Process of care events in transplantation: effects on the cost of hospitalization.

Deviations in the processes of healthcare delivery that affect patient outcomes are recognized to have an impact on the cost of hospitalization. Whether deviations that do not affect patient outcome affects cost has not been studied. We have analyzed process of care (POC) events that were reported in a large transplantation service (n = 3,012) in 2005, delineating whether or not there was a health consequence of the event and assessing the impact on hospital resource utilization. Propensity score matching was used to adjust for patient differences. The rate of POC events varied by transplanted organ: from 10.8 per 1000 patient days (kidney) to 17.3 (liver). The probability of a POC event increased with severity of illness. The majority (81.5%) of the POC events had no apparent effect on patients' health (63.6% no effect and 17.9% unknown). POC events were associated with longer length of stay (LOS) and higher costs independent of whether there was a patient health impact. Multiple events during the same hospitalization were associated with the highest impact on LOS and cost. POC events in transplantation occur frequently, more often in sicker patients and, although the majority of POC events do not harm the patient, their effect on resource utilization is significant.

Granular cell tumor of the penis shaft: case report and literature review.

INTRODUCTION: Granular cell tumors (GCT) are uncommon soft tissue neoplasms of presumed neural origin that rarely involve the male external genitalia. Penile lesions are distinctly uncommon with less than 20 cases reported till now. OBJECTIVE: In the present paper we describe the clinicopathological and immunohistochemical findings in a case of GCT of the penis shaft in a 31-years-old man. RESULTS AND CONCLUSIONS: On physical examination the patient was found to have a small ovoid mass, 20 x 10 mm in diameter, at the left postero-lateral area of the penis' base. The mass was firm on palpation with no fixation on the neighboring tissues. The lesion was completely excised under loco-regional anesthesia. The surgical specimen was an ovoid, gray-white, elastic mass, of 10 x 5 mm. Microscopically, the tumor was moderately cellular and was composed of polygonal-shaped cells with abundant granular eosinophilic cytoplasm. Tumor cells were disposed in nests, cords, and trabeculae and showed perineural invasion. The tumor presented bland cytological features with only focal slight nucleo-megaly. Mitotic activity was undetectable. The tumor cells showed diffuse immunohistochemical expression for S100 protein. At 6 month after surgery the patient was free of persistent/recurrent disease or metastatic spread of the tumor. We discuss the clinical, histo-immunohistochemical and therapeutical features of this unusual penile tumor, the single one encountered in the Department of Pathology from Timisoara County Hospital and, to our knowledge, the only one reported in the Romanian medical literature.

Antifungal effect of gaseous nitric oxide on mycelium growth, sporulation and spore germination of the postharvest horticulture pathogens, Aspergillus niger, Monilinia fructicola and Penicillium italicum.

AIM: To evaluate the antifungal activity of nitric oxide (NO) against the growth of the postharvest horticulture pathogens Aspergillus niger, Monilinia fructicola and Penicillium italicum under in vitro conditions. METHODS AND RESULTS: Different volumes of NO gas were injected into the Petri dish headspace to obtain the desired concentrations of 50-500 microl l(-1). The growth of the fungi was measured for 8 days of incubation in air at 25 degrees C. All concentrations of NO were found to produce an antifungal effect on spore germination, sporulation and mycelial growth of the three fungi, with the most effective concentration for A. niger and P. italicum being 100 and 500 microl l(-1) for M. fructicola. CONCLUSIONS: Short-term exposure to a low concentration of NO gas was able to inhibit the subsequent growth of A. niger, M. fructicola and P. italicum. SIGNIFICANCE AND IMPACT OF THE STUDY: NO gas has potential use as a natural fungicide to inhibit microbial growth on postharvest fruit and vegetables.

Transforming growth factor alpha: mutation of aspartic acid 47 and leucine 48 results in different biological activities.

To study the relationship between the primary structure of transforming growth factor alpha (TGF-alpha) and some of its functional properties (competition with epidermal growth factor (EGF) for binding to the EGF receptor and induction of anchorage-independent growth), we introduced single amino acid mutations into the sequence for the fully processed, 50-amino-acid human TGF-alpha. The wild-type and mutant proteins were expressed in a vector by using a yeast alpha mating pheromone promoter. Mutations of two amino acids that are conserved in the family of the EGF-like peptides and are located in the carboxy-terminal part of TGF-alpha resulted in different biological effects. When aspartic acid 47 was mutated to alanine or asparagine, biological activity was retained; in contrast, substitutions of this residue with serine or glutamic acid generated mutants with reduced binding and colony-forming capacities. When leucine 48 was mutated to alanine, a complete loss of binding and colony-forming abilities resulted; mutation of leucine 48 to isoleucine or methionine resulted in very low activities. Our data suggest that these two adjacent conserved amino acids in positions 47 and 48 play different roles in defining the structure and/or biological activity of TGF-alpha and that the carboxy terminus of TGF-alpha is involved in interactions with cellular TGF-alpha receptors. The side chain of leucine 48 appears to be crucial either indirectly in determining the biologically active conformation of TGF-alpha or directly in the molecular recognition of TGF-alpha by its receptor.

Transforming growth factor alpha: an aromatic side chain at position 38 is essential for biological activity.

Site-directed mutagenesis has been performed in the human transforming growth factor alpha gene. When tyrosine 38 is mutated into phenylalanine or tryptophane, biological activity is retained. In contrast, other alterations between cysteine 34 and cysteine 43 and disruption of disulfide bonds 8 to 21 and 34 to 43 resulted in loss of activities. The presence of an aromatic side chain at position 38 of transforming growth factor alpha seems to be essential for its activity.

[An unusual splenic tumor. Littoral cell angioma]. / O tumora splenica neobisnuita. Angiomul cu celule litorale.

Littoral cell angioma is a rare splenic tumor which develops from specialised endothelial cells of the splenic red pulp. Numerous papers published since 1991 when the tumor was firstly described till now were focused on the radiologic characteristics of the lesion. This paper presents the clinical, imaging and morpho-immunohistochemical features of a littoral cell angioma diagnosed in a 51 year - old woman, to our knowledge, the first documented case in the Romanian medical literature. The lesion might be suspected on the basis of the clinical and imaging signs, but the diagnosis of certitude is provided by the gross and microscopic examination supplemented with immunohistochemical methods.

Roundness of grains in cellular microstructures.

Many physical systems are composed of polyhedral cells of varying sizes and shapes. These structures are simple in the sense that no more than three faces meet at an edge and no more than four edges meet at a vertex. This means that individual cells can usually be considered as simple, three-dimensional polyhedra. This paper is concerned with determining the distribution of combinatorial types of such polyhedral cells. We introduce the terms fundamental and vertex-truncated types and apply these concepts to the grain growth microstructure as a testing ground. For these microstructures, we demonstrate that most grains are of particular fundamental types, whereas the frequency of vertex-truncated types decreases exponentially with the number of truncations. This can be explained by the evolutionary process through which grain growth structures are formed and in which energetically unfavorable surfaces are quickly eliminated. Furthermore, we observe that these grain types are "round" in a combinatorial sense: there are no "short" separating cycles that partition the polyhedra into two parts of similar sizes. A particular microstructure derived from the Poisson-Voronoi initial condition is identified as containing an unusually large proportion of round grains. This microstructure has an average of 14.036 faces per grain and is conjectured to be more resistant to topological change than the steady-state grain growth microstructure.

[Natural history of portal cavernoma without liver disease. A single centre retrospective study of 32 cases]. / Évolution naturelle des cavernomes portaux non liés à une hépatopathie. Étude rétrospective monocentrique de 32 observations.

PURPOSE: Portal cavernoma follows a chronic occlusion of the portal vein. The long-term consequences of portal cavernoma are not well known. The objective of this study was to report the aetiology of the portal cavernoma and its natural course after excluding liver diseases causes. METHODOLOGY: A single centre retrospective study based on the data collected from the radiology department of the Clermont-Ferrand hospital was conducted from 2000 to 2011. All the patients for whom an imagery found a portal cavernoma have been looked for excluding the patients having a liver disease whatever the aetiology and the Budd-Chiari syndrome. RESULTS: Thirty-two cases (18 women and 14 men) were selected. The mean age at diagnosis was 54.2 years and the mean follow-up period was 5.4 years. The discovery of a portal cavernoma was incidental for 8 cases. An aetiology was found for 24 cases: it was an haematological aetiology in 15 cases (10 myeloproliferative syndromes, 2 antiphospholid syndromes, 1 thalassemia major, 1 hyperhomocysteinemia, 1 prothrombin gene mutation), a general aetiology in 2 cases (1 coeliac disease, 1 pancreatic neoplasia), and a local inflammation in 7 cases. A dysmorphic aspect of the liver was noticed on medical imaging for 11 out of the 32 cases. A liver biopsy was performed in 4 patients and was normal for all of them. Sixteen patients developed oesophageal varices, 4 patients developed ascites, 3 developed asymptomatic biliary compression by the portal cavernoma, and the patient who had been followed for the longest time (15 years) developed an encephalopathy. CONCLUSION: In addition to its underlying etiology, the prognosis of portal is mainly related to the occurrence of oesophageal varices that may develop during the follow-up of the patients.

Severe hyperkalemia during piroxicam therapy.

Severe hyperkalemia developed in an 85-year-old man after he had been receiving piroxicam treatment for several months. At admission his serum potassium level was 9.3 mEq/L; total CO2 level, 11 mmole/L; chloride level, 122 mEq/L; serum urea nitrogen level, 54 mg/dL; and creatinine level, 2.5 mg/dL. Hyperkalemia resolved after withdrawal of the drug and polystyrene sodium sulfonate therapy and the nonanion gap acidosis subsided concomitantly. His serum urea nitrogen and creatinine levels remained unchanged. He had abnormally low plasma renin activity, which gradually returned to normal, and aldosterone concentration, which remained low. The nonsteroidal drug may have impaired renin secretion, adrenal responsiveness to angiotensin, or the action of aldosterone on the renal tubule.

Respiratory muscle dysfunction in hereditary motor sensory neuropathy, type I.

Pulmonary function tests were performed on ten patients who were shown to have hereditary motor sensory neuropathy, type I. Mean values for spirometry, static lung volumes, and diffusion capacity were all greater than 80% of the predicted normal values for the group. In contrast, both inspiratory and expiratory muscle testing showed substantial reductions in function for the group. These abnormalities have not previously been reported, and they may be important in the management of these patients and in patients with other neuromuscular diseases.

Oral contraceptives and other risk factors for gallbladder disease.

Prior studies of the association between oral contraceptives (OCs) and gallbladder disease (GBD) have yielded conflicting results. To clarify this association, a retrospective (historical) cohort study was performed on a very large data base including 1980 and 1981 Medicaid billing data from the states of Michigan and Minnesota in which 138,943 users of OCs were compared with 341,478 nonusers. The crude relative risk (RR) and 95% confidence interval (CI) for symptomatic GBD resulting in medical care was 1.14 (CI 1.09 to 1.20), with a clear dose-response (P less than 0.001). Age markedly modified the effect of OCs on GBD. The RR (CI) decreased from 3.1 (2.7 to 3.6) in women 15 to 19 years old to 1.2 (0.9 to 1.5) in women 40 to 44 years old, providing an explanation for previously conflicting reports. The effects of a number of other risk factors on GBD, some which have been controversial, were also confirmed. Adjustment for these did not change the results. In conclusion, OCs are risk factors for GBD, although the risk is of sufficient magnitude to be of potential clinical importance only in young women.

PIP: To clarify the association between oral contraceptives (OCs) and gallbladder disease (GBD), a retrospective (historical) cohort study was performed with 1980 and 1981 Medicaid billing data from the states of Michigan and Minnesota in which 138,943 users of OCs were compared to 341,478 nonusers. There were 12,292 cases of GBD that required medical attention during the 2-year study, giving an overall prevalence rate of 25.6/1000 persons over the 2 years. Of the 138,943 OC users in this study, 3889 had GBD, giving a prevalence of 28.0/1000 persons in the 2-year study. Of the 341,478 nonusers, 8403 had GBD, resulting in a prevalence rate of 24.6/1000 persons in these 2 years. The overall prevalence rate in the unexposed subjects in Michigan was higher than that in Minnesota (28.5 vs. 12.3/1000 persons in the 2 year, respectively). This difference in prevalence by state may rest in part from differences in urbanization or to the known differences in racial distribution. Comparing Minnesota with Michigan, blacks are markedly underrepresented (5.9% versus 35.6%), Indians are overrepresented (3.9% versus 0.37%), and Orientals are overrepresented (5.7% versus 0.48%). Alternatively, this difference in prevalence by state may result from administrative dissimilarities between the 2 Medicaid programs, such as in differences in the number of diagnoses that can be provided per visit and the number of visits that can be included on each claim form. The results indicate that subsequent analyses need to be state specific or state adjusted. The crude relative risks confidence intervals for the effect of OCs on GBD were 1.14 overall, 1.08 for Michigan, and 1.39 for Minnesota. While the proportion of subjects using OCs decreased with advancing age, the prevalence of GBD increased steadily with age in both users and nonusers. Stratification by 5-year age intervals revealed age to be a strong modifier of the effect of OCs on GBD, with younger women at a higher risk of GBD from OCs than middle-aged women. The effects of a number of other risk factors on GBD also were confirmed. Adjustment for these failed to change the results. The relationship between OCs and GBD remained statistically significant even after age, state, and each confounding variable was controlled for logistic regression. In sum, OCs are risk factors for GBD, although the risk is of sufficient magnitude to be of potential clinical importance only in young women.

Transplantation of Y79 cells into rat eyes: an in vivo model of human retinoblastomas.

PURPOSE: To develop an in vivo model of human retinoblastoma by returning cultured Y79 retinoblastoma cells to the retinal environment of a widely available laboratory animal. In so doing, to study the survival, integration, and invasive characteristics expressed by tumoral cells grafted into an intraocular milieu from which these progenitor cells originated more than 20 years ago. METHODS: Using the retinal grafting method of Lazar and del Cerro, Y79 cells were injected under direct visualization into the subretinal space of Fischer 344 rats. The host rats included 36 animals that received daily injections of cyclosporin A and 4 that did not. All hosts were sacrificed 30 to 60 days after transplantation. RESULTS: Clinical examination showed vitreal invasion by masses of flocculent white material or the intravitreal formation of solid tumors. Histologic examination showed these formations to be outgrowths of grafted tumoral cells into the host retina and vitreal cavity. Highly anaplastic tumoral cells were also found lodged in subretinal and intraretinal locations. There were signs of continued and intense cell division within the grafts, with no indication of cell-mediated host reaction against the grafted cells. CONCLUSIONS: After intraretinal xenografting, human Y79 retinoblastoma cells retain a highly tumoral nature despite many years of in vitro propagation. When xenografted, these cells survive, grow, and express their malignancy within the retina of the common laboratory rat protected by a moderate immunosuppressive regimen. This partial immunosuppression is a requirement for the xenografts to prosper. This model offers a valuable opportunity to study in vivo the cellular and molecular biology of this and other human retinoblastomas, and it may facilitate the evaluation of antitumoral treatments.

Pharmacokinetic optimisation of therapy with beta-adrenergic blocking agents.

beta-Adrenergic blockade has provided one of the major pharmacotherapeutic advances of this century. The drugs in this class have the common property of blocking the binding of catecholamines to beta-adrenergic receptor sites; however, there are pharmacodynamic and pharmacokinetic differences between the individual agents which are of clinical importance. Among these differences are the completeness of gastrointestinal absorption, degree of hepatic first-pass metabolism, lipid solubility, protein binding, brain penetration, concentration within cardiac tissue, rate of hepatic biotransformation, and renal clearance of drug and/or metabolites. Long-acting formulations of existing beta-blockers are currently in use, and ultrashort-acting agents are also available. The pharmacokinetics of beta-blocking drugs can also be influenced by race, age, cigarette smoking and concomitant drug therapy. The wide interpatient variability in plasma drug concentration observed with beta-blockers makes this parameter unreliable in routine patient management. Despite the pharmacokinetic differences among the beta-blockers, these drugs should always be titrated in the individual patient to achieve the desired clinical response.

Reduction of mortality, sudden death and non-fatal reinfarction with beta-adrenergic blockers in survivors of acute myocardial infarction: a new hypothesis regarding the cardioprotective action of beta-adrenergic blockade.

Beta-adrenergic blockers have been shown definitely to reduce the incidence of total mortality, cardiovascular mortality, sudden death and nonfatal reinfarction in survivors of an acute myocardial infarction. The mechanisms to explain this protective action of beta blockers have never been elucidated conclusively, and include the antiarrhythmic and myocardial oxygen demand-reducing effects of the drugs. An antithrombotic mechanism has also been suggested. However, beta blockers have relatively weak antiplatelet activity, suggesting that their antithrombotic effects may be related to prevention of coronary artery plaque rupture and the subsequent propagation of an occlusive arterial thrombus rather than direct anticoagulant action. The therapeutic ability of beta blockers to attenuate the hemodynamic consequences of catecholamine surges, may protect a vulnerable atherosclerotic plaque from fracture, thereby reducing risk of coronary thrombosis, myocardial infarction and death.

Celiprolol in systemic hypertension.

The safety and efficacy of orally administered celiprolol, a new beta 1-selective adrenergic blocking drug with peripheral beta 2-agonist properties, were assessed in 91 patients with mild to moderate systemic hypertension (supine diastolic blood pressure [BP] 95 to 114 mm Hg without medication) using a placebo-controlled, double-blind, randomized, titration-to-effect study design. All patients received placebo for 4 weeks and were then randomized to receive placebo (n = 46) or once-daily celiprolol (n = 45), which was titrated every 2 weeks (200, 400, 600 mg/day) over a 6-week period to achieve a reduction in supine diastolic BP to less than or equal to 90 mm Hg. Plasma lipids and lipoproteins were also assessed at baseline, during placebo and after randomization to active therapy in a subgroup of patients. Compared with placebo, celiprolol reduced supine and standing BP (reduction of supine BP -0.4/-2.1 mm Hg with placebo, -5.7/-6.4 with celiprolol, p less than 0.05; reduction of standing BP -1.7/-1.0 with placebo, -7.2/-4.9 with celiprolol, p less than 0.05). Supine heart rate was reduced by 6.8 beats/min with celiprolol compared with 2.0 beats/min with placebo (p less than 0.05). No differences were seen when the effects of placebo and celiprolol on plasma lipoproteins were compared. Celiprolol is a safe, effective and well tolerated once-daily antihypertensive drug and has no detrimental effects on plasma lipids.

Prevalence, incidence and prognosis of recognized and unrecognized myocardial infarction in persons aged 75 years or older: The Bronx Aging Study.

The prevalence, incidence and prognosis of recognized and unrecognized Q-wave myocardial infarction (MI) was assessed in an 8-year prospective study of 390 community-based subjects (age 75 to 85 years at entry, mean 79 years). Subjects were studied at baseline and with annual follow-up electrocardiographic (ECG) exams. At baseline, 7.9% had a history of MI without ECG evidence, 6.4% had ECG evidence of Q-wave MI without clinical history, 4.1% had both clinical history and ECG evidence and 81.5% had neither history nor ECG evidence (control subjects). After an average follow-up period of 76.2 months, the total mortality rate was 5.9/100 person-years for subjects with some evidence of MI at baseline versus 3.9 in the control group (p = 0.059). The incidence of cardiovascular disease in subjects with evidence of MI was 8.8/100 person-years versus 4.7 among control subjects (p = 0.002). During the follow-up period, 115 new Q-wave MIs occurred (50 unrecognized, rate 2.4/100; 65 recognized, rate 3.2/100). There was no difference in mortality and morbidity outcome between subjects with recognized and unrecognized MIs. Those with only a history of MI at baseline had a threefold greater risk of a new MI (recognized and unrecognized) than the control group (p = 0.003). Unrecognized Q-wave MI is a common occurrence in the "old old" with subsequent morbidity and mortality prognosis comparable to that of recognized MI. History of MI alone in this age group is also associated with an increased risk of MI, suggesting the need for better diagnostic markers of myocardial ischemia in the old.

Profile of an ideal antianginal agent.

Many antianginal agents are available for the treatment of coronary artery disease. These agents act by influencing the determinants of myocardial oxygen supply and demand. The 3 main classes of agents are the nitrates, beta-adrenergic blocking agents and the calcium entry blockers. Agents from all 3 classes have shown efficacy in treating both symptomatic and asymptomatic myocardial ischaemia. However, some patients cannot be treated with these agents because of side effects or contraindications. An ideal antianginal drug should effectively treat both angina and silent ischaemia. Additionally, it should be free of side effects, allow for maintenance of physical performance and be metabolically neutral. New agents are being developed which strive for this goal.

Determinants of physician reluctance to perform mouth-to-mouth resuscitation.

OBJECTIVES: Mouth-to-mouth resuscitation (MMR) is widely taught and promoted. The purpose of this study was to better characterize the observation that health professionals are reluctant to perform MMR and to identify determinants of this reluctance. METHODS: 324 residents and faculty at a New York City teaching hospital were anonymously surveyed regarding their reluctance to perform MMR. One year later, medical staff were resurveyed. RESULTS: Reluctance varied across scenarios: 70-80% of physicians were willing to perform MMR on a newborn or child, 40-50% for an unknown man, and 20-30% for a trauma victim or potentially gay man. Physicians reported very similar percentages for each scenario in the two surveys. Factors associated with MMR reluctance were female gender (OR = 2), resident physician (OR = 2), and higher perceived risk of contracting HIV from MMR (OR = 1.4 per unit on 5-point scale). In the year before the survey, 30% of all respondents witnessed an apneic patient who required MMR for whom ventilation was not provided for at least 2 minutes. CONCLUSIONS: Many physicians are reluctant to perform MMR. Marked delays in ventilation of apneic patients are occurring.

Endocarditis of a tricuspid prosthesis causing valvular stenosis and shunting through a patent foramen ovale.

A young intravenous drug user presented with Staphylococcus aureus endocarditis involving the tricuspid valve, which was replaced with a Hancock bioprosthesis. She presented again with fever and dyspnea five months later and was found to be cyanotic. Recurrent endocarditis involving the prosthesis with right-to-left shunting through a patent foramen ovale was documented by echo and confirmed at autopsy.