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Biomedical subjects

A Childs

Publications and source records attributed to A Childs.

At least 19 recordsLinked to original sources
PubMed2001

Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise.

There has been no investigation to determine if the widely used over-the-counter, water-soluble antioxidants vitamin C and N-acetyl-cysteine (NAC) could act as pro-oxidants in humans during inflammatory conditions. We induced an acute-phase inflammatory response by an eccentric arm muscle injury. The inflammation was characterized by edema, swelling, pain, and increases in plasma inflammatory indicators, myeloperoxidase and interleukin-6. Immediately following the injury, subjects consumed a placebo or vitamin C (12.5 mg/kg body weight) and NAC (10 mg/kg body weight) for 7 d. The resulting muscle injury caused increased levels of serum bleomycin-detectable iron and the amount of iron was higher in the vitamin C and NAC group. The concentrations of lactate dehydrogenase (LDH), creatine kinase (CK), and myoglobin were significantly elevated 2, 3, and 4 d postinjury and returned to baseline levels by day 7. In addition, LDH and CK activities were elevated to a greater extent in the vitamin C and NAC group. Levels of markers for oxidative stress (lipid hydroperoxides and 8-iso prostaglandin F2alpha; 8-Iso-PGF2alpha) and antioxidant enzyme activities were also elevated post-injury. The subjects receiving vitamin C and NAC had higher levels of lipid hydroperoxides and 8-Iso-PGF2alpha 2 d after the exercise. This acute human inflammatory model strongly suggests that vitamin C and NAC supplementation immediately post-injury, transiently increases tissue damage and oxidative stress.

Acetylcysteine↗
PubMed2000

The influence of reduced liver blood flow on the pharmacokinetics and pharmacodynamics of recombinant tissue factor pathway inhibitor.

OBJECTIVES: Recombinant tissue factor pathway inhibitor (rTFPI) has been shown to be an effective treatment in animal models of sepsis and is under investigation for human use. Reduced liver blood flow during septic shock may substantially alter the pharmacokinetics of rTFPI because clearance of rTFPI approaches liver blood flow. The aim of this study was to examine the effect of exercise-induced reduction in liver blood flow on the pharmacokinetics and pharmacodynamics of rTFPI. METHODS: This was a two-way, open-label, randomized crossover study in eight healthy male volunteers. The subjects in both treatment groups received a continuous intravenous infusion of rTFPI (0.2 mg/kg/h) concurrently with intravenous sorbitol (50 mg/min) for 4 hours. Sorbitol was used as a biomarker for liver blood flow. The subjects were randomized to remain supine or to exercise on a bicycle ergometer for 30 minutes starting at the beginning of the third hour of the infusion. RESULTS: Exercise reduced liver blood flow (mean +/- SEM) from 1.44 +/- 0.06 L/min to 0.40 +/- 0.03 L/min. The average clearance of rTFPI decreased from 0.73 +/- 0.04 L/min in the supine position to 0.25 +/- 0.02 L/min during exercise. This decrease in rTFPI clearance resulted in an 80% (95% confidence interval [CI], 60% to 102%) increase in plasma rTFPI levels during exercise. The average maximal prothrombin time and activated partial thromboplastin time values during exercise were 1.4 (95% CI, 0.4 to 2.5) and 4.4 (95% CI, 2.7 to 6.1) seconds higher compared with the supine steady-state level. CONCLUSIONS: Reduction in liver blood flow by exercise markedly increased rTFPI concentrations and induced a slight but variable prothrombin time and activated partial thromboplastin time increase at the rTFPI dose studied.

Adult↗
PubMed2000

Evaluating the usage of droperidol in acutely agitated persons with brain injury.

The objective of this study was to compare the effectiveness and safety of intramuscular droperidol to other intramuscularly administered agents used in the management of acutely agitated patients. Twenty-seven inpatients with a history of brain injury were prospectively monitored over a period of 2 months. Data collected for each episode of agitation include: dose, number of doses, time to achieve an adequate response or calming effect, post-episodic functioning, treatment-emergent side effects, and other patient demographics. A retrospective medical records review was also performed on the same cohort, to compare clinical outcomes associated with other intramuscular agents previously used for acute agitation. Time to achieve calming was significantly shorter with intramuscular droperidol (mean = 27.0 minutes) compared to intramuscular haloperidol, lorazepam, or diphenhydramine (group mean = 36.2 minutes, p = 0.02). Of the three comparative agents, the time to achieve calming was the fastest with lorazepam (mean = 35.0 minutes), and slower with diphenhydramine (mean = 42.6 minutes) and haloperidol (mean = 43.0 minutes). Single doses of droperidol controlled agitation more frequently than did single doses of comparative agents, and there was less post-episodic sedation with droperidol following release from seclusion or restraints. Both groups were similar in regard to the incidence of treatment-emergent events. This data represents the first published experience supporting the effectiveness of droperidol in reducing acute agitation in persons with brain injury. Follow-up studies with prospective, double-blind, parallel treatment groups should be performed to validate these preliminary findings.

Adult↗
PubMed1999

Endurance times for low back stabilization exercises: clinical targets for testing and training from a normal database.

OBJECTIVE: To establish isometric endurance holding times, as well as ratios between torso extensors, flexors, and lateral flexors (stabilizers), for clinical assessment and rehabilitation targets. DESIGN: Simple measurement of endurance times in four tests performed in random order by a healthy cohort. To measure reliability, a subsample also performed the tests again 8 weeks later. SETTING: University laboratory. PARTICIPANTS: Seventy-five young healthy subjects (31 men, 44 women). RESULTS: Women had longer endurance times than men for torso extension, but not for torso flexion or for the "side bridge" exercise, which challenges the lateral flexors (stabilizers). Men could sustain the "side bridge" for 65% of their extensor time and 99% of their flexion time, whereas women could sustain the "side bridge" for only 39% of their extensor time and 79% of their flexion time. The tests proved reliable, with reliability coefficients of >.97 for the repeated tests on 5 consecutive days and again 8 weeks later. CONCLUSION: Healthy young men and women possess different endurance profiles for the spine stabilizing musculature. Given the growing support for quantification of endurance, these data of endurance times and their ratios between extensor, flexor, and lateral flexor groups in healthy normal subjects are useful for patient evaluation and for providing clinical training targets.

Adult↗
PubMed1998

The use of unproven methods of treatment by cancer patients. Frequency, expectations and cost.

The use of unproven therapies is of concern for a number of reasons, including the lack of scientific evidence of support them, their potential financial costs and the possibility of interference with conventional treatment. This study explored the prevalence, predictors and experiences of unproven therapy use by cancer patients attending an oncology clinic at an Australian teaching hospital. A questionnaire was administered to patients whilst they were waiting for a consultation with their oncologist. A total of 173 patients were invited to participate, and 156 consented to complete the survey (90%). Over half the patients (81, 52%) had used at least one unproven therapy since their diagnosis, and 28% had used three or more. Patients most commonly practised mediation/relaxation, changed their diet and used multi-vitamins. Most expected that the therapies would aid their conventional treatments and make them feel more in control of their situation. Benefits reported were largely psychological, such as an increased sense of control or a reduction in anxiety. Younger patients, those with early stage or advanced metastatic disease and those who had used unproven therapies prior to developing cancer were more likely to use unproven therapies. Health professionals involved in the care of cancer patients should be prepared to discuss the use of unproven therapies and try to identify and deal with unmet needs to help patients to cope with their illness.

Adult↗
PubMed1997

Establishing a programme for continuous ambulatory infusion chemotherapy.

BACKGROUND: The development of venous access devices (VADs) and portable infusion pumps has enabled chemotherapy to be administered continuously within the home environment. AIM: The objective of this study was to describe the experience of establishing an ambulatory chemotherapy programme for patients receiving protracted infusions (PVIs) of 5-fluorouracil (5-FU). METHODS: The files of all patients receiving PVI 5-FU as a component of their treatment for gastrointestinal malignancy were reviewed. The types of VADs, infusion pump systems and their management were documented. Information packages and education programmes were developed for patients. RESULTS: Seventy-four patients with gastrointestinal cancer were studies. At the end of the period the Portacath was the preferred VAD, while both pumps used were found to have advantages and disadvantages. The choice of pump was decided more by patient preference than systematic differences in performance of the pumps. CONCLUSIONS: The findings in this review confirm that, with close attention to the potential pitfalls of ambulatory chemotherapy, an acceptable service can be provided.

Adult↗
PubMed1994

Effect of a clinical psychopharmacy consultation service on patient outcomes.

The effect of a psychopharmacy consultation service on outcomes in patients with psychiatric disorders was studied. The medical records of 30 randomly selected patients who had been hospitalized between August 1990 and July 1992 at a private psychiatric institution and who had been seen by the psychopharmacy consultation service during that period were reviewed. Data obtained included (1) patient demographics, (2) patient information generated by the psychopharmacy consultation, (3) the types of recommendations made by the psychopharmacy specialist and whether the recommendations were accepted by the physician, and (4) the clinical outcome. Forty-three psychopharmacy consultations for the 30 patients were evaluated. A total of 125 recommendations were made by the consultation service; of these, 75 (60%) were accepted. The consultations were divided into consultations for which at least a majority of the resulting recommendations were accepted by the physician (n = 29) and consultations for which less than a majority of the recommendations were accepted (n = 14). For the majority group, 23 (79%) of the 29 consultations were associated with a positive outcome, compared with 2 (14%) of the 14 consultations in the less-than-majority group. Similarly, positive outcomes were significantly more frequent in the majority-group patients (16/21 [76%]) than in the less-than-majority-group patients (2/9 [22%]). The frequency of positive outcomes was higher among patients for whom most of the recommendations of a clinical psychopharmacy consultation service were accepted than among patients for whom most recommendations were not accepted.

Adolescent↗
PubMed1994

Phase I trial of subcutaneous recombinant macrophage colony-stimulating factor: clinical and immunomodulatory effects.

PURPOSE: Recombinant human macrophage colony-stimulating factor (rM-CSF) has been demonstrated to control the growth, differentiation, and function of mononuclear phagocytes. Preclinical studies have indicated antitumor effects, and therefore a phase I trial of rM-CSF in patients with malignancy was initiated. The toxicity and hematologic and immunologic effects were investigated. PATIENTS AND METHODS: rM-CSF was administered as a subcutaneous injection on days 1 through 5 and 8 through 12. Cycles were repeated every 28 days. Cohorts of four to seven patients received rM-CSF at dose levels from 0.1 to 25.6 mg/m2/d. Forty-two patients received 88 cycles of rM-CSF. All patients had metastatic solid tumors refractory to standard therapy. RESULTS: The toxicity of rM-CSF was mild. Dose-limiting toxicity included thrombocytopenia (two patients) and iritis (one patient) occurring at a dose of 25.6 mg/m2/d. Hematologic studies demonstrated dose-related monocytosis occurring routinely at doses > or = 3.2 mg/m2/d, and thrombocytopenia. Immunologic studies demonstrated enhanced secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta) by monocytes after in vitro stimulation with lipopolysaccharide, and increased expression of TNF-alpha mRNA at higher rM-CSF dose levels. Pharmacokinetic studies demonstrated that the systemic clearance rate of M-CSF increases during week 1 of therapy, resulting in lower blood levels of M-CSF during the second week of therapy. CONCLUSION: rM-CSF can be safely administered to patients, and has biologic activity on peripheral-blood monocytes.

Adult↗
PubMed1994

Buspirone's efficacy in organic-induced aggression.

The objectives of this study were to (1) identify and characterize hospitalized patients with an organic-related psychiatric diagnosis who had received buspirone therapy and (2) assess the effect of buspirone on aggressive behaviors. A retrospective medical records review was conducted on all patients who were admitted to our psychiatric/rehabilitation facility over a 36-month period and who had received buspirone therapy. Monthly behavioral therapy records were used to determine the quality and quantity of aggressive-related behaviors. Study endpoint was reached in each subject when buspirone was discontinued or when records were unavailable. Twenty subjects, ranging in age from 15 to 55 years old (mu = 26.1 +/- 9.8), were identified for study. Nine (90%) of 10 subjects for whom data were available for at least 3 months showed an improvement in behavior by study endpoint, and 6 (60%) showed at least a 50% reduction in behavioral symptoms by study endpoint. Results from this study suggest that buspirone is well tolerated and may be effective in the treatment of aggressive and other maladaptive behaviors in individuals with an organic component to their psychiatric illness, particularly traumatic brain injury. Prospective, controlled trials are needed to validate these findings.

Adolescent↗
PubMed1993

Clozapine response and adverse effects in nine brain-injured patients.

Clozapine was used to treat nine brain-injured patients with psychotic symptoms or outbursts of rage and aggression refractory to other medications. Verbal and physical aggression decreased markedly in two patients, and one additional patient had a dramatic decrease in bizarre behaviors. Mild improvement occurred in three patients with a decrease in agitation and frequency of auditory hallucinations. Response was indeterminate in three patients because of inadequate length of treatment. The incidence of side effects appeared to be higher than expected, with seizures occurring in two of nine patients. These case reports illustrate that clozapine may be useful in the treatment of psychosis and aggressive behavior after brain injury, despite the occurrence of adverse effects.

Activities of Daily Living↗
PubMed1992

Suppression and transient induction of lymphokines in cancer patients after administration of polyethylene glycolated interleukin-2.

Polyethylene glycolated (pegylated) interleukin-2 (PEG IL-2) was administered as a weekly i.v. bolus to patients with metastatic cancer in a phase-I trial. Efficacy, toxicity and pharmacokinetics have been described previously. To explore mechanism of IL-2 action and discover predictors of efficacy, the levels of several lymphokines were measured in pharmacokinetic serum samples. IL-1 beta and IL-6 were elevated in many patients before PEG IL-2 administration, forming a continuous, log-normal distribution among patients. The levels of the two lymphokines were strongly correlated. However, no significant correlation could be found between these levels, clinical chemistry, or tumor regression seen after PEG IL-2 administration. Three hours after PEG IL-2 administration, IL-1 beta and IL-6 levels, if elevated, fell to normal. In all patients, independent of initial levels, IL-6 and IFN-gamma, but not IL-1 beta, increased 4 to 6 h after the injection and then fell rapidly, even though PEG IL-2 levels were high and often changed only slightly during this period. This suggests an active shut down of lymphokine synthesis, or an increase in elimination rate. After the fourth administration of PEG IL-2, the peak level of IFN-gamma was 2 to 20 times higher than after the first, while the peak level of IL-6 did not change in a consistent direction. Responding patients had typical peak levels of IL-6 and IFN-gamma. Low levels of TNF and IL-4 were occasionally seen before and after PEG IL-2 administration, but no consistent pattern was evident.

C-Reactive Protein↗
PubMed1992

Severe vascular adverse effects with thrombocytopenia and renal failure following emetogenic chemotherapy and ondansetron.

During late 1991, a series of severe adverse events involving thrombocytopenia, renal insufficiency and thrombotic episodes was observed in patients receiving emetogenic chemotherapy. Two patients died, one of renal failure and one of cerebral haemorrhage in the presence of thrombocytopenia. Other severe side effects included thrombosis of the aorta causing paraplegia and multifocal cerebral infarctions. Common exposure features included the use of ondansetron and dexamethasone as antiemetics, and in most of the cases high dose (100 mg/M2 or more) cisplatin. Retrospective review of a series of patients treated with similar cytotoxic regimens for similar diseases before the use of ondansetron revealed no similar adverse effects, but no substantial differences were observed in renal function or haematologic toxicity in the two groups overall. Sporadic adverse vascular events have been observed before the use of ondansetron. The mechanism remains unknown, and it is not clear whether ondansetron was a factor in the unusual incidence of such events in the present series.

Adult↗
PubMed1992

A phase I trial of recombinant human macrophage colony-stimulating factor by rapid intravenous infusion in patients with refractory malignancy.

Twenty patients with advanced cancer for which there was no effective standard therapy or whose disease was refractory to standard therapy were treated with recombinant macrophage colony-stimulating factor (rM-CSF). The rM-CSF was administered by intravenous bolus infusion for 5 consecutive days every other week for 2 treatment weeks. The doses administered ranged from 30 to 33,000 micrograms/m2/day. There was no intrapatient dose escalation. There were minimal to no systemic side effects seen, except for acute dyspnea noted in three patients. The dyspnea was felt to be related to the rate of infusion and did not recur in one patient given additional rM-CSF at a slower infusion rate. The major hematologic effect seen was a mild decrease in platelet count, which began to recover while the patients continued to receive the rM-CSF. The clearance of rM-CSF was dose dependent. Lower doses resulted in a saturable mechanism felt to represent cellular uptake. Clearance at higher doses demonstrated both a first-order mechanism at high serum rM-CSF concentrations, representing renal clearance, as well as a saturable mechanism at low serum concentrations. The maximum mean serum half-life was reached at dose levels of greater than or equal to 3,690 micrograms/m2 and was in the range of 234-258 min. By this route of administration, rises in absolute monocyte count were slight and seen only at doses of greater than or equal to 450 micrograms/m2 during the second therapy week. The maximum tolerated dose was not reached in this study because of lack of availability of rM-CSF.

Adult↗
PubMed1992

Intravenous administration of recombinant human macrophage colony-stimulating factor to patients with metastatic cancer: a phase I study.

PURPOSE: Recombinant human macrophage colony-stimulating factor (M-CSF) has been shown to stimulate specifically macrophage lineage differentiation in vitro and to induce cells capable of antitumor activity alone or in combination with an antibody. The administration of M-CSF to mice has demonstrated antitumor therapeutic effects in vivo. Therefore, a phase I trial of M-CSF administration to patients with metastatic cancer was undertaken. PATIENTS AND METHODS: M-CSF was given by intermittent intravenous bolus infusion every 8 hours for 7 days; the treatment cycle was repeated once after a week of rest. Cohorts of three patients underwent dose escalation from 10 to 100,000 micrograms/m2/d; 23 patients received 27 courses of M-CSF administration. All patients had metastatic solid tumors refractory to conventional therapy, including renal cell carcinoma (RCC) (nine), melanoma (seven), and colorectal carcinoma (seven). RESULTS: Treatment-related toxicity was minimal; five patients developed transient signs of ocular or periorbital inflammation, with iridocyclitis as the most severe manifestation. At the highest doses, platelet counts decreased with therapy (but remained > 100,000/mm3) and the absolute monocyte count increased during the course of therapy. Only at 30,000 and 100,000 micrograms/m2/d was treatment limited because of toxicity (iritis and malaise). Pharmacokinetic studies demonstrated up to a 1,000-fold increase in circulating serum M-CSF after bolus infusion; half-life varied from 1 to 6 hours. Complete regression of mediastinal adenopathy and multiple pulmonary metastases were observed in one patient with RCC. CONCLUSION: Recombinant M-CSF can be administered safely to patients with metastatic cancer at doses that demonstrate biologic activity.

Adult↗
PubMed1992

Hypercholesterolemia after chemotherapy for testis cancer.

PURPOSE: The study was designed to determine prospectively the prevalence of fasting serum lipid abnormalities in patients who were treated with cisplatin-based chemotherapy for germ cell tumors. We unexpectedly had demonstrated hypercholesterolemia in 20 of 30 nonfasting patients in a prior study of long-term toxicity of chemotherapy for germ cell tumors. The present study was designed to explore this phenomenon further. PATIENTS AND METHODS: Seventeen unselected patients with biopsy-proven germ cell tumors, who underwent cisplatin-based chemotherapy and who had no prior history of cardiac disease nor known hypercholesterolemia, were studied. In addition to the standard staging tests, blood was drawn for a pretreatment fasting lipid screen, which included cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and apolipoproteins A1, B, and (a). Repeat samples were drawn 24 hours after the administration of cisplatin and at intervals of 6 to 24 months after the completion of treatment. RESULTS: Seven of 17 patients (41%) had higher than desirable levels of total serum cholesterol and low-density lipoprotein cholesterol. Two of them had normal levels before treatment, four had preexisting hypercholesterolemia that increased further, and one patient had an elevated pretreatment level that did not alter. Absolute increases in serum cholesterol were noted in 14 of 17 patients. No consistent patterns of change beyond the reference ranges were found for other serum lipids. CONCLUSIONS: We have confirmed our initial observation that serum cholesterol increases in patients who received cisplatin-containing chemotherapy regimens for germ cell tumors. Further studies will be necessary to define whether other lipid abnormalities occur and the biologic significance of these findings.

Adolescent↗
PubMed1987

Ganser syndrome and its management.

The literature on the Ganser syndrome is reviewed, and a case history is described. A brief hospital admission is worthwhile for patients with this syndrome, but planning and persuasion are needed.

Adult↗