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Biomedical subjects

D Malone

Publications and source records attributed to D Malone.

At least 19 recordsLinked to original sources
PubMed2005

Drunken patients in the general hospital: their care and management.

In Britain alcohol consumption is increasing, 1 in 4 men and 1 in 10 women drink hazardously, 1 in 3 young men, and 1 in 4 young women regularly binge drink. Mortality rates attributable to alcohol have doubled; with 1 in 5 male inpatients having an alcohol related problem. The increasing problem of managing drunken behaviour in accident and emergency departments is discussed. Although an alcohol history is recommended for all admissions, because of various reasons, hazardous drinkers continue to miss the opportunity of effective interventions. In addition to the more formal treatments for alcohol problems, there is a wealth of evidence reporting the effectiveness of brief interventions carried out by a range of health professionals can lead to long term reductions in alcohol consumption. This review discusses practical and legal issues of the assessment, screening tools, and management of intoxicated patients.

Alcohol-Related Disorders↗
PubMed2001

Total cytokine immunoassay: a more accurate method of cytokine measurement?

BACKGROUND: Cytokines signal the normal processes of inflammation and repair in all organs, yet the aberrant expression of these peptide mediators is associated with significant organ dysfunction. The accurate measurement of cytokines is therefore critical. In this study, we sought to investigate the alterations in cytokine expression early after trauma in humans using a new competitive binding immunoassay that measures both free and bound cytokine and compare this with standard enzyme-linked immunosorbent assay (ELISA), which measures only free cytokine. METHODS: Peripheral blood was obtained from trauma patients at admission. Exclusion criteria were transfers, death within 24 hours, pregnancy, known acquired immunodeficiency syndrome, chemotherapy, transplant, or other chronic immune disorder. "Total" cytokine immunoassay was compared with ELISA for cytokines (interleukin [IL]-1, IL-6, and IL-10) measured in serum. RESULTS: Cytokine concentrations measured by total immunoassay were significantly higher (10- to 500-fold increase) than those measured by ELISA, and correlation between the two methods was poor (r2 = 0.193 for IL-10). No significant differences in mean serum cytokine concentrations were noted between trauma patients and normal controls for IL-1 (56 vs. 37 pg/mL), IL-6 (16 vs. 25 pg/mL), and IL-10 (4 vs. 26 pg/mL) using the ELISA method. In contrast, trauma patients had significantly higher serum concentrations of IL-1 (3,320 vs. 1,470 pg/mL, p < 0.05), IL-6 (2,415 vs. 1,048 pg/mL, p < 0.05), and IL-10 (2,307 vs. 1,480 pg/mL, p < 0.05) at admission compared with normal controls using total cytokine immunoassays. CONCLUSION: Cytokine measurements in peripheral blood in trauma patients and normal controls are significantly (10- to 500-fold) higher when using a total cytokine assay that measures both free and bound cytokine. Competitive immunoassays may be the method of choice when measuring endogenous cytokine levels in biologic fluids, and new normal ranges for cytokines must be established for future accurate research in critical care and trauma.

Adult↗
PubMed2000

Assessing the structure and process for providing pharmaceutical care in Veterans Affairs medical centers.

The structure and process used in providing pharmaceutical care to ambulatory care patients at nine Veterans Affairs medical centers (VAMCs) were studied. Institutions participating in the IMPROVE (Impact of Managed Pharmaceutical Care on Resource Utilization and Outcomes in Veterans Affairs Medical Centers) study were selected. To assess the level of pharmaceutical care services provided to ambulatory care patients, 10 critical domains were identified. Six instruments with questions related to each domain were then designed, including a clinical pharmacist survey and an outpatient pharmacist survey. Each center was assessed through three surveys and an onsite visit. The investigators used both direct observation and a consensus approach to score the level of ambulatory care pharmaceutical services provided. The clinics in which IMPROVE study patients would be seen were run by pharmacists (33%), physicians (44%), and multidisciplinary teams (22%). Of the 51 clinical pharmacists surveyed, 23 (45%) had prescribing authority via protocols, 14 (28%) had unrestricted prescribing privileges, and 14 did not have prescribing authority. The sites varied greatly in referral patterns, methods of identifying patients, and whether patient visits were scheduled or on a walk-in basis. There was a strong correlation between observed activities by clinical pharmacists and their self-reports and between observed activities by outpatient pharmacists and their self-reports. Activities reported by clinical pharmacists were moderately but not significantly correlated with consensus scores, and activities reported by outpatient pharmacists were poorly correlated with consensus scores. The structure and process for providing pharmaceutical care to ambulatory care patients at VAMCs were evaluated with surveys, direct observation, and a consensus-based scoring system.

Ambulatory Care↗
PubMed2000

Evaluation of voriconazole pharmacodynamics using time-kill methodology.

Voriconazole is an investigational azole antifungal agent with activity against a variety of fungal species, including fluconazole-susceptible and -resistant Candida species and Cryptococcus neoformans. In this study, we employed in vitro time-kill methods to characterize the relationship between concentrations of voriconazole and its fungistatic activity against Candida albicans, Candida glabrata, Candida tropicalis, and C. neoformans. Isolates were exposed to voriconazole concentrations ranging from 0.0625 to 16 times the MIC, and the viable colony counts were determined over time. The 50 and 90% effective concentrations (EC(50) and EC(90), respectively) were determined at 8, 12, and 24 h following the addition of voriconazole. At each time point, near-maximal fungistatic activity, as indicated by the EC(90), was noted at a drug concentration of approximately three times the MIC. Additionally, EC(50) and EC(90) did not change over time, thus suggesting that the rate of activity was not improved by increasing concentrations. Voriconazole exhibits non-concentration-dependent pharmacodynamic characteristics in vitro.

Antifungal Agents↗
PubMed1998

Phase II trial of paclitaxel and topotecan with granulocyte colony-stimulating factor support in stage IV breast cancer.

PURPOSE: This multicenter phase II trial investigated the efficacy and safety of a combination of paclitaxel and topotecan in patients with pretreated metastatic breast cancer. Plasma levels of paclitaxel and topotecan were obtained during cycle 1 to correlate pharmacokinetic parameters with toxicity. PATIENTS AND METHODS: Paclitaxel was administered intravenously (i.v.) at 230 mg/m2 over 3 hours on day 1 followed by topotecan 1.0 mg/m2 i.v. over 30 minutes on days 1 to 5. Patients received an abbreviated premedication regimen that consisted of ranitidine 50 mg, diphenhydramine 50 mg, and a single 20-mg dose of dexamethasone, all administered i.v. 30 minutes before paclitaxel. Granulocyte colony-stimulating factor (GCSF) was administered at 5 micrograms/kg/d subcutaneously starting on day 6 and continuing until the absolute granulocyte count (AGC) was greater than 10,000/microL. Plasma paclitaxel and topotecan concentrations were assessed during the first cycle using limited-sampling strategies. RESULTS: Seventeen patients were treated. The majority had visceral metastases. Four patients experienced neutropenic fever and one had mild bronchospasm. Only one partial response (PR) was observed. Nadir AGC correlated strongly with both duration of paclitaxel levels greater than 0.05 mumol/L and maximum concentration (Cmax) of paclitaxel. CONCLUSION: This regimen does not produce a response rate superior to that expected with single-agent paclitaxel at doses that do not require growth factor support.

Adenocarcinoma↗
PubMed1998

Retropharyngeal effusion in acute calcific prevertebral tendinitis: diagnosis with CT and MR imaging.

Three patients with the diagnosis of acute calcific prevertebral tendinitis underwent CT or a combination of CT and MR imaging, which showed previously described findings of calcifications within the tendons of the longus colli muscles. In addition, however, we detected a retropharyngeal effusion in all three patients. The importance of this finding lies in the need to differentiate this effusion from retropharyngeal infection.

Acute Disease↗
PubMed1997

Regulation of the cfos serum response element by C/EBPbeta.

Serum response element binding protein (SRE BP) is a novel binding factor present in nuclear extracts of avian and NIH 3T3 fibroblasts which specifically binds to the cfos SRE within a region overlapping and immediately 3' to the CArG box. Site-directed mutagenesis combined with transfection experiments in NIH 3T3 cells showed that binding of both serum response factor (SRF) and SRE BP is necessary for maximal serum induction of the SRE. In this study, we have combined size fractionation of the SRE BP DNA binding activity with C/EBPbeta antibodies to demonstrate that homodimers and heterodimers of p35C/EBPbeta (a transactivator) and p20C/EBPbeta (a repressor) contribute to the SRE BP complex in NIH 3T3 cells. Transactivation of the SRE by p35C/EBPbeta is dependent on SRF binding but not ternary complex factor (TCF) formation. Both p35C/EBPbeta and p20C/EBPbeta bind to SRF in vitro via a carboxy-terminal domain that probably does not include the leucine zipper. Moreover, SRE mutants which retain responsiveness to the TCF-independent signaling pathway bind SRE BP in vitro with affinities that are nearly identical to that of the wild-type SRE, whereas mutant SRE.M, which is not responsive to the TCF-independent pathway, has a nearly 10-fold lower affinity for SRE BP. We propose that C/EBPbeta may play a role in conjunction with SRF in the TCF-independent signaling pathway for SRE activation.

3T3 Cells↗
PubMed1996

Pharmacodynamics of fluorouracil-based induction chemotherapy in advanced head and neck cancer.

PURPOSE AND METHODS: To optimize the biochemical modulation of fluorouracil (5-FU), we administered the pure I-stereoisomer of leucovorin (LV) as a 132-hour continuous intravenous infusion (CIV) with cisplatin 100 mg/m2, 5-FU 640 mg/m2/d as a 120-hour CIV, and interferon alfa-2b (IFN) at 2 MU/m2/d for 6 days for three cycles (I-PFL-IFN). Pharmacologic parameters included morning (AM) and afternoon (PM) plasma concentrations of 5-FU, LV and its active metabolite 5-methyl tetrahydrofolate (MTHF), and dihydropyrimidine dehydrogenase (DPD) activity in peripheral mononuclear cells. RESULTS: Eighty-nine patients were treated (86 stage IV). Neutropenia and mucositis were the most common toxicities. Sixty-six percent achieved a complete remission (CR). There was a trend for higher PM versus AM 5-FU concentrations (median, 1.64 v 1.51 mumoles/L; P = .08), but not for LV plus MTHF (P = .66). The mean +/- SD DPD activity was 0.21 +/- 0.14 nmol/min/mg and did not correlate with plasma concentrations of 5-FU or LV plus MTHF or clinical toxicities. Higher PM 5-FU concentrations correlated with worse leukopenia (P = .04) and severity of mucositis (P = .04). PM 5-FU concentration was higher in women than in men (P = .07), with no apparent difference in severity of toxicities. The maximum 5-FU concentration was higher in CR than non-CR patients (median, 2.01 v 1.54 mumoles/L; P = .02) and higher in women than men who achieved a CR (median, 2.77 v 1.91 mumoles/L; P = .03). No correlation of CR with dose-intensity was found. CONCLUSION: L-PFL-IFN is active in stage IV head and neck cancer. 5-FU concentration is a significant predictor of toxicity. In women, optimization of response outcome requires a higher 5-FU concentration. Individualized 5-FU dosing to obtain higher 5-FU plasma concentrations may be indicated.

Adolescent↗
PubMed1995

The role of paclitaxel in the treatment of head and neck cancer.

Current chemotherapeutic approaches to recurrent head and neck cancer have routinely yielded response rates of 10% to 30% (for single agents) and 30% to 50% (for combination chemotherapy). However, median survival times for patients with metastatic and/or recurrent disease have stagnated at around 6 months since the 1970s. The investigation of new drugs and treatment approaches thus continues to be a high priority. One such agent, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), has shown good single-agent activity and is also believed to potentiate the effects of radiation therapy in patients with head and neck cancer. We have focused on the addition of paclitaxel to the previously established combination of 5-fluorouracil, hydroxyurea, and radiation therapy. The study goals are to establish the maximum tolerated dose and dose-limiting toxicity of paclitaxel when added to this combination as a 5-day continuous infusion on a biweekly schedule. Preliminary results of this ongoing study have demonstrated activity in patients with poor-prognosis head and neck cancer. Major dose-limiting toxicities have consisted of neutropenia and mucositis, and definition of a recommended phase II dose is in progress.

Adult↗
PubMed1995

Hydroxyurea with continuous infusion paclitaxel, 5-fluorouracil, and concomitant radiotherapy for poor-prognosis head and neck cancer.

Concomitant chemoradiotherapy holds promise in the therapy of advanced head and neck cancer. We have previously reported on the combination of 5-fluorouracil, hydroxyurea, and concomitant chemoradiotherapy administered on an alternate-week basis. In this ongoing study, we are testing the feasibility of adding continuous-infusion paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to this combination. Background information and early clinical data are presented.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

The impact of posthospital home care on patients with cancer.

Symptom distress, mental health status, enforced social dependency and health perceptions were measured in two groups of cancer patients, one receiving home care services (n = 49) and the other receiving no such services (n = 11). Data were obtained at hospital discharge and 3 months later. Patients receiving home care demonstrated statistically significant improvement on mental health and social dependency; patients not receiving home care did not improve on any variable. After controlling for baseline scores, the home care group had significantly higher mental health status at the second interview than the no home care group.

Aftercare↗
PubMed1994

Pneumatic reduction of intussusception using carbon dioxide.

Pneumatic reduction using air has recently become popular for the initial non-surgical management of intussusception. Since carbon dioxide (CO2) is rapidly absorbed from body surfaces, it should theoretically result in less cramping and distension following reduction. We reviewed our recent experience with the pneumatic reduction of intussusception using CO2 in 26 children. In 22 of these the intussusception was reduced (85%). There was one performation with CO2; the patient did not suffer any postoperative complications. Five additional children who had been treated unsuccessfully with barium had intussusception subsequently reduced with CO2. Following CO2 reduction, most children were fed within hours, and there were no instances of significant abdominal distension or cramping. We conclude that pneumatic reduction of intussusception using CO2 is safe and effective, and has the theoretical advantage of more rapid absorption from the gastrointestinal tract than air.

Carbon Dioxide↗
PubMed1993

Unmet needs of black patients with cancer posthospitalization: a descriptive study.

This article describes self-reported unmet needs of black patients with cancer posthospitalization and suggests a plan of research. The study sample consisted of 63 black patients with solid cancerous tumors who were discharged from seven hospitals in the Philadelphia, PA, area. The investigators collected data using the Enforced Social Dependency Scale (ESDS) and the Symptom Distress Scale (SDS). They added a checklist to the end of the ESDS to collect self-reported needs areas. The patients reported demographic data such as race and income. The investigators abstracted other demographic data, along with medical factors and complex problems, from the patients' hospital or home health agency medical records. Descriptive statistics and t-tests were used to analyze the data. Personal care and home activity needs were not being met adequately for this sample of low-income, urban-dwelling, black patients with cancer. The SDS revealed that the patients had significantly greater symptom distress related to frequency of nausea, intensity of pain, and difficulty breathing. Overall, patients with breast and gynecologic cancers reported the highest levels of symptom distress. Women who were elderly, black, alone, poor, and chronically ill were likely to have unmet needs and high levels of symptom distress.

Activities of Daily Living↗
PubMed1992

Safety and efficacy of high kV biliary lithotripsy: preliminary experience.

Despite intense interest in laparoscopic cholecystectomy, biliary lithotripsy (BL), by avoiding the need for general anesthesia, could remain a useful alternative in approximately 10% of patients with symptomatic gallstones. The poor stone clearance rates reported by the Dornier National Biliary Lithotripsy Study has led to disenchantment with biliary lithotripsy. However, the results may reflect the relatively low kV (18.7 +/- 1.7) used. We have compared symptomatic gallbladder stone/cholecystolithiasis patients with one to five stones of aggregate diameter < 60 mm treated with one to three sessions on an MPLS 9000 (Dornier) lithotripter at moderate kV (22.7 +/- 1.7 kV; mean number of shocks 1473 +/- 356) with a similar group treated with high kV (26 kV, mean number of shocks 1357 +/- 507). Ultrasound stone diameter measurements were made pre- and post-BL; 12-wk results are reported. Treatment safety was assessed by recording adverse experiences and serum, urine, hematology, and chemistry. For patients with single stones, the high kV treatment took significantly (p < 0.05) less time (74 +/- 30 min) than moderate kV treatment (118 +/- 33 min). At 3 months, the moderate kV-treated single-stone group had a residual maximum fragment size of 3.2 +/- 3.3 mm versus 1.8 +/- 2.3 mm in the high kV-treated single-stone group. The 3-month stone-free rate for patients with single stones treated at high kV was 44% compared with 46% for the moderate kV-treated group (NS). At 1 wk, 11 patients had microscopic or macroscopic hematuria and six patients had mildly elevated liver function tests. At 6 wk, however, all urine and hematological measurements had returned to normal. Two patients suffered pancreatitis, one in each group. High kV BL appears to be safe and, for patients with single stones, gives better fragmentation and takes less time to administer than moderate kV. Whether a high kV treatment protocol can achieve improved long-term stone-free rates remains to be assessed.

Cholelithiasis↗
PubMed1991

Myocardial collagen network in dilated cardiomyopathy. Morphometry and scanning electron microscopy study.

Although some form of myocyte damage is probably the main abnormality responsible for heart failure in dilated cardiomyopathy, abnormalities of the supporting interstitial collagen meshwork also occur. To see if abnormal collagen could be detected in cardiomyopathic hearts, which did not have interstitial fibrosis by routine light microscopy, we examined interstitial collagen using scanning electron microscopy and a novel digestion technique. Cardiomyopathetic collagen fibrils were significantly thicker and more densely packed than normal. We conclude that an ultrastructural collagen abnormality occurs early in dilated cardiomyopathy, this abnormality may contribute to the pathophysiology of this disease.

Cardiomyopathy, Dilated↗
PubMed1991

A chest radiograph scoring system in adult cystic fibrosis: correlation with pulmonary function.

The Birmingham scoring system for chest radiographs was assessed in 40 adult cystic fibrosis patients, with particular reference to correlation with pulmonary function values. Forty 'initial' and forty 'follow-up' chest radiographs were scored. The mean initial age of the group was 17.5 +/- 5.0 years, and the mean age at follow-up was 23.3 +/- 5.3 years. The cross-sectional radiographic score correlated significantly with the values of three commonly measured, pulmonary function parameters (r = 0.65, 0.67, 0.58, P less than 0.0001). There was a significant correlation (r = 0.64, P less than 0.0001), between the change in radiographic score, and the change in percent predicted forced vital capacity (FVC%). There was a less significant correlation (r = 0.45, P less than 0.006) between the change in radiographic score and the change in per cent predicted forced expiratory volume in one second (FEV1%). We conclude that the Birmingham radiographic scoring system is suitable for quantitative radiological evaluation in adult cystic fibrosis.

Adolescent↗
PubMed1989

Failure of ultrasound to detect extra-pancreatic abscesses in severe acute pancreatitis.

The development of intra-abdominal abscesses in patients with severe acute pancreatitis can be associated with a mortality as high as 100%. The clinical findings in these patients may be non specific and therefore imaging is essential. Computed tomography (CT) is the imaging modality of choice. However, a satisfactory ultrasound examination may be regarded as sufficient, particularly when there is limited availability of CT. A case of extra-pancreatic abscess complicating severe acute pancreatitis, in whom sonography was "normal", but CT demonstrated the abscess is presented. The importance of CT in these patients in whom an abscess is suspected and our experience with similar cases is discussed.

Abdomen↗