Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: PHYSIOLOGICAL ACTIONS OF ANGIOTENSIN II MEDIATED BY AT1 AND AT2 RECEPTORS IN THE BRAIN

• 1 Autoradiographic binding studies have shown that the AT₁ receptor is the predominant angiotensin II (AngII) receptor subtype in the central nervous system (CNS). Major sites of AT₁ receptors are the lamina terminalis, hypothalamic paraventricular nucleus, the lateral parabrachial nucleus, rostral and caudal ventrolateral medulla, nucleus of the solitary tract and the intermediolateral cell column of the thoraco-lumbar spinal cord.
• 2 While there are differences between species, AT₂ receptors are found mainly in the cerebellum, inferior olive and locus coeruleus of the rat.
• 3 Circulating AngII acts on AT₁ receptors in the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) to stimulate neurons that may have a role in initiating water drinking.
• 4 Centrally administered AngII may act on AT₁ receptors in the median preoptic nucleus and elsewhere to induce drinking, sodium appetite, a sympathetic vasoconstrictor response and vasopressin secretion.
• 5 Recent evidence shows that centrally administered AT₁ antagonists inhibit dipsogenic, natriuretic, pressor and vasopressin secretory responses to intracerebroventricular infusion of hypertonic saline. This suggests that an angiotensinergic neural pathway has a role in osmoregulatory responses.
• 6 Central angiotensinergic pathways which include neural inputs to the rostral ventrolateral medulla may use AT₁ receptors and play a role in the function of sympathetic pathways maintaining arterial pressure.

     

Correlation of heterogeneous blood flow and fatty acid uptake in the normal dog heart

Summary Blood flow heterogeneity in normal myocardium may be caused by heterogeneous metabolic demand. We studied, from 80 tissue samples of the left ventricle (LV) of eight anesthetised, open-chest dogs (with prior -blockade (metoprolol) in four dogs), the radioactivity of²⁰¹Thalliumchloride (²⁰¹Tl), an indicator of blood flow, and of the fatty acid¹³¹-Iodine-heptadecanoic acid (¹³¹I-HDA), an indicator of metabolic demand, 3 min after intravenous injection. Global LV uptake (in percent of injected dose ×10^–2, per g tissue; mean ±SD) was 4.94±0.71 for²⁰¹Tl and 4.48±0.58 for¹³¹I-HDA in the dogs without -blockade, and 2.08±0.26 and 1.69±0.20, respectively, in dogs with -blockade (p<0.05). Beta-blockade thus decreased the fraction of cardiac output delivered to the LV, concurrently with a decreased heart rate and arterial blood pressure (p<0.05) and, thus, global metabolic demand and fatty acid uptake. Regional radioactivities per gram were normalized for mean LV radioactivities and heterogeneity was expressed as the coefficient of variation (CV). For pooled data (n=320) in dogs without -blockade, regional²⁰¹Tl and¹³¹I-HDA radioactivities varied from a factor of 0.1 to 1.6 and 0.3 to 1.8 of mean radioactivities, with a CV of 22.9 and 19.4%, respectively, and correlated (r=0.77, p<0.005). For pooled data (n=320) in dogs with -blockade, regional²⁰¹Tl and¹³¹I-HDA radioactivities varied from a factor of 0.2 to 1.5 and 0.2 to 1.6 of mean radioactivity and CV was 23.6% and 24.8%, respectively: r=0.92 (p<0.005). The endo/epi ratio for both radioactivities exceeded unity in each dog. In normal myocardium, blood flow and fatty acid uptake are thus heterogeneous, both transmurally and circumferentially, and matched, concomitantly with coupling of global blood flow to global metabolic demand and fatty acid uptake. This supports the idea that heterogeneous myocardial O₂ supply reflects heterogeneous metabolic demand.     

Effects of an information booklet on well-being of hospital patients

Although informational booklets are being used increasingly in Dutch hospitals, little is known of their effects and the conditions for optimal use. Various aspects of the use and effects of a specially developed information booklet were investigated in two surgical wards of a general hospital. The booklet gave information about ward procedures, operative routines, narcosis, and psychosocial care possibilities. Both before and after introduction of the booklet we gathered data on the satisfaction, knowledge, and emotional state of patients on the two wards and their perception of the care climate. Patients on the control ward received just the booklet. On the experimental ward staff nurses were trained in nondirective therapeutic skills, and measurements were repeated on both wards after this intervention. In a third manipulation on the experimental ward, some of the patients had a supportive and informative talk with a trained nurse. Although patients appreciated and read the booklet better than a general hospital leaflet, the results show that the booklet and other supporting measures had no effect on the patients' perception of their well-being.     

Nucleic acid analysis of antibiotic resistance

The past 15 years the field of molecular biology and especially DNA technology has developed rapidly. This did not leave microbiology unaffected. DNA sequencing and the use of DNA probes led to new insights in the evolution and spread of antibiotic resistance genes. It became clear that resistance determinants often show partial homology even when species are not closely related. DNA probes have established their value as epidemiological tools and currently efforts are being made to introduce them into routine diagnostics.     

Gender differences in stage-adjusted bladder cancer survival

OBJECTIVES: Gender differences have been observed in the prognosis of patients with bladder cancer. It has also been suggested that these differences are caused by a worse stage distribution at diagnosis among women. The purpose of this study was to evaluate whether women with bladder cancer have a worse prognosis even after adjustment for disease stage at first presentation. METHODS: Data on patients with bladder cancer diagnosed between 1973 and 1996 and registered by one of the nine population-based Surveillance, Epidemiology, and End Results (SEER) cancer registries in the United States (n = 80,305) were obtained from the National Cancer Institute public domain SEER*Stat 2.0 package. Similar data on patients with bladder cancer diagnosed between 1987 and 1994 and registered by two population-based registries in the Netherlands (n = 1722) were obtained through the Comprehensive Cancer Centers, Amsterdam and South. Survival rates adjusted for mortality owing to other causes (ie, relative survival) were calculated for men and women within each category of the American Joint Committee on Cancer (SEER data) and TNM (Netherlands data) stage groupings.Results. In the United States, the 5-year relative survival rate of male patients with bladder cancer was calculated to be 79.5% (95% confidence interval 79.0% to 80.0%). Among women, the 5-year relative survival rate was significantly worse: 73.1% (95% confidence interval 72.2% to 74.0%). The male versus female 5-year survival rate among stage groups I, II, III, and IV was 96.5% versus 93.7%, 65.5% versus 59.6%, 58.8% versus 49.6%, and 27.1% versus 15.2%, respectively. The (sparser) data from the Netherlands were less conclusive. Women with Stage II and Stage IV disease fared worse than men but the reverse seemed to be true in Stage I disease. CONCLUSIONS: Female patients with bladder cancer have a worse prognosis than male patients. It is unlikely that the difference can explained entirely by the more frequent diagnosis of higher stages at first presentation among women.     

Treatment of localized prostate cancer using a combination of high dose rate Iridium‐192 brachytherapy and external beam irradiation: Initial Australian experience

Combination high dose rate brachytherapy (HDRB) and external beam radiation therapy is technically and clinically feasible as definitive treatment for localized prostate cancer. We report the first large Australian experience using this technique of radiation dose escalation in 82 patients with intermediate‐ and high‐risk disease. With a median follow up of 3 years (156 weeks), complications were low and overall prostate‐specific antigen progression‐free survival was 91% using the American Society for Therapeutic Radiology and Oncology consensus definition. The delivery of hypofractionated radiation through the HDRB component shortens overall treatment time and is both biologically and logistically advantageous. As a radiation boost strategy, HDRB is easy to learn and could be introduced into most facilities with brachytherapy capability.     

Intestinal permeability in kwashiorkor

Intestinal permeability can be assessed non-invasively using the lactulose-rhamnose (L-R) test, which is a reliable measure of small intestinal integrity. AIMS: To determine risk factors for abnormal intestinal permeability in kwashiorkor, and to measure changes in L-R ratios with inpatient rehabilitation. DESIGN: A case-control study of 149 kwashiorkor cases and 45 hospital controls. The L-R test was adapted to study kwashiorkor in Malawi, with testing at weekly intervals during nutritional rehabilitation. Urine sugars were measured by thin layer chromatography in London. RESULTS: The initial geometric mean L-R ratios (x100) (with 95% confidence interval) in kwashiorkor were 17.3 (15.0 to 19.8) compared with 7.0 (5.6 to 8.7) for controls. Normal ratios are < 5, so the high ratios in controls indicate tropical enteropathy syndrome. Abnormal permeability in kwashiorkor was associated with death, oliguria, sepsis, diarrhoea, wasting and young age. Diarrhoea and death were associated with both decreased L-rhamnose absorption (diminished absorptive surface area) and increased lactulose permeation (impaired barrier function) whereas nutritional wasting affected only L-rhamnose absorption. Despite, clinical recovery, mean L-R ratios improved little on treatment, with mean weekly ratios of 16.3 (14.0 to 19.0), 13.3 (11.1 to 15.9) and 14.4 (11.0 to 18.8). CONCLUSION: Abnormal intestinal permeability in kwashiorkor correlates with disease severity, and improves only slowly with nutritional rehabilitation.