Transformation and release of micronized Cu used as a wood preservative in treated wood in wetland soil.

Micronized Cu (µ-Cu) is used as a wood preservative, replacing toxic chromated copper arsenate (CCA). Micronized Cu is malachite [Cu2CO3(OH)2] that has been milled to micron/submicron particles, with many particle diameters less than 100 nm, mixed with biocides and then used to treat wood. In addition to concerns about the fate of the Cu from µ-Cu, there is interest in the fate of the nano-Cu (n-Cu) constituents. We examined movement of Cu from µ-Cu-treated wood after placing treated-wood stakes into model wetland ecosystems. Release of Cu into surface and subsurface water was monitored. Surface water Cu reached maximum levels 3 days after stake installation and remained elevated if the systems remained inundated. Subsurface water Cu levels were 10% of surface water levels at day 3 and increased gradually thereafter. Sequential filtering indicated that a large portion of the Cu in solution was associating with soluble organics, but there was no evidence for n-Cu in solution. After 4 months, Cu in thin-sections of treated wood and adjacent soil were characterized with micro X-ray absorption fine structure spectroscopy (µ-XAFS). Localization and speciation of Cu in the wood and adjacent soil using µ-XAFS clearly indicated that Cu concentrations decreased over time in the treated wood and increased in the adjacent soil. However, n-Cu from the treated wood was not found in the adjacent soil or plant roots. The results of this study indicate that Cu in the µ-Cu-treated wood dissolves and migrates into adjacent soil and waters primarily in ionic form (i.e., Cu2+) and not as nano-sized Cu particles. A reduced form of Cu (Cu2S) was identified in deep soil proximal to the treated wood, indicating strong reducing conditions. The formation of the insoluble Cu2S effectively removes some portion of dissolved Cu from solution, reducing movement of Cu2+ to the water column and diminishing exposure.

Systemic ventricular assist device support in Fontan patients: A report by ACTION.

BACKGROUND: The size of the Fontan population with end-stage heart failure is growing. In this population, heart transplantation has been the only option. This study sought to investigate the efficacy of ventricular assist device (VAD) support in Fontan patients. METHODS: We conducted a retrospective study of Fontan patients in the Advanced Cardiac Therapies Improving Outcomes Network. We evaluated patient characteristics, and the clinical and physiologic outcomes after VAD implantation. RESULTS: We identified 45 Fontan patients implanted with VAD. The average age of patients was 10 years (interquartile range: 4.5-18) and 30% were female. The majority had a morphologic right ventricle (69%), moderate or greater ventricular dysfunction (83%), and moderate or greater atrioventricular valve regurgitation (65%). The majority of implants were as a bridge to transplantation (76%), and the majority of patients were Interagency Registry for Mechanically Assisted Circulatory Support Profile 2 (56%). The most commonly employed device was the Medtronic HeartWare HVAD (56%). A total of 13 patients were discharged on device support, and 67% of patients experienced adverse events, the most common of which were neurologic (25%). At 1 year after device implantation, the rate of transplantation was 69.5%, 9.2% of patients continued to be VAD supported, and 21.3% of patients had died. Hemodynamically, VAD was effective in decreasing both Fontan and ventricular end-diastolic pressures in some individuals. CONCLUSIONS: VAD is effective in supporting patients with end-stage Fontan failure awaiting heart transplantation. Future research should focus on identifying clinical and physiologic characteristics predictive of a favorable response to VAD support.

Suppression of sleep-related prolactin secretion and enhancement of sleep-related growth hormone secretion.

Methysergide, a clinically-used blocker of serotonin receptors, was administered to 10 normal young men at a dose of 2 mg every 6 h for 48 h. After drug treatment, serum levels of growth hormone during sleep were 41.9% higher than placebo values (less than 0.001). In contrast, drug treatment was associated with a 36.4% decrease in stimulated growth hormone secretion during insulin tolerance testing (P less than 0.01). These opposite effects of methysergide suggest that different mechanisms are responsible for sleep-related and insulin-induced growth hormone secretion. Accordingly, data obtained with pharmacologic stimuli may lead to erroneous inferences regarding physiologic growth hormone control mechanisms. Administration of methysergide profoundly suppressed sleep-related prolactin secretion; overall nocturnal mean prolactin fell by 70.3% from 4.30+/-0.19 to 1.28+/-0.06 ng/ml (P less than 0.0001). It appears that serotonin may be significant modulating neurotransmitter for the control of growth hormone secretion, limiting sleep-related release, and enhancing insulin-induced release. It seems likely from these data that the role of serotonin in the control of prolactin secretion is relatively more important, since serotonin receptor blockade dramatically reduced sleep-related prolactin secretion.

Serotonin inhibition and sleep.

Methysergide a clinically used blocker of serotonin receptors, was given for 48 hr to 11 normal adults, at a dose of 8 mg per 24 hr. Total REM sleep time was decreased, although total sleep time was unchanged. Stage 4 decreased and stage 3 increased, while total slow wave sleep remained constant. There was a tendency toward a decrease in the number of intact sleep cycles. The relationship of these data to published reports on p-chlorophenylalanine is discussed.

A comparison of two benzodiazepine hypnotics administered with alcohol.

Two benzodiazepine hypnotics were administered alone or in combination with alcohol to normal male volunteers. In the doses given, alcohol potentiated the effects of the benzodiazepines on some but not all performance measures.

Pathophysiology of radiocontrast nephropathy: a role for medullary hypoxia.

Recent experimental data underlies the role of hypoxic tubular injury in the pathophysiology of radiocontrast nephropathy. Although systemic transient hypoxemia, increased blood viscosity, and a leftward shift of the oxygen-hemoglobin dissociation curve may all contribute to intrarenal hypoxia, imbalance between oxygen demand and supply plays a major role in radiocontrast-induced outer medullary hypoxic damage. Low oxygen tension normally exists in this renal region, reflecting the precarious regional oxygen supply and a high local metabolic rate and oxygen requirement, resulting from active salt reabsorption by medullary thick ascending limbs of Henle's loop. Radiologic contrast agents markedly aggravate outer medullary physiologic hypoxia. This results from enhanced metabolic activity and oxygen consumption (as a result of osmotic diuresis and increased salt delivery to the distal nephron) because the regional blood flow and the oxygen supply actually increase. The latter effect may result in part from the activation of various regulatory mediators of outer medullary blood flow to ensure maximal regional oxygen supply. Low-osmolar radiocontrast agents may be less nephrotoxic because of the smaller osmotic load and vasomotor alterations. Experimental radiocontrast-induced renal failure requires preconditioning of animals with various insults (for example, congestive heart failure, reduced renal mass, salt depletion, or inhibition of nitric oxide and prostaglandin synthesis). In all these perturbations, which resemble clinical conditions that predispose to contrast nephropathy, outer medullary hypoxic injury results from insufficiency or inactivation of mechanisms designed to preserve regional oxygen balance. This underlines the importance of identifying and ameliorating predisposing factors in the prevention of this iatrogenic disease.

Likelihood ratios: getting diagnostic testing into perspective.

In modern medicine, sophisticated laboratory tests and imaging studies are often emphasized at the expense of history and physical examination, rather than complementing clinical assessment. Ancillary testing often fails to advance the diagnostic process, and increases patient risk and the expense of medical care. The relative value of clinical evaluation and technological methods is rarely considered, and the power of the clinical evaluation is therefore underestimated. The likelihood ratio (LR) is a semiquantitative measure of the performance of diagnostic tests which indicates how much a diagnostic procedure modifies the probability of disease, and is calculated from the sensitivity and specificity of the test (or directly from the change in probability associated with the test result). We review the performance of frequently-used tests by their LRs, and compare them to the power of clinical assessment, with clinical cases to illustrate the application of LRs in the diagnostic process. The discriminative power of clinical assessment and ancillary tests is often similar, and the combination of the two greatly increases accuracy in the diagnostic process. Clinical assessment is indeed frequently more informative than current technical modalities. LRs assist in putting the value of testing in proper perspective. Practice in evaluating pre-test probabilities of disease and in the application of LRs should be enhanced in medical training.

Age-related glucose metabolism alterations in nondiabetic and potentially diabetic women.

The incidence of pathological glucose tolerance was investigated in women of three age groups: 20--39, 40--59 and over 60 yr, by means of oral glucose tolerance tests and the Danowski Index. The incidence was found to be significantly higher in older women: thus an age-related deterioration of glucose metabolism was confirmed. The women in each are group were further divided into "healthy" nondiabetic and "potentially diabetic" women. The parameter of "potential diabetes" was found to be associated to a greater extent with age-related glucose tolerance deterioration than advancing age alone. The existing theories for the etiology of carbohydrate metabolism alteration in older women are reviewed. it is suggested that in view of the age-related deterioration of glucose metabolism, a new normal range of glucose tolerance should be established in an ageing population.

Dimensions of agoraphobia assessed by the Mobility Inventory.

Factor analyses of the When Accompanied and When Alone subscales of the Mobility Inventory (Chambless, Caputo, Jasin, Gracely & Williams, Behaviour Research and Therapy, 23, 35-44, 1985) were conducted using the responses of 177 panic disorder with agoraphobia patients. For both subscales a three-factor model was the most appropriate and accounted for approx. 60% of the variance in each case. The three factors were reliable and theoretically meaningful: fear of public places, enclosed spaces and open spaces. The fear of public places factor accounted for most of the explained variance and is discussed in relation to the social evaluation component of panic attacks.

Precipitating events, locations and reactions associated with initial unexpected panic attacks.

This study examined the phenomenology of the initial panic attack in 85 panic disorder patients with or without agoraphobia. Patients were divided into minimal and extensive avoiders and three domains were assessed: precipitating factors, location of initial panic, and reaction to the panic. No apparent precipitating factor could be identified in approx 40% of the patients. The most common precipitants were injury/illness and interpersonal conflict. Extensive avoiders were more likely to have experienced the initial panic in classic agoraphobic situations. Public transportation was the most common location for the total sample. In reaction to the panic, minimal avoiders were more likely to have gone to a hospital emergency room (ER) whereas extensive avoiders were more likely to have done nothing in terms of help-seeking. Many patients with either minimal or extensive avoidance avoided the locations where the initial panic occurred, suggesting that circumscribed avoidance does not always generalize.

Gender effects and alcohol use in panic disorder with agoraphobia.

Previous studies have found some significant, but weak, gender differences in panic and agoraphobia with females generally being more symptomatic. The present study sought to expand this line of research by examining alcohol use and self-medication in relation to gender differences and measures of psychopathology. Seventy-four male and 162 female patients with panic disorder with agoraphobia were compared. There were some significant, but relatively small, gender differences with females reporting higher levels of phobic avoidance. Males reported significantly more weekly alcohol intake and also perceived alcohol to be a more effective strategy in coping with anxiety. Alcohol-related factors were significantly correlated with several measures of psychopathology for males but this was less evident in females. The correlations were not large but the results do suggest that a subset of males consume moderate to large amounts of alcohol, believe self-medication to be an effective anti-anxiety strategy, and yet report higher levels of psychopathology such as social fears.

Ovarian pregnancy: association with IUD, pelvic pathology and recurrent abortion.

Six cases of ovarian pregnancy were reviewed and their relationship with the IUD, fibromyoma of the uterus and previous spontaneous abortion was examined. In fact, 5 patients had an IUD in situ, in 2 women fibroids were found; 4 of the women had spontaneous abortions in their past history. The latter fact has been discussed, and it is suggested that this association may possibly contribute to an early diagnosis of ectopic pregnancy resulting in improved chances for conservative microsurgery. Attention is drawn to the fact that the diagnosis of ovarian pregnancy is often made only on microscopic examination. Thus, it is concluded that the true incidence of ovarian pregnancy may be higher than is apparent.

PIP: 6 cases of ovarian pregnancy were reviewed and their relationship with the IUD, fibromyoma of the uterus, and previous spontaneous abortion was examined. 5 of the patients had in situ IUDs, and 1 patient was treated in conjunction with a 20 week size fibroid uterus. 1 of the patients with an IUD also had a fibroid uterus. 4 of the women had spontaneous abortions in their past history. All cases met Spiegelberg's requirements for the diagnosis of ovarian pregnancy. The 6 cases are summarized in table form. During the 4 year period that these 6 patients were treated, a total of 59 ectopic pregnancies were treated at the Hasharon Hospital in Petah-Tikva, Israel. 18 or 30.5% occurred in patients with in situ IUDs. Ovarian pregnancies constituted 10.2% of all the ectopic pregnancies and 20% of the ectopic pregnancies in the group of patients using IUDs. The possibility that the IUD may potentiate ovarian nidation must be considered. It has been suggested that the IUD causes changes in the synthesis of prostaglandins so that tubal peristalsis is increased, and this could increase the incidence of both tubal and ovarian pregnancies. 2 of the patients were initially treated for vaginal bleeding and pelvic pain by removal of their IUDs, and the proper treatment was delayed for 14 days. The ovarian pregnancy in the patient with the fibroid uterus was diagnosed only after histological examination of an incidental hemorrhagic mass found at laparotomy. The series of 6 cases of ovarian ectopic pregnancy seems to confirm the association, and it must also be noted that mild chronic salpingitis was reported on histopathological examination in only 1 case. No conclusion can be reached on the basis of such a small group of patients.

Secondary cervical perforation by the Copper-T intrauterine device.

Five cases of cervical perforation have been observed in women with a Copper-T IUCD, over a period of 5 yr. In all cases, the distal end of the stem (vertical limb) of the T had perforated through the cervical wall into one of the fornices of the vagina. Only 2 cases had symptoms leading to the discovery of the device, while the other 3 were discovered accidentally or on routine examination.

PIP: 5 cases of IUD perforation of the cervix were encountered during a 5-year period (1973-78). In these cases, the distal end of the stem (vertical limb) of the T had penetrated through the cervical wall into 1 of the fornices of the vagina. Case 3 involves a 31-year old gravida 3, para 1 who presented at the Hasharon Hospital in the 10th week of pregnancy complaining of lower abdominal pain and mild bleeding. Her physician had previously recommended removal of IUD upon finding out of her pregnancy, but she had refused because the IUD removal "might harm the pregnancy". The present examination revealed cervical perforation by the copper T-IUD, which was then removed through the tiny fistula in the cervix. Bleeding and pain disappeared within 3 days. The woman delivered a normal healthy baby 29 weeks later. Case 4 concerns a 24-year old gravida 3, para 2 who presented at the clinic at the 12-monthly check-up. The string of the IUD was found protruding through the cervical os, while the copper-covered long arm of the IUD had perforated the cervix and was felt in the posterior fornix. The fistula disappeared after the IUD was removed. Although cervical perforations rarely consititute a risk to the woman and are easily removed without permanent damage to the cervix, such complications if they do occur should be reported in view of their extensive use world wide. In addition, risk of pregnancy is increased due to the displacement of the device.

Bacteriologic studies in second-trimester pregnancy termination: a comparison of intra- and extra-amniotic methods.

Vaginal and cervical cultures were obtained in 20 women undergoing intra-amniotic saline infusion and 20 women having extraamniotic saline infusion for second-trimester abortion. Following expulsion intrauterine cultures were taken and the patients were followed for signs of clinical infection. Sixty percent of the patients had pathogenic bacteria cultured intrauterine cultures after abortion and 7.5% had clinical infection. There was a positive correlation between infection-abortion time and pathogenic intrauterine cultures. No significant differences in the incidence of positive intrauterine cultures or clinical infection between the two groups were found. Of those patients with positive preabortion cultures 70% had identical pathogens cultured from the uterus after expulsion suggesting that most postabortal pathogens arise from endogenous vaginal and cervical sites rather than from exogenous sources.

Intracerebral and subarachnoid hemorrhage in patients with cancer.

OBJECTIVE: To analyze the risk factors, presentation, etiologies, and outcomes of adult cancer patients with intracranial hemorrhage (IH). METHODS: We analyzed 208 patients retrospectively with the diagnosis of IH from the Memorial Sloan-Kettering neurology database from January 2000 through December 2007. Charts were examined for clinical and radiographic data. Survival was calculated using the Kaplan-Meier method. Survival between groups was compared via the log-rank test. Logistic regression models were used to assess for prognostic indicators of 30- and 90-day mortality. RESULTS: There were 181 intracerebral and 46 subarachnoid hemorrhages. Sixty-eight percent of patients had solid tumors, 16% had primary brain tumors, and 16% had hematopoietic tumors. Hemiparesis and headache were the most common symptoms. Intratumoral hemorrhage (61%) and coagulopathy (46%) accounted for the majority of hemorrhages, whereas hypertension (5%) was rare. Median survival was 3 months (95% confidence interval [CI] 2-4), and 30-day mortality was 31%. However, nearly one-half of patients were completely or partially independent at the time of discharge. Patients with primary brain tumors had the longest median survival (5.9 months, 95% CI 2.9-11.8, p = 0.05). Independent predictors of 30-day mortality were not having a primary brain tumor, impaired consciousness, multiple foci of hemorrhage, hydrocephalus, no ventriculostomy, and treatment of increased intracranial pressure. CONCLUSIONS: Intracranial hemorrhage in patients with cancer is often due to unique mechanisms. Prognosis is poor, but comparable to intracranial hemorrhage in the general population. Aggressive care is recommended despite high mortality, because many patients have good functional outcomes.