OPTN/SRTR 2016 Annual Data Report: Pancreas.

The number of pancreas transplants performed in the United States increased by 7.0% in 2016 over the previous year, the first such increase in more than a decade, largely attributable to an increase in simultaneous kidney pancreas transplants. Transplant rates increased in 2016, and mortality on the waiting list decreased. The declining enthusiasm for pancreas after kidney (PAK) transplants persisted. The uniform definition of graft failure was approved by the OPTN Board of Directors in 2015 and will be implemented in early 2018. Meanwhile, SRTR continues to refrain from reporting pancreas graft failure data. The OPTN/UNOS Pancreas Transplantation Committee is seeking to broaden allocation of pancreata across compatible ABO blood types in a proposal out for public comment July 31 to October 2, 2017. A new initiative to provide guidance on the benefits of PAK transplants is also out for public comment.

Broadened Allocation of Pancreas Transplants Across Compatible ABO Blood Types.

BACKGROUND: Current Organ Procurement and Transplantation Network (OPTN) policy restricts certain blood type-compatible simultaneous pancreas and kidney (SPK) transplants. Using the Kidney Pancreas Simulated Allocation Model, we examined the effects of 5 alternative allocation sequences that allowed all clinically compatible ABO transplants. METHODS: The study cohort included kidney (KI), SPK, and pancreas alone (PA) candidates waiting for transplant for at least 1 day between January 1, 2010, and December 31, 2010 (full cohort), and kidneys and pancreata recovered for transplant during the same period. Additionally, because the waiting list has shrunk since 2010, the study population was reduced by random sampling to match the volume of the 2015 waiting list (reduced cohort). RESULTS: Compared with the current allocation sequence, R4 and R5 both showed an increase in SPK transplants, a nearly corresponding decrease in KI transplants, and virtually no change in PA transplants. Life-years from transplant and median years of benefit also increased. The distribution of transplants by blood type changed, with more ABO:A, B, and AB transplants performed, and fewer ABO:O across all transplant types (KI, SPK, PA), with the relative percent changes largest for SPK. DISCUSSION: Broadened ABO compatibility allowances primarily benefitted SPK ABO:A and AB candidates. ABO:O candidates saw potentially reduced access to transplant. The simulation results suggest that modifying the current allocation sequence to incorporate broadened ABO compatibility can result in an increase in annual SPK transplants.

Feasibility, acceptability, and tolerability of RGN107 in the palliative wound care management of chronic wound symptoms.

OBJECTIVE: To assess the feasibility, acceptability and tolerability of RGN107 use, a natural powder blend of Arnica Montana, Calendula Officinalis, Mentha Arvensis and Santalum Album, among hospice patients and their wound caregivers in the palliative wound care management of chronic wound symptoms at end-of-life. METHOD: Data were collected between May 2013 and November 2015. A pilot trial conducted among 50 hospice patients with symptomatic (pain, odour, or exudate) chronic wounds. Caregivers received initial RGN107 protocol training, actively applied the powder to patient wounds for 4-weeks, and completed an 8-week retrospective survey. Feasibility was assessed by measuring process outcomes, including the number and proportion of participants referred, screened eligible, enrolled, withdrawn and successfully completed. Acceptability measures included: a protocol training evaluation, caregiver pre and post self-efficacy ratings, retrospective usability, symptom control management and comparative technique caregiver ratings, and recorded open-ended comments. Tolerability was assessed through a 12-week cumulative review of the study adverse event profile. RESULTS: Feasibility, tolerability and acceptability of use of the RGN107 powder for chronic wounds were established. Recruitment goals were achieved and 92 % of the patients successfully completed the study. 95 % of wound caregivers would recommend the powder for use in this population. CONCLUSION: This study supports the feasibility, acceptability and tolerability of a wound care powder that espouses a multi-symptom palliative comfort care approach for hospice patients with chronic wounds at end-of-life. Further research is needed to establish the efficacy of the powder.

OPTN/SRTR 2015 Annual Data Report: Pancreas.

The number of pancreas transplants performed in the United States stabilized over the last 3 years after nearly a decade of steady decline. Numbers of new additions to the list also stabilized during the same period. Notably, the persistent decline in pancreas after kidney transplants also seems to have abated, at least for now. The first full year of data after implementation of the new pancreas allocation system revealed no change in the distribution of organs between simultaneous pancreas-kidney (SPK) transplant and pancreas transplant alone. The percentage of kidneys used in SPK transplants was also unchanged. While a uniform definition of pancreas graft failure was approved in June 2015, it is awaiting implementation. Meanwhile, SRTR will refrain from publishing pancreas graft failure data in the program-specific reports. Therefore, it is difficult to track trends in outcomes after pancreas transplant over the past 2 years. New initiatives by the OPTN/UNOS Pancreas Transplantation Committee include facilitated pancreas allocation and broadened allocation of pancreata across compatible ABO blood types to increase organ utilization.

Pancreas.

Even though pancreas transplant numbers have steadily declined over the past decade, new listings increased in 2014 compared with the previous year, notably for pancreas transplant alone (PTA) and simultaneous pancreas-kidney transplant. The number of new PTAs also increased over the past two years. Whether this is a sustainable trend remains to be seen. Significant events in 2014 included implementation of a new pancreas allocation system and development of a proposed uniform definition of pancreas graft failure. Meanwhile, overall pancreas transplant rates and outcomes continued to improve. Substantial decline in pancreas after kidney transplants remains a serious concern. SRTR has not published pancreas graft failure data in the program-specific reports for the past two years. While this will not change in the near future, the acceptance of a uniform definition of graft failure is a crucial first step toward resuming graft failure reporting. Continued improvements and innovation, both surgical and immunological, will be critical to keep pancreas transplant as a viable option for treatment of insulin-dependent diabetes. As alternative therapies for diabetes such as islet transplant and artificial pancreas are evolving, improved outcomes with minimizations of complications are more important than ever.

Transforming growth factor-beta 1 and its receptors in human lung cancer and mouse lung carcinogenesis.

The transforming growth factor-betas (TGF-beta s) are multifunctional proteins that inhibit the proliferation of many epithelial cells through a set of cell protein receptors that includes the TGF-beta type I (RI) and type II (RII) receptors. Loss of growth inhibition by TGF-beta is thought to contribute to the development of many types of tumors. In the present study, we have examined expression of the proteins and mRNAs for TGF-beta 1, TGF-beta RI, and TGF-beta RII in normal human lung, well-characterized non-small cell lung cancer (NSCLC) cell lines, and primary NSCLC specimens. Immunohistochemical staining for TGF-beta 1, TGF-beta RI, and TGF-beta RII using specific antibodies in normal human lung showed expression of the 3 proteins in the epithelium of bronchi and bronchioles as well as in alveoli. Differential expression of TGF-beta RI and TGF-beta RII proteins was detected in 5 NSCLC cell lines using Western blot analysis, with reduced levels in 3 cell lines. A panel of 45 formalin-fixed and paraffin-embedded NSCLC specimens showed positive immunostaining for TGF-beta 1, TGF-beta RI, and TGF-beta RII, with reduced TGF-beta RII in poorly differentiated adenocarcinomas and squamous cell carcinomas and some moderately differentiated adenocarcinomas. In situ hybridization studies conducted with specific riboprobes for TGF-beta 1, TGF-beta RI, and TGF-beta RII showed corresponding localization of expression of the mRNAs in the specimens that showed positive immunostaining for the proteins. To investigate the roles of TGF-beta 1, TGF-beta RI, and TGF-beta RII in chemically induced mouse lung tumorigenesis, we examined the expression of their proteins and mRNAs in 2 mouse model systems. Whereas expression of the proteins and mRNAs for TGF-beta 1 and TGF-beta RI was comparable in lung adenomas and bronchioles of A/J mice treated with benzo(alpha)pyrene, decreased immunostaining and hybridization for TGF-beta RII protein and mRNA was detected in 50% of lung adenomas in these mice. Interestingly, expression of TGF-beta 1 and the TGF-beta receptor proteins was similar to that of bronchioles in C57B1/6 mice and their littermates heterozygous for deletion of the TGF-beta 1 gene treated with diethylnitrosamine. These data show that reduced levels of expression of TGF-beta RII occur in some, but not all, human and mouse lung tumors. This suggests that different mechanisms of action, some of which may involve the TGF-beta signaling pathway, may contribute to the progression of lung tumorigenesis.

Human pulmonary acinar aplasia: reduction of transforming growth factor-beta ligands and receptors.

Pulmonary hypoplasia has been found in the human neonatal autopsy population and has been attributed to an alteration in epithelial-mesenchymal interactions during development of the lung. Pulmonary acinar aplasia is a very rare and severe form of pulmonary hypoplasia. The transforming growth factor-betas (TGF-beta) are multifunctional regulatory peptides that are secreted by a variety of normal and malignant cells and are expressed in developing organs including the lung; their tissue distribution patterns have possible significance for signaling roles in many epithelial-mesenchymal interactions. Here, we report our examination of TGF-beta in the lungs of a term female infant diagnosed with pulmonary acinar aplasia whose autopsy revealed extremely hypoplastic lungs with complete absence of alveolar ducts and alveoli. Immunohistochemical and in situ hybridization analyses were used to localize and measure the proteins and mRNA, respectively, for TGF-beta1, TGF-beta2, TGF-beta3, and TGF-beta type I and type II receptors (TGF-beta RI and RII) in formalin-fixed and paraffin-embedded sections of these hypoplastic lungs and normal lungs. Immunostaining for TGF-beta1, TGF-beta2, and TGF-beta RI and RII was significantly lower in the bronchial epithelium and muscle of the hypoplastic lungs than in normal lungs, whereas no difference was detected in staining for other proteins including Clara cell 10-kD protein, adrenomedullin, hepatocyte growth factor/scatter factor, and hepatocyte growth factor receptor/Met in the hypoplastic and normal lungs or in the liver and kidneys of this infant compared with normal liver and kidney. In addition, in situ hybridization showed that TGF-beta1 and TGF-beta RI transcripts were considerably reduced in the bronchial epithelium of the hypoplastic lung compared with normal lung. These results show that there is a selective reduction of TGF-beta in pulmonary acinar aplasia and suggest that the signaling action of TGF-beta in epithelial-mesenchymal interactions in the lungs of this developmental condition may be compromised.

Coordinate expression of transforming growth factor-beta1 and adrenomedullin in rodent embryogenesis.

Transforming growth factor-beta (TGFbeta) and adrenomedullin (AM) are multifunctional regulatory peptides that are secreted by a variety of normal and malignant cells. The TGFbetas are expressed in developing organs and adults, and their tissue distribution pattern has possible significance for signaling roles in many epithelial-mesenchymal interactions. AM is also expressed in a variety of embryonic and adult tissues. The present study reports a comparison of the patterns of expression of the proteins and messenger RNAs (mRNAs) for TGFbeta1 and AM in the developing mouse embryo. Immunohistochemical and in situ hybridization analyses were performed on formalin-fixed paraffin-embedded sections of developing embryonic mouse tissues using specific antibodies and complementary RNA probes for TGFbeta1 and AM. The early placenta, including the giant trophoblastic cells, showed high levels of staining and hybridization for TGFbeta1 and AM proteins and mRNAs. The heart was the first organ that showed expression of TGFbeta1 and AM during embryogenesis. The spatio-temporal patterns of expression of TGFbeta1 and AM in cardiovascular, neural, and skeletal-forming tissues as well as in the main embryonic internal organs showed striking similarities. The lung, kidney, and intestine, in which epithelial-mesenchymal interactions occur, showed similar patterns of TGFbeta1 and AM expression. These data show colocalization of TGFbeta1 and AM in specific cell types associated with several tissues in the developing mouse embryo. Additionally, RT-PCR amplification and Northern blot hybridization showed expression of TGFbeta1 and AM mRNAs in all embryonic and adult mouse and rat tissues examined. Our data show that the expression of TGFbeta1 and AM is regulated in a spatial and temporal manner such that overlapping patterns of expression of TGFbeta1 and AM occur in several tissues at the same stage of development and in the same cellular location in rodent embryogenesis.

Concurrent and distinct transcription and translation of transforming growth factor-beta type I and type II receptors in rodent embryogenesis.

The transforming growth factor-betas (TGF-betas) are multifunctional regulatory polypeptides that play a crucial role in many cell processes and function through a set of cell surface protein receptors that includes TGF-beta type I (RI) and type II (RII). The present study reports a comprehensive comparison of the patterns of expression of TGF-beta RI and RII proteins and mRNAs in the developing mouse embryo using immunohistochemical and in situ hybridization analyses. Although widespread expression of both TGF-beta receptors was detected throughout the embryonic development period so that many similarities occur in localization of the TGF-beta receptors, TGF-beta RI was expressed in a well-defined, non-uniform pattern that was different in many respects from that of TGF-beta RII. Whereas higher levels of TGF-beta RI compared to TGF-beta RII were detected in some tissues of the embryo at the beginning of organogenesis, the level of TGF-beta RII increased more dramatically than that of TGF-beta RI during late organogenesis; this was especially true in many neural structures where TGF-beta RI and RII were comparable by day 16. The lung, kidney and intestine, in which epithelial-mesenchymal interactions occur, showed a complex pattern of TGF-beta RI and Rll expression. Additionally, northern blot hybridization and reverse transcription-polymerase chain reaction (RT-PCR) amplification showed non-uniform expression of the transcripts for TGF-beta RI and RII in embryonic and adult mouse and rat tissues. These data show that regulation of TGF-beta1 RI and RII occurs concurrently, but distinctly, in a spatial and temporal manner in rodent embryogenesis which may allow control of signal transduction of TGF-beta during development.

Accumulating experience in a child abuse clinic.

OBJECTIVE: To examine the patient profile encountered in the first year of operation of the Child Abuse and Neglect Clinic of the Transvaal Memorial Institute. DESIGN: Record review of all cases presenting to the Clinic from May 1988 to April 1989. RESULTS: Females comprised just over 80% of the 227 patients. Sexual abuse was the presenting complaint in 89.8%. Most were young, 7% under 3 and 55% under 10 years of age. Almost one-third of the boys and 5.0% of the girls had chronic signs of anal abuse. Of the girls 56% had signs of chronic and 10% signs of acute vaginal abuse. Where the certainty of sexual abuse was high, 60% of the girls and 45% of the boys had suffered penetrative abuse. The perpetrators were almost invariably known to the child; biological family members accounted for 38% of perpetrators, and if all relations are included (biological, step and 'common law'), family members were the perpetrators in 66% of cases. Strangers were the perpetrators in only 7% of our cases. The majority of perpetrators were male. Behaviour problems were recorded in 73% of cases. Many different problems were noted; the most common were school problems (21%), masturbation (19%), 'clingy' behaviour (12%), and withdrawal and depression (11.5%). CONCLUSIONS: Certainty of diagnosis should be specified. We use four categories: proven, highly suspected, unproven but still suspected, and no abuse. For sexual abuse we also differentiate between penetrative, non-penetrative, 'type uncertain' and no abuse. Training of other health personnel in child abuse management is now a priority in our setting.

Sexually transmitted disease surveillance in a child abuse clinic.

The sexually transmitted disease surveillance system instituted at the Child Abuse and Neglect (CAN) clinic of the Transvaal Memorial Institute for Child Health and Development was evaluated after 1 year. The presenting complaint of the vast majority of the 227 patients was sexual abuse. In more than half (52%), child abuse was medically proven, and it was highly suspected in another 18%. In only 6% did no abuse take place. About half the patients suffered non-penetrative sexual abuse, 40% penetrative abuse and 10% suffered non-sexual abuse. Smears for gonorrhoea were positive in 2 out of 152 patients; for Chlamydia in 1 out of 140; for Gardnerella and Trichomonas in 2 and 1 case, respectively. Syphilis serology yielded 3 positive results out of 162, and hepatitis B, 6 out of 143. No positive results were found in tests for HIV and herpes. With the exception of hepatitis B tests, all positive results occurred in children considered on clinical grounds to have medically proven or highly suspected sexual abuse. These results will allow modification of the surveillance system and testing of those children more likely to test positive, while doing fewer tests overall.

A field-evolved differential filtration method for recovery of schistosome cercariae.

Modifications to Theron 's (1979) differential filtration technique are described which improve both sensitivity and reliability. Following pre-filtration to remove larger debris and some plankton, the sample is formalized; constant stirring prevents losses due to the cercarial stickiness normally caused by the fixation process. Once fixed, Schistosoma mansoni cercariae are reliably retained and well displayed on nylon monofilament cloth of 50 micrometers pore size. Such a coarse recovery filter permits very large samples to be processed and results in filters which are easy to read. Field comparison showed the method improved sensitivity by a factor of more than 20 times and laboratory evaluation indicated a recovery rate of over 80%.

Displacement of Biomphalaria glabrata by the snail Thiara granifera in field habitats in St. Lucia, West Indies.

Thiara granifera is a melaniid snail capable of maintaining very high densities in a variety of habitats. It has been introduced into the New World from the Far East and is now spreading rapidly throughout the Caribbean. In Puerto Rico and Dominica casual observations following natural invasion by T. granifera suggest that it may exert a powerful restraining influence on populations of Biomphalaria glabrata, the major intermediate host of Schistosoma mansoni in the Caribbean. The potential of T. granifera in biological control is being investigated in St. Lucia. In four field trials, B. glabrata was apparently eliminated from marshes and streams six to 22 months after the introduction of T. granifera. Thiara granifera shows promise as a major factor in the suppression of schistosomiasis in the Caribbean, but it is unsuitable for universal use as it is an intermediate host of the lung fluke, Paragonimus westermani.

La esquistosomiasis y sus huéspedes intermediarios en las Pequeñas Antillas / Schistosomiasis and its intermediate hosts in the Lesser Antillean Islands

La esquistosomiasis representa una amenaza importante para la salud en la región del Caribe. Este artículo analiza la situación en relación con esta enfermedad y diversos factores que contribuyen a su transmisión en las Pequeñas Antillas (AU)

Reduction in transmission of Schistosoma mansoni by a four-year focal mollusciciding programme against Biomphalaria glabrata in Saint Lucia.

The effect of transmission of Schistosoma mansoni of a focal snail control programme was investigated over four years amongst approximately 1250 people living in five communities in the steep-sided Soufriere river valley, St. Lucia, West Indies. Bayer 6076 was applied from constant flow drip cans to 12 stream sections at a target dose of 8 mg/litre clonitralide every four weeks. Only proven and potential transmission sites were treated; marsh habitats, where Biomphalaria glabrata were widespread, were ignored. In the stream snail numbers were reduced by 94% in the first year and by 100% thereafter. Incidence of new S. mansoni infections amongst children fell from 18% in the last year before control to 6% and 9% after three and four years respectively. Amongst children and adults in the four years of control the conversion/reversion ratio declined leading to a lowering of the over-all prevalence from 40% to 22%. Parasitologically the results were similar to those of a previously evaluated area-wide mollusciciding programme. The mean annual cost per person protected was US $2.60. This figure is atypically high because the topography of the area severely limited the population size.