Disseminated toxoplasmosis presenting as septic shock five weeks after renal transplantation.

We discuss a case of acute disseminated toxoplasmosis in a renal transplant recipient presenting with septic shock. Our literature review of disseminated toxoplasmosis presenting as septic shock reveals a disease process that is rapid and almost uniformly fatal. This unusual presentation warrants a high index of suspicion in transplant recipients with immediate administration of appropriate empiric antimicrobials.

Stabilization of reactive nitroxides using invasomes to allow prolonged electron paramagnetic resonance measurements.

The detection of the antioxidative capacity of the skin is of great practical relevance since free radicals are involved in many skin damaging processes, including aging and inflammation. The nitroxide TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxyl) in combination with electron paramagnetic resonance spectroscopy was found suitable for measuring the antioxidative capacity since its reaction with reducing agents is considerably fast. Yet, in order to achieve longer measurement times, e.g. in inflammatory skin diseases, the stabilizing effect of an invasome (ultraflexible vesicle/liposome) suspension with TEMPO was investigated ex vivo on porcine skin and in vivo on human skin. Invasomes increased the measurement time ex vivo 2-fold and the reduction was significantly slowed down in vivo, which is due to membrane-associated and therefore protected TEMPO. Furthermore, TEMPO accumulation in the membrane phase as well as the decreasing polarity of the ultimate surroundings of TEMPO during skin penetration explains the stabilizing effect. Thus, an invasome suspension with TEMPO exhibits stabilizing effects ex vivo and in vivo.

Pennsylvania coordinated specialty care programs for first-episode psychosis: 6- and 12-month outcomes.

AIM: Pennsylvania (PA) first-episode psychosis (FEP) program evaluation is a statewide initiative, supported by the PA Office of Mental Health and Substance Abuse Services (PA-OMHSAS) and administered by PA Early Intervention Center/Heads Up, which evaluates fidelity and outcomes of PA Coordinated Specialty Care (CSC) programs. Programs participate in standard computerized measures of CSC outcomes using centralized informatics. The aims of the current report are to describe implementation of this core battery for program evaluation in PA and to present 6- and 12-month outcomes. METHODS: Participants (n = 697) from nine PA CSC programs completed the core battery at admission. The battery was re-administered at 6- and 12-month follow-up, and data were analysed for individuals (n = 230) who had completed 12-months of treatment. Domains assessed via clinician report and/or self-report included symptoms, role and social functioning, self-perceived recovery and service utilization. RESULTS: PA FEP CSC participants showed improvement over time in several domains, including decreased symptoms, higher role and social functioning, decreased hospitalizations, and improved self-perception of recovery, quality of life, and services satisfaction. Trends towards improvements were observed for participant happiness, hopelessness, and school-enrolment. Nearly all improvements were observed at 6-month follow-up, with earlier gains maintained at 12-months. CONCLUSIONS: PA FEP CSC programs demonstrate the ability to assess and improve critical outcomes of coordinated specialty care in PA. Improved outcomes by 12 months in treatment provides evidence of an effective treatment model and supports the continuation of these programs in pursuit of our goal of reducing schizophrenia disease burden on individuals and society.

Longitudinal study of neurofibromatosis 1 associated plexiform neurofibromas.

BACKGROUND: Plexiform neurofibromas are benign tumours that occur in more than half of people with neurofibromatosis 1 (NF1). These tumours can cause serious complications and can also progress to malignant peripheral nerve sheath tumours (MPNSTs), one of the leading causes of death among NF1 patients. Plexiform neurofibromas are clinically heterogeneous, and knowledge of their natural history is limited. In order to characterise the growth of plexiform neurofibromas better, we performed serial magnetic resonance imaging (MRI) in NF1 patients with such tumours. METHODS: MRI was done on 44 plexiform neurofibromas in 34 NF1 patients (median age 10 years; range 1-47 years). Each tumour was measured in two dimensions from the MRI scan, and the area and growth rate were calculated. The median length of follow-up was 6 years, with an average interval of 3 years between scans. RESULTS: 36 tumours remained stable in size throughout the period of follow-up. 8 tumours increased in size; all occurred in patients who were under 21 years of age when first studied. The single exception was a man who developed rapid tumour growth and pain in a plexiform neurofibroma that had been followed for 10 years. Biopsy showed the presence of an MPNST. CONCLUSION: Longitudinal MRI is a valuable means of monitoring the growth of plexiform neurofibromas in individuals with NF1.

[Intoxication with cyclopentolate eye drops]. / Zentralnervöse Nebenwirkung von Cyclopentolat-Augentropfen.

We report on an accidental intoxication with cyclopentolate eye drops. A 90-year-old patient became confused and was admitted to the emergency department. His symptoms consisted of disorientation, ataxia, and psychomotor agitation. Similar cases have been described in the literature. With this case report we would like to draw attention to this little known differential diagnosis when confronted with confused patients.

Cobalt accumulation in horses following repeated administration of cobalt chloride.

OBJECTIVE: To monitor cobalt concentrations in urine, red blood cells and plasma after chronic parenteral administration of cobalt chloride evaluate these results against the current International Federation of Horseracing Authorities thresholds for detecting cobalt misuse. DESIGN: Eight mares were randomly assigned to four treatment groups, with two mares in each group: Group 1 - control group, Group 2 - 25 milligrams cobalt intravenously as CoCl2 weekly, Group 3 - 50 milligrams cobalt intravenously as CoCl2 weekly, and Group 4 - 25 milligrams cobalt intravenously mid-week and at the end of the week. Urine and blood samples were collected before each weekly administration so that trough levels were assessed. In the group receiving two doses per week, urine and blood were collected prior to the dose given at the end of each week. Samples were initially collected at time zero then weekly for 10 weeks. Three further collections of urine and blood were made at days 81, 106 and 127. METHODS: Urine creatinine measurements to assess horse hydration status were performed by the Jaffe reaction method. Cobalt determinations in plasma, blood and urine were by inductively coupled plasma-mass spectrometry. Haematocrit concentrations, used to calculate red cell cobalt levels, were performed using a microhematocrit centrifuge. Statistical analyses were conducted in Genstat (v17, VSNi). RESULTS: Marked cobalt accumulation was evident with increasing cobalt concentrations for all sample matrices in specimens collected immediately prior to cobalt administration. Correlation between the sample matrices improved when urine cobalt concentration was adjusted for creatinine level. Red cell cobalt levels remained elevated for at least 12 weeks after cessation of administration, consistent with the lifespan of the red cell. There was no significant change in haematocrit concentrations for the duration of the study. CONCLUSION: The current urine cobalt threshold was only effective at detecting acute cobalt exposure while the plasma cobalt threshold was able to consistently identify chronic high-level cobalt exposure and potential cobalt misuse. The threshold values legislated for urine cobalt do not correlate with those set for plasma. The acute nature of urinary cobalt excretion provides a relatively small window through which cobalt administration is detected. Plasma and red cell cobalt concentrations can provide a clearer picture of potential cobalt misuse.

The influence of continuous venovenous haemodialysis on the pharmacokinetics of multiple oral moxifloxacin administration to patients with severe renal dysfunction.

AIM: We investigated single dose and steady-state pharmacokinetics of moxifloxacin in eight venovenous haemodialysis patients. METHODS: Plasma, dialysate and urine pharmacokinetic parameters for moxifloxacin and its main metabolites were calculated after single and multiple (7 days) dosing with 400 mg day(-1). RESULTS: Moxifloxacin pharmacokinetics after a single dose and at steady state (multidose day 7) were comparable in patients with impaired renal function and healthy subjects (geometric mean/%CV AUC mg l(-1) h single dose 37.0/24.3 in haemodialysis patients vs. 29.8/22.6 in healthy subjects, 95% CI for ratio of haemodialysis patients to healthy subjects 99.34%, 154.60%; steady state 40.4/29.1 haemodialysis patients vs. 33.9/20.1 in healthy subjects, 95% CI for ratio of haemodialysis patients to healthy subjects 90/39%, 156.93%). In haemodialysis patients plasma concentrations of moxifloxacin at steady-state were elevated compared with those after a single 400 mg dose (AUC mg l(-1) h, geometric mean/%CV, 40.4/29.1) compared with 37.0/24.3; 95% CI for ratio of steady-state to single dose 87.29%, 136.52%, as were concentrations of metabolite M1 3.21/34.6 compared with 2.02/45.3, 95% CI for ratio of steady state to single dose 14.21%, 175.07%. Haemodialysis cleared about 9% of the dose as unchanged moxifloxacin. CONCLUSIONS: No dose adjustments are required for venovenous haemodialysis patients on oral moxifloxacin therapy.

Inflammatory response and clinical course of adult patients with nosocomial bloodstream infections caused by Candida spp.

Candida spp. are an important cause of nosocomial bloodstream infection (nBSI) and are associated with significant morbidity and mortality. An historical cohort study was performed to evaluate the clinical course of 60 randomly selected adult patients with nBSIs caused by Candida spp. Patients with BSI caused by Candida albicans (n = 38) and non-albicans spp. (n = 22) were compared with 80 patients with Staphylococcus aureus BSI by serial systemic inflammatory response syndrome (SIRS) and APACHE II scores. The patients had a mean age of 52 years, the length of hospital stay before BSI averaged 21 days, and 57% of patients required care in an intensive care unit before BSI. The mean APACHE II score was 17 on the day of BSI, and 63% of BSIs were caused by C. albicans. Antifungal therapy within the first 24 h of onset of BSI was appropriate in 52% of patients. Septic shock occurred in 27% of patients, and severe sepsis in an additional 8%. Overall mortality was 42%, and the 7-day mortality rate was 27%. The inflammatory response and clinical course were similar for patients with BSI caused by C. albicans and non-albicans spp. In univariate analysis, progression to septic shock was correlated with high overall mortality, as was an APACHE II score >25 at the onset of BSI. In multivariate analysis, the APACHE II score at the onset of BSI and a systemic inflammatory response independently predicted overall mortality, but the 7-day mortality rate was only predicted independently by the APACHE II score. Clinical course and mortality in patients with Candida BSI were predicted by systemic inflammatory response and APACHE II score, but not by the infecting species.

Contribution of polycyclic aromatic hydrocarbons and polar polycyclic aromatic compounds to the carcinogenic impact of flue gas condensate from coal-fired residential furnaces evaluated by implantation into the rat lung.

For identification of the substances chiefly responsible for the carcinogenic action of the emission condensate from coal-fired residential furnaces, the implantation method was used as a carcinogen-specific bioassay for comparison of the carcinogenic effect of various fractions with that of a total sample of flue gas condensate tested in 2 or 3 different doses. After implantation into the lungs of Osborne-Mendel rats, the condensate from coal-fired residential furnaces, a fraction containing polycyclic aromatic hydrocarbons (PAHs) and thiaarenes [sulfur-containing polycyclic aromatic compounds (S-PACs)] with 4-7 rings, as well as fraction containing more polar polycyclic aromatic compounds (PACs) and PAHs with higher molecular weight, induced lung carcinomas and sarcomas. According to probit analysis, the fraction containing PAHs plus S-PACs with 4-7 rings accounted for about 68.2% of the total carcinogenicity of flue gas condensate, whereas the fraction containing more polar PACs and higher PAHs accounted for about 54.6%. All other fractions, such as nonaromatic compounds and PACs with 2 and 3 rings, constituting about 70% of the weight of the total condensate, seemed not to be carcinogenic. Only 1.4% of the total carcinogenicity of the flue gas condensate was found to be attributable to the amount of benzo[a]pyrene (CAS: 50-32-8) present in the condensate (1.14 mg/g condensate). The contribution of more than 100% of both active fractions to the total carcinogenicity (68.2 and 54.6%) may suggest an interrelation of the fractions.

Experimental studies in rat lungs on the carcinogenicity and dose-response relationships of eight frequently occurring environmental polycyclic aromatic hydrocarbons.

The biologic activity of eight highly purified polycyclic aromatic hydrocarbons (PAH) widely distributed in the human environment was tested in the respiratory tracts of rats. These studies were performed for the examination of carcinogenic activity of the compounds and determination of a dose-response relationship. The lung implantation method was used in 3-month-old female OM rats. A dose-response relationship was obtained for benzo[a]pyrene (BaP), anthanthrene (ANT), benzo[b]fluoranthene (BbF), indeno[1,2,3-cd]pyrene (IND), benzo[j]fluoranthene (BjF), and benzo[k]fluoranthene (BkF). Benzo[e]pyrene and benzo[ghi]perylene showed no tumor-producing effect in this system when given at doses of 5 mg. The histologic and mathematical evaluations indicated that the investigated compounds had distinct carcinogenic potencies. After probit analysis of the results, the carcinogenic potencies of PAH investigated in the lung implantation model rank as follows: BaP, 1.00; ANT, 0.19; BbF, 0.11; IND, 0.08; BkF, 0.03; and BjF, 0.03.

Contribution of polycyclic aromatic hydrocarbons to the carcinogenic impact of gasoline engine exhaust condensate evaluated by implantation into the lungs of rats.

An attempt was made to identify the substances chiefly responsible for the carcinogenicity of gasoline engine exhaust condensate. A carcinogen-specific bioassay was performed by a comparison of the carcinogenic effect of various fractions with that of a total sample of automobile exhaust condensate, tested in two or three different doses. The results were examined by Probit analysis. After implantation into the lungs of OM rats, the condensate emitted from a gasoline-driven automobile and the fraction of polycyclic aromatic compounds consisting of more than 3 rings induced lung carcinomas and sarcomas. The tumor incidence demonstrated a clear-cut dose-response relationship. The fraction of polycyclic aromatic hydrocarbons (PAH) consisting of more than 3 rings accounted for about 81% of the total carcinogenicity of automobile exhaust condensate. This fraction represented only 2.8% by weight of the condensate. The content of benzo[a]pyrene (CAS: 50-32-8; 0.483 mg/g condensate) accounted for 2.4% of the total carcinogenicity of automobile exhaust condensate. Regarding the minor effect of the PAH-free fraction (approximately equal to 87% by wt), no evidence of cocarcinogenic activity was observed, since the total condensate as well as the PAH fraction consisting of more than 3 rings applied proportionally caused about the same tumor incidence.

Nosocomial pneumonia in adult patients undergoing bone marrow transplantation: a 9-year study.

Two hundred seventy-five consecutive patients treated with bone marrow transplantation (BMT) during a 9-year interval were analyzed for the incidence and etiology of nosocomial pneumonia. Cases included adults who acquired pneumonia during the first hospitalization period within 100 days of the transplant. Fifty-five (20%) of the 275 patients developed nosocomial pneumonia, and the crude mortality during the hospitalization period was 74.5%. An etiology was established in 67.3% (37 of 55) of episodes. Thirty-six percent (20 of 55) of the cases were caused by Aspergillus species, either as the sole agent (15 patients) or in association with others. The crude mortality for patients with Aspergillus pneumonia was 95%. Elimination of 90% of Aspergillus cases in our unit would have the effect of reducing the overall attack rate of nosocomial pneumonia to 13.4% and the associated crude mortality to 43.4%.

Differential activation of cardiac and peripheral sympathetic nervous system by nifedipine: role of pharmacokinetics.

OBJECTIVES: We sought to study the effects of short-acting and long-acting nifedipine on the sympathetic nervous system (SNS), heart rate (HR) and blood pressure (BP) of normotensive subjects under baseline conditions and during SNS stimulation. BACKGROUND: Calcium channel antagonists in different pharmacokinetic formulations are widely used in patients with coronary artery disease or hypertension. Short-acting formulations activate the SNS, an action that may be disadvantageous in patients with coronary disease, especially if left ventricular function is impaired. The effects of slow-release formulations on the SNS are unknown. METHODS: We used microneurography to investigate the influence of nifedipine (5 mg; 10 mg; and slow-release [GITS], 60 mg) on muscle sympathetic nerve activity (MSA) and skin sympathetic nerve activity (SSA) in healthy volunteers. RESULTS: Peak plasma levels after short-acting and slow-release nifedipine were achieved within 60 min and 330 min, respectively. Short-acting (10 mg, n = 10) and slow-release (n = 10) nifedipine, but not placebo, markedly activated MSA and increased plasma norepinephrine; plasma endothelin increased only with slow-release nifedipine. HR increased after short-acting nifedipine, but not after nifedipine GITS. Nifedipine had no effect on SSA (n = 6). Blockade of cardiac sympathetic activity (with esmolol) led to similar decreases in HR with or without nifedipine, whereas parasympatholysis (with atropine) led to similar increases in HR with or without nifedipine. The cold pressor test markedly increased MSA in all treatment groups and further increased MSA beyond the increase induced by nifedipine. CONCLUSIONS: Nifedipine markedly increased MSA, but not SSA, independently of drug release formulation. In contrast, HR increased with short-acting, but not with slow-release, nifedipine. Therefore, nifedipine activates cardiac and peripheral sympathetic nerves differently depending on pharmacokinetics. These effects of nifedipine may be disadvantageous in cardiac patients with increased sympathetic activity or congestive heart failure, or both.

Resistant hypertension in patients with chronic aortic dissection.

Strict blood pressure control is pivotal in the management of patients with aortic dissection (AD), but is frequently difficult to achieve. We determined antihypertensive medical therapy and levels of blood pressure (BP) control in 40 patients with chronic AD. Patient charts were reviewed for clinical variables, serial BP measurements, and antihypertensive drug therapy. Patients were divided into two groups: patients in group 1 had effective BP control (<135/80 mmHg), patients in group 2 had resistant hypertension (BP>/=135/80 mmHg despite prescription of at least three antihypertensive drugs). Overall, systolic BP (SBP) was 130+/-20 mmHg, and diastolic BP (DBP) was 72+/-13 mmHg. Patients received a median of 4 (1-6) antihypertensive drugs. beta-blockers were used in 38/40 (95%) patients. Effective BP control was achieved in 24/40 (60%) patients (group 1), while 16/40 (40%) patients had resistant hypertension (group 2) despite receiving significantly more antihypertensive drugs (5 [4-6] vs 4 [1-5], P=0.001). Mean SBP was 116+/-9 (101-132) mmHg in group 1 and 151+/-13 (137-181) mmHg in group 2 (P<0.001); there was no difference in DBP. Group 2 patients had a significantly higher body mass index and were younger than patients in group 1. In conclusion, in the majority of patients with chronic AD, effective BP control can be achieved, but usually requires the combination of multiple antihypertensive drugs. However, in a significant proportion of patients (40%), who appear to be younger and more obese, medical therapy fails to achieve effective BP control despite use of a multiple drug regimen.

Nosocomial bloodstream infections. Secular trends in rates, mortality, and contribution to total hospital deaths.

BACKGROUND: Nosocomial bloodstream infections occur at a rate of 1.3 to 14.5 per 1000 hospital admissions and are believed to lead directly to 62,500 deaths per year in the United States. Measures of the incidence and the proportion of all hospital deaths related to deaths from these infections provide estimates of their impact. The objectives of the study were to characterize the secular trends in nosocomial bloodstream infection at a single institution and to estimate the population-attributable risk for death among patients experiencing the infection. METHODS: A 12-year retrospective study using prospectively collected data from a hospital-wide surveillance system for nosocomial infections in a 900-bed tertiary care institution. All patients (N = 260,834) admitted to the institution between 1980 and 1992 were included in the study. Bloodstream infection rates were calculated for the 10 leading groups of pathogens, and trends were analyzed using simple linear regression. In-hospital mortality rates from patients who did or did not develop nosocomial blood stream infections were compared. RESULTS: Between 1980 and 1992, a total of 3077 patients developed 3464 episodes of nosocomial bloodstream infection. The crude infection rates increased linearly from 6.7 to 18.4 per 1000 discharges (0.83 to 1.72 episodes per 1000 patient-days) during the 12-year study period (r = .87). Increases in the infection rates were due to gram-positive cocci (r = .96) and yeasts (r = .95) and essentially explained by infections caused by coagulase-negative staphylococci, Staphylococcus aureus, enterococci, and Candida species, respectively. Although the crude mortality in patients with nosocomial bloodstream infections decreased from 51% in 1981 to 29% in 1992, the in-hospital population-attributable mortality among infected patients increased from 3.55 deaths per 1000 discharges in 1981 to 6.22 per 1000 discharges in 1992 (r = .67). The etiologic fraction or the proportion of deaths in patients with bloodstream infection to all deaths occurring in the hospital increased from 11.4% in 1981 to 20.4% in 1992 (r = .59). CONCLUSIONS: The incidence, the etiologic fraction, and the population-attributable risk for death among patients experiencing nosocomial bloodstream infections increased progressively during the last decade.

Nosocomial urinary tract infections due to enterococcus. Ten years' experience at a university hospital.

From 1975 through 1984, 473 cases of enterococcal nosocomial urinary tract infection (UTI) were identified by prospective hospital-wide surveillance at the University of Virginia Hospital, Charlottesville. The rate of infection increased progressively from 12.3 to 32.2 cases per 10 000 patient discharges, and the proportion of nosocomial UTIs due to this organism increased from 6% to 16%. During the study period, crude mortality was 15%. Patients with the diagnosis of neurogenic bladder accounted for 26% of cases and had a crude mortality of 7.3%; all other cases (74%) had a crude mortality of 18.1%. Risk factors associated with fatal outcome in cases having a nosocomial enterococcal UTI included age of more than 50 years, concurrent acute respiratory failure, hospitalization on the internal medicine service, and concurrent gastrointestinal hemorrhage. Enterococcus is the second most frequent cause of nosocomial UTI in our hospital. The emergence of this pathogen may reflect, in part, its selective advantage imparted by resistance to cephalosporin antibiotics.