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PubMedDate not supplied

Prenatal maternal stress: differential effects upon male and female offspring responses to restraint stress as adults.

Pregnant primiparous rats were subjected to four days of light restraint stress on postconception days 7 through 10, inclusive, coincident with the development of the fetal gastrointestinal system. Twenty male and twenty female offspring from prenatally stressed and nonstressed rats were then subjected to two hours of supine cold-restraint as adults. Eighty percent of nonprenatally stressed offspring developed gastric lesions, while 47.5% of offspring of prenatally stressed mothers displayed lesions. A significant sex-stress interaction was detected, indicating that male offspring from prenatally stressed mothers display less severe gastric lesions in response to restraint stress as adults than do male offspring from nonprenatally stressed mothers. Female offspring from both prenatal stress conditions showed similar levels of stress-induced lesions.

Animals↗
PubMedDate not supplied

Disposition of a new rate-controlled formulation of prazosin in the treatment of hypertension during pregnancy: transplacental passage of prazosin.

Prazosin (PRZ) in conventional tablet form (P-CT) has the disadvantages of a relatively short terminal half-life, a slight solubility in water and the well-recognized adverse effect of symptomatic orthostatic hypotension. The pharmacokinetic study of a new rate-controlled formulation of prazosin (Prazosin-Gastrointestinal System: P-GS) was performed in 9 pregnant women during the third trimester of pregnancy. Patients had persistent elevation of blood pressure. The subjects gave their informed consent for oral administration of 1 daily dose of 5 mg P-GS at 8 a.m. A first analysis period on day 1 enabled definition of the initial pharmacokinetic behavior of the drug, while the aim of a second was to evaluate its fate at plateau. The clinical course of both mother and fetus was subsequently monitored. This was an open, non-randomized study, each patient serving as her own control. For 3 patients, we aimed to determine the possible transplacental passage of PRZ at delivery. PRZ levels were measured by HPLC and data were analysed by noncompartmental linear pharmacokinetic methods. The data show: (i) P-GS was well tolerated by all patients and there were no significant changes in fetal heart rate during the study. (ii) A significant decrease in diastolic blood pressure was observed after the 36th hour following the first dose of P-GS while a reduction in systolic blood pressure was observed on day 4. (iii) An approximated relative bioavailability (f'P-GS) of 36.5% was calculated. P-GS appears to have a lower bioavailability than P-CT in women of similar gestational age. (iv) Both Cmax and AUC0-->infinity are significantly increased at plateau. Further, terminal half-life is increased with regard to the value determined with P-CT. No accumulation of PRZ was noted at steady-state. (v) P-GS is an example of an oral zero-order absorption product that offers one approach to control and improve the outcome of hypertensive therapy during pregnancy. This treatment could represent an alternative to methyldopa as a first treatment of pregnancy-associated hypertension. (vi) There is a slight transplacental passage of the drug (of the order of 10-20%).

Adrenergic alpha-Antagonists↗
PubMed2005

Toxicity and survival results of a phase II study investigating the role of postoperative chemo-radioimmunotherapy for gastric adenocarcinoma.

BACKGROUND AND PURPOSE: To investigate the role of postoperative concomitant chemo-radioimmunotherapy in gastric adenocarcinoma patients. PATIENTS AND METHODS: 59 patients, who underwent total or subtotal gastrectomy, with lymph node involvement, positive microscopic surgical margins or serosal involvement were included in the study. Radiotherapy started concomitantly with chemotherapy and levamisole. Extended-field radiotherapy was given to gastric bed and regional lymphatics via two anterior-posterior/posterior-anterior fields. A total dose of 45 Gy in 25 fractions with a fraction size of 1.8 Gy was planned. In 28 patients (48%) with positive surgical margins a 10-Gy boost dose was given to the anastomosis site. An adjuvant i.v. bolus of 450 mg/m(2)/day 5-fluorouracil (5-FU) was administered concomitantly during the first 3 days and at the 20th day of irradiation. After completion of radiotherapy, i.v. boluses of 450 mg/m(2)/day 5-FU and 25 mg/m(2)/day rescuvorin were continued for 6 months once a week. Levamisole 40 mg/day orally was started at the 1st day of radiotherapy and also continued for 6 months. Median follow-up was 37 months (7-112 months). RESULTS: Median survival was 23 months. Overall 3- and 5-year survival rates amounted to 35% and 14%, respectively. Median survival of the patients with positive surgical margins was 22 months. The 3- and 5-year locoregional control rates were 59% and 55%, respectively. The most common toxicity was upper gastrointestinal system toxicity, which was observed in 42 patients (71%). Four patients (7%) died on account of early toxic effects, and six (10%) could not complete treatment. CONCLUSION: Although 48% of the study population involved patients with microscopic residual disease, the survival results as a whole were satisfactory. However, due to high toxicity, radiotherapy must be delivered with the most proper techniques along with adequate nutrition and supportive care.

Adenocarcinoma↗
PubMed2004

New ABCC6 gene mutations in German pseudoxanthoma elasticum patients.

Pseudoxanthoma elasticum (PXE; OMIM 177850 and 264800) is a rare heritable disorder of the connective tissue affecting the extracellular matrix of the skin, eyes, gastrointestinal system, and cardiovascular system. It has recently been found that mutations in the ABCC6 gene encoding the multidrug resistance-associated protein (MRP) 6 cause PXE. This study examined novel mutations in the ABCC6 gene in our cohort of 76 German PXE patients and 54 unaffected or not yet affected relatives with a view to expanding the known mutational spectrum of the gene. Mutational analysis was performed using denaturing high-performance liquid chromatography and direct sequencing. The mutational screening revealed a total of 22 different ABCC6 sequence variations. We identified seven novel and four previously described PXE-associated mutations as well as eight novel neutral ABCC6 sequence variants. The new PXE-associated mutations included five missense mutations, one single base pair deletion, and one larger out-of-frame deletion. We suspect that the novel missense mutations lead to an impaired function of MRP6. Both deletions are predicted to result in a dysfunctional MRP6 protein. The seven new ABCC6 mutations were not present in 200 alleles from healthy blood donors which served as a control cohort. Most of the PXE patients who were found to carry PXE-causing ABCC6 mutations were assumed to manifest the PXE phenotype because of a compound heterozygous genotype. However, a genotype-phenotype correlation could not be established for the detected ABCC6 mutations. In summary, our data give a further insight into the spectrum of ABCC6 mutations in PXE patients.

Adolescent↗
PubMed2005

Staged abdominal repair for treatment of moderate to severe secondary peritonitis.

The aim of this study was to evaluate the effects of planned relaparotomy and to assess factors that may contribute to mortality in patients with moderate to severe secondary peritonitis. A total of 36 consecutive patients with an Acute Physiologic and Clinical Health Evaluation (APACHE) II score of >10 were enrolled the study for a 2-year period. The mean age of the patients was 56 years (17-92 years), and 23% of them were male. One-third of them had postoperative peritonitis; 152 scheduled operations were done, and the overall mortality rate was 36%. For patients whose septic source was in the upper gastrointestinal system, control of the source was more difficult (p = 0.004). Overall, 28 complications developed in 61% of the patients. Initial and second-day APACHE II scores were 14.5 (11-27) and 12.0 (9-25), respectively. The initial APACHE II score of survivors was lower than that of nonsurvivors [p = 0.0001, 95% confidence interval (CI) -9.5, -3.6]. Second-day APACHE II scores were not different (p = 0.19; 95% CI -3.79, 0.80). Striking end or lateral duodenal leaks were clearly associated with high mortality. It is found that the initial APACHE II score, the success of controlling the source, the occurrence of complications, and the type of illness are independent factors that may affect mortality. We concluded that staged abdominal repair should be used with caution in the treatment of lateral or end duodenal leaks. It is a good alternative to conventional laparotomy for moderate to severe forms of secondary peritonitis from other sources.

APACHE↗
PubMed2003

The effects of intestinal ischemia on the levels of serum immunoglobulin A in rats.

Many biochemical markers have been investigated in intestinal ischemia. However, the effects of intestinal ischemia on the level of serum immunoglobulin A (IgA) has apparently not been investigated in the literature, although the gastrointestinal system is one of the main sources of serum IgA. The aim of our study was to evaluate the changes of serum IgA levels during intestinal ischemia of varying duration in rats. Group 1 ( n=5) was created for control purposes, including the detection of the baseline values and the effects of the anesthetic agents. Group 2 ( n=20) rats underwent sham laparotomy. Group 3 ( n=20) had 50% of small intestine ischemia by the strangulated obstruction model. Serum samples were obtained by cardiac puncture 1 h after anesthetic agents were given in group 1. On the other hand, serum and intestine samples were obtained at 1 (T1, n=5), 2 (T2, n=5), 4 (T4, n=5) and 6 (T6, n=5) h after the operation in groups 2 and 3. The levels of serum IgA, lactic dehydrogenase (LDH) and alkaline phosphatase (ALP) were determined. Pathologic specimens were graded in a masked manner. IgA levels were abruptly decreased to 8.49+/-1.58 mg/dl in rats with intestinal ischemia at 1 h after the operation. This decrease in serum IgA at T1 in group 3 was statistically significant compared with the control and sham-operated groups (18.80+/-1.15 mg/dl, 22.07+/-1.54 mg/dl, respectively; P<0.01). On the other hand, IgA levels were significantly elevated at T2 in the sham-operated group compared with control and intestinal ischemia groups (26.99+/-2.96 mg/dl, 18.80+/-1.15 mg/dl, 14.35+/-2.62 mg/dl, respectively; P<0.05). The serum IgA levels decreased to above baseline values at T6 in group 2 (19.60+/-2.78 mg/dl), while they increased to below baseline values in group 3 (17.60+/-1.28 mg/dl). In group 3, IgA levels were elevated to baseline values, while a significant ischemia occurred at 4 and 6 h after operation. These results suggested that serum IgA is affected earlier by intestinal ischemia and intestinal manipulation. The increase in serum IgA levels may be related to stimulation of the local immune responses in the intestine. On the other hand, abruptly decreasing serum IgA levels in this experimental study may be related to inadequate transport of the synthesized IgA to the systemic circulation, because serum IgA levels were returned to baseline values while a significant ischemia occurred at T4 and T6. According to these results, we conclude that serum and peritoneal fluid IgA levels may be changed by intestinal ischemia and may be used to make an early diagnosis of intestinal ischemia in humans.

Alkaline Phosphatase↗
PubMed2006

Metastases to the thyroid gland: seventeen cases operated on in a single clinical center.

BACKGROUND AND AIMS: In spite of its rich vasculature, the thyroid gland is rarely the site of metastatic disease. The incidence of such metastases differs depending on the type of the analyzed material. In clinical papers, the incidence is low and, according to various sources, amounts to 2-3% of all malignant tumors of the thyroid. Most commonly, the primary tumor is located in the breast, bronchi, gastrointestinal system, (the colon, esophagus, or stomach) and kidneys. Usually, metastatic thyroid disease is identified upon autopsy, and only sporadic cases are encountered in clinical material. The authors present their experience in treating metastatic disease involving the thyroid gland based on the analysis of their clinical material consisting of patients operated on in a single center. MATERIALS AND METHODS: Seventeen patients presented with metastatic tumors of the thyroid. The material was further analyzed retrospectively. The group included four men and 13 women, with the male to female ratio of 1:4.25. The age of the patients ranged from 46 to 76 years, with the mean age amounting to 62+/-9.78 years. Eleven patients were diagnosed based on fine needle aspiration biopsy (FNAB). RESULTS: In 13 patients, the primary lesion was a clear cell carcinoma of the kidney, in one breast cancer, in another one uterine carcinoma. In two patients, no primary focus location was established. All the patients were treated surgically. Twelve patients were consistently followed up after the surgery. Of this group, seven are still alive, including five individuals with metastases of renal carcinomas, but without recurrent disease. Five patients died due to disseminated neoplastic disease. No data are available on three patients. The mean follow-up time after thyroid surgery was 3.9 years. The longest followed-up survival time was 11 years. CONCLUSIONS: The most commonly clinically detected and treated surgically metastatic lesion of the thyroid gland is clear cell cancer of the kidney. In cases of renal cancer metastases to the thyroid gland, a total thyroidectomy seems to be warranted, although it does not affect the survival time.

Aged↗
PubMed2006

Extramedullary hematopoiesis mimicking acute appendicitis: a rare complication of idiopathic myelofibrosis.

Extramedullary hematopoiesis (EMH) is rarely found in the gastrointestinal tract. To our knowledge, EMH involving the appendix was not described. We report a case with a previous history of idiopathic myelofibrosis, which presented with clinical findings of acute appendicitis that necessitate appendectomy after the relief of his anemia. Microscopic examination and immunohistochemistry revealed foci of EMH throughout the mucosa and the submucosa. In the latter, small clusters of hematopoietic cells were also detected in a few dilated vascular structures. The histopathological features of acute appendicitis were not observed. Our case supports that EMH might develop in organs that are not involved in hematopoiesis. Although in gastrointestinal system, obstruction and bleeding are the most common symptomatic manifestations, this case emphasizes that EMH might also present clinically as acute appendicitis. The absence of histopathological features of acute appendicitis raises the possibility that local production of some mediators from hematopoietic precursor cells might contribute to this clinical presentation.

Acute Disease↗
PubMed1999

Proteolytic activity of the Gymnorhynchus gigas plerocercoid: purification and properties of a collagenase from the crude extract.

The present report demonstrates that the Gymnorhynchus gigas plerocercoid possesses various types of endo- and exoproteases with activity against general (azocoll, azocasein, and azoalbumin) and specific substrates (elastin, keratin, collagen, hemoglobin, fibrinogen, plasma, and immunoglobulin G). The activity against collagen is principally due to a 24-kDa collagenase with an isoelectric point of 7.5 and without isoforms or sugar residues. Moreover, its high degree of proteolytic activity against collagen under conditions similars to those encountered by the parasite in its hosts (pH and temperature) and its similarity to metallo- and cysteine proteases (the principal protease types implicated in degradation of tissues) suggests the importance of this molecule as a lytic enzyme principally implicated in penetration processes across the teleost muscle or/and into the gastrointestinal system of elasmobranch fishes as well as in molting processes.

Animals↗
PubMed2006

The effect of tryptophan administration on ileum contractility and oxidant status in mice.

L-tryptophan (TRP) is the precursor amino acid for the synthesis of serotonin (5-HT). 5-HT is effective both on the food intake and gastrointestinal system contractility. The aim of this study was to search the effects of systemic TRP treatment on 5-HT levels of ileum and searching the effect of ileal contractility and oxidant status. Swiss-albino mice were divided into two groups: 1. Control, 2. TRP-treated (100 mg/kg/24 h, i.p., for 7 days). Body weights were recorded at the beginning and at the end of experiments. Acetylcholine-induced contractile responses in the isolated ileum were recorded on polygraph. Ileal tissue malondialdehyde and glutathione levels determined by spectrophotometric and ileal tissue 5-HT levels were measured by immunohistochemical methods. TRP treatment decreased body weight and increased ileal contractile response. In the TRP-treated group, ileum malondialdehyde levels increased and glutathione levels decreased. Immunohistochemical detection showed that ileal 5-HT levels were increased by TRP treatment. There is a relationship between increased oxidative stress and increased contractility in the ileal tissue of the TRP-treated animals. These effects may be related to increased ileal 5-HT synthesis.

Acetylcholine↗
PubMed2004

Severe hyperreninemic hypertension associated with spontaneous renal cholesterol crystal embolization.

A 70-year-old man was admitted because of severe hypertension and renal insufficiency. Marked elevation in plasma renin activity (PRA; 34.2 ng/ml per h) was noted. Five days later, the patient developed hemorrhagic duodenal ulcers and panperitonitis, went into shock, and died. An autopsy revealed severe atherosclerosis with marked ulceration in the abdominal aorta. Renal histology showed multiple cholesterol crystal embolization (CCE) associated with infarction. Cholesterol crystals were also detected in the vessels of the gastrointestinal system, including the liver, stomach, colon, and pancreas. Although not common, spontaneous CCE should be considered in elderly patients who present with abrupt onset of severe hypertension associated with renal insufficiency. The most important finding in this patient was severe hyperreninemia. Although potentiation of the renin-angiotensin-aldosterone system is the suggested mechanism for the hypertension in renal CCE, we could not find any reported case of renal CCE with hyperreninemia. It is reasonable to consider that severe hyperreninemia might be overlooked in renal CCE. PRA should be measured in patients with renal CCE, because it may give important information for selecting antihypertensive agents and improving the prognosis. To clarify this possibility, an accumulation of similar cases is necessary.

Acute Kidney Injury↗
PubMed2005

Fecal fungal flora of pediatric healthy volunteers and immunosuppressed patients.

Most hematogenous candidiasis originates from endogeneous host flora. Fungal flora of gastrointestinal system are important source of infection especially in immunosupressed patients. The purpose of this study was to investigate the fecal fungal flora of pediatric patients with hematologic malignancy or disorders and to compare the results with healthy volunteers. For this purpose, fungal etiological agents were investigated retrospectively in stool samples of 80 patients followed in Bone marrow transplantation and Hematology-Oncology units. The diagnosis of patients were as follows: 26 acute myelogeneous leukemia, 19 acute lymphocytic leukemia, 5 lymphoma, 3 chronic myelogeneous leukemia, 2 solid tumor, 4 neuroblastoma and 21 hematologic disorders. In patients, totally 102 fungal growth was detected and 42 (41.2%) C. albicans and 51 (50%) non-albicans Candida species and 9 (8.8%) yeast other than Candida and mould was isolated. The results were compared prospectively with growth in stool samples of 61 healthy children. C. albicans was detected in 16 (43.2%) and non-albicans Candida species in 15 (40.5%) and yeasts other than Candida and mould in 6 (16.2%) of 37 fungal growth in controls. Non-albicans Candida species growth was found significantly higher and C. glabrata was more prevelant in patients than in controls (p < 0.001).

Adolescent↗
PubMed2000

Carcinoid Heart Disease.

Carcinoid syndrome originates from metastatic carcinoid tumors localized in the gastrointestinal system, pancreas, biliary vessels, bronchi, ovaries, and testes; it is characterized by flushing, telangiectasias, diarrhea, bronchoconstriction, and fibrous endocardial plaques in the heart. Cardiac involvement is detected by echocardiography in over 50% of patients with this syndrome. Right-sided valvular heart disease occurs frequently in patients with carcinoid syndrome, involving most commonly the tricuspid and pulmonary valves. Involvement of the left-sided valves rarely occurs. Medical therapy for carcinoid heart disease includes digitalis and diuretics for congestive heart failure symptoms; the effects of carcinoid syndrome can be treated with the use of somatostatin analogues. Conventional chemotherapy has been of little beneficial value, with response rates of only 10% to 30%. The use of octreotide, a long-acting and potent somatostatin analogue, is a major advance in the management of carcinoid tumors. In addition to providing effective symptom relief in malignant carcinoid syndrome, octreotide can also be used for diagnostic purposes. Despite its expense, octreotide is the current agent of choice for the treatment of this condition. Analogues with different receptor specificities and pharmacokinetics hold promise for the future. Valve surgery is the only definitive treatment for intractable right-sided heart failure. Although cardiac surgery carries high perioperative mortality, marked symptomatic improvement occurs in survivors. Surgical intervention therefore should be considered in the appropriate patients when cardiac symptoms become severe. Balloon valvulotomy in patients with severe pulmonary artery stenosis often results in palliation of symptoms; however, surgery still is required often in these patients.

Journal Article↗
PubMed1976

Chronic neutropenia in childhood. Analysis of 16 cases and a review of the literature.

We analyzed the clinical histories and hematologic information concerning 16 persons in whom chronic neutropenia was discovered early in life. Only two of them, those with the lowest mean neutrophil counts, had frequent and severe pyogenic infections. Almost all the infections were caused by Staphylococcus aureus or by enteric microorganisms and involved the skin, respiratory tract or gastrointestinal system. The prognosis in our subjects or in patients described in the literature could not be predicted from the bone marrow morphology, presence or absence of blood monocytosis, pattern of genetic transmission or results of special tests of neutrophil function. We propose that the complex nomenclature associated with chronic neutropenic states be discarded until a better basis for classification becomes available.

Adolescent↗
PubMed1985

Review of adverse experiences and tolerability in the first 2,516 patients treated with imipenem/cilastatin.

The clinical and laboratory data relating to the adverse experiences and tolerability of imipenem/cilastatin in the first 2,516 patients treated with the antibiotic are reviewed, with special reference to the last 793. Clinical adverse experiences were predominantly related to the gastrointestinal system (nausea and vomiting), local injection site, and allergy (rash). A low frequency of drug-related seizures was also reported. The most frequent adverse laboratory experiences were transient elevations of liver function test values. In general, the safety profile was similar to that of other beta-lactam antibiotics.

Adolescent↗
PubMed1987

Comparison of the safety and efficacy of nabumetone and aspirin in the treatment of osteoarthritis in adults.

A six-month, multicenter, double-blind study compared the efficacy and safety of two therapeutic regimens in 332 patients with osteoarthritis. The patients received either 1,000 mg of nabumetone as a single bedtime dose or 900 mg of aspirin in four divided doses. At the end of the study, patients in both treatment groups showed significant improvement from baseline for all five parameters; no statistically or clinically significant differences were observed between the groups. The safety data did reveal clinically and statistically significant differences between the groups. Aspirin-treated patients experienced a greater frequency of withdrawal from the study because of adverse experiences (34 percent versus 13 percent), a greater incidence of having at least one treatment-related adverse experience (73 percent versus 52 percent), a greater percentage of patients with at least one moderate or severe treatment-related adverse experience (47 percent versus 22 percent), and a greater percentage of patients with treatment-related adverse experiences affecting the gastrointestinal system (43 percent versus 32 percent) or the inner ear (32 percent versus 10 percent). The results of this study demonstrated that nabumetone, 1,000 mg at bedtime, is as efficacious as aspirin, 900 mg four times daily, produces fewer adverse effects, and is indicated in the treatment of osteoarthritis.

Adult↗
PubMed1991

Acute bronchodilating effects of ipratropium bromide and theophylline in chronic obstructive pulmonary disease.

The bronchodilator effects of a single dose of ipratropium bromide aerosol (36 micrograms) and short-acting theophylline tablets (dose titrated to produce serum levels of 10-20 micrograms/mL) were compared in a double-blind, placebo-controlled crossover study in 21 patients with stable, chronic obstructive pulmonary disease. Mean peak forced expiratory volume in 1 second (FEV1) increases over baseline and the proportion of patients attaining at least a 15% increase in the FEV1 (responders) were 31% and 90%, respectively, for ipratropium and 17% and 50%, respectively, for theophylline. The average FEV1 increases during the 6-hour observation period were 18% for ipratropium and 8% for theophylline. The mean duration of action was 3.8 hours with ipratropium and 2.4 hours with theophylline. While side effects were rare, those experienced after theophylline use did involve the cardiovascular and gastrointestinal systems. These results show that ipratropium is a more potent bronchodilator than oral theophylline in patients with chronic airflow obstruction.

Adult↗
PubMed1989

Abnormal fetal heart rate patterns and placental inflammation.

Can acute inflammation in the placental membranes, amniotic fluid, or both, predispose to the development of abnormal fetal heart rate patterns? One hundred cases in which bradycardia was noted were compared with 48 cases in which abnormal fetal heart rate patterns did not occur. Case and control subjects were matched to provide an equivalent risk of developing ascending infection in the two groups. Fetoplacental weight ratio and the presence of other placental diseases were also considered. The presence of acute inflammation in the umbilical cord (p = 0.03), amnion (p = 0.01), and choriodecidua (p = 0.03), and higher grades of inflammation in chorionic plate (p = 0.03) were linked to the presence of abnormal fetal heart rate patterns. No other placental factors were associated with increased risk of fetal bradycardia. The association of abnormal fetal heart rate patterns with acute inflammation suggests that intra-amniotic inflammation is important in the genesis of fetal bradycardias. The inflamed amniotic fluid could alter fetal metabolism via effects on the pulmonary or gastrointestinal systems or effects on umbilical and chorionic vessels.

Acute Disease↗