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Biomedical subjects

M Malone

Publications and source records attributed to M Malone.

At least 73 records · Page 4Linked to original sources

Chromium picolinate toxicity.

OBJECTIVE: To describe a case of toxicity secondary to chronic ingestion of 6-12 times the recommended daily allowance of over-the-counter (OTC) chromium picolinate. CASE SUMMARY: A 33-year-old white woman presented with weight loss, anemia, thrombocytopenia, hemolysis, liver dysfunction (aminotransferase enzymes 15-20 times normal, total bilirubin 3 times normal), and renal failure (serum creatinine 5.3 mg/dL; blood urea nitrogen 152 mg/dL). She had ingested chromium picolinate 1200-2400 microg/d for the previous 4-5 months to enhance weight loss. The patient had chromium plasma concentrations 2-3 times normal. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome were ruled out by clinical findings, peripheral blood smears, and a bone marrow biopsy. The patient was managed with supportive measures and received blood product transfusions and hemodialysis. Hemolysis stabilized and liver function improved over 6 days. Liver function returned to normal prior to discharge. Renal function began to return on day 12 and her serum creatinine on discharge was 1.3 mg/dL. One year later, all laboratory values were within normal limits. DISCUSSION: Trivalent chromium is an essential trace element that is considered safe when ingested in normal quantities. Trivalent chromium compounds are used by patients to enhance weight loss, increase lean body mass, and/or improve glycemic control. Information regarding the toxicity of chromium picolinate is limited. CONCLUSIONS: Chromium supplements may cause serious renal impairment when ingested in excess. Medication histories should include attention to the use of OTC nutritional supplements often regarded as harmless by the public and lay media.

Acute Kidney Injury↗

Drug-food interactions in hospitalised patients. Methods of prevention.

Drug-food interactions in hospitalised patients may result in decreased drug efficacy or increased drug toxicity. The increasing complexity of drug therapy regimens has increased the potential for drug-food interactions to occur, reinforcing the need to develop methods to prevent clinically significant drug-food interactions. Before selecting the optimal method, in terms of feasibility of implementation and successful outcome, drugs with the potential for clinically significant interactions with food must be identified. From an analysis of the literature, 6 methods to prevent drug-food interactions have been suggested as useful tools. Each method has its own advantages and disadvantages. Most have been developed in response to guidelines from the most well recognised agency for quality review in the US, the Joint Commission on Accreditation of Healthcare Organisations (JCAHO). Based on those recommendations, an ideal programme to prevent drug-food interactions would be a combined patient counselling and label system to select the most appropriate drug administration times and increase nurse and patient awareness of the potential for drug-food interactions. However, because of time constraints and limited resources, a label system or the provision of a drug-food interaction pamphlet to the patient before discharge would be a more practical method. Newsletters and educational in-services combined with patient counselling or a label system would be a valuable method to prevent drug-food interactions in hospitalised patients.

Drug Administration Schedule↗

Outcomes of pharmacological and surgical treatment for obesity.

The purpose of this article is to review the data from pharmacotherapeutic and surgical intervention studies for the management of obesity. Clinical outcomes assessed include weight changes over time and the effects of weight loss on blood pressure, serum lipid profiles and blood glucose control. Quality of life and economic data have been incorporated where available. Double-blind, randomised controlled trials were used preferentially over shorter term open studies. The literature evaluation was based on a Medline search of published data between January 1990 and January 1998. Obesity affects 65 million adults in the US. Estimates based on 1990 data suggest that obesity and comorbid illness contributed to $US46 billion in direct costs and $US23 billion in indirect costs in the US. Obesity is a chronic condition which requires long term management. The risk of developing cardiovascular disease, hypertension, type 2 (non-insulin-dependent) diabetes mellitus, osteoarthritis, Pickwickian syndrome and cancer is increased in the obese population, resulting in excess morbidity and mortality. There are no long term prospective studies that have demonstrated that weight reduction in obese patients improves survival. However, on the basis of epidemiological data using the prevalence of disease and associated body mass index, it is generally accepted that weight reduction of 5 to 10% in obese patients is associated with significant health benefits. Current treatment modalities include diet and behaviour modification, exercise and, where indicated, pharmacological intervention. Surgical intervention is reserved for the clinically severe obese patient [body mass index (BMI) > 40 kg/m2]. Many studies have demonstrated weight loss and improved metabolic fitness over 6 to 12 months. Few studies have been conducted over a longer period. Limited data are available regarding reduced morbidity and mortality, improved quality of life and functional or employment status and even fewer have incorporated any economic assessments of the impact of medical or surgical intervention. Although prospective data have demonstrated reduced morbidity following surgical intervention, only retrospective data have demonstrated reduced mortality. Studies of new drugs and interventions under development should demonstrate long term safety and efficacy in terms of sustained weight loss and subsequent weight maintenance. Future studies should incorporate assessment of patient perceived satisfaction with weight loss, health status and quality-of-life evaluations and pharmacoeconomic data to aid clinicians in the decision-making process in terms of weight management of their obese patients.

Humans↗

Hospice care.

Explore the source record for details and available documents.

Aftercare↗

Comparison of programs for preventing drug-nutrient interactions in hospitalized patients.

Three programs with different levels of pharmacist intervention designed to prevent drug-nutrient interactions (DNIs) were studied. Six drugs were selected for the study on the basis of their potential for involvement in significant DNIs and the hospital's drug-use profile. During a two-week control phase, the existing pharmacy system, in which no patient-specific information on DNIs is provided, was assessed. During the next four weeks, patients were randomly assigned to intervention 1, placement of a brightly colored label in the medication drawer and on the cover of the nursing medication card flip-chart, or to intervention 2, placement of the labels plus a five-minute structured patient-counseling session. Occurrence of DNIs and nurses' and patients' knowledge of DNIs were assessed. A DNI was defined as potentially altered drug absorption due to inappropriate timing or administration of a drug in relation to food. The occurrence of DNIs decreased significantly under the label system (from 24% to 19%) and under the combined label-counseling system (to 16%). However, the frequency of DNIs did not differ significantly between the two intervention groups. Patients' and nurses' knowledge of DNIs improved as a result of the interventions. The frequency of DNIs decreased when labels were used to alert nurses to proper medication timing.

Adult↗

Clinical outcome of geriatric patients in the United States receiving home parenteral and enteral nutrition.

In this study the use of home parenteral and enteral nutrition (HPEN) therapy in geriatric patients and the effect of aging on the clinical outcome of HPEN therapy was assessed between 1985 and 1992. Data were obtained from Medicare (part B) parenteral and enteral nutrition workload statistics, Blue Cross and Blue Shield of South Carolina, and the North American HPEN Patient Registry. On the basis of these data it was estimated that in 1992 there were 40,000 HPN patients and 152,000 HEN patients nationwide. One-quarter to one-third of the HPN group was aged > or = 65 y, depending on the underlying diagnosis. Geriatric HPN patients had a generally good outcome but did not do as well as their younger counterparts; however, they had fewer therapy-related complications than children. In the HEN group, 44% of cancer patients and 69% of patients with neuromuscular swallowing disorders were geriatric. Geriatric HEN patients with swallowing disorders had a poorer outcome (i.e., lower survival, poorer rehabilitation, and fewer resumed full oral nutrition) than younger patients after 1 y of follow-up. In conclusion, although aging was associated with a poorer outcome for HPN patients, it was still reasonably good; therefore, age per se should not exclude geriatric subjects from therapy. For HEN, the poorer outcome in geriatric dysphagic patients raises concern regarding the appropriateness of this therapy.

Adolescent↗

Pulmonary alveolar microlithiasis in childhood: diagnosis by transbronchial biopsy.

A 7-year-old girl of Arabic origin by consanguineous parents presented with a miliary pattern on chest x-ray. Transbronchial lung biopsy revealed a histological diagnosis of pulmonary alveolar microlithiasis, a condition rarely described in childhood. This report highlights the clinical and radiological features, documents the transbronchial lung biopsy as a useful diagnostic procedure, and suggests a possible genetic etiology with autosomal recessive inheritance.

Bronchoalveolar Lavage Fluid↗

Primary hepatic malignant tumor with rhabdoid features. A histological, immunocytochemical, and electron microscopic study of four cases and a review of the literature.

Malignant tumors of the liver with rhabdoid features (MTR) are uncommon: Only 14 previous cases are reported in the literature. These tumors are characterised morphologically by sheets of large polygonal cells with abundant eosinophilic cytoplasm containing a periodic acid Schiff's-positive hyaline globular inclusion and vesicular nuclei with a central prominent nucleolus. Immunohistochemically, the inclusions at least show positivity for vimentin and epithelial markers and sometimes for other antigens. Ultrastructurally, the inclusions are composed of whorled intermediate filaments. Despite the superficial resemblance to cells of muscle origin implied in the term rhabdoid, there is no immunohistochemical or ultrastructural evidence to support such a derivation. We describe four additional children with tumors of this type, in three of whom tumor cells showed focal membrane positivity for MIC-2 on immunostaining. Its expression in an hepatic MTR may indicate neuroepithelial differentiation. Hepatic MTR should be considered in the differential diagnosis of an undifferentiated primary liver tumor in an infant in whom the alpha-fetoprotein concentration is normal or only slightly elevated for age.

Antibodies↗

Outcomes assessment of drug treatment in multiple sclerosis clinical trials.

The purpose of this review is to evaluate the clinical outcomes of drug therapy in the treatment of multiple sclerosis (MS) in those studies which purported to include an assessment of quality of life. Pharmacological management of MS is primarily directed towards control of symptoms and prevention of disease progression or relapse. Although there are many drug and nondrug approaches used in the treatment of MS, this review focuses largely on approaches that incorporate some method of clinical outcome assessment. To aid in the interpretation of the data presented, a short descriptive summary of these assessment methods has been included. Although most studies incorporate at least one clinical outcome measure into the evaluation of efficacy, only one study has examined the economic impact of intervention in MS. The authors of that study demonstrated good correlation between the level of disability assessed using conventional quality-of-life measures and associated healthcare costs. Surprisingly, although many treatment approaches used in MS have significant associated toxicity and only modest benefits in terms of disease control, there is a remarkable paucity of data on the impact of these treatments on patients' quality of life. Studies that incorporate pharmacoeconomic and health-related quality-of-life consequences related to the treatment of MS are required.

Clinical Trials as Topic↗

Predictive accuracy of the TRISS survival statistic is improved by a modification that includes admission pH.

OBJECTIVE: To determine if pH measured at the time of hospital admission and corrected for PCO2 was an independent predictor of trauma survival. DESIGN: Phase 1 was a retrospective case-control analysis of 1708 patients, followed by multivariate multiple logistic regression analysis of a subset of 919 patients for whom the Revised Trauma Score (RTS), Injury Severity Score (ISS), and pH were available. Phase 2 was a prospective comparison of a mathematical model of survival derived in phase 1 (pH-TRISS) with the TRISS method in 508 of 1325 subsequently admitted trauma patients. SETTING: Urban level 1 trauma center. PATIENTS: All patients admitted with blunt or penetrating trauma during the study period. MAIN OUTCOME MEASURES: Survival vs mortality. RESULTS: In phase 1, factors significantly associated with mortality by t test and chi 2 analysis included the RTS, ISS< Glasgow Coma Scale, corrected pH (CpH), and sum of the head, chest, and abdominal components of the Abbreviated Injury Scale-85 (AIS85) (HCAISS) (for all, P < .0001). The TRISS statistic was also a significant predictor of survival (P < .004). Age, sex, and the extremity and soft tissue components of the AIS85 were not associated with mortality. In a multivariate analysis of the RTS, HCAISS, and CpH, all were significant predictors of mortality. Even when controlling for RTS and HCAISS, CpH remained a significant predictor of mortality (P < .008). In phase 2, when pH-TRISS was tested prospectively against TRISS in a new group of patients, the new statistic appeared to provide a more accurate prediction of survival. CONCLUSIONS: The arterial pH measurement obtained on hospital arrival and corrected for PCO2 is a significant independent predictor of survival and adds to the predictive accuracy of the TRISS survival statistic. Age, sex, and the extremity and soft tissue components of the AIS85 did not contribute to the accuracy of the TRISS statistic in this patient population.

Abbreviated Injury Scale↗

Improved outcome for children with hepatoblastoma.

Between 1981 and 1993, 41 children were treated for hepatoblastoma. Clinical, radiological and pathological data were reviewed retrospectively, focusing on surgical aspects of treatment and outcome. Fourteen children underwent primary resection of the hepatic tumour. One infant with severe congenital anomalies received only palliative treatment. Of 26 with irresectable disease, pulsed cytotoxic chemotherapy (cisplatin and doxorubicin) enabled subsequent surgical excision in 22 and one child with persistent extensive intrahepatic disease was successfully treated by liver transplantation. Thus, with a policy of selective preoperative chemotherapy, 90 per cent of hepatoblastomas were resectable. There were no perioperative deaths from haemorrhage but one child died from an intraoperative tumour embolus. A total of 28 survivors, 27 of whom are disease-free, were followed for a median of 5 years. The cumulative probability of survival in patients treated with intent to cure was 67 per cent. Analysis of survival data suggested a favourable outcome for those with a pure fetal histological tumour subtype. These results demonstrate significant progress in the treatment of hepatoblastoma.

Child↗

BCL-2 expression by leukaemic blasts in a SCID mouse model of biphenotypic leukaemia associated with the t(4;11)(q21;q23) translocation.

Acute leukaemia of infancy is associated with abnormalities at chromosome band 11q23, and has a poor prognosis. The gene involved. Mixed Lineage Leukaemia (MLL), has been identified and has the characteristics of a transcription factor. The BCL-2 gene responsible for blocking of programmed cell death is highly expressed in a number of haematological malignancies, both with and without the t(14;18) translocation. Those without the translocation include acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML) and chronic lymphocytic leukaemia (CLL). In these diseases the BCL-2 protein is implicated in drug resistance to apoptosis-inducing chemotherapeutic agents. High BCL-2 expression is also associated with autonomous growth of leukaemic blasts in culture and predicts a poor prognosis. The SEM cell line, established using blood lymphoblasts from a 5-year-old girl in first relapse with t(4;11) ALL, expresses lymphoid (CD19) and myeloid (CD13) cell surface markers. In cell culture, a subpopulation of cells (< 30%) express the BCL-2 protein. A reproducible model of true biphenotypic leukaemia in the SCID mouse has been established using the SEM-K2 cell line (a subclone of the SEM cell line). Between 5 and 50 million cells injected intravenously (i.v.) produce complete replacement of the murine bone marrow by day 30, associated with blood lymphoblastosis and infiltration of the spleen. No tumour masses were seen. Fluorescence in situ hybridization (FISH) analysis of the cell line and blood from the SCID-human (SCID-hu) chimaera has confirmed the presence of the t(4;11). Reverse transcriptional-polymerase chain reaction (RT-PCR) reveals that the breakpoint lies between exons 7 and 8 of the MLL-1 gene on chromosome 11 (the main breakpoint region). A further translocation, t(7;13), has been identified. Fluorescent antibody cell sorter (FACS) analysis of tumour material recovered from the SCID-hu model confirms expression of CD19 and CD13 identical to that of the cell line. In addition, BCL-2 expression in SCID-hu marrow is now seen in the majority of tumour cells. BCL-2 expression appears to confer a survival advantage to the blast cells in vivo. This reproducible model of biphenotypic leukaemia suggests that BCL-2 expression may play a role in leukaemogenesis. The model is suitable for the investigation of gene-targeted therapy, including antisense oligonucleotides, directed towards the MLL and BCL-2 genes.

Animals↗

Desmin expression in rhabdomyosarcoma: influence of the desmin clone and immunohistochemical method.

AIM: To determine which, if any, of five commercially available desmin clones is most reliable at labelling desmin filaments and whether the enhanced polymer one step (EPOS) method of labelling is of any advantage in the routine diagnostic laboratory. METHODS: Thirty four rhabdomyosarcomas from the files at The Hospital for Sick Children, Great Ormond Street, London, were studied. Four different desmin clones, DE-R-11, D33, DE-U-10, and PDE, were applied to each using the conventional extravidin biotin peroxidase method. The D33 clone was also applied using the EPOS method. RESULTS: The EPOS method incorporating D33 persistently scored more cells as desmin positive and was positive in four cases which were negative on staining with the other clones. CONCLUSIONS: The D33 desmin clone used with the EPOS method is more reliable for identifying desmin filaments in tumours than other desmin antibodies tested. Different desmin clones using a routine technique label different rhabdomyosarcoma cells and therefore it is justifiable to use more than one clone.

Desmin↗

Glutathione in health and disease: pharmacotherapeutic issues.

OBJECTIVE: To review the current research and importance of glutathione (GSH) therapy in health and disease and to provide a basic overview of the widespread use and interest in this compound. DATA IDENTIFICATION: Articles were obtained via a MEDLINE search of the term glutathione in conjunction with specific disease states mentioned, and via extensive review of references found in articles identified by computer search. STUDY SELECTION: Emphasis was placed on the most recent research, human research, and in discussing multiple disease states. DATA EXTRACTION: The literature was reviewed for methodology, quality, and practical aspects of interest to clinical pharmacists. DATA SYNTHESIS: GSH is a tripeptide of extreme importance as a catalyst, reductant, and reactant. It continues to be investigated in diverse areas such as acute respiratory distress syndrome, toxicology, AIDS, aging, oncology, and liver disease. Despite the widespread clinical interest in GSH, we were not able to identify an in-depth review of this compound in the pharmacy literature. CONCLUSIONS: The list of potential indications for modulation of GSH is extensive and broad. This review introduces clinicians to what GSH is, its basic chemistry, and some areas of active research.

Acquired Immunodeficiency Syndrome↗

Gastric Bypass and Vertical Banded Gastroplasty- a Prospective Randomized Comparison and 5-Year Follow-up.

BACKGROUND: a prospective randomized study was undertaken to compare the outcome of vertical banded gastroplasty (VBG) and gastric bypass (GBP) in patients with clinically severe obesity. METHODS: eligibility criteria included Class IV obesity, < 50 years old and a history of at least one attempt of non-operative weight loss. Patients were managed conservatively for 3 months prior to surgery. Patients were followed post-operatively and monitored for early and late complications and their weight loss outcome for up to 5 years. RESULTS: 44 patients were recruited. Two patients withdrew within 4 weeks and were excluded. Twenty subjects had a GBP and 22 a VBG. There were no significant differences with respect to age, gender, maximum or pre-operative weight between the groups (p > 0.05). Patients who underwent GBP demonstrated significantly greater post-operative weight loss (p < 0.05) which was apparent from 6 months onwards. There were no deaths, pulmonary emboli, post-operative leaks or wound dehiscence. There were no instances of staple-line disruption. Symptomatic ulcer disease, confirmed endoscopically, developed in 25% of GBP patients. Nine patients developed gallstones post-operatively of whom five were in the VBG and four in the GBP group. CONCLUSIONS: weight loss following GBP was maintained, while VBG patients slowly regained.

Journal Article↗