Lymphocytic colitis: a distinct clinical entity? A clinicopathological confrontation of lymphocytic and collagenous colitis

BACKGROUND AND AIMS: It is not known whether lymphocytic colitis and collagenous colitis represent different clinical entities or constitute part of a spectrum of disease. METHODS: Detailed clinical features and histological findings were compared in a large series of patients with confirmed lymphocytic and collagenous colitis. RESULTS: Histological diagnosis was confirmed in 96 patients with collagenous colitis and 80 with lymphocytic colitis. Twenty eight per cent of patients with collagenous colitis and 26% of patients with lymphocytic colitis had overlapping but less pronounced histological features. Both groups were equal in terms of age, use of aspirin and non-steroidal anti-inflammatory drugs, associated autoimmune conditions, arthritis, diarrhoea, and abdominal pain. The male:female ratio was 27:73 for collagenous colitis and 45:55 for lymphocytic colitis (p=0.013). Twenty five per cent of patients with collagenous colitis compared with 14% of patients with lymphocytic colitis were active smokers; only 8.3% of patients with collagenous colitis had stopped smoking compared with 23% of patients with lymphocytic colitis (p=0.013). Drug induced disease was suspected for ticlopidine (two collagenous colitis, four lymphocytic colitis) and flutamide (four lymphocytic colitis). Mean duration of symptoms before diagnosis was two months for lymphocytic colitis and four months for collagenous colitis. Overall prognosis was generally mild; 84% of patients with lymphocytic colitis and 74% of patients with collagenous colitis reported resolution or significant improvement (p=0.033). CONCLUSIONS: Collagenous and lymphocytic colitis are similar but not identical. Patients with lymphocytic colitis present somewhat earlier and are less likely to be active smokers. Symptoms are milder and more likely to disappear in lymphocytic colitis. Ticlopidine and flutamide should be added to the list of drugs inducing colitis.     

Normoalbuminuric diabetic kidney disease: a distinct entity?

International Journal of Diabetes in Developing Countries -     

Is heart failure in African Americans a distinct entity?

Heart failure remains a major health problem in the United States and is particularly problematic in the African American community where the disease exhibits excessive morbidity and mortality. Hypertension is a predominant etiology for heart failure among African Americans with an aggressive incidence of end-organ damage. Despite the advances in treatment of heart failure with neurohormonal attenuation, there appears to be inconsistency in the response of African Americans compared to Caucasians. This discordance with regard to response to treatment and etiology of heart failure between African Americans and Caucasians begets the question whether heart failure in African Americans is indeed a distinct clinical entity.     

First endoscopic-histologic follow-up in patients with body-predominant atrophic gastritis: when should it be done?

BACKGROUND: Body-predominant atrophic gastritis is considered a risk factor for gastric cancer and carcinoid. Timing of follow-up for patients with this disorder has not been defined. This study was undertaken to determine the optimal time for the first endoscopic/histologic follow-up in patients with body-predominant atrophic gastritis. METHODS: Forty-two patients with body-predominant atrophic gastritis were randomly assigned to 1 of 2 follow-up intervals: group A (n = 22) at 24 months and group B (n = 20) at 48 months. At baseline and follow-up patients underwent gastroscopy at which biopsies were obtained from the antrum and body for histopathology and evaluation for enterochromaffin-like cells. RESULTS: In group A patients, 2 antral hyperplastic polyps (9.1%) were present at baseline and 4 antral hyperplastic polyps (18.2%) were found at follow-up. In group B patients, baseline gastroscopy revealed 2 antral hyperplastic polyps (10%) and follow-up 2 antral hyperplastic polyps (10%) and 1 carcinoid tumor (5%) in the body. Atrophy and intestinal metaplasia scores in gastric body and antral mucosa in both groups did not change significantly between baseline and follow-up, except an increase in antral mucosa atrophy in group B patients (p = 0.02) was revealed. CONCLUSIONS: The results of this study indicate that performing the first follow-up in patients with body-predominant atrophic gastritis need not be earlier than at 4 years after diagnosis. This interval is satisfactory for detection of potential neoplastic lesions.     

Wheezy bronchitis in childhood: a distinct clinical entity with lifelong significance?

BACKGROUND: Historically, clinicians have recognized the existence of the clinical syndrome of childhood wheezy bronchitis. In the late 1960s, children with this syndrome were relabeled as having asthma, and the term wheezy bronchitis was abandoned. In a 1989 study of a cohort that originally had been studied in 1964, we reported that those who had childhood wheezy bronchitis had as adults attained lung function similar to that of healthy control subjects and had less significant symptoms than did those who had experienced childhood asthma, in whom lung function was reduced. In this study, we reexamined these subjects 12 years later to determine whether the improved outcome of the wheezy bronchitis group had been maintained. METHODS: In 2001, we followed up the 283 participants of the 1989 study, who were now aged 45 to 50 years. In interviews, respiratory symptoms and smoking status were assessed. Spirometry was measured. RESULTS: One hundred seventy-seven subjects (63%) completed the study. After adjusting for age, height, gender, socioeconomic status, smoking status, and number of pack-years smoked, the current FEV(1) in the childhood asthma group (mean, 2.45 L; 95% confidence interval, 2.29 to 2.62) was significantly lower than the wheezy bronchitis group (2.78 L, 95% confidence interval, 2.64 to 2.91; p < 0.01) and the control group (2.96 L; 95% confidence interval, 2.83 to 3.1; p < 0.01). The difference between the wheezy bronchitis group and the control subjects was not significant (p = 0.06). Between 1989 and 2001, both the childhood wheezy bronchitis group (p < 0.01) and the childhood asthma group (p = 0.01) had greater declines in FEV(1) than did the control group (asthma group decline, - 0.75 L [95% confidence interval, - 0.66 to - 0.84]; wheezy bronchitis group decline, - 0.75 L [95% confidence interval, - 0.68 to - 0.83]; control group decline, - 0.59 L [95% confidence interval, - 0.52 to - 0.67]). In 2001, the asthma group had more symptoms than did the wheezy bronchitis group (p < 0.01), who were more symptomatic than the control group (p < 0.01). CONCLUSION: Those with childhood wheezy bronchitis, having achieved normal lung function in earlier adulthood, now show a more rapid decline in lung function than did control subjects. If this rate of decline persists, these subjects may develop obstructive airways disease in later life.     

Idiopathic hemoptysis in pregnant women: A distinct entity?

In pregnant women, the reported cases of hemoptysis were most often mild and had an identified cause. Between November 2003 and January 2006, three pregnant women at 16-20 weeks gestation were admitted to our respiratory intensive care unit for massive hemoptysis. One of the women had experienced mild hemoptysis, considered as idiopathic, during her first pregnancy, with no recurrence until her second pregnancy. In all three cases, hemoptysis was massive. CT scan after iodine injection did not reveal any cause. Opacification of the bronchial artery showed hyperemia from abnormally dilated and tortuous bronchial arteries. Bronchial artery embolization (BAE) was performed in all three patients, successfully in two. Intravenous vasopressin was used as second-line treatment for recurrent bleeding after BAE in one patient. The women carried the pregnancy to term with delivery of healthy infants. Further complete investigation after the births did not identify any possible local (pulmonary) or general cause of bleeding in these three patients. Although these cases could be considered idiopathic, the close association with duration of pregnancy suggests the hemoptysis may be related to hormonal changes.     

Two cases of Schizophyllum asthma: is this a new clinical entity or a precursor of ABPM?

Background

There is a close link between fungal sensitization and asthma severity. Although Schizophyllum commune (S. commune, “suehirotake” in Japanese), one of the basidiomycetous (BM) fungi, is a fungus that can cause allergic bronchopulmonary mycosis (ABPM) and allergic fungal sinusitis (AFS), whether the fungus causes or sensitizes subjects to asthma is unclear.

Methods

The bronchial provocation test using S. commune antigen was performed in two asthmatics who had demonstrated positive skin reactions to the S. commune antigen, and low dose of itraconazole (50 mg/day) was prescribed as an adjunctive therapy for 2 weeks. The allergological features and clinical manifestations of these patients are herein evaluated and discussed.

Results

Case 1 was a 71-year-old female, and case 2 was a 69-year-old male. Both patients demonstrated positive reactions to the inhalation test. A diagnosis of AFS or ABPM was excluded in both patients because of the lack of a history of pulmonary infiltrates, central bronchiectasis, a history of expectoration of brown plugs or flecks, or sinusoidal findings. Although the efficacy of itraconazole in our cases was unclear, the elevated titer of the specific IgG-for S. commune in case 2 gradually decreased during the period of antifungal therapy.

Conclusions

The two patients described herein were diagnosed to have bronchial asthma caused by S. commune; so-called Schizophyllum asthma. S. commune may also be a causative fungal antigen of bronchial asthma.     

Gastric juice nitrite and vitamin C in patients with gastric cancer and atrophic gastritis: is low acidity solely responsible for cancer risk?

BACKGROUND: N-nitroso compounds are carcinogens formed from nitrite, a process that is inhibited by vitamin C in gastric juice. Helicobacter pylori infection has been reported to increase nitrite and decrease vitamin C in gastric juice. Therefore, susceptibility to gastric cancer in H. pylori-infected patients may be derived from increased N-nitroso compounds in gastric juice. However, most H. pylori-infected patients do not develop gastric cancer. OBJECTIVE: To investigate additional factors that may affect susceptibility to gastric cancer, we compared nitrite and vitamin C levels in gastric juice from H. pylori-infected patients with and without gastric cancer. METHODS: Serum and gastric juice were obtained from 95 patients undergoing diagnostic endoscopy, including those with normal findings, duodenal ulcer, gastric ulcer, atrophic gastritis and gastric cancer. Serum was analysed for H. pylori antibody, nitrate and nitrite, gastrin and pepsinogens; gastric juice was analysed for pH, nitrite and vitamin C. RESULTS: pH and nitrite levels were increased and vitamin C levels decreased in the gastric juice of patients with atrophic gastritis and gastric cancer compared with other patients. However, in patients with a similar gastric acidity (pH 5-8), nitrite concentrations in the gastric juice were significantly higher and vitamin C levels significantly lower in patients with gastric cancer than in those with atrophic gastritis. CONCLUSION: Although hypochlorhydria increases intraluminal nitrite and decreases intraluminal vitamin C, which increases the intraluminal formation of N-nitroso compounds, our results indicate that patients with gastric cancer may have additional factors that emphasize these changes.     

Chronic basophilic leukemia: a distinct clinico‐pathologic entity?

OBJECTIVE: We sought to better define a group of rare and poorly understood myeloproliferative disorders that are characterized by prominent chronic basophilia in the absence of the Philadelphia chromosome (Ph) or its molecular equivalent. METHODS: We screened our institution's electronic database from 1975 onwards, and identified four such cases. Clinical data and bone marrow pathology were carefully reviewed for these patients. RESULTS: Two patients had prominent manifestations of basophil mediator-release and another presented with pituitary dysfunction. Bone marrow examination uniformly revealed trilineage hyperplasia with basophilia and eosinophilia, dysplastic megakaryocytic hyperplasia, and the absence of megakaryocyte clustering. An abnormal pattern of atypical mast cells was noted in two cases. While disease palliation was effectively achieved with hydroxyurea for one patient, transformation to acute myeloid leukemia was eventually observed in this case. Another patient has achieved long-term disease-free survival after undergoing allogeneic stem cell transplantation. CONCLUSIONS: Our observations reveal a striking pathologic similarity among all four cases, and suggest this disease, which may be aggressive with the potential to transform into acute leukemia, to possibly represent a distinct clinico-pathologic entity (chronic basophilic leukemia).     

Pathogenesis of hypothyroidism-induced NAFLD: Evidence for a distinct disease entity?

Nonalcoholic fatty liver disease (NAFLD), the most common liver disease worldwide, may be associated with primary hypothyroidism. However, the pathogenesis underlying such an association is complex and not completely understood. Here, we specifically discuss the pathogenic mechanisms potentially involved in hypothyroidism-induced NAFLD. To this end, we summarize the general pathophysiology of thyroid hormones (TH). Next, we analyze the published data from rodent studies by discussing whether hypothyroid rats may develop NAFLD via hyperphagia; whether mitochondria become energetically more efficient; what the overall energy balance is and if diversion of fatty substrates occurs; and the latest advancements in molecular pathogenesis brought about by metabolomics, cell imaging, lipophagy, autophagy and genetically engineered mouse models. Moreover, we discuss the data published regarding humans on the pathogenic role of TH, metabolic syndrome and other risk factors in hypothyroidism-related NAFLD as well as the putative mechanisms underlying the development of NAFLD-related hepatocellular carcinoma in hypothyroidism. In conclusion, although many research questions still remain unanswered, the pathophysiology of hypothyroidism-induced NAFLD makes this a potentially curable and distinct disease entity. However, further studies are needed to better elucidate the underlying mechanisms, and to ascertain whether treatment with either TH or thyromimetic agents improves NAFLD.     

Acute myeloid leukemia with mutated nucleophosmin (NPM1): is it a distinct entity?

After the discovery of NPM1-mutated acute myeloid leukemia (AML) in 2005 and its subsequent inclusion as a provisional entity in the 2008 World Health Organization classification of myeloid neoplasms, several controversial issues remained to be clarified. It was unclear whether the NPM1 mutation was a primary genetic lesion and whether additional chromosomal aberrations and multilineage dysplasia had any impact on the biologic and prognostic features of NPM1-mutated AML. Moreover, it was uncertain how to classify AML patients who were double-mutated for NPM1 and CEBPA. Recent studies have shown that: (1) the NPM1 mutant perturbs hemopoiesis in experimental models; (2) leukemic stem cells from NPM1-mutated AML patients carry the mutation; and (3) the NPM1 mutation is usually mutually exclusive of biallelic CEPBA mutations. Moreover, the biologic and clinical features of NPM1-mutated AML do not seem to be significantly influenced by concomitant chromosomal aberrations or multilineage dysplasia. Altogether, these pieces of evidence point to NPM1-mutated AML as a founder genetic event that defines a distinct leukemia entity accounting for approximately one-third of all AML.