A case of Fanconi syndrome due to a deferasirox overdose and a trial of plasmapheresis.

WHAT IS KNOWN AND OBJECTIVE: Deferasirox has nephrotoxic effects in the context of chronic therapy. This case report illustrates proximal tubular dysfunction (Fanconi syndrome) due to an acute deferasirox overdose. CASE DESCRIPTION: In response, we trialled plasmapheresis to eliminate the drug. Deferasirox levels were obtained in the context of three rounds of plasmapheresis. Given the half-life model of decay, we concluded that plasmapheresis may not have been successful. The patient ultimately recovered normal tubular function after 2 months. WHAT IS NEW AND CONCLUSION: This report is the first to describe acute deferasirox-induced nephrotoxicity, and the application of plasmapheresis that, ultimately, did not change the typical time to recovery.

In utero exposure to heat stress during late gestation has prolonged effects on the activity patterns and growth of dairy calves.

Exposure to heat stress during late gestation exerts negative carryover effects on the postnatal performance of the calf. In this study, we evaluated the health, growth, and activity patterns of calves born to cows exposed to heat stress (HT, provided only shade, n = 31) or cooling (CL, fans, soakers, and shade, n = 29) during late gestation (∼46 d, maternal dry period). Calves' body weight, rectal temperature, suckling reflex, and movement scores were recorded at birth, and calves were fed 6.6 L of maternal colostrum in 2 meals. Blood samples were collected at birth (before feeding), 24 h after birth, and at d 10 and 28 of age. Calves were housed in individual pens, fed pasteurized milk (6 L/d), and had ad libitum access to grain and water until weaning (49 d). Activity was assessed during the first week of life (wk 1), at weaning (wk 7), and in the first week postweaning (wk 8) using electronic data loggers. Health and body weight were monitored weekly. At birth, calves born to CL cows were heavier (41.9 vs. 39.1 ± 0.8 kg), their temperature was lower (38.9 vs. 39.3 ± 0.08°C), and they were more efficient at absorbing IgG than HT calves. Suckling reflex and movement score at birth were not different between groups, but calves born to CL cows spent more time (50 min/d) standing in the first week of life as a result of longer standing bouts. In wk 7 and 8, calves born to CL cows had less frequent standing bouts than HT heifers, but CL heifers maintained greater total daily standing time (36 min/d) due to longer (7 min/bout) standing bouts. All calves were healthy, but HT heifers tended to have higher (looser) fecal scores on d 10. Heifers born from CL cows gained 0.2 kg/d more from birth to weaning, weighed 4 kg more at weaning, and had greater concentrations of IGF-1 than HT calves, particularly on d 28. In utero heat stress during late gestation had immediate and prolonged effects on passive immunity, growth, and activity patterns in dairy calves.

Assessment of serum 25-hydroxyvitamin D concentrations of beef cows and calves across seasons and geographical locations.

Vitamin D is critical for the growth and development of calves and positively contributes to immune function of cattle. Serum 25-hydroxyvitamin D (25(OH)D) concentrations above 20 ng/mL have traditionally been considered adequate for growth and development of cattle, but recent evidence has indicated that concentrations below 30 ng/mL are insufficient for immunity. Because little information is available regarding vitamin D status of beef cattle, the objective of this study was to evaluate vitamin D status of beef cow-calf herds on pasture as affected by season and location. Serum samples were collected from 43 cow-calf pairs plus an additional 54 calves in herds located in Florida, Idaho, and Minnesota in the spring calving season. Samples were collected again over the summer months from animals in the Florida and Minnesota herds. Effects of subcutaneous injection of vitamins A, D, and E also were investigated in a subset of calves from the Idaho herd. All cows sampled had serum 25(OH)D concentrations above 30 ng/mL at the time of calving in the spring. The average serum 25(OH)D concentrations of cows rose from near 60 ng/mL in the spring to 75 ng/mL in the summer ( < 0.001). Most calves, on the other hand, had serum 25(OH)D concentrations below 20 ng/mL. The calves in the Florida and Minnesota herds similarly rose from averages of 10 to 15 ng/mL at birth to near 50 ng/mL by the end of summer. Serum 25(OH)D of severely deficient calves increased from 3 ng/mL in nonsupplemented calves to 11 ng/mL at 48 h after birth if given a bolus supplementation of 40,000 IU of vitamin D via subcutaneous injection of a vitamin A, D, and E supplement at birth ( < 0.001). Vitamin D supplementation of cows late in pregnancy has been shown to increase serum 25(OH)D of calves; however, beef cattle generally receive very little supplemental vitamin D, as was the case for the cows studied here. The lower serum 25(OH)D of cows in spring compared with summer and the prevalence of vitamin D deficiency of calves observed here indicate that increased vitamin D supplementation of cows over the winter months or vitamin D supplementation of newborn calves would be beneficial.

Cerebral activations during viewing of food stimuli in adult patients with acquired structural hypothalamic damage: a functional neuroimaging study.

BACKGROUND/OBJECTIVES: Obesity is common following hypothalamic damage due to tumours. Homeostatic and non-homeostatic brain centres control appetite and energy balance but their interaction in the presence of hypothalamic damage remains unknown. We hypothesized that abnormal appetite in obese patients with hypothalamic damage results from aberrant brain processing of food stimuli. We sought to establish differences in activation of brain food motivation and reward neurocircuitry in patients with hypothalamic obesity (HO) compared with patients with hypothalamic damage whose weight had remained stable. SUBJECTS/METHODS: In a cross-sectional study at a University Clinical Research Centre, we studied 9 patients with HO, 10 age-matched obese controls, 7 patients who remained weight-stable following hypothalamic insult (HWS) and 10 non-obese controls. Functional magnetic resonance imaging was performed in the fasted state, 1 h and 3 h after a test meal, while subjects were presented with images of high-calorie foods, low-calorie foods and non-food objects. Insulin, glucagon-like peptide-1, Peptide YY and ghrelin were measured throughout the experiment, and appetite ratings were recorded. RESULTS: Mean neural activation in the posterior insula and lingual gyrus (brain areas linked to food motivation and reward value of food) in HWS were significantly lower than in the other three groups (P=0.001). A significant negative correlation was found between insulin levels and posterior insula activation (P=0.002). CONCLUSIONS: Neural pathways associated with food motivation and reward-related behaviour, and the influence of insulin on their activation may be involved in the pathophysiology of HO.

The effect of sex and handedness on white matter anisotropy: a diffusion tensor magnetic resonance imaging study.

Diffusion tensor magnetic resonance imaging provides a way of assessing the asymmetry of white matter (WM) connectivity, the degree of anisotropic diffusion within a given voxel being a marker of coherently bundled myelinated fibers. Voxel-based statistical analysis was performed on fractional anisotropy (FA) images of 42 right- and 40 left-handers, to assess differences in underlying WM anisotropy and FA asymmetry across the whole brain. Right-handers show greater anisotropy than left-handers in the uncinate fasciculus (UF) within the limbic lobe, and WM underlying prefrontal cortex, medial and inferior frontal gyri. Significantly greater leftward FA asymmetry in cerebellum posterior lobe is seen in left- than right-handers, and males show significantly greater rightward (right-greater-than-left) FA asymmetry in regions of middle occipital lobe, medial temporal gyrus, and a region of the superior longitudinal fasciculus underlying the supramarginal gyrus. Leftward (left-greater-than-right) anisotropy is found in regions of the arcuate fasciculus (AF), UF, and WM underlying pars triangularis in both handedness groups, with right-handers alone showing additional leftward FA asymmetry along the length of the superior temporal gyrus. Overall results indicate that although both handedness groups show anisotropy in similar WM regions, greater anisotropy is observed in right-handers compared with left-handers. The largest differences in FA asymmetry are found between males and females, suggesting a greater effect of sex than handedness on FA asymmetry.

On coenrollment in clinical resuscitation studies: review and experience from randomized trials.

CONTEXT: Patients with acute life-threatening illness are candidates for enrollment in multiple trials. Whether patients are enrolled in multiple trials has implications for patient safety, trial enrollment duration, and study validity. OBJECTIVE: We review issues related to coenrollment and propose guidelines for when it should be allowed. RESULTS: There is no regulatory prohibition on coenrollment of patients in more than one study. Randomized trials of interventions for a variety of clinical conditions have allowed coenrollment without any reported deleterious impact on either study. Guidelines for coenrollment are proposed.

Old age, vulnerability and sexual violence: implications for knowledge and practice.

AIM: This paper seeks to offer further analysis on the relationship between abuse of power, elder abuse and sexual violence. Importantly, current definitions are examined and the existing literature is reviewed to establish what the current level of debate is on sexual violence in its relationship to elderly women. METHODS: Through the analysis of available literature it is possible to observe which and how older people have been marginalized both in particular disciplines of study and policy spaces. FINDINGS: We conclude that marginalization results in inadequate redress to issues of violence and power that may manifest against the older person, and which leads to feelings of vulnerability. There are important implications for helping health professionals, especially nurses, for understanding the policy, theory and practice. The need for empirical research in this difficult area is paramount.

An unexpectedly high incidence of Epstein-Barr virus lymphoproliferative disease after CD34+ selected autologous peripheral blood stem cell transplant in neuroblastoma.

The risk of Epstein-Barr virus lymphoproliferative disease (EBV-LPD) increases with the use of highly immunosuppressive therapies. Allogeneic BMT, especially supported by T-cell-depleted stem cell products, is a risk factor for EBV-LPD. Although the risk of EBV-LPD after autologous transplantation is low, case reports of this complication in the autologous setting exist. We report a higher incidence than previously described of EBV-LPD in children undergoing sequential high-dose chemotherapy supported with CD34 selected peripheral blood stem cells (CD34+ PBSC). The median time to LPD after tandem transplant was 3 months (range 1-5 months). Five patients out of 156 (3.5%) developed EBV-LPD while enrolled on two trials of tandem autologous SCT in high-risk pediatric malignancies. Both studies employed five cycles of induction therapy, followed by tandem autologous PBSC transplants. In all, 108 out of 156 patients received CD34+ PBSC; 48 received unselected PBSC. All patients contracting LPD were from the CD34 selected group. Treatment of EBV-LPD included rituximab in four out of five patients, i.v.Ig in two out of five patients, and gancyclovir in two out of five patients. EBV-LPD resolved in four out of five patients. We conclude that the combination of tandem SCT and CD34 selection may have increased immunosuppression in these patients to a point where there is an elevated risk of EBV-LPD.

Identification of a group 1-like capsular polysaccharide operon for Vibrio vulnificus.

Virulence of Vibrio vulnificus correlates with changes in colony morphology that are indicative of a reversible phase variation for expression of capsular polysaccharide (CPS). Encapsulated variants are virulent with opaque colonies, whereas phase variants with reduced CPS expression are attenuated and are translucent. Using TnphoA mutagenesis, we identified a V. vulnificus CPS locus, which included an upstream ops element, a wza gene (wza(Vv)), and several open reading frames with homology to CPS biosynthetic genes. This genetic organization is characteristic of group 1 CPS operons. The wza gene product is required for transport of CPS to the cell surface in Escherichia coli. Polar transposon mutations in wza(Vv) eliminated expression of downstream biosynthetic genes, confirming operon structure. On the other hand, nonpolar inactivation of wza(Vv) was specific for CPS transport, did not alter CPS biosynthesis, and could be complemented in trans. Southern analysis of CPS phase variants revealed deletions or rearrangements at this locus. A survey of environmental isolates indicated a correlation between deletions in wza(Vv) and loss of virulent phenotype, suggesting a genetic mechanism for CPS phase variation. Full virulence in mice required surface expression of CPS and supported the essential role of capsule in the pathogenesis of V. vulnificus.

Resumption of driving after life-threatening ventricular tachyarrhythmia.

BACKGROUND: Although the privilege of driving must be respected, it may be necessary to restrict driving when it poses a threat to others. The risks associated with allowing patients with life-threatening ventricular tachyarrhythmias to drive have not been quantified. METHODS: The Antiarrhythmics versus Implantable Defibrillators (AVID) trial compared antiarrhythmic-drug therapy with the implantation of defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. In the current study, we sent patients who participated in the AVID trial a questionnaire, to be completed anonymously, requesting information about driving habits and experiences. RESULTS: The questionnaire was returned by 758 of 909 patients (83 percent). Of these, 627 patients drove during the year before their index episode of ventricular tachyarrhythmia. A total of 57 percent of these patients resumed driving within 3 months after randomization in the AVID trial, 78 percent within 6 months, and 88 percent within 12 months. While driving, 2 percent had a syncopal episode, 11 percent had dizziness or palpitations that necessitated stopping the vehicle, 22 percent had dizziness or palpitations that did not necessitate stopping the vehicle, and 8 percent of the 295 patients with an implantable cardioverter-defibrillator received a shock. Fifty patients reported having at least 1 accident, for a total of 55 accidents during 1619 patient-years of follow-up after the resumption of driving (3.4 percent per patient-year). Only 11 percent of these accidents were preceded by symptoms of possible arrhythmia (0.4 percent per patient-year). CONCLUSIONS: Most patients with ventricular tachyarrhythmias resume driving early. Although it is common for them to have symptoms of possible arrhythmia while driving, accidents are uncommon and occur with a frequency that is lower than the annual accident rate of 7.1 percent in the general driving population of the United States.

Androgen-producing, atypically proliferating endometrioid tumor arising in endometriosis.

A case of androgen-secreting borderline endometrioid tumor arising in endometriosis of the rectovaginal septum is presented. It occurred 10 years after total abdominal hysterectomy and bilateral salpingo-oophorectomy for extensive endometriosis of the fallopian tubes and ovaries, adenomyosis, and leiomyomas of the uterus. We believe 7 years of unopposed continuous oral estrogen replacement therapy contributed to the malignant transformation of the endometriosis.

A Foucauldian analysis of old age and the power of social welfare.

It is argued that the question of social welfare is a key, if often overlooked, component in the construction of power relations and identities in later life that can take its place next to debates on bioethics and consumer lifestyle. Foucault's (1977) claim, that identities are kept in place through the deployment of integrated systems of power and knowledge and a routine operation of surveillance and assessment, is critically examined in this context. Trends in social welfare in the United Kingdom are used as a case example that sheds light on wider contemporary issues associated with old age. Finally, implications for the creation of particular narratives about later life are discussed and grounded through Foucault's (1988) notion of "technologies of self."

Patients at lower risk of arrhythmia recurrence: a subgroup in whom implantable defibrillators may not offer benefit. Antiarrhythmics Versus Implantable Defibrillator (AVID) Trial Investigators.

OBJECTIVES: The goal of this study was to identify subgroups of arrhythmia patients who do not benefit from use of the implantable cardiac defibrillator (ICD). BACKGROUND: Treatment of serious ventricular arrhythmias has evolved toward more common use of the ICD. Since estimates of the cost per year of life saved by ICD therapy vary from $25,000 to perhaps $125,000, it is important to identify patient subgroups that do not benefit from the ICD. METHODS: Data for 491 ICD patients enrolled in the Antiarrhythmics Versus Implantable Defibrillators Study were used to create a hazards model relating baseline factors to time to first recurrent arrhythmia. The model was used to predict the hazard for recurrent arrhythmia among all trial patients. A priori cut points provided lower and higher recurrent arrhythmia risk strata. For each stratum the incremental years of life due to ICD versus antiarrhythmic drug therapy were calculated. RESULTS: Factors that predicted recurrent arrhythmia were: ventricular tachycardia as the index arrhythmia, history of cerebrovascular disease, lower left ventricular ejection fraction, a history of any tachyarrhythmia before the index event and the absence of revascularization after the index event. Survival times (over a follow-up of three years) were identical in each arm of the lowest risk sextile (survival advantage 0.03 +/- 0.12 [se] years), while the survival advantage for patients above the first sextile was 0.27 +/- 0.07 (se) years (two-sided p = 0.05). CONCLUSIONS: Patients presenting with an isolated episode of ventricular fibrillation in the absence of cerebrovascular disease or history of prior arrhythmia who have undergone revascularization or who have moderately preserved left ventricular function (left ventricular ejection fraction > 0.27) are not likely to benefit from ICD therapy compared with amiodarone therapy.

Management of recurrent juvenile granulosa cell tumor of the ovary.

BACKGROUND: Juvenile granulosa cell tumors of the ovary are a rare form of neoplasm that makes up less than 5% of ovarian tumors in childhood and adolescence. About 90% are diagnosed in stage I with a favorable prognosis. More advanced stages (FIGO stages II--IV) have a poor prognosis. CASE: A patient was initially diagnosed at age 17 with FIGO stage IIIC disease and treated with a right salpingo-oophorectomy, debulking, and staging followed by six cycles of carboplatin and etoposide chemotherapy. Tumor recurrence in the liver and adjacent to the spleen occurred 13 months after completion of primary therapy. Aggressive surgical removal of tumor followed by six cycles of bleomycin and taxol as salvage chemotherapy resulted in 44 months of disease-free survival. On November 27, 2000, she had a cesarean delivery of a 2335-g normal male due to a breech presentation. Exploration revealed no evidence of tumor. CONCLUSION: This is the second case report of a patient with advanced juvenile granulosa cell tumor to become pregnant after apparently successful chemotherapy. These results are encouraging, but the best treatment for extensive and recurrent disease has yet to be determined.

Those who hesitate lose: the relationship between assertiveness and response latency.

Individuals who are low in assertiveness may take longer to sort out, process, and state their own perceptions, attitudes and priorities, which puts them at a disadvantage in getting their needs met. The reason for this may not be inhibition in social situations or cognitive ability, but a lack of clarity regarding their own attitudes, opinions, preferences, goals, and priorities. 101 undergraduate students (57% women and 43% men) completed a demographics questionnaire, the Wonderlic Personnel Test, a self-monitoring scale, the Marlowe-Crowne Social Desirability Scale, the Rosenberg Self-esteem Scale, the College Self-expression Scale, and a test of the false-consensus effect. Response latencies to questions were measured. Individuals with higher scores on the Wonderlic Personnel Test answered items more quickly but, even when cognitive ability was controlled, individuals low in assertiveness still took significantly longer to respond to questions about themselves, their opinions, and their preferences. If individuals fall behind at this early step in the process of asserting themselves, then they may be more likely to miss opportunities to be assertive.

Treatment of vaginal dysplasia: just a simple loop electrosurgical excision procedure?

We report a case of sigmoid perforation, peritonitis, and adult respiratory distress syndrome after a loop excision procedure for carcinoma in situ of the cervix and dysplasia of the vagina. Treatment of vaginal dysplasia with loop excision is potentially dangerous. Safer methods of management include carbon dioxide laser, topical 5-fluorouracil, and fulguration.

Androgen-secreting steroid cell tumor of the ovary.

We present the case of a 93-year-old virilized woman with an androgen-secreting ovarian tumor. This rare ovarian sex cord stromal tumor behaved in a malignant fashion. Various aspects of the presentation, diagnosis, and treatment of these tumors are discussed.