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PubMed1997

Extrapulmonary small cell carcinoma.

BACKGROUND: Extrapulmonary small cell carcinoma (EPSCCA) is often an underrecognized clinicopathologic entity, distinct from small cell lung carcinoma. The purpose of this study was to review the study institution's experience with EPSCCA with specific emphasis on the epidemiology and response to treatment of these uncommon neoplasms. METHODS: Using the tumor registry database of the study institution, the authors retrieved and reviewed the records of all patients with EPSCCA treated between 1974 and 1994. Study eligibility required that the patients had a normal chest radiograph, computed tomography scan of the chest, sputum cytology, and/or negative bronchoscopy. Patients with well differentiated neuroendocrine carcinomas and Merkel cell carcinomas of the skin were excluded. RESULTS: Primary sites of EPSCCA in the current series were: gastrointestinal system in 29 patients, ear, nose, and throat in 14, genitourinary system in 12, internal genitalia in 10, upper respiratory system in 5, unknown primary-lymph nodes in 5, unknown primary-other in 2, the thymus in 3, and the peritoneum in 1. After the initial evaluation and confirmation of histologic diagnosis, 10 of 81 patients had been lost to follow-up. Of the remaining 71 patients, 54 had limited disease. Forty of the 54 patients underwent surgical treatment of their malignancy; 10 patients (25%) remained alive and disease free at least 3 years after surgery, whereas 30 patients (75%) relapsed with a median disease free survival of 6 months. Six patients of 54 with limited disease were treated with chemotherapy and radiation. Five of these 6 (83%) relapsed at a median time of 11.5 months. Another 8 of the total of 54 patients received only radiation therapy and all had disease recurrence at a median time of 5 months. In the group of patients with extensive or recurrent disease, platinum-based chemotherapy was employed in 22 patients. There was a 72% response rate with a median duration of 8.5 months. Seven patients had doxorubicin-based chemotherapy. There was a 57% response rate with a median duration of 4.5 months. In the current study group of patients, the 3-year disease free and overall survival rates were 26% and 38%, respectively, whereas the 5-year disease free and overall survival rates were each 13%. CONCLUSIONS: EPSCCA is usually a fatal disease, with a 13% 5-year survival rate. In a small percentage of patients, surgery can be curative if the tumor is small and confined to the organ of origin. Because of the poor overall outcome, one needs to consider the possible use of adjuvant chemotherapy in appropriate circumstances if surgery is to be employed. In most patients with limited disease, the combination of chemotherapy and radiation as the primary treatment can be as effective as surgery. EPSCCA is responsive to commonly employed regimens for small cell lung carcinoma; however, the responses are short-lived. The extent of disease at diagnosis represents the most sensitive predictor of survival.

Adult↗
PubMed1996

Distribution of dopamine D1-D4 receptor subtypes in human dorsal vagal complex.

The distribution of D1/D5, D2/D3, D2/D3/D4, and individually, putative D2-D4 receptors across the dorsal vagal complex of the human medulla was assessed with quantitative receptor autoradiography. D1/D5 receptors were found in very low levels. D2 receptors were concentrated in the intermediate and medial subnuclei of the nucleus of the solitary tract (NTS), and in the dorsal motor nucleus of the vagus (DMN), while D3 receptors were more homogeneous across the entire NTS, area postrema (AP), and DMN. In contrast, D4 receptors were found almost exclusively in the intermediate and medial subnuclei of the NTS, and in the DMN. These findings suggest that the "D2 family" of receptors is an important component of brain stem mechanisms regulating visceral function, including gastrointestinal systems, such as emesis, along with cardiovascular and pulmonary systems. Compounds with individual selectivity for D2, D3, or D4 receptors may be useful in the manipulation of neural networks regulating these visceral systems.

Adolescent↗
PubMed1976

Primary extramedullary esophageal plasmacytoma: First case report.

Solitary extramedullary plasmacytomas are rare tumors, reported to occur most commonly in the upper respiratory passages, but which also are rarely seen in the middle and lower gastrointestinal system. This report documents the first primary plasmacytoma of the esophagus. A 67-year-old Caucasian man complained of dysphagia and weight loss. Preoperative diagnosis, based on functional inquiry, radiology, and biopsy, was undifferentiated carcinoma involving the lower third of esophagus. The patient was treated by esophagogastrectomy. The pathology specimen revealed the typical histology of plasmacytoma. The extramedullary nature of the tumor was established postoperatively on the basis of the following criteria: 1) Absence of Bence-Jones proteinurea; 2) normal serum electrophoresis; 3) normal bone marrow biopsy; and 4) absence of distant metastases on liver scan and bone survey.

Aged↗
PubMed2000

Studies on concentration-time profiles of nimodipine enantiomers following intravenous and oral administration of nimodipine in patients with subarachnoid hemorrhage.

After i.v. and oral administration of nimodipine the concentration-time profiles of the drug and its enantiomers were studied in seven patients with subarachnoid hemorrhage. Concentrations of nimodipine, (+)-(R)-, and (-)-(S)-nimodipine were analyzed using a new stereoselective high-performance liquid chromatographic method. During the first 3 h after oral administration the concentrations of (+)-(R)- and (-)-(S)-nimodipine were significantly different, the (-)-(S)-enantiomer being found in much lesser concentrations compared to the (+)-(R)-enantiomer. The results indicate that if uptake from the gastrointestinal system is equal for the two enantiomers, then (-)-(S)-nimodipine is metabolized at a much faster rate compared to (+)-(R)-nimodipine after oral administration of the drug in patients with subarachnoid bleeding. After i.v. administration; no significant differences between the concentrations of the (-)-(S) and the (+)-(R) isomers were demonstrated.

Administration, Oral↗
PubMed1994

von Voss-Cherstvoy syndrome: a variable perinatally lethal syndrome of multiple congenital anomalies.

We report 4 cases and review 7 from the literature with a pattern suggesting a variable early lethal multiple congenital anomaly syndrome. This was first reported by von Voss et al. [1979: "Klinische Genetik in der Pädiatrie," pp 70-74] and Cherstvoy et al. [1980: Lancet ii:485], and can affect upper limbs, face, brain, heart, lungs, urogenital and gastrointestinal systems, vertebrae and ribs, and can include thrombocytopenia. The initial cases had occipital encephaloceles and phocomelia, but milder cerebellar anomalies and radial ray defects may be seen instead. Both sexes are affected and parental age is not increased. This may be heterogeneous, but two consanguineous families, one with recurrences, suggest autosomal recessive inheritance in at least some instances, although the recurrences had milder brain findings than the other cases. The original designation of DK-phocomelia syndrome is inaccurate, since arm findings may be limited to radial anomalies; we suggest instead the von Voss-Cherstvoy syndrome. This may be heterogeneous, but at present, phenotypic overlap prevents differentiation of subgroups. The disorder appears to be part of a group of syndromes with radial and hematologic abnormalities.

Abnormalities, Multiple↗
PubMed2003

Cranio-cerebello-cardiac (3C) syndrome: follow-up study of the original patient.

In 1987, Ritscher et al. described two sisters with brain malformations of the posterior fossa, congenital heart defects, and similar craniofacial dysmorphisms. Subsequently, more than 20 cases have been reported and the syndrome became known as 3C (cranio-cerebello-cardiac) or Ritscher-Schinzel syndrome. The majority of patients were younger than six years of age at the time of observation. Here we present a follow-up study of one of the two sisters described by Ritscher et al. in 1987. At 21 years of age she is the oldest patient reported to date. We delineate growth, intellectual development, and evolution of her congenital developmental defects. We also provide evidence that the originally reported immune deficiency in this patient is not a primary B-cell defect but a secondary loss of IgG via the gastrointestinal system.

Abnormalities, Multiple↗
PubMed1999

Gastrointestinal glutathione peroxidase.

The gastrointestinal glutathione peroxidase (GI-GPx) is the fourth member of the GPx family. In rodents, it is exclusively expressed in the gastrointestinal tract, in humans also in liver. It has, therefore, been discussed to function as a primary barrier against the absorption of ingested hydroperoxides. A vital function of GI-GPx can be deduced from the unusual stability of its mRNA under selenium-limiting conditions, the presence of low amounts of GI-GPx protein in selenium deficiency where cGPx is absent, and the fast reappearance of the GI-GPx protein upon refeeding of cultured cells with selenium compared to the slower reappearance of cGPx protein. Furthermore, the Secis efficiency of GI-GPx is low when compared to cGPx and PHGPx. It is, however, almost independent of the selenium status of the cells tested. All these characteristics rank GI-GPx high in the hierarchy of selenoproteins and point to a role of GI-GPx which might be more crucial than that of cGPx, at least in the gastrointestinal system.

Animals↗
PubMed2005

Coexistence of a Meckel's diverticulum and a urachal remnant.

Meckel's diverticulum, which is a remnant of the omphalomesenteric or vitelline duct, is the most common congenital abnormality of the gastrointestinal system. Urachal abnormalities, resulting from anomalous urogenital development, are not observed frequently and case reports are mainly represented in literature. The presence of these two congenital anomalies together is a very rare pathology. Complications arising from a Meckel's diverticulum or urachal remnant may clinically mimic acute appendicitis and other surgical pathologies. We report on a patient who underwent surgery for acute appendicitis when it was discovered that the symptoms were produced by a perforated Meckel's diverticulitis. In the course of the surgery, a urachal remnant was found to coexist with the diverticulum.

Adolescent↗
PubMed2004

Endoscopic ultrasound-guided fine-needle aspiration of lymph nodes: the Hennepin County Medical Center experience.

Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) allows for the sampling and diagnosis of lesions of the gastrointestinal system and adjacent tissues. It has also proved helpful with the sampling of lymphadenopathy both for the staging of malignancy and for the diagnosis of lymphadenopathy of other causes. We review our experience with EUS-guided FNA of lymph nodes. The cytology files were searched at Hennepin County Medical Center (HCMC) for all cases of lymph nodes sampled by EUS. Clinical history, biopsy site, diagnosis, and follow-up information (including ancillary testing) were reviewed. Between January 1, 2000 and December 5, 2002, 217 lymph nodes from 185 different patients were sampled by EUS at HCMC. Biopsy sites included 62 mediastinal, 9 paraesophageal, and 146 intra-abdominal lymph nodes. Diagnoses were as follows: metastatic non-small cell carcinoma (n = 69); benign, reactive lymph node (n = 76); granulomatous lymphadenopathy (n = 18); malignant lymphoma (n = 7); atypical-suspicious for malignancy (n = 5); metastatic small cell carcinoma (n = 2); necrotic debris (n = 4), and foreign material (n = 1); 35 cases were nondiagnostic (16.1%) in 22 of 185 patients (11.9%). Ancillary tests including flow cytometry, cytogenetics, and cultures were performed. EUS-guided FNA of mediastinal and intra-abdominal lymph nodes provides diagnostic material from which ancillary testing may be performed.

Adult↗
PubMed2006

A systematic review of the clinical effectiveness of donepezil, rivastigmine and galantamine on cognition, quality of life and adverse events in Alzheimer's disease.

BACKGROUND: The use of cholinesterase inhibitors for Alzheimer's disease (AD) is currently being appraised by the National Institute for Clinical Evidence (NICE). This article provides the latest evidence that NICE will be using as part of this appraisal process. OBJECTIVE: To provide a systematic review of the best quality evidence of the effects of donepezil, rivastigmine and galantamine on cognition, quality of life and adverse events in people with mild to moderately-severe AD. DESIGN: Electronic databases were searched, references of all retrieved articles were checked, and experts were contacted for advice, peer review and to identify additional references. Randomised controlled trials (RCTs) were included if they fulfilled pre-specified criteria. Data were synthesised through a narrative review. RESULTS: Twenty-six RCTs that compared any one of the cholinesterase inhibitors with either a control group or with another cholinesterase inhibitor were included. The quality of reporting and methodology was varied. Treatment with donepezil, rivastigmine or galantamine resulted in significantly better cognitive performance using the ADAS-cog scale when compared with placebo. These findings were generally supported using the MMSE scale. Results from head to head comparisons were limited by the low number of studies and the study quality; generally showing no robust support for any one drug. Few studies evaluated quality of life. Adverse events were generally related to the gastrointestinal system, with a tendency for these to be more common in the treatment arms. CONCLUSIONS: The cholinesterase inhibitors donepezil, rivastigmine, and galantamine can delay cognitive impairment in patients with mild to moderately-severe AD for at least 6 months duration.

Alzheimer Disease↗
PubMed1993

Clinical cardiotoxicity of 5-fluorouracil.

5-Fluorouracil is widely known to be toxic to the hematopoietic and gastrointestinal systems. It also has cardiac toxicity, but this is perceived to be rare. During a 16-month period from January 1990 through April 1991, approximately 910 patients were treated with 5-fluorouracil. Five of these developed life-threatening toxicity consistent with coronary artery spasm for an incidence of .55%. The acute events occurred on the third or fourth day of the 5-day infusion and after the fourth intravenous bolus in the patient on bolus therapy. Each of the patients had ST elevation and ventricular arrhythmias, four had acute myocardial infarction, and two had cardiac arrests. In these cases and those previously reported, cardiac toxicity is consistent with drug- or metabolite-mediated increases in coronary vasomotor tone and spasm, leading to the full spectrum of signs and symptoms of myocardial ischemia in susceptible individuals.

Aged↗
PubMedDate not supplied

Pharmacology, clinical efficacy, and adverse effects of piroxicam, a new nonsteroidal anti-inflammatory agent.

Piroxicam, a new non-steroidal anti-inflammatory drug, possesses analgesic, antipyretic, and anti-inflammatory properties and inhibits platelet aggregation in animal models. Its elimination half-life is 38 hours, and hepatic metabolism to inactive metabolites is the primary route of elimination. Less than 10% of a dose appears unchanged in the urine. Clinical studies demonstrate that piroxicam's analgesic and anti-inflammatory properties are useful in the management of rheumatoid arthritis and osteoarthritis. Limited clinical studies suggest that piroxicam may be useful in the management of acute gouty arthritis, ankylosing spondylitis, acute musculoskeletal disorders, and as an analgesic. The gastrointestinal system is the major site of adverse effects. Piroxicam is currently marketed in 20 mg capsules and once daily dosing has proven effective for many patients.

Animals↗
PubMedDate not supplied

Clinical experience with diltiazem in Japan.

In a cooperative postmarketing study, 3,913 Japanese patients received diltiazem, an orally administered calcium channel blocking agent, for 30 to over 360 days. Drug safety was assessed by monthly evaluations of subjective symptoms, electrocardiographic recordings, adverse experiences, vital signs, and biochemical profiles. Original case report forms were processed and analyzed in the United States. None of the observed adverse experiences were serious or life threatening. They occurred in 1.8% of the patients and primarily involved the gastrointestinal system; anorexia and nausea were the most common adverse effects. The majority of the other adverse experiences were extensions of the drug's pharmacologic effects. Diltiazem appears to cause relatively minor clinical toxicity at a low frequency.

Aged↗
PubMed2004

The prenatal diagnosis of cloacal dysgenesis sequence in six cases: can the termination of pregnancy always be the first choice?

OBJECTIVE: Cloacal dysgenesis sequence is a lethal malformation, which usually requires termination. In this study, our aim was to evaluate the prenatal and postnatal diagnostic features of cloacal dysgenesis sequence and review the management of the patients. MATERIAL AND METHODS: The data of six cases of cloacal dysgenesis sequences were collected from the ultrasonography and neonatal records. The findings were evaluated in prenatal and postnatal periods. Chromosomal analysis was performed in all the cases. The evaluation of primary and secondary malformations was done. Coexisting anomalies were searched for by radiology and histopathology. RESULTS: Malformations in six cases (two females and four males) were described. The absence of anal, genital, and urinary openings with intact perineum covered by smooth skin were common findings. These features were considered as primary malformations for cloacal dysgenesis sequence. Secondary anomalies (urinary and gastrointestinal system malformations, pulmonary hypoplasia, and other coexisting anomalies) were evaluated. CONCLUSION: The prenatal differential diagnosis of cloacal dysgenesis sequence from other urinary obstructive diseases was essential regarding fetal prognosis, prenatal, and neonatal management. The bladder outlet obstruction and pulmonary hypoplasia due to reduced amniotic fluid and/or kidney disease were considered prognostic factors for neonatal death. Termination of pregnancy is almost always recommended instead of intrauterine shunt procedures; but if we take into consideration one of our cases and a few reported cases who survived in the neonatal period, the prenatal management of these pregnancies needs to be reevaluated.

Abnormalities, Multiple↗
PubMed2005

Adverse drug events in emergency department population: a prospective Italian study.

PURPOSE: There is little evidence concerning adverse drug events (ADEs) in outpatients and related hospital admissions. In Italy, only one investigation was conducted on this important health issue. We therefore carried out a study to determine ADE incidence and ADE-related hospital admissions among emergency department (ED) visits, and to identify the risk factors for serious ADE leading to ED visit. METHODS: During the year 2000, we performed a prospective study in two observational periods of 10 days each in 22 Italian EDs. Demographic, clinical and pharmacological data about all patients admitted to ED were collected by trained and qualified monitors. Records related to ADE were analysed and validated by a specific scientific committee. RESULTS: On 18,854 enrolled patients, 629 (3.3%) were affected by ADE. Among these, 244 (38.8% of ADE patients) reported a serious event. Patients with ADE, accounting for 4.3% (193 cases) of total hospitalisations, were significantly more likely to be hospitalised (30.7% vs. 23.7%; p<0.0001), females (57.2% vs. 46.3%; p<0.0001) and elders, compared with the total sample. Serious ADE resulted significantly associated with male gender and old age. NSAIDs (16.5% of total ADE visits) and antibiotics (12.9%) were the drugs mostly involved in ADE occurrence. ADE affected mostly skin (213 ADE visits) and gastrointestinal system (211). CONCLUSION: Old age and male gender resulted risk factors involved in the development of serious ADE. The high ADE-related hospitalisation incidence highlights the need for prevention strategies targeted to reduce the impact of ADE in the general population.

Adolescent↗
PubMed2003

Adverse drug reactions in a south Indian hospital--their severity and cost involved.

PURPOSE: The study was aimed to assess the pattern of occurrence of adverse drug reactions (ADRs) in the local population, severity of reported ADRs and additional financial resource utilisation associated with ADRs. METHODS: This was a prospective, spontaneous reporting study conducted over a period of 7 months by clinical pharmacists. The WHO definition of an ADR was adopted. Each ADR was assessed for its causality by using the WHO Probability Scale. The severity of each reported ADR was assessed using the criterion developed by Hartwig et al. The average cost incurred in treating the ADRs was calculated. RESULTS: A total of 270 suspected ADRs were reported and evaluated from 164 patients. A total of 3.7% of the hospitalised patients experienced an ADR, 0.7% of the admissions were due to ADRs and 1.8% had a fatal ADR. The gastrointestinal system (36.3%) was most commonly involved with an ADR. The drug class most commonly implicated with ADRs was cardiovascular (18.3%). Majority (47%) of the reactions were 'moderate' in severity. The total cost incurred in managing all the reported ADRs was Rs 76,564 (US$ 1595) with an average cost of Rs 690 (US$ 15) per ADR. CONCLUSION: Detection and prevention of ADRs at the earliest is very important as they can cause not only morbidity and mortality but also involve high health care cost in their management. Well-trained pharmacists in the area of ADR detection, reporting and monitoring could prove as an asset in providing better patient care.

Adult↗
PubMed1997

Norepinephrine-induced expression of the K99 pilus adhesin of enterotoxigenic Escherichia coli.

This study examined whether the provision of norepinephrine, as would be encountered within the highly innervated gastrointestinal system, affected the growth rate of enterotoxigenic Escherichia coli (ETEC) and the expression of the K99 pilus adhesin virulence-related factor. The addition of norepinephrine to serum-containing medium resulted in a 3- to 7-fold increase in the growth rate of the K99+ ETEC strain B44 as compared to growth in vehicle supplemented medium or medium supplemented with normetanephrine, a norepinephrine metabolite that contains one more methyl group than norepinephrine. ELISA analysis revealed that K99 pilus adhesin expression was increased in norepinephrine supplemented culture as compared to normetanephrine and vehicle supplemented controls. This increase occurred from 9 to 15 hours of incubation which represented the exponential growth phase for the norepinephrine supplemented culture. These results indicate that addition of norepinephrine affects both ETEC growth and expression of a specific virulence factor.

Adhesins, Bacterial↗