Determining the optimal method for proteinuria detection in chronic spinal cord injury.

STUDY DESIGN: A retrospective analysis. OBJECTIVES: The objective of this study is to determine whether dipstick protein analysis (DSP) or random urine protein:creatinine ratios (UPC) are accurate in predicting clinical proteinuria in the chronic spinal cord injury (SCI) population. METHODS: A retrospective analysis was performed in 219 veterans with SCI, comparing DSP and 24-h urine protein excretion. Sensitivity, specificity, predictive values (PV) and receiver-operator characteristic (ROC) curves of DSP in predicting clinical proteinuria were calculated with and without correction for specific gravity (SG). A prospective study was also performed in 62 SCI patients, comparing the UPC and 24-h urines. Sensitivity, specificity, PV and ROC curves of UPC in predicting clinical proteinuria were calculated. RESULTS: Any level of positive DSP had high specificity, but low sensitivity, for detecting the presence of clinical proteinuria. ROC curves of DSP for identifying clinical proteinuria yielded area under the curve of 0.749 (95% confidence interval 0.699-0.794), and adjustment for SG did not significantly improve accuracy. A UPC of <0.3 was sensitive with a high negative PV for ruling out clinical proteinuria, whereas a ratio >0.8 was specific with a high positive PV. A UPC between 0.3-0.8 had an intermediate sensitivity and specificity. CONCLUSION: Urine collections of 24-h are still needed in the chronic SCI population for accurate detection of clinically significant proteinuria. DSP may not reliably detect low-grade clinical proteinuria, whereas a UPC below 0.3 may be used to rule out clinical range proteinuria.

Patterns of injury in mycophenolate mofetil-related colitis.

Mycophenolate mofetil (MMF) was introduced as a new immune-suppression drug in the mid-1990s. It is widely utilized in solid-organ transplantation immune-suppression regimens. Side effects include gastrointestinal (GI) toxicity in the form of nausea, vomiting, and diarrhea. Physicians tend to reduce the dose of MMF or switch their patients to an enterio-coated formula to overcome the side effects. Because GI side effects are well linked to MMF, colonoscopy is not utilized in most of the cases to investigate the diarrhea. However, Crohn's disease-like changes in the colon, erosive enterocolitis, and graft versus host disease-like colonic changes associated with the use of MMF have been reported. Colonic findings in five patients whose symptoms resolved after substituting another agent for MMF are described in the present report. Repeat colonoscopy 4 months following discontinuation of MMF showed reparative changes in one of our patients. MMF is an important drug in organ transplantation immune-suppression regimens; however, with its widespread usage, additional side effects continue to be recognized.

Predictors of mortality in end-stage renal disease patients with mitral annulus calcification.

OBJECTIVE: Mitral annulus calcification (MAC) is an independent predictor of cardiovascular mortality in the general population. The purpose of the current historical cohort study is to assess risk factors for long-term mortality in end-stage renal disease (ESRD) patients with MAC (n = 30; age, 62 +/- 2 yr), as compared to ESRD patients without MAC (n = 30; age, 63 +/- 2 yr). Additional analysis compared ESRD patients with MAC to non-ESRD patients with MAC (n = 32; age, 66 +/- 2 yr). METHODS: The groups included age-matched male patients followed at a single center. Long-term survival was assessed by Kaplan-Meier analysis. Regular and stepwise Cox proportional hazards models were used to determine risk factors for mortality. RESULTS: There was a similarly high prevalence of cardiovascular complications, including hypertension, coronary artery disease, left ventricular hypertrophy, atrial fibrillation, and congestive heart failure, in all three groups. Median survival time was significantly longer in non-ESRD patients (90 months), compared with the ESRD with MAC (45 months) and ESRD without MAC (45 months) patients (log-rank test; P < 0.001). With stepwise Cox proportional hazards model, including ESRD patients with MAC and ESRD patients without MAC, increased calcium x phosphate product, decreased serum creatinine concentration, and the presence of coronary artery disease and lower extremity amputations were independent predictors of mortality for patients with ESRD. With stepwise Cox proportional hazards model, including ESRD patients with MAC and non-ESRD patients with MAC, the presence of ESRD, atrial fibrillation, diabetes, aortic valve calcification, coronary artery disease, and tricuspid regurgitation were independent predictors of mortality. CONCLUSION: The mortality rate was high in ESRD patients, approximately 15% per year. After accounting for baseline cardiovascular disease and traditional risk factors, the presence of MAC did not confer additional risk for mortality.

"Definite lines of influence": Catholic sisters and nurse training schools, 1890-1920.

BACKGROUND: Standard histories of the nurse training school movement have focused on national leaders and organizations and have generally not included Catholic sisters, even though nuns had established approximately 220 nursing schools by 1915. OBJECTIVES: This study asks how Catholic sisters used their distinct understanding of nursing to shape their nursing schools and the nurse training movement in the United States between 1890 and 1920. METHOD: Historical methodology draws upon primary sources in archives of three women's religious congregations, the Catholic Health Association, and the University of Notre Dame. These include nuns' constitutions and letters, hospital chronicles, journals, minutes of meetings, training school records, annual reports, yearbooks, census records, and educational reports. Secondary sources include nursing, hospital, religious, and labor histories. RESULTS: Catholic sisters adapted their nursing to bring it into line with modern society by establishing nurse training schools for both religious and secular women. This legitimized their nursing practice and enhanced their influence with students, physicians, and hospital groups. As nuns admitted laywomen into their schools and worked toward accepted standards of professionalization, they stamped their distinct understanding of nursing onto secular society. DISCUSSION: The development of professionalized nursing drew Catholic sisters' schools toward common goals with non-Catholic programs. On the other hand, the sisters' historical construction of nursing in the 19th century, their unique relationship with physicians, and the obstacles they faced later, such as the Roman Catholic clergy's attempt to control evaluation processes, indicate a distinct approach to Catholic nursing. Questions remain as to whether nuns could hold onto their authority later in the 20th century.

Acute renal failure secondary to spontaneous acute tumor lysis syndrome in myelofibrosis.

A 70-year-old man with myelofibrosis developed nonoliguric acute renal failure in association with acute uric acid nephropathy in the absence of chemotherapy or radiotherapy. The patient had an 18-month history of transfusion-dependent myelofibrosis and moderate chronic renal insufficiency. Admission laboratory findings were remarkable for severe hyperuricemia, hyperphosphatemia, hyperkalemia, and hypocalcemia with acute deterioration of renal function, consistent with a diagnosis of acute uric acid nephropathy. Treatment, including hemodialysis and allopurinol administration, resulted in clinical improvement with normalization of serum uric acid concentrations and resolution of acute renal failure. With long-term allopurinol therapy, renal function has remained at his previous baseline, and there has been no transformation to acute leukemia. This case represents a rare instance of acute renal failure related to the occurrence of acute uric acid nephropathy associated with myelofibrosis and emphasizes the importance of early recognition and aggressive management, which can lead to recovery of renal function.

Cardiovascular effects of vasopressin following V(1) receptor blockade compared to effects of nitroglycerin.

Studies to more clearly determine the mechanisms associated with arginine vasopressin (AVP)-induced vasodilation were performed in normal subjects and in quadriplegic subjects with impaired efferent sympathetic responses. Studies to compare the effects of AVP with the hemodynamic effects of nitroglycerin, an agent that primarily affects venous capacitance vessels, were also performed in normal subjects. Incremental infusions of AVP following V(1)-receptor blockade resulted in equivalent reductions in systemic vascular resistance (SVRI) in normal and in quadriplegic subjects. However, there were major differences in the effect on mean arterial pressure (MAP), which was reduced in quadriplegic subjects but did not change in normal subjects. This difference in MAP can be attributed to a difference in the magnitude of increase in cardiac output (CI), which was twofold greater in normal than in quadriplegic subjects. These observations are consistent with AVP-induced vasodilation of arterial resistance vessels with reflex sympathetic enhancement of CI and are clearly different from the hemodynamic effects of nitroglycerin, i.e., reductions in MAP, CI, and indexes of cardiac preload, with only minor changes in SVRI.

Inducible nitric oxide synthase in the bladder of spinal cord injured patients with a chronic indwelling urinary catheter.

PURPOSE: Spinal cord injured patients are at increased risk for bladder carcinoma. Nitric oxide production in areas of chronic inflammation may provide a stimulus for carcinogenesis by serving as a source of nitrosating agents that generate potentially carcinogenic nitrosamines from secondary amines normally present in urine. MATERIALS AND METHODS: To determine whether inducible nitric oxide synthase is expressed as a catalyst for sustained nitric oxide production by cellular elements in chronically inflamed bladder mucosa immunohistochemical studies were performed on mucosal biopsies obtained from 37 adults with spinal cord injury. All participants had required a chronic indwelling urethral or suprapubic catheter for greater than 8 years. RESULTS: Histopathological studies revealed active inflammatory infiltrates in all 37 biopsy specimens, squamous metaplasia in 20, epithelial dysplasia in 3 and carcinoma in 1. Inducible nitric oxide synthase was detected in inflammatory cells localized to the lamina propria. Inducible nitric oxide synthase positive cells were identified as macrophages using monoclonal antibodies to macrophage antigen. There was no inducible nitric oxide synthase expression in the urothelial cell layers. Immunostaining for inducible nitric oxide synthase was not detected in bladder mucosal biopsy specimens obtained from cadaveric organ donors. CONCLUSIONS: Inducible nitric oxide synthase is expressed in inflammatory macrophages in areas of chronic inflammation in the bladder mucosa of spinal cord injured patients with a chronic indwelling bladder catheter. The expression of inducible nitric oxide synthase may potentially lead to the sustained production of nitric oxide and its oxidative products, the nitrosation of urinary amines and the formation of potentially carcinogenic nitrosamines in the bladder.

Livedo reticularis: an underutilized diagnostic clue in cholesterol embolization syndrome.

BACKGROUND: Cholesterol embolization syndrome (CES) is an increasingly recognized cause of acute renal insufficiency, which must be differentiated from other forms of systemic vasculitis by histologic examination of biopsies from involved organs. This report describes the optimal methods for detection and biopsy of areas of skin involved with livedo reticularis to confirm the diagnosis of CES. METHODS: This report describes 8 patients with unexplained acute renal insufficiency in whom the diagnosis of CES was suspected based on their clinical history. RESULTS: A detailed skin examination performed in both supine and upright postures demonstrated the presence of previously unrecognized livedo reticularis, which was more evident during upright posture in all subjects. In 2 subjects, questionable areas of livedo reticularis noted in supine posture became readily demonstrable during upright posture. Livedo reticularis was apparent only during upright posture in 2 subjects. Biopsies of areas of skin involved with livedo reticularis demonstrated cholesterol emboli in 6 of 8 patients and were normal in the remaining 2 patients. One patient progressed to end-stage renal disease and one was lost to follow-up. In the remaining 6 patients, renal insufficiency initially progressed but did not require dialytic therapy. Renal function returned to baseline levels and livedo reticularis resolved without recurrence in these patients. No subjects developed clinical or laboratory evidence of systemic vasculitis. CONCLUSIONS: Livedo reticularis is a common but often unrecognized finding in CES that may not be evident during routine examination performed in the supine posture. Deep cutaneous biopsy of areas of livedo reticularis can be safely used to confirm the presence of cholesterol emboli, thus avoiding the increased morbidity of biopsy of either pregangrenous skin lesions or visceral organs. Many patients with CES regain renal function during long-term follow-up.

Influences on renal function in chronic spinal cord injured patients.

PURPOSE: The optimal method of bladder management in the spinal cord injured population remains controversial. We determined the significance of bladder management and other factors on renal function in this population. MATERIALS AND METHODS: We retrospectively reviewed the medical records and upper tract imaging studies of 308 patients with a mean followup of 18.7 years since injury. Renal function was assessed by serum creatinine, creatinine clearance and proteinuria measurement, and by upper tract abnormalities on renal ultrasound and nuclear medicine renal scan. Independent variables evaluated for an influence on renal function included patient age, interval since injury, injury level and completeness, vesicoureteral reflux, history of diabetes mellitus and bladder management method. RESULTS: Mean serum creatinine plus or minus standard deviation in patients on chronic Foley catheterization, clean intermittent catheterization and spontaneous voiding was 1.08 +/- 0.99, 0.84 +/- 0.23 and 0.97 +/- 0.45 mg./dl. (analysis of variance p = 0.05, Student's t test p = 0.10), and mean creatinine clearance was 91.1 +/- 46.5, 113.4 +/- 39.8 and 115 +/- 49 ml. per minute, respectively (analysis of variance and Student's t test p <0.01), respectively. Proteinuria was present in 19 patients (6.2%) in the Foley catheterization, 3 (1%) in the clean intermittent catheterization and 4 (1.3%) in the spontaneous voiding group (chi-square test p <0.01), while there were upper tract abnormalities in 56 (18.2%), 20 (6.5%) and 24 (7.8%) patients, respectively (chi-square test p <0.01). Multiple regression analyses revealed no significant predictors of serum creatinine, although older patient age and Foley catheterization significantly predicted low creatinine clearance. Additional logistic regression analyses showed that Foley catheterization was associated with proteinuria and vesicoureteral reflux was associated with upper tract abnormalities. CONCLUSIONS: While renal function may be preserved by all forms of bladder management, chronic indwelling catheters may contribute to renal deterioration.

Acute fulminant lactic acidosis complicating metastatic cholangiocarcinoma.

A patient with cholangiocarcinoma, metastatic to the liver and lungs, developed acute fulminant lactic acidosis in the absence of overt hepatic failure, sepsis, hypoxia, or circulatory failure. Despite extensive tumor replacement of hepatic parenchyma, no acid-base disorder was present during initial evaluation. The onset of acute lactic acidosis was temporally associated with the development of otherwise asymptomatic episodes of intermittent atrial arrhythmias. Once established, lactic acidosis was inexorably progressive, despite resolution of arrhythmias. Extensive areas of acute necrosis within the large hepatic metastases were demonstrated on postmortem examination, suggesting that local tissue ischemia, precipitated by cardiac arrhythmias, lead to excessive lactic acid production.

Management of diabetic ketoacidosis.

Diabetic ketoacidosis is an emergency medical condition that can be life-threatening if not treated properly. The incidence of this condition may be increasing, and a 1 to 2 percent mortality rate has stubbornly persisted since the 1970s. Diabetic ketoacidosis occurs most often in patients with type 1 diabetes (formerly called insulin-dependent diabetes mellitus); however, its occurrence in patients with type 2 diabetes (formerly called non-insulin-dependent diabetes mellitus), particularly obese black patients, is not as rare as was once thought. The management of patients with diabetic ketoacidosis includes obtaining a thorough but rapid history and performing a physical examination in an attempt to identify possible precipitating factors. The major treatment of this condition is initial rehydration (using isotonic saline) with subsequent potassium replacement and low-dose insulin therapy. The use of bicarbonate is not recommended in most patients. Cerebral edema, one of the most dire complications of diabetic ketoacidosis, occurs more commonly in children and adolescents than in adults. Continuous follow-up of patients using treatment algorithms and flow sheets can help to minimize adverse outcomes. Preventive measures include patient education and instructions for the patient to contact the physician early during an illness.

Risk factors for development of proteinuria in chronic spinal cord injury.

A retrospective, case-control study was performed to investigate the risk factors that may contribute to the development of proteinuria in patients with chronic spinal cord injury (SCI). During an 18-month period, 31 subjects with a 24-hour protein excretion of 1.0 g or greater were identified. Three control subjects with SCIs with a 24-hour urinary protein excretion of less than 1.0 g during the same time period were randomly selected for each study subject with proteinuria. Clinical data, including level and duration of injury, age, presence of indwelling bladder catheter, number of decubitus ulcer procedures, serum albumin and creatinine concentrations, hematocrit, creatinine clearance, and the presence of hypertension and diabetes mellitus, were obtained from medical records. Subjects with proteinuria had other evidence of renal dysfunction with greater serum creatinine concentrations and reduced creatinine clearances, serum albumin concentrations, and hematocrits. Proteinuric subjects were older, had a longer duration of injury, had undergone a greater number of decubitus ulcer procedures, and were more likely to have hypertension and indwelling bladder catheters. The independent predictors for the development of proteinuria using logistic stepwise multiple linear regression analysis were the use of chronic indwelling bladder catheters, number of decubitis ulcer procedures, presence of hypertension, and older age. These data suggest that inflammatory complications associated with complications of chronic SCI, rather than SCI per se, contribute to the development of proteinuria. SCI patients with proteinuria have more impaired renal function and increased mortality compared with SCI patients without proteinuria.

Religion, gender, and autonomy: a comparison of two religious women's groups in nursing and hospitals in the late nineteenth and early twentieth centuries.

Modern historical research of women and nursing has largely neglected the role of religious groups, particularly in the American frontier. The image of women at the end of the 19th century was one of submission to male authority and confinement to the domestic sphere. However, in the pluralistic West, a variety of organized religious women built and administered hospitals, initiated professional nursing, and provided effective health care services. This article compares cases of Catholic nuns and Mormon women as exemplars in a conceptual context of religious devotion, gender roles, and autonomy among women's religious organizations at the dawn of the 20th century.

Hemodynamic response to vasopressin in dehydrated human subjects.

BACKGROUND: Despite the known potent vasoconstrictor effects of vasopressin, the role of this hormone in the maintenance of blood pressure is incompletely understood. In studies performed in animals with increased plasma vasopressin concentrations, several complex cardiovascular effects have been noted, including decreases in heart rate and cardiac output, which may account for a lack of effect on arterial pressure despite the vasopressin-induced increase in total peripheral resistance. Only a few studies have been done to assess the cardiovascular effects of vasopressin in human subjects, and most of these have been limited to measurement of heart rate and arterial pressure only. The present study was designed to identify more fully the cardiovascular effects of vasopressin when plasma vasopressin concentrations are increased by osmotic stimulation without the superimposition of major nonosmotic stimuli associated with severe volume depletion. METHOD: Studies were performed on 11 normal human subjects in supine and erect posture before and after 24 hours of fluid deprivation, and following administration of a selective V1 receptor antagonist, [d(CH2)5Tyr(ME)]AVP, after dehydration. Cardiovascular parameters were measured noninvasively by thoracic electrical bioimpedance cardiography and blood samples for measurements of plasma concentrations of vasopressin and other hormones affected by dehydration and differences in posture were collected for subsequent analysis. RESULTS: After 24 hours of fluid restriction, plasma osmolality was increased from 287 +/- 0.9 to 294 +/- 0.7 mosm/kg H20 and plasma vasopressin concentrations (Pavp) were increased in both supine and erect posture. Mean arterial (MAP) and systolic blood pressure (SBP) were reduced by fluid restriction but were higher in erect than in supine posture both before and after fluid restriction. Heart rate (HR), diastolic blood pressure (DBP), and systemic vascular resistance (SVRI) were also higher in erect than in supine posture, while cardiac index (CI), stroke index (SI), end-diastolic index (EDI), and an index of total thoracic fluid content (TFC) were all reduced in erect posture, both before and after dehydration. Plasma renin activity (PRA) and plasma norepinephrine concentrations (Pne) were increased in erect posture, both before and after dehydration, but there was no effect of erect posture on plasma vasopressin concentrations (Pavp), either before or after dehydration. Administration of the V1 receptor antagonist after dehydration had no effect on hemodynamic parameters other than small reductions in DBP and cardiac preload. CONCLUSION: It is concluded from these studies that small increases in Pavp associated with moderate dehydration do not play a role in the maintenance of arterial pressure in normal human subjects in either supine or erect posture.

Inappropriate antidiuresis and hyponatremia with suppressible vasopressin in Guillain-Barré syndrome.

Studies in which plasma osmolality was altered acutely by oral water loading and hypertonic sodium chloride infusion were performed to further identify the mechanisms involved in the pathogenesis of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in a patient with Guillain-Barré syndrome. Although resetting of the osmotic threshold for vasopressin release was demonstrated in these studies, this does not seem to have been a primary factor in the development of SIADH in this patient. Downward resetting of the osmotic threshold by sustained hypoosmolality has been previously demonstrated, and it is possible that this may account for the initially low osmotic threshold identified by our studies. These studies suggest that inappropriate antidiuresis, as shown by the absence of a diuretic response to low threshold suppression of the plasma arginine vasopressin concentration was due either to a vasopressin-independent mechanism or to markedly increased renal tubular sensitivity to vasopressin.