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Biomedical subjects

A Fuller

Publications and source records attributed to A Fuller.

At least 37 records · Page 2Linked to original sources
PubMed1999

A phase I/II dose escalation study of intensified cyclophosphamide and autologous blood stem cell rescue in severe, active rheumatoid arthritis.

OBJECTIVE: Based on animal studies and anecdotal case reports, high-dose therapy and autologous blood stem cell rescue have been proposed as an experimental treatment for severe, refractory rheumatoid arthritis (RA). This study aimed to establish the toxicity of this treatment and obtain preliminary efficacy data upon which to base future clinical trials. METHODS: Two cohorts of 4 patients who fulfilled criteria for severe, active, treatment-resistant RA were recruited into a dose-escalation study of cyclophosphamide (CYC) (100 mg/kg or 200 mg/kg) followed by unmanipulated peripheral blood stem cell rescue. Patient treatment was managed according to a standard supportive care protocol. Disease-modifying drugs were discontinued before treatment, but corticosteroids were maintained and later tapered where possible. Patients' conditions were assessed using World Health Organization toxicity criteria and standard parameters for rheumatic disease. RESULTS: Dose-dependent differences in hematologic toxicity were observed between cohorts 1 and 2, although toxicity was similar for other systems and was most significant in the gastrointestinal system. Patients in cohort 1 had only transient responses to therapy, lasting 2-3 months. Substantial improvements were sustained beyond 17-19 months in cohort 2, including steroid-independent disease remission for 1 patient, although the procedure did not completely abolish disease activity. CONCLUSION: High-dose CYC and unmanipulated autologous blood stem cell rescue has acceptable dose-dependent toxicity in severe, treatment-resistant RA, and 200 mg/kg of CYC induces substantial clinical responses. Refinement of this intensive approach might include further intensification of the preparation regimen, graft manipulation, and posttransplant immunomodulation.

Adult↗
PubMed1999

Non-thermal signals govern selective brain cooling in pigs.

We used implanted miniature data loggers and fine thermistors to measure arterial blood and brain temperatures in four female pigs, to a resolution of 0.04 degree C, every 5 min, for 4 weeks. Within that period, pigs were exposed on different days, and in random order, to a cold (5 degrees C) or hot (38 degrees C) environment. In the thermoneutral environment of the pigs' home pens, brain temperature was usually lower than blood temperature. Such selective brain cooling was absent for 2 days after surgery, during handling and transport stress, and on waking. The magnitude of selective brain cooling was greatest when pigs were sleeping and body temperatures were low, and was smallest, or even absent, during hyperthermia and natural fever. Our results showed that selective brain cooling was present in pigs, but there was no clear relationship between blood temperature and the magnitude of selective brain cooling. Instead, the degree of selective brain cooling in pigs was governed by non-thermal factors, especially those associated with high sympathetic nervous system activity. Our results further support the concept that selective brain cooling does not serve to protect the brain from thermal damage during heat stress.

Animals↗
PubMed1999

Evaluation of miniature data loggers for body temperature measurement during sporting activities.

We recorded body temperatures in four runners, two squash players and one swimmer at 1-min intervals using miniature data loggers. These single-channel loggers are small and light (25 g), and were easily carried by the athletes during their sporting activities. Wide-range loggers (-37 degrees C to +46 degrees C), which had a temperature resolution of 0.4 degrees C, were used to measure thigh skin temperature. Auditory canal temperature and rectal temperature were measured with narrow-range loggers (+34 degrees C to + 46 degrees C) which had a considerably higher resolution (0.04 degrees C). With the aid of visual analogue scales subjects reported that the thermometric equipment caused very little discomfort or impairment of exercise performance. Loggers connected to uncoated bead thermistors (used for skin and auditory canal temperatures) had a thermal time constant of 0.4 s, and that of the coated thermistors (rectal probes) was 6 s. We were able to waterproof the equipment and measure rectal temperature in a swimmer. Hot (35 degrees C) or cold (5 degrees C) ambient temperatures had an insignificant effect on the intrinsic accuracy of the data loggers, even when used without recalibration at those temperatures. We believe that miniature temperature loggers are convenient and accurate thermometers for use during sporting activities and may provide new insights into thermoregulation during exercise.

Adult↗
PubMed1999

Brain, abdominal and arterial blood temperatures of free-ranging eland in their natural habitat.

Using implanted miniature data loggers we measured brain, arterial blood and abdominal temperatures at 5-min intervals in two free-ranging eland (Tragelaphus oryx) in their natural habitat. The animals were subjected to a nychthemeral range of globe temperature which exceeded 40 degrees C. Arterial blood exhibited a moderate amplitude (2.3 degrees C) nychthemeral rhythm, with a temperature peak at 1600-1800 hours, and a trough in the early morning at 0600-0800 hours. Mean abdominal temperature was 0.2-0.3 degrees C lower than the corresponding blood temperature, and had a peak-to-trough amplitude of 2.6 degrees C. Brain temperature closely paralleled changes in blood temperature but usually exceeded blood temperature by about 0.5 degrees C. Sporadic episodes of selective brain cooling occurred in one animal, but the duration and magnitude of such cooling was small (less than 0.4 degrees C), and took place only well above the mode of blood temperature. Our results do not support the concept that eland routinely employ adaptive heterothermy and selective brain cooling to survive in their natural environment.

Abdomen↗
PubMed1999

Maternal and child constitutional factors and the frequency of melanocytic naevi in children.

This study examined the association between numbers of benign melanocytic naevi in 7-year-old children in Oxfordshire born in 1988-9 with their mother's arm naevus count, and maternal and child pigmentation factors. We believe this is the first time that the relationship between child and maternal naevus counts has been reported. A high naevus count in the child was associated with male sex (P = 0.009), freckling (P = 0.001) and propensity of the child to burn in the sun (P = 0.05). A low naevus count was observed in red-haired children (P = 0.02). The strongest association of child's naevus count was with a high maternal arm naevus count, independent of the child's pigmentation factors (trend P < 0.0001). Maternal pigmentation factors were not associated with child's naevus count independent of the child's own pigmentation factors. Maternal arm naevus counts may be a better predictor of child naevus count than the child's own pigmentation factors and children. There has not been examination, however, of the relationship between naevus counts in children and those in their parents. We therefore conducted a study of the occurrence of naevi in children aged 7-8 years in Oxfordshire, examining, in addition to sex and pigmentation factors in the child, the relationship of maternal pigmentation factors and maternal naevus counts with naevi in their offspring.

Age Factors↗
PubMed1999

Oral antibiotics reduce body temperature of healthy rabbits in a thermoneutral environment.

Nonabsorbable oral antibiotics, which reduce gut flora, decrease the daytime and night-time body temperatures of rats and mice. We investigated whether oral antibiotics would also lower the body temperature of healthy rabbits. Six rabbits received neomycin sulphate in their drinking water for ten days, and seven rabbits received a mixture of chloramphenicol and dihydroxystreptomycin for six days. Body temperatures, recorded using intra-abdominal radiotelemeters, decreased significantly, by 0.2-0.3 degree C, after three days of antibiotic treatment in both groups of rabbits. The drop in body temperature was transient; after six days body temperatures returned to pre-antibiotic levels. Antibiotic treatment had no effect on either the acrophase or the amplitude of the circadian rhythm in body temperature. Oral antibiotics therefore reduce body temperature of rabbits, without influencing the circadian rhythm in body temperature. Our results are consistent with the hypothesis that an agent arising from intestinal bacteria sustains an elevated body temperature in healthy animals.

Animals↗
PubMed1999

Applying the Sheffield tables to data from general practice.

Lowering cholesterol with drugs of the statin class reduces the risk of a coronary event. Recent guidelines recommend use of the 'Sheffield tables' to detect individuals who might be offered drug treatment in whom the annual absolute risk of a first coronary event is > or = 3%. Using these tables in a general practice cohort aged 35-68 years, we found that 3% of men and 0.05% of women were above the treatment threshold. Smokers aged over 50 accounted for 85% of people recommended for statin therapy. Almost all smokers would fall below the treatment threshold if they quit smoking.

Adult↗
PubMed1998

Fatal Legionella longbeachae infection following heart transplantation.

A case of fatal Legionella longbeachae infection following heart transplantation is described. Gram stains of respiratory secretions on day 17 posttransplant revealed leucocytes and gram-negative bacilli, but there was no growth on routine bacterial culture. Legionella longbeachae serogroup 1 was isolated from respiratory specimens, blood, and postmortem lung tissue. Legionella longbeachae is a common cause of legionellosis in Australia, and infection has been associated with exposure to potting mixes. Specific culture for Legionella spp. should be performed for any patient who develops pneumonia following organ transplantation.

Cross Infection↗
PubMed1998

Brain abscesses caused by Burkholderia pseudomallei.

Burkholderia pseudomallei is an important human pathogen in tropical areas, particularly South East Asia and Northern Australia. A fatal case of meliodosis presenting as brain abscesses is described. The patient deteriorated despite treatment and died 21 days after admission. Burkholderia pseudomallei was only isolated after administration of corticosteroids, whilst on treatment with antibiotics to which the organism later showed in vitro sensitivity. Magnetic resonance imaging was more sensitive than computed tomography in diagnosing early brainstem infection in this patient. Physicians working outside the endemic areas must be attuned to the possibility of melioidosis in any patient with an appropriate history of travel to endemic areas. The combination of striking early, extensive, confluent T2 hyperintensity with disproportionately small enhancing lesions may be characteristic of meliodosis.

Adult↗
PubMed1998

A randomised, blinded, placebo-controlled, dose escalation study of the tolerability and efficacy of filgrastim for haemopoietic stem cell mobilisation in patients with severe active rheumatoid arthritis.

Autologous haemopoietic stem cell transplantation (HSCT) represents a potential therapy for severe rheumatoid arthritis (RA). As a prelude to clinical trails, the safety and efficacy of haemopoietic stem cell (HSC) mobilisation required investigation as colony-stimulating factors (CSFs) have been reported to flare RA. A double-blind, randomised placebo-controlled dose escalation study was performed. Two cohorts of eight patients fulfilling strict eligibility criteria for severe active RA (age median 40 years, range 24-60 years; median disease duration 10.5 years, range 2-18 years) received filgrastim (r-Hu-methionyl granulocyte(G)-CSF) at 5 and 10 microg/kg/day, randomised in a 5:3 ratio with placebo. Patients were unblinded on the fifth day of treatment and those randomised to filgrastim underwent cell harvesting (leukapheresis) daily until 2 x 10(6)/kg CD34+ cells (haemopoietic stem and progenitor cells) were obtained. Patients were assessed by clinical and laboratory parameters before, during and after filgrastim administration. RA flare was defined as an increase of 30% or more in two of the following parameters: tender joint count, swollen joint count or pain score. Efficacy was assessed by quantitation of CD34+ cells and CFU-GM. One patient in the 5 microg/kg/day group and two patients in the 10 microg/kg/day group fulfilled criteria for RA flare, although this did not preclude successful stem cell collection. Median changes in swollen and tender joint counts were not supportive of filgrastim consistently causing exacerbation of disease, but administration of filgrastim at 10 microg/kg/day was associated with rises in median C-reactive protein and median rheumatoid factor compared with placebo. Other adverse events were well recognised for filgrastim and included bone pain (80%) and increases in alkaline phosphatase (four-fold) and lactate dehydrogenase (two-fold). With respect to efficacy, filgrastim at 10 microg/kg/day was more efficient with all patients (n = 5) achieving target CD34+ cell counts with a single leukapheresis (median = 2.8, range = 2.3-4.8 x 10(6)/kg, median CFU-GM = 22.1, range = 4.2-102.9 x 10(4)/kg), whereas 1-3 leukaphereses were necessary to achieve the target yield using 5 microg/kg/day. We conclude that filgrastim may be administered to patients with severe active RA for effective stem cell mobilisation. Flare of RA occurs in a minority of patients and is more likely with 10 than 5 microg/kg/day. However, on balance, 10 microg/kg/day remains the dose of choice in view of more efficient CD34+ cell mobilisation.

Adult↗
PubMed1998

Brain and abdominal temperatures at fatigue in rats exercising in the heat.

We measured brain and abdominal temperatures in eight male Sprague-Dawley rats (350-450 g) exercising voluntarily to a point of fatigue in two hot environments. Rats exercised, at the same time of the day, in three different trials, in random order: rest 23 degrees C, exercise 33 degrees C; rest 23 degrees C, exercise 38 degrees C; and rest 38 degrees C, exercise 38 degrees C. Running time to fatigue was 29.4 +/- 5.9 (SD), 22.1 +/- 3.7, and 14.3 +/- 2.9 min for the three trials, respectively. Abdominal temperatures, measured with intraperitoneal radiotelemeters, at fatigue in the three trials (39.9 +/- 0.3, 39.9 +/- 0.3, and 39.8 +/- 0.3 degrees C, respectively) were not significantly different from each other. Corresponding brain temperatures, measured with thermocouples in the hypothalamic region (40.2 +/- 0.4, 40.2 +/- 0.4, and 40.1 +/- 0.4 degrees C), also did not differ. Our results are consistent with the concept that there is a critical level of body temperature beyond which animals will not continue to exercise voluntarily in the heat. Also, in our study, brain temperature was higher than abdominal temperature throughout exercise; that is, selective brain cooling did not occur when body temperature was below the level limiting exercise.

Abdomen↗
PubMed1997

Risk reversals in predictive testing for Huntington disease.

The first predictive testing for Huntington disease (HD) was based on analysis of linked polymorphic DNA markers to estimate the likelihood of inheriting the mutation for HD. Limits to accuracy included recombination between the DNA markers and the mutation, pedigree structure, and whether DNA samples were available from family members. With direct tests for the HD mutation, we have assessed the accuracy of results obtained by linkage approaches when requested to do so by the test individuals. For six such individuals, there was significant disparity between the tests. Three went from a decreased risk to an increased risk, while in another three the risk was decreased. Knowledge of the potential reasons for these changes in results and impact of these risk reversals on both patients and the counseling team can assist in the development of strategies for the prevention and, where necessary, management of a risk reversal in any predictive testing program.

Adult↗