Classification of surgical causes of and approaches to the chronically failing ileoanal pouch.

BACKGROUND: Although there are various surgical causes of and therapeutic approaches to the chronically failing ileoanal pouch (PF), cases are often detailed without distinguishing the exact cause and corresponding treatment. The aim of our study was to classify causes of PF and corresponding surgical treatment options, and to establish efficacy of surgical approach per cause. METHODS: This retrospective study included all consecutive adult patients with chronic PF surgically treated at our tertiary hospital between July 2014 and March 2021. Patients were classified according to a proposed sub-classification for surgical related chronic PF. Results were reported accordingly. RESULTS: A total of 59 procedures were completed in 50 patients (64% male, median age 45 years [IQR 34.5-54.3]) for chronic PF. Most patients had refractory ulcerative colitis as indication for their restorative proctocolectomy (68%). All patients could be categorized according to the sub-classification. Reasons for chronic PF were septic complications (n = 25), pouch body complications (n = 12), outlet problems (n = 11), cuff problems (n = 8), retained rectum (n = 2), and inlet problems (n = 1). For these indications, 17 pouches were excised, 10 pouch reconstructions were performed, and 32 pouch revision procedures were performed. The various procedures had different complication rates. Technical success rates of redo surgery for the different causes varied from 0 to 100%, with a 75% success rate for septic causes. CONCLUSIONS: Our sub-classification for chronic PF and corresponding treatments is suitable for all included patients. Outcomes varied between causes and subsequent management. Chronic PF was predominantly caused by septic complications with redo surgery achieving a 75% technical success rate.

Magnetic resonance imaging after ligation of the intersphincteric fistula tract for high perianal fistulas in Crohn's disease: a retrospective cohort study.

AIM: Ligation of the intersphincteric fistula tract (LIFT) is increasingly being used for surgical closure of high perianal fistulas in Crohn's disease. Currently, data on postoperative MRI findings are scarce, although they are considered important for assessing healing and recurrence. Our aim, therefore, was to evaluate fistula characteristics on MRI and their relationship with clinical outcomes after LIFT. METHOD: Consecutive Crohn's patients treated with LIFT between 2007 and 2018 who underwent baseline and follow-up MRI were retrospectively included. MRIs were scored by two radiologists according to characteristics based on the original and modified Van Assche indices. MRI findings, with emphasis on fibrosis, and the relationship with clinical healing, re-interventions and recurrences are described. RESULTS: Twelve patients were included [four men, median age 34 (interquartile range 28-39) years]. Follow-up MRI was performed at a median of 5.5 months (interquartile range 2.5-6.0) after LIFT. At baseline, all patients showed a tract with predominantly granulation tissue, which changed to predominantly fibrotic in seven (in three of whom it was completely fibrotic). All patients with a (predominantly) fibrotic tract had clinical closure and no re-interventions or recurrences during long-term follow-up. In contrast, of the five patients with persisting granulation tissue, two reached clinical healing, two needed re-intervention and one had a recurrence. CONCLUSION: Markedly decreased fistula activity can be observed on MRI after LIFT. The majority of patients develop a predominantly fibrotic tract relatively soon after LIFT without clinical recurrence, suggesting a highly effective therapy. Unfavourable clinical outcomes were only present in patients with persisting granulation tissue, indicating the potential prognostic value of MRI.

The Influence of Body Contouring Surgery on Weight Control and Comorbidities in Patients After Bariatric Surgery.

INTRODUCTION: A considerable number of patients experience some long-term weight regain after bariatric surgery. Body contouring surgery (BCS) is thought to strengthen post-bariatric surgery patients in their weight control and maintenance of achieved improvements in comorbidities. OBJECTIVES: To examine the impact of BCS on long-term weight control and comorbidities after bariatric surgery. METHODS: We performed a retrospective study in a prospective database. All patients who underwent primary Roux-en-Y gastric bypass (RYGB) and presented for preoperative consultation of BCS in the same hospital were included in the study. Linear and logistic mixed-effect model analyses were used to evaluate the longitudinal relationships between patients who were accepted or rejected for BCS and their weight loss outcomes or changes in comorbidities. RESULTS: Of the 1150 patients who underwent primary RYGB between January 2010 and December 2014, 258 patients (22.4%) presented for preoperative consultation of BCS. Of these patients, 126 patients eventually underwent BCS (48.8%). Patients who were accepted for BCS demonstrated significant better ∆body mass index (BMI) on average over time (- 1.31 kg/m2/year, 95% confidence interval (CI) -2.52 - -0.10, p = 0.034) and percent total weight loss (%TWL) was significantly different at 36 months (5.79, 95%CI 1.22 - 10.37, p = 0.013) and 48 months (6.78, 95%CI 0.93 - 12.63, p = 0.023) after body contouring consultation. Patients who were accepted or rejected did not differ significantly in the maintenance of achieved improvements in comorbidities. CONCLUSION: BCS could not be associated with the maintenance of achieved improvements in comorbidities after bariatric surgery, whereas it could be associated with improved weight loss maintenance at 36 and 48 months after body contouring consultation. This association should be further explored in a large longitudinal study.

Systematic review and meta-analysis of endorectal advancement flap and ligation of the intersphincteric fistula tract for cryptoglandular and Crohn's high perianal fistulas.

Background: High perianal fistulas require sphincter-preserving surgery because of the risk of faecal incontinence. The ligation of the intersphincteric fistula tract (LIFT) procedure preserves anal sphincter function and is an alternative to the endorectal advancement flap (AF). The aim of this study was to evaluate outcomes of these procedures in patients with cryptoglandular and Crohn's perianal fistulas. Methods: A systematic literature search was performed using MEDLINE, Embase and the Cochrane Library. All RCTs, cohort studies and case series (more than 5 patients) describing one or both techniques were included. Main outcomes were overall success rate, recurrence and incontinence following either technique. A proportional meta-analysis was performed using a random-effects model. Results: Some 30 studies comprising 1295 patients were included (AF, 797; LIFT, 498). For cryptoglandular fistula (1098 patients), there was no significant difference between AF and LIFT for weighted overall success (74·6 (95 per cent c.i. 65·6 to 83·7) versus 69·1 (53·9 to 84·3) per cent respectively) and recurrence (25·6 (4·7 to 46·4) versus 21·9 (14·8 to 29·0) per cent) rates. For Crohn's perianal fistula (64 patients), no significant differences were observed between AF and LIFT for overall success rate (61 (45 to 76) versus 53 per cent respectively), but data on recurrence were limited. Incontinence rates were significantly higher after AF compared with LIFT (7·8 (3·3 to 12·4) versus 1·6 (0·4 to 2·8) per cent). Conclusion: Overall success and recurrence rates were not significantly different between the AF and LIFT procedure, but continence was better preserved after LIFT.

Feto-maternal interface of human placenta inhibits angiogenesis in the chick chorioallantoic membrane (CAM) assay.

The rapidly growing chorionic villi of the human placenta characteristically show constant blood vessel growth and differentiation. In contrast, the underlying decidua reveals tissue remodeling without apparent angiogenesis. Using the chick chorioallantoic membrane (CAM) assay, we found marked inhibition of angiogenesis by the feto-maternal interface tissue derived from nine human placentas obtained minutes after delivery. Inhibition was prevented by the addition of monensin, which blocks the release of synthesized cell products, and was markedly reduced by drying or freezing the tissue before the assay. Histology, combined with statistical analysis of the constituent cell types, correlated inhibition of angiogenesis with the number of fetally-derived extravillous trophoblasts in the feto-maternal interface tissue. Electron microscopy revealed endothelial cell damage in preexisting small (but not large) CAM vessels. We conclude that decidual tissue inhibited angiogenesis by releasing a water soluble factor which was under apparent constant production by vaible trophoblast on the CAM. The extravillous trophoblast population resembles tumor cells in its migratory and invasive properties but, in contrast to tumor induced angiogenesis, it is angiostatic, perhaps to counteract angiogenic proteins leaking from the intervillous space which could be detrimental to the maternal organism if active.

Antiretroviral interventions to reduce mother-to-child transmission of human immunodeficiency virus: challenges for health systems, communities and society.

This paper examines the ethical, economic and social issues that should be considered when antiretroviral interventions are being planned to reduce mother-to-child transmission of the human immunodeficiency virus. Interventions aiming to reduce mother-to-child transmission should be concerned with the rights of both the child and the mother. Women should not be seen as vectors of transmission but as people entitled to adequate health care and social services in their own right. For women accepting mother-to-child transmission interventions it is important to consider their medical and emotional needs and to ensure that they are not stigmatized or subjected to abuse or abandonment following voluntary counselling and testing. Seropositive women who do not wish to continue with pregnancy should have access to facilities for safe termination if this is legal in the country concerned. Problems arise in relation to the basic requirements for introducing such interventions via the health services in developing countries. A framework is given for making decisions about implementation of interventions in health care systems with limited resources where there is a relatively high prevalence of human immunodeficiency virus infection among pregnant women.

Rhythmic activity of uptake hydrogenase in the prokaryote Rhodospirillum rubrum.

Growth of Rhodospirillum rubrum was followed in cultures kept under anoxic conditions at constant temperature in either continuous light (LL, 32 degrees C) or continuous darkness (DD, 32 degrees C and 16 degrees C). In DD, only small modifications of the turbidity were detected; linear regression analysis nevertheless gives a very significant slope (t(34) = 13.07, p < 10(-14), with R2 of 0.834). Mean generation times reflected these differences of growth with 11.9+/-0.5 h in LL and 43.2+/-1.1 h in DD at 32 degrees C and 37.4+/-1.0 h at 16 degrees C cultures. The uptake hydrogenase (Hup) activity has been followed in situ in whole cells of R. rubrum grown in the same conditions, and a clear ultradian rhythm of activity has been observed. Indeed, after about 12 h in the new media, a rapid rise of hydrogenase activity was observed in both LL and DD cultures after which it decreased again to very low values. The activity of Hup continued to show such fluctuations during the rest of the experiment, both in DD and in LL, during the growth and stationary phases. The Lomb-Scargle power periodogram method demonstrates the presence of a clear rhythmic Hup activity both in LL and DD. In the LL-grown cultures, the oscillating activity is faster and continues throughout the growth and the stationary phases, with an ultradian period of 12.1+/-0.5 h. In DD, the slow-growing bacteria showed an ultradian oscillatory pattern of Hup activity with periods of 15.2+/-0.5 h at 32 degrees C and 23.4+/-2.0 h at 16 degrees C. The different periods obtained for LL- and DD-grown bacteria are significantly different.

Effect of buffer solutions on activation of Shamouti orange pyrophosphate-dependent phosphofructokinase by fructose 2,6-bisphosphate.

Shamouti phosphofructokinase (PFP) activation depends on the presence of fructose 2,6-bisphosphate (Fru-2,6-P2) in the glycolytic reaction. The effect of activation by Fru-2,6-P2 differs considerably, however, according to the buffer (pH 8.0) in which the reaction is performed: Ka = 2.77 +/- 0.3 nM in Hepes-NaOH and 7.75 +/- 1.49 nM in Tris-HCl. The presence of chloride ions (39 mM) in the Tris-HCl buffer inhibits PFP. Indeed, when using a Hepes-NaOH buffer and then adding 39 mM NaCl, Ka = 8.12 +/- 0.52 nM. The Ki for chloride ions is approximately 21.7 mM. In the gluconeogenic reaction, Shamouti PFP generally showed a high endogenous activity. Addition of Fru-2,6-P2 did not modify the velocity and the Vmax of the enzyme; however, its presence increased the affinity of the enzyme for Fru-1,6-P2 from 200 +/- 15.6 microM in absence of Fru-2,6-P2 to 89 +/- 10.3 microM in its presence (10 microM). In the presence of chloride (39 mM), the affinity for the substrate decreased with K(m) = 150 +/- 14 microM. The calculated Ki for chloride ions equals 56.9 mM. In both the glycolytic and the gluconeogenic reactions, Vmax is not affected; therefore, the inhibition mode of chloride is competitive.

Kinetic properties of ATP-dependent phosphofructokinase from grapefruit juice sacs: effect of TCA cycle intermediates.

Grapefruit juice sac ATP-PFK was studied kinetically for its substrates ATP and Fru-6-P at pH = 7.5. The Km for ATP is equal to 39.8 +/- 4.6 microM. ATP becomes inhibitory at concentrations above 80 microM. The Km for ATP is not affected by the addition of citrate (10 mM). For Fru-6-P, the saturation curve is sigmoidal, with an S0.5 equal to 0.17 +/- 0.03 mM, in the presence of Mg++ (2.5 mM) and ATP (1 mM). ATP-PFK shows a negative cooperativity at lower concentrations of Fru-6-P (h = 0.5), while higher concentrations of the substrate induce a positive cooperation (h = 1.5). The presence of citrate affects the S0.5 affinity value, but not the Vmax. The presence of citrate (10 mM) removes the cooperative effect at higher concentrations of the substrate, as h = 1.0. A theoretical Ki for citrate was calculated and equals 1.30 mM.

Fru 2,6-P2 and citrate: intracellular distribution in citrus tissues and effect on grapefruit leaf PFP.

Grapefruit leaf PFP was studied for its activation by fructose 2,6-bisphosphate (Fru 2,6-P2) in the forward and reverse reactions. In the glycolytic reaction, a Ka of 4.0 +/- 0.12 nM was obtained. This constant is affected by the presence of increasing concentrations of citrate (1, 5 and 20 nM) with a Ka(citrate) of 4.5 +/- 0.09, 6.9 +/- 0.05 and 38.2 +/- 1.4 respectively. The inhibition mode of citrate is competitive with Fru 2,6-P2, but non-linear in relation of increasing concentrations of the inhibitor. The intracellular distribution and concentration of the key regulatory metabolite Fru 2,6-P2 was further investigated in citrus leaves and juice cells. Fru 2,6-P2 was only found in the cytosol of juice cells. Fru 2,6-P2 was detected under both conditions with higher concentrations found under aerobiosis.

Kinetic properties of cytosolic fructose 1,6-bisphosphatase from grapefruit. Effect of citrate.

cFBP is studied for its affinity to Mg++ and Fru-1,6-P2. The affinity for Mg++ is not very high with a Km of 0.24 +/- 0.01 mM. High concentrations of Mg++ are inhibitory. The saturation curve for Fru-1,6-P2 is hyperbolic with a Km of 0.54 +/- 0.014 microM. The presence of citrate (10 mM) induces a sigmoidal curve, modifying both Vmax and S0.5. Citrate affects the allosteric properties of cFBPase: at low substrate concentration cooperativity becomes negative while at higher concentration it is positive. Addition of higher concentrations of Mg++ shows a synergistic effect with citrate, decreasing of the affinity for Fru-1,6-P2: S0.5 equals 7.6 +/- 0.25 mM, 9.0 +/- 0.86 mM and 21.5 +/- 1.46 mM in presence of 5, 7.5 and 10 mM Mg++, respectively.

Participatory evaluation of counselling, medical and social services of The AIDS Support Organization (TASO) in Uganda.

The AIDS Support Organization (TASO) is an indigenous non-governmental organization (NGO) of HIV-infected and affected people in Uganda. TASO provides counselling, social support, medical and nursing care for opportunistic infections at 7 centres affiliated to district hospitals in Uganda. Between 1993 and 1994, the services provided by TASO were evaluated through a participatory approach between staff and clients. TASO counselling services helped clients and their families to cope with HIV and AIDS, with 90.4% of clients revealing their serostatus, and 57.2% reporting consistent use of condoms in the past 3 months. TASO was also the main source of medical care for clients with opportunistic infections in the last 6 months (63.8%). As a result of counselling, over half of the clients (56.9%) made plans for the future and 51.3% wished to make wills. There was a high level of acceptance of people living with HIV/AIDS (PWAs) by families (79%) and the community (76%). Care was provided to PWAs at home mainly by women (86.2%). TASO has demonstrated that individuals and their families are able to live positively with HIV/AIDS. Through counselling, medical care and material support to clients and their families, TASO has effected change in people's attitudes, knowledge and lifestyles. In particular, TASO has demonstrated a strong capacity to overcome four problems that haunt AIDS care in most places: (1) revealing one's HIV-serostatus to relevant others; (2) accepting PWAs in family and community; (3) seeking early treatment; and (4) combining prevention and care. In general, TASO has shown that specialized services to meet AIDS care needs can be added to existing health services at district levels. As a result of the participatory evaluation, a well-accepted monitoring system was established.

PIP: The AIDS Support Organization (TASO) is an indigenous nongovernmental organization of HIV-infected and affected people in Uganda. The organization provides counseling, social support, and medical and nursing care for opportunistic infections at seven centers affiliated with district hospitals in Uganda. TASO's services were evaluated during 1993-94 via a participatory approach involving staff and clients. The organization's counseling services helped clients and their families to cope with HIV and AIDS, with 90.4% of clients revealing their serostatus, and 57.2% reporting the consistent use of condoms during the preceding 3 months. TASO was the main source of medical care for clients with opportunistic infections during the preceding 6 months. As a result of counseling, 56.9% of clients made plans for the future and 51.3% wished to make wills. The evaluation further found a high level of acceptance of people with HIV/AIDS (PWA) by families (79%) and the community (76%). Women provided 86.2% of in-home care to PWA. TASO's experience demonstrates that individuals and their families can live positively with HIV/AIDS and that specialized AIDS care services can be readily added to existing health services at the district level.

Use of 3-D computer modelling and kinetic studies to analyse grapefruit pyrophosphate-dependent phosphofructokinase.

The glycolytic reaction of grapefruit PPi-dependent phosphofructokinase (PFP) depends on the presence of Fru-2,6-P2 (Ka = 6.7 nM). This molecule was further demonstrated in grapefruit juice sac cells. Citrate, alpha-ketoglutarate and isocitrate competitively inhibited the binding of Fru-2,6-P2 to PFP. The affinity for Fru-6-P (Km = 159 microM) and PPi (Km = 33 microM) were not affected by the addition of these molecules. In the gluconeogenic reaction, the presence of Fru-2,6-P2 did not affect the Km of Fru-1,6-P2 (61 microM) in contrast to orange fruit PFP. These results led to the building of a computer model of PFP, based on the known structure of Bacillus stearothermophilus ATP-dependent phosphofructokinase (ATP-PFK). The results show that catalysis of Fru-6-P in the alpha chain is most unlikely, due to amino-acid substitutions and that Fru-2,6-P2 can bind between the alpha and beta subunits.

Caring for patients with HIV and AIDS in middle income countries.

PIP: Increased access, in middle-income countries, to innovative but costly medical technologies for the treatment of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) raises important policy considerations about how to optimize their use. Realizing the full potential of antiretroviral therapy, for example, requires widespread availability of HIV tests to identify those in the early stage of HIV infection, counseling services to inform people of their test results and explain the therapeutic options, available and affordable drugs, monitoring of drug efficacy and toxicity, mechanisms to ensure long-term compliance, and well functioning psychosocial support systems. In Thailand, a cost-effectiveness study modelling the use of different antiretroviral treatment options demonstrated that investments in antiretroviral therapy and formula feeding to prevent maternal-child HIV transmission were more effective and affordable than providing antiretroviral agents to those with established HIV infection. The cost of preventing vertical HIV transmission amounted to 16% of Thailand's national AIDS budget. The cost of extending access to and compliance with treatment and preventing opportunistic infections would be 129% of the budget, while that of providing antiretroviral drugs to all those with symptomatic HIV infection would be 235-630% of the budget (depending on the complexity of the regimen). More such studies are needed to develop a conceptual framework for policy development.^ieng

Shared responsibility between all affected by HIV / AIDS. "Comprehensive care across a continuum".

PIP: The needs of persons with AIDS (PWAs), their partners or families, and their health care providers are very extensive and complex. AIDS is different due to its impact on individual lives, families, communities, and the society at large. Southern and Central Africa and South Asia comprise more than 75% of all HIV infections (late 1994, 18 million adults and 1.5 million children). The people most affected are the younger, most productive age groups, particularly women. In Africa and Asia, 50% of HIV-infected persons have tuberculosis (TB); care and community projects need to address not only HIV/AIDS but also TB. TB prevention therapy is being introduced in some countries. In countries heavily affected by HIV/AIDS, HIV-infected patients occupy 50-70% of hospital beds for adult patients. The number of beds for other conditions is decreasing. Economic austerity packages have reduced the financing of hospitals and health services. The lifetime medical costs for PWAs in Europe and North America are about US $100,000. Staff and maintenance comprise the largest proportion of costs. The response to HIV/AIDS care among health care providers has ranged from negative attitudes to positive attitudes of listening and explaining. Comprehensive HIV/AIDS care involves a holistic approach. The comprehensive HIV/AIDS care continuum framework consists of various points where discharge planning and referral can occur between each of the points. These points in the continuum include voluntary counseling and testing, health facilities, community-based services, blood transfusion services, self-help groups, and home care.^ieng