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.

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.

Isotopic composition of strontium in volcanic rocks from oahu.

Analysis of several well-documented specimens from each of the three volcanic series on Oahu gives the following mean ratios of Sr(87) to Sr(86): the Waianae series, 0.7030 +/- 0.00010 (sigma); the Koolau series, 0.70385+/- 0.00009 (sigma); and the Honolulu series, 0.7029 ++/- 0.00006 ( sigma). The mean ratio of Sr(87) to Sr(86) of the Koolau series specimens is significantly higher than the means of the other two series. With one exception, significant differences in Sr(87)/ Sr(86) within a series were not found, even though some large compositional differences existed.

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.

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.

Intermediate filamentous proteins in adult granulosa cell tumors. An immunohistochemical study of 25 cases.

Adult granulosa cell tumors (AGCTs) are classified as sex cord-stromal tumors of the ovary. However, they may be confused with other primary ovarian neoplasms. Intermediate filaments, specifically vimentin and cytokeratins, have been identified in AGCTs by immunohistochemistry performed on frozen and formalin-fixed, paraffin-embedded tissue and two-dimensional electrophoresis. Recently, however, immunohistochemical demonstration of cytokeratin has been used as supporting evidence of epithelial rather than sex cord-stromal differentiation in ovarian neoplasia. To investigate further intermediate filamentous proteins in AGCTs, 25 such tumors were studied by immunohistochemistry in formalin-fixed, paraffin-embedded sections. Cytoplasmic staining was observed, frequently in a distinct punctate, paranuclear pattern, in 14 of 25, 14 of 25, and seven of 17 tumors using monoclonal antibodies AE1/AE3, CAM 5.2, and 35BH11, respectively, which share the ability to detect low molecular weight cytokeratins. Staining for cytokeratin was not seen in any of the 17 tumors studied using the antibody 34BE12. Twenty-three of 25 tumors showed strong positivity for vimentin, characteristically seen as globoid paranuclear staining. Nine of 25 tumors contained desmin, which was restricted to the intermixed spindle cell, cortical type stromal component of the tumors. These patterns of immunoreactivity for intermediate filaments, particularly cytokeratins, are different than in common epithelial tumors of the ovary and may be useful in the differential diagnosis of ovarian neoplasia. Moreover, the immunohistochemical detection of cytokeratins should not be used as a criterion for excluding AGCT from the differential diagnosis of an ovarian neoplasm.

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.

Hemangioma of the cervix managed with the Nd:YAG laser.

A large hemangioma of the cervix was treated successfully with the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. A survey of the literature disclosed 39 cases of hemangioma of the cervix and vagina. Hysterectomy was the primary mode of therapy in 15 cases. More conservative approaches have been used in young women requesting preservation of their childbearing ability, including CO2 laser excision, knife excision, cryotherapy, and electrocauterization. In the case presented, the Nd:YAG laser was used in the non-contact mode for a photocoagulative effect. This technique results in destruction of the lesion with less danger of bleeding than with any other surgical technique.

Panniculectomy to facilitate gynecologic surgery in morbidly obese women.

OBJECTIVE: To determine whether abdominal panniculectomy done in conjunction with pelvic surgery in morbidly obese women is safe and useful. METHODS: Twenty morbidly obese women had excision of large abdominal panniculi in conjunction with pelvic surgery at New Hanover Regional Medical Center between November 1994 and September 1998. Panniculectomy was to improve surgical exposure and to decrease the incidence of wound necrosis, infection, and dehiscence among those high-risk women who all had chronic intertrigo in the skin folds under their panni. RESULTS: The women were 38-65 years old (mean 51 years) and weighed 202-475 pounds (mean 305 pounds). Their body mass indices were 35-76 (mean 51.5). Three women had superficial partial wound dehiscence, which was treated successfully with office debridement. There were no pulmonary emboli or operative deaths. CONCLUSION: Abdominal panniculectomy is safe and useful in morbidly obese women.

Histiocytosis X of the vulva: a case report and review of the literature.

Histiocytosis X of the female genital tract is unusual. Thirty-two cases have been reported to date in the world literature. An additional case is reported herein, presenting as a vulvar ulcer in a 2.5-year-old child with osteolytic lesions of the skull, splenomegaly, and otitis media. The diagnosis of histiocytosis X may be established by identifying the Langerhans histiocyte, characterized by nuclear grooves, immunoreactivity for S-100 protein, and pentalamellar cytoplasmic structures seen by electron microscopy. Prognosis is difficult to determine with certainty. However, age of less than 2 years at presentation, multi-organ involvement, and/or organ dysfunction appear to be associated with a less favorable prognosis. The patient presented herein is currently receiving vinblastine chemotherapy for recurrence of disease, manifested as an osteolytic lesion in the skull.

Cytoreductive surgery for ovarian cancer with the Cavitron Ultrasonic Surgical Aspirator and the development of disseminated intravascular coagulation.

OBJECTIVE: To explore the association between the use of the Cavitron Ultrasonic Surgical Aspirator for cytoreduction of ovarian cancer and the intraoperative development of disseminated intravascular coagulation (DIC). METHODS: A retrospective chart review was performed of all patients undergoing surgery for ovarian cancer from September 1991 to February 1993. Data were extracted to correlate clinical and hematologic evidence of DIC with and without intraoperative use of the Cavitron Ultrasonic Surgical Aspirator. Statistical analyses were done by chi 2 and analysis of variance. RESULTS: Fifty-one patients underwent surgery for ovarian cancer; 33 had stage IIIB, IIIC, IV, or recurrent disease and could be evaluated for this study. Nineteen patients were treated with the surgical aspirator, five of whom developed an intraoperative coagulopathy, as compared to none of 14 patients treated with conventional cytoreduction (P < .04, chi 2). The duration of use of the surgical aspirator correlated with the risk of coagulopathy (P < .001, analysis of variance). CONCLUSION: These data suggest a potential risk of developing DIC after extended use of the Cavitron Ultrasonic Surgical Aspirator for cytoreduction of ovarian cancer.

Uterine and ovarian conservation in advanced small cell carcinoma of the ovary.

BACKGROUND: The decision to recommend removal or conservation of a normal ovary and uterus in a young woman with advanced ovarian cancer is difficult and controversial. CASE: A 21-year-old patient with a large-cell variant of small-cell carcinoma of the ovary stage IIIc underwent optimal debulking surgery with preservation of the normal appearing uterus and opposite adnexa followed by aggressive multi-agent chemotherapy. She is menstruating normally and is free of disease, more than 2 years since completion of chemotherapy. CONCLUSION: In selected cases, conservation of the uninvolved ovary and uterus in patients with advanced-stage, small-cell carcinoma of the ovary may not compromise survival.

Vibrio species.

Vibrios are an important cause of human food-borne illness associated with the consumption of seafood worldwide, and contaminated food and drinking water in developing countries. Clinical syndromes induced by vibrios such as Vibrio cholerae, V. parahaemolyticus, V. vulnificus, and others range from mild, self-limiting gastroenteritis to life-threatening primary septicemia. As natural inhabitants of the aquatic environment, these bacteria pose a continual threat to food safety.

Pitfalls in cervical colposcopy.

An awareness of the pitfalls associated with the various aspects of the colposcopic examination should minimize erroneous diagnosis and inappropriate treatment. The colposcopist, armed with current knowledge and guided by a diagnostic and therapeutic protocol, should be able to avoid them (summarized in Table 1).

Impact of the loop electrosurgical excision procedure on future fertility.

OBJECTIVE: The loop electrosurgical excision procedure (LEEP) is a popular and effective method of conservatively treating premalignant lesions of the cervix in reproductive-age women. While the safety and effectiveness of LEEP has been documented, few data have been collected on the long-term effect of LEEP of the cervix on subsequent fertility. The purpose of this study was to determine that effect. STUDY DESIGN: A retrospective, cohort study with chart review and telephone or mail-in survey. One hundred fifty-eight women seen in the colposcopy clinic at New Hanover Regional Medical Center for abnormal cervical cytologic smears from January 1991 through December 1992 were surveyed concerning their reproductive history since undergoing colposcopy. The study group consisted of 79 women who had been treated with LEEP after demonstrating abnormalities on colposcopically directed cervical biopsy. The control group consisted of 79 women who underwent colposcopy and cervical biopsy without subsequent LEEP of the cervix. RESULTS: One hundred eleven women responded to the survey. In this study group, 11 of the 12 women who desired pregnancy actually became pregnant in the in interval between treatment and completion of the survey. All 17 patients in the control group who desired pregnancy became pregnant. CONCLUSION: In our patient population there appeared to be no significant detrimental effect of LEEP on future fertility. These preliminary findings are reassuring, however, due to the small sample size, the study lacked sufficient power for us to draw definitive conclusions.

Gynecologic and dermatologic electrosurgical units: a comparative review.

Electrosurgery is a popular surgical technique in which high-frequency, low-voltage electrical energy produced by an electrosurgical unit is used to excise abnormal tissue with hemostasis. In this study, electrosurgical units were critically evaluated for safety, electrical specifications, design, and performance characteristics. Quantitative electrical specification and histologic thermal artifact measurements and qualitative observations were recorded for 13 electrosurgical units representing 11 manufacturers. The Aspen Sabre 180 and Laerscope e10 were considered exemplary units based on safety criteria alone. Cut-mode thermal artifact was less than 10 microns for the Cooper Leep 6000, Laserscope e10, and Utah Finesse. A maximum fulguration distance of greater than 0.5 mm was demonstrated by the Gyne-Tech Autolepe 2000 and 4000, Laserscope e10, and the Elmed ESU 30. For gynecologic electrosurgery, the Aspen Sabre 180 and Laserscope e10 were rated best, followed closely by the Utah Finesse and Finesse II and the Gyne-Tech Autolepe 4000. Dermatologic electrosurgery may be well accomplished with many of the electrosurgical units, except as noted.

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.

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.