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Role of growth factors in pancreatic endocrine cells. Growth and differentiation.

Although previously thought to arise from neural ectoderm, the endocrine cells of the gastrointestinal system are now believed to derive from endoderm. The role of different growth factors in initiation of endocrine cell growth, commitment of the cells to a particular growth pathway, and the initiation and maintenance of tumor growth and remission remains unclear. This article briefly reviews factors controlling cell growth and differentiation of gastrointestinal endocrine cells and presents data on new candidate growth factors pertinent to the authors' model of induction of endocrine cell differentiation in the pancreas.

Cell Differentiation↗

Yield of the screening review of systems: a study on a general medical service.

STUDY OBJECTIVE: To determine the usefulness of screening reviews of the cardiopulmonary and gastrointestinal systems during medical admissions. DESIGN: Case series. SETTING: General internal medicine ward of a university hospital. PATIENTS: 550 consecutive medical patients were initially screened at admission. The authors excluded 265 patients with life-limiting medical conditions, and they studied 98 patients with no known cardiopulmonary disease and 207 patients with no known gastrointestinal disease. INTERVENTIONS: Positive responses to screening systems review questions were evaluated using a standardized testing algorithm. MAIN OUTCOME MEASURES: Numbers of new diagnoses; potential for patient benefit. MAIN RESULTS: The authors made 26 new diagnoses for 25 patients (95% confidence limits, 16 to 37 patients), two of whom may have gained years of life as a result. CONCLUSIONS: The absolute yield of the screening cardiopulmonary and gastrointestinal reviews of systems of 550 patients admitted to an internal medicine service of a university hospital was a new diagnosis in about 5% of patients. An estimate of the cost-effectiveness compares favorably with those of other accepted screening practices.

Adult↗

Ancillary tests for assessment of the ruminant digestive system.

This article reviews the ancillary tests that are available to evaluate disease and function of the gastrointestinal system. Procedures and tests such as abdominocentesis and peritoneal fluid cytology; rumen fluid analysis; abomasal pH and pepsinogen; upper digestive tract endoscopy; ultrasonography and radiology; hematologic and biochemical assessments; cytology, culture, and histopathology of aspirates; serology, liver function tests and biopsy; exploratory laparotomy; fecal examination; and microbiology are described.

Abomasum↗

Gastrointestinal manifestations associated with systemic lupus erythematosus.

Gastrointestinal symptoms are often difficult to interpret in patients with systemic lupus erythematosus. Symptoms can develop either from symptomatic autoimmune tissue injury, complications of lupus-related organ dysfunction, infections, thrombembolic manifestations of anti-phospholipid antibody syndrome, medication or unrelated disorders. We describe the gastrointestinal manifestations of lupus and discuss the diagnostic approach and therapy.

Diagnosis, Differential↗

A phase I/II dose escalation study of intensified cyclophosphamide and autologous blood stem cell rescue in severe, active rheumatoid arthritis.

OBJECTIVE: Based on animal studies and anecdotal case reports, high-dose therapy and autologous blood stem cell rescue have been proposed as an experimental treatment for severe, refractory rheumatoid arthritis (RA). This study aimed to establish the toxicity of this treatment and obtain preliminary efficacy data upon which to base future clinical trials. METHODS: Two cohorts of 4 patients who fulfilled criteria for severe, active, treatment-resistant RA were recruited into a dose-escalation study of cyclophosphamide (CYC) (100 mg/kg or 200 mg/kg) followed by unmanipulated peripheral blood stem cell rescue. Patient treatment was managed according to a standard supportive care protocol. Disease-modifying drugs were discontinued before treatment, but corticosteroids were maintained and later tapered where possible. Patients' conditions were assessed using World Health Organization toxicity criteria and standard parameters for rheumatic disease. RESULTS: Dose-dependent differences in hematologic toxicity were observed between cohorts 1 and 2, although toxicity was similar for other systems and was most significant in the gastrointestinal system. Patients in cohort 1 had only transient responses to therapy, lasting 2-3 months. Substantial improvements were sustained beyond 17-19 months in cohort 2, including steroid-independent disease remission for 1 patient, although the procedure did not completely abolish disease activity. CONCLUSION: High-dose CYC and unmanipulated autologous blood stem cell rescue has acceptable dose-dependent toxicity in severe, treatment-resistant RA, and 200 mg/kg of CYC induces substantial clinical responses. Refinement of this intensive approach might include further intensification of the preparation regimen, graft manipulation, and posttransplant immunomodulation.

Adult↗

Nicotine as a psychoactive drug.

Nicotine is a paradoxical drug in that it both stimulates and depresses functions. It affects the central nervous system, the peripheral nervous system, the cardiovascular, the skeletal, and the gastrointestinal systems. Its psychoactive effects and drug dependency potential as well as some therapeutic approaches to smoking cessation have been reviewed here. More research information is needed for professionals working with those who want to quit smoking.

Animals↗

Systematic meta-analysis of the toxicities and side effects of the targeted drug lenvatinib.

BACKGROUND: Lenvatinib, an effective targeted drug for various cancers, has clinical medication safety concerns due to its toxicities and side effects. OBJECTIVE: This study evaluated lenvatinib-induced any adverse events (any AEs) and nine aspects: vascular toxicities related to the circulatory system (vascular toxicities, blood system, and heart), toxicities of the skin and its appendages (skin/subcutaneous tissue and taste system), toxicities of the respiratory system (respiratory, thoracic, and mediastinal and respiratory tract), toxicities of the nervous system (nervous system and general), toxicities of the digestive system (gastrointestinal and liver), toxicities of the urinary system, toxicities of the endocrine and metabolic system (endocrine and metabolism/nutrition), toxicities of the musculoskeletal system, and other severe toxicities. Toxicities and side effects were stratified by severity into any and &#x2265;3 grades for analysis. PATIENTS/MATERIALS AND METHODS: Multiple databases were searched for lenvatinib cancer clinical studies (cohort studies and randomized controlled trials) from inception to December 31, 2024; toxicity and side effect data were extracted and analyzed. RESULTS: Nine high-quality studies were included, showing that lenvatinib is effective in cancers but has notable toxicities. Taking hypertension as an example, for any grade, the risk ratio (RR) was 2.34 with a 95% confidence interval (CI) of [2.09, 2.62], a Z-value of 14.74, and a P-value <0.00001; for grade &#x2265;3, the RR was 2.60 with a 95% CI of [2.21, 3.06], a Z-value of 11.44, and a P-value <0.00001. CONCLUSION: Lenvatinib is effective for cancer but toxic, and this study supports its rational clinical use.

Humans↗

CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas.

CDX2 is a recently cloned homeobox gene that encodes an intestine-specific transcription factor, expressed in the nuclei of epithelial cells throughout the intestine, from duodenum to rectum. While expression of CDX2 protein in primary and metastatic colorectal carcinomas has been previously documented, neither the sensitivity nor the specificity of CDX2 expression, as determined by immunohistochemistry, for colorectal adenocarcinoma has been determined. We performed an immunohistochemical survey of 476 tumors with a monoclonal antibody, CDX2-88, including 89 tumors from the colon and duodenum and 95 tumors from other gastrointestinal sites, including the esophagus, stomach, pancreatobiliary system, gastrointestinal carcinoids, and liver. CDX2 was expressed uniformly (that is, in 76-100% of tumor cells) in all but one of the evaluated colorectal and duodenal tumors. High-level expression of CDX2 was also found, however, in mucinous ovarian carcinomas and adenocarcinomas primary to the urinary bladder of which 64% and 100% were positive, respectively. Gastric, gastroesophageal, and pancreatic adenocarcinomas and cholangiocarcinomas all showed similar, heterogeneous patterns of CDX2 expression. Most tumors in each group showed CDX2 expression by a minority of cells, whereas a substantial minority of cases in each group was completely negative and a smaller minority was uniformly positive. Gastrointestinal carcinoids gave similarly varied results, but the majority (58%) was negative. Hepatocellular carcinomas showed no expression of CDX2. Only very rare examples of carcinomas of the genitourinary and gynecologic tracts, breast, lung, and head and neck showed significant levels of CDX2 expression. In this study of primary and metastatic epithelial tumors, uniform CDX2 expression is demonstrated to be an exquisitely sensitive and highly, but incompletely, specific marker of intestinal adenocarcinomas. Compared with villin, a previously described marker of GI adenocarcinomas, CDX2 demonstrated superior sensitivity and comparable specificity. CDX2 expression can be seen, however, in selected non-GI adenocarcinomas such as mucinous ovarian carcinomas and adenocarcinomas of the urinary bladder.

Adenocarcinoma↗

Cervical inlet patch: case series and literature review.

Heterotopic gastric mucosa patch (HGMP) has been reported to occur in various parts of the gastrointestinal system from mouth to anus. Extra-gastrointestinal locations have also been reported. Presence of ectopic gastric mucosa has been associated with complications such as ulceration, bleeding, perforations and malignant transformations. Most complications are probably related to acid production. Meckel diverticulum is the most commonly reported ectopic location. Similarly, esophageal HGMP, also known as cervical inlet patch (CIP), has been increasingly reported. Nonspecific oropharyngeal symptoms are common and thought to be due to laryngopharyngeal reflux. CIP is often missed due to its location in the esophagus, just distal to the upper esophageal sphincter, making endoscopic evaluation difficult. Hence the condition is most likely to be under-reported. This article presents a series of five cases of CIP and discusses the pathogenesis, clinical presentations and management of this interesting entity.

Adult↗

[Italian Cystic Fibrosis Registry: 10 years of activity].

Cystic Fibrosis (CF) is a recessive autosomic genetic disease with an incidence in mediterranean countries of about 1:3500 born alive. In Italy the considerable genetic variability makes it difficult to identify all the homozygous subjects and, consequently, to estimate the incidence of the disease in healthy carriers. The disease is evolutive and affects various systems, most of all the respiratory and gastrointestinal systems. Not many years ago, when the clinical definition of CF was first introduced, average survival did not exceed the pediatric age. Nowadays with ever advancing diagnostic and therapeutical techniques many CF patients survive until an adult age. It is therefore necessary to plan adequate health service interventions so as to satisfy as much as possible the needs of both the patients and their families. To this end data collected since 1.1.1988 by the Italian registry for CF (year of birth, sex, region of birth and residence, diagnosis procedures, results of sweat test, pancreatic insufficiency, DNA analysis, status: alive, dead, lost to follow up) of all the patients, diagnosed in the 18 Reference Centres and the 3 local Centres for CF, have proved to be extremely useful. Since the birth of the Registry on 31.12.1997, data relating to 2458 patients alive on 1.1.1988 and 1159 born during the last ten years, for a total of 3617 subjects (1756 females and 1861 males), have been recorded. As already mentioned a considerable increase in life expectancy of CF patients (from 1988 to 1990 the average age of death was 14 years, from 1994 to 1997 it was 19) and a consequent increase in the percentage of adult patients have been observed.

Adolescent↗

[Diagnosis and therapy of diseases of the endocrine system: new trends in nuclear medicine].

Diagnosis and therapy of endocrine disorders in nuclear medicine has been improved through the implementation of new techniques especially with positron emission tomography (PET). In modern concepts of parathyroid gland surgery an exact anatomic localisation of adenomas is necessary, which may be achieved with MIBI-Scintigraphy being the most sensitive method in primary hyperparathyroidism. The optimal access to localise adenomas is the investigation with combined SPECT/X-CT systems. The use of such systems for diagnosing neuroendocrine tumors of the gastrointestinal system may also be helpful. For neoplasms of the adrenal gland PET systems could be used to differentiate between benign and malignant entities or to detect primary tumours. In case of incidentalomas J131-Norcholesterol and MIGB-scintigraphy has been proven helpful. Indications for nuclear medicine studies to detect abnormalities of the hypothalamic-hypophyseal system are established rarely.

Endocrine System Diseases↗

Presence and distribution of neuroendocrine cells in the gastroenteropancreatic endocrine system of fallow deer foetuses.

The gastroenteropancreatic endocrine system was studied in 11- and 17-week-old fallow deer foetuses using an immunocytochemical technique. In the gastrointestinal tract, gastrin-, serotonin-, somatostatin- and cholecystokinin-containing cells were found: their frequency and distribution were also determined. Anti-glucagon and anti-insulin antibodies did not stain any cells along the gut. In the pancreas, somatostatin-, pancreatic polypeptide-, insulin- and glucagon-immunoreactive cells were detected. The different distribution and number of neuroendocrine cells, in the two investigated stages of foetal life, are discussed. Data obtained in this study were compared with those published in a previous study on the gastrointestinal system of the adult fallow deer.

Animals↗

[Malignant tumors of the gastrointestinal autonomic nervous system (GAN tumors or plexosarcomas). Report of a case].

The plexosarcomas or gastrointestinal autonomic nerve tumors (GAN tumors) are very rare neoplasms originating from the gastrointestinal autonomic nervous system. They have been differentiated from the other gastrointestinal stromal tumors due to ultrastructural features showed by electronic microscopy. Their mesenteric localization rare than the gastric and intestinal localization, and it gives a very poor and specific clinical symptomatology. It's very difficult to make a correct diagnosis. The most important prognostic factors influencing the survival seem to be the tumor size and the mitotic activity. The authors describe a case of multiple Plexosarcomas occurred in a young patient one year after a surgical intervention for ileal resection to remove a benign schwannoma. This patient wasn't a carrier of multiple Neurofibromatosis. The diagnostic difficulties before surgical operation are stressed and the importance of surgery as the only diagnostic and therapeutic choice is underlined, even if local recurrences occurred in more than 50% of the treated cases.

Adult↗

Evaluation of drug prescription at the Geneva prison's outpatient service in comparison to an urban outpatient medical service.

PURPOSE: To analyse non-psychotropic drug prescription in a prison outpatient clinic in comparison with an urban medical outpatient service. METHODS: Comparative study during 3 weeks at Geneva: prison outpatient service and medical policlinic (MP) of the University Hospital. RESULTS: The most often prescribed non-psychotropic drugs at the Geneva prison were systemic analgesics (mostly non-steroidal anti-inflammatory drugs (NSAID) and paracetamol), dermatologicals, systemic anti-infectives and drugs for the gastrointestinal system. For most types of non-psychotropic drugs, frequency of prescription as well as the prescribing patterns were similar in the prison ambulatory service and the urban MP. Dermatologicals were prescribed more frequently at the prison than at the MP. Analgetics have been prescribed mainly for osteoarticulary reasons, especially low back pain at the MP, and for traumatism and headache at the prison. CONCLUSIONS: The higher frequency of dermatological prescriptions could be due to prison environmental factors. We do not have arguments for any overprescription of analgesics or other non-psychotropic drugs. The data did not show any prescription or co-prescription of several substances that violated clinical guidelines.

Adult↗

Fetal malformations associated with chronic polyhydramnios in singleton pregnancies.

Forty-one congenital malformations were found in 28 newborns in a group of 197 cases of chronic polyhydramnios in singleton pregnancies. Of these, a total of 61% (17/28) was antenatally diagnosed ultrasonically. Nine newborns (4.5%) had malformations of the central nervous system (CNS), 9 (4.5%) cardiovascular malformations, 8 (4.1%) musculoskeletal anomalies, 7 (3.6%) malformations of the urinary and reproductive system, 4 (2%) respiratory system anomalies and 3 (1.6%) anomalies of the gastrointestinal system. Chromosomal abnormalities were found in three cases. As the association of polyhydramnios with fetal congenital anomalies is quite high (14.2% in our series), it is imperative to make a major effort to antenatally detect as many cases as possible. This means that in the case of hydramnios the following are required: ultrasound examination by an expert, echo ultrasonography when no other abnormalities are detected, and maybe even a chromosomal analysis.

Brain↗

Kinetics of human aging: I. Rates of senescence between ages 30 and 70 years in healthy people.

A calculation of loss rates is reported for human structural and functional variables from a substantially larger data set than has been previously studied. Data were collected for healthy, nonsmoking human subjects of both sexes from a literature search of cross-sectional, longitudinal, and cross-sequential studies. The number of studies analyzed was 469, and the total number of subjects was 54,274. A linear model provided a fit of the data, for each variable, that was not significantly different from the best polynomial fit. Therefore, linear loss rates (as a percent decline per year from the reference value at age 30) were calculated for 445 variables from 13 organ systems, and additionally for 24 variables even more integrative, such as maximum oxygen consumption and exercise performance, that express effects of multiple contributing variables and systems. The frequency distribution of the 13 individual system linear loss rates (as percent loss per year) for a very healthy population has roughly a unimodal, right-skewed shape, with mean 0.65, median 0.5, and variance 0.32. (The actual underlying distribution could be a truncated Gaussian, an exponential, Poisson, gamma or some other). The linear estimates of loss rates were clustered between 0% and 2% per year for variables from most organ systems, with exceptions being the endocrine, thermoregulatory, and gastrointestinal systems, for which wider ranges (up to approximately 3% per year) of loss rates were found. We suggest that this set of linear losses over time, observed in healthy individuals between ages (approximately) 30 to 70 years, exposes the underlying kinetics of human senescence, independent of effects of substantial disease.

Adult↗

Acp. Best practice no 155. Pathological investigation of deaths following surgery, anaesthesia, and medical procedures.

The pathological investigation of deaths following surgery, anaesthesia, and medical procedures is discussed. The definition of "postoperative death" is examined and the classification of deaths following procedures detailed. The review of individual cases is described and the overall approach to necropsy and interpretation considered. There are specific sections dealing with the cardiovascular system (including air embolism, perioperative myocardial infarction, cardiac pacemakers, central venous catheters, cardiac surgery, heart valve replacement, angioplasty, and vascular surgery); respiratory system (postoperative pneumonia, pulmonary embolism, pneumothorax); central nervous system (dissection of cervical spinal cord), hepatobiliary and gastrointestinal system; musculoskeletal system; and head and neck region. Deaths associated with anaesthesia are classified and the specific problems of epidural anaesthesia and malignant hyperthermia discussed. The article concludes with a section on the recording of necropsy findings and their communication to clinicians and medicolegal authorities.

Anesthesia↗