplantation between September 1988 and December 1993 were reviewed retrospectively. The routine clinical practice followed until 1992 was to initiate oral aspirin therapy on the first postoperative day (81 mg daily in adults and 40 mg daily in children) as prophylaxis for vascular thrombosis. This was done in 354 patients. Aspirin was not administered to the remaining 175 patients. Hepatic artery thrombosis occurred in 13 patients treated with aspirin (3.7%) and in 7 patients not treated with aspirin (4.0%) (P = .85). Recipient age of younger than 2 years and low donor liver weight were the only factors that predisposed the patients to hepatic artery thrombosis. A total of 1,651 percutaneous liver biopsies were performed in this series, with 1,111 performed in patients treated with aspirin. Significant bleeding after liver biopsy occurred in 12 patients treated with aspirin (1.1%) and in 3 patients not treated with aspirin (0.6%) (P = .29). Gastrointestinal bleeding occurred in 66 patients treated with aspirin (18.9%) and in 23 patients not treated with aspirin (12.8%) (P = .08). Low-dose aspirin therapy is not shown to be effective in preventing hepatic artery thrombosis after liver transplantation. Although aspirin does not produce a statistically significant increase in the risk of bleeding after liver biopsy, there is a trend toward an increased incidence of gastrointestinal bleeding.

Adolescent↗
PubMed1996

Domestic violence: diurnal mismatch between need and availability of services.

OBJECTIVE: To determine whether a diurnal discordance exists between need and availability of services for victims of domestic violence. METHODS: A consecutive sample of women presenting to a municipal hospital ED with physical injuries suspected to be related to domestic violence were entered into a registry. Date and time of presentation and perceived need for services information were collected from all patients who answered affirmatively a screening question for domestic violence and whose conditions did not preclude administration of the data collection instrument. The Social Service Departments of all of the 53 911-receiving hospitals in New York City were contacted to ascertain availability of social services for victims of domestic violence by time of day. RESULTS: Twenty-eight of 32 (88%; 95% CI: 71%, 97%) victims of domestic violence presented to the ED during hours other than weekday 9 AM to 5 PM. Of these, 63% desired counseling, 32% lacked a safe place to go, and 82% had children. Of those who had children, 48% were concerned for the children's safety. In-hospital social services were universally available weekday daytime (9 AM to 5 PM) but were available in only 11% of hospital (95% CI: 4%, 23%) at other times. CONCLUSION: Approximately nine of ten victims of domestic violence presented to the ED during hours when only about one hospital in ten can provide the special services these patients require. A marked diurnal mismatch appears to exist between availability of domestic violence services in New York City and the need for these services as measured by a representative sample drawn from an ED population.

Adult↗
PubMed1993

Quantitative determination of pentane in exhaled air correlates with colonic inflammation in the rat colitis model.

Oxygen radicals play a key role in inflammation and inflammatory tissue damage. Quantitative determination of pentane, a hydrocarbon generated by membrane lipid peroxidation initiated by oxygen radicals, in expired air has been used as a noninvasive determinant or index of inflammation in various conditions. Herein we report the first examination of the relationship between exhaled pentane and colonic inflammation in a rodent model of colitis. Colitis was induced in rats (n = 33) using the trinitrobenzene-sulfonic acid (TNB) model of colitis. Exhaled air was collected in a closed chamber on randomly selected animals on days 1, 2, 4, 7, 11, 13, 15, 20, and 25 post-TNB treatment, and pentane was assayed by means of gas chromatography. Gross and microscopic evidence of inflammation was compared with exhaled pentane levels. Pentane levels varied from 0.0 to 14.6 nmol/l of air and were significantly increased in TNB-treated rats compared with control rats only on days 7 to 15 after treatment (P < 0.05). Gross inspection showed severe colonic inflammation through the first week (mean score = 4.7 out of a possible 5), persistent inflammation on days 7 to 15 (3.2), and healing and fibrosis from the end of week two until day 25 (1.9 to 0). Histologic evaluation confirmed a progression of inflammation from acute ulceration to chronic inflammation to fibrosis and scarring. We have demonstrated that pentane exhalation is increased after the induction of colonic inflammation, with a seven-day lag time, and returns rapidly to normal as acute inflammation resolves. This suggests that pentane exhalation can be used as a noninvasive measure of colonic inflammation in rodent models of colitis and perhaps clinically in humans.

Air↗
PubMed1993

An integrative ideology to guide community-based multidisciplinary care of severely mentally ill patients.

Most practitioners working in community support settings understand the need to provide a comprehensive array of well-coordinated services to individuals with severe mental disabilities. However, a lack of consensus about the conceptual basis of mental health care, especially between advocates of psychosocial rehabilitation and psychiatric practitioners who favor a more medically oriented approach, has hindered efforts to optimize the effectiveness of the multidisciplinary teams found in most community support programs. The authors articulate 18 basic assumptions that have been helpful in their clinical practice in building an integrative ideology among professionals with disparate training and orientations. The assumptions attempt to balance the reality of psychiatric disorders with a fundamental interest in maintaining the autonomy and dignity of people with severe mental disorders.

Combined Modality Therapy↗
PubMed1989

Frozen shoulder and other shoulder disturbances in Parkinson's disease.

The frequency of shoulder disturbances, particularly frozen shoulder, has not been assessed previously in Parkinson's disease. In a survey of 150 patients compared with 60 matched control subjects a significantly higher incidence of both a history of shoulder complaints (43% vs. 23%) and frozen shoulder (12.7% vs. 1.7%) was found in the Parkinson's disease population. Those developing a frozen shoulder had initial disease symptoms indicative of akinesia twice as frequently as tremor while the ratio was reversed in those without frozen shoulder. In at least 8% of the patients frozen shoulder was the first symptom of disease, occurring 0-2 years prior to the onset of more commonly recognised features. Parkinson's disease should be added to the list of causes of frozen shoulder, and clinicians must be aware that the latter is often the presenting symptom of Parkinson's disease.

Activities of Daily Living↗
PubMed1986

Levodopa dose-related fluctuations in presumed olivopontocerebellar atrophy.

The parkinsonism that occurs in some patients with olivopontocerebellar atrophy (OPCA) can cause diagnostic confusion with idiopathic Parkinson's disease (IPD). The response to levodopa is usually a distinguishing feature, the OPCAs either failing to benefit or losing efficacy relatively quickly. A fluctuating response to levodopa in those OPCA patients who do benefit has not been emphasized in the literature previously. Reported here are three patients with presumed OPCA, dominated by parkinsonian features, who eventually developed typical fluctuations with morning akinesia, wearing off, and periodic lack of response related to meals. These fluctuations were a major source of disability and an important reason for diagnostic confusion with IPD. The possible mechanisms of these fluctuations are discussed.

Aged↗
PubMed1972

The random phenotype concept, with applications.

A random phenotype is defined as a probability distribution over any given set of phenotypes. This includes as special cases the kinds of phenotypes usually considered (qualitative, quantitative, and threshold characters) and all others. Correspondingly general methods are indicated for analyzing data of all forms in terms of the classical Mendelian factor concept (as distinct from the biometrical methods usually applied to measurement and graded data, associated with the effective factor concept). These are applied in a new analysis of the data of E. L. Green (1951, 1954, 1962) on skeletal variation in the mouse. The adequacies of various classical one-factor and several-factor models are considered. Indications of an underlying scale are found from this new standpoint. The results are compared with those obtained by Green using the scaling approach. An illustrative application is also made to some of Bruell's (1962) continuous behavioural data on mice. This work was substantially completed in 1959 but not previously prepared for publication. The same approach was originated and developed independently by R. L. Collins who has treated a wider range of theoretical problems (cf. Collins 1967, 1968a, 1969b, 1970c) and a wider range of applications (cf. Collins and Fuller 1968; Collins 1968b, 1969a, 1970a). A less general independent development is that of Mode and Gasser 1972.

Animals↗