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Coordinating care for children with Turner syndrome.

Turner syndrome is a systemic disease requiring a multi-system management approach. This includes attention to the endocrine system, cardiovascular system, renal system, gastrointestinal system, ears, eyes, skeletal system, and skin, as well as to the psychology of the patient and the family. The primary care physician is central to the care of these patients. In addition to anticipating, diagnosing, and treating the various problems that may arise in patients with Turner syndrome, the primary care physician must coordinate the fairly large healthcare team needed for optimal care.

Adolescent↗

Poisoning with calcium channel blockers--a case report and review of the literature.

The incidence of poisoning with calcium channel blockers, accidental or intentional, has increased in recent years, associated with more frequent use. We present a clinical case of bradycardia and shock of unknown cause, which came to be revealed a poisoning by 3240 mg of slow-release diltiazem, managed with temporary transvenous pacing and dopamine in high concentration. We make a review of the cardiovascular manifestations of the three classic calcium channel blockers: verapamil, diltiazem and nifedipine; namely, hypotension, rhythm and conduction disturbances. We point out the late appearance of the beginning of manifestations with the use of slow releasing formulations. The toxicity by calcium channel blockers can lead to a wide variety of manifestations in the central nervous system, gastrointestinal system, endocrine-metabolic, hematologic and respiratory systems. There is a high clinical suspicion when the following factors are present: hypotension with bradycardia, mental state disturbances, lactic acidosis, hyperglycemia, sinus pauses and refractory shock. Treatment is based on general measures of intoxication support, decreasing the drug absorption and improvement of cardiac function. The bradyarrhythmias are corrected with the use of intravenous calcium, glucagon, atropine and pacemaker. If the intoxication causes depression of cardiac contractility, the use of calcium or/and glucagon is indicated. If there is refractoriness with these measures, catecholamines should be employed. There are alternative and adjuvant drugs such as amrinone, insulin-glucose, 4-aminopyridine and calcium entry promoters. Charcoal hemoperfusion can be useful in the overdose of sustained release preparations, but hemodialysis is unworthy of therapeutical interest.

Aged↗

[Creatine kinase (CK)].

Creatine kinase is a key enzyme for energy metabolism of contraction and relaxation in skeletal muscle. This enzyme also correlated to mitochondrial oxidative phosphorylation. Distribution of this enzyme is quite wide, including skeletal muscle, myocard, central nervous system, and smooth muscle. Creatine kinase has three main isoenzymes; CK-MM, CK-MB, and CK-BB. Mitochondrial isoenzyme (CKm) is the fourth isoenzyme migrating electrophoretically toward the cathode. Moreover serum creatine kinase isoenzyme (mainly CK-MB and CK-BB) and lesions in the myocard, skeletal muscle, central nervous system, gastrointestinal system, renal and urogenital systems, or acute psychosis, intoxication, pregnancy, labor, and cord blood are also explained. A compendium on CK-BB is also done.

Biomarkers↗

Unusual manifestations of Mycoplasma pneumoniae infection in children.

Mycoplasma pneumoniae infection is no longer a benign condition it was originally thought to be. Many extrapulmonary manifestations affecting major organ systems like the central nervous system, cardiovascular system, haematological system, gastrointestinal system, musculoskeletal system and renal system have been described. Early recognition of these manifestations is often difficult and serological diagnosis may not be helpful. Three patients with large pleural effusions, encephalitis, hemiplegia, hepatitis, autoimmune haemolytic anaemia and renal failure are discussed to highlight the many varied presentations associated with this infection.

Child↗

Lithium acetate gastrointestinal diffusion system. Part 1: Lithium acetate single-unit gastrointestinal diffusion system: preparation and release rate studies.

The gastrointestinal diffusion system (GDS), containing lithium acetate (1), releases the drug by a controlled source of diffusion energy. The unit can possibly be used for all soluble drugs in which solubility is independent from the pH of the gastrointestinal contents as is the case with 1. The one-compartment unit is obtained by tabletting the drug and coating the tablets with a membrane of cellulose acetate to which soluble porofores-gum arabic, sodium chloride, 1-are added. When the pore-creating substance is dissolved out of the coating, there remains a porous film, which controls the rate of release of the drug. The release characteristics depend on membrane composition and mass. The systems reported here provided for zero-order drug delivery in vitro.

Acetates↗

Lithium acetate gastrointestinal diffusion system. Part 2: Lithium acetate multi-unit gastrointestinal diffusion system: preparation and release rate studies.

The method of obtaining the multi-unit gastrointestinal diffusion system (m-GDS), containing lithium acetate, consists in encapsulating the lithium acetate in a form of microballs and thereafter coating the resulting microballs with a porous membrane which controls the diffusion rats of the drug. For the coating, a water-insoluble polymer (cellulose acetate) and two types of polymer-modifying agents (cetyl alcohol and shellac) were used. In this paper in vitro studies of drug release from the unit in relation to the microballs' coating and mass, and exposed surface area of the capsules are presented. Most in vitro systems provide zero-order dry delivery by appropriate selection of manufacturing parameters.

Cellulose↗

Have gastrointestinal nematodes outwitted the immune system?

Gastrointestinal (GI) nematodes are incredibly successful parasites. Choosing to live in an exposed extracellular niche, in confrontation with a potentially hostile environment, their persistent, chronic lifestyle is persuasive evidence in itself for their profound ability to modulate their hosts' immune response. Modulation is essential to avoid their own destruction but also subtly balanced to avoid compromising host survival. This review describes the early circumstantial evidence that gave clues to the immunomodulatory capabilities of the GI nematodes, the roles that T regulatory cells and alternatively activated macrophages play in this immunomodulation and provides examples of the types of specific parasite-derived factors that are known to modulate host immunity, potentiating parasite survival.

Animals↗

Quality of life and calcium channel blockade with nifedipine GITS versus amlodipine in hypertensive patients in Spain. Gastrointestinal Therapeutic System.

OBJECTIVE: Compliance with hypertension treatment is affected by treatment-related factors (complexity, side effects), efficacy and compound-specific effects that impact on quality of life. This study examined the differences in quality of life produced by two once-daily calcium channel blockers using different delivery systems: nifedipine gastrointestinal therapeutic system (GITS) and amlodipine. DESIGN: This was a double-blind, double-dummy, randomized clinical trial comparing nifedipine GITS (30 mg) and amlodipine (5 mg) for 24 weeks following a placebo run-in. Clinical, laboratory evaluations and quality-of-life data were assessed at screening, baseline randomization and three times during active therapy. SETTING: The study was conducted in 13 medical clinics in Spain. PATIENTS: The sample comprised 430 screened and 356 randomized patients with mild to moderate hypertension (diastolic blood pressure 95-114 mmHg). MAIN OUTCOME MEASURES: Change in systolic and diastolic blood pressure and in health-related quality of life were the main outcome measures. RESULTS: There were no significant differences between active treatment groups in the blood pressure changes (systolic blood pressure: nifedipine GITS -15.5 mmHg; amlodipine -15.7 mmHg). Spontaneous adverse events consistent with calcium channel blockage were not different. The nifedipine GITS group improved in all quality-of-life measures except Sexual Symptom Distress and showed a significantly greater improvement than amlodipine in overall Quality of Life (P< 0.05), General Perceived Health (P < 0.026) and its subscale Vitality (P < 0.019). The amlodipine group declined in overall Quality of Life, General Perceived Health, Vitality and Sleep Disturbance, and significantly in Sexual Symptom Distress (P < 0.045). However, this group improved in self-reported Cognitive Functioning (P=0.036), Mental Acuity (P < 0.005) and Detachment/disorientation (P=0.01). CONCLUSIONS: These results suggest compound-specific effects on quality of life that may be due to differences in the delivery system. Nifedipine GITS is short-acting (2 h half-life) and is delivered continuously over a 24 h period, while amlodipine has a half-life of 40 h, which may produce more sustained low-level effects. While a more beneficial profile was observed for nifedipine, amlodipine demonstrated potential positive effects on cognitive functioning.

Adolescent↗

[Clinical characteristics of 143 Chinese HIV/AIDS patients].

OBJECTIVE: To investigate the clinical characteristics of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients in China. METHODS: Totally 143 HIV/AIDS patients who were first diagnosed in Peking Union Medical College Hospital form January 1988 to April 2006 were enrolled in this study. Clinical characteristics were retrospectively analyzed. RESULTS: Among 143 HIV/ AIDS patients, 57 patients had no clinical symptoms and were confirmed by routine examinations; 86 patients had clinical symptoms, including fever (n = 50), weight loss (n = 18), and discomforts involving respiratory system (n = 34), gastrointestinal system (n = 16), and derma and mucosa (n = 17). Opportunistic infections (OIs) such as pneumocystis jiroveci pneumonia (PCP) (n = 27), oropharyngeal candidiasis (n = 16), tuberculosis (n = 15) , and cytomegalovirus (CMV) infection (n = 9) were also observed in patients whose CD4 + T cell counts were less than 200/mm3. Most CMV infection and cryptococcal meningitis occurred in patients whose CD4 + T cell counts were less than 100/mm3. CD4 + T cell count was negatively correlated with plasma viral load (r = -0.420, P = 0.001). CONCLUSIONS: Fever, dyspnea, and weight loss are the most common symptoms in the patients of this study. The respiratory system, gastrointestinal system, derma and mucosa are the most commonly affected areas by OIs, and PCP is the most common OI. The occurrence of OIs corelates with CD4 + T cell count.

AIDS-Related Opportunistic Infections↗

[Relation between cardiovascular and gastrointestinal neuropathy in diabetics].

BACKGROUND: The presence of autonomic neuropathy impairs the quality of life (orthostatic hypotension, impotence, gastroparesis) or endangers the life of diabetics (sudden death, unawareness of hypoglycemia). The purpose of the investigation was: 1. To assess the presence of the autonomic neuropathy of the cardiovascular and the gastrointestinal systems and their mutual relationship. 2. To assess the relationship of found autonomic neuropathy and the subjective symptoms which are typical to affected particular systems (cardiovascular, gastrointestinal, genitourinary, sudomotor systems and the syndrome of unawareness of hypoglycemia). METHODS AND RESULTS: The group comprised of 25 type 1 diabetic patients (12 women and 13 men) mean age 40.5 +/- 11.6 (range 21-57 years) with a mean duration of diabetes of 17.8 +/- 7.9 (range 4-35 years), treated with intensified insulin regimens. The cardiovascular autonomic neuropathy was automatically examined by the VariaPulse TF 3 computer system. Scintigraphy was used to investigate the gastric emptying time of 99mTc labelled rice. The information about the subjective symptoms we collected from the questionnaire. For statistic analysis we used Spearmen correlations and ANOVA. RESULTS: 1. A statistically significant correlation was found between the presence of the autonomic neuropathy of cardiovascular and gastrointestinal systems (r = 0.634, p < 0.0007). 2. We didn't find any relation among the cardiovascular autonomic neuropathy and the subjective symptoms of cardiovascular system, respectively the gastrointestinal neuropathy (impair gastric emptying) and the subjective symptoms of gastrointestinal system. We found a significant correlation between cardiovascular and gastrointestinal neuropathy and erectile dysfunction (r = 0.48, p < 0.0078), (r = 0.42, p < 0.0388) and with the syndrome of hypoglycemia unawareness (r = 0.49, p < 0.0057), (r = 0.52, p < 0.0075). CONCLUSIONS: The evidence of the cardiovascular autonomic neuropathy is warning signal for the affected autonomic neuropathy in other systems which are more complicated for diagnostic. The subjective symptoms don't correlate with the presence of the visceral neuropathy.

Adult↗

Effects of gastrointestinal nematode infection on the ruminant immune system.

Gastrointestinal (GI) nematodes of ruminants evoke a wide variety of immune responses in their hosts. In terms of specific immune responses directed against parasite antigens, the resulting immune responses may vary from those that give strong protection from reinfection after a relatively light exposure (e.g. Oesophagostomum radiatum) to responses that are very weak and delayed in their onset (e.g. Ostertagia ostertagi). The nature of these protective immune responses has been covered in another section of the workshop and the purpose of this section will be to explore the nature of changes that occur in the immune system of infected animals and to discuss the effect of GI nematode infections upon the overall immunoresponsiveness of the host. The discussion will focus primarily on Ostertagia ostertagi because this parasite has received the most attention in published studies. The interaction of Ostertagia and the host immune system presents what appears to be an interesting contradiction. Protective immunity directed against the parasite is slow to arise and when compared to some of the other GI nematodes, is relatively weak. Although responses that reduce egg output in the feces or increase the number of larvae undergoing inhibition may occur after a relatively brief exposure (3-4 months), immune responses which reduce the number of parasites that can establish in the host are not evident until the animal's second year. Additionally, even older animals that have spent several seasons on infected pastures will have low numbers of Ostertagia in their abomasa, indicating that sterilizing immune responses against the parasite are uncommon. In spite of this apparent lack of specific protective immune responses, infections with Ostertagia induce profound changes in the host immune system. These changes include a tremendous expansion of both the number of lymphocytes in the local lymph nodes and the number of lymphoid cells in the mucosa of the abomasum. This expansion in cell numbers involves a shift away from a predominant classic T cell population (CD2 and CD3 positive), to a population where T cell percentages are decreased and B cells (immunoglobulin-bearing) and gamma-delta cells are increased. At the same time the expression of messenger RNAs for T cell cytokines (IL2, IL4, IL10 and gamma-interferon) is changed to that of increased expression of IL4 and IL10 and decreased expression of IL2 and perhaps of gamma-interferon. The reasons for these changes remain to be elucidated, but it is evident that the lack of protective immune responses is not the result of a poor exposure of the host to parasite products, or to the stomach being an immunoprivileged site. In fact, a superficial look at the responses elicited indicates that Ostertagia induces responses (the so-called TH2 mediated responses) that are widely considered to be the type of responses necessary for protection against GI nematodes. There are many factors that could lead to this apparent lack of immunity in the face of a strong stimulation of immune responses including: (1) the elicitation of suboptimal responses; (2) the failure of the abomasum to function as an efficient effector organ; (3) active evasion of the functional immune response by the parasite; and (4) that these classic responses are not protective in this particular ruminant-parasite system and that novel protective mechanisms may be required. The strong stimulation of the host gut immune system by Ostertagia and perhaps by other GI nematode infections, raises questions about the potential effects of such infections on the overall well-being of the host. A number of authors have indicated that Ostertagia infections may diminish the host's ability to mount subsequent immune responses to antigenic challenges such as vaccination against other infectious organisms. In addition, recent studies have indicated that infections with GI nematodes may result in increased circulatory levels of stress-related hormo

Animals↗

Gastrointestinal patch systems for oral drug delivery.

Gastrointestinal patch systems with integrated multifunctions could surmount the challenges associated with conventional drug delivery. Several gastrointestinal patch systems provide bioadhesion, drug protection and unidirectional release. This combination of function could improve the overall oral bioavailability of large molecules that can currently be delivered only by injection, for example, epoetin-alpha and granulocyte-colony-stimulating factor, which are commonly used to treat chemotherapy-associated anemia and leukopenia, respectively. Furthermore, self-regulated release and cell-specific targeting provide additional 'smart' characteristics to this innovative therapeutic platform.

Administration, Oral↗

Comparison of glucan detection and galactomannan enzyme immunoassay in gastrointestinal and systemic murine candidiasis.

Mouse models of systemic and gastrointestinal infection with the yeast Candida albicans were used to investigate the ability of a commercial mannan antigen enzyme immunoassay and a commercial (1-->3) beta-D-glucan limulus assay to detect systemic infection and to differentiate between colonization and infection. Both assays were positive in all i.v. infected mice and negative in all uninfected control mice. In gastrointestinal infection both tests were positive whenever organ cultures were positive. In colonized mice with no detectable dissemination, there were mostly negative results with the glucan assay whereas the mannan assay was positive or intermediate in all colonized mice. Therefore, in the mouse model used, glucan detection appeared to be superior for differentiation between colonization and dissemination.

Animals↗

Prospective evaluation of the gastrointestinal tract in patients with iron deficiency and no systemic or gastrointestinal symptoms or signs.

BACKGROUND: Although endoscopic evaluation of the gastrointestinal tract is commonly performed to evaluate iron deficiency, little data is available regarding the underlying causes, yield of evaluation, and long-term outcome for those in whom gastrointestinal and systemic symptoms and signs are absent. METHODS: In- or out-patients seen by the gastroenterology consultative service at a large inner-city hospital over a 56-month period were considered eligible for the study when iron deficiency (serum ferritin <50 ng/mL) was documented. Exclusion criteria included: any gastrointestinal or systemic symptoms/signs, radiographic or endoscopic examinations of the gastrointestinal tract within 3 and 5 years, respectively, or obvious source of blood loss. Patients underwent colonoscopy and if no lesions other than carcinoma were found, upper endoscopy was then performed with a pediatric colonoscope. RESULTS: Fifty-two patients were evaluated (mean age, 66 +/- 13 years; range, 20 to 89 years; 32 men/20 women). At the time of evaluation, the mean (+/-SD) hematocrit was 25% +/- 7% (range, 14% to 42%). Overall, 23 patients (44%; 95% CI 30% to 59%) had an identifiable gastrointestinal lesion considered the cause of iron deficiency, including: colonic carcinoma, 11 (21%); colonic and/or esophagogastric/duodenal vascular ectasias, 9 (17%); and gastric carcinoma, colonic polyposis, and colonic ulcers in 1 patient each. Long-term follow-up (median 24 months, range 2 to 63 months) identified only 1 patient with a cause found (colonic carcinoma), and in this patient, complete colonoscopy was not technically possible at the time of initial evaluation. There were no clinical or laboratory features that distinguished patients with an etiology for iron deficiency to the idiopathic group. CONCLUSIONS: Approximately half of patients with iron deficiency in whom gastrointestinal or systemic signs or symptoms are absent have an underlying gastrointestinal lesion. Nevertheless, despite a thorough endoscopic evaluation, some patients will have no etiology found; the prognosis for these patients is excellent.

Adult↗

Efficacy, safety, and dose-response characteristics of glipizide gastrointestinal therapeutic system on glycemic control and insulin secretion in NIDDM. Results of two multicenter, randomized, placebo-controlled clinical trials. The Glipizide Gastrointestinal Therapeutic System Study Group.

OBJECTIVE: To investigate the efficacy, safety, and dose-response characteristics of an extended-release preparation of glipizide using the gastrointestinal therapeutic system (GITS) on plasma glucose, glycosylated hemoglobin (HbA1c), and insulin secretion to a liquid-mixed meal in NIDDM patients. RESEARCH DESIGN AND METHODS: Two prospective, randomized, double-blind, placebo-controlled, multicenter clinical trials were performed in 22 sites and 347 patients with NIDDM (aged 59 +/- 0.6 years; BMI, 29 +/- 0.3 kg/m2; known diabetes duration, 8 +/- 0.4 years) were studied. Each clinical trial had a duration of 16 weeks with a 1-week washout, 3-week single-blind placebo phase, 4-week titration to a fixed dose, and 8-week maintenance phase at the assigned dose. In the first trial, once-daily doses of 5, 20, 40, or 60 mg glipizide GITS were compared with placebo in 143 patients. In the second trial, doses of 5, 10, 15, or 20 mg of glipizide GITS were compared with placebo in 204 patients. HbA1c, fasting plasma glucose (FPG), insulin, C-peptide, and glipizide levels were determined at regular intervals throughout the study. Postprandial plasma glucose (PPG), insulin, and C-peptide also were determined at 1 and 2 h after a mixed meal (Sustacal). RESULTS: All doses of glipizide GITS in both trials produced significant reductions from placebo in FPG (range -57 to -74 mg/dl) and HbA1c (range -1.50 to -1.82%). Pharmacodynamic analysis indicated a significant relationship between plasma glipizide concentration and reduction in FPG and HbA1c over a dose range of 5-60 mg, with maximal efficacy achieved at a dose of 20 mg for FPG and at 5 mg for HbA1c. PPG levels were significantly lower, and both postprandial insulin and C-peptide levels significantly higher in patients treated with glipizide GITS compared with placebo. The percent reduction in FPG was comparable across patients with diverse demographic and clinical characteristics, including those with entry FPG > or = 250 mg/dl, resulting in greater absolute decreases in FPG and HbA1c in patients with the most severe hyperglycemia. Despite the forced titration to a randomly assigned dose, only 11 patients in both studies discontinued therapy because of hypoglycemia. Glipizide GITS did not alter lipids levels or produce weight gain. CONCLUSIONS: The once-daily glipizide GITS 1) lowered HbA1c, FPG, and PPG over a dose range of 5-60 mg, 2) was maximally effective at 5 mg (using HbA1c) or 20 mg (using FPG) based on pharmacokinetic and pharmacodynamic relationships, 3) maintained its effectiveness in poorly controlled patients (those with entry FPG > or = 250 mg/dl), 4) was safe and well tolerated in a wide variety of patients with NIDDM, and 5) did not produce weight gain or adversely affect lipids.

Adult↗

[Detection of H-ras and K-ras in tumors of gastrointestinal-pancreatic system].

The Gastro-Entero-Pancreatic System (GEP) defined a group of highly differentiated neuroendocrine tumors (Insulinomas, Gastrinomas, PP-omas, Somatostatinomas, Carcinoids). In this kind of tumors the multistage carcinogenesis is really unknown. Activated ras oncogenes could play an important role in initiation or process of carcinogenesis in different human cancers. The purpose of our study was to determe if H-ras or K-ras play a role in the carcinogenesis of GEP tumors. 20 paraffin embedded tumor tissues (1 Vipom, 1 Somatostatinom, 10 Carcinoids, 1 Gastrinoma, 4 livermetastasis of a Carcinoid, 3 Insulinomas) were analysed immunohistologic of H-ras and K-ras oncogene protein expression. Immunohistologic investigations showed a H-ras expression in 65% (13/20). K-ras protein could detected in 10% (2/20). On the basis of these data H-ras oncogene expression could play a role in the multistage carcinogenesis of GEP tumors.

Carcinoid Tumor↗