Neurogenic disorders of osmoregulation

The osmolality of body fluids is normally maintained within a narrow range. This constancy is achieved largely via hypothalamic osmoreceptors that regulate thirst and arginine vasopressin, the antidiuretic hormone (ADH). Anything that interferes with the full expression of either osmoregulatory function exposes the patient to the hazards of abnormal increases or decreases in plasma osmolality. Hyposmolarity is almost always due to a defect in water excretion. Increased intake may contribute to the problem but is rarely, if ever, a sufficient cause. Impaired water excretion can be due to a primary defect in the osmoregulation of ADH (inappropriate antidiuresis) or secondary to nonosmotic stimuli like hypovolemia or nausea. The two types differ in clinical presentation and treatment. Resetting of the ADH osmostat is commonly associated with resetting of the thirst osmostat. Hyperosmolarity is almost always due to deficient water intake. Excessive excretion may contribute to the problem but is never a sufficient cause. Impaired water intake can result from a defect in either the osmoregulation of thirst or the necessary motor responses. Thirst may be deficient because of primary osmoreceptor damage as in the syndrome of adipsic hypernatremia or secondary to nonomsotic influences on the set of the system. They are distinguishable by the clinical presentation as well as the type of ADH defects with which they are associated. So-called essential hypernatremia due to primary resetting of the osmostat has been postulated, but unambiguous evidence for such an entity has not yet been reported.     

Blunted muscle responsiveness to insulin in the neonatal rat

Peripheral muscle responsiveness to insulin was studied in neonatal rats in vivo by measuring net incorporation of radiolabeled glucose to glycogen in diaphragm. D(U-¹⁴C) glucose, 0.03 μCi/g rat pup weight, was injected i.p. with or without (control) insulin 5000 μU/g rat pup weight into pups from 86 litters of Sprague-Dawley rats as well as into 16 adult rats by the technique of Rafaelson. Diaphragms were excised after a 30-min in vivo exposure at birth, 24, 48, 72, or 168 hr of age and in the adult rats. Insulin increased net incorporation of radiolabeled glucose into diaphragm glycogen in comparison to age-matched controls (p < 0.025). The percent stimulation by insulin of labeled glucose into diaphragm glycogen was low at birth (250%) and at 24 hr (200%), but increased with advancing age and approached adult levels by 168 hr (1270%). At birth and at 24 hr, a 5-log insulin dose-response curve showed significant net incorporation only at 5000 μU insulin/g rat pup weight; by 72 hr a significant increase was noted at 50 μU insulin/g rat pup weight. Muscle glycogen concentration was high at birth ($\text{1.22 mg}\text{100 mg tissue}$), fell to 50% of the birth value from 24 through 168 hr, and could not account for the decreased insulin response noted. Decreased uptake of deoxyglucose into diaphragm in vivo paralleled the reduced net incorporation of radiolabeled glucose into diaphragm glycogen during the time period studied. The data are interpreted to indicate a blunted responsiveness of skeletal muscle to insulin during the first 48 hr in rats, which is related to decreased sensitivity of hexose transport to insulin.     

Portal and peripheral vein concentrations of insulin and glucagon after arginine infusion in morbidly obese subjects

Five morbidly obese subjects with fasting normoglycemia underwent catheterization of portal and peripheral veins immediately prior to jejunoileal bypass surgery. Levels of immunoreactive insulin (IRI), immunoreactive glucagon (IRG), and glucose were determined in simultaneously obtained serum samples before and after infusion of arginine. Portal levels exceeded peripheral levels by at least 50% with IRI and by 30%–40% with IRG. These results were similar to those reported in nonobese subjects and show that in morbid obesity as well as in nonobese states, peripheral insulin to glucagon molar ratios ($\text{I}\text{G}$) underestimate portal $\text{I}\text{G}$. Although hepatic extraction was not specifically measured, the data suggest that the peripheral levels of insulin and glucagon reported in morbid obesity result from alterations in secretion and not altered extraction.     

Histologic diagnosis of diseases of malabsorption

The diagnoses which may be arrived at by examination of peroral small bowel mucosal biopsy specimens are presented. Celiac sprue, unclassified sprue (refractory sprue), infectious gastroenterititis, stasis syndrome and kwashiorkor have a severe mucosal lesion. Other clinical conditions are required to establish the diagnosis in these diseases. A number of diseases have specific diagnostic features. Included are Whipple's disease, abetalipoproteinemia, collagenous sprue, primary intestinal lymphoma, eosinophilic gastroenteritis, giardiasis, coccidiosis, strongyloidiasis, lymphangiectasis and the intestinal immunodeficiency diseases. Mucosal abnormalities may be present in other diseases but the diagnoses are usually made on other criteria than small bowel biopsy. These include vitamin B12 or folic acid deficiency, Crohn's disease, gastrinoma, acrodermatitis enteropathica, amyloidosis, chronic granulomatous disease, lipid storage diseases, histoplasmosis, capillariasis, cytomegalovirus infection, schistosomiasis and macroglobulinemia.     

Mid-systolic click and mitral valve prolapse following mitral commissurotomy

Five patients with rheumatic mitral stenosis were observed to have mid-systolic clicks with murmurs of mitral regurgitation at various intervals after mitral commissurotomy. In two patients echocardiography showed an unusually rapid posterior deflection of the mitral valve coinciding exactly with a systolic nonejection click. It is speculated that the shortened, fused chordae tendineae, compromised by mitral commissurotomy, rigidly hold the valve leaflets fixed at the onset of systole. During systole, ventricular conformational changes, in the face of marginal coaptation of thickened and fibrotic mitral leaflets, allow the mitral valve to be forced abruptly towards the left atrium with great velocity. This is manifested by a loud systolic click and, in some patients, a near vertical posterior systolic deflection of the mitral valve on the echocardiogram. The systolic click may occur without echocardiographic or angiographic evidence of mitral valve prolapse. Unusually loud mid-systolic clicks can be heard in patients with rheumatic heart disease after mitral commissurotomy and may be accompanied by a distinctive echocardiographic appearance of the mitral valve.     

Quantitative evaluation of vitamin E in the treatment of angina pectoris.

Because of previous reports of the beneficial effect of vitamin E in angina pectoris patients, 48 patients, with both stable angina and positive (chest pain plus ishemic ST depression) maximal exercise treadmill tests, participated in a double-blind cross-over study of 6 months of vitamin E and 6 months of placebo therapy, separated by a 2 month no treatment period. All 48 patients had positive selective coronary arteriograms (75 per cent obstruction of at least a major coronary artery) and/or Q wave ECG evidence of previous myocardial infarction (Minnesota criteria). Evaluation of drug effectiveness was based on performance of serial maximal exercise treadmill tests, serial systolic time interval measurements, and daily angina diaries. No statistically significant differences between the two treatment studied. It is concluded that a large dose of vitamin E (1,600 I.U. of d-alpha-tocopherol succinate daily) for 6 months in patients with stable angina pectoris fails to increase the exercise capacity, improve left ventricular function, or reduce the frequency of chest pain.     

Alpha 1-antitrypsin deficiency associated with PZ and MP phenotypes. Clinical and laboratory correlations

In a large kindred we have identified two siblings with the hitherto unreported PZ phenotype and eight other subjects with the MP phenotype. In subjects with the MP phenotype serum alpha₁-antitrypsin levels are near the lower limits of normal. In contrast, subjects with the PZ phenotype have severely depressed alpha₁-antitrypsin levels. One subject with the PZ phenotype at age 34 already shows evidence of obstructive lung disease. We found no convincing evidence of obstructive lung disease in family members with the MP phenotype. After purification of alpha₁-antitrypsin from the serum, isoelectric focusing and acrylamide gel electrophoresis can be used to distinguish normal protein from the products of the Pi^P and Pi^Z alleles. Subjects with the PZ phenotype have more Pi^P than Pi^Z product.     

Anterolateral ST segment depression in acute inferior myocardial infarction: angiographic and clinical implications

We examined the relationship between coronary anatomy and anterolateral ST segment depression during inferior acute myocardial infarction (AMI) in 84 consecutive survivors of inferior AMI, who underwent prospective coronary angiography a median time of 2 weeks after AMI. Multivessel disease was defined as two or more significantly (greater than 70%) stenosed vessels. A QRS scoring system was used to estimate myocardial infarct size. Patients with ST depression had more multivessel disease compared to patients with no ST depression (53% vs 6%, p less than 0.01), more left anterior descending stenoses (36% vs 10% p less than 0.05), and higher QRS scores (5.8 +/- 3.2 vs 2.6 +/- 1.8, p less than 0.01) indicating larger infarcts. Patients with ST depression and one-vessel disease (47%) still had higher QRS scores compared to patients with no ST depression (4.8 +/- 2.9 vs 2.6 +/- 1.8, p less than 0.001) and had an increased prevalence of infarct-related vessels with a terminal branch supplying the left ventricular lateral wall or apex. We conclude that anterolateral ST depression during inferior AMI may indicate the presence of additionally stenosed vessels or that the infarct-related vessel has a large vascular territory. The absence of ST depression virtually precludes multivessel disease.