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PubMed2003

Beta-thalassaemia: emergence of new and improved iron chelators for treatment.

Beta-thalassaemia is an inherited blood disorder which through repeated blood transfusions and enhanced iron uptake from the gastrointestinal tract, results in marked iron overload. Untreated, the iron accumulation results in the dysfunction of vital organs such as the heart and liver. At present, the most effective treatment for beta-thalassaemia is the use of the iron chelator, desferrioxamine, which is expensive, orally inactive and requires long subcutaneous infusions. In this concise review, we will focus on novel chelators which show therapeutic potential to replace desferrioxamine. Furthermore, we will discuss the potential of combined iron chelation therapy and the principle that, in the future, the use of more than just one chelator may be beneficial in tailoring individual iron chelation regimens.

Humans↗
PubMed1997

Chronic intestinal pseudoobstruction associated with fetal alcohol syndrome.

Alcohol acts as a teratogen in the fetus, resulting in prenatal or postnatal growth failure, characteristic facial dysmorphic features, and central nervous system dysfunction. The toxic effects of alcohol on the developing brain are well recognized, but gastrointestinal neuropathy has not been described in fetal alcohol syndrome (FAS). Five children with FAS presented in infancy with signs and symptoms suggestive of chronic intestinal pseudoobstruction. They were not able to sustain adequate caloric intake by mouth, and all required prolonged special methods of alimentation. We performed antroduodenal manometry in these children to determine whether their symptoms were associated with a gastrointestinal motility disorder. All patients had abnormally propagating phase III-like episodes during fasting (retrograde in four, simultaneous in two). Persistent clusters of stationary contractions were a prominent feature in two patients. In utero neurotoxicity of alcohol may not be limited to the central nervous system, but may also cause an enteric neuropathy presenting in infancy as chronic intestinal pseudoobstruction.

Child↗
PubMed1998

Idiopathic megacolon associated with oesophageal achalasia.

We report a rare case of achalasia coexistent with megacolon. The patient, a 25-year-old woman, presented at our hospital with a history of abdominal pain with distension, and was finally operated on for a megacolon. Five months later she presented symptoms of progressive dysphagia and heartburn. Oesophageal manometry of the upper and lower oesophageal sphincter and X-ray studies showed images compatible with achalasia. Oesophagomyotomy of the oesophagogastric junction (Heller procedure with Dor haemifundoplication technique) was performed. In the specimens taken for biopsy, neither pathology of the myenteric plexuses, nor atrophy of the muscle fibres was evident. Chagas' disease serological diagnosis for Trypanosoma cruzii, neurological disease, diabetes and all the pathological events related with neuromuscular disorders of the gastrointestinal tract proved negative. We believe that the pathological findings are related to a dysfunction of the physiological mediators of the upper and lower digestive tract motility. The present case is extraordinary and, to our knowledge, extremely rare. The association of the two pathological diseases is questionable, and the literature is reviewed.

Adult↗
PubMed2003

Cocaine and the critical care challenge.

OBJECTIVE: Cocaine, which first made its appearance >1,000 yrs ago, is now widely used throughout the world. The physiologic responses to cocaine may cause severe pathologic effects. This review highlights the many critical care challenges resulting from these effects. DESIGN: Historical vignettes, epidemiologic factors, modes of preparation and delivery, and the physiologic and pharmacologic effects of these agents are presented. SETTING: Cocaine causes intense vasoconstriction, which potentially causes damage to all organ systems. Examples of these toxicities are presented. PATIENTS: The adverse multisystem responses to cocaine exposure produce organ failure, which challenges diagnostic accuracy and therapeutic intervention. Organ system failure involves the brain, heart, lung, kidneys, gastrointestinal tract, musculature, and other organs. These harmful effects are additive to preexisting organ dysfunction. INTERVENTION: Recognition of associated cocaine injury alerts the physician that organ dysfunction is more likely to occur and to be more severe. Such anticipation helps plan for therapy in the critical care setting. RESULTS AND CONCLUSIONS: Cocaine use is an expanding health hazard, despite intense governmental efforts to contain its distribution and use. Recognition of the signs and symptoms of cocaine toxicity help anticipate the subsequent organ dysfunction and implement earlier organ system support.

Cocaine↗
PubMed1996

Elevated aminotransferase activity as an indication of muscular dystrophy: case reports and review of the literature.

Five male children are reported in whom incidental recognition of elevated serum alanine aminotransferase (ALT) activity initiated investigation to identity the cause of suspected hepatocellular injury. All five were later diagnosed with X chromosome-linked muscular dystrophy. The serum level of ALT, generally considered to be specific for hepatocellular injury, was increased two to 25 times above normal in all the reported cases. Paradoxically, the increase in ALT activity was greater than that of serum aspartate aminotransferase (three to 16 times normal), an enzyme whose elevation is generally recognized as being less specific and indicative of muscle, cardiac, kidney, pancreatic, red blood cell or hepatic injury. At presentation to the gastrointestinal service, one case, age 2.5 months, had no symptoms or signs of neuromuscular dysfunction, while the other four had previously unrecognized hypertrophy of the calves, proximal limb weakness, positive Gower's sign or delayed gross motor skills. All five patients had marked elevation of serum creatine kinase activity and histopathologically confirmed muscular dystrophy. The practical clinical implication of this report is that children with elevated serum ALT, in the absence of other signs and symptoms of hepatic injury, may have occult muscular disease--most frequently muscular dystrophy. Although the clinical signs of muscular dystrophy may be subtle or absent, early determination of creatine kinase will suggest the correct diagnosis and minimize extensive and invasive investigation focusing on hepatic injury.

Adolescent↗
PubMed1997

Clinical role for a superantigen in Yersinia pseudotuberculosis infection.

Yersinia pseudotuberculosis is an enteric pathogen that causes a variety of clinical symptoms in the human. Recently, we reported the production of a superantigen (Y. pseudotuberculosis-derived mitogen, YPM) by this organism and characterized the gene structure of ypm. To further study the potential pathogenic role of YPM in Y. pseudotuberculosis infection, we assayed IgG anti-YPM antibodies and T cell antigen receptor-Vbeta expression of the T cells in peripheral blood and in mesenteric lymph node in patients acutely infected with Y. pseudotuberculosis. 20 out of 33 patients (61%) had an elevated antibody titer compared with healthy controls (P = 0.0001). Patients with systemic symptoms such as lymphadenopathy, transient renal dysfunction, and arthritis had significantly higher titers of anti-YPM than patients with gastrointestinal tract symptoms alone. T cells bearing the Vbeta3 gene segment were significantly increased (P = 0.009) among acute phase patients compared with healthy children. During the convalescence phase of the illness, there was a reduction in the abnormal level of Vbeta3 T cells. Moreover, in the mesenteric lymph node, an elevated level of Vbeta3 T cells compared with peripheral blood and a sequence diversity in the junctional region of the T cell antigen receptor beta-chain containing Vbeta3 element was observed in one patient. Together, these findings suggest that YPM was produced in vivo and played an important role in the pathogenesis of Y. pseudotuberculosis infection.

Adolescent↗
PubMed1989

Carbamazepine in Fabry's disease: effective analgesia with dose-dependent exacerbation of autonomic dysfunction.

Seven patients with Fabry's disease and severe pain received carbamazepine (CMZ). Five of 7 patients had moderate to complete relief based upon self-assessment of pain levels. Preexisting autonomic dysfunction was exacerbated by CMZ in 2. Complications encountered were ileus, urinary retention, and gastrointestinal disturbance. Although CMZ was useful in treatment of pain, caution should be employed in this disease.

Adult↗
PubMedDate not supplied

Suspected myelinolysis following rapid correction of hyponatremia in a dog.

A dog developed signs of neurological dysfunction five days after rapid correction of severe electrolyte derangements, including hyponatremia, caused by gastrointestinal parasitism (i.e., trichuriasis). History, laboratory findings, and onset of neurological signs following correction of hyponatremia led to a diagnosis of myelinolysis. Myelinolysis is a noninflammatory, demyelinating brain disease caused by sudden, upward osmotic shifts in central nervous system plasma, often a result of rapid correction of chronic hyponatremia. The pathogenesis is complex, but recovery is possible. Iatrogenic damage due to myelinolysis can be avoided by adherence to therapeutic guidelines for correction of chronic hyponatremia.

Animals↗
PubMed1990

[A combined chemo-endocrine therapy with tegafur, adriamycin, methotrexate and tamoxifen for advanced renal cell carcinoma].

Six patients with advanced renal cell carcinoma was treated with a new chemo-endocrine regimen consisting of Tegafur, Adriamycin, Methotrexate and Tamoxifen. Estrogen receptor was measured in four cases from renal or metastatic tumors by DCC method, presenting 14.7, 9.7, 1.0 and 0 f moles/mg protein respectively. The patients were medicated with 800-1,200 mg of Tegafur and 20 mg of Tamoxifen daily po, and 20 mg of Adriamycin and 10 mg of Methotrexate intermittently for two weeks interval iv. According to a criteria of Japan Society for Cancer Therapy, two were regarded as CR, one as PR, one as NC and two as PD. The one out of two cases with and without estrogen receptor responded favourably to this therapy. Side effects observed in the treatment were mild gastrointestinal disorders including nausea and vomiting, slight degree of leukopenia, stomatitis, pigmentation and liver dysfunction. The patients were found to be in good quality of life during the treatment because of less toxicity. This therapy can be regarded as a good modality for a treatment of advanced renal cell carcinoma. This is a first report of combined chemo-endocrine therapy with Tegafur, Adriamycin, Methotrexate and Tamoxifen for renal cell carcinoma in the world.

Aged↗
PubMed1988

[Clinical observations of hepatic artery infusion therapy combined with hepatic artery ligation in metastatic liver cancers].

Twenty-five patients with liver metastases from advanced gastrointestinal cancers were treated by hepatic arterial infusion chemotherapy by insertion of a catheter into the hepatic artery. All patients also underwent ligation of the hepatic artery. The anticancer agents used were adriamycin 10-30 mg, mitomycin C 10-20 mg and 5-fluorouracil 250-500 mg. The effect was assessed according to the criteria for clinical evaluation of chemotherapy for solid cancers by Koyama and Saito. The response rate for partial response was 24.0% among all 25 patients, including 25.0% (2/8) for stomach cancer and 28.6% (4/14) for colorectal cancer. The survival time with palliative resection of the primary lesion was prolonged significantly (p less than 0.05) in comparison with no resection. As for the side effects of hepatic arterial infusion chemotherapy, bone marrow suppression was most frequently found in 80.0% of patients, followed by gastrointestinal symptoms in 68.0%. In addition, fever occurred in 20.0%, stomatitis in 20.0%, liver dysfunction in 16.0% and alopecia in 4.0%. However, the side effects were all controllable. As to hepatic artery ligation, there was no serious complication except for one case of liver abscess.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Neuroendocrine syndromes of the hypothalamus.

These brief reviews of selected neuroendocrine or hypothalamic syndromes reinforce several important concepts. Although the hypothalamus may be relatively inaccessible to the neurologic clinician, it is, paradoxically, the region of the CNS that most closely communicates with virtually all other physiologic systems. This is evident by the fact that hypothalamic dysfunction is frequently associated with "non-neurologic" symptoms such as manifestations of endocrine, gastrointestinal, or gynecologic disease. Traditionally, the hypothalamus has been difficult to study, and progress in understanding hypothalamic disorders has been slow in both neuropathology as well as clinical neurology. Nevertheless, as neurology evolves from a descriptive specialty into one increasingly characterized by therapeutic intervention, the challenge of clinical hypothalamic disease offers many exciting possibilities to the neuropharmacologist, neuroendocrinologist, and all astute bedside clinicians.

Acetylcholine↗
PubMed1983

[Pilot studies with aclacinomycin in patients with breast cancer or gastrointestinal tumors].

Aclacinomycin (ACM), a new anthracycline antibiotic compound, was given intravenously q x 3 to 6 weeks in a dosage of 4 x 60 mg/4 days to 10 patients with metastasizing breast cancer and 5 patients with gastric carcinoma. Breast cancer patients, prior to ACM had extensive cytotoxic and hormonal treatments, gastric cancer patients received ACM as a first chemotherapeutic tumor treatment. No life-threatening hematologic toxicities could be noticed. All patients experienced moderate to severe gastrointestinal toxicities. No patient had considerable hair loss. 4 patients showed clinical signs of cardiac dysfunction: 1 ECG changes, 4 developed edema of lower extremities, 2 developed pericardial effusion. Moreover, 1 patient developed significant elevation of the pulmonary capillary wedge pressure (PCW) and prolongation of the systolic time intervals indicating pulmonary congestion grade I to II (Braunwald). No significant increase in heart volume was registered. Clear signs of cardiotoxicity could be demonstrated in patients pretreated with adriamycin exclusively. In animal experience, ACM had been reported as less cardiotoxic as compared to adriamycin. Present studies seem to indicate ACM being considerably cardiotoxic at relatively low cumulative dosages. Among the 15 patients there was one with metastatic breast cancer pretreated with adriamycin and resistant to that drug in whom partial remission was achieved. The other patients did not objectively respond to ACM therapy. 3 out of 5 patients with gastric cancer had stabilisation of the disease but no objective response.

Aclarubicin↗
PubMed2003

Review article--involvement of gastric APUD cells in chronic renal failure.

Uremia leads to a number of metabolic and hormonal disorders induced by renal failure with definite biological and clinical sequels. Most frequently, alimentary disorders are the first to appear, followed by symptoms from other organs and systems. The gastrointestinal tract is a site of synthesis of many compounds that have hormonal or hormonal-like biological activity. These substances are produced by highly-specialised receptor-effector cells, that are dispersed in the gastrointestinal mucosa and classified as APUD cells. The present review is an attempt to make a synthesis of current opinions and views concerning the effect of homeostatic dysfunction of the kidneys on the morphology and action of APUD cells in the stomach.

APUD Cells↗
PubMed1996

Intestinal mucosal permeability to 51Cr-ethylenediaminetetraacetic acid is increased after bilateral lower extremity ischemia-reperfusion in the rat.

BACKGROUND: Despite successful revascularization of ischemic extremities, multiorgan dysfunction syndrome develops in some patients. Mechanisms responsible for this are not known; however, the gastrointestinal tract has been implicated as a possible mediator. Our objective was to demonstrate increased intestinal mucosal permeability after bilateral hindlimb ischemia-reperfusion (I-R) in a rodent model. METHODS: Sixteen male Wistar rats were randomized either to 4 hours of bilateral hindlimb tourniquet ischemia and 24 hours of reperfusion (n = 8) or control groups (n = 8). The animals received 10 MuCi 51Cr-ethylenediaminetetraacetic acid (EDTA) by gavage, and excretion was measured in urine collected every 8 hours in 16 animals and every 4 hours in 8 animals. Arterial blood pressure was monitored continuously. Intravenous normal saline solution (3 ml/hr) with fentanyl (2 microgram/100 gm/hr) was continuously administered. Immediately before death complete blood count and levels of arterial lactate, creatinine, and urea were obtained. Mesenteric lymph nodes were harvested from the ileocecal region and cultured. Distal small bowel and proximal colon were preserved for histologic analysis. An additional 11 rats, six experimental and five control, were evaluated for mesenteric lymph node cultures only. RESULTS: Urinary excretion of 51Cr-EDTA was significantly greater in the I-R group between 0 and 8 hours (p < 0.02) and 8 to 16 hours (p < 0.0002) of reperfusion. This increase occurred as early as 4 to 8 hours of reperfusion (p < 0.0001). Urine volume in the I-R group was significantly reduced during 0 to 4 hours of reperfusion (p < 0.002). Hemoglobin and lactate level were significantly different in the I-R group. Leukocyte and platelet counts, levels of creatinine and urea, and colony counts from mesenteric lymph nodes were similar in I-R and control groups. Blinded histologic analysis of bowel segments did not reveal morphologic differences. CONCLUSIONS: Bilateral hindlimb I-R produces remote intestinal mucosal injury shown by significantly increased permeability to 51Cr-EDTA. Such increased mucosal permeability may be important in the development of multiorgan dysfunction syndrome in patients who sustain lower extremity I-R injury.

Animals↗
PubMed2002

Immune response, nitric oxide, autonomic dysfunction and stroke: a puzzling linkage on Trypanosoma cruzi infection.

Trypanosoma cruzi (T. cruzi) is a tissue parasite causing American trypanosomiasis or Chagas' disease (ChD) affecting, mostly, the cardiovascular and gastrointestinal systems. We have recently found that people infected by T. cruzi are also more prone to developing ischemic strokes than the general population, even without heart complications; the pathomechanism of it is not yet well understood. However, after infection occurs, immune response induces endothelial dysfunction due to an endothelial nitric oxide synthase (eNOS) inhibition and increased activity of inducible nitric oxide synthase (iNOS). These factors are active in inducing vasoconstriction and cerebral microvascular spasms, leading to ischemic stroke. In addition, patients with ChD, regardless of cardiopathy, also have autonomic dysfunction, all of which may enhance the risk of developing ischemic stroke. Moreover, the possibility that these neuroimmunomodulatory pathways are disturbed in patients with other types of stroke seems possible, and is worthy of investigation.

Animals↗
PubMed1996

Development of multiple organ dysfunction syndrome in critically ill patients with perforated viscus. Predictive value of APACHE severity scoring.

OBJECTIVE: To determine whether scoring on the Acute Physiology and Chronic Health Evaluation (APACHE) III at admission can predict the development of multiple organ dysfunction syndrome and mortality in critically ill surgical patients. DESIGN: Prospective, inception-cohort study. SETTING: Surgical intensive care unit of an urban, tertiary-care hospital. PATIENTS: One hundred fourteen critically ill patients with surgically treated perforated gastrointestinal viscus. INTERVENTIONS: Calculation of APACHE II and APACHE III scores 24 hours after admission to the surgical intensive care unit and serial quantitation of organ dysfunction for the duration of critical care according to two different predefined scoring systems. Patients were stratified by survival, the development of organ dysfunction, and colon vs noncolonic perforation. MAIN OUTCOME MEASURES: Hospital mortality, length of stay in the surgical intensive care unit, and the development of organ dysfunction or overt organ failure. RESULTS: The mean (+/- SEM) APACHE II and APACHE III scores were 17.4 +/- 0.6 (range, 6 to 37) and 59.0 +/- 2.2 (range, 15 to 141), respectively. The incidence of organ dysfunction was 73% (64% in survivors). All severity scores were identical for colon perforation and noncolonic perforation subgroups. Nonsurvivors invariably had organ dysfunction. Overall length of stay in the intensive care unit was 12.0 +/- 1.6 days (8.7 +/- 1.2 days for survivors and 22.7 +/- 5.0 days for nonsurvivors). The APACHE scores and organ dysfunction or failure scores were significantly higher in nonsurvivors, and APACHE scores were higher in survivors with organ dysfunction than in those without it. Significant linear relationships were identified for APACHE II vs APACHE III scores (R2 = .66) and for all four combinations of APACHE scores and organ dysfunction or failure scores (R2 = .43 to .52). By multivariate analysis of variance, independent predictors of organ dysfunction or failure were APACHE III, increased age, and a prolonged stay in the surgical intensive care unit, but not the type of perforation. Neither APACHE II or APACHE III predicted mortality independently. CONCLUSIONS: The development of multiple organ dysfunction syndrome correlated with higher APACHE III scores but was independent of the type of perforation. Only the development of overt multiple organ failure predicted death. Combined use of APACHE III and the multiple organ dysfunction score provides improved prediction of multiple organ dysfunction syndrome, but further enhancements are needed before prediction of outcome in individual patients is reliable.

APACHE↗