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General pharmacology of indole [2',3':3,4]pyrido[2,1-b]quinazolinium- 5,7,8,13-tetrahydro-14-methyl-5-oxo-chloride, a new anti-dementia agent.

The general pharmacological properties of indolo[2',3':3,4]pyrido[2,1-b]quinazolinium-5,7,8,13-tetrahydro-14- methyl-5-oxo-chloride (dehydroevodiamine-HCl, DHED, CAS 67909-49-3), a new potential anti-dementia agent, were studied to investigate side effects using various experimental animals. Both oral and intraperitoneal administration of DHED had no effects on the central nervous system except that they showed an analgesic activity. DHED had no significant effect on heart rate, blood pressure and coronary flow in isolated rat hearts. DHED had negligible effects on the autonomic nervous system and smooth muscle in isolated rat ileum, rat vas deferens and rat aorta. DHED did not influence the gastrointestinal system except that it inhibited the intestinal travel of a charcoal meal in mice. Neither blood coagulation mechanism nor liver function was affected by DHED. Therefore, it is concluded from these general pharmacological studies that DHED does not induce any serious side effects at the dose levels showing anticholinesterase and memory enhancing activities in the experimental animals.

Alkaloids↗

[Use of an automated classifying system for the dispensary system of the population].

While processing blood values by an automatic classifying system, human beings can be divided into healthy (normal) and unhealthy (ill) persons. In so doing, one can evaluate the status of the body's individual systems (gastrointestinal tract, respiratory organs, locomotor apparatus, heart and vessels, urinary, endocrine, hemopoietic, and female genital organs, the central nervous system), which allows a physician to find a source of poor health from the very onset of disease.

Adult↗

Gastrointestinal involvement in POEMS syndrome: a novel clinical manifestation.

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) is characterised by a rare multisystem disorder of unknown pathogenesis. Although its pathophysiology is not well understood, overexpression of proinflammatory cytokines has been implicated. Gastrointestinal system disorders have not been reported among the components of the syndrome. A case is reported of POEMS syndrome with gastrointestinal involvement shown by gastrointestinal endoscopy.

Adult↗

[Gastrointestinal stromal tumor: case report].

INTRODUCTION: Gastrointestinal stromal tumors represent extremely rare tumors of the gastrointestinal system, especially when localized on the small intestine. CASE REPORT: We report a case of a female patient, with recurrent gastrointestinal bleeding and severe anemia, caused by gastrointestinal stromal tumor of the small intestine. After negative endoscopic findings, she underwent radiological examination of the small intestine. Primary diagnostic radiological evaluation included: small intestine passage enteroclysis, computed tomography of the abdominal cavity and selective angiographic study of the three major aortic branches that supply the gastrointestinal tract in the abdomen (celiac axis, superior mesenteric artery and inferior mesenteric artery). Secondly, ultrasound of abdominal cavity was performed. Findings of small intestine passage and enteroclysis were negative. The tumor was visualized by computed tomography and ultrasound, but without distinctive anatomical localization in the abdominal cavity. DISCUSSION: The diagnostic dilemma has been resolved by using selective angiographic examination of celiac axis and superior mesenteric artery and thus a tumor formation was visualized in the mesenterium of the small intestine. Radiological findings were confirmed by surgery. Histopathological findings were positive for gastrointestinal stromal tumor. CONCLUSION: Gastrointestinal stromal tumors of the small intestine rarely cause recurrent bleeding, but they should be included in differential diagnosis.

Diagnosis, Differential↗

[Acute respiratory distress syndrome].

Acute respiratory distress syndrome (ARDS) - is a life-threatening acute clinical syndrome of pulmonary insufficiency with high mortality. The causes of the syndrome are of every description - from crustacean poisoning to cardiopulmonary bypass. The rate of ARDS is not clear, because of diagnostical variety of ARDS and acute pulmonary dysfunction. The discussion on ARDS diagnostical criteria lasted for many years. The clinical criteria depend on how the essence of the disease is understood, on the size of lung infiltration, lung compliance and failure as well as degree of hypoxemia. The risk of ARDS increases with the increase of number of predisposing factors. The investigation data depend mainly on used datum-point for diagnostics of ARDS. It is obvious that non-cardiogenic light pulmonary edema is found very often, and serious lung lesions are rare enough. The aim of nowadays treatment is to cure the disease that causes the syndrome and to sustain vital functions. The early diagnostics of ARDS predisposing factors and minimization of their influence, the prevention, early diagnostics and timely treatment of complications are essential. In many cases ARDS caused by collateral factors is the constituent of multiple organ dysfunction syndrome. Anyway the ARDS predisposed by direct factors is often complicated by other organ (cardiovascular, renal, hepatic, hematogenous, central nervous system, gastrointestinal tract, etc.) dysfunction. In this case the treatment becomes more difficult and includes therapy correcting the function of other systems. In spite of intensive treatment, mortality of this syndrome still remains 50-90% according to the literature data. Though some authors state that recently the ARDS mortality decreased, but most of the authors did not notice any improvement during the last 20 years. The prognosis is determinated not only by pulmonary insufficiency itself (the cause of death in 5% of patients), but by the ARDS predisposing factor (the worst is sepsis and septic shock), multiple organ dysfunction syndrome, difficult physical state of the patient, sepsis as a cause or as a complication of ARDS, nosocomial pneumonia, progressive fibroproliferation in the lung. Considering the actuality of ARDS, the diagnostical criteria of ARDS, pathogenesis, clinical course and new treatment methods are reviewed in the publication.

APACHE↗

General pharmacology of the new quinolone antibacterial agent levofloxacin.

The general pharmacological properties of (-)-(S)-9-fluoro-2,3-dihydro-3- methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4] benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4), an optically active isomer of ofloxacin, were examined. 1. Central nervous system (CNS): DR-3355 at 200-600 mg/kg p.o. showed depressant activity on the CNS, as was indicated by the depressant syndrome (mice), decreased spontaneous motor activity (mice) and hypothermia (mice and rabbits). In the cat behavior and EEG experiments, it had both stimulant and depressant effects at 30-100 mg/kg i.p., and caused transient slow waves followed by seizures at 20-30 mg/kg i.v. DR-3355 had no effect on convulsion, hexobarbital anesthesia, pain reaction to a tail pinch, or conditioned avoidance response, except that it showed mild analgesic activity in acetic acid writhing at 600 mg/kg p.o. 2. Respiratory and cardiovascular system: DR-3355 produced a hypotensive and a bradycardiac effect after the rapid i.v. injection of 6 mg/kg or more in anesthetized dogs, accompanied by an increase in plasma histamine concentration. Both changes were markedly reduced when the test drug was administered by continuous i.v. infusion. 3. Autonomic nervous system: DR-3355 inhibited nictitating membrane contraction induced by both pre- and post-ganglionic stimulation, and inhibited the depressor response to acetylcholine at 20 mg/kg i.v. It had no influence on pupil size or on pressor response to norepinephrine. 4. Gastrointestinal system: DR-3355 at 600 mg/kg p.o. inhibited gastric secretion. Dog gastrointestinal motility was slightly inhibited, and was then stimulated over the dose range of 2-20 mg/kg i.v. It had no influence on gastrointestinal propulsion, the gastric emptying rate or the gastric mucosa. 5. Isolated smooth muscle: At a concentration of 5 x 10(-4) g/ml, DR-3355 was devoid of spasmogenic or smasmolytic activity, except for showing a slight relaxation effect (trachea), inhibition of nicotine-induced contraction (ileum) and spontaneous or oxytocin-induced motility (pregnant uterus). 6. Miscellaneous: DR-3355 inhibited the urine output and carrageenin-induced paw edema at 600 mg/kg p.o. It had no effect on skeletal muscle contraction or the corneal reflex.

Animals↗

New oral macrolide and fluoroquinolone antibiotics: an overview of pharmacokinetics, interactions, and safety.

During the past decade, there has been a resurgence of interest in the development of oral macrolide and fluoroquinolone antimicrobial agents. Azithromycin and clarithromycin are two new oral macrolides whose pharmacokinetics (compared with those of erythromycin) are characterized by improved oral bioavailability, increased tissue penetration and persistence, and longer elimination half-lives. A limited number of interactions with other drugs have been reported for azithromycin and clarithromycin. The most common adverse reactions to the new macrolide agents include nausea, diarrhea, and abdominal pain. Norfloxacin, ciprofloxacin, ofloxacin, temafloxacin, and lomefloxacin are the oral fluoroquinolones that have been marketed in the United States thus far. In comparison to nalidixic acid, the newer fluoroquinolones have improved pharmacokinetic properties, including greater oral absorption, increased peak serum concentrations and areas under the curve, higher tissue concentrations, and longer elimination half-lives. Divalent or trivalent cations can alter the absorption of all fluoroquinolones. Some of the fluoroquinolones (norfloxacin, ciprofloxacin, and ofloxacin) can inhibit the cytochrome P-450 enzyme system and thereby cause increased serum concentrations of drugs like theophylline and caffeine. Adverse reactions to the fluoroquinolones primarily involve the gastrointestinal system, skin, and central nervous system.

Administration, Oral↗

Pharmacological studies on taurohyodeoxycholic acid.

In this study we investigated the anticholelithogenic and choleretic activities and the general pharmacological action of taurohyodeoxycholic acid (THDCA, Io, Praxis, CAS 2958-04-5), a new biliary acid advocated for use as anticholelithogenic agent. THDCA had no significant activity on the CNS (spontaneous locomotor activity, body temperature, coordinated movement, respiration); it also had no significant anticonvulsant or central anticholinergic actions. With regard to the action on the cardiovascular system, THDCA administration did not give rise to significant changes in blood pressure or ECG. Investigation of its action on the gastrointestinal system revealed no significant changes in the intestinal transport of charcoal after treatment. However, biliary flow and biliary solids content were increased by THDCA intraduodenal doses of 300 mg/kg b.w. In mice fed with lithogenic diet THDCA administration (230 and 450 mg/kg b.w. for 8 weeks) significantly decreased gallstone and steatosis incidence.

Animals↗

Tumor thrombi in the portal vein system originating from gastrointestinal tract cancer.

Intraluminal tumor thrombus in the portal vein (PV) system originating from gastrointestinal (GI) tract cancer is a rare condition. There are two types of such thrombi, one arising indirectly from metastatic liver cancer and the other directly from the primary lesion. We report here three patients with the direct type and two with the indirect type; i.e., a total of five patients with gastric or large intestinal cancer with PV tumor thrombus. In all patients, the primary lesion was surgically resected; in two patients, the tumor thrombus was easily extirpated by direct opening of the PV. It is noteworthy that a patient whose tumor thrombus could not be treated died of cancer with liver failure, caused by expansive growth of the PV tumor thrombus, 4 months after the finding of the PV thrombus. Because PV tumor thrombus may, possibly, determine the patient's length of survival, in addition to causing cancer progression, surgical thrombectomy, combined with resection of the primary cancer and metastatic liver cancer, should be considered for prolongation of survival, if all macroscopic lesions can be controlled and if the tumor thrombus is a synchronous and recent one.

Adenocarcinoma↗

Investigations and management of gastrointestinal and hepatic manifestations of systemic lupus erythematosus.

Gastrointestinal (GI) manifestations of systemic lupus erythematosus (SLE) are protean. Any part of the GI tract and the hepatobiliary system can be involved. Up to two-third of SLE patients develop GI symptoms at some stage of their illnesses. Clinical presentations of GI lupus are non-specific and can be difficult to differentiate from infective, thrombotic, therapy-related and non-SLE etiologies. Clinical acumen and appropriate endoscopic, biopsy and imaging procedures are essential for establishing the correct diagnosis. Acute abdominal pain in SLE patients can herald an intra-abdominal catastrophe and should be evaluated promptly. Surgical intervention should be instituted without delay if conservative management fails or when there is clinical or radiological suspicion of visceral perforation or intra-abdominal collections.

Diagnostic Imaging↗

Noninfectious diseases, metabolic diseases, toxicities, and neoplastic diseases of South American camelids.

Although the SAC generally are healthy and tolerant of a wide variety of management schemes, a number of noninfectious diseases have been documented to occur, affecting all body systems. Gastrointestinal diseases appear to be the most common afflictions, particularly dental diseases, indigestion, ulceration of the third compartment, and the various causes of colic, such as enteritis, peritonitis, and intestinal accidents. Diseases of the urinary system (urolithiasis, amyloidosis, and glomerulonephritis in particular), the nervous system (especially various compressive lesions of the spinal cord), and the respiratory system (such as obstructive pulmonary diseases) are not uncommon. Diseases of the cardiovascular system (other than congenital defects), hemolymphatic system, and nonsurgical diseases of the musculoskeletal system only rarely are encountered. Heat stress appears to be a very common problem in certain areas, but other metabolic diseases (ketosis, hypocalcemia, and hypothyroidism) are of minor importance. It is assumed that SAC are susceptible to most of the same toxicities that affect domestic livestock species. The best documented examples appear to be the Ericaceae family of plants (laurels, rhododendrons, and so on) and the organophosphate chlorpyrifos. Neoplasia occasionally is seen; examples include lymphosarcoma, gastric squamous cell carcinoma, and adenocarcinoma. As the longevity of these species increases because of their pet status, neoplasia can be expected to become more common. The treatment of most of these conditions is based upon extrapolation from domestic ruminants.

Animals↗

Review of adverse reactions associated with cinoxacin and other drugs used to treat urinary tract infections.

The evaluation of adverse drug reactions (ADR) in clinical practice is difficult and imprecise. Establishing a causal relationship may not be possible, and data on incidence cannot be obtained because the number of patients treated is not known. This article describes the ADR reported during the clinical trial program of cinoxacin, a synthetic antibacterial drug used to treat urinary tract infections. Results from 2,801 patients who received cinoxacin showed that 5 per cent reported ADR that were probably or definitely drug induced, and 10 per cent reported ADR in which the relationship was uncertain. There was no relationship between number of reports and patient's age, drug dose, or duration of treatment. Adverse drug reactions affecting the gastrointestinal system were reported by 5.5 per cent of the patients, those involving the central nervous system by 4.3 per cent, and hypersensitivity reported by 2.4 per cent. In the comparative studies, patients treated with cinoxacin reported fewer ADR than those treated with nalidixic acid, furadantin, amoxicillin, or trimethoprim-sulfamethoxazole. Although problems in the assessment and evaluation of ADR still exist, it is hoped that the results from the formal trial program will be representative of those seen in clinical practice.

Adult↗

Effect of a surfactant, Tween 80, on the formation and secretion of chylomicrons in the rat.

Effects of Tween 80, a nonionic surfactant, on size and number of chylomicrons (CM) secreted during lipid absorption in the rat model are reported. Fasted rats were loaded with either 154 mM NaCl or 25% (w/w) olive oil emulsion in 154 mM NaCl with 0, 0.1, 1 or 10% (w/w) Tween 80. After 3 h, either mesenteric lymph or blood was collected and their triacylglycerol-rich lipoprotein fraction (Sf>20 and Sf>400, respectively) isolated. Triacylglycerol (TAG) and apolipoprotein B48 (apoB48) concentrations in the lipoprotein fractions were assayed and their fluxes (lymph) calculated. TAG:apoB48 ratios, indicative of CM size, were determined. The data support the hypothesis that fat loading is accommodated mainly by increased average size, rather than number, of CM. Co-administration of Tween 80 with olive oil resulted in a significant increase in CM apoB48 secretion into the mesenteric lymph duct and in an increased concentration of apoB48 in the blood (Sf>400). Also, Tween 80-treated groups exhibited smaller mean CM size relative to the olive oil only group in both lymph and blood. The observed effect on CM size and number did not appear to be dose dependent at concentrations of Tween 80 above 0.1% (w/w). Incorporation of Tween 80 in the diet at 1 or 10% (w/w) concentrations reduced the TAG concentration in the stools; however, a significant increase in water content was observed at 10% (w/w) concentration. In conclusion, Tween 80 at 1 or 10% (w/w) doses can improve the efficiency of the digestive system to absorb dietary fat but at high concentrations (10%, w/w) it appeared to have a toxic or irritating effect on the gastrointestinal system. More importantly, the effect of Tween 80 on size and number of CM is a condition that favours a delay in their clearance rate.

Animals↗

Risk of selected birth defects with prenatal illicit drug use, Hawaii, 1986-2002.

The literature on the association between prenatal illicit drug use and birth defects is inconsistent. The objective of this study was to determine the risk of a variety of birth defects with prenatal illicit drug use. Data were derived from an active, population-based adverse pregnancy outcome registry. Cases were all infants and fetuses with any of 54 selected birth defects delivered during 1986-2002. The prenatal methamphetamine, cocaine, or marijuana use rates were calculated for each birth defect and compared to the prenatal use rates among all deliveries. Among all deliveries, the prenatal use rate was 0.52% for methamphetamine, 0.18% for cocaine, and 0.26% for marijuana. Methamphetamine rates were significantly higher than expected for 14 (26%) of the birth defects. Cocaine rates were significantly higher than expected for 13 (24%) of the birth defects. Marijuana rates were significantly higher than expected for 21 (39%) of the birth defects. Increased risk for the three drugs occurred predominantly among birth defects associated with the central nervous system, cardiovascular system, oral clefts, and limbs. There was also increased risk of marijuana use among a variety of birth defects associated with the gastrointestinal system. Prenatal uses of methamphetamine, cocaine, and marijuana are all associated with increased risk of a variety of birth defects. The affected birth defects are primarily associated with particular organ systems.

Adult↗

Locomotive disorders associated with sow mortality in Danish pig herds.

Given the increase in sow mortality in Danish pig herds over the last 10 years, we have investigated the causes of spontaneous death and killing of sows, especially those due to locomotive disorders. A total of 265 culled sows (93 spontaneously dead sows and 172 killed sows) from 10 different herds were sent for complete necropsy, and grouped according to primary diagnoses. From 35 of these sows, tissue for histological evaluation and samples for bacteriological cultivation were also collected, and secondary diagnoses and body condition were recorded. The main causes for killing were related to the locomotive system (72%), arthritis (24%) and fractures (16%) being the most frequent lesions. The main causes of spontaneous death were related to the gastrointestinal system and spleen (45%) and the reproductive system (24%). Arthrosis was a secondary diagnosis in 88% of the killed sows and in 92.5% of the spontaneously dead sows. Arcanobacterium pyogenes was the main cause of arthritis. The killed sows had significantly lower body condition compared with spontaneously dead sows. The first two parities and the time around farrowing were associated with the highest mortality in both groups. Hopefully, these observations can guide breeding units attempting to monitor, control and reduce sow mortality.

Animals↗

Endoscopic ultrasound-guided fine-needle aspiration findings of gastrointestinal leiomyomas and gastrointestinal stromal tumors.

True leiomyomas of the gastrointestinal system are rare but remain the most common mesenchymal tumors of the esophagus. It has become important to distinguish these tumors from gastrointestinal stromal tumors (GISTs) because the neoplasms have different prognoses and treatment options. We describe and compare clinical findings and the following fine-needle aspiration (FNA) features of 9 gastrointestinal leiomyomas and 19 GISTs sampled with endoscopic ultrasound: overall cellularity, cell group features, cell shape and cytoplasmic features, nuclear characteristics, background, cell block features, and immunohistochemical results. Gastrointestinal leiomyomas and GISTs have different clinical and cytologic features that help pathologists distinguish these tumors, and the immunohistochemical findings that help define these lesions can be derived readily from cell block material obtained by endoscopic ultrasound-guided FNA.

Biopsy, Needle↗

[The influence of aging on autonomic nervous system activity and gastric myoelectric activity in humans].

The study was performed on 84 healthy volunteers (33 women, 52 men) of age 20-71 years with no history of the circulatory or gastrointestinal system disease. The gastric myoelectrical activity (EGG) was recorded with the cutaneous electrodes--electrogastrography Synectics (Sweden). The activity of the cardiac autonomic nervous system was measured by HRV (heart rate variability) recorded with EGG and computer assisted programme Proster (Poland). Subject were divided into 5 groups according to the decade of age (20-70). Percentage of basal electrical rhythm (BER) dysrhythmias increased (1.9 +/- 0.5% vs 21.1 +/- 3.2% in fasting and 2.4 +/- 1.2% vs 24.6 +/- 5% postprandially but decrease of the EGG amplitude after the meal was observed (270 +/- 20% vs 90 +/- 7%) in youngest and oldest group respectively. With the ageing the cardiac sympathetic and parasympathetic activity (LF and HF) decreased in first and last group respectively. In the forth decade in man and women the sympathetic activity system prevalence expressed by the LF/HF rate increased (1.09 +/- 0.2 vs. 2.14 +/- 0.5) (p < 0.05). The results of our study suggest the deleterious influence of the ageing on the of autonomic system activity as shown by changes in HRV and dysrhythmia of the gastric slow waves in EGG.

Adult↗