The accumulation of Zn, Se, Cd, and Pb and physiological condition of Anadara trapezia transplanted to a contamination gradient in Lake Macquarie, New South Wales, Australia.

The benthic bivalve, Anadara trapezia, was collected from a 'clean' reference site and transplanted along a suspected trace metal contamination gradient in Lake Macquarie, NSW. At monthly intervals, Zn, Se, Cd and Pb concentrations were measured in the surficial sediments and whole tissues of the cockle as well as their physiological condition (Scope for Growth). Zinc, Cd and Pb concentrations in sediments decreased together, southward, with the highest concentrations in the Cockle Bay area, suggesting that this is the main source of contamination. Zinc, Cd and Pb concentrations were near or above [ANZECC/ARMCANZ, 2000. National water quality management strategy paper 4. Australian and New Zealand Guidelines for Fresh and Marine Water Quality, Australian and New Zealand Conservation Council and Agriculture and Resource Management Council of Australia and New Zealand. pp. 3.5.-1-3.5-10] sediment quality guidelines at Cockle Creek, Warners Bay and Koorooa Bay. Significant differences in trace metal concentrations could not be attributed to grain size or Fe concentration differences. Se concentrations were highest in fine grain Fe rich sediments of Whiteheads Lagoon, and likely to be associated with power generation operations. Trace metal concentrations did not vary significantly over time. Zinc, Cd and Pb concentrations in the tissues of A. trapezia followed a similar pattern to that of sediments. Zinc and Pb concentrations in cockles and sediments were highly correlated, indicating significant exposure-dose relationships. Selenium concentrations in the tissues of A. trapezia were higher after transplantation to the lake, however, Se concentrations were similar in all transplanted cockles, indicating that Se in contaminated sediments is not the major source of Se to organisms. There was a decline in the physiological condition of A. trapezia transplanted to Lake Macquarie after a 90-day-period with marked differences in clearance rates and respiration rates at some locations and absorption efficiencies at all locations. The mean Scope for Growth value at the most contaminated location, Cockle Bay, was markedly lower than at other locations. A significant Zn exposure-dose response relationship indicates that Zn bioaccumulation is occurring in response to sediment contamination. A significant Cd exposure-response relationship indicates that Cd may be influencing the health of cockles. Significant Pb exposure-dose, exposure-response and dose-response relationships indicate that Pb probably is affecting the health of cockles in Lake Macquarie. Therefore, Zn, Cd and Pb concentrations in sediments are likely to be affecting the health of cockles in Lake Macquarie.

Quality of life is decreased after treatment for nonfunctioning pituitary macroadenoma.

OBJECTIVE: Although a reduced quality of life (QoL) has been reported after long-term cure of functioning pituitary adenomas, the effect of successful treatment of nonfunctioning pituitary macroadenoma (NFMA) on QoL has not been fully addressed. Therefore, we evaluated a broad spectrum of QoL parameters in patients successfully treated for NFMA in our center. DESIGN: We conducted a case-control study. PATIENTS AND METHODS: We assessed QoL in 99 adult patients (mean age, 61.9 yr; range, 24-86 yr) in remission during long-term follow-up after surgical (n = 99) and additional radiotherapeutic (n = 37) treatment for NFMA by four validated health-related questionnaires (Hospital Anxiety and Depression Scale, Multidimensional Fatigue Index, Nottingham Health Profile, and Short Form-36). Patient outcomes were compared with 125 controls and with age-adjusted reference values derived from the literature. RESULTS: NFMA patients reported significantly impaired QoL in all questionnaires compared with the 125 controls and the age-adjusted reference values. All subscales of fatigue, assessed using the Multidimensional Fatigue Index (general fatigue, physical fatigue, reduction in activity, reduction in motivation, and mental fatigue) were impaired. The scores in the Nottingham Health Profile pointed toward reduced energy and affected emotional reaction. In several subscales of the Short Form-36 (social functioning, role limitations due to physical problems, role limitations due to emotional problems, and general health perception), NFMA patients reported a reduced QoL. CONCLUSION: QoL is considerably reduced in patients after successful treatment of NFMA.

Entecavir: a potent new antiviral drug for hepatitis B.

Entecavir, a new deoxyguanine nucleoside analogue, is a selective inhibitor of the replication of the hepatitis B virus. In vitro this compound has proven to be far more effective than other nucleoside analogues. In animal models, an impressive reduction of serum viral DNA has been observed with covalently closed circular DNA and hepatitis B viral core antigen negativity in liver biopsy specimens. In clinical studies, entecavir revealed excellent suppression of hepatitis B virus replication without significant side effects or evidence of mitochondrial toxicity. Until now, no entecavir-resistant viral mutants have been described. Prolonged therapy as well as prophylactic therapy, for example, in liver transplant recipients, is feasible and not limited by breakthrough infections. Data on entecavir therapy for treatment of nucleoside-naive, wild-type hepatitis B virus is being generated in Phase III clinical trials worldwide for both hepatitis B envelope antigen-positive and -negative subpopulations, as well as in lamivudine-resistant patients. Based on mechanism and potency of interferon and entecavir, clinical trials with combination therapy are eagerly awaited.

Benign anastomotic strictures after transhiatal esophagectomy and cervical esophagogastrostomy: risk factors and management.

UNLABELLED: Benign stricture formation at the cervical anastomosis after transhiatal esophagectomy with gastric tube interposition is an important source of morbidity. In a large group of patients (n = 269) who had undergone transhiatal esophagectomy with gastric tube interposition, we examined surgical and nonsurgical risk factors for the development of benign strictures at the cervical anastomosis. In addition, we evaluated the results of endoscopic bougie dilation in patients in whom an anastomotic stricture developed. RESULTS: During follow-up, 114 patients (42%) had a benign anastomotic stricture. Only a history of cardiac disease (P = 0.03), postoperative leakage at the anastomosis (p = 0.002), and a stapled rather than a hand-sewn anastomosis (p = 0.04) were found to be independent risk factors for the development of a stricture. In 27 of 60 patients with anastomotic leakage, contrast swallow examination demonstrated only a leak at the anastomosis. Endoscopic bougie dilation of anastomotic strictures was successful in 78% of patients after a median of three dilation sessions (range 1 to 28). In 3% of patients dilations were still being performed, and 19% of patients had died before normal swallowing had been achieved. In two of 519 (0.4%) dilation sessions a major complication occurred. CONCLUSIONS: (1) Patients with preoperative cardiac disease are at an increased risk for anastomotic stricture. (2) Even in patients having no symptoms, a contrast swallow can detect anastomotic leakage that results in an increased risk for the development of anastomotic strictures. (3) The benefit of the stapler device for anastomosis remains to be determined. (4) Endoscopic bougie dilation with the patient mildly sedated is a safe and effective method for the treatment of anastomotic strictures.

A survey of liver pathology in needle biopsies from HBsAg and anti-HBe positive individuals.

AIMS: To use laboratory data and liver biopsies, prospectively obtained from hepatitis B surface antigen (HBsAg) and anti hepatitis B e antigen (anti-HBe) positive patients, for the assessment of: (1) the relation between biopsy length/number of portal tracts and sampling error; (2) the relation between the severity of piecemeal necrosis and the new grading terminology (minimal, mild, moderate, and severe chronic hepatitis); and (3) liver pathology, which has not been studied in patients with this specific serological profile. METHODS: The study group (n = 174) included 104 patients with normal aminotransferase concentrations and no cases with clinically apparent cirrhosis. The specimen length and number of portal tracts were measured at light microscopy examination. Sampling error analysis was related to the discrepancies between aminotransferase concentrations versus histological grade. Detailed histological scorings were undertaken by the reference pathologist and compared with laboratory and hepatitis B virus (HBV) DNA precore sequence data. RESULTS: Sampling error seemed to be a constant feature, even for biopsies > or = 20 mm, but increased dramatically in biopsies < 5 mm long and/or containing less than four portal tracts. Between 25% and 30% of biopsies, graded as "mild" or "moderate" activity showed features of moderate and severe piecemeal necrosis, respectively. Ten per cent of the patients with normal aminotransferase values had stage III-IV hepatic fibrosis, and 20% had piecemeal necrosis. Only cytoplasmic, not nuclear, core antigen expression was a strong predictor of high hepatitis B viraemia. There was no association between precore stop codon mutations, grade/stage of liver disease, and hepatitis B core antigen (HBcAg) expression. CONCLUSIONS: The specimen available for light microscopical examination should be > 5 mm long and should contain more than four portal tracts. In addition, the new grading terminology might give the clinician an inappropriately mild impression of the severity of piecemeal necrosis. Furthermore, even in the presence of normal aminotransferase concentrations, considerable liver pathology can be found in 10-20% of HBsAg and anti-HBe positive individuals; such pathology is not associated with the occurrence of precore stop codon mutations.

Mitochondrial injury. Lessons from the fialuridine trial.

Fialuridine is an antiviral agent with potent activity against hepatitis B virus replication in vitro and in vivo. In a phase II study, 7 of 15 patients experienced severe toxicity due to the drug after 9 to 13 weeks of treatment. Adverse effects included nausea, vomiting and painful paraesthesia; subsequently, hepatic failure, pancreatitis, neuropathy, myopathy and lactic acidosis developed, probably due to multisystem mitochondrial toxicity. Possible mechanisms of fialuridine toxicity include mitochondrial injury and pyruvate oxidation inhibition. While other nucleoside analogues have shown evidence of inducing mitochondrial injury (zidovudine, didanosine, zalcitabine), others to date have not (lamivudine, famciclovir). Specific recommendations for future study of existing and new nucleoside analogues include testing for toxicity after prolonged incubation, specific investigations to measure mitochondrial function, toxicological tests and well designed clinical trials with appropriate testing to monitor for any adverse effects on mitochondrial integrity and function.

[The treatment of myocardial infarction during the hospital stage and shortly thereafter: now and 10 years ago]. / De behandeling van het myocardinfarct gedurende de ziekenhuisfase en kort daarna: nu en 10 jaar geleden.

OBJECTIVE: Comparison between the early and the late eighties of the application of thrombolysis and revascularisation in the acute phase of a myocardial infarction. LOCATION: University Hospital, Rotterdam. DESIGN: Prospective with historical comparison. METHODS: All patients admitted between May 1987 and May 1990 with a myocardial infarction and aged up to 71 years were included (n = 430). Numbers of procedures and survival during the following year were compared with data of patients admitted from 1981 to the end of 1983 (n = 706). RESULTS: In 1981-1983 thrombolytics were administered to 9% of the patients, in 1987-1990 to 40%. Revascularisation procedures during the next year were performed in 17% and 50% of the patients respectively. Hospital mortality decreased from 14% to 10% (p < 0.05), one-year survival increased from 75% to 83% (p < 0.05). For patients from 1987-1990 one-year survival was higher after thrombolysis treatment: 90% versus 78% without (p < 0.01), and after revascularisation: 94% versus 87% without (p < 0.01). CONCLUSION: Compared with 1981-1983 the treatment is at present more directed towards reperfusion and revascularisation of the ischaemic myocardium, resulting in invasive treatment in 50% of the patients now as opposed to 25% in the early eighties. The survival rate during the first year has improved.

[Collagenous colitis: macroscopically invisible, but with various treatment options]. / Collagene colitis: macroscopisch onzichtbaar, maar niet onbehandelbaar.

Two female patients, aged 54 and 67 years, respectively, had suffered from watery diarrhoea for several weeks or months without cramps or blood in the stools. The findings upon physical examination, blood and faecal examination and endoscopy were normal, and subsequent histological examination of intestinal biopsies revealed collagenous colitis. After treatment with a high-fibre diet, sulphasalazine and either prednisone or budesonide, the symptoms subsided. Collagenous colitis is a chronic watery diarrhoea disorder with unknown aetiology and pathogenesis. It is characterised by macroscopically normal mucosa, while histopathologically an abnormal thickening of the subepithelial collagenous layer and an increase in the number of intra-epithelial lymphocytes is found. There are various treatment options such as dietary fibre, mesalazine or bismuthsubsalicylate. Recently budesonide has been found to have a favourable effect both clinically and histologically. Complications of the disease are rare.

[Liver transplantation in a HIV-positive patient receiving potent antiretroviral therapy; the first case in The Netherlands]. / Orthotope levertransplantatie bij HIV-positiviteit en krachtige antiretrovirale behandeling; de eerste patient in Nederland.

In a 49-year-old woman infected with HIV who was receiving highly-active antiretroviral treatment (HAART), terminal liver failure developed. She also had an acute exacerbation of hepatitis B. She was treated by means of liver transplantation and was in good condition two years later. At that time she was treated with tacrolimus, lamivudine, tenofovir, nelfinavir and hepatitis-B immunoglobulin. HIV-RNA and the DNA of hepatitis-B virus could not be detected, her CD4-count was not abnormal and the liver transplant functioned well. No opportunistic infections had developed. HIV infection has long been considered an absolute contraindication to solid organ transplantation, due to the increased risk of infection and rapid progression to AIDS. With HAART, restoration of immune function is possible. Currently, international experience with liver transplantation for HIV-positive patients that are not infected with hepatitis C has shown promising results. Specifically, the risks of transplant rejection, opportunistic infections and progression to AIDS are not increased. Therefore, criteria have been defined for solid organ transplantation in HIV-positive recipients.

[Major psychiatric side effects of interferon alpha-2b]. / Ernstige psychiatrische bijwerkingen van interferon alfa-2b.

The Netherlands Pharmacovigilance Foundation Lareb and the Drug Safety Unit of the Inspectorate for Health Care in 1997 received 6 reports of serious psychiatric symptoms during the use of interferon alpha-2b. Of these patients, three men aged 42, 49 and 62 years and three women aged 31, 40 and 33 years, two had had psychic symptoms before. Depression or psychosis developed 12-24 weeks after the start of the use of interferon alpha-2b with 3-10 million IU per week subcutaneously because of chronic hepatitis B or C. After cessation of the medication, four patients recovered after a few days or weeks; the course of one patient was unknown, one patient had committed suicide. Knowledge of these psychiatric adverse drug reactions to interferon alpha-2b can contribute to early recognition by the physician and timely treatment of the symptoms.

[Chronic hepatitis-b-virus infections: new options for antiviral therapy]. / Chronische hepatitis-B-virusinfecties: nieuwe mogelijkheden voor antivirale therapie.

The possibilities for antiviral treatment of patients with chronic hepatitis B virus (HBV) infections have been in flux for the last few years. Apart from interferon alpha, oral nucleoside analogues are given a place. The treatment focuses on the group of patients with active virus multiplication (hepatitis B e antigen (HBeAg) and HBV DNA are demonstrable), abnormal liver enzyme values and histologically demonstrated inflammatory activity in the liver. For the individual patient the pros and cons of protracted virus inhibition should be weighted by means of an orally administered nucleoside analogue such as lamivudine, immunostimulation with injections of interferon alpha or a combination of these two.

Dutch guidance for the treatment of chronic hepatitis C virus infection in a new therapeutic era.

BACKGROUND: A new era for the treatment of chronic hepatitis C is about to transpire. With the introduction of the first-generation protease inhibitors the efficacy of hepatitis C treatment improved significantly. Since then, the therapeutic agenda has moved further forward with the recent approval of sofosbuvir and the expected approval of agents such as simeprevir and daclatasvir. This paper, developed parallel to the approval of sofosbuvir, is to serve as a guidance for the therapeutic management of chronic hepatitis C. METHODS: We performed a formal search through PubMed, Web of Science and ClinicalTrials.gov to identify all clinical trials that have been conducted with EMA-approved new agents in hepatitis C; for this version (April 2014) we focused on sofosbuvir. For each disease category, the evidence was reviewed and recommendations are based on GRADE. RESULTS: We identified 11 clinical trials with sofosbuvir and for each disease category recommendations for treatment are made. Not all disease categories were studied extensively and therefore in some cases we were unable to provide recommendations. CONCLUSION: The recent approval of sofosbuvir will most likely change the therapeutic landscape of chronic hepatitis C. The use of sofosbuvir-containing regimens can shorten the duration of therapy, increase efficacy and result in less side effects, compared with standard of care. The efficacy relative to standard of care needs to be weighed against the increased costs of sofosbuvir. With future approval of the other direct-acting antivirals, the outcome of hepatitis C treatment will likely improve further and this guidance will be updated.

The 2012 revised Dutch national guidelines for the treatment of chronic hepatitis B virus infection.

In 2008, the Netherlands Association of Gastroenterologists and Hepatologists (Nederlands Vereniging van Maag-Darm-Leverartsen) published the Dutch national guidelines for the treatment of chronic hepatitis B virus infection. New insights into the treatment of chronic hepatitis B with relevance for clinical practice have been adopted in these concise, revised guidelines. The most important changes include the choice of initial antiviral therapy, licensing of tenofovir for the treatment of chronic hepatitis B and the management of antiviral resistance.

Progressive improvement of impaired visual acuity during the first year after transsphenoidal surgery for non-functioning pituitary macroadenoma.

OBJECTIVE: Improvement of visual field defects continues even years after the initial surgical treatment. Because this process of continuing improvement has not been documented for visual acuity, we audited our data to explore the pattern of recovery of visual acuity until 1 year after transsphenoidal surgery for non-functioning pituitary macroadenoma. DESIGN: Retrospective follow-up study. PATIENTS: Forty-three patients (mean age 56 +/- 14 years), treated by transsphenoidal surgery for non-functioning pituitary macroadenoma, were included in this analysis. RESULTS: Visual acuity improved significantly within 3 months after transsphenoidal surgery. The mean visual acuity increased from 0.65 +/- 0.37 to 0.75 +/- 0.36 (P < 0.01) (right eye), and from 0.60 +/- 0.32 to 0.82 +/- 0.30 (P < 0.01) (left eye). Visual acuity was improved 1 year after transsphenoidal surgery compared to the 3 months postoperative values. The mean visual acuity increased from 0.75 +/- 0.36 to 0.82 +/- 0.34 (P < 0.05) (right eye), and from 0.82 +/- 0.30 to 0.88 +/- 0.27 (P < 0.05) (left eye). CONCLUSION: Visual acuity improves progressively after surgical treatment for non-functioning pituitary macroadenomas, at least within the first year after transsphenoidal surgery.

Physiological costs of reproduction in the Sydney rock oyster Saccostrea glomerata. How expensive is reproduction?

In this study, triploid Sydney rock oysters Saccostrea glomerata, which do not reproduce and have only limited gonadal development, were used to calculate the cost of producing and maintaining somatic tissues. The consumption of oxygen was measured and converted to units of energy expended. The consumption of oxygen of diploid oysters, in different stages of the reproductive cycle, was also measured. Knowing the costs of producing and maintaining somatic tissues (obtained from the triploid oysters), it was possible to calculate the energy demand of somatic and reproductive tissues of diploid oysters. The focus of this study was to test whether this method would work, to investigate if this method would give results in accordance with modern life-history theory and to test hypotheses about costs of reproduction in oysters. It was found that in diploid oysters, 27% of the consumed oxygen was needed for reproductive processes. It was also found that the costs of production and maintenance of reproductive tissues were on average 84% of those of somatic tissues. Costs for the production and maintenance of somatic tissues decreased over time. Costs for reproduction also decreased, but were dependent on the stage of gonadal development. If the relative mass of gametes in the gonads was large, the costs were relatively small; if the mass was relatively small, the costs were large. Differences between traits of males and females were never significant, suggesting that reproductive effort and costs were similar in males and females. It was estimated that if diploid oysters did not reproduce, they could gain 64% more somatic ash-free dry mass. Thus, in terms of growth, reproduction is an expensive activity.

Precipitating and aggravating factors of migraine versus tension-type headache.

OBJECTIVE: We conducted the present study to determine whether there are headache precipitating and aggravating factors that differentiate migraine from tension-type headache and headache precipitating and aggravating factors that differentiate tension-type headache from migraine. METHODS: We interviewed 38 patients with migraine and 17 patients with tension-type headache (diagnosed using International Headache Society criteria) by telephone, using a questionnaire. The questionnaire inquired about the following precipitating and aggravating headache factors: (1) physical activity, (2) straining, (3) bending over, (4) stress/tension, (5) coughing/sneezing, (6) fatigue, (7) reading, (8) driving, (9) lack of sleep, (10) specific foods/drinks, (11) alcohol, (12) not eating on time, (13) smoke, (14) smell, (15) light, (16) noise, (17) menstruation, and (18) weather. RESULTS: The most common precipitating factors acknowledged by both groups of patients were stress/tension, not eating on time, fatigue, and lack of sleep. Weather, smell, smoke, and light were the precipitating factors that differentiated migraine from tension-type headache. Excluding those factors that are part of the International Headache Society migraine diagnosis, the aggravating factors were straining, bending over, and smell. We found no precipitating or aggravating factors differentiating tension-type headache from migraine. CONCLUSION: Apparently there are precipitating and aggravating factors differentiating migraine from tension-type headache but not vice versa. It is interesting that three of the migraine-specific precipitating factors (ie, weather, smell, and smoke) involve the nose/sinus system, suggesting a greater significance of this system in headache than is generally considered.

Chronic daily headache: a time perspective.

OBJECTIVE: To determine the development and outcome of chronic daily headache in 258 headache practice patients, consisting of 50 men and 208 women. Chronic daily headache was defined as headaches occurring on at least 5 days per week for at least 1 year. METHODS: Two hundred fifty-eight patients with headache were interviewed and evaluated. Ninety-one patients were contacted by telephone for follow-up. RESULTS: Twenty-two percent of the patients had daily headaches from the onset, and 78% initially experienced intermittent headaches. Of the patients with initially intermittent headaches, 19% experienced an abrupt transition into daily headaches and 81%, a gradual one. In the patients with gradual transition, the transition of the initial, intermittent headaches into daily headaches took an average of 10.7 years. The initial headaches were mild in 33% of the patients and severe in 67%. The severe headaches were associated with nausea and vomiting significantly more often than the mild ones. However, the daily headaches that these patients ultimately developed were the same, regardless of whether the initial headaches were mild or severe. The patients who gradually developed daily headaches from initially intermittent headaches were contacted to determine the outcome of their headaches. Of these patients, 33% continued to have daily headaches and 67% again experienced intermittent headaches. Of the latter group, 88% of the patients who now had migraine also had migraine initially.

Psychophysical precedents of migraine in relation to the time of onset of the headache: the migraine time line.

We conducted a prospective study of 19 female migraine patients who kept a diary four times per day at 8 AM, 1 PM, 6 PM, and 11 PM for 10 consecutive weeks. In the diary, the patients recorded the occurrence as well as the features and associated symptoms of their headaches. They also rated five mood states: alertness, tension, irritability, depression, and fatigue, as well as the quality of sleep and the incidence and stressfulness of daily hassles as measurements of stress. They quantified the variables through the use of 100-mm visual analog scales. In the diaries, we identified 68 migraine headaches of which 23 developed during the night, 19 during the morning, 16 during the afternoon, and 10 during the evening. The headaches which developed during the evening or night were preceded by an increased incidence of daily hassles during the afternoon. The headaches which developed during the morning or afternoon were preceded by increased tension the previous days. The day before the headaches which developed during the morning, the incidence of daily hassles was increased during the morning, afternoon, and evening. The increased tension at 1 PM was followed by increased fatigue at 6 PM, which was still present at 8 AM of the morning during which the headaches developed. The day before the headaches which developed during the afternoon, the increased tension at 6 PM was followed by increased alertness at 11 PM. The next morning, the stressfulness of daily hassles was increased at 8 AM, followed by increased tension and irritability at 1 PM. We conclude that there are three different sequences of events with regard to the psychophysical precedents of migraine, depending on the time of onset of the headache: the migraine time line.