Pancreatitis following administration of iodixanol in patients on hemodialysis: a pilot study.

BACKGROUND AND OBJECTIVES: We previously described the association of pancreatitis with the use of iodixanol radiocontrast in two patients on hemodialysis. This study was designed to determine whether there might be a causal link. DESIGN: 30 consecutive hemodialysis patients without predisposition for pancreatitis who were undergoing de-clotting and angioplasty of their arteriovenous access were randomly assigned to either iodixanol or iohexol radiocontrast. RESULTS: The demographics and volume of contrast used were similar between the groups. 2 of the 15 patients who received iodixanol developed elevations in serum amylase and lipase as well as signs and symptoms of pancreatitis. No patient who received iohexol developed pancreatitis. CONCLUSION: The use of iodixanol appears to be associated with pancreatitis in a small population of hemodialysis patients. Although the pathogenesis of iodixanol-induced pancreatitis is unclear, we speculate that it is possibly related to the hyperviscosity of this agent, which may decrease pancreatic blood flow. Larger studies are needed to verify these findings.

Sustained low-efficiency daily dialysis with hemofiltration for acute kidney injury in the presence of sepsis.

AIMS: Acute kidney injury (AKI) commonly occurs in critically ill patients with sepsis and is associated with poor outcomes. Unfortunately, the ideal mode of renal replacement therapy remains unknown. Because both higher doses of dialysis and hemofiltration have been associated with improved survival, we postulated that adding hemofiltration to the diffusive clearance achieved by sustained low-efficiency daily dialysis (SLEDD-f) would provide a survival advantage over SLEDD. METHODS: From December 2003 to October 2005, we retrospectively analyzed all patients with multisystem organ failure, vasopressor-dependent hypotension and oliguric acute kidney failure secondary to nonoperative sepsis who were treated with renal replacement therapy (RRT). After exclusionary criteria were applied, 8 patients received SLEDD-f and 13 patients received SLEDD. All treatments were for 8 - 16 h/day. SLEDD-f was continued until vasopressors were reduced to a minimal dose. Outcomes were mortality and recovery of renal function at 30 days after initiation of RRT. APACHE- II scores were calculated at the time of dialysis initiation to predict mortality. RESULTS: Despite higher APACHE II scores, 30-day survival was 100% in the SLEDD-f group and 38% in the SLEDD group. Furthermore, most of the SLEDD-f patients were able to have vasopressors weaned quickly and all patients in the SLEDD-f group recovered significant renal function to allow discontinuation of RRT. CONCLUSIONS: While the optimal treatment remains unknown, this small study raises the possibility that SLEDD-f offers a survival advantage and increases the chance of renal recovery while decreasing the need for vasopressors. A large randomized trial comparing SLEDD-f with other forms of renal replacement therapy is needed.

Respiratory complications of pregnancy.

The pregnant woman is susceptible to a variety of respiratory complications. When a pregnant patient presents with an abnormal chest x-ray or a pulmonary complaint, an understanding of the pathophysiology of pregnancy will guide the clinician in establishing a diagnosis. Pregnancy brings about many changes to a woman's body. One of the more intriguing is a decrease in the T helper cells, resulting in a state of relative immunosuppression. Despite this, the prevalence of infectious pneumonia is not increased in pregnancy. Complications from pneumonia, however, are increased in the pregnant host. Most notably are increases in both mortality related to influenza infection and the risk for dissemination of coccidioidomycosis. Other physiologic changes predispose the pregnant woman to certain disease processes. Hypercoagulability associated with pregnancy results in a marked increase in the incidence of thromboembolic disease. Although rare, pregnancy is also associated with other embolic phenomena including amniotic fluid embolism, air embolism, and trophoblastic embolism. Because of the increases in intravascular volume and cardiac output that occur in pregnancy, women with underlying structural heart disease will frequently present for the first time or have an exacerbation of their disease. This is especially true of mitral stenosis. Peripartum cardiomyopathy also can occur, and for the majority of patients, the heart remains damaged for life. Finally, although uncommon, lymphangioleiomyomatosis will often present or become exacerbated during pregnancy. Patients with this disorder need to be counseled concerning the increased risk associated with pregnancy. This paper reviews the various respiratory complications associated with pregnancy.

Human immunodeficiency virus infection in elderly patients.

BACKGROUND: The proportion of older individuals infected with the human immunodeficiency virus (HIV) is rising. METHODS: We performed a retrospective case-control study of 58 patients more than 60 years old at the time of diagnosis of HIV infection and compared them with 232 controls (matched by CD4+ lymphocyte count). Clinical and demographic data were obtained from the Adult Spectrum of Diseases (ASD) database at the Medical Center of Louisiana. RESULTS: Patients in the older age group were more likely to be male and African American or Hispanic. The most common risk factor for acquisition of HIV infection among the patients was homosexual contact (53%). Disease staging was similar in both groups as determined by CD4+ lymphocyte counts and history of opportunistic infections. There was no difference in the use of antiretroviral therapy. In a Cox proportional hazard model and regression models, age > or = 60 years was associated with shorter survival. CONCLUSION: Patients who are older than 60 years at the time of diagnosis of HIV infection have a shorter survival than younger patients.

Residency program director evaluations do not correlate with performance on a required 4th-year objective structured clinical examination.

BACKGROUND: Assessment of resident performance is a complex task. PURPOSE: To correlate performance on a 4th-year objective structured clinical examination (OSCE) with residency program director assessment, class rank, and U.S. Medical Licensing Examination (USMLE) scores. METHODS: We surveyed program directors about the performance of 50 graduates from our medical school chosen to represent the highest (OSCEHI) and lowest (OSCELO) 25 performers on our required 4th-year OSCE. Program directors were unaware of the OSCE scores of the graduates. RESULTS: OSCE scores did not correlate with Likert scores for any survey parameter studied (r < .23, p > .13 for all comparisons). Similarly, program director evaluations did not correlate with class rank or USMLE scores (r < .26, p > .09 for all comparisons). CONCLUSIONS: We concluded that program director evaluations of resident performance do not appear to correlate with objective tests of either clinical skills or knowledge taken during medical school. These findings suggest that more structured and objective evaluative tools might improve postgraduate training program assessment of trainees.

Respiratory bronchiolitis: an unusual cause of pulmonary infiltrates in a pregnant woman.

Numerous mechanical, biochemical, and immunologic changes occur during pregnancy. Because of these changes, pregnant women are more susceptible to infection, thromboembolic disease, exacerbation of underlying immunologic disease, and heart failure than women who are not pregnant. The differential diagnosis of diffuse pulmonary infiltrates in a pregnant woman is broad; thus, the work-up can be very challenging. If the patient fails to respond to conservative measures, such as antibiotics, the cause of the infiltrate must be aggressively evaluated because the treatment may be essential for the survival of the mother and fetus. We report a case of a pregnant woman who presented with diffuse bilateral infiltrates. After video-assisted thoracoscopic lung biopsy, this patient was found to have respiratory bronchiolitis, a disease not previously reported during pregnancy. Treatment with glucocorticoids resulted in a prompt improvement in symptoms.

Reemergence of sucrose nephropathy: acute renal failure caused by high-dose intravenous immune globulin therapy.

Sucrose nephropathy was first described more than 50 years ago. The disorder is characterized by acute renal failure caused by the uptake of sucrose by renal proximal tubule cells with subsequent cellular swelling and occlusion of the tubule lumen. Approximately 114 cases of renal failure have been associated with high-dose intravenous immune globulin (IVIG) therapy. Almost all cases were caused by preparations containing large amounts of sucrose. Clinicians should consider using IVIG preparations containing no sucrose in patients who are at high risk for renal failure. Risk factors include older age, baseline renal failure, and volume contraction.

Air embolism after intravenous injection of contrast material.

Venous air embolism, though considered rare, occurs more frequently than it is recognized. We report the case of a 54-year-old man who was incidentally found to have air in the left brachiocephalic vein and right ventricle after contrast-enhanced computed tomography (CT). Air embolism has been noted to occur after contrast-enhanced CT examination in up to 23% of patients. Because these emboli are small to moderate size and are usually venous, the patients are usually asymptomatic. We review the pathophysiology of air embolization and the recommended treatment.

Anion gap acidosis.

Although an anion gap at less than 20 mEq/L rarely has a defined etiology, significant elevations in the anion gap almost always signify presence of an acidosis that can be easily identified. Anion gap acidoses can be divided into those caused by lactate accumulation, ketoacid production, toxin/drugs, and uremia. Lactic acidoses caused by decreased oxygen delivery or defective oxygen utilization are associated with high mortality. The treatment of lactic acidosis is controversial. The use of bicarbonate to increase pH is rarely successful and, by generating PCO2, may worsen outcome. Ketoacidosis is usually secondary to diabetes or alcohol. Treatment is aimed at turning off ketogenesis and repairing fluid and electrolyte abnormalities. Methanol, ethylene glycol, and salicylates are responsible for the majority of toxin-induced anion gap acidoses. Both methanol and ethylene glycol are associated with severe acidoses and elevated osmolar gaps. Treatment of both is alcohol infusion to decrease formation of toxic metabolites and dialyses to remove toxins. Salicylate toxicity usually is associated with a mild metabolic acidosis and a respiratory alkalosis. Uremia is associated with a mild acidosis secondary to decreased ammonia secretion and an anion gap caused by the retention of unmeasured anions. A decrease in anion gap is caused by numerous mechanisms and thus has little clinical utility.

The teaching of cellular and molecular biology: a survey of program directors in internal medicine.

PURPOSE: Although there has been an explosion in our knowledge of cellular and molecular biology, it is unclear if medical students entering internal medicine residency programs have been adequately trained in these basic sciences. To ascertain the perceived importance of these subjects to the practice of medicine and to determine if medical schools are properly training their students, a survey was sent to internal medicine program directors. METHODS: A survey was sent to 401 internal medicine program directors. Repeat questionnaires were sent if no response was received within 6 months. RESULTS: Questionnaires were returned by 309 program directors (77%). Only 41% of the program directors felt that their residents had received adequate training in cellular and molecular biology. Directors of university programs were significantly more likely to think that knowledge of these sciences was essential to the practice of medicine and that their residents were inadequately trained than directors from nonuniversity programs. Only 30% of programs offered any formal training in these sciences. CONCLUSION: Medical schools need to reevaluate their curricula in order to integrate the basic sciences into all 4 years. Training in these sciences, however, should not stop with graduation. The importance of a knowledge of these sciences should be emphasized at all training programs.

Analysis of the costs and benefits of using standardized patients to help teach physical diagnosis.

BACKGROUND: Although a majority of medical schools use standardized patients (SPs) for teaching or evaluating students, the costs and benefits of such programs have not been examined in depth. In 1992-93 the Tulane University School of Medicine reduced by 40% the faculty-precepted sessions in its physical diagnosis program in order to incorporate seven focused examinations using SPs to teach basic examination skills. METHOD: Costs for the revised program included costs for SPs, staff, supplies, and faculty. Faculty cost was estimated at a minimum to equal hourly salary and at a maximum to equal this salary plus potential collectible billings. An objective structured clinical examination (OSCE) was used to assess the skill acquisitions of 150 second-year students in 1991-92, before SPs were used, and in 1992-93, when SPs were used. An unpaired t-test was then used to compare the OSCE performances of the two groups of students. Chi-square analysis was used to compare the evaluations of the physical diagnosis program by the 1992-93 and 1991-92 students. RESULTS: The cost of incorporating SPs into the program was $43,800. The amount of time spent teaching by faculty was reduced by 608 hours, costing between $33 (salary) and $108 (salary plus potential revenue) per hour. Thus, the total savings in the cost of faculty time was between $20,064 and $65,664. Despite the reduction in faculty involvement, the students' performance on the OSCE did not change, and the students' evaluations of the course became significantly more favorable. CONCLUSION: The incorporation of SPs as instructors in the physical diagnosis program was accomplished at a minimal cost and resulted in an increase in students' enthusiasm for the purpose, with no loss of skill acquisition as measured by the OSCE.

Comparison between acetate and bicarbonate dialysis for the treatment of lithium intoxication.

Lithium is used to treat manic-depressive disorders, but toxic side effects commonly occur. The preferred treatment of severe lithium intoxication is hemodialysis. No data, however, exist comparing the effectiveness of acetate to bicarbonate dialysis for the removal of lithium. We present a case of lithium intoxication treated with both. During acetate dialysis, lithium removal occurred exclusively from the extracellular fluid space, while during bicarbonate dialysis, lithium removal occurred equally from both the extracellular and intracellular fluid spaces. We hypothesize that acetate but not bicarbonate activates the sodium-hydrogen antiporter on cell membranes, and that lithium, substituting for sodium, is driven into cells. This may explain the rebound in lithium levels commonly noted after conventional dialysis. We recommend bicarbonate hemodialysis as the therapy of choice for severe lithium intoxication.

Aldosterone-induced glycoproteins: further characterization.

Aldosterone induces the synthesis of a group of glycoproteins (GP65,70) in toad urinary bladders which are potential effectors of the natriferic action of this hormone. The GP65,70 complex is composed of two molecular weight classes of proteins (Mr 65 and 70 kDa), each class being composed of several discrete proteins of varying isoelectric points (5.8-6.2). These proteins can be partially enriched (approximately 20-fold) using wheat germ agglutinin-sepharose affinity chromatography, are neuraminidase-resistant, and can be N-deglycosylated by endoglycosidase-H and N-glycanase. Treatment with N-glycanase leads to the appearance of a microheterogeneous group of proteins, all having the same Mr (approximately 40 kDa). From these studies it can be concluded that these particular aldosterone-induced proteins: (1) are heavily glycosylated, (2) contain multiple high mannose and hybrid oligosaccharides side chains, and (3) contain similar (if not identical) peptide backbones. Post-translational N-glycosylation accounts, at least in part, for their electrophoretic polymorphism (variation in Mr) but not for their electrophoretic microheterogeneity (variation in pI). The latter may reflect other types of post-translational modification (e.g. O-glycosylation, phosphorylation) or may be due to subtle differences in amino acid composition. The partial purification and biochemical characterization of GP65,70 should ultimately lead to a better understanding of the function of these putative "effectors" of aldosterone-stimulated Na+ transport.

Aldosterone-induced proteins: purification and localization of GP65,70.

Aldosterone stimulates sodium transport in responsive epithelia by inducing "effector" proteins that control or modulate transcellular sodium flux. We have previously identified a group of electrophoretically microheterogeneous (pI 5.8-6.2) and polymorphic (Mr 65 and 70) glycoproteins that are specifically induced by aldosterone in toad urinary bladders (TUBs) and cultured toad kidney cells (A6 cell line). We raised a series of monoclonal antibodies (MAb) to these proteins and, using light and electron immunohistochemistry, localized the higher Mr glycoproteins (GP70) to the apical plasma membrane and subapical granules of the sodium-transporting cell of the TUB epithelium, the granular cell. GP70 appears to be discharged into the bladder lumen; this process is increased by phorbol myristate acetate, an agent known to induce granule exocytosis. These findings are consistent with the possibility that GP70 represent components or modulators of the "high-resistance" renal epithelial sodium channel. MAbs reactive against GP65 did not identify these glycoproteins within TUB epithelial cells; these lower Mr aldosterone-induced proteins may be incompletely processed forms of GP70.

Effect of renal impairment on disposition of pentopril and its active metabolite.

Disposition of pentopril was studied in 15 male volunteers with varying renal functions. Mild to moderate compromise in renal function did not demonstrate any appreciable changes in plasma concentration of pentopril, the prodrug ester of the active angiotensin-converting enzyme (ACE) inhibitor CGS 13934. This is consistent with the known elimination pattern for pentopril, which is eliminated primarily by hydrolysis to the active inhibitor. In contrast, the plasma concentration of the active ACE inhibitor was sensitive to moderate changes in renal function. Because of the reciprocal relationship of AUC and clearance, AUC did not change to any appreciable extent until creatinine clearance (CLCR) dropped to about 50 ml/min. Below 50 ml/min of CLCR, AUC and half-life increased sharply with reduced kidney function. Because of the significant contribution of the renal secretion process to total renal elimination of both pentopril and the active metabolite, prediction of renal clearance from CLCR was poor at relatively normal kidney function (CLCR greater than 80 ml/min). However, renal secretory clearances for both pentopril and metabolite were well correlated to p-aminohippuric acid clearance. In patients with moderately compromised renal function (glomerular filtration rate less than 40 ml/min), tubular secretion rate of creatinine approaches its glomerular filtration rate and hence CLCR could be used as a predictor of renal clearance and other disposition parameters. Plasma ACE activity also demonstrated prolonged inhibition with decreased renal function. Based on the prolonged blockade of plasma ACE activity, some correction in dose or dosing interval is anticipated in patients with moderately compromised renal function (CLCR less than 50 ml/min).

Aldosterone-induced glycoproteins: electrophysiological-biochemical correlation.

Aldosterone induces the synthesis of a group of glycoproteins (GP65,70) in toad urinary bladders which are potential effectors of the natriferic action of this hormone. In the present study we have confirmed that aldosterone produces a two-phase electrophysiological response. During the early phase (less than 3 h) short-circuit current and transepithelial conductance increase in parallel, while during the late phase (greater than 3 h) short-circuit current continues to increase without any further change in conductance. By biosynthetically labeling aldosterone-treated toad bladders with [35S]methionine either during the early (h 0-2 or 1-3) or the late (h 4-6 or 7-9) phases of the natriferic response, we have demonstrated that GP65,70 is synthesized as a late effect of aldosterone. Since synthesis of GP65,70 occurs at a time when the electromotive force of the Na+ pump is increasing, and since GP65,70 biochemically resembles the beta subunit of Na+/K+-ATPase, studies were undertaken to examine whether GP65,70 is the beta subunit. Purified amphibian renal beta subunit was analyzed by two-dimensional polyacrylamide gel electrophoresis and was found to have an isoelectric point and Mr value similar to those of GP65,70. However, when nitrocellulose blots containing wheat germ agglutinin-purified proteins from aldosterone-treated bladders were stained with monospecific polyclonal antibodies developed against the beta subunit, GP65,70 was not recognized, whereas a group of slightly more acidic proteins of similar Mr were recognized. Thus, GP65,70 is not the beta subunit of Na+/Ka+-ATPase. Further studies are needed to determine the cellular function of GP65,70.