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PubMed2004

Diabetes mellitus and optic atrophy: a study of Wolfram syndrome in the Lebanese population.

Wolfram syndrome (WFS) is a rare hereditary neurodegenerative disorder also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). WFS seems to be a heterogeneous disease that has not yet been fully characterized in terms of clinical features and pathophysiological mechanisms because the number of patients in most series was small. In this study we describe 31 Lebanese WFS patients belonging to 17 families; this, to our knowledge, is the largest number of patients reported in one series so far. Criteria for diagnosis of WFS were the presence of insulin-dependent diabetes mellitus and optic atrophy unexplained by any other disease. Central diabetes insipidus was found in 87% of the patients, and sensorineural deafness confirmed by audiograms was present in 64.5%. Other less frequent features included neurological and psychiatric abnormalities, urodynamic abnormalities, limited joint motility, cardiovascular and gastrointestinal autonomic neuropathy, hypergonadotropic hypogonadism in males, and diabetic microvascular disease. New features, not reported in previous descriptions, such as heart malformations and anterior pituitary dysfunction, were recognized in some of the patients and participated in the morbidity and mortality of the disease. Genetic analysis revealed WFS1 gene mutations in three families (23.5%), whereas no abnormalities were detected in mitochondrial DNA. In conclusion, WFS is a devastating disease for the patients and their families. More information about WFS will lead to a better understanding of this disease and hopefully to improvement in means of its prevention and treatment.

Adolescent↗
PubMed2004

Benefit-risk assessment of tegaserod in irritable bowel syndrome.

Tegaserod is a new partial agonist of serotonin 5-HT4 receptors specifically developed for the treatment of nondiarrhoeal forms of irritable bowel syndrome (IBS). Among its various effects is the stimulation of the peristaltic reflex with its promotility action appearing to affect the whole length of the gastrointestinal tract. Tegaserod has been assessed in a number of international multicentre trials and its use leads to an improvement in abdominal pain and bowel dysfunction as well as global well-being, at the expense of remarkably few adverse effects. It is noteworthy that it also appears to improve bloating, a benefit that has not been previously reported for a medication used in IBS. The optimal dose is 6 mg twice daily and the advantage of tegaserod over placebo in different trials varies from 5-20% with the number needed to treat ranging from 5-15 depending on the time at which this effect is calculated during the course of a trial. Recent experience with other drugs acting on 5-HT receptors has focused attention on possible safety issues such as prolongation of the QTc interval on the electrocardiogram and ischaemic colitis. However, data from efficacy trials and studies specifically designed to address the safety of tegaserod have not revealed any evidence of cardiotoxicity or the potential for causing ischaemic colitis. Furthermore, investigation of possible interactions with other drugs such as warfarin or the oral contraceptive have not resulted in any prescribing restrictions. Inappropriate prescription of tegaserod to a subgroup of IBS patients for which the drug was not designed, does not appear to have any serious consequences. Most of the efficacy data on tegaserod has been accumulated in females, simply as a result of the failure to recruit adequate numbers of males or restriction of trials to females. There is therefore insufficient information to assess whether there might be any potential gender differences in responsiveness. For this reason, the drug is currently only licensed for use in females.

Animals↗
PubMed1999

Tolerability and patient compliance.

Currently available antidepressants interact with several types of receptors, which may explain both wanted and unwanted effects of these drugs. These effects are different and distinctive, and knowledge about them may help clinicians understand differences between compounds in terms of their tolerability profiles. Given roughly comparable efficacy, tolerability profile is the critical determinant in selecting an antidepressant medication for a particular patient. In addition, tolerability is inseparably linked to patient compliance, both in acute and long-term treatment, and ultimately to overall success of treatment. Refinement in pharmacologic profiles of all newly introduced antidepressants resulted in overall advantages in tolerability in comparison with older tricyclic compounds. However, differences in receptor interactions between antidepressants are directly reflected in tolerability (adverse event) profiles. Among new antidepressants, mirtazapine and the selective serotonin reuptake inhibitors share favorable overall tolerability and safety, especially with respect to low premature termination rates because of adverse events, cardiac safety, and safety in overdose. However, the different pharmacologic profile of mirtazapine is reflected in its different tolerability profile. Because of interactions with the histamine (H1) receptor, mirtazapine may be related to transient initial somnolence and weight gain in some patients. Its serotonin-2 (5-HT2)-blocking properties may account for lack of sexual dysfunction, insomnia, nervousness, and agitation. Mirtazapine's 5-HT3-blocking properties are unique among all currently available antidepressants and may account for lack of gastrointestinal adverse events.

Adrenergic alpha-Antagonists↗
PubMed2000

Pulmonary, gastrointestinal and liver vascular malformations in Rendu-Osler disease.

Hereditary hemorrhagic telangiectasia (HHT) is an angiodysplastic disorder transmitted in autosomal dominant fashion. This case report describes a 46-year-old woman with multiple arteriovenous malformations that eventually caused multiorgan failure. The diagnosis was made in the early childhood based on frequently recurring episodes of severe epistaxis. Telangiectases were found in the skin, the visible mucosal linings, gastrointestinal and bronchial mucosa and liver. Episodes of severe hemoptysis necessitated partial resection of the right lung middle lobe at the age of 22. Liver dysfunction associated with the primary disease was diagnosed by the characteristic clinical picture, laboratory findings and instrumental examinations including abdominal ultrasonography, upper endoscopy, liver CT venography.

Blood Vessels↗
PubMed1992

Cadmium, metallothionein and renal tubular toxicity.

Cadmium-induced nephrotoxicity develops at cadmium concentrations in the renal cortex of 10-300 micrograms/g wet weight. The actual concentration at which it develops depends on a number of factors, e.g., exposure route, chemical species of cadmium administered, rate of administration and simultaneous exposure to other metals. The role of these factors can be explained by a mechanism of cadmium nephrotoxicity in which both extracellular and intracellular metallothionein binding play an essential role. In reindeer used for human food, cadmium was shown to be bound to metallothionein-like proteins. If cadmium bound to such proteins enters the blood plasma via the gastrointestinal tract, this is of special toxicological significance. Metallothionein-bound cadmium in the plasma of experimental animals is efficiently transported to the kidney. Tubular dysfunction in the kidney following a normally tubulotoxic dose of cadmium bound to metallothionein was prevented by preinduction of metallothionein synthesis by small non-toxic doses of cadmium.

Animals↗
PubMed1991

[Clinical evaluation of imipenem/cilastatin sodium as a second line regimen in severe infections associated with hematologic disorders].

Imipenem/cilastatin sodium (IPM/CS), which has a broad spectrum of activity against both Gram-positive and -negative bacteria including methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, was used as the second choice for severe infections associated with hematological disorders. Sixty-five patients were treated with IPM/CS. Among them, 53 patients were evaluable for the clinical efficacy. Twelve patients were not evaluable due to the following reasons: 5 patients were treated with combinations of other regimens such as cefzonam, cefmenoxime, ciprofloxacin or gamma-globulin, 5 were patients to whom IPM/CS was administered as the first choice, and the remaining 2 patients were thought to be suffering not from febrile infections but from febrile tumor. Excellent responses were observed in 10 (18.9%) patients and good responses in 23 (43.4%) patients, with an overall rate of efficacy of 62.3%. The efficacy in septic patients was 75% (3/4), and that in patients whose peripheral granulocytes were continuously below 100/microliter was also 75% (6/8). Two patients who suffered from tumor fever and 5 patients who had received no chemotherapy before IPM/CS administration were included in the final evaluation of side effects. Side effects were observed in 16 patients (16/60, 26.7%). In a 61 years, female patient, a skin eruption was found 4 days after IPM/CS therapy was started. In 15 patients, mild gastrointestinal symptoms such as nausea and vomiting were identified within a few days after IPM/CS treatment was started. Abnormal laboratory data such as eosinophilia, liver dysfunction or renal dysfunction were also identified in 4 patients (4/60, 6.7%). Degrees of these abnormalities were very slight, however, and the continuation of treatment was not disturbed. These results indicated that IPM/CS was an effective second line regimen of chemotherapy for the treatment of severe infections in patients with hematological disorders.

Adult↗
PubMed2006

The effect of abdominal massage on bowel function in patients with spinal cord injury.

OBJECTIVES: To investigate the effect of abdominal massage on clinical aspects of bowel dysfunction and colonic transit time in patients with spinal cord injury. Twenty-four patients were placed on a standard bowel program (phase I), after which abdominal massage was added to the regimen (phase II). Parameters of gastrointestinal system function and colonic transit times were evaluated. DESIGN: Uncontrolled clinical study. RESULTS: Eleven (45.8%) of the 24 patients had abdominal distention, and 10 (41.7%) had fecal incontinence in phase I; corresponding results for phase II were three (12.5%) and four (16.7%) (P = 0.008 and 0.031, respectively). There were no significant differences between the proportions of patients with difficult intestinal evacuation or abdominal pain or in mean time required for bowel evacuation in phase I vs. phase II. The mean frequencies of defecation in phases I and II were 3.79 +/- 2.15 (2.75-4.55) and 4.61 +/- 2.17 (3.67-5.54) bowel movements per week, respectively (P = 0.006). Mean total colonic transit time decreased from 90.60 +/- 32.67 (75.87-110.47) hrs in phase I to 72 +/- 34.10 (58.49-94.40) hrs in phase II (P = 0.035). CONCLUSIONS: Abdominal massage has positive effects on some clinical aspects of neurogenic bowel dysfunction in patients with spinal cord injury.

Abdomen↗
PubMed1993

Cyclosporin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in immunoregulatory disorders.

Cyclosporin is a lipophilic cyclic polypeptide which produces calcium-dependent, specific, reversible inhibition of transcription of interleukin-2 and several other cytokines, most notably in T helper lymphocytes. This reduces the production of a range of cytokines, inhibiting the activation and/or maturation of various cell types, including those involved in cell-mediated immunity. Thus, cyclosporin has immunosuppressive properties, and has a proven place as first line therapy in the prophylaxis and treatment of transplant rejection. Cyclosporin has also been evaluated in a large range of disorders where immunoregulatory dysfunction is a suspected or proven aetiological factor, and this is the focus of the present review. In patients with severe disease refractory to standard treatment, oral cyclosporin is an effective therapy in acute ocular Behçet's syndrome, endogenous uveitis, psoriasis, atopic dermatitis, rheumatoid arthritis, active Crohn's disease and nephrotic syndrome. Concomitant low dose corticosteroid therapy may improve response rates in some disorders. The drug can be considered as a first line therapy in patients with moderate or severe aplastic anaemia who are ineligible for bone marrow transplantation, with the additional benefit of reducing platelet alloantibody titres. It may also be of considerable therapeutic benefit in patients with primary biliary cirrhosis, particularly those with less advanced disease. Limited evidence suggests cyclosporin is effective in patients with intractable pyoderma gangrenosum, polymyositis/dermatomyositis or severe, corticosteroid-dependent asthma. Indeed, the steroid-sparing effect of cyclosporin is a significant advantage in a number of indications. Furthermore, the drug has shown some efficacy in a wide range of other, generally uncommon disorders in which controlled clinical trials are lacking and/or are unlikely to be performed. Cyclosporin does not appear to be effective in patients with allergic contact dermatitis, multiple sclerosis or amyotrophic lateral sclerosis. It is only temporarily effective in patients with type I (insulin-dependent) diabetes mellitus and should not be used in this indication. To avoid relapse after control of active disease, patients should receive cyclosporin maintenance therapy at the lowest effective dosage. However, maintenance therapy appears to be of no benefit in patients with Crohn's disease and cyclosporin should be discontinued in these patients once active disease is controlled. Hypertrichosis, gingival hyperplasia, and neurological and gastrointestinal effects are the most common adverse events in cyclosporin recipients, but are usually mild to moderate and resolve on dosage reduction. Changes in laboratory variables indicating renal dysfunction are relatively common, although serious irreversible damage is rare.(ABSTRACT TRUNCATED AT 400 WORDS)

Arthritis, Rheumatoid↗
PubMed1981

The megacystis microcolon intestinal hypoperistalsis syndrome: report of a case.

An infant girl with the megacystis microcolon intestinal hypoperistalsis syndrome is reported. The presence of polyhydramnios and the absence of upper urinary tract abnormalities, differentiate this patient from similar cases previously reported. Although the etiology of this disease is unknown, partial success with the use of bethanechol suggests that the deranged intestinal motility may be related to dysfunction of the autonomic nerve endings of the gut.

Colon↗
PubMed1985

Medical problems encountered during rehabilitation of patients with head injury.

In the past few years patients having severe head trauma have survived in growing numbers, and it is likely that they will be more frequently seen on rehabilitation units. They display, in addition to direct structural damage, medical and neurologic problems which may be encountered during their rehabilitative phase. The purpose of this study will be to identify those medical and neurologic problems of consequence and describe their frequency of occurrence within a population of head injured patients. A consecutive series of 180 patients with head trauma undergoing rehabilitation were therefore reviewed, and the type and frequency of medical problems were noted. Neurologic, gastrointestinal, genitourinary, respiratory, cardiovascular, skin, musculoskeletal, and endocrinologic problems were encountered most frequently. Of these, ventricular dilatation, posttraumatic seizures, abnormal liver function tests, hypertension, thrombophlebitis, respiratory infections, periarticular heterotopic ossification, and pituitary-hypothalamic dysfunction are discussed in terms of their morbidity, clinical significance, and therapeutic approach. In many instances, these problems were not identified in the acute care hospital. Awareness of these potential conditions during the rehabilitation period can result in early detection and treatment.

Adolescent↗
PubMed1997

[Verotoxin induced hemolytic uremic syndrome: pathophysiology of neurological involvement].

Hemolytic uremic syndrome (HUS) is caused by endothelial cell damages. Ninety percent of children with HUS have verotoxin-producing E.coli infection. Verotoxin binds to glycolipid receptors globotriaosyl ceramide (Gb3), and the difference of Gb3 expression level in each organ would lead to specific organ involvement. The receptors are expressed in human renal cortex and medulla. The expression level of Gb3 in normal human brain has not been characterized completely. However involvement of central nervous system is a severe complication of HUS. Spreading of microvascular thrombosis caused by combined effects of lipopolysaccharide, cytokine, enhanced shear stress, and verotoxin would play a major role in the development of central nervous dysfunction.

Bacterial Toxins↗
PubMed1998

Fenfluramine and idiopathic pain: a serotonergic study in non-psychiatric patients with functional gastrointestinal disorder.

BACKGROUND: We investigated prolactin and cortisol response to fenfluramine in non-psychiatric patients with chronic functional gastrointestinal disorder (FGD). METHODS: Sixty milligrams fenfluramine was given orally to 55 subjects without any DSM-III axis-1 psychopathology and 29 healthy control subjects matched for sex and age. Serum cortisol and prolactin levels were analysed at base line and after 120, 180, and 240 min. RESULTS: Fenfluramine challenge induced an increase in mean prolactin and cortisol serum values in both patients and controls. Female patients showed lower base-line values of prolactin and higher delta values of cortisol than controls. Male patients and controls showed very uniform values for all variables. Length of illness history influenced delta cortisol values in both sexes. CONCLUSIONS: The cortisol and prolactin responses to fenfluramine suggest a psychobiologic gender difference with a possible stress-induced central serotonergic dysfunction in female patients but not in male patients. The close relationship between length of illness and delta cortisol may also suggest an increased state of distress in females with chronic functional gastrointestinal disorder.

Adult↗
PubMed1996

Gastrointestinal features of scleroderma.

Gastrointestinal involvement occurs in most patients with systemic sclerosis and is subclinical in about one third. Early pathology is characterized by vasculopathy, resulting in tissue ischemia and progressive dysfunction. Noninvasive esophageal studies using semisolid bolus scintigraphy are sensitive but lack specificity. Long-term treatment of reflux with high-dose proton pump inhibitors appears safe and effective for symptom relief and may prevent recurrence of esophagitis and stricture. Dyspepsia may result from gastroparesis and antral distension. Gastric antral vascular ectasia is a vascular manifestation, and bleeding may be controlled endoscopically. Prokinetic agents effective in pseudoobstruction include metoclopramide, domperidone, cisapride, octreotide, and erythromycin. Patients with intestinal neuropathy or response to bolus octreotide are more probable long-term responders. The combination of octreotide and erythromycin may be particularly effective in systemic sclerosis. The combination of cisapride and erythromycin may cause serious cardiac arrhythmia and is contraindicated. Omeprazole may predispose to small intestinal bacterial overgrowth. Malabsorption not responding to antibiotic therapy should be investigated with small-bowel biopsy to rule out more unusual causes. Pneumatosis cystoides intestinalis may be due to excessive hydrogen production by intestinal bacteria altering the partial pressure of nitrogen in the intestinal wall. In selected cases, surgery for intestinal failure is an option with resection or bypass of affected segments or placement of enterostomy tubes for feeding or decompression. Careful preoperative characterization of intestinal segments is required.

Esophageal Diseases↗