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Biomedical subjects

J Potter

Publications and source records attributed to J Potter.

At least 19 recordsLinked to original sources
PubMed1997

Energy balance and colon cancer--beyond physical activity.

Low levels of physical activity and high levels of energy intake and body mass have all been directly associated with colon cancer. The purpose of this study was to determine how physical inactivity interacts with other components of energy balance (energy intake and body mass) in determining colon cancer risk. Data were obtained from 2073 first primary cases of colon cancer and 2466 age- and sex-matched controls identified from 8 counties in Utah, the Northern California Kaiser Permanente Medical Care Program, and the Twin Cities metropolitan area in Minnesota. Recent and lifetime physical activity was assessed by intensity of activities performed at home, leisure, and at work; energy intake was estimated from an extensive diet history questionnaire; and body mass index (BMI) was calculated from measured height at the time of interview and reported weight for the referent year. For both men and women, lack of lifetime vigorous leisure-time activity was associated with increased risk of colon cancer [odds ratio (OR), 1.63 and 95% confidence interval (CI), 1.26-2.12 for men and OR, 1.59 and 95% CI, 1.21-2.10 for women, comparing the lowest to highest level of activity]. There were no differences in risk associated with physical activity by tumor site within the colon or by age at diagnosis. High levels of energy intake were also associated with increased risk of colon cancer in men and women (OR, 1.74 and 95% CI, 1.14-2.67 for men and OR, 1.70 and 95% CI, 1.07-2.70 for women). A large BMI was more associated with increased risk in men (OR, 1.94 and 95% CI, 1.49-2.54) than in women (OR, 1.45 and 95% CI, 1.08-1.94). Those at greatest risk of colon cancer were those who had the most unfavorable energy balance in that they were physically inactive, had high energy intakes, and had a large BMI (OR, 3.35 and 95% CI, 2.09-5.35). However, when physical activity was high, having a high energy intake and large BMI resulted in a nonsignificant increased colon cancer risk (OR, 1.28 and 95% CI, 0.81-2.03). This pattern was consistent between the sexes, but there was some evidence that men may be at higher risk than women, especially older women, as a result of unfavorable energy balance. These results support previous findings that physical inactivity, high energy intake, and large body mass are associated with increased risk of developing colon cancer. However, energy balance as a whole seems to be associated with risk of colon cancer. These findings suggest systemic metabolic influences on carcinogenesis and have important implications for prevention.

Adult↗
PubMed1997

Influenza vaccination of health care workers in long-term-care hospitals reduces the mortality of elderly patients.

Vaccination of health care workers (HCWs) is recommended as a strategy for preventing influenza in elderly patients in long-term care. However, there have been no controlled studies to show whether this approach is effective. During the winter of 1994-1995, 1059 patients in 12 geriatric medical long-term-care sites, randomized for vaccination of HCWs, were studied. In hospitals where HCWs were offered vaccination, 653 (61%) of 1078 were vaccinated. Vaccination of HCWs was associated with reductions in total patient mortality from 17% to 10% (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.40-0.80) and in influenza-like illness (OR, 0.57; 95% CI, 0.34-0.94). Vaccination of patients was not associated with significant effects on mortality (OR, 1.15; 95% CI, 0.81-1.64). Results of this study support recommendations for vaccination against influenza of HCWs in long-term geriatric care. Vaccination of frail elderly long-term-care patients may not give clinically worthwhile benefits.

Aged↗
PubMed1996

The tumor suppressor gene Brca1 is required for embryonic cellular proliferation in the mouse.

Mutations of the BRCA1 gone in humans are associated with predisposition to breast and ovarian cancers. We show here that Brca1+/- mice are normal and fertile and lack tumors by age eleven months. Homozygous Brca1(5-6) mutant mice die before day 7.5 of embryogenesis. Mutant embryos are poorly developed, with no evidence of mesoderm formation. The extraembryonic region is abnormal, but aggregation with wild-type tetraploid embryos does not rescue the lethality. In vivo, mutant embryos do not exhibit increased apoptosis but show reduced cell proliferation accompanied by decreased expression of cyclin E and mdm-2, a regulator of p53 activity. The expression of cyclin-dependent kinase inhibitor p21 is dramatically increased in the mutant embryos. Buttressing these in vivo observations is the fact that mutant blastocyst growth is grossly impaired in vitro. Thus, the death of Brca1(5-6) mutant embryos prior to gastrulation may be due to a failure of the proliferative burst required for the development of the different germ layers.

Alternative Splicing↗
PubMed1996

Fibromyalgia and work disability: Is Fibromyalgia a disabling disorder?

Fibromyalgia appears to be an increasingly important source of disability claims and payments. Twenty-five percent of patients seen in rheumatology clinics have received disability payments. Yet fibromyalgia is a clinical rather than a legal construct, and there remain very important limitations regarding the reliability and validity of diagnosis and severity assessments outside of the clinic and in the medicolegal setting. Even so, preparation of disability assessments that cover key requirements can provide substantial assistance to disability adjudicators.

Disability Evaluation↗
PubMed1996

Improvement of debilitating tardive dyskinesia with risperidone.

This case vignette illustrates dramatic improvement of tardive dyskinesia (TD) in an elderly female with a long history of neuroleptic exposure, following treatment with low-dose risperidone. The TD continued to be in remission at 1-year follow-up. This observation calls for well-designed randomized studies to evaluate the efficacy of risperidone in treating TD.

Aged↗
PubMed1996

The quantitation of metabolites of quercetin flavonols in human urine.

The flavonoid quercetin, or its metabolites, inhibit chemical carcinogenesis in rodents and may have a role in the prevention of human cancers. Quercetin exposure in human populations results from the dietary intake of various plant foods; high concentrations of quercetin are found in apples, onions, tea, and red wine. Determination of the relationship between dietary intake and cancer risk depends on the characterization of quercetin intake. The development and use of biomarkers for quercetin intake may provide a basis for the objective classification of this exposure. One possible biomarker is metabolic products of quercetin. We report the development of a high-performance liquid chromatography (HPLC)-based assay for quantitation of quercetin metabolites in human urine. The metabolites include 3,4-dihydroxyphenylacetic acid (homoprotocatechuic acid), metahydroxyphenylacetic acid, and 4-hydroxy-3-methoxyphenylacetic acid (homovanillic acid). The assay has only two major steps, ether extraction and HPLC analysis, and is suitable for analysis of large sample numbers. Analytical characteristics of the assay include a sensitivity of less than 1 microgram, precision with coefficients of variation < 10%, and metabolite recoveries > 90%. The mean concentrations of 3,4-dihydroxyphenylacetic acid, metahydroxyphenylacetic acid, and homovanillic acid in two human urine samples are approximately 0.7, 4.8, and 2.8 micrograms/ml, respectively. The identification of each metabolite is confirmed by HPLC, UV absorbance scans, and gas chromatography-mass spectrometry analysis. These results verify the occurrence of quercetin metabolites in human urine and the feasibility of quercetin metabolite quantitation, by the assay described herein, for epidemiological studies. Development of the analytical procedure is an essential first step for validation of the metabolites as biomarkers of quercetin intake.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Spontaneous resistance to acute T-cell leukaemias in TCRV gamma 1.1J gamma 4C gamma 4 transgenic mice.

The concept of tumour surveillance implies that specific and non-specific components of the immune system eliminate tumours in the early phase of malignancy. The immunological mechanisms that control growth of preneoplastic cells are, however, not known. T cells expressing gamma delta T-cell receptors (TCR) were first described as lymphocytes with reactivity against various tumour cells, which suggests that gamma delta T cells could mediate tumour surveillance. Here we show that TCRV gamma 1.1J gamma 4C gamma 4 transgenic mice are spontaneously resistant to acute T-cell leukaemias but cannot reject non-haematopoietic tumours. TCRV gamma 1.1J gamma 4C gamma 4+ hybridomas isolated from these mice react in vitro against almost all haematopoietic tumour cell lines tested. Recognition of tumour cells depends on the gamma delta TCR but is independent of major histocompatibility complex (MHC) class I, MHC class II, or TAP-2 peptide transporter expression. Ligand recognition is influenced by the murine Nromp gene, which confers resistance or susceptibility to tuberculosis, lepra and leishmaniasis. These data indicate that TCRV gamma 1.1+ T cells confer spontaneous immunity against haematopoietic tumours in vivo and link innate resistance to bacterial infections with tissue-specific tumour surveillance by gamma delta+ T cells.

3T3 Cells↗
PubMed1995

Changes in the sweatspot test with ageing and relation to cardiovascular autonomic function.

The sweatspot test assesses the local sweat response to an intradermal injection of acetylcholine. It has been reported as a more sensitive indicator of autonomic dysfunction in important diabetic men than either pupillary or cardiovascular tests, and has been used to establish the presence of autonomic dysfunction in patients with idiopathic chronic constipation. However, the usefulness of this test as a simple and quick method of diagnosing autonomic dysfunction in an elderly population has not been established. This is important given the high prevalence of reduced autonomic function with ageing and hypertension. We compared the age-associated responses in the sweatspot test and its relation to cardiovascular autonomic function in elderly normotensive and hypertensive subjects. We studied eleven normotensive and 24 untreated hypertensive elderly subjects (mean age 75.7 years, range 63-85) and compared the results of the sweatspot test to a young control group (n = 11, mean age 32.0 years, range 25-41), and to a standard battery of cardiovascular autonomic function tests. The median sweatspot score was significantly lower in the elderly compared with young subjects (1.9 vs. 12.0, p < 0.0001) although there was no difference between elderly normotensive and hypertensive subjects (1.6 vs. 2.4, p = 0.8). No correlation was demonstrated between the median sweatspot score and the number of abnormal cardiovascular tests. The sweatspot test was grossly abnormal in all elderly subjects and was not correlated to changes in cardiovascular autonomic function. Its diagnostic use in the elderly is therefore of very limited value.

Acetylcholine↗
PubMed1995

Energy intake and expenditure in elderly patients admitted to hospital with acute illness.

Studies on hospitalized elderly subjects have demonstrated that negative energy balance is common during hospitalization, but have concentrated primarily on long-stay and psychogeriatric patients. There is little information on energy balance in elderly patients admitted with acute illness from the community, despite the importance of this patient group and the presence of a number of factors likely to predispose such patients to negative energy balance. In the present study energy balance was quantified in twenty patients (eight males, mean age 82 (SD 5) years; twelve females, mean age 84 (SD 6) years) admitted from the community with acute illness, and predicted basal metabolic rate (BMR) was compared with measured resting metabolic rate (RMR). Most patients were in negative energy balance during hospitalization, and median measured energy intake (EI): measured RMR ratio was 1.0 (range 0.7-1.8). The mean difference between measured EI and estimated total energy expenditure was -1.3 MJ/d (range -3.4 to +2.5 MJ/d). Estimated total energy expenditure exceeded measured EI in fifteen of the patients and there was a significant decline in mid-arm muscle circumference (paired t, P < 0.05) during hospitalization. We conclude that moderate negative energy balance is common in this patient group, and that these patients are at risk of undernutrition during their hospital stay.

Acute Disease↗
PubMed1995

The nutritional status and clinical course of acute admissions to a geriatric unit.

Undernutrition of long-stay hospital patients and those in surgical units is well documented. This study was designed to determine the extent of the problem in elderly people admitted to hospital with acute medical problems and to assess the relationship between nutritional status and course of hospital stay. Sixty-nine patients underwent a nutritional assessment on admission and at intervals throughout their hospital stay and episodes of sepsis were documented. Severely malnourished patients were identified using body mass index, BMI (22%) and corrected arm muscle area, CAMA (26%). Episodes of sepsis occurred significantly more often in the severely undernourished group (p < 0.04). The median length of stay of the group was 16 days (range 2-113): during this time there was no significant change in markers of nutritional status apart from actual muscle circumference (AMC), which showed a reduction in measurement between admission and discharge which was statistically significant (p < 0.0003). This study indicated that severe malnutrition is common in elderly medical admissions, and that it is associated with an increased risk of sepsis. Additional nutritional depletion may occur during hospital stay, and is not easily recognized unless anthropometry is undertaken.

Aged↗
PubMed1995

The influence of anesthetic agents on rat hepatic cytochromes P450 in vivo.

The objective of this study was to identify which anesthetics when used acutely will affect cytochrome P450 (CYP) activity in male Sprague-Dawley rats in vivo. The anesthetics tested were fentanyl citrate, alpha-chloralose, ketamine, urethane (ethyl carbamate), halothane, and ether. CO2 anesthesia was used as the control comparator. Theophylline was used as a probe for CYP1A activity, phenobarbital for CYP2B/2C, flecainide for CYP2D1, and ethosuximide for CYP3A activity. All probes were administered via tail vein injection after anesthetic-induced loss of the righting reflex. Single sample probe clearances were estimated, and used as an index of CYP activity. Fentanyl citrate, alpha-chloralose, halothane, and ether did not have statistically significant effects on any of the CYP activities. Ketamine did not significantly affect CYP1 or CYP2B/2C activity. However, it decreased the clearance of flecainide (i.e. CYP2D1 activity) by 13.4% (p < 0.001) and the clearance of ethosuximide (i.e. CYP3A activity) by 17.6% (p < 0.0001). Urethane increased the clearance of theophylline by 91.5% (p < 0.0001), and decreased the clearance of ethosuximide by 40.5% (p < 0.0001) though it did not affect CYP2B/2C or CYP2D1 activities significantly. From this data, we conclude that a single dose of ketamine mildly inhibits the activity of CYP2D1 and CYP3A, and a single dose of urethane strongly inhibits CYP3A but increases CYP1A activity.

Analysis of Variance↗
PubMed1995

What method should be used to define 'night' when assessing diurnal systolic blood pressure variation in the elderly?

Diurnal blood pressure (BP) variation can be assessed by cusums-derived measures and by the day-night BP difference from time-, activity- and diary-defined 'night' periods. Reproducibility of diurnal systolic BP (SBP) variation by these different methods was studied in 19 active elderly normotensives, mean age 68.5 years. Subjects underwent simultaneous 24 h BP (Spacelabs 90207) and activity (Gaehwiler wrist actigraph) monitoring on two occasions (median interval 70 days). On the first occasion, mean diurnal SBP variation was 15.1 +/- 8.1 mm Hg by fixed-time definition of 'night' (22.07). When compared with 22-07 defined 'night' period, actigraph- and diary-defined 'night-time' was significantly reduced (-60 +/- 49, and -48 +/- 51 min, respectively) and consequently diurnal SBP variation was significantly greater at 18.2 +/- 8.1 mm Hg and 17.6 +/- 8.4 mm Hg, respectively. Actigraph recordings were also used to exclude 'night' BP readings associated with activity, but this did not significantly alter the diurnal SBP variation. Cusums-derived circadian alteration magnitude resulted in the greatest value for SBP variation (23.4 +/- 6.7 mm Hg). However, reproducibility of diurnal SBP variation was poor by fixed-time method with a coefficient of variation (CV) of > 50%, and only improved to 40% with diary use. Actigraph measurements, even if used to exclude BP values associated with disturbed sleep, did not improve this further. Cusums-derived measures of diurnal variation slightly improved reproducibility with a CV of 34.6% and may be a better method in the assessment of diurnal BP variation in the elderly.

Aged↗
PubMed1994

Primary cutaneous infection by Aspergillus ustus in a 62-year-old liver transplant recipient.

We report the first case of primary cutaneous aspergillosis caused by Aspergillus ustus, a species that seldom infects human beings. The patient, a 62-year-old liver transplant recipient with end-stage hepatitis C-induced cirrhosis, was receiving the experimental immunosuppressive drug FK-506. Trauma to the skin of the right arm from tape and from an arm board holding intravenous and intraarterial catheters in place and to the left leg from an occlusive knee brace may have contributed to this unusual mycosis. The patient's cutaneous aspergillosis responded to a combination of intravenous amphotericin B and topical terbinafine cream. Although the patient died shortly thereafter from hepatic failure, there was no evidence of systemic aspergillosis.

Aspergillosis↗
PubMed1994

The acute effects of a single dopamine infusion in elderly patients with congestive cardiac failure.

1. Dopamine (DA) at low doses (2.5 micrograms kg-1 min-1) produces a measurable increase in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in young healthy subjects and has a therapeutic effect in younger patients with congestive cardiac failure (CCF). In elderly healthy subjects, DA increases ERPF but does not increase GFR in all subjects. 2. To determine the potential therapeutic use of DA in elderly subjects with CCF, we studied 17 patients (5 male) aged 79.9 years (range 68 to 93 years) admitted to hospital for inpatient treatment of CCF resistant to diuretic and angiotensin converting enzyme inhibitor therapy. The effects of a single infusion DA at 2.5 micrograms kg-1 min-1 on GFR and ERPF were assessed in a double-blind, placebo controlled prospective study. 3. There were no significant differences in GFR or ERPF between control and DA. A reduction in GFR was seen in some patients. 4. DA at low dosage was not shown to benefit elderly patients with resistant CCF, and in some patients was detrimental. Higher doses or a combination with other inotropes may be necessary for a renal effect in elderly patients.

Aged↗
PubMed1994

The Hypertension in the Very Elderly Trial (HYVET). Rationale, methodology and comparison with previous trials.

The Hypertension in the Very Elderly Trial (HYVET) is a multicentre, open, randomised, controlled trial. The aim of this trial is to investigate the effect of active treatment on stroke incidence in hypertensive patients over the age of 80 years. Secondary end-points include total cardiovascular mortality and morbidity. Entry criteria include a sustained sitting systolic blood pressure of 160 to 219mm Hg plus a sustained sitting diastolic pressure of 95 to 109mm Hg. Also required is a standing systolic blood pressure of at least 140mm Hg. Patients must give their informed consent, and be free of congestive heart failure requiring treatment, gout, renal failure or a recent cerebral haemorrhage. Patients are to be randomised to 3 groups-(i) no treatment; (ii) treatment with a diuretic [bendroflumethiazide (bendrofluazide)]; or (iii) treatment with an angiotensin converting enzyme (ACE) inhibitor (lisinopril). Starting dosage for bendroflumethiazide and lisinopril is 2.5 mg/day. In order to achieve goal sitting systolic and diastolic blood pressures (< 150/80 mm Hg), a doubling of the dosage is allowed. Furthermore, slow release diltiazem (120 mg/day increasing to 240 mg/day if required) may be added to the medication of the actively treated groups. These drugs have been chosen as inexpensive and appropriate representatives of their therapeutic classes. 700 patients in each group (a total of 2100) will be sufficient to detect a 40% difference in cerebrovascular events between no treatment and active treatment (alpha = 0.01, 1-beta = 0.90). These numbers will also detect a difference in total mortality of 25% and in cardiovascular mortality of 35%. The pilot phase of the trial has been started with support from the British Heart Foundation. Centres which are interested in taking part should contact C.J. Bulpitt or any of the other authors.

Aged↗