Treatment of gastric carcinoids type 1 with the gastrin receptor antagonist netazepide (YF476) results in regression of tumours and normalisation of serum chromogranin A.

BACKGROUND: Patients with chronic atrophic gastritis have long-term gastric hypoacidity, and secondary hypergastrinaemia. Some also develop gastric ECL cells carcinoids (type 1 GC). Most type 1 GC remain indolent, but some metastasise. Patients undergo surveillance, and some are treated with somatostatin analogues, endoscopic resection or surgery. Netazepide (YF476) is a highly selective, potent and orally active gastrin receptor antagonist, which has anti-tumour activity in various rodent models of gastric neoplasia driven by hypergastrinaemia. Netazepide has been studied in healthy volunteers. AIM: To assess the effect of netazepide on type 1 GC. METHODS: Eight patients with multiple type 1 GC received oral netazepide once daily for 12 weeks, with follow-up at 12 weeks in an open-label, pilot trial. Upper endoscopy was performed at 0, 6, 12 and 24 weeks, and carcinoids were counted and measured. Fasting serum gastrin and chromogranin A (CgA) and safety and tolerability were assessed at 0, 3, 6, 9, 12 and 24 weeks. RESULTS: Netazepide was well tolerated. All patients had a reduction in the number and size of their largest carcinoid. CgA was reduced to normal levels at 3 weeks and remained so until 12 weeks, but had returned to pre-treatment levels at 24 weeks. Gastrin remained unchanged throughout treatment. CONCLUSIONS: The gastrin receptor antagonist netazepide is a promising new medical treatment for type 1 gastric carcinoids, which appear to be gastrin-dependent. Controlled studies and long-term treatment are justified to find out whether netazepide treatment can eradicate type 1 gastric carcinoids.

Modeling active muscle contraction in mitral valve leaflets during systole: a first approach.

The present study addresses the effect of muscle activation contributions to mitral valve leaflet response during systole. State-of-art passive hyperelastic material modeling is employed in combination with a simple active stress part. Fiber families are assumed in the leaflets: one defined by the collagen and one defined by muscle activation. The active part is either assumed to be orthogonal to the collagen fibers or both orthogonal to and parallel with the collagen fibers (i.e. an orthotropic muscle fiber model). Based on data published in the literature and information herein on morphology, the size of the leaflet parts that contain muscle fibers is estimated. These parts have both active and passive materials, the remaining parts consist of passive material only. Several solid finite element analyses with different maximum activation levels are run. The simulation results are compared to corresponding echocardiography at peak systole for a porcine model. The physiologically correct flat shape of the closed valve is approached as the activation levels increase. The non-physiological bulging of the leaflet into the left atrium when using passive material models is reduced significantly. These results contribute to improved understanding of the physiology of the native mitral valve, and add evidence to the hypothesis that the mitral valve leaflets not are just passive elements moving as a result of hemodynamic pressure gradients in the left part of the heart.

Alcohol in a series of medico-legally autopsied deaths in northern Norway 1973-1992.

It is well established that use of alcohol increases the risk of fatal injuries. The presence of blood alcohol in autopsied deaths is regularly encountered in medico-legal practices. The aim of this study was to investigate the prevalence and concentration of alcohol in 1539 medico-legal autopsies in two counties in northern Norway in the period 1973-1992, and the reporting of acute alcohol influence among these deaths to the official cause-of-death statistics. Blood alcohol concentration (BAC) >/=0.5 per thousand (50 mg/100 ml) was found in 47.6% (n=456) of violent deaths tested, and in 93% (n=426) of these the BAC was >/=1.0 per thousand. In 17.4% (n=55) of tested natural deaths the BAC was >/=0.5 per thousand. Acute alcohol-influenced violent deaths were under-reported to the cause-of-death statistics. Deaths by motor vehicle traffic accidents did not differ from other violent deaths in this respect. The under-reporting among violent deaths was 41% in cases with BAC >/=0. 5 per thousand and 37% where the BAC was >/=1.0 per thousand during the whole period. It is concluded that post-mortem BAC >/=0.5 per thousand, should be regarded as a possible contributory cause in all violent deaths, and reported accordingly.

Unexplained and explained natural deaths among persons above 1 year of age in a series of medico-legal autopsies.

The aim of this study was to describe unexplained and explained natural deaths among decreased above 1 year of age in a series of medico-legal autopsies collected over a 20-year period (1972-1992). Unexplained natural deaths can be defined as those deaths where no cause-of-death is revealed after post-mortem and without circumstances indicating violent death. The death was considered to be natural in 491 cases above 1 year of age among a total of 2004 medico-legal autopsies. In 428 of these cases an explanation as to the cause-of-death was reached. The three most frequently encountered causes-of-death were complications to coronary atherosclerosis (62.6%), diseases of the lung (12.4%) and diseases in the central nervous system (9.8%). Among 59 cases with unexplained natural death, 50 had various chronic diseases or fatty liver. In 43 of these cases the deceased had epilepsy or chronic alcoholism. In nine cases (1.8% of the natural deaths) no explanation to the cause-of-death could be given.

Medicolegal autopsies of violent deaths in northern Norway 1972-1992.

The aim of this paper is to describe the characteristics of medicolegal autopsies of violent deaths in northern Norway over a period of 20 years. On request by the police, 1446 violent deaths were examined--82.6% males and 17.4% females. The mean age was 40.2 years (range 0-98). The most frequent violent manners of death were suicides (24.9%), deaths caused by motor vehicle traffic accidents (18.6%), accidental poisoning (11.5%) and boating incidents (8.4%). Homicides and involuntary manslaughter came to 4.4% and 1.7%, respectively, whereas in 11.4% of cases the manner of death was unknown. The five most frequent causes of death were blunt injury (31.4%), drowning (17.4%), suffocation (11.8%), firearm (11.3%) and poisoning (10.5%). In 3.5% of the cases the cause of death was unknown. The spectrum of the manner of death and the cause of death in a subarctic population is discussed with reference to legislation, practise of request and information given by the police.

Forensic pathology in northern Norway. Requested medico-legal autopsies in the counties of Finnmark and Troms 1973-1992.

The aim of this study was to analyse medico-legal autopsy rates among Norwegian citizens who died in the two northernmost counties of Norway during the 20-year period 1973-1992. Medico-legal autopsy rate was defined as the number of medico-legal autopsies divided by the total number of deaths. The rates were calculated according to year of death, manner of death, sex, age, police district and county. The material included 1539 medico-legal autopsies. In the total 20-year period 37.9% (n = 1113) of the violent deaths and 1.2% (n = 426) of the natural deaths were subjected to medico-legal autopsy. The annual rates increased gradually up to 1987. In the last 5-year period 51.7% of the violent deaths and 2.1% of the natural deaths were subjected to medico-legal autopsy. Among violent deaths in this period the medico-legal autopsy rates were: suicides 65.7%, motor vehicle traffic accidents 58.3%, falls 8.6%, and other violent deaths 77.1%. Females dying after a fall and due to natural causes were significantly less frequently than males subjected to medico-legal autopsy. These two categories of death also revealed a significant decrease in autopsy rate with increasing age (age group 0-29, 30-59 and > or = 60 years) in each 5-year period. In cases of violent death the medico-legal autopsy rate according to police district varied from 24.1% to 88.9% in the last 5-year period. In conclusion, medico-legal autopsy rates depended on manner of death, sex, age and police district, besides changes in legislation.

Remote frozen section service in Norway.

Remote frozen section service has been in regular use in northern Norway since 1990. Two local hospitals are equipped with a motorized video microscope remote controlled from the workstation at the University Hospital. The video images are transmitted via a two ways audio and video telenetwork. This dynamic telepathology system utilizes a videocodec for image compression and a transfer rate of 384 Kbit/s. The video images of surgical specimens and frozen sections are displayed on monitors at both the sender and receiver site. From 1990 until 1. July 1994 tissue from 100 patients have been examined. Breasts and thyroid tissues accounts for 74 of cases. Correct benign versus-malignant diagnosis has been given obtained in 89 cases. One false positive, three false negative and seven deferred diagnosis regarding malignancy have occurred. The false positive diagnosis had no major consequences for the patient. Two of the deferred diagnosis turned out to be malignant. The average time taken for examination of each frozen section was 12 minutes (range, 3 to 45 min). Our concept of remote frozen section service can be recommended for hospitals without a local service in surgical pathology.

Current status of telepathology.

Telepathology is moving from the experimental stage to become a regular feature of pathology practice. This has been made possible by technical advances in telecommunications and image processing. Since 1990 the University Hospital of Tromsø has provided local hospitals in northern Norway with a remote frozen section service and with access to video conferences for the review of microscopic findings and for the discussion of major diagnostic issues. Several other hospitals in Norway are now participating in this development and practical relations among pathology laboratories for the purpose of consultation and education will be the next step in the procedure. Similar developments in telepathology have taken place in other countries. Standardization of network and telepathology workstations will be needed before extensive international collaboration can be achieved. Progress in high quality video devices, high capacity telecommunication lines and improved image compression techniques will increase the usage of telepathology services and make them cost-effective. Thus, telepathology will contribute to the development of pathology services in the next century.

Telemedicine in rural Norway.

Trials are reported from Norway on the use of videoconference facilities to make remote diagnoses in the fields of pathology, dermatology, otorhinolaryngology, cardiology and radiology. Telemedicine is moving from the experimental stage to become a regular feature of practice.

The validity of frozen section diagnosis based on video-microscopy.

To investigate the accuracy of video-microscopy of frozen sections, two pathologists reexamined 80 cases of archival material, on which frozen sections had previously been performed. Diagnoses based on the two trials (Observer 1 and 2) and diagnoses obtained in the original frozen section situation were compared with the final diagnoses based on paraffin embedded material. Observer 1 had two false negative diagnoses, but no false positive, whereas Observer 2 had one false positive, but no false negative diagnosis when compared with the final diagnoses. No false positive or false negative diagnoses were made in the original frozen sections situation and the number of inconclusive diagnoses were 5, as compared with 6 and 8 in the two trials based on video-microscopy. More experience with video-microscopy will probably achieve a quality of frozen section diagnoses similar to that of direct light-microscopy.

Frozen section service via the telenetwork in northern Norway.

We present preliminary results of remote frozen section service for two local hospitals in Northern Norway. The service is arranged by remote controlling microscopes with motorized X, Y and Z stage movements, magnification and illumination located at Kirkenes and Harstad Hospitals at a distance up to 400 km apart from the workstation at the University Hospital in Tromsø. The video-images of the frozen section are transmitted via a two-ways phone and video telenetwork with 2 Mbit/s capacity. The images are displayed on a monitor as both still and live images and diagnosed by pathologists in Tromsø. To data, 50 patients are examined by remote frozen section service. Correct benign versus malignant diagnoses are given in all cases compared with final diagnoses based on formalin fixed and paraffin embedded material except for two false negative malignant cases and two deferred diagnoses. The average time taken for examining each case of frozen section was 13 minutes. For hospitals with limited requirement of local pathology service and for hospitals with deficiency of specialists, remote frozen section service may be a worthwhile substitute.

Remote frozen section service: a telepathology project in northern Norway.

We discuss the organization of a remote frozen section service in northern Norway. The service is operated by remote control of a motorized video-microscope located at Kirkenes Hospital, at a distance of more than 400 km from the workstation at the University Hospital in Tromsø. The video images of the frozen section are transmitted via a two-way telephone and video telenetwork with a 2 Mbit/s capacity. The images are displayed on monitors and diagnosed by pathologists in Tromsø. To date, 17 patients have been examined by remote frozen section. Correct benign versus malignant diagnoses have been given in all 17 cases compared with final diagnoses based on formalin-fixed and paraffin-embedded material. The average time taken for examining each frozen section was 15 minutes (range, 5 to 30 minutes). In none of the cases was the interpretation of the slides difficult due to deficient quality of the video images. For small hospitals with limited availability of local pathology services and for hospitals with a deficiency of specialists, telepathology may be a worthwhile substitute.

[Use of telecommunications in pathology and anatomy services]. / Bruk av telekommunikasjon i patologisk-anatomisk service.

Telepathology comprises the transmission of microscopic images via the telecommunications network. This paper describes the first experiences from this new technology in Norway. These include teleconferences based on showing histologic slides from the Department of Pathology at the University Hospital in Tromsø to clinicians at local hospitals. A frozen section service to Kirkenes Hospital, based on remote control of a robotic microscope and transmission of high quality video images of the slide, has also been successfully established.