Search

Fanconi anemia is an autosomal recessive disease resulting in bone-marrow failure, phenotypical abnormalities and predisposition to malignancy. The authors reviewed 257 clinical and neuropathology results from the International Fanconi Anemia Registry at The Rockefeller University. Two patients had hydrocephalus and ventriculoperitoneal shunts. Of 15 neuropathology reports, 10 found CNS abnormalities, with the most common--ventriculomegaly--seen in six, two of whom required shunts. Aqueductal stenosis, agenesis of the corpus callosum and septum pellucidum, and holoprosencephaly were found. The authors conclude that neurological derangements are probably more common in Fanconi anemia than previously recognised. Fanconi anemia cells in culture are highly sensitive to oxidative stress and alkylating agents; Fanconi anemia may provide a model for a genetic disorder potentially predisposing to environmental insults.

Irritable bowel syndrome (IBS), which is characterized by abdominal pain or discomfort that is associated with altered bowel function (diarrhea, constipation, or alteration between the two), is one of several gastrointestinal motility disorders. IBS affects up to one in five North Americans, mostly women. The reason(s) this disorder is reported more often by women than men, and the role of gender and biological sex in the prevalence, pathophysiology, symptom presentation, impact on quality of life, diagnosis, and response to treatment, are poorly understood. The purpose of this article is to review the evidence surrounding the roles of gender and biological sex in IBS.

To determine the prevalence of Helicobacter pylori (H pylori) infection in North American patients with immune thrombocytopenic purpura (ITP) and the effect of H pylori eradication on the platelet count, a prospective study was performed. Seventy-four patients aged 10 years and older (mean age of 41 years) with chronic ITP and a platelet count below 60 × 109/L were enrolled. H pylori infection was found in 22% of patients by means of a breath test and could not be predicted by gastrointestinal symptoms. H pylori–positive patients (52.5 years of age) were older than H pylori–negative patients (38.5 years of age; P = .0035). Fifteen of the 16 H pylori–positive patients were treated and the bacteria was eradicated in 14 (93%). After 3 months, a significant response (platelet count > 50 × 109/L and doubling the initial count) was observed in only one patient. After a median follow-up of 11.5 months, none of the 14 patients had responded. Ten H pylori–negative patients treated with the same regimen also did not increase their platelet counts. In conclusion, unlike several previous reports, this study does not implicate H pylori in the pathogenesis of ITP since the prevalence of H pylori infection was low and eradication of H pylori did not positively influence the course of the ITP.

The differential diagnosis of nausea and vomiting is extensive and the underlying cause can be difficult to diagnose. Treatment of nausea and vomiting also can be unsatisfactory because the available pharmacotherapy does not correct the fundamental underlying pathophysiologic abnormalities. In contrast, the diagnosis of nausea and vomiting of pregnancy generally is straightforward. Almost 80% of women have some degree of nausea in the first trimester of pregnancy, and the diagnosis of pregnancy is established easily by the patient or physician. The spectrum varies from mild nausea to hyperemesis gravidarum. Various treatment approaches are addressed.

Gastroesophageal reflux disease is a complex, multifaceted disorder affecting a large proportion of the US population. Its management is based on the principle of optimal antisecretory therapy, mainly with proton pump inhibitors (PPIs). The optimal treatment outcome is complete symptom relief, which can be achieved with optimal use of PPIs. PPI treatment requires an understanding of the pharmacology of these agents as well as their clinical efficacy, strengths, and weaknesses. This paper reviews the pharmacology of PPIs, the principles of optimal dosing, nocturnal gastric acid breakthrough and its clinical importance, and a treatment approach to gastroesophageal reflux disease using these agents.

Irritable bowel syndrome (IBS) is a difficult disease to treat because of its ill-defined triggers, variable clinical course, and unpredictable myriad of symptoms of varying severity. Both doctors and patients are frustrated by the insidious nature of IBS--a nonlethal disorder that destroys lives, relationships, and careers. Traditional therapies are sometimes effective in mild disease but are often self-limiting because they focus primarily on individual symptoms. A combination of lifestyle and diet modifications, pharmacologic agents, and therapeutic interventions is usually necessary to address the multiple symptoms characteristic of IBS. One of the major advancements in the treatment of patients with IBS has been the development of US Food and Drug Administration--approved serotonergic therapeutics that specifically target the underlying causes of IBS and provide multisymptom relief by improving gastrointestinal function. Although they are controversial, alternative treatment approaches that target normalization of intestinal bacterial microflora may be helpful for some patients in whom intestinal bacterial overgrowth is present. Patients who have co-existing pelvic floor dysfunction may benefit from physical therapy. Overall, treatment approaches for IBS should address multisymptom relief and improvement of overall patient well-being.

Irritable bowel syndrome with constipation (IBS-C) and chronic constipation are 2 common gastrointestinal motility disorders that place a substantial burden on patients and society. Symptoms of both disorders are chronic, sometimes severe, and often respond poorly to treatment with traditional approaches, resulting in reduced quality of life, polypharmacy, and frequent healthcare utilization. Because structural, physical, or biochemical markers cannot be used to identify either disorder, diagnosis is symptom-based. In the absence of alarm features suggestive of organic disease or secondary causes of symptoms, these disorders can be positively and confidently diagnosed. In general, traditional agents used to treat patients with constipation target only a single symptom, and do not provide adequate relief of symptoms in the majority of IBS-C patients. Although patients with mild constipation symptoms may respond to treatment with fiber and laxatives, others with moderate-to-severe symptoms may require additional therapies and/or referral to a specialist for further evaluation. The advent of novel serotonergic agents has rejuvenated the therapeutic approach to patients with IBS-C and chronic constipation.

Irritable bowel syndrome (IBS) is one of several highly prevalent, multi-symptom gastrointestinal motility disorders that have a wide clinical spectrum and are associated with symptoms of gastrointestinal dysmotility and visceral hypersensitivity. Symptom overlap and comorbidity between IBS and other gastrointestinal motility disorders (eg, chronic constipation, functional dyspepsia, gastroesophageal reflux disease), with gastrointestinal disorders that are not related to motility (eg, celiac disease, lactose intolerance), and with somatic conditions (eg, fibromyalgia, chronic fatigue syndrome), are frequent. The clinical associations and pathophysiologic links between IBS and these disorders continue to be explored. This review discusses overlapping symptoms and comorbidity of IBS with select gastrointestinal and non-gastrointestinal disorders and attempts to identify commonalities among these conditions.

Irritable bowel syndrome genophenomics: correlation of serotonin-transporter polymorphisms and alosetron response

Irritable bowel syndrome is difficult to treat because of poorly defined pathophysiology, lack of diagnostic marker, and until recently, limited pharmacotherapy. After diagnosis, treatment includes diet and behavior modifications, along with pharmacologic treatment for mild disease and severe cases.

We have identified six new cases of Fanconi's anaemia (FA) who had pregnancies, and reviewed 11 others from the literature. At least 110 FA females have reached 16 years of age or more, of whom 15% became pregnant. There were a total of 26 pregnancies, resulting in 19 births and 18 surviving children. Anaemia and/or thrombocytopenia worsened during pregnancy in 10 patients, but five subsequently improved: seven had no haematological problems. Seven of the FA patients who had pregnancies died subsequently from cancer, and two from thrombocytopenic bleeding 3 and 20 years later. There were no peripartum deaths. Pregnancy in FA is clearly possible, with increased risks that are manageable from both the haematological and the obstetric aspects.