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.

     

Effectiveness of methyl-GAG (methylglyoxal-bis[guanylhydrazone]) in patients with advanced malignant lymphoma

We treated 51 patients with advanced malignant lymphoma refractory to conventional therapy with methyl-glyoxal-bis(guanylhydrazone) (methyl- GAG) at doses ranging from 400 to 800 mg/sq m. Therapy was started on a weekly schedule and was switched to every other week in responding patients at the onset of toxicity. Partial responses were observed in 6 of 13 evaluable patients with Hodgkin's disease (46%), 5 of 10 patients with diffuse poorly differentiated lymphocytic lymphoma (50%), 2 of 4 patients with nodular poorly differentiated lymphocytic lymphoma (50%), and 3 of 13 patients with diffuse histiocytic lymphoma (23%). Two of six patients with mycosis fungoides showed objective improvement in cutaneous disease. Toxicity was generally mild and included muscular weakness, myalgia, mucositis, and diarrhea; two patients developed bronchospasm following drug infusions. We conclude that methyl-GAG has major antitumor activity when administered on this schedule to patients with advanced malignant lymphoma. The low degree of toxicity, unique mechanism of action, and minimal myelosuppressive effects suggest that methyl-GAG will prove useful in future trials of combination chemotherapy regimens for the treatment of lymphoma.     

Artifacts seen during CT pelvimetry: implications for digital systems with scanning beams

During computed tomography (CT) pelvimetry of two pregnant women, bony abnormalities of the fetuses were noted on the scout images that were not confirmed at delivery. To explore the cause of these artifacts, specimen long bones were manipulated in various ways during CT scout imaging. Artifacts like those seen during in vivo imaging were found to be caused by motion of the object. The CT scout view is an example of an image produced by a digital system that uses a scanning beam. This type of digital system is being used for several types of body imaging including screening for scoliosis and chest radiography. Attention to motion artifacts should decrease diagnostic errors and aid further development of these systems.     

Extracorporeal shock wave lithotripsy performed on woman with a cardiac pacemaker

A 73-year-old woman with a sick sinus syndrome and a 3-year-old ventricular demand pacemaker underwent extracorporeal shock wave lithotripsy without incident. There was no damage or malfunction of the pacemaker during or acutely after this therapy. The lithotriptor had no difficulty in sensing all paced or spontaneous ventricular complexes.     

Analgesic nephropathy

Many questions about analgesic nephropathy (AN) lack clear-cut answers. We present available evidence for and against proposed answers to many of these questions. These include: (1) Is acetaminophen (AC) nephrotoxic when taken as the sole analgesic? (2) Is the combination of acetylsalicylic acid (ASA) and AC more nephrotoxic than AC taken alone, and if so, why? (3) What are the minimum doses and durations of ingestion required to produce analgesic nephrotoxicity? (4) Is the combination of ASA and AC (a major metabolite of phenacetin) less nephrotoxic than that of phenacetin and ASA combined? (5) Does caffeine in combination with analgesics contribute to nephrotoxicity? (6) What is the incidence of end-stage renal disease (ESRD) due to AN? (7) What uniform diagnostic criteria should be established for AN? (8) What are the earliest anatomic and biochemical abnormalities? (9) What are the mechanisms of renal injury? (10) Does AC cause uroepithelial neoplasia? (11) What research might be most beneficial? Based mainly on associations, some strong, we suggest that AN still exists as a cause of ESRD in the United States, where AC/ASA combinations are available over the counter, and in Canada, where they are not. We also suggest that the evidence needed to recommend that the AC/ASA combination be excluded from over-the-counter analgesic preparations still has limitations. A prospective multicenter study comparing incidence related to AC/ASA in the United States and to AC in Canada and the United States may be needed to answer this question. For such a study to be worthwhile, an adequate incidence in both countries is required.     

Radiologic diagnosis of oat cell cancer in a high-risk screened population

A screening program of 10,040 cigarette-smoking men over 45 years of age was undertaken in an attempt to achieve earlier diagnosis, thereby increasing the cure rate, of oat cell lung cancer. Of the 155 men who were found to have lung cancer, 27 (17%) had confirmed oat cell cancer. Only one case was diagnosed at the first examination. The other 26 cases (called incidence cancer) were diagnosed by subsequent examinations. In 24 of the 26 patients, the tumor was not found until it was advanced (Stage III), and of these patients, only one is alive at 21 months follow-up. Two tumors were diagnosed as oat cell carcinoma at an early stage (Stage I), and both patients are alive with no evidence of disease at seven and 24 months. The screening program used in this study did not succeed in detecting oat cell cancer at an early stage.