Coffee drinking and colorectal cancer and its subsites: A pooled analysis of 8 cohort studies in Japan

Coffee is a rich source of bioactive compounds that have potential anticarcinogenic effects. However, it remains unclear whether coffee drinking is associated with colorectal cancer. Also, despite different etiological factors involved in gut physiology, few studies have investigated this association by anatomical site of the lesion. To address these issues, this study examined the association between coffee drinking and colorectal cancer in a pooled analysis from 8 cohort studies conducted in Japan. Among 320,322 participants followed up for 4,503,274 person‐years, 6,711 incident colorectal cancer cases were identified. Study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using the random effects model. Coffee drinking was not materially associated with colorectal cancer risk in men or women (pooled HR 0.92, 95% CI 0.82–1.03 in men and pooled HR 0.90, 95% CI 0.76–1.07 in women). Analysis by subsite showed a lower risk of colon cancer among female drinkers of ≥3 cups coffee/day (pooled HR 0.80, 95% CI 0.64–0.99). There was no such association in men. Coffee drinking was not associated with risk of rectal cancer in men or women. Results were virtually the same among never smokers except for an increased risk of rectal cancer associated with frequent coffee consumption. Coffee drinking may be associated with lower risk of colon cancer in Japanese women.     

Retinopathy of prematurity (1) birth weight, gestational age and maximum PaCO2

The eyes of neonates who were premature or had been exposed to increased ambient oxygen from May 1979 to February 1985 were examined. Twenty out of 256 infants were found to have retinopathy of prematurity (ROP) of stage 3 or worse in at least one eye. Using uivariate statistics (chi-square analysis or the Wilcoxon test), the variables representing the maximum arterial carbon dioxide tension (PaCO2), birth weight and gestational age were found to be significantly associated with ROP. It is recommended to maintain PaCO2 values under 50 mmHg, especially in less mature newborns (less than 1,300g in birth weight or 210 days of gestational age).     

The presence of Hypodense Eosinophilic Granulocytes in Allergic Children.

To evaluate hypodense eosinophils known very little in children, peripheral blood from asthmatic, allergic-non-asthmatic and non-allergic children was evaluated by density Percoll gradient techniques. A significantly higher number of eosinophils were hypodense in asthmatic children (n = 24) compared with allergic non-asthmatic (n = 10) and non-allergic children (n = 13), namely 484 ± 348 cells/40 μl versus 113 ± 109 and 39 ± 61 (p <0.001) respectively. We also observed by light and electron microscopy that the hypodense eosinophils of asthmatic children were swollen and their granules were dispersed, but the normodense eosinophils of the same patient were small and compact. In three cases of severe asthmatic attack, hypodense eosinophils found on admission decreased in number after intravenous aminophylline therapy and relief of symptoms. Moreover, a decreased number of hypodense eosinophils were found in seven cases of allergic children (p < 0.05) after 2 weeks of antiallergic drug treatment associated with relieved symptoms. From these data we concluded that the presence of hypodense eosinophils in the peripheral blood might be related to the development of allergic symptoms and might participate in the pathophysiology of allergic diseases in children.     

Direct nerve crossing with the intercostal nerve to treat avulsion injuries of the brachial plexus

One hundred seventy-nine patients with root avulsion brachial plexus injuries were treated with direct nerve crossing with the intercostal nerve and 159 cases were followed more than 1 1/2 years after the operation. When suture was done to the musculocutaneous nerve, 90% of 10 children who had operation within 7 months of injury and 81.8% of 110 adults, younger than 40 years with operation within 6 months of injury regained grade 3 or 4 elbow flexion power. This direct method seems to produce better results than those of nerve crossing, which uses intermediary nerve grafts.     

Enterovirus Infection, CXC Chemokine Ligand 10 (CXCL10), and CXCR3 Circuit: A Mechanism of Accelerated ��-Cell Failure in Fulminant Type 1 Diabetes

OBJECTIVE

Fulminant type 1 diabetes is characterized by the rapid onset of severe hyperglycemia and ketoacidosis, with subsequent poor prognosis of diabetes complications. Causative mechanisms for accelerated β-cell failure are unclear.

RESEARCH DESIGN AND METHODS

Subjects comprised three autopsied patients who died from diabetic ketoacidosis within 2–5 days after onset of fulminant type 1 diabetes. We examined islet cell status, including the presence of enterovirus and chemokine/cytokine/major histocompatibility complex (MHC) expressions in the pancreata using immunohistochemical analyses and RT-PCR.

RESULTS

Immunohistochemical analysis revealed the presence of enterovirus-capsid protein in all three affected pancreata. Extensive infiltration of CXCR3 receptor–bearing T-cells and macrophages into islets was observed. Dendritic cells were stained in and around the islets. Specifically, interferon-γ and CXC chemokine ligand 10 (CXCL10) were strongly coexpressed in all subtypes of islet cells, including β-cells and α-cells. No CXCL10 was expressed in exocrine pancreas. Serum levels of CXCL10 were increased. Expression of MHC class II and hyperexpression of MHC class I was observed in some islet cells.

CONCLUSIONS

These results strongly suggest the presence of a circuit for the destruction of β-cells in fulminant type 1 diabetes. Enterovirus infection of the pancreas initiates coexpression of interferon-γ and CXCL10 in β-cells. CXCL10 secreted from β-cells activates and attracts autoreactive T-cells and macrophages to the islets via CXCR3. These infiltrating autoreactive T-cells and macrophages release inflammatory cytokines including interferon-γ in the islets, not only damaging β-cells but also accelerating CXCL10 generation in residual β-cells and thus further activating cell-mediated autoimmunity until all β-cells have been destroyed.Fulminant type 1 diabetes is characterized by abrupt onset of severe hyperglycemia and ketoacidosis preceded by flu-like symptoms including fever, abdominal pain, and headache (1–3). Due to the rushed clinical course in most cases, patients with fulminant type 1 diabetes are sometimes untreated until becoming comatose and/or entering a critical, life-threatening state (4). Endogenous insulin secretion is completely abolished over time and diabetic microangiopathies develop over a short duration (5,6). The mechanisms underlying the aggressive and rapid destruction of β-cells have remained one of the major questions regarding this subtype of type 1 diabetes. However, in situ human data on affected islets and pancreas and possible mechanisms have been completely lacking for fulminant type 1 diabetes.Viral infection with subsequent immunological mechanisms represents one of the leading candidates for destruction of β-cells in fulminant type 1 diabetes (3,7). Some studies on the mouse model of lymphocytic choriomeningitis virus–induced type 1 diabetes have demonstrated that islet β-cells can be destroyed as follows: within 1 day after virus infection, CXC chemokine ligand 10 (CXCL10) (8), a key chemoattractant for activated T-cells and macrophages, is produced in β-cells and secreted from islets (9). Activated T-cells bearing the receptor for CXCL10, named CXCR3 (8), infiltrate and accumulate in islets secreting CXCL10 (10). Accumulated T-cells at the islets then destroy β-cells through cell-mediated mechanisms (11). With this mechanism, CXCL10 is necessary and sufficient for accelerated T-cell response with complete β-cell destruction and resulting type 1 diabetes (10,12,13). We have recently found that serum CXCL10 levels are increased at the onset of fulminant type 1 diabetes, suggesting a crucial role of the CXCL10-CXCR3 axis in the aggressive β-cell destruction in this syndrome (14). We therefore examined in situ status with regard to enterovirus infection, CXCL10-CXCR3 axis, major histocompatibility complex (MHC) molecule expression, and islet dysfunction in pancreata from patients with fulminant type 1 diabetes who died due to diabetic ketoacidosis within 2–5 days after outset of flu-like symptoms. Our in situ findings for affected pancreata provide new insights into understanding the pathogenesis of and developing interventional strategies against human type 1 diabetes.