IgG4-related disease of the hepatobiliary tract : 2 case reports and review of the literature.

IgG4-related disease is a rare inflammatory disorder that may mimic many infectious, malignant, and autoimmune conditions. The biliary tract is frequently involved, but hepatic lesions are rarely seen. Diagnosis is often delayed due to the absence of specific clinical and radiological signs, and the lack of an accurate diagnostic marker. Differential diagnosis includes cholangiocarcinoma, primary sclerosing cholangitis and intrinsic or metastatic liver disease. Corticosteroids are the cornerstone of therapy but treatment has not been standardized and relapse is common. Based on two cases of IgG4-related hepatobiliary disease, we review the current literature on this pathological entity.

Hepatic involvement in hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler Weber syndrome.

BACKGROUND AND STUDY AIMS: Hepatic involvement in hereditary hemorrhagic telangiectasia (HHT) is usually asymptomatic and does not require treatment. However, when present, clinical manifestations can cause considerable morbidity and mortality. Current expertise in the variable clinical manifestations and recommendations for diagnostic approach and management of hepatic involvement in HHT are outlined. METHODS AND MATERIALS: A review of current literature was performed using the MEDLINE search string: "Hereditary hemorrhagic telangiectasia [ALL] OR Rendu-Osler-Weber [ALL] AND (liver OR hepatic [ALL])". RESULTS: Due to the lack of therapeutic consequence, systematic screening for hepatic involvement in asymptomatic patients with HHT is currently not recommended. In symptomatic patients, diagnostic tools include non-invasive techniques such as abdominal color Doppler ultrasound, CT and/or MRI. In any case, liver biopsy should be avoided in patients with suspected HHT because of the high bleeding risk. Liver transplantation is currently the only curative option for symptomatic hepatic involvement in HHT. Except for biliary or hepatocellular necrosis, which require urgent liver transplantation, consensus on the most appropriate timing of transplantation is lacking. Recent studies have shown a promising role for angiogenesis inhibitors as a causative treatment for hepatic involvement in HHT and its complications. CONCLUSIONS: Identification of specific risk factors for progression to the symptomatic phase is one of the main future challenges. This would subsequently allow for individualized and cost-effective screening of high-risk patients when they are still in the asymptomatic stage. However, until then screening in asymptomatic patients is not recommended. Additionally the effect of preventive measures in this high-risk population on the development of symptomatic liver involvement and on poor outcome should be established.

Pirandello's analogy: a source for a better understanding of the social impact of stroke.

BACKGROUND: Suffering a stroke has major implications for the patient. To understand human suffering, one should understand society. Pirandello described society as a higher entity than the individual, thereby justifying human adaptability to society. We explore a qualitative finding that suggests that social trends may influence how stroke patients prioritize aspects of their rehabilitation. METHODS: We compare a contemporary patient's experience of stroke recovery with that of a fictional character from the works of Luigi Pirandello. Both patients had two main residual symptoms: hemiparesis and aphasia. RESULTS: The rehabilitation priorities of the two patients differed, and appeared to reflect the contemporaneous demands of society. Mobility was prioritized in 1910; communication was prioritized in 2010. However, essential aspects of 'being a stroke patient' remained unchanged; both patients retained a sense of self and both coped emotionally by being hopeful. CONCLUSIONS: We conclude that stroke patients respond to society's contemporaneous demands and expectations. Currently, society demands participation in a large social environment and this is reflected in stroke patients' priorities. This analogy could enable medical professionals to better understand the social impact of stroke, and consequently offer appropriate interventions to improve rehabilitation outcomes for individual patients.

The surgical history of the amputated limb according to the indication for revascularization: diabetic foot, acute ischaemia, aneurysmal disease, chronic arterial occlusive disease.

BACKGROUND: To investigate whether the indication for the first revascularization (diabetic foot, acute ischaemia, aneurysmal disease, chronic occlusive disease) determines the surgical history and survival time in amputated limbs. METHODS: The surgical history of lower extremities amputated between 2002 and 2009 was reviewed for the number of (endo)vascular procedures, minor amputations, wound debridements, complications requiring surgery (acute ischaemia, bleeding, graft infection) and limb survival time (LST). RESULTS: 100 limbs were included in the study. The four groups underwent a similar number of surgical procedures (mean 4.1). Diabetic foot limbs had fewer revascularizations (mean 1.3, p = 0.003) and complications (mean 0.1, p = 0.005), but more minor amputations and wound debridements (mean 1.3, p = 0.002), in a significantly shorter LST (mean 555 days, p = 0.003). Acute ischaemic limbs showed the shortest LST (mean 179 days, p = 0.003) and significantly more complications (mean 0.8, p = 0.005). Limbs initially treated for aneurysmal disease or chronic occlusive disease had the highest number of revascularizations (mean resp. 2.7 and 2.6) and the longest LST (mean resp. 1669 and 1459 days, p = 0.001). Limbs with advanced chronic occlusive disease (rest pain or gangrene) presented with fewer revascularisations (mean resp. 2.5 and 1.8, p = 0.01) and a shorter LST (mean resp. 1284 and 794 days, p = 0.004) compared to claudicants. CONCLUSIONS: Our study suggests that the surgical history and limb survival in amputated limbs is disease and stage specific, and determined by the indication of the first revascularisation.

Early arterial revascularization after hepatic artery thrombosis may avoid graft loss and improve outcomes in adult liver transplantation.

BACKGROUND: Hepatic artery thrombosis (HAT) represents a devastating complication after liver transplantation (LT), occurring in 1.6%-9.2% of adult recipients. Treatments of HAT include thrombectomy and thrombolysis (with or without redo of the arterial anastomosis), percutaneous thrombolysis through an angiogram, liver retransplantation, and clinical observation. METHODS: We retrospectively analyzed data from 739 adult LTs between January 1992 and September 2009. HAT was classified as early (E-HAT), when occurring within the first 30 days after LT, or late HAT (L-HAT), when diagnosed from the 2nd month onward. HAT suspected clinically was confirmed by Doppler ultrasound and angiography in all cases. Attempted revascularization was defined as early (ER) if performed within the first 2 weeks after LT and late (LR) if performed between 15 and 30 days. RESULTS: After a median follow-up (FU) of 62 months (range, 1-227 months), HAT occurred in 31/739 grafts (4.3%). E-HAT was recorded in 25/31 cases (3.4%) and L-HAT in 11/31 cases (0.8%). ER was performed in 20/31 patients (65%) leading to 62% graft salvage; it was 81% when the revascularization was performed within the first week after LT (P = ns). LR was unsuccessful in all cases (P = .08). The overall incidence of BC among rescued grafts was 54% without graft loss during FU. Graft survival was 79% versus 71%; and 50% versus 50% at 1 and 3 years for E-HAT and L-HAT, respectively (P = ns). CONCLUSIONS: Urgent revascularization in cases of early HAT may decrease graft loss, especially when performed within the first week after LT, with improved overall outcomes.

Influence of chemotherapy on the biodistribution of [99mTc]hydrazinonicotinamide annexin V in cancer patients.

AIM: The aim of this study was to determine whether administration of chemotherapy interferes with the quantitative uptake of [(99m)Tc]hydrazinonicotinamide (HYNIC) annexin V in normal human tissues at 5-7 h and 40-44 h after treatment initiation. METHODS: Eleven cancer patients were prospectively included in this study after written informed consent. Five patients underwent two scintigraphic scans with [(99m)Tc]HYNIC annexin V within 40-44 h from each other without any treatment given in between (control group or group 1). Six other patients starting a new chemotherapy or bisphosphonate regimen (treated group or group 2) underwent a scintigraphic scan with [(99m)Tc]HYNIC annexin V pretreatment (within 1 week of treatment initiation) and at 5-7 h and 40-44 h following treatment initiation. Whole-body and organ-specific geometric mean counts, corrected for background activity, were obtained from regions of interest drawn on the earliest images and kept constant over all subsequent images per patient. Differences in whole-body and organ uptake between successive scans were assessed using non-parametric statistics. RESULTS: No significant differences in mean percentages of injected dose uptake in whole body or organ tissues were observed between scan 1 and scan 2 in the control group and between scan 1, 2, and 3 in the treated group. CONCLUSIONS: Prior administration of [(99m)Tc]HYNIC annexin V and administration of chemotherapy does not interfere with quantitative specific uptake in healthy human tissues when using a schedule of baseline and 5-7 h and 40-44 h post-treatment imaging.

[Clozapine and selective serotonin reuptake inhibitors: risks of toxicity]. / Clozapine en selectieve serotonineheropnameremmers: risico's op toxiciteit.

A 25-year-old woman, known to have schizoaffective disorder, presented with symptoms that had arisen a few weeks earlier. The symptoms indicated that she had a toxic clozapine blood level. The probable cause of the toxicity was a pharmacokinetic interaction between citalopram and clozapine at the level of the cytochrome P450 system. A literature search reveals the importance of monitoring the interactions between selective serotonin reuptake inhibitors and clozapine, a procedure which should, if possible, be accompanied by blood level measurements. Caution is called for, particularly when non-smokers are involved.

[Benzodiazepines in the treatment of catatonia]. / Benzodiazepinen bij de behandeling van katatonie.

A patient who developed acute catatonia during benzodiazepine withdrawal is discussed. The case prompted us to review the literature on the role of benzodiazepines in the treatment of acute catatonia. Only retrospective and open studies were found which indicate that benzodiazepines do have a beneficial effect. Lorazepam is the most widely studied benzodiazepine and at present is the best treatment option. In the specific case of acute catatonia brought on by benzodiazepine withdrawal the recommended dosage is the same as for acute catatonia caused by something other than benzodiazepine withdrawal.

Oestrogen-mediated regulation of somatostatin receptor expression in human breast cancer cell lines assessed with 99mTc-depreotide.

Investigating three somatostatin receptor (SSTR)-positive (+) human breast cancer cell lines, Xu et al. found a time- and dose-dependent up- or down-regulation of SSTR2 mRNA expression by 17beta-oestradiol (E(2)) or the anti-oestrogen tamoxifen, respectively, in the two oestrogen receptor-positive (ER+) cell lines but not in the oestrogen receptor-negative (ER-) cell line. This study aimed to confirm the findings of Xu et al. at the protein level by means of western blotting and saturation binding studies using (99m)Tc-depreotide (NeoSpect). The ER+/SSTR+ ZR75-1 and T47D and SSTR+/ER- MDA MB231 breast cancer cell lines were exposed to 1 n M E(2) or a combination of 1 n M E(2) plus 100 n M tamoxifen or ICI 182 780 (Faslodex) for 48 h. Exposed and non-exposed controls were incubated with increasing concentrations of (99m)Tc-depreotide (0.5 n M-15 n M) in the absence and the presence of 20 micro M of octreotide. Scatchard-Rosenthal plots were derived using commercially available software. SSTR subtypes responsible for E(2)-induced changes in (99m)Tc-depreotide binding were identified by means of western blotting. Mean K(d) values for (99m)Tc-depreotide were 13 n M, 7 n M and 4 n M for T47D, ZR75-1 and MDA MB231 cells, respectively. After stimulation with E(2), the ER+ cell line T47D demonstrated a mean increase of 81% ( P<0.05) in (99m)Tc-depreotide binding. Adding the partial agonist tamoxifen and full antagonist ICI 182 780 to E(2) blocked the induced increase in T47D cells, either reducing SSTR expression or restoring it to control levels. ZR75-1 cells stimulated with E(2) showed a mean decrease in (99m)Tc-depreotide binding of 36% as compared to control cells; this difference, however, proved to be not statistically significant. Similarly, B(max) values did not change in ZR75-1 cells exposed to E(2) in combination with an ER antagonist as compared to control cells. Finally, no influence of E(2) on (99m)Tc-depreotide binding was observed in the ER- cell line MDA MB231. Both SSTR2 and SSTR5 were expressed at high levels in T47D cells and ZR75-1 cells. SSTR5 drastically increased in the absence of E(2) and was restored to the original detection level after E(2) treatment. The presented findings support an oestrogen-dependent regulation of SSTR expression in breast cancer cell lines.

Biodistribution and dosimetry study of 123I-rh-annexin V in mice and humans.

This study reports on the optimization of the labelling procedure of clinical grade 123I-rh-annexin V and on the investigation of the biodistribution and dosimetry of 123I-rh-annexin V, a tracer proposed for the study of apoptosis in mice and humans. Research grade 123I-rh-annexin V was prepared as described previously, whereas clinical grade 123I-rh-annexin V was prepared according to a modified IodoGen method. NMRI mice, 3-4 weeks of age, received research grade 123I-rh-annexin V (74.0+/-3.7 kBq/mouse) by intravenous (i.v.) injection and killed at preset time points. Afterwards, the collected organs, blood, urine and faeces were counted for radioactivity and determined as %ID/g tissue or %ID over time. Secondly, six volunteers with normal liver and kidney function underwent whole-body scans up to 21 h after i.v. injection of clinical grade 123I-rh-annexin V (345+/-38 MBq). Time-activity curves were generated for the organs of interest, e.g., thyroid, heart, liver, kidneys and whole body, by fitting the organ specific geometric mean counts, obtained from region of interest analysis of acquired images in humans. The MIRD formulation was applied to calculate the absorbed radiation doses for various organs. Clinical grade 123I-rh-annexin V was obtained in radiochemical yields of 87.0+/-6.5% and radiochemical purities >98%. In mice, research grade 123I-rh-annexin V accumulated primarily in liver, kidney, stomach and lung tissue, limiting its usefulness for imaging of ongoing apoptosis in the abdominal and thoracic region. Clearance was predominantly urinary. In humans, acquired images with the clinical grade radioligand showed low lung uptake, resulting in good imaging conditions for the thoracic region. On the other hand, delayed imaging of the abdominal region was impeded due to extensive bowel activity. The highest absorbed doses were received by the thyroid, the kidneys, the heart wall, the liver and bone surfaces. The average effective dose of 123I-rh-annexin V was estimated to be 0.02 mSv.MBq-1. The amount of 123I-rh-annexin V required for in vivo imaging, results in an acceptable effective dose to the patient.

18FDG PET versus high-dose 67Ga scintigraphy for restaging and treatment follow-up of lymphoma patients.

To date, only one published study has directly compared 67Ga scintigraphy (low dose, planar) with planar dual-head gamma camera 18F-fluorodeoxyglucose (18FDG) imaging for the purpose of treatment follow-up monitoring in lymphoma patients, and no data on restaging are available. The present study reports the direct comparison of high-dose (297-370 MBq) 67Ga planar and single photon emission computed tomography (SPECT) imaging and conventional 18FDG positron emission tomography (PET) for restaging and treatment follow-up of lymphoma patients versus a gold standard consisting of morphological imaging, including plain radiography and computed tomography (CT) scanning, bone marrow examination and long-term follow-up (<12 months). Sixteen patients, 10 with non-Hodgkin's lymphoma and six with Hodgkin's disease, were included (10 men, six women; median age, 43 years; range, 16-64 years). The median follow-up time was 27 months (range, 12-34 months). In two patients, 67Ga and 18FDG PET (370 MBq) were performed twice, resulting in 18 cross-sectional episodes. In 11 episodes, the results obtained by both imaging modalities were in agreement with regard to the presence or absence of disease when compared with the gold standard. However, the abnormalities found on 18FDG PET were always more extensive. In two episodes, 67Ga imaging normalized after treatment, whereas PET showed significant regression followed by subsequent normalization. In four additional episodes, 67Ga images were negative, whereas 18FDG PET visualized non-tumour-related pathology, such as lung infection, rib fracture or dense thymic tissue. In one gold standard-negative patient, the underlying cause of sternal FDG uptake remained undetermined. The data presented, although limited in number, suggest that 18FDG PET performs better than Ga imaging in monitoring lymphoma disease status. However, a correlation with clinical history and a knowledge of the characteristics of benign lesions are mandatory. Further studies are recommended.

Leakage assessment in adjustable laparoscopic gastric banding: radiography versus (99m)Tc-pertechnetate scintigraphy.

The least invasive of all surgical weight-lowering procedures is the adjustable laparoscopic gastric banding (ALGB) technique. A rare complication (0.9%-1.8% of patients) but one that may require surgical revision is leakage of the gastric banding device. This paper reports on the usefulness of technetium-99m scintigraphy for the assessment of gastric band leaks as compared with radiography. Between March 1997 and October 2001, 23 obese patients (20 women and 3 men; mean age 35 years; range 23-60 years; mean body mass index before gastric banding procedure, 39.2 kg/m(2); range 29.3-52.1 kg/m(2)) were referred for exclusion of gastric banding leakage by means of radiography and (99m)Tc-pertechnetate scintigraphy. Both procedures were performed on the same day in all patients. Two patients underwent both procedures, respectively two and three times. A total of 27 radiographic and scintigraphic examinations were performed. Radiographs were judged positive for leakage when escape of contrast agent through a defect in the gastric banding device was visualised or when indirect criteria, e.g. smooth passage of barium suspension through the stoma after injection of contrast agent, were present. Scintigraphic images were judged positive when tracer disappearance out of the banding device and uptake in the thyroid gland as well as enhancement of the gastric mucosa were observed 30 min and/or 3 h post injection. Overall sensitivity, specificity and accuracy for radiography and (99m)Tc scintigraphy were 81.8% vs 81.8%, 75% vs 100% and 77.7% vs 92.6%. Leakage from the reservoir or the connecting tube is a late complication of ALGB. The presented data suggest that (99m)Tc-pertechnetate scintigraphy is more efficient than radiography in determining the presence of such leaks.

Three-loop critical exponents, amplitude functions, and amplitude ratios from variational perturbation theory.

We use variational perturbation theory to calculate various universal amplitude ratios above and below Tc in minimally subtracted straight phi4 theory with N components in three dimensions. In order to best exhibit the method as a powerful alternative to Borel resummation techniques, we consider only two- and three-loops expressions where our results are analytic expressions. For the critical exponents, we also extend existing analytic expressions for two loops to three loops.

Computed tomography of the brain in unipolar depression.

Several authors have reported enlarged lateral brain ventricles in major depressive patients as compared to healthy controls. Also, the enlargement of brain lateral ventricles has been related to delusions, psychomotor retardation and some biochemical data such as cortisol secretion and L-tryptophan serum levels. The present study was undertaken to investigate if melancholic depressives are characterised by a higher degree of brain atrophy than normal controls and minor depressives, the origin of any brain atrophy, and whether measures of brain atrophy are related to cortisol secretion and L-tryptophan serum levels. We investigated 10 healthy controls and 35 depressive patients categorised according to DSM-III. In contrast to previous studies, we determined a combination of indices which makes it possible to differentiate between central and cortical diffuse atrophy. We found no evidence for the existence of abnormal atrophy of the brain in melancholics; nor did we find any correlation between CT scan measurements and cortisol or tryptophan.