The Effects of Angiotensin II on Renal Water and Electrolyte Excretion in Normal and Caval Dogs.

The effects of intravenous administration of angiotensin II on renal water and electrolyte excretion were examined during hydropenia, water diuresis, and hypotonic saline diuresis in anesthetized normal dogs and dogs with thoracic inferior vena cava constriction and ascites (caval dogs). The effects of unilateral renal artery infusion of a subpressor dose were also examined.During hydropenia angiotensin produced a decrease in tubular sodium reabsorption, with a considerably greater natriuresis in caval dogs, and associated with a decrease in free water reabsorption (T(c) (H(2)O)). Water and hypotonic saline diuresis resulted in an augmented angiotensin natriuresis, with a greater effect still observed in caval dogs. In these experiments free water excretion (C(H(2)O)) was limited to 8-10% of the glomerular filtration rate (GFR), although distal sodium load increased in every instance. In the renal artery infusion experiments a significant ipsilateral decrease in tubular sodium reabsorption was induced, particularly in caval dogs.These findings indicate that angiotensin has a direct effect on renal sodium reabsorption unrelated to a systemic circulatory alteration. The attenuation or prevention of the falls in GFR and effective renal plasma flow (ERPF) usually induced by angiotensin may partially account for the greater natriuretic response in caval dogs and the augmentation during water or hypotonic saline diuresis. However, a correlation between renal hemodynamics and the degree of natriuresis induced was not always present and, furthermore, GFR and ERPF decreased significantly during the intrarenal artery infusion experiments. Therefore, the present experiments indicate that another mechanism is operative in the control of the angiotensin natriuresis and suggest that alterations in intrarenal hemodynamics may play a role.The decrease in T(c) (H(2)O) and the apparent limitation of C(H(2)O) associated with an increase in distal sodium load localize the site of action of angiotensin to the ascending limb of Henle's loop and the proximal tubule.

Intrarenal distribution of blood flow in the transplanted dog kidney: effect of denervation and rejection.

Serial measurements of intrarenal distribution of blood flow have been recorded in anesthetized dogs with the (133)xenon "washout" technique. The results showed that normal kidneys redistributed their blood flow after laparotomy and mobilization of the kidney. This alteration consisted of a diminution in percentage of total renal blood flow supplied to the fastest flowing component, and a diminution of renal mass supplied by that component. This effect lasted for as long as 7 days. Thereafter, the blood flow distribution remained stable. Autotransplanted kidneys had a stable distribution of blood flow between 0 and 77 days after operation, the values being identical with the stable normal kidney. Homotransplanted kidneys had the same intrarenal distribution of blood flow after operation as the autotransplanted kidneys. Whereas the intrarenal distribution of blood flow of the autotransplanted kidneys remained stable, a redistribution occurred in the homotransplanted kidneys as rejection progressed. This phenomenon occurred before marked elevation of blood urea nitrogen. The redistribution was due to a decrease in percentage of blood flow supplied to the fastest flowing component, and a relative reduction of tissue mass perfused by this component. Radioautography of the kidneys before rejection demonstrated that the cortex was homogeneously perfused by the fastest flowing component of blood flow. As rejection progressed, a reduced area of cortex was perfused by this component. Terminally, the fastest flowing component was located in the outer medulla. It is suggested that the reduction in cortical blood flow produced by immunological mechanisms may play a prominent role in the ensuing renal failure.

Hemodialysis of acute arsenic intoxication with transient renal failure.

A striking reduction in serum arsenic level was achieved after four hours of hemodialysis in a patient with acute arsenic intoxication and transient renal failure. Quantitative dialysance of arsenic and a comparison of daily urinary excretion of arsenic with amount removed by dialysis suggested that hemodialysis is indicated in the treatment of acute arsenic intoxication if there is concomitant renal failure. In the presence of normal renal function, supportive measures, including dimercaprol (BAL in Oil) therapy, constitute the best available treatment.

Nephrotoxicity of paraquat in man.

Renal function studies were performed in three cases of paraquat poisoning. Acute renal failure was observed in all three cases. Glomerular filtration rate improved for two patients who survived three weeks, illustrating the reversible nature of paraquat-induced acute renal failure. A mild to moderate transient proteinuria was observed during the first and second weeks following paraquat ingestion. Renal glucosuria, marked amino aciduria, and increased fractional excretion of phosphorus, sodium, and uric acid were observed. These findings, which have not been previously described in man, are indicative of proximal tubular dysfunction and parallel observations previously made in experimental animals.

Degree of heterogeneity of binding specificities of antibodies to the phenylarsonate group that share a common idiotype.

We have investigated the microheterogeneity of hybridoma products (HP) expressing the major idiotype (CRIA) associated with A/J antibodies to the p-azophenylarsonate (Ar) hapten group. The properties investigated were affinity for a phenylarsonate derivative and the fine specificity of the combining sites of the various HP. The fine specificity was approached by measuring relative affinities for a series of related haptens. It was found that, although variations exist, there are strong similarities in affinities and fine specificities of the antigen-binding sites of CRI+A HP. The range of affinities for (p-azobenzenearsonic acid)-N-3H-acetyl-L-tyrosine was 0.41 x 10(6)-2.2 x 10(6) M-1. In all cases the addition of a second ring structure (benzene or histidine) and an azo group greatly increased the binding affinity. Some differences in fine specificity among the HP were seen with respect to affinities for o-arsanilate or the arsanilate derivative of histidine. However, the two HP which are the strongest inhibitors in the conventional assay for CRIA were virtually identical to one another and to induced A/J anti-Ar antibodies in their fine specificities. Together with previous data on amino acid sequences and serological properties, the results indicate that, despite their microheterogeneity, members of the CRIA family are closely related in structure and hapten-binding specificity.

Redistribution of Renal Blood Flow in Haemorrhagic Hypotension Role of Renal Nerves and Circulating Catecholamines* *.

Haemorrhagic hypotension (HH) causes a redistribution of intrarenal blood flow characterized by a patchy cortical hypoperfusion. Previous studies indicated that the sYmpathoadrenergic system is mainly responsible for these redistribution processes. The relative role of renal nerves and of circulating catecholamines was studied in the present experiments. Intrarenal haemodynamics were analysed by means of the 133 Xenon washout technique and 83 Krypton autoradiographics. 8 autotransplanted (and, therefore, chronically denervated) kidneys showed the same typical response to severe and prolonged HH as 11 normal control organs. In 2 additional dogs, the intrarenal distribution of blood flow (IDBF) and local blood flow rates (Fi ) of an acutely denervated kidney before and during HH did not show any differences as compared with the contralateral control organ. It is concluded that the patchy cortical hypoperfusion observed in the dog during severe haemorrhagic hypotension does not depend on an intact innervation of the kidney, but that it is mainly mediated by circulating catecholamines.

Compression neuropathy subsequent to renal transplantation.

Compression neuropathy occurred in 7 patients who underwent renal transplantation. The neuropathy occurred on the same side as the surgery and was associated with the use of selfretaining retractors. Other contributing factors were presence and degree of uremia and diabetes. We suggest that self-retaining retractors be used carefully and length of application reduced to a minimum. Efficient dialysis prior to transplantation may decrease the incidence and severity of neurologic deficit by reducing the extent of uremia.

Transdermal fentanyl: seeding trial in patients with chronic cancer pain.

In this study, 6 patients with pain from advanced cancer were enrolled in a multicenter, open-label seeding trial of transdermal fentanyl. Following equianalgesic dose conversion, transdermal fentanyl patches were applied every 3 days. Mean fentanyl dosage doubled by week 2 and tripled by week 4. Pain control improved in all patients. There were no significant changes in mood, constipation, nausea, sedation, daily activities, or interpersonal relationships from pretrial to posttrial analyses. Following the study period, 5 patients were monitored for a mean total of 55 days with a mean final fentanyl dose of 240 micrograms/hr. As part of a comprehensive cancer pain management program, transdermal fentanyl appears to be safe and effective, and should prove to be a useful addition to currently available opioid analgesics.

Achieving and sustaining full employment.

Human rights and public health considerations provide strong support for policies that maximize employment. Ample historical and conceptual evidence supports the feasibility of full employment policies. New factors affecting the labor force, the rate of technological change, and the globalization of economic activity require appropriate policies--international as well as national--but do not invalidate the ability of modern states to apply the measures needed. Among these the most important include: (I) systematic reduction in working time with no loss of income, (2) active labor market policies, (3) use of fiscal and monetary measures to sustain the needed level of aggregate demand, (4) restoration of equal bargaining power between labor and capital, (5) social investment in neglected and outmoded infrastructure, (6) accountability of corporations for decisions to shift or reduce capital investment, (7) major reductions in military spending, to be replaced by socially needed and economically productive expenditures, (8) direct public sector job creation, (9) reform of monetary policy to restore emphasis on minimizing unemployment and promoting full employment. None are without precedent in modern economies. The obstacles are ideological and political. To overcome them will require intellectual clarity and effective advocacy.

Supportive care in oncology.

Pain management, nutritional support, and psychosocial support are fundamental services that enhance patients' ability to cope with their cancer and its therapy. The common goal of symptom prevention mandates that each of these supportive services be provided to all patients throughout their cancer experience. Comprehensive cancer pain management begins with identifying the origin of all of the patient's pains and treating each one specifically. Pain prevention can be achieved through around-the-clock opioid administration with as-needed supplements for breakthrough pain and dose titration. Common narcotic side effects such as constipation and nausea also must be prevented. Successful opioid analgesia requires that patient and family concerns regarding addiction and tolerance be dispelled at the outset. Cancer pain prevention can be further optimized with the use of appropriate coanalgesics in response to the pathophysiology of the patient's pains. Cognitive and behavioral therapies may also be useful adjuncts to reduce both pain and suffering. Procedure-oriented pain control should be considered when systemic pharmacologic therapy does not provide adequate pain relief or is associated with intolerable side effects. The only absolute contraindications for pain-relieving procedures are untreatable coagulopathy and a decrease in mental status not related to medical pain management. Useful neurodestructive techniques include radiofrequency lesioning, cryoanalgesia, and chemical neurolysis with agents such as phenol, alcohol, and hypertonic saline. The most beneficial pain-relieving procedures and percutaneous cordotomy, spinal narcotics, celiac and hypogastric plexus ablation, spinal neurolysis, and epidural injection of steroids and hypertonic saline. Procedure selection depends on the cause of the pain and the patient's prognosis. Common indications for pain-relieving procedures include unilateral pain below the shoulder, upper abdominal visceral pains, pelvic visceral pain, perineal pain, vertebral body metastasis, discogenic pain, and spinal stenosis. As results of well-conducted scientific trials begin to appear in the literature, the indications for these procedures will be better understood, resulting in their more appropriate use. Principles of nutritional support in patients with cancer include an awareness of the problem of malnutrition and its impact on performance status, quality of life, prognosis, and treatment; identification of those patients at risk; prophylactic versus therapeutic intervention; and analysis and management of the specific impediment(s) to adequate nutrient intake and absorption. The primary goals for nutritional support in cancer patients are prevention of weight loss and maintenance of adequate protein status. Appreciation of practical issues of nutritional support will enable the practicing physician to achieve these goals using primarily oral nutrition options.(ABSTRACT TRUNCATED AT 400 WORDS)

Use of expanded polytetrafluoroethylene grafts for vascular access in hemodialysis: laboratory and clinical evaluation.

Vascular access for chronic hemodialysis has evolved considerably over the past 10 years with development of vascular substitutes. The bovine heterograft is the choice of most dialysis centers when a subcutaneous conduit is needed in lieu of an in situ arteriovenous fistula. Bovine grafts have solved some problems, but further improvement in blood access prostheses is needed. Polytetrafluoroethylene (PTFE) grafts were evaluated in a laboratory and clinical study. In animals, PTFE proved to be satisfactory for fistula construction based on patency, incorporation into tissue, and ease of puncture. Ten patients underwent 11 vascular access procedures using PTFE grafts as a conduit. There were no technical operative complications. One graft was occluded by extravasation during dialysis and flow could not be restored. Otherwise, all grafts are patent 9 to 18 months postoperatively. Grafts of 8.0 mm in diameter have not given desirable flow rates, whereas 6.0 mm grafts have. Prolonged bleeding from puncture has been a problem in some cases. Otherwise, PTFE appears to be a satisfactory conduit for hemodialysis vascular access.

Preparation of pentachlorophenol derivatives and development of a microparticle-based on-site immunoassay for the detection of PCP in soil samples.

Pentachlorophenol (PCP) is used as a herbicide in agriculture and as an insecticide for termite control. Because of the apparent hazard associated with its usage, there is a need for an efficient and economic on-site screening method. A 5-min on-site test has been developed for the detection of PCP based on the OnTrak format, a successful Roche on-site test format for drugs of abuse, utilizing the principle of latex agglutination immunoassay. The test detects 1 ppm of PCP in soil samples.

Chronic post thoracotomy pain.

Chronic post-thoracotomy pain (CPP) is a vexing clinical problem whose management has received scant attention. In order to identify the risk factors associated with CPP and determine the optimal treatment, the records of 238 consecutive patients who underwent thoracotomy were reviewed. CPP was defined as discomfort requiring the regular administration of analgesics that continued more than three months following surgery. CPP was present in 25 (11%) patients: 10/20 (50%) chest wall resections, 5/25 (20%) pleurectomies, 10/193 (5%) pulmonary resections. Among the 23 patients who required preoperative narcotics, 12 (52%) developed CPP. Improved pain control and decreased narcotic use was achieved via the administration of nonsteroidal anti-inflammatory medication and tricyclic anti-depressants. In addition, 10/25 patients required 11 pain procedures: trigger-point injection, intercostal blocks, injections of epidural steroids, stellate ganglion block. Recurrent pain occurred in 20 patients following initial control. All were found to have tumor regrowth. We conclude that CPP occurs more commonly following chest-wall resection and pleurectomy, and that preoperative narcotic use is a predictor of CPP. Worsening pain following initial relief should prompt a vigorous search for recurrent cancer.