Colonic Mucosal Necrosis Following Administration of Calcium Polystryrene Sulfonate (Kalimate) in a Uremic Patient

Colonic necrosis is known as a rare complication following the administration of Kayexalate (sodium polystryrene sulfonate) in sorbitol. We report a rare case of colonic mucosal necrosis following Kalimate (calcium polystryrene sulfonate), an analogue of Kayexalate without sorbitol in a 34-yr-old man. He had a history of hypertension and uremia. During the management of intracranial hemorrhage, hyperkalemia developed. Kalimate was administered orally and as an enema suspended in 20% dextrose water to treat hyperkalemia. Two days after administration of Kalimate enema, he had profuse hematochezia, and a sigmoidoscopy showed diffuse colonic mucosal necrosis in the rectum and sigmoid colon. Microscopic examination of random colonic biopsies by two consecutive sigmoidoscopies revealed angulated crystals with a characteristic crystalline mosaic pattern on the ulcerated mucosa, which were consistent with Kayexalate crystals. Hematochezia subsided with conservative treatment after a discontinuance of Kalimate administration.     

Rectal stenosis caused by foreign body reaction to sodium polystyrene sulfonate crystals (Kayexalate)

Sodium polystyrene sulfonate (SPS) (Kayexalate) is a cation-exchange resin used to treat hyperkaliema. Administered with sorbitol, it usually has minor adverse effects, but it may cause colonic or intestinal necrosis in uremic patients. We report an unusual case of rectal stenosis due to SPS crystals in a 46-year-old man. The patient had been involved in a car accident with severe thoracic and abdominal trauma. During his hospitalization, he presented traumatic acute pancreatitis with ischemic colitis because of hypotension, and acute renal insufficiency treated by hemofiltration and Kayexalate administered by nasogastric tube without sorbitol. Left colon was resected and Hartmann's procedure was performed. Restoration of the colon continuity was performed 13 months later. The rectal lumen was narrowed with a thickened rectal wall. Microscopic examination revealed fibrosis of the submucosa containing numerous basophilic polygonal crystals surrounded by macrophages. This is the first case report of rectal stenosis caused by foreign body reaction to SPS crystals after ischemic colitis.     

Drug-induced pathology of the upper gastrointestinal tract

Drugs can produce a wide range of pathology in the upper gastrointestinal tract. Often, the injury pattern is non-specific. Pill-induced oesophagitis usually affects the mid oesophagus. In the stomach, many drugs, particularly non-steroid anti-inflammatory drugs (NSAIDs), can cause ulcers, erosions or reactive gastropathy. Some drugs produce specific injury patterns that can be recognized by pathologists. Proton pump inhibitors cause parietal cell hyperplasia and fundic gland polyps. Kayexalate may cause erosions or ulcers, with ‘mosaic’ crystals within the exudate, but other resins may show crystals that can be confused for Kayexalate. Iron therapy, mucosal calcinosis, and mucosal lanthanum deposition share the presence of crystals in the mucosa of affected patients. Various agents can cause non-specific mucosal changes that mimic celiac disease, GVHD, or inflammatory bowel disease, such as olmesartan, idelalisib, and checkpoint inhibitors. Colchicine causes variable injury, and interference with microtubule assembly results in mitotic arrest. Hepatic arterial infusion chemotherapy may cause gastroduodenal ulcers associated with marked epithelial atypia that can be mistaken for carcinoma. Recognition of these histological patterns enables pathologists to make a diagnosis of drug-induced upper gastrointestinal injury and potentially to identify the specific agent responsible.     

Successful treatment of a colonic ulcer penetrating the urinary bladder caused by the administration of calcium polystyrene sulfonate and sorbitol.

A 77-year-old woman was urgently admitted for the treatment of diabetic ketoacidosis and a duodenal ulcer hemorrhage in March 1999. She had a history of diabetes and angina pectoris. After admission, she received oral calcium polystyrene sulfonate and sorbitol to treat hyperkalemia. Nine days later, severe abdominal pain developed. A colonoscopic examination revealed a sigmoid colonic ulcer and stenosis; the patient was treated conservatively. At a 1-year follow-up examination, the colonic stenosis was found have worsened; pneumaturia developed in January 2001. The patient was found to have a sigmoidovesical fistula and underwent sigmoidectomy and partial resection of the ileum and urinary bladder. The histological findings were a benign colonic ulcer with the infiltration of inflammatory cells, mainly lymphocytes. Rhomboidal, dark violet Kayexalate crystals were observed on microscope examination in the submucosa in both the first and second colonic biopsy specimens. We concluded that the colonic ulcer and the sigmoidovesical fistula had been caused by the administration of calcium polystyrene sulfonate and sorbitol. Reports of colonic perforation as a result of the administration of calcium polystyrene sulfonate and sorbitol are rare. Here, we report the successful treatment of a colonic ulcer that had penetrated the urinary bladder.     

Sleep state instabilities in major depressive disorder: Detection and quantification with electrocardiogram‐based cardiopulmonary coupling analysis

Sleep disruption is an important aspect of major depressive disorder but lacks an objective and inexpensive means of assessment. We evaluated the utility of electrocardiogram (ECG)‐based cardiopulmonary coupling analysis to quantify physiologic sleep stability in patients with major depression. Relative to controls, unmedicated depressed patients had a reduction in high‐frequency coupling, an index of stable sleep, an increase in low‐frequency coupling, an index of unstable sleep, and an increase in very‐low‐frequency coupling, an index of wakefulness/REM sleep. The medicated depressed group showed a restoration of stable sleep to a level comparable with that of the control group. ECG‐based cardiopulmonary coupling analysis may provide a simple, cost‐efficient point‐of‐care method to quantify sleep quality/stability and to objectively evaluate the severity of insomnia in patients with major depression.     

Calculation of the Outcomes of Remodeling of Arteries Subjected to Sustained Hypertension Using a 3D Two-Layered Model

Arteries manifest a remodeling response to long-term alterations in arterial pressure and blood flow by changing geometry, structure, and composition through processes driven by perturbations of the local stresses in the vascular wall from their baseline values. The objective of this study is twofold—to develop a general method for calculating the remodeling responses of an artery considered as a two-layered tube; and to provide results for adaptive and maladaptive remodeling of a coronary artery. By formulating an inverse problem of vascular mechanics, the geometrical dimensions and mechanical properties of an artery are calculated from a prescribed deformed configuration, stress field, structural stiffness, and applied load. As an illustrative example we consider a human LAD coronary artery in both a perfect and incomplete adaptive response to a sustained step-wise change in pressure and a maladaptive response due to impaired remodeling of adventitia. The results obtained show that adventitia plays an important role in vascular mechanics when an artery is subjected to high arterial pressure. In addition to its well-known short term function of preventing over-inflation of an artery, it seems reasonable to accept that the manner by which adventitia remodels in response to a chronic increase in pressure is essential for preserving normal arterial function or may lead to an increased risk of developing vascular disorders.     

The cost of medical education in an ambulatory neurology clinic

Decreased revenue from clinical services has required academic hospitals and physicians to improve productivity. Medical student education may be a significant hindrance to increased productivity and income. This study quantifies the amount of time spent by faculty members teaching medical students in an ambulatory neurology clinic as well as the amount of time students occupied rooms when seeing patients on their own. Over a three-week period in an ambulatory neurology clinic, an observer noted these quantities of time, and the opportunity costs of both amounts of time were determined. Attending physicians spent an average of 19.6 minutes per medical student per half-day teaching, which translates to an average cost of $20.78 per half-day clinic. Students spent an average of 49.9 minutes per half-day seeing patients in the absence of an attending physician, an opportunity cost to the clinic of $142.50 per student per half-day.     

The multidimensional and developmental nature of infidelity: practical applications

When a partner has been unfaithful, an important therapeutic task is to assess factors that contributed to the affair and that may affect the individual's and couple's healing. This article provides a framework to assess multiple factors and their influence on an affair over time, as well as on responses to an affair. We address factors related to the person involved in an affair, his or her partner, their relationship, and the external context. These factors are considered across six phases of an affair: predisposition, approach, initial involvement, maintenance, disclosure or discovery, and response. A case study is presented to illustrate the usefulness of the framework in working with couples in which there has been an affair.     

Pulmonary vasodilatation and augmentation of right ventricular function following terbutaline infusion in severe chronic pulmonary disease

Twenty patients with a median age of 61 years and a median forced expired volume in 1 s (FEV1) after bronchodilating therapy of 0.55 l were studied in order to measure the effect of intravenous terbutaline on bronchial tone, cardiac function, pulmonary haemodynamics, gas exchange, and oxygen transport capacity during rest and in 10 patients during exercise. Terbutaline infusion during rest resulted in an increase in heart rate from 84 to 103 beats min-1 (P less than 0.01), a decrease in mean systemic arterial pressure from 95 to 80 mmHg (P less than 0.02), an unchanged mean pulmonary arterial pressure (18 mmHg), an increase in cardiac index from 2.89 to 3.86 l min-1 m-2 (P less than 0.01), an increase in right ventricular ejection fraction from 45 to 53% (P less than 0.01), an increase in left ventricular ejection fraction from 63 to 67% (NS), an unchanged arterial oxygen tension, and an increase in calculated oxygen delivery from 533 to 638 ml O2 min-1 m-2 (P less than 0.01). During exercise terbutaline infusion resulted in an increase in heart rate from 108 to 120 beats min-1 (P less than 0.05), a decrease in mean systemic arterial pressure from 117 to 106 mmHg (P less than 0.01), a decrease in mean pulmonary arterial pressure from 29 to 22 mmHg (P less than 0.01), an increase in cardiac index from 4.53 to 4.64 min-1 m-2 (NS), an unchanged arterial oxygen tension, and an increase in the calculated oxygen delivery from 834 to 856 ml O2 min-1 m-2 (NS). It was concluded that terbutaline augments right ventricular function: increases right ventricular ejection fraction and decreases right ventricular end-diastolic volume, and further decreases pulmonary vascular resistance without decreasing arterial oxygen tension, and increases oxygen delivery in patients with chronic pulmonary disease during rest and exercise.     

Increasing screening uptake amongst those intending to be screened: the use of action plans

This experimental study investigates an intervention designed to increase rates of antenatal screening uptake in those intending to undergo antenatal screening. Eighty-eight pregnant women intending to undergo prenatal screening were alternately allocated to standard care or asked to write a simple plan for attending or making an appointment. Twenty-five (63%) in the intervention group made an action plan. There was no difference in uptake of screening between the intervention group and the control group, nor between those making an action plan and the control group. Within the intervention group, those making an action plan had higher screening uptake (21/25, 84%) than those not making one (7/15, 47%; CI(95) difference = 8-66%, P = 0.017). Asking women who intend to undergo screening to make an action plan does not increase screening uptake. This result raises doubts about introducing simple action plans in a clinical situation as an effective means of changing behaviour.     

A demonstration of classical conditioning of the human eyeblink to an olfactory stimulus.

While acquisition of the eyeblink conditioned response to a variety of stimuli has been widely studied, it has yet to be established that humans will demonstrate a conditioned response to an olfactory stimulus. In this study we present data to show that humans will demonstrate a classically conditioned eyeblink response to an olfactory stimulus. Ten participants were tested in a delay conditioning procedure with an olfactory stimulus presented in a heated, humidified stream of air via an olfactometer, allowing the precise control over stimulus duration necessary for delay conditioning. Trials on which odor alone was presented were administered to four additional participants. Establishing that humans will demonstrate an eyeblink conditioned response to an olfactory stimulus will allow further exploration of the pathways involved in classical conditioning and associative learning, as well as an analysis of conditioning pathways across sensory modalities.     

Chronic experimental bacteremia in Yucatan micropigs

The Yucatan micropig has been used to develop an experimental model of chronic bacteremia. This animal exhibits clinical and biological characteristics that are close to those in humans, and the pharmacokinetic behaviours of many classes of drugs in this model are similar to those in man. Six adult female were intravenously inoculated with a mean Escherichia coli inoculum of 5.1 x 10(9) bacteria. During five days of spontaneous evolution, the medical follow-up includes biological, clinical and bacteriological parameters. A systemic inflammatory syndrome, a sepsis, an organ insufficiency and positive blood cultures mimic the human disease. In all animals there is an adynamia, a lack of motor coordination, an anorexia, a tachypnea, a fever, a leuconeutropenia followed by an hyperleucocytosis, an anemia, a thrombopenia, an acute tubulonephritis and an elevated sedimentation rate. In some cases, there is an increase of the C reactive protein, in others, an increase of IL-6 and IL-8. At day five, all animals are alive, and five micropigs have positive blood cultures. This chronic, reproducible model is thus suitable for further antibacterial treatments evaluations.     

A homogeneous bioelectrochemical immunoassay for thyroxine

Thyroxine has been modified with a ferrocene derivative to produce an immunologically reactive conjugate which remains capable of functioning as an electron transfer mediator, shuttling electrons between an oxido-reductase enzyme and an electrode. On binding with an anti-thyroxine antibody the conjugate's ability to function as a mediator is impaired. The conjugate has been used as a tracer in an homogeneous competitive assay to quantify the total thyroxine concentration in serum, the assay being measured electrochemically after the addition of a suitable oxidoreductase enzyme (glucose oxidase) and its substrate (glucose) on completion of antibody/antigen binding. This results in a simple and sensitive assay for thyroxine.     

Adaptive increase in force variance during fatigue in tasks with low redundancy

We tested a hypothesis that fatigue of an element (a finger) leads to an adaptive neural strategy that involves an increase in force variability in the other finger(s) and an increase in co-variation of commands to fingers to keep total force variability relatively unchanged. We tested this hypothesis using a system with small redundancy (two fingers) and a marginally redundant system (with an additional constraint related to the total moment of force produced by the fingers, unstable condition). The subjects performed isometric accurate rhythmic force production tasks by the index (I) finger and two fingers (I and middle, M) pressing together before and after a fatiguing exercise by the I finger. Fatigue led to a large increase in force variance in the I-finger task and a smaller increase in the IM-task. We quantified two components of variance in the space of hypothetical commands to fingers, finger modes. Under both stable and unstable conditions, there was a large increase in the variance component that did not affect total force and a much smaller increase in the component that did. This resulted in an increase in an index of the force-stabilizing synergy. These results indicate that marginal redundancy is sufficient to allow the central nervous system to use adaptive increase in variability to shield important variables from effects of fatigue. We offer an interpretation of these results based on a recent development of the equilibrium-point hypothesis known as the referent configuration hypothesis.     

Antiviral therapy with non-selective beta-blockers: preliminary experimental and clinical corroboration

Treatment with non-selective beta-blockers has been proposed to have an indirect antiviral activity acting via an enhanced performance of the immune system, and the mechanism of this activity has been laid out earlier. Experimental and clinical findings are presented that corroborate the hypothesis that inhibiting the immunosuppressive and stress-related cAMP-PKA pathway will enhance the immune system's ability to recognize foreign antigen and to access its vast repertory in an improved way, resulting in an indirect antiviral activity. Other drugs having an inhibitory effect on the cAMP-PKA pathway in cells of the immune system and therefore expected to have a comparable activity spectrum with different specific side-effects are presented, for example aspirin. Additionally the so far unexplained anticancer activity of aspirin is related to the same mechanism of an enhanced performance of the immune system.     

Cellular and protein changes in bronchial lavage fluid after late asthmatic reaction in patients with red cedar asthma

To investigate the sequence of cellular and protein changes after a late asthmatic reaction (LAR), bronchial lavage was carried out in 44 patients with red cedar asthma at different time intervals after bronchial challenge with plicatic acid. The results were compared to five patients with red cedar asthma who became asymptomatic after removal from exposure to red cedar for more than 2 months and 31 healthy subjects without asthma. The LAR was found to be associated with an increase in eosinophils in the lavage fluid, an increase in sloughing of bronchial epithelial cells, and an increase in degenerated cells consisting mainly of degenerated epithelial cells and alveolar macrophages. There was an increase in vascular permeability as reflected by an increase in albumin in the lavage fluid. Although there was a slight but significant increase in neutrophils 48 hours after bronchial challenge, neutrophil infiltration was not a prominent feature earlier. The potential role of loss of epithelial cells to account for an increase in nonspecific bronchial hyperresponsiveness after an LAR was discussed.     

Academic Portfolio in the Digital Era: Organizing and Maintaining a Portfolio Using Reference Managers

The academic portfolio has become an integral part of the promotions process. Creating and maintaining an academic portfolio in paper-based or web-based formats can be a cumbersome and time-consuming task. In this article, we describe an alternative way to efficiently organize an academic portfolio using a reference manager software, and discuss some of the afforded advantages. The reference manager software Papers (Mekentosj, Amsterdam, The Netherlands) was used to create an academic portfolio. The article outlines the key steps in creating and maintaining a digital academic portfolio. Using reference manager software (Papers), we created an academic portfolio that allows the user to digitally organize clinical, teaching, and research accomplishments in an indexed library enabling efficient updating, rapid retrieval, and easy sharing. To our knowledge, this is the first digital portfolio of its kind.     

Sexual Risk Following a Sexually Transmitted Disease Diagnosis: The More Things Change the More They Stay the Same

The purpose of this study is to assess changes in sexual risk behaviors, attitudes toward using condoms, and perceived susceptibility to fiuture STDs for adolescent females who recently were diagnosed with an incident STD compared to those who were not diagnosed with an incident STD. Adolescent females (N = 308) were assessed at two time points, 6 months apart. Ninety-two participants were diagnosed with an STD, and 216 were not diagnosed with an STD in between the two time points. Results indicated that adolescents did not significantly change their behaviors, attitudes, or perceptions following the diagnosis of an incident STD compared to those who were not diagnosed with an incident STD. This suggests that an STD diagnosis alone is not sufficient to motivate adolescent females to reduce their sexual risk behavior and change their sexual risk attitudes and perceptions.     

Anticipatory postural adjustments and the latency of compensatory stepping reactions in humans

A compensatory stepping response is a commonly used strategy in recovering balance control after a postural perturbation. Unlike gait initiation, the compensatory stepping often occurs without an anticipatory postural adjustment (APA), in which body weight is shifted to the swing leg first and then back to the stance leg prior to foot lifting. In postural perturbation studies using a moving platforms stepping responses without an APA were found to have shorter latency to foot lifting than trials with an APA. We studied stepping responses of healthy young adults under postural perturbation of a pulling force impulse on the subject's waist. In contrast to previous studies, the latency of foot lifting was found in the current study to be shorter in the trials with an APA than trials without an APA. Furthermore, greater amplitude of an APA was associated with a shorter latency of foot lifting. Response with an APA of large amplitude may indicate high level of determinant for foot lifting. A pause as to whether or not to initiate/complete a stepping response is suggested to be partially the cause of delayed foot lifting in trials without an APA or with small amplitude of the APA.     

Cost-effectiveness of enfuvirtide in treatment-experienced patients with advanced HIV disease

OBJECTIVE: Enfuvirtide (ENF) has been shown to improve short-term virologic responses when given to highly treatment-experienced patients with advanced HIV disease. Because of the high cost of ENF compared with other antiretroviral agents, our objectives were to determine the potential long-term clinical impact and cost-effectiveness of ENF in these patients. METHODS: We used a computer simulation model of HIV disease to project life expectancy, quality-adjusted life expectancy, cost, and cost-effectiveness of ENF in treatment-experienced patients. Input data were from the T-20 versus Optimized Regimen Only (TORO) 1 and 2 trials, 2 studies comparing ENF plus an optimized background regimen (OBR) with an OBR alone. RESULTS: ENF plus an OBR increased projected discounted quality-adjusted life expectancy from 45.4 months with an OBR alone to 54.9 months, a difference of 9.5 quality-adjusted life-months. At the current annual ENF cost of US 18,500 dollars per year (in 2001 US dollars), the incremental cost-effectiveness ratio for ENF plus an OBR was US 69,500 dollars per quality-adjusted life-year (QALY) compared with an OBR alone. When 48-week virologic suppression rates for ENF plus an OBR were varied from a 50% reduction to a 250% increase in the suppression rate attributable to ENF, gains in quality-adjusted life expectancy ranged from 4.5 to 25.9 quality-adjusted life-months compared with an OBR alone, with cost-effectiveness ratios ranging from US 97,900 dollars per QALY to US 52,300 dollars per QALY gained. If ENF is continued after the HIV RNA level returns to the pretreatment baseline, the cost-effectiveness ratio increases to US 168,200 dollars per QALY. CONCLUSIONS: In highly treatment-experienced patients, ENF plus an OBR provides substantial gains in quality-adjusted life expectancy compared with an OBR alone. Although ENF plus an OBR is less cost-effective than other commonly used interventions in HIV disease, its use may be justified, given the poor prognosis of these patients and their otherwise limited options for antiretroviral therapy.