Biomedical subjects

J Gardiner

Publications and source records attributed to J Gardiner.

At least 37 records · Page 2Linked to original sources

PubMed2001

Oltipraz concentrations in plasma, buccal mucosa cells, and lipids: pharmacological studies.

Oltipraz is considered one of the most potent cancer chemoprevention agents, as shown in preclinical studies. Its pharmacological effects in humans have been associated with unusual toxicity affecting the fingers and toes. This study was designed to test intermittent dosing schedules using two dosage levels: 500 mg as a single weekly dose and 200 mg as a biweekly dose, each for 30 days. Fifteen men and women were studied in each dosing group. All were heavy smokers considered to be at high risk for developing lung cancer. Plasma, buccal mucosa cell, and lipoprotein concentrations were measured at different intervals corresponding to the time period when most of the adverse effects occur. No serious toxicities were observed using these doses and schedules. The plasma and buccal mucosa cell concentrations of Oltipraz showed substantial interindividual variations at each sampling. Some subjects had no detectable plasma or buccal mucosal cell Oltipraz concentrations. The distribution of Oltipraz incorporation into the lipid fractions and albumin was changed by the administration of different schedules of Oltipraz. The results of this study suggest that the intermittent dosing is well tolerated and does not result in steady state in plasma or buccal mucosa cells. The variation and lack of detectable Oltipraz concentration in plasma, buccal mucosa cells, and lipids may affect both the toxicity and the pharmacological effects when these doses and schedules are used.

Administration, Oral↗

PubMed2000

Diurnal variation in orexin A immunoreactivity and prepro-orexin mRNA in the rat central nervous system.

Orexins are a family of neuropeptides originally believed to be important mediators of food intake. The wide distribution of orexins and their receptors, however, has suggested other regulatory functions for these peptides including involvement in sleep and arousal mechanisms. In this study, we have demonstrated diurnal variation in orexin A immunoreactivity in the pons, from where locus coeruleus noradrenergic neurones innervate other brain areas to stimulate arousal, and in the preoptic/anterior hypothalamic region, an area implicated in the regulation of sleep and circadian rhythms. Orexin A immunoreactivity decreased by 50% in the preoptic/anterior hypothalamus from 09:00 to 21:00 h (P < 0.0001), whilst in the pons, it increased by over 30% from 09:00 to 01:00 h (P = 0.02). Prepro-orexin mRNA also displayed diurnal variation. This further suggests that orexins are involved in the regulation of the sleep/wake cycle.

Animals↗

PubMed2000

Menstrual cycle irregularity and the incidence of nausea and vomiting after laparoscopy.

Gender is an important risk factor for postoperative nausea and vomiting. Menstrual cycle phase has also been implicated as a further variable in female patients. It is not clear whether a history of an irregular menstrual cycle is a significant variable and studies to date have not examined this. The influence of an irregular menstrual cycle on nausea and vomiting after laparoscopy was evaluated in a blinded, prospective, observational study. One hundred and fifty-nine patients scheduled for laparoscopy and dye investigation were included. Anaesthetic technique and postoperative analgesia were standardised. In comparison with patients who had a regular cycle, an irregular menstrual cycle increased the incidence of nausea or vomiting from 20.5% to 40.5% (absolute difference 20%; 95% CI 0.03-0.37, p = 0.01). Other variables were similar between the groups. An irregular menstrual cycle appears to increase the risk of postoperative nausea and vomiting.

Adult↗

PubMed2000

Clinical-histopathological correlation of the abnormal retinal vessels in cerebral malaria.

BACKGROUND: Clinically abnormal retinal vessels unique to cerebral malaria have previously been shown to be associated with a poor outcome in African children. There have been no studies of the histopathological correlates of these vessels. DESIGN: This is a descriptive study of the clinical-histopathological correlates of the retinal vessels of 11 children who died with cerebral malaria. RESULTS: The retinal vessels in children with cerebral malaria contained many parasitized red blood cells; these cells tended to cluster at the periphery of vessels or, in the case of capillaries, to fill the vessel. Those with late-stage parasites had markedly reduced amounts of hemoglobin. The pattern of dehemoglobinization corresponds to the pattern of clinically abnormal vessels. CONCLUSIONS: The sequestration of late-stage parasitized red blood cells with reduced amounts of hemoglobin accounts for the unique white and pale orange retinal vessels seen in cerebral malaria. Clinical examination of these "marked" vessels offers a method to monitor a basic pathophysiological process of cerebral malaria in vivo. Arch Ophthalmol. 2000;118:924-928

Animals↗

PubMed1999

Miltefosine as a topical treatment for cutaneous metastases in breast carcinoma.

BACKGROUND: Recurrent cutaneous breast cancer is difficult to manage, with surgery, radiotherapy and systemic therapy all having their limitations. Miltefosine is a topical cytostatic agent which may provide an alternative approach in its treatment. PATIENTS AND METHODS: Patients with previously treated progressive cutaneous lesions from breast cancer were treated with miltefosine on a named-patient compassionate supply basis. Miltefosine was applied topically to the skin at a dose of 2 drops/10 cm(2) skin area. RESULTS: Twenty-five patients were treated, most of whom had been heavily pre-treated. Treatment was continued for a median of 14 weeks (range 2-164). In 7 patients grade I skin toxicities were observed, and in 4 patients grade 3 local toxicities necessitated dose adjustments. A response was seen in 9 patients (1 complete response, 2 partial responses, 6 minor responses) giving a total response rate of 36%, with stable disease in 11 patients (44%) and progressive disease in 5 (20%). Those lesions which were superficial or < 2 cm in diameter were most likely to respond. CONCLUSIONS: Miltefosine, either used alone or in conjunction with other therapies for distant metastases, is an effective and tolerable local treatment for cutaneous breast cancer.

Administration, Topical↗

PubMed1999

Intact proprioception and control of labour pain during epidural analgesia.

BACKGROUND: Accurate proprioception is critical while walking, yet an ambulatory epidural regimen that provides adequate analgesia for labour while simultaneously preserving proprioceptive input has not been described. METHODS: Sixty primigravidae in established labour received bupivacaine 15 mg (15 ml of 0.1% w/v) and fentanyl 100 micrograms through a lumbar epidural catheter. Clinical assessment of dorsal column sensory function included: vibration sense, distal proprioception and the Romberg test, and were all performed before catheter insertion and 30 min after the study bolus. Sensory modalities were also tested compared to an unblocked dermatome. Pain was scored on a 0-10 cm visual analogue scale (VAS) before and 30 min after induction. Intensity of the motor block was tested using a modified Bromage score (grade 1-6). RESULTS: The study bolus provided reliable analgesia with 43 parturients attaining a VAS pain score of zero. Mean duration of analgesia was 67.5 min (SD 22.85). All parturients retained the ability to perform a partial knee bend while standing (grade 6). No mothers exhibited impaired distal proprioception, altered vibration sense or a positive Romberg sign. CONCLUSION: This study confirms that the addition of lumbar epidural fentanyl 100 micrograms to 15 mg of epidural bupivacaine provides good control of labour pain with no motor block and establishes that this combination preserves dorsal column sensory function.

Adult↗

PubMed1999

Acupressure and the prevention of nausea and vomiting after laparoscopy.

The efficacy of currently available antiemetics remains poor. Concern with their side effects and the high cost of the newer drugs has led to renewed interest in non-pharmacological methods of treatment. We have studied the efficacy of acupressure at the P6 point in the prevention of nausea and vomiting after laparoscopy, in a double-blind, randomized, controlled study of acupressure vs placebo. We studied 104 patients undergoing laparoscopy and dye investigation. The anaesthetic technique and postoperative analgesia were standardized. Failure of treatment was defined as the occurrence of nausea and/or vomiting within the first 24 h after anaesthesia. The use of acupressure reduced the incidence of nausea or vomiting from 42% to 19% compared with placebo, with an adjusted risk ratio of 0.24 (95% CI 0.08-0.62; P = 0.005). Other variables were similar between groups.

Acupressure↗

PubMed1999

Putrefactive pleural effusions as an alternative sample for drug quantification.

In the investigation of drug-related deaths it is occasionally necessary to examine putrefied bodies. In such cases the availability of conventional body fluids for toxicologic analysis is usually limited, whereas blood-stained pleural effusion is often present in adequate quantity in the pleural cavity. Fifty-five cases involving numerous drugs are presented in which pleural effusion drug concentrations are compared with corresponding blood or liver concentrations. More than 90% of comparisons produced coincident interpretations of the role that drugs played in the deaths. In most instances pleural effusion analysis was shown to be a valid alternative to the analysis of blood or other conventional fluids or tissues in cases exhibiting advanced putrefaction.

Autopsy↗

PubMed1999

Creation and testing of a practical visual function assessment for use in Africa: correlation with visual acuity, contrast sensitivity, and near vision in Malawian adults.

AIM: To develop and test a practical visual function assessment for use in developing countries. METHODS: Using focus group discussions and interviews with eyecare workers and low vision specialists in Malawi, 13 questions related to visual characteristics of activities of daily living were designed. Patients presenting to an eye clinic were recruited and interviewed. Visual acuity, near vision, and contrast sensitivity were measured. Analysis sought to determine the degree of correlation between the vision indices and visual function. RESULTS: The visual function questionnaire was easy to administer. Visual function correlated with visual acuity, contrast sensitivity, near vision, and patient reported visual problem. People with a higher frequency of "not applicable" responses had lower visual function scores. Multivariate modelling revealed that visual acuity and number of questions felt to be applicable were independently associated with visual function. Reducing the questionnaire to nine questions did not affect the degree of correlation with any of the visual indices. CONCLUSION: The authors' visual function assessment correlates well with different measures of visual acuity. People with reduced vision for a prolonged period may no longer consider doing certain tasks and the number of questions considered appropriate by an individual may be an additional measure of visual function. Assessment of visual function by health workers may be a valuable tool in improving surgical uptake by encouraging both health personnel and patients to recognise that they have difficulties undertaking activities of daily living as well as a measure of monitoring and evaluating cataract outcomes.

Contrast Sensitivity↗

PubMed1998

Pharmacological and biochemical determinants of the antitumour activity of the indoloquinone EO9.

EO9 is a novel bioreductive drug which has recently undergone extensive clinical evaluation. Its mechanism of action remains to be clearly defined. Antitumour activity of EO9 has been determined in 2 human colon cancer xenografts (HT-29 and BE) and 2 murine colon adenocarcinomas (MAC 16 and 26) after intratumoural injection of 250 microg of drug. Levels of the major bioreductive enzymes (DT-diaphorase, cytochrome P-450 reductase and cytochrome b5 reductase) were measured in tumours using cytochrome c reduction and menadione as the intermediate electron acceptor. There was no correlation between chemosensitivity (T/C: HT-29, 15%; BE, 27%; MAC 16, 33% and MAC 26, 60%) and enzyme activity (r2 = 0.47 for DT-diaphorase, r2 = 0.1 for cytochrome P-450 reductase and r2 = 0.52 for cytochrome b5 reductase). Drug metabolism was followed in vitro using tumour homogenates incubated under aerobic and anaerobic conditions. Four metabolites were identified by HPLC and characterised bv UV-visible spectroscopy. With the exception of the hydrolysis product EO5A, all other metabolites appeared to be drug adducts. No correlation was observed between the kinetics of metabolite formation and antitumour activity. A good correlation (r2 = 0.86) was found with the rate of disappearance of parent drug and antitumour activity. These data show that the overall capacity of a tumour to metabolise EO9 is the most important determinant of antitumour activity rather than the expression of the major bioreductive enzymes and that the parent drug rather than a metabolite leads to the active form of the drug.

Adenocarcinoma↗

PubMed1997

Peptide analogue studies of the hypothalamic neuropeptide Y receptor mediating pituitary adrenocorticotrophic hormone release.

Hypothalamic neuropeptide Y (NPY) is thought to be important in the regulation of feeding and also in the release of Adrenocorticotrophic hormone (ACTH). Intracerebroventricular administration of NPY to male rats significantly increased plasma ACTH 10 min after injection and stimulated 2-h food intake. A series of analogues of NPY that have a greatly reduced affinity for the Y1 [human pancreatic polypeptide (human PP), NPY(3-36)], the Y2 ([Pro34]NPY, human PP), the Y3 (peptide YY), and the Y6 (human PP) receptor, all markedly stimulated ACTH release. Rat PP, which binds with high affinity to the Y4 receptor, was unable to stimulate ACTH release. A novel analogue fragment [Pro34]NPY(13-36) was synthesized as a ligand with low Y1 and Y2 receptor affinity. Interestingly, neither [Pro34]NPY(13-36) nor the selective Y5 receptor agonist [D-Trp32]NPY stimulated food intake, whereas both significantly increased plasma ACTH. Thus the hypothalamic NPY receptor mediating increases in plasma ACTH has a fragment activation profile unlike the Y1-Y4 or Y6 receptors and appears distinct from the NPY receptor controlling food intake.

Adrenocorticotropic Hormone↗

PubMed1997

Carcinoid heart disease with severe hypoxia due to interatrial shunt through patent foramen ovale.

Carcinoid heart disease occurs in approximately half of patients who have carcinoid syndrome and is the leading cause of death among these patients. It is typically manifest as right-sided valvular lesions, usually tricuspid insufficiency and pulmonary valve stenosis. This case report describes the unusual presentation of a patient with carcinoid heart disease and a large right-to-left shunt through a patent foramen ovale.

Adult↗

PubMed1996

A pilot study of infusional CMF (CMF-inf): active and well tolerated in breast cancer. The Edinburgh Breast Group.

BACKGROUND: We have previously shown that 5-fluorouracil (5-FU) given by continuous infusion is well tolerated and active in the treatment of breast cancer [1, 2]. We found that given infusional 5-FU could produce responses in patients whose disease was resistant to bolus 5-FU and speculated that it could be combined safely with methotrexate/cyclophosphamide in a manner analogous to i.v. CMF bolus. Using a modification of the i.v. CMF regimen, comprising a standard dosage of bolus cyclophosphamide at 750 mg/m2 and bolus methotrexate at 50 mg/m2 given every 3 weeks we altered the continuously infused 5-FU schedule to 200 mg/m2/24 hours and treated 28 patients of whom 23 had had previous chemotherapy (18 containing anthracycline, 4 bolus CMF and 19 infusional 5-FU alone or in combination with other drugs) and 4 post menopausal patients with locally advanced breast cancer. RESULTS: Fourteen responded (2 CR, 12 PR) out of 27 evaluable patients with onset of response between 3 and 9 weeks. Toxicity was relatively mild in the 28 evaluable patients and did not require cessation of treatment, with one exception (vomiting leading to dehydration at home and moderate transient uraemia). The main toxicities seen were WHO grade 3 neutropenia in 13/28 patients and grade 2 mucositis in 2 further patients. Grade 2 palmar/planter syndrome was reported in 4/28 patients and grade 2 or 3 nausea/vomiting was reported in 7/28 patients. CONCLUSION: This well tolerated regimen is clearly active in patients with heavily pretreated breast cancer and should be tested against intravenous or classical CMF in a randomised trial.

Adult↗

PubMed1996

Nonfatal firearm misuse: licence status of perpetrators and legality of the firearms.

The primary aim of this study was to identify the licence status of those involved in incidents of nonfatal firearm-related misuse and to determine the involvement of legal firearms in such incidents. Firearm-related attempted suicides were excluded. The study also sought to identify the types of firearms most likely to be misused. Over a three-month period in early 1994, all nonfatal firearm-related incidents reported in any New Zealand newspaper were identified by a commercial clipping bureau. Data pertaining to the licence status and the legality of the firearm involved in these incidents were obtained from the police who completed a standardized questionnaire under the Official Information Act (1982). Over the study period, 78 incidents yielded information on 97 perpetrators and 100 firearms. Of the 97 perpetrators, 66 per cent were unlicensed, 20 per cent were licensed, the licence status of 8 per cent of the perpetrators was unknown and the remaining 7 per cent were using air guns and therefore a licence was not required. Half of the perpetrators involved in domestic disputes were licensed. Of the 100 firearms, 44 per cent were classified as "legal firearms' and 56 per cent were classified as "illegal firearms'. These findings suggest that strategies aimed at reducing or preventing injury due to firearm misuse must focus on both licensed and unlicensed individuals and both legal and illegal firearms.

Accident Prevention↗

PubMed1996

Incidence of injuries and other health problems in the Auckland Citibank marathon, 1993.

OBJECTIVE: To describe the incidence of injuries and other health problems sustained during participation in a marathon. METHODS: A cohort study was undertaken involving the 1993 Auckland Citibank marathon participants. Demographic data and information on injuries and other health problems sustained during, immediately after, and 7 d following the marathon were obtained from a pre-race questionnaire, the medical aid posts, and a post-race questionnaire. RESULTS: Of the 1219 starters, 916 (75.1%) completed both questionnaires. Seventy five individuals (6.2%) sought assistance at the medical aid posts. During or immediately after the marathon, 283 systemic health problems were reported by 218 respondents (23.8%) and 2671 specific health problems were reported by 846 respondents (92.4%). In the 7 d following the marathon, 1905 specific health problems were reported by 723 respondents (79.2%). The majority of the specific health problems were blisters, stiffness, and pain, predominantly involving the lower limbs. CONCLUSIONS: Although a high proportion of participants experienced health problem during the race, very few of these problems were serious. Many of the entrants were still experiencing problems 7 d after the marathon.

Edema↗

PubMed1995

U.S. farm women's participation in breast cancer screening practices.

BACKGROUND: Surveys of women in the general population indicate that women are being screened for breast cancer at a much lower rate than recommended. There has been a concern that women living in rural areas may be screened for breast cancer even less often than women in urban or suburban areas because of reduced access to health practitioners. METHODS: A random sample of farm women age 40 years or older from 4 rural counties in Michigan was surveyed on knowledge, attitudes, and use of breast cancer screening. RESULTS: Six hundred eighty farm women completed a questionnaire. This was a response rate of 63.8%. The percentages of farm women who reported ever having had a mammogram, having had a mammogram in the past 3 years, and having had a mammogram in the last year were 80.6, 73.7, and 51.9%, respectively. The frequency of clinical breast examinations parallelled mammography usage at slightly higher percentages. Mammogram usage increased with higher education, income, and insurance coverage. Usage decreased in women age 75 years or older (ever 63.1%, in the last 3 years 58.2%, and in the last year 40.4%). Farm women were generally knowledgeable about symptoms and signs of breast cancer and understood the benefit of screening. There was, however, a range of answers on when to start or stop having a mammogram. Among farm women who reported not having a mammogram recently, the most important reasons were: haven't had any problems (29.4%), wasn't recommended by a doctor (14.3%), and procrastinated (11.3%). CONCLUSIONS: Farm women in this survey reported having had breast cancer screening at rates similar to or above those in the general population. Because of a limited response rate (63.5%) and the relative affluence of the farming community in the 4 counties surveyed, these results are probably not generalizable to all populations of farm or rural women.

Adult↗

PubMed1995

Evaluating and improving the cost-effectiveness of the implantable cardioverter-defibrillator.

The implantable cardioverter defibrillator (ICD) is an expensive, widely used device for severe ventricular arrhythmias. Marginal cost-effectiveness analysis is a technique to examine the incremental cost of treatment strategy in relation to its effectiveness. In this study, we used this technique to analyze the cost-effectiveness of the ICD compared with that of electrophysiology (EP)-guided drug therapy and examined ways in which it may be improved. We analyzed Michigan Medicare discharge abstracts (1989 to 1992) and local physician visit, test, and ICD charges. Effectiveness was from 218 previously described patients with ICDs in whom the time of first event (first appropriate shock or death) was determined and presumed to represent "control" (EP-guided drug therapy) mortality. We assumed a 4-year life cycle for the ICD generator and 3.4% operative mortality and used a 5% discount to prevent value. Data were analyzed in a 1-month cycle Markov decision model over a 6-year horizon, and results were updated to 1993 dollars. ICD effectiveness was an increase in discounted mean life expectancy of 1.72 years. Cost-effectiveness was $31,100/year of life saved (YLS). Results were minimally or modestly sensitive to variations in preoperative mortality; resource use; consideration only of patients with ICDs who were receiving any antiarrhythmic drug or specifically amiodarone; and to a decrease in the percentage of first shocks that would equal death without the ICD until the assumed percentage decreased to < 38%. At ejection fraction of < 0.25 and > or = 0.25, cost-effectiveness was $44,000/YLS and $27,200/YLS, respectively, and without preimplant EP study was $18,100/ YLS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

The space blanket and shivering during extradural analgesia in labour.

The incidence of shivering in women during epidural analgesia in labour is up to 33%, and may be highly distressing. Its mechanism is unclear, but the most widely held theory is that it is thermogenic. Pharmacological suppression may adversely effect the foetus or induce maternal hypothermia, and although physical remedies such as direct heat application are effective, they are also expensive and cumbersome. We recently found that the space blanket, a simple aluminised metallic foil, used pre-emptively, reduces shivering after general anaesthesia. We investigated the effect of the space blanket on the incidence and intensity of shivering, axilliary skin temperature, and subjective perception of cold during epidural analgesia for labour in 50 women over a four-hour time frame. Patients were randomised into group 1, who were wrapped in a space blanket immediately after commencement of epidural analgesia with bupivacaine, and group 2 (matched controls). Shivering was defined as visible tremor of the head, neck, trunk or limbs as observed by the attending midwives. Twenty-nine percent of group 1 and 35% of group 2 shivered (not significant), but a reduction in shivering intensity was observed in group 1 (P < 0.05). There was no significant difference in skin temperatures in either group, and no significant temperature change within the groups. Both groups had similar thermal comfort scores throughout the study, which correlated poorly with the presence of shivering. We conclude that there is no benefit in application of the space blanket to reduce epidural-analgesia related shivering in labour, which may indicate a non-thermogenic mechanism for this phenomenon.

Adult↗