Emerging treatments in neurogastroenterology: a multidisciplinary working group consensus statement on opioid-induced constipation.

BACKGROUND: Opioids are effective for acute and chronic pain conditions, but their use is associated with often difficult-to-manage constipation and other gastrointestinal (GI) effects due to effects on peripheral µ-opioid receptors in the gut. The mechanism of opioid-induced constipation (OIC) differs from that of functional constipation (FC), and OIC may not respond as well to most first-line treatments for FC. The impact of OIC on quality of life (QoL) induces some patients to decrease or stop their opioid therapy to relieve or avoid constipation. PURPOSE: At a roundtable meeting on OIC, a working group developed a consensus definition for OIC diagnosis across disciplines and reviewed current OIC treatments and the potential of treatments in development. By consensus, OIC is defined as follows: 'A change when initiating opioid therapy from baseline bowel habits that is characterized by any of the following: reduced bowel movement frequency, development or worsening of straining to pass bowel movements, a sense of incomplete rectal evacuation, or harder stool consistency'. The working group noted the prior validation of a patient response outcome and end point for clinical trials and recommended future efforts to create treatment guidelines and QoL measures specific for OIC. Details from the working group's discussion and consensus recommendations for patient care and research are presented in this article.

Immunohistochemical expression and prognostic significance of oestrogen receptor-alpha, oestrogen receptor-beta, and progesterone receptor in stage 1 adult-type granulosa cell tumour of the ovary.

AIMS: To assess oestrogen receptor (ER)α, ERß, and progesterone receptor (PR) expression in stage I ovarian adult-type granulosa cell tumours (AGCTs) and correlate the findings with clinical outcome. METHODS: ERα, ERß and PR immunohistochemistry was performed on 56 primary, stage I AGCTs. Twelve cases (21%) recurred and hormone receptor staining was compared in the corresponding primary and metastatic tumours. RESULTS: All primary AGCTs expressed ERß and PR, usually with strong and diffuse staining, whereas only 20% of tumours were focally ERα positive. There was no correlation between ERα or PR expression and outcome. However, primary AGCTs with low ERß expression had a significantly higher risk of recurrence. In contrast, all metastatic tumours exhibited strong ERß staining. No relationship between ER staining and tumour morphology was identified but there was more consistent PR expression in cells at the tumour-stromal interface. CONCLUSIONS: Primary AGCTs typically show an ERα negative and ERß/PR positive immunophenotype. Low ERß expression is an adverse prognostic factor in primary AGCT but metastatic tumours often show up-regulation of ERß. Local microenvironmental factors may influence PR expression. Hormone receptor expression in AGCT may become increasingly relevant due to developments in selective therapy.

Histopathologic indicators of breast cancer biology: insights from population mammographic screening.

Histopathologic features of breast cancer such as tumour size, grade and axillary lymph node (LN) status variably reflect tumour biology and time. Recent evidence suggests that the biological character of breast cancer is established at an early stage and has a major impact on clinical course. The aim of this study was to distinguish the impact of biology on breast cancer histopathology by comparing features of breast cancers diagnosed following population mammographic screening with prevalent vs incident detection and screening interval. Central histopathology review data from 1147 cases of ductal in situ and/or invasive breast cancer were examined. Size, grade and LN status of invasive cancers were positively correlated (P < 0.001). Prevalent invasive cancers were larger (P < 0.001) and more likely to be LN positive (P = 0.02) than incident cases, but grade was not associated with screening episode (P = 0.7). Screening interval for incident cancers was positively associated with invasive cancer size (P = 0.05) and LN status (P = 0.002) but not grade (P = 0.1). Together, these data indicate that biology and time both impact on size and LN status of invasive breast cancer, but grade reflects biology alone. In view of the clinical importance of breast cancer biology, grade as its most direct indicator assumes particular significance.

Heavy contamination of operating room air by Penicillium species: identification of the source and attempts at decontamination.

Increased rates of nosocomial infection caused by filamentous fungi in immunocompromised patients prompted microbiologic surveillance of the central air handling systems in our hospital. During a 4-year period, Penicillium species were isolated from 47 patients, including two with surgical wound infections caused by Penicillium. Counts of Penicillium in operating room air were much higher (195 colony-forming units [CFU]/m3) than in 95% filtered corridor air (14.6 CFU/m3; p less than 0.01). Ventilation ducts and terminal units lined with fiberglass in the operating room air handling system were heavily contaminated by Penicillium; the fiberglass was also contaminated with Aspergillus species. Corrective measures included filter replacement and decontamination of the ventilation system with aerosolized chlorine solution. Although operating room air remained free of filamentous fungi during the next 7 months, contamination eventually recurred and required repeated decontamination. We believe that certification guidelines are highly desirable for hospital ventilation systems, especially if the system serves immunocompromised patients.

Relationship between colonization of hospital building with Legionella pneumophila and hot water temperatures.

Legionella pneumophila was isolated from four hospital buildings that maintained hot water storage temperatures at 43 to 45 degrees C. Two adjacent hospital buildings with negative cultures maintained temperatures at 58 to 60 degrees C.

Hemodilution and induced hypotension for insertion of a Harrington rod in a Jehovah's Witness patient.

The case of a 28-year-old Jehovah's Witness illustrates the feasibility of using a combined technique of induced hypotension and hemodilution to minimize the surgical loss of red blood cells during the insertion of a Harrington rod. A Swan-Ganz catheter with thermister tip was inserted to measure pulmonary arterial pressure, pulmonary arterial wedge pressure and cardiac output. Other intraoperative monitoring included continuous arterial pressure, electrocardiography, oropharyngeal temperature, esophageal stethoscope, arm-cuff blood pressure and urinary output from an indwelling Foley catheter. A total of 10 L of crystalloid was infused over a 2 1/2-hour period while hypotension was induced by intravenous nitroprusside and enflurane anesthesia. Hematocrit was diluted from 46% to 26% intraoperatively with an estimated surgical blood loss of 2,740 ml. The 24-hour postoperative hematocrit was 30% and recovery was uneventful. This method may be useful in any orthopedic procedure in which heavy blood loss is anticipated and the patient refuses transfusion of blood or blood products. However, the patient must be in good health and have an uncompromised cardiopulmonary system.

Cardiovascular responses to nitrous oxide exposure for two hours in man.

Cardiovascular responses to increasing (20, 40, and 60%) concentrations of nitrous oxide or nitrogen in oxygen for 15 minutes as well as responses to 2 hours of exposure to 60% nitrous oxide or nitrogen in oxygen were determined and compared in 30 healthy, supine, untrained volunteers who received no other drugs or medications. No concentration of nitrogen produced a significant change in any cardiovascular variable measured, nor did 20 and 40% N2O. Sixty percent nitrous oxide for 15 minutes significantly increased PaCO2, heart rate, stroke volume, cardiac output, mean arterial blood pressure, and central venous pressure. Inhalation of 60% nitrogen also produced no significant change in any cardiovascular variable. In contrast, inhalation of nitrous oxide for 2 hours transiently increased arterial blood pressure (at 15 minutes), heart rate (at 15 and 30 minutes), stroke volume (at 15, 30, and 45 minutes) and decreased systemic vascular resistance (at 15 minutes). Cardiac output significantly increased for the 1st hour of exposure to 60% nitrous oxide but returned to values similar to control (room air) during the 2nd hour. Prolonged inhalation of nitrous oxide resulted in a constant increase in PaCO2 and progressive but mild decreases in arterial pH and calculated base deficit but no change in dead space/tidal volume ratios. These findings demonstrate that nitrous oxide stimulates the cardiovascular system in supine, healthy, untrained volunteers but that the stimulation is transient. The data suggest that early stimulation of the cardiovascular system during nitrous oxide breathing may be related to central nervous system excitation secondary to incomplete anesthesia and/or an increase in PaCO2.