Human gut microbiome adopts an alternative state following small bowel transplantation

Small bowel transplants provide an exceptional opportunity for long-term study of the microbial ecology of the human small bowel. The ileostomy created at time of transplant for ongoing monitoring of the allograft provides access to samples of ileal effluent and mucosal biopsies. In this study, we used qPCR to assay the bacterial population of the small bowel lumen of 17 small bowel transplant patients over time. Surprisingly, the posttransplant microbial community was found to be dominated by Lactobacilli and Enterobacteria, both typically facultative anaerobes. This represents an inversion of the normal community that is dominated instead by the strictly anaerobic Bacteroides and Clostridia. We found this inverted community also in patients with ileostomies who did not receive a transplant, suggesting that the ileostomy itself is the primary ecological determinant shaping the microbiota. After surgical closure of the ileostomy, the community reverted to the normal structure. Therefore, we hypothesized that the ileostomy allows oxygen into the otherwise anaerobic distal ileum, thus driving the transition from one microbial community structure to another. Supporting this hypothesis, metabolomic profiling of both communities demonstrated an enrichment for metabolites associated with aerobic respiration in samples from patients with open ileostomies. Viewed from an ecological perspective, the two communities constitute alternative stable states of the human ileum. That the small bowel appears to function normally despite these dramatic shifts suggests that its ecological resilience is greater than previously realized.     

Response to oral β-carotene supplementation in patients with cystic fibrosis: a 16-month follow-up study

The aim of this study was to determine the efficacy of long-term oral β -carotene supplementation for correcting impaired β -carotene status in cystic fibrosis patients. Thirty-five patients (2.3-30.5 years of age) with coefficients of fat absorption of 46-96% (median 88%) received β -carotene 0.5 mg/kg daily and were followed over a 16-month treatment period. Baseline plasma β -carotene concentrations in patients (meanSD, 0.090.06 μ mol/1) were significantly lower than those of age-matched controls (0.860.56 μ mol/1) ( p < 0.0001). Concentrations increased rapidly and reached a plateau at or before 3 weeks that was maintained throughout the study period. Values obtained at 3 weeks (0.890.64 μ mol/1) were significantly higher ( p < 0.0001) than those at baseline and did not differ from controls. Plasma retinol and α -tocopherol concentrations increased during the observation period, but remained within normal ranges. Plasma retinyl palmitate, which was below the detection limit in all but one patient at baseline, did not increase. Thus oral β -carotene supplementation is effective and normalizes β -carotene status of cystic fibrosis patients without evidence of significant side effects. β -Carotene, cystic fibrosis, LDL-cholesterol, oral supplementation, retinol, α-tocopherol     

Quality of life after lobectomy for adult liver transplantation

INTRODUCTION: Adult-to-adult living donor liver transplants are being increasingly performed. Although considerable data are available on the quality of life after kidney donation, there is little comparable information on liver donors. METHODS: Between August 1998 and July 2000, 48 adults received liver grafts from living donors. At least 2 months after donation, donors were mailed a structured questionnaire and the standardized Medical Outcomes Study Short-Form Health Survey (SF-36), a generic measure assessing health-related quality of life outcomes using eight scales: mental health, emotional limits, vitality, social function, physical function, physical limits, pain, general health. RESULTS: Thirty donors (62.5%) responded at a mean of 280+/-157 days after donation. Fifteen (50%) of their recipients had major complications (two deaths, four retransplants, nine biliary complications). Regarding overall satisfaction, all said they would donate again. Compared to published U.S. norms (n=2474), our group of donors scored higher than the general population in seven of eight domains on the SF-36. Donors whose recipients had no complications scored significantly higher in mental health (P<0.007) and general health (P<0.008) compared with U.S. norms. Donors whose recipients had major complications scored significantly lower on the mental health scale than those with recipients without major complications. CONCLUSIONS: Donors did not regret their decision to donate; several felt the experience had changed their lives for the better. Donors scored as well as or better than U.S. norms in general health. Quality of life after donation must remain a primary outcome measure when we consider the utility of living-donor liver transplants.     

Long-term results with multimodal adjuvant therapy and liver transplantation for the treatment of hepatocellular carcinomas larger than 5 centimeters

OBJECTIVE: To determine the long-term results of liver transplantation for hepatocellular carcinoma (HCC) measuring 5 cm or larger treated in a multimodality adjuvant protocol. SUMMARY BACKGROUND DATA: Transplant has been established as a viable treatment of HCC measuring less than 5 cm, but the results for larger tumors have been disappointing. Several studies have shown promising preliminary results when combining transplant with preoperative transarterial chemoembolization and/or perioperative systemic chemotherapy in the treatment of advanced HCC that is not amenable to resection. However, follow-up in the studies has been limited and the number of patients has been small. METHODS: Beginning in October 1991, all patients with unresectable HCC measuring 5 cm or larger, as measured by computed tomography, were considered for enrollment in the authors' multimodality protocol. Entry criteria required that all patients be free of extrahepatic disease based on computed tomography scans of the chest and abdomen and bone scan and have a patent main portal vein and major hepatic veins on duplex ultrasonography. Patients received subselective arterial chemoembolization with mitomycin C, doxorubicin, and cisplatin at the time of diagnosis, repeated as necessary based on tumor response. Patients received a single systemic intraoperative dose of doxorubicin (10 mg/m(2)) before revascularization of the new liver and systemic doxorubicin (50 mg/m(2)) every 3 weeks as tolerated, for a total of six cycles, beginning on the sixth postoperative week. RESULTS: Eighty patients were enrolled; 37 were eventually excluded, due mainly to disease progression while on the waiting list, and 43 underwent liver transplant. Mean pathologic tumor diameter was 5.8 +/- 2.7 cm. Median follow-up of surviving transplanted patients was 55.1 +/- 24.9 months. There were two (4.7%) perioperative deaths. Median overall survival was significantly longer in transplanted patients (49.9 +/- 10.42 months) than in those who were excluded (6.83 +/- 1.34 months). Overall and recurrence-free survival rates in transplanted patients at 5 years were 44% and 48%, respectively. A tumor size larger than 7 cm and the presence of vascular invasion correlated significantly with recurrence. Recurrence-free survival at 5 years was significantly higher for the 32 patients with tumors measuring 5 to 7 cm (55%) than the 12 patients with tumors larger than 7 cm (34%). CONCLUSIONS: A significant proportion of patients with HCC measuring 5 cm or larger can achieve long-term survival after liver transplantation in the context of multimodal adjuvant therapy. Patients with tumors measuring 5 to 7 cm have significantly longer recurrence-free survival compared with those with larger tumors.     

Avoiding the boomerang: testing the relative effectiveness of antidrug public service announcements before a national campaign

OBJECTIVES: This study examined the relative perceived effectiveness of 30 antidrug public service announcements (PSAs) and assessed the extent to which judgments of effectiveness are related to judgments of realism, amount learned, and positive and negative emotional responses. METHODS: Data were obtained from 3608 students in grades 5 through 12 in 10 schools. The ethnically diverse sample was 50.8% male. Students in 5 experimental conditions viewed sets of 6 antidrug PSAs and filled out a brief evaluation questionnaire following each PSA. Those in the control condition viewed a non-drug-related television program. RESULTS: The relative perceived effectiveness of the 30 PSAs varied considerably. Sixteen were rated as significantly more effective, and 6 as significantly less effective, than the control program. Relative rated effectiveness was highly related to realism (r =.87), amount learned (r =.88), negative emotion (r =.87), and positive emotion (r = -.35). CONCLUSIONS: Evaluative research is necessary to prevent broadcast of PSAs that could have a negative impact. PSAs should point out the negative consequences of drug use behavior rather than telling adolescents to "just say no."     

Job satisfaction and job success as moderators of the self-esteem of people with mental illnesses

This study investigated job satisfaction and job success as moderators of the self-esteem of people with mental illnesses. Prior studies and models had produced contradictory findings so that the appropriateness of self-esteem as an outcome variable for psychiatric rehabilitation employment services was in doubt. Job satisfaction and success measures for 65 employed and 170 unemployed individuals with mental illnesses along with their work status and work status duration measures were combined in a single multiple regression analysis with self-esteem as the criterion. The job satisfaction and success measures were found to be significant and moderate level moderators of self-esteem for the combined sample and separately for the employed and unemployed samples. It appears that self-esteem varies with satisfaction and success with the work status and not with work status alone. These findings suggested that self-esteem was an appropriate and modifiable outcome measure for psychiatric rehabilitation services. Some practical, theoretical, and policy implications of these results were also discussed.     

Demonstration of electrical and anatomic connections between Marshall bundles and left atrium in dogs: implications on the generation of P waves on surface electrocardiogram

INTRODUCTION: The muscle bundles within the ligament of Marshall (LOM) are electrically active. The importance of these muscle bundles (Marshall bundle [MB]) to atrial activation and the generation of the ECG P wave is unclear. METHODS AND RESULTS: We used optical mapping techniques to study epicardial activation patterns in isolated perfused left atrium in four dogs. In another seven dogs, P waves were studied before and after in vivo radiofrequency (RF) ablation of the connection between coronary sinus (CS) and the LOM. Computerized mapping was performed before and after RF ablation. Optical mapping studies showed that CS pacing resulted in broad wavefronts propagating from the middle and distal LOM directly to the adjacent left atrium (LA). Serial sections showed direct connection between MB and LA near the orifice of the left superior pulmonary vein in two dogs. In vivo studies showed that MB potentials were recorded in three dogs. After ablation, the duration of P waves remained unchanged. In the other four dogs, MB potentials were not recorded. Computerized mapping showed that LA wavefronts propagated to the MB region via LA-MB connection and then excited the CS. After ablation, the activation of CS muscle sleeves is delayed, and P wave duration increased from 65.3 +/- 14.9 msec to 70.5 +/- 17.2 msec (P = 0.025). CONCLUSION: In about half of the normal dogs, MB provides an electrical conduit between LA free wall and CS. Severing MB alters the atrial activation and lengthens the P wave. MB contributes to generation of the P wave on surface ECG.