Re-evaluation of chronic hepatitis B and hepatitis C patients lost to follow-up: results of the Northern Holland hepatitis retrieval project.

BACKGROUND: Many persons infected with Hepatitis B virus (HBV) and Hepatitis C virus (HCV) in the past are now lost to follow-up. The aim of the Northern Holland Hepatitis Retrieval Project (NHHRP) is to retrieve and re-evaluate persons previously diagnosed with HBV or HCV and bring them back into care. Chronic HBV infection was defined as two positive Hepatitis B surface antigen (HBsAg) tests within 6 months and chronic HCV infection with 2 positive HCV RNA tests by polymerase chain reaction (PCR). METHODS: Data files of the local public health services and microbiology laboratory were explored to identify all registered HBV and HCV cases in the Alkmaar region, the Netherlands, for the past 15 years. Identified cases were compared with patients currently known in our hospital. Patients without follow-up in primary or hospital care were approached via their primary health care physician and invited for evaluation at our hospital. RESULTS: In total, 552 cases of HBV were identified. 356 (64.5%) had no follow-up. Only 113/356 (31.7%) were eligible for retrieval and 44.2% were evaluated in our hospital resulting in a change of management in 22/50 (44%) of patients. Four hundred ninety nine cases of HCV were identified, 150/499 (30.1%) were lost to follow-up. Only 20/150 (13.3%) were eligible for retrieval and 4/20 (20%) were evaluated at our clinic. Resulting in a change of management in 3/4 (75%). CONCLUSION: Only a limited part of HBV and HCV persons lost to follow-up is eligible for retrieval, nonetheless re-evaluation of these persons will lead to a change of management in the majority of persons.

The diagnostic yield of open-access endoscopy of the upper gastrointestinal tract in the Netherlands.

BACKGROUND AND STUDY AIMS: Since the introduction of open-access esophago-gastroduodenoscopy (OAE) there is an increase in the total number of performed OAEs whilst the frequency of clinical relevant findings has decreased. The aim of this study was to assess the appropriate use and the diagnostic yield of OAE in the Netherlands and to determine which patient variables are able to predict a malignant finding. PATIENTS AND METHODS: A retrospective chart review of all referrals for diagnostic OAE between October 2012 and October 2016 at the Northwest Clinics was performed. The indications were recorded from the referral letter and were classified as "appropriate" or "inappropriate" according to the NHG guideline. Logistic regression was used to detect significant predictive variables for a malignancy. RESULTS: A total of 2006 patients were included, of whom 59.6 % had an 'appropriate' referral indication. The diagnostic yield of finding a clinical relevant finding was significantly higher for OAEs with an "appropriate" referral indication. Independent risk factors for malignancy were alarm symptoms, age and male gender with a combined AUC of 0.868. CONCLUSIONS: Only 3.8 % of the malignancies would be missed by strict adherence to the guideline. This indicates that the open-access system in the Netherlands works well. Further improvement of the system can be achieved by only accepting appropriate indications for OAE and by treating patients under the age of 40 without OAE. We showed that a risk-prediction model based on the variables age, alarm symptoms and male gender is a good predictor of malignant finding.

[Online tool to prepare patient for colonoscopy; development and implementation of a patient-education app]. / Digitaal de patiënt voorbereiden op coloscopie.

Optimal patient education prior to colonoscopy is essential for an optimal outcome of the procedure. Patients benefit from adequate information regarding laxatives, risks and alternatives, and must provide informed consent. The endoscopist also has to have access to patient data in advance of the procedure in order to carry out an adequate risk assessment for the use of sedation. Most centres in the Netherlands usually make use of a pre-endoscopy consultation to exchange this information, but here is now pressure on this practice because the number of colonoscopies is increasing rapidly as a result of the introduction of the national screening programme for colorectal cancer.

PML-RARα kinetics and impact of FLT3-ITD mutations in newly diagnosed acute promyelocytic leukaemia treated with ATRA and ATO or ATRA and chemotherapy.

The APL0406 study showed that arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) are not inferior to standard ATRA and chemotherapy (CHT) in newly diagnosed, low-intermediaterisk acute promyelocytic leukaemia (APL). We analysed the kinetics of promyelocytic leukaemia-retinoic acid receptor-α (PML-RARα) transcripts by real-time quantitative PCR (RQ-PCR) in bone marrow samples from 184 patients and assessed the prognostic impact of fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) in 159 patients enrolled in this trial in Italy. After induction therapy, the reduction of PML-RARα transcripts was significantly greater in patients receiving ATRA-CHT as compared with those treated with ATRA-ATO (3.4 vs 2.9 logs; P=0.0182). Conversely, at the end of consolidation, a greater log reduction of PML-RARα transcripts was detected in the ATRA-ATO as compared with the ATRA-CHT group (6.3 vs 5.3 logs; P=0.0024). FLT3-ITD mutations had no significant impact on either event-free survival (EFS) or cumulative incidence of relapse in patients receiving ATRA-ATO, whereas a trend for inferior EFS was observed in FLT3-ITD-positive patients receiving ATRA-CHT. Our study shows at the molecular level that ATRA-ATO exerts at least equal and probably superior antileukaemic efficacy compared with ATRA-CHT in low-intermediaterisk APL. The data also suggest that ATRA-ATO may abrogate the negative prognostic impact of FLT3-ITD.

CAPD peritonitis after colonoscopy: follow the guidelines.

We present two cases of peritonitis shortly after endoscopic examination of the large bowel with polypectomy in patients on continuous ambulant peritoneal dialysis (CAPD) despite the standard preventive measure to drain the dialysate from the abdomen prior to the procedure. We have reviewed the current literature on this topic. These cases demonstrate that the administration of prophylactic broad-spectrum antibiotics next to the drainage of the abdomen prior to colonoscopy in CAPD patients should be considered as recommended in the International Society for Peritoneal Dialysis (IS PD) guidelines 2005.

Surgery for right-sided colonic diverticulitis: results of a 10-year-observation period.

INTRODUCTION: In contrast to sigmoid diverticular disease, right colonic diverticulitis is a rare disease in Western countries. The clinical presentation is often similar to acute appendicitis. OBJECTIVE: The aim of this study was to analyze surgical challenge in right-sided diverticulitis. MATERIALS AND METHODS: All patients who underwent resection for both right-sided and sigmoid diverticular disease were registered prospectively in a database (observation period, 1996-2005). A retrospective analysis of all patients who underwent resection for right-sided colonic diverticulitis (ileocolic resection, right colectomy) was performed. Special focus was set on incidence, clinical symptoms, indication, procedure, clinical outcome, and histopathologic findings including immunohistochemistry. RESULTS: From a total of 593 patients treated surgically for recurring or acute complicated diverticular disease, the majority (97.8%) suffered from sigmoid diverticulitis (n = 580), whereas 2.2% (n = 16) underwent surgery for right-sided diverticulitis (including three patients with combined sigmoid and cecal diverticulitis). Related to the total number of appendectomies (n = 1167), this represented an incidence of 1.4%. In five of 16 patients, acute appendicitis was presumed preoperatively. Most common diagnostic was ultrasonography. In the group of patients with right-sided diverticulitis, the most common procedure was right hemicolectomy (n = 10), followed by ileocolic resection (n = 3) and combined right colonic resection with sigmoid resection (n = 3). Histopathological investigation confirmed complicated diverticulitis of the cecum with local perforation or abscess in 75% of the patients (12/16). Hypoganglionosis or aganglionosis was diagnosed in seven of the 16 resected specimens. DISCUSSION: As right-sided diverticulitis is a rare colonic disease in Western countries, the differentiation from acute appendicitis may be difficult. In general, there is no difference in the treatment of right-sided diverticulitis compared to left-sided diverticulitis. As most cases will remain clinically unimminent, surgery is only indicated in complicated right-sided cases. Resection of the inflamed colonic segment with primary anastomosis is safe and can be performed laparoscopically. It can only be speculated whether hypoganglionosis or aganglionosis is a causative factor in the etiology of right-sided diverticulitis.

Differential coding of humoral stimuli by timing and amplitude of intracellular calcium spike trains.

The ubiquitous Ca2(+)-phosphoinositide pathway transduces extracellular signals to cellular effectors. Using a mathematical model, we simulated intracellular Ca2+ fluctuations in hepatocytes upon humoral stimulation. We estimated the information encoded about random humoral stimuli in these Ca2+ spike trains using an information-theoretic approach based on stimulus estimation methods. We demonstrate accurate transfer of information about random humoral signals with low temporal cutoff frequencies. In contrast, our results suggest that high-frequency stimuli are poorly transduced by the transmembrane machinery. We found that humoral signals are encoded in both the timing and amplitude of intracellular Ca2+ spikes. The information transmitted per spike is similar to that of sensory neuronal systems, in spite of several orders of magnitude difference in firing rate.

Humoral coding and decoding.

Humoral communication systems are dynamically regulated. Most hormones are released in a pulsatile or burst-like manner into the bloodstream. It is well known that information coded in the frequency and amplitude of secretory pulses allows for the differential regulation of specific target cell function and structure. However, despite intensive study of transmembrane signalling relatively little is known about how the temporal dynamics of extracellular humoral stimuli specifically regulates the temporal pattern of intracellular signalling pathways, such as Ca2+-dependent signalling. Repetitive spikes of Ca2+ encode this information in their amplitude, duration and frequency, and are in turn decoded into the pattern of gene expression and phosphorylation of target proteins. Using a mathematical model for G protein-coupled Ca2+ signalling and information-theoretic approaches to stimulus reconstruction we have systematically quantified the amount of information coded in the Ca2+-signal about the dynamics of the stimulus, which allows us to explore the temporal bandwidth of transmembrane signalling. These in silico approaches permit us to differentiate the amount of information coded in the frequency, temporal precision, amplitude and the complete Ca2+-signal. This may open an avenue to the quantification of information flow and processing in the intra- and intercellular coding and decoding machinery.

Fludarabine treatment in B-cell chronic lymphocytic leukemia: response, toxicity and survival analysis in 47 cases.

BACKGROUND AND OBJECTIVE: Fludarabine monophosphate (FAMP) is a purine analog with specific therapeutic activity in B-cell chronic lymphocytic leukemia (CLL). Its current use as front-line therapy of CLL is still a matter of debate both because of the controversial results of the clinical trials so far reported and because of the toxicity profile of the drug. In order to contribute to clarifying the possible role of FAMP, we report a retrospective analysis of the results obtained with the purine analog in CLL patients in different phases of the disease. DESIGN AND METHODS: Forty-seven patients affected by advanced CLL, 36% untreated, 31.9% relapsed and 31.9% resistant, were treated with FAMP 25 mg/m2/day, either for 4 days every 3 weeks in 29 cases, or for 5 days every 4 weeks in 18. The median number of FAMP cycles was 6 (range 2-11). Response was defined according to total tumor mass (TTM) score reduction and toxicity was expressed according to WHO grading criteria. The median follow-up of the series was 13 months from the beginning of FAMP therapy. RESULTS: Out of 47 evaluable patients the response rate was 74.4%, with 34% complete response (CR). The overall response rate was 94%, 80% and 46.6% in untreated, relapsed and resistant cases, respectively; a significantly higher number of responses was associated with no previous treatment and number of FAMP cycles. Fifty-three percent of all cases and 58.8% of untreated ones did not experience any toxicity. Treatment-related side effects were mainly autoimmune phenomena in untreated patients and infectious complications in treated ones. One heavily pre-treated patient died because of neurologic complications. Median time to re-treatment was18 months (range 1-30) and was influenced by age and previous treatment. The overall median survival was 35.7 months with a significantly higher proportion of surviving cases among RAI 0-II stages, responders and patients receiving more than 5 FAMP cycles. INTERPRETATION AND CONCLUSIONS: The present report confirms the high efficacy of FAMP in previously pre-treated cases with acceptable toxicity and encourages its use as front-line treatment provided that the results of randomized trials demonstrate its superiority over conventional chemotherapy. The possible development of autoimmune phenomena should, however, be considered seriously.

["Modality shift" paradigms and subjective basic symptoms in schizophrenic patients with various developmental biological risk anamnesis]. / "Modality-Shift"-Paradigma und subjektive Basissymptome bei Schizophrenen mit unterschiedlicher entwicklungsbiologischer Risikoanamnese.

Clinical experimental research on schizophrenia does not consider maturation processes of brain function in the majority of cases. In the course of neuronal organization and the differentiation phases of cerebral systems, early traumas in functionally important regions of the brain are accompanied by a facultative impairment of complex systems of information processing. Against the background of the comprehensively coherent "integrative psychobiological model of schizophrenia" (Ciompi) with high construct validity, (experimental) psychology investigations are reported on in the context of the "high-risk" concept in 44 young (20-37 years old) and mainly chronic schizophrenic patients with formation of a specific hypothesis for the developmental biology of the condition. In two homogeneous groups with the same structure, it is checked whether a discriminative appraisal concerning a different organization principle of central information processing systems is possible with "crossmodal" choice-reaction times (cCRT) and certain subscales of the Frankfurt symptom questionnaire (FBF) with regard to alternatively distributed and specially operationalized anamnestic biological risk factors. It can be objectively established in terms of experimental psychology that postpsychotically de-actualized "risk-free" schizophrenics differ from the reference group with a high-risk anamnesis in terms of significantly prolonged cCRT, but not from healthy subjects and an "MBD" control group. In addition, the FBF subscores "weakness of selective attention" and "loss of automatized skills" correlate with poor cCRT.(ABSTRACT TRUNCATED AT 250 WORDS)

[The hypnotic effect of the new benzodiazepine derivative lormetazepam when given intravenously (author's transl)]. / Der hypnotische Effekt des neuen Benzodiazepinderivates Lormetazepam nach intravenöser Injektion.

1. 7 groups of 3 healthy male volunteers each, at the age of 21--27 years received various doses of Lormetazepam (0.0635 to 4.0 mg/70 kg). -- 2. The drug was injected intravenously during 60 s. Before, during and up to 4 hours after the injections the EEG, eye-movements, ECG and respiration was recorded and blood pressures measured at given time intervals. -- 3. The vigilo-somnograms showed after the injections a change in the EEG-stages, indicating a reduction of alertness, transitions into reduced wakefulness or beginning stages of sleep. Corresponding to clinical signs one can speak with i.v. applied doses of 0.0635 to 0.5 mg/70 kg of tranquilizing, with 1 mg/70 kg of sedative and with 2--4 kg of hypnotic effects. There has been a good dosage-efficiency relation. -- 4. Side-effects or unwarranted symptoms have not been seen during the clinical observations.