Roles of the jejunum and ileum in the first-pass effect as absorptive barriers for orally administered tacrolimus

BACKGROUND: The immunosuppressant tacrolimus shows poor and variable bioavailability following oral administration in clinical use. Recently, the hepatic and intestinal metabolisms, or first-pass effect, of tacrolimus have been suggested to be responsible for its bioavailability. In the present study, we investigated the respective contribution of the jejunum and ileum to the first-pass effect of tacrolimus in rats. METHODS: The metabolism of tacrolimus in everted sacs of the duodenum, jejunum, and ileum was examined. Tacrolimus was administered intravenously or intraintestinally to sham-operated, jejunum-resected, or ileum-resected rats. Blood samples were collected over a 240-min period, and whole-blood tacrolimus concentrations were measured by semiautomated microparticle enzyme immunoassay. The pharmacokinetic parameters of tacrolimus in each group were estimated. RESULTS: The metabolic activity of tacrolimus appeared to be the highest in the everted sacs of the duodenum. The bioavailability of tacrolimus in the jejunum- or ileum-resected rats was higher than that in sham-operated controls. On the other hand, the time to peak concentration in the jejunum-resected rats was about twofold slower than those in ileum-resected and sham-operated rats. CONCLUSIONS: These results suggested that the first-pass effect of tacrolimus in the small intestine shows regional differences and the extraction of tacrolimus in the small intestine consists of the amount of extraction in the jejunum and ileum. In addition, the ileum rather than the jejunum as a graft of segmental small bowel transplantation would be useful to avoid the adverse effects of tacrolimus.     

Glenoid shape in atraumatic posterior instability of the shoulder

Glenoid shape is related closely to shoulder stability and its abnormality is thought to affect the humeral head position in shoulders with atraumatic instability. However, it is unclear how the glenoid shape in shoulders with atraumatic instability is different from the glenoid shape in normal shoulders. The current authors investigated glenoid shape of 45 healthy individuals (20 males and 25 females; average age, 22 years) and 20 patients with atraumatic posterior instability with multidirectional laxity (six males and 14 females; average age, 19 years) using three-dimensional magnetic resonance imaging. The tilting angles of the glenoid bone were measured in five consecutive planes perpendicular to the long axis of the glenoid and cross sections were divided into three types (concave, flat, convex). In healthy individuals, the average tilting angles from the bottom to the top of the glenoid bone were 3.0 degrees +/- 3.6 degrees, 1.0 degrees +/- 3.2 degrees, -1.0 degrees +/- 2.0 degrees, -2.3 degrees +/- 3.9 degrees, and -6.9 degrees +/- 3.7 degrees anteriorly, and tilting angles of patients were -6.1 degrees +/- 4.0 degrees, -4.0 degrees +/- 3.6 degrees, -4.8 degrees +/- 3.2 degrees, -5.5 degrees +/- 2.7 degrees, and -7.5 degrees +/- 3.1 degrees. The type of cross section also was different on the bottom plane where the concave shape accounted for 78% of healthy individuals whereas it accounted for 0% of patients. The loss of tilting angles and concavity of the inferior glenoid would correlate with the direction of the head translation in posterior instability.     

Clinical effectiveness research in managed-care systems: lessons from the Pediatric Asthma Care PORT. Patient Outcomes Research Team

OBJECTIVE: To highlight the unique challenges of evaluative research on practice behavior change in the "real world" settings of contemporary managed-care organizations, using the experience of the Pediatric Asthma Care PORT (Patient Outcomes Research Team). STUDY SETTING: The Pediatric Asthma Care PORT is a five-year initiative funded by the Agency for Healthcare Research and Quality to study strategies for asthma care improvement in three managed-care plans in Chicago, Seattle, and Boston. At its core is a randomized trial of two care improvement strategies compared with usual care: (1) a targeted physician education program using practice based Peer Leaders (PL) as change agents, (2) adding to the PL intervention a "Planned Asthma Care Intervention" incorporating joint "asthma check-tips" by nurse-physician teams. During the trial, each of the participating organizations viewed asthma care improvement as an immediate priority and had their own corporate improvement programs underway. DATA COLLECTION: Investigators at each health plan described the organizational and implementation challenges in conducting the PAC PORT randomized trial. These experiences were reviewed for common themes and "lessons" that might be useful to investigators planning interventional research in similar care-delivery settings. CONCLUSIONS: Randomized trials in "real world" settings represent the most robust design available to test care improvement strategies. In complex, rapidly changing managed-care organizations, blinding is not feasible, corporate initiatives may complicate implementation, and the assumption that a "usual care" arm will be static is highly likely to be mistaken. Investigators must be prepared to use innovative strategies to maintain the integrity of the study design, including: continuous improvement within the intervention arms, comanagement by researchers and health plan managers of condition-related quality improvement initiatives, procedures for avoiding respondent burden in health plan enrollees, and anticipation and minimization of risks from experimental arm contamination and major organizational change. With attention to these delivery system issues, as well as the usual design features of randomized trials, we believe managed-care organizations can serve as important laboratories to test care improvement strategies.     

Cortical involvement for action imitation of hand/arm postures versus finger configurations: an fMRI study

We used fMRI to study the human imitation of hand/arm postures and finger configuration, subjects imitated hand/arm postures in the hand condition, and they imitated finger configurations in the finger condition. Compared with the control condition, only the finger condition showed significant activation in Broca's area and symmetrical activation in the bilateral inferior parietal lobes, while the hand condition showed left lateralised superior parietal activation pattern. Our findings suggest that Broca's area might be involved more in the imitation of finger configuration than that of hand/arm postures. The result of parietal activation patterns was fully consistent with formerly reported clinical findings, and the relationship between the lesion laterality and the patients' perfomance of hand/finger action imitation.     

Cancer anorexia-cachexia syndrome: current issues in research and management

Cachexia is among the most debilitating and life-threatening aspects of cancer. Associated with anorexia, fat and muscle tissue wasting, psychological distress, and a lower quality of life, cachexia arises from a complex interaction between the cancer and the host. This process includes cytokine production, release of lipid-mobilizing and proteolysis-inducing factors, and alterations in intermediary metabolism. Cachexia should be suspected in patients with cancer if an involuntary weight loss of greater than five percent of premorbid weight occurs within a six-month period. The two major options for pharmacological therapy have been either progestational agents, such as megestrol acetate, or corticosteroids. However, knowledge of the mechanisms of cancer anorexia-cachexia syndrome has led to, and continues to lead to, effective therapeutic interventions for several aspects of the syndrome. These include antiserotonergic drugs, gastroprokinetic agents, branched-chain amino acids, eicosapentanoic acid, cannabinoids, melatonin, and thalidomide--all of which act on the feeding-regulatory circuitry to increase appetite and inhibit tumor-derived catabolic factors to antagonize tissue wasting and/or host cytokine release. Because weight loss shortens the survival time of cancer patients and decreases performance status, effective therapy would extend patient survival and improve quality of life.     

Aneurysmal fibrous histiocytoma showing transition from factor XIIIa-positive to -negative

A 39-year-old woman visited us because of a subcutaneous induration on her forehead of 7 months' duration. The tumor was tender, firm, and colored blue-black. Microscopically, the tumor was composed of fibroblastic and histiocytic cells showing no atypicality. In some part intra- or extracellular haemosiderin was diffusely seen. There were some blood-filled spaces of varying size without endothelial lining. From these findings, this case was diagnosed as aneurysmal fibrous histiocytoma (AFH), a variant form of dermatofibroma. Immunohistochemical analysis showed that factor XIIIa-positive histiocytic cells were distributed in the area without haemosiderin, but such cells were absent in the area with its deposition. Furthermore, the cells near the blood-filled space showed transition from factor XIIIa-positive to -negative, suggesting that the stromal instability induced by the attenuation of factor XIII may lead the formation of the blood-filled spaces in AFH.     

Early carcinoma of the gastric cardia in Japan: is it different from that in the West?

BACKGROUND: The incidence of adenocarcinoma of the gastric cardia has increased recently in the West. However, in Japan, most patients with gastric carcinoma have disease that is situated in the body and the distal stomach. The objectives of this study were to compare the clinicopathologic findings of patients with early gastric carcinoma (EGC) arising at the cardia and those with carcinoma in more distal parts of the stomach, then comparing the findings with those from patients with carcinoma of the gastric cardia in the West. METHODS: Three thousand one hundred forty-four patients with EGC who underwent surgical resection between 1962 and 1997 at the National Cancer Center Hospital in Tokyo were studied. Seventy patients with EGC at the cardia were compared with those who had lesions in the middle and lower parts of the stomach. The body mass index (BMI), smoking, and drinking were evaluated using all patients with cardia EGC and 344 patients in a matched cohort in the latter group. RESULTS: Seventy patients had an EGC located just at the cardia, whereas 2796 patients had lesions in the lower two-thirds of the stomach. The former lesions were different from those in the distal two-thirds of the stomach: More often, they were of an elevated type (34% vs. 14%, respectively, they were histologically well differentiated in 89% (vs. 59%), and there were more submucosal tumors (53% vs. 41%). The BMI, smoking, and drinking in the two groups were not different. The incidence of Barrett esophagus and gastroesophageal reflux disease (GERD) in patients with EGC were 2. 9% (2 of 70 patients) and 5.7% (4 of 70 patients), respectively. CONCLUSIONS: There were many significant differences in clinicopathologic characteristics between patients with carcinoma of the cardia and patients with carcinoma of the distal stomach in Japan. The incidence of early cardia carcinoma was very low in Japan, and obesity, smoking, drinking, Barrett esophagus, or GERD were not related to its occurrence, in contrast to reports in the West.     

Magnetic resonance imaging of endolymphatic space in patients with sensorineural hearing loss: comparison between fluctuating and idiopathic sudden sensorineural hearing loss

Abstract

Background: Recently, 3-Tesla magnetic resonance imaging (MRI) after an intravenous gadolinium injection has been used to describe the endolymphatic space (ELS).

Objectives: This study described the histopathological differences between idiopathic sudden sensorineural hearing loss (ISSNHL) and fluctuating sensorineural hearing loss (FSNHL) by examining the ELS. Additionally, the relationship between the affected cochlear and vestibular ELS/total fluid space (TFS) volume ratio and the duration from the onset to MRI in patients with FSNHL were evaluated.

Material and methods: This study included 205 individuals without vertigo: 47 controls, 94 with ISSNHL, and 64 with FSNHL. The TFS and ELS volumes were measured and the ELS/TFS volume ratios (%) were evaluated.

Results: The cochlear and vestibular ELS/TFS volume ratios of the affected ear in patients with FSNHL were significantly higher than that in those with ISSNHL. There was no correlation between the duration from FSNHL onset to the MRI scan in the affected cochlea and vestibule.

Conclusion and significance: There were differences in the form of hearing fluctuation and the extended ELS volume between ISSNHL and FSNHL. ISSNHL cases with severe ELS extension were likely to change to FSNHL.     

Acute aortic dissection with new massive cerebral infarction - a successful repair with ligature of the right common carotid artery.

It remains unclear whether or not the infarcted brain caused by aortic dissection should be reperfused when an emergency operation is needed for aortic arch dissection. A 64-year-old woman presented with severe back pain and syncope with a sudden left hemiplegia. CT scan demonstrated an aortic dissection of the entire aorta, obstruction of the right common carotid artery by extended aortic dissection, cerebral infarction of the right middle cerebral artery territory, brain edema and pericardial effusion. Though she was unable to communicate with us, she underwent an emergent aortic arch replacement and ligature of the right common carotid artery nine hours after the onset of stroke, when massive cerebral infarction was established. She survived the operation and regained full consciousness. When brain infarction was established by extended aortic dissection in emergent aortic surgery, concomitant ligature of the responsible artery to the brain infarction may be allowed for avoiding cerebral damage leading to brain death.