Diabetic nephropathy as the mode of presentation of diabetes mellitus.

Diabetic nephropathy have only rarely been described in patients who have minimal or no glucose intolerance. We herein report the case of a 59-yr-old man who presented with nephrotic syndrome and minimal glucose intolerance whose renal biopsy showed the nodular (Kimmelsteil-Wilson) and diffuse glomerulosclerosis lesions characteristic of diabetes. We critically review the literature on this subject, pointing out the pitfalls in diagnosis and establishing strict criteria for the diagnosis of diabetic nephropathy in patients wihout overt clinical diabetes.     

Tritiated digoxin. XIX. Turnover studies in diabetes insipidus

The effect of chronically increased urinary volumes on renal digoxin excretion and digoxin turnover was studied in 2 patients with nephritogenic diabetes insipidus and urinary volumes in excess of 9 liters/ 24 hours. The serum half-lives were 48 and 54 hours and the 7 day urinary excretion totals 46 and 41 percent, respectively. Comparison with values obtained in patients with congestive heart failure demonstrated no increase in excretion of renal digoxin. Increased urinary volume without change in glomerular filtration rate does not increase excretion of digoxin, and would not be expected to decrease the duration of digitalis toxicity.     

Potentiation of Cd-induced pulmonary injury in α1-antitrypsin suppressed rats

The interrelationship of α₁-antitrypsin (α₁-AT) or serum trypsin inhibitor capacity (TIC) level and cadmium exposure in the induction of pulmonary lesions was investigated. Sprague-Dawley rats were exposed to CdCl₂, galactosamine, or galactosamine + CdCl₂ for 24 hr. Biochemical study indicated a 20% reduction of serum TIC in animals exposed to galactosamine. A marked, 50%, reduction of serum TIC was induced in animals exposed to galactosamine + CdCl₂. Histopathological study revealed no major morphological lesions in lungs of animals exposed to either CdCl₂ or galactosamine. However, extensive lesions, including polymorphonuclear leukocyte (PMN) infiltration, distortion and distention of the alveolar spaces, and massive hemorrhages were observed in the lungs of animals exposed to galactosamine + CdCl₂. It is believed that cadmium can induce rapid lesions in the pulmonary tissues when the α₁-AT is significantly suppressed. The present investigation has provided direct evidence on the importance and interrelationship of cadmium and α₁-AT in pulmonary lesion development.     

Chronic low-level lead toxicity in the rat: III. An integrated assessment of long-term toxicity with special reference to the kidney

Male and female rats whose mothers had been exposed to Pb before and during pregnancy and lactation at exposure levels of 0, 0.5, 5, 25, 50, and 250 ppm Pb as Pb-acetate in drinking water were continued on the respective regimens for 6 or 9 months. Body weights of males and females were not significantly different from controls at 6 months of age; however, female body weights were significantly decreased at 250 ppm at 9 months of age. In males at 9 months of age, spleen weights were significantly increased at 250 ppm Pb and kidney weights were increased at 0.5 ppm Pb and above; in females the liver, pituitary, and heart weights were affected at 250 ppm Pb. No significant Pb effects were found in sperm counts or sperm morphology, hematology profiles, or serum chemistries. Blood, brain, femur, and kidney Pb levels as well as urinary ALA excretion were all significantly dose related. Histopathological lesions were noted in the spleen (250 ppm) and in the kidney as evidenced by cytomegaly/karyomegaly (beginning at 5 ppm in males; 25 ppm in females), nuclear inclusion body formation and increased numbers of iron-positive granules within renal proximal tubule cells. These effects were more marked after 9 months exposure. Ultrastructural studies revealed mitochondrial swelling and the presence of increased numbers of lysosomes within renal proximal tubule cells. Energy-dispersive X-ray microanalysis, performed on adjacent sections, showed the highest intracellular Pb concentrations in nuclear inclusion bodies within renal proximal tubule cells. Inhibition of renal mitochondrial respiration for both succinate and NAD-linked substrates was found in 50- and 250-ppm Pb exposure groups at 9 months but not at 6 months. Mitochondrial δ-aminolevulinic acid synthetase and ferrochelatase, but not δ-aminolevulinic dehydratase, were also found to be inhibited at these Pb levels at 9 months. The lowest exposure level resulting in a detectable effect of Pb (cytomegaly/karyomegaly in renal proximal tubule cells) was 5 ppm associated with a median blood Pb concentration of 11 μg/dl.     

Chronic low-level lead toxicity in the rat: II. Effects on postnatal physical and behavioral development

This report is the second in a series dealing with the chronic exposure of rats to lead (Pb) in drinking water. Weanling female CD rats were provided semipurified diets and deionized water containing 0, 0.5, 5, 25, 50, or 250 ppm Pb (as lead acetate). Following exposure for 6–7 weeks, females were mated with unexposed males and exposure continued throughout pregnancy and lactation. At 21 days of age, offspring were weaned onto the same concentration their mothers had been given, and exposure continued until sacrifice at 6 or 9 months of age. Significant depressions in body weight were seen at most time points for offspring exposed to 50 and 250 ppm Pb. Clinical signs of respiratory infection, as well as poor fur condition, tail-tip necrosis, and sialodacryoadenitis were noted to occur at 250 ppm. Highly significant delays in age at vaginal opening were noted in 25-, 50-, and 250-ppm females. Surface righting and air righting were delayed in 50- and 250-ppm animals. Locomotor development was unaffected except for an increase in pivoting in 250-ppm animals at Day 14 of age. Postweaning activity levels were unaltered when measured in either the open field or the circular photocell activity cage and evaluations of motor coordination using the rotorod test showed no effects of Pb. Food and water consumption based on body weight were essentially unchanged. Overall, the “lowest effect level” for Pb using chronic oral exposure was 25 ppm, a level associated with alterations in reproductive development. In other reports from this study, immune function and performance of an operant task in adults were altered at 25 ppm (blood Pb, 20–40 μg/dl), and renal morphology after 9 months of exposure was altered at 5 ppm (blood Pb, 10–16 μg/dl). The importance of reporting blood and tissue Pb concentrations for comparing Pb dose-effect among studies is emphasized.     

Latent defects of atrioventricular conduction in right coronary artery disease

The purpose of this study was to investigate the occurrence of latent defects in AV conduction in patients with right coronary artery disease. Twenty-two patients with greater than 50 per cent obstruction of the right coronary artery and a predominant right coronary artery system or pattern were studied with His bundle electrograms and determinations were made of the functional refractory period of the AV node and the point at which AV Wenckebach developed during rapid atrial pacing with a fixed cycle length. The patients were studied prior to or at least six months after the onset of clinical or electrocardiographic evidence of acute infarction. Similar measurements were made in eighteen control subjects with less than 50 per cent occlusion of the right coronary artery. The results showed significant prolongation of the functional refractory period (467 ± 63 msec. for patients with right coronary disease versus 408 ± 43 msec. in the control group; P <0.01) and earlier development of atrioventricular Wenckebach during rapid atrial pacing (143 ± 22 BPM in the coronary obstruction group versus 172 ± 19 BPM in the control group; P<0.01) in patients with significant disease of the right coronary artery when compared to the control group. Although all patients were found to have resting intervals on the His bundle electrogram within normal limits, the group with right coronary obstruction had slightly longer values for the resting P-H interval (122 ± 19 msec. versus 101 ± 31 msec. in the control group; P<0.05). This study establishes that latent defects in atrioventricular conduction exist in patients with significant disease of the right coronary artery in the absence of acute infarction.     

Association of accelerated idioventricular rhythm and paroxysmal ventricular tachycardia in acute myocardial infarction

Although previous studies have suggested that accelerated idioventricular rhythm rarely coexists with paroxysmal ventricular tachycardia, this relation has not been systematically evaluated in acute myocardial infarction. To examine this relation, the frequency and characteristics of the two arrhythmias were analyzed by performing 24 hour Holter monitoring during the initial 24 hours of acute myocardial infarction in 52 successive patients. Twenty-four of these patients had documented accelerated idioventricular rhythm; 28 patients did not. Paroxysmal ventricular tachycardia occurred in 83 percent of patients with accelerated idioventricular rhythm but in only 18 percent of patients without this arrhythmia (P < 0.001). The results remained at the same level of significance whether paroxysmal ventricular tachycardia was defined by rates greater than 100, 120 or 140 beats/min. These findings suggest that accelerated idioventricular rhythm complicating acute myocardial infarction is not always benign and is frequently associated with more serious forms of ventricular arrhythmia.     

Tritiated digoxin. XX. Tissue distribution in experimental myocardial infarction

The role and potential hazards of digitalis glycoside administration in acute myocardial infarction remain controversial. We investigated the concentration of tritiated digoxin in normal, ischemic, and infarcted left ventricular myocardium of the dog after ligation of the anterior interventricular coronary artery. The normal homogeneous distribution of tritiated digoxin in the normal canine left ventricle was altered following acute myocardial infarction. The ischemic and infarcted zones exhibited a marked diminution in digoxin concentration. Oxidative phosphorylation determinations confirmed tissue hypoxia in the infarcted zone. The gradient of digoxin concentration between normal, ischemic, and infarcted zones of myocardium may potentiate the development of an arrhythmia in the electrically unstable infarcted myocardium.     

The effects of triethyltin and trimethyltin in rats responding under a DRL schedule of reinforcement

Rats were trained to respond under a schedule of reinforcement in which only those responses separated by a 10-to 14-sec period of no responding produced a feed pellet (DRL 10 to 14 sec). Each rat received a single dose of trimethyltin (TMT) (5.6, 7.5, or 10 mg/kg) or triethyltin (TET) 1, 3, 4.25, or 5.6 mg/kg). The lowest dose of TMT (5.6 mg/kg) and the lowest dose of TET (1 mg/kg) were without significant effect. At 7.5 mg/kg and 10 mg/kg TMT, the percentage of the total responses spaced 10 to 14 sec apart decreased over the first 8 to 12 days after TMT. Those rats receiving 7.5 mg/kg TMT gradually returned to control values over the next 2 to 3 weeks while those rats receiving 10 mg/kg never recovered. Rats receiving 3, 4.25, and 5.6 mg/kg TET showed a decrease in the percentage of reinforced responses immediately after receiving TET. The behavior of those rats receiving 3 mg/kg returned to control values in 24 hr. Following 4.25 mg/kg TET, the health of the rats deteriorated rapidly. They were kept alive through heroic measures, but then were killed after testing on the 12th day following TET due to their failing health. At 5.6 mg/kg, the rats were killed on the 4th day due to failing health. These results indicate that TMT and TET differ with respect to potency and time course. The behavioral deficits produced by TET parallel the time course of general toxicity while the behavioral effects of acute TMT administration can persist in time long after the general appearance of the rats has returned to normal.