On the mechanism of the splay in the glucose titration curve in advanced experimental renal disease in the rat.

Glucose titration studies were performed in rats with unilateral chronic pyelonephritis before and after removal of the contralateral control kidneys. Identical studies were performed in animals with unilateral partial renal infarction in which the experimental kidneys had a marked reduction in nephron population but no anatomic deformation in the surviving nephrons. In the initial studies, both groups of animals were free of clinical and chemical abnormalities of uremia. In the follow-up studies uremic abnormalities were present. Minimal splay was observed in the titration curves in the initial studies; marked splay was present in the group data from the same kidneys in the subsequent studies. Thus a marked reduction in the nephron population was associated with the evolution of splay in both groups of animals. In association with the increase in splay, the mean values for maximal glucose transport increased; thus a defect in glucose transport can be excluded as the basis of the splay. Glomerular filtration rate increased proportionately more than the maximal transport of glucose; hence the ratios of glomerular filtration rate to maximal glucose transport increased consistently. The possibility of asymmetric hypertrophy of glomerular and tubular functions among the nephron population imposed by scar tissue or other anatomic deformities was considered, but the results in the animals with partially infarcted kidneys militate against this explanation. The splay also could reflect an asymmetric alteration in the distribution of glomerulotubular balance among the residual units initiated by functional adaptations. Finally, the splay could relate to an alteration in the kinetics of glucose transport without any change in the level of functional homogeneity. The possible nature of these has been considered in the text.

Glucose titration studies in patients with chronic progressive renal disease.

Glucose titration studies were performed on 17 patients with either chronic pyelonephritis or chronic glomerulonephritis. Glomerular filtration rates for the group ranged from 4.3 to 58.1 ml per minute. In none of the patients in whom the glomerular filtration rate was over 15 ml per minute was there appreciable splay, and the mean titration curve for these patients resembled that obtained by Smith and associates in normal man (1). In half of this group of eight patients, GFR ranged from 16.6 to 22.7 ml per minute; in the other half values ranged from 42.3 to 58.1 ml per minute. Yet, the mean titration curves were identical for the two groups. In addition, no difference was observed in the titration curves for patients with pyelonephritis and those with glomerulonephritis. In patients with GFR values below 15 ml per minute, increased splay was observed, and below a GFR of 10 ml per minute, the splay was very marked. Both the absence of exaggerated splay in patients with reduction of glomerular filtration rate by as much as 85%, and the emergence of exaggerated splay in patients with more marked reduction of GFR, require explanation. Theoretical considerations are presented in the text.

Acute multisystem toxicity associated with the use of nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been implicated as a cause of acute liver failure, acute renal failure, and acute autoimmune hemolytic anemia. Since NSAIDs are capable of causing serious injury to multiple organ systems, it is surprising that no one has observed multisystem involvement in any of the described patients. We describe two patients with multisystem involvement presumed to be secondary to NSAIDs. Both patients had renal failure consistent with acute tubular necrosis. Both patients had liver failure, one with hepatocellular disease and the other with a cholestatic picture. One patient had a Coombs'-positive hemolytic anemia.

Acute renal failure and glomerulopathy caused by nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs are now one of the most common causes of acute renal failure (ARF). To define more clearly the magnitude of the problem, we reviewed all cases of ARF in the Reno (Nev) area from 1972 through 1986. Twenty-seven cases of ARF and seven cases of glomerulopathy were identified, primarily during the last 5 years of the study period. Twenty-three of the cases of ARF and six of the cases of glomerulopathy cleared an average of 23 and 118 days, respectively, after treatment with the nonsteroidal anti-inflammatory drug was stopped. Two cases of ARF persisted, and two patients died. Proteinuria, hematuria, and casts were prominent in both ARF and glomerulopathy but were more pronounced in the glomerulopathies. The treatment of choice is to stop the use of the nonsteroidal anti-inflammatory drug. The role of steroids has not been evaluated.

Effects of nonsteroidal anti-inflammatory drugs on prostaglandins and renal function.

In the past 15 years, there has been an explosion in the number of nonsteroidal anti-inflammatory drugs on the market. Along with this explosion have come increasing reports of the physiologic and pathologic changes seen in the kidneys. This report reviews the effects of prostaglandins on the kidney and the physiologic changes that result when prostaglandin synthesis is blocked. The world literature on renal complications of nonsteroidal anti-inflammatory drugs is reviewed and 274 cases of acute renal disease associated with their use are reported. The following cases are described: nephrotic syndrome (34); acute interstitial nephritis (51); acute tubular necrosis (29); papillary necrosis (53); poor perfusion with renal failure (40); acute glomerulitis or vasculitis (13); and unspecified renal failure (102). Fenoprofen appeared to be more nephrotoxic than other nonsteroidal anti-inflammatory drugs and resulted in multiple renal lesions in the same patient.

Alveolar hemorrhage associated with a membranoproliferative glomerulonephritis and smooth muscle antibody.

Alveolar hemorrhage along with glomerulonephritis developed in a 31-year-old black man. Renal biopsy demonstrated a granular pattern of immunofluorescence along basement membrane glomeruli, suggesting an immunologically mediated illness; however, light microscopy revealed a pure membranoproliferative glomerulonephritis, which has not been described to date in association with the alveolar hemorrhage syndromes. The patient's immunologic profile revealed a positive antinuclear antibody titer along with the presence of smooth muscle antibodies.

Blue digit syndrome: transesophageal echocardiographic identification of thoracic aortic plaque-related thrombi and successful outcome with warfarin.

We describe two patients with blue digit syndrome in whom transesophageal echocardiography was able to identify mobile thrombotic masses attached to the irregular intimal surface of the descending thoracic aorta. These patients were treated with heparin and warfarin and did not have recurrent episodes of peripheral arterial embolization. In this article we discuss the diagnostic and therapeutic approaches in patients with peripheral arterial embolization and blue digit syndrome.

Reversible uremia and its effect on the glomerular filtration rate.

As the nephron population diminishes and azotemia develops, each remaining nephron adapts and increases its function by as much as 80%. To determine whether this adaption is permanent or transient, a rat model utilizing one remnant kidney and one normal control kidney was used. In stage one, immediately after ligation of the ureter to the control kidney, the glomerular filtration rate in the remnant kidney was 0.185 cm3/min. 1 week after ligation of the ureter to the control kidney, the glomerular filtration rate in the remnant kidney had increased to 0.336 cm3/min (stage two), and 2 weeks later, after removal of the obstruction to the control kidney, the glomerular filtration rate in the remnant kidney was 0.155 cm3/min (stage three), p less than 0.01.

Teaching the resident in internal medicine. Present practices and suggestions for the future.

There appears to be a trend to move clinical teaching from bedside to conference room. While much emphasis is placed on conducting teaching rounds, no one asks how they are conducted. To evaluate how teaching is done, questionnaires on composition of teaching services and management of rounds including resident, patient care, attending, and teaching rounds were sent to 463 medicine residency programs. Responses were solicited from the program directors and chief residents. Two hundred twenty-one responded, but only for 123 programs did both the program director and the chief resident respond; these 123 programs formed the basis of our study. Fifteen percent of teaching rounds were held only in conference rooms, while 77% were made both at bedside and in conference rooms. The figures for attending rounds were 7% and 74%, respectively. Our data indicate a trend away from bedside teaching to the conference room.

Pneumobilia associated with small-bowel obstruction.

We present a patient who was admitted complaining of nausea, vomiting, and abdominal distention. A roentgenogram of the abdomen revealed a dilated stomach and pneumobilia. At surgery, he was found to have proximal small-bowel obstruction. To our knowledge, this is the first case of pneumobilia associated with proximal small-bowel obstruction not associated with a gallstone.