Platelet adhesion and thrombus formation on subendothelium in platelets deficient in glycoproteins IIb-IIIa, Ib, and storage granules

Patients whose platelets are deficient in glycoprotein (GP) Ib, IIb- IIIa (thrombasthenia), or granule substances (storage pool deficiency, SPD) were studied to define further the properties of platelets that mediate platelet adhesion and thrombus formation on subendothelium. Both nonanticoagulated and citrated blood were exposed to everted, de- endothelialized rabbit vessel segments under controlled flow conditions and shear rates varying from 650 to 3,300 sec-1. Morphometry was used to measure platelet thrombus dimensions and the percentage of the subendothelial surface covered with contact (C) or spread (S) platelets. Adhesion was defined as C + S. The results in SPD demonstrated (1) reduced thrombus dimensions in delta-SPD (pure dense granule deficiency) in proportion to the magnitude of the dense granule defect; (2) an even greater reduction in thrombus dimensions in patients with combined deficiencies of alpha and dense granules (alpha delta-SPD); and (3) impaired platelet adhesion at several conditions in alpha delta-SPD and, in delta-SPD, a hematocrit-dependent impairment of adhesion in citrated blood at 2,600 sec-1. In thrombasthenia, platelets were present as a monolayer on the subendothelial surface in both nonanticoagulated and citrated blood, indicating an absolute requirement for GPIIb-IIIa in promoting platelet-platelet interaction at all shear rates and perfusion times. Two types of abnormalities in platelet-vessel wall interactions were observed. In nonanticoagulated blood, the percentage of platelets in the C phase was consistently increased at all shear rates, but C + S values were normal. These observations indicate that platelets deficient in GPIIb-IIIa do not spread normally on the subendothelial surface exposed to nonanticoagulated blood. With citrated blood, the C + S value in thrombasthenia was reduced at both 800 and 2,600 sec-1, as in von Willebrand's disease, and a similar degree of reduction (about 50%) was observed in normal blood treated with a monoclonal antibody to GPIIb- IIIa. The findings, together with theoretical considerations, are consistent with an hypothesis that GPIIb-IIIa mediates the spreading of platelets on subendothelium following the initial attachment through GPIb and that GPIIb-IIIa may be considered an adhesion site on the platelet membrane. Abnormalities of GPIIb-IIIa may, depending on the conditions of study, result in either increased values of C platelets or decreased values of C + S. The results of the study further suggest that a complex interaction of platelet granule factors and membrane GP mediate platelet adhesion and thrombus formation.     

Immunosuppression in pregnancy: choices for infant and maternal health

Successful pregnancy outcomes are possible after all types of solid organ transplantation and thousands of successful pregnancies in such women have been reported. As immunosuppressive medications are required to maintain adequate graft and maternal survival, major concerns are the effect of these agents on the fetus and the effect of pregnancy on the well being of mother and graft, against a background of continuing advances and modifications in immunosuppressive therapy. Women should avoid unnecessary medications during pregnancy but clinicians worry most about teratogens; agents (environmental, pharmaceuticals or other chemicals) that cause abnormal development, whether this be an overt structural birth defect or more subtle derangements of embryonic or fetal development. A concern is that any agent or combination of agents and maternal condition(s) may be teratogenic, a risk that is increased in the transplant population. The goal of immunosuppression is to ensure graft and patient survival by preventing acute rejection. Combinations of agents allow for synergistic effects while minimising drug toxicities. No specific combination has been deemed optimal and the effects of more recently available combinations require further study. Although there are known theoretical risks to mother and fetus, successful pregnancies are now the rule in transplant recipients. This is without an apparent increase in the type or incidence of malformations in the newborns, and usually with no evidence of graft dysfunction and/or irreversible deterioration either related to prepregnancy graft problems or unpredictable gestational factors. For immunosuppression, what is best for the mother and her survival should ensure the best outcome for the fetus and, although no specific malformation pattern has been reported to date, there are some interesting trends worthy of continued analyses. A balance of good maternal and graft outcome with the lowest risk of fetal toxicity must be the goal of management.     

Patterns of volunteerism, testing, and exclusion among potential living kidney donors

We found that in kidney transplantation, more females donate. We analyzed transplant recipients for patterns of potential donor exclusion and found that equal proportions of male and female potential donors existed among first-degree biological relatives. More male recipients were married and therefore had more spousal potential donors. Among friends and non-first-degree relatives, significantly fewer males offered to donate to females. Equal proportions of female and male potential donors were excluded from donating for medical comorbidities, blood type incompatibility, recipient refusal, and potential donor reluctance. We concluded that female transplant candidates had fewer potential donors among spouses and opposite sex volunteers from friends and non-first-degree relatives.     

Pregnancy in female pediatric solid organ transplant recipients

This article from the National Transplantation Pregnancy Registry (NTPR) describes the pregnancy outcomes of female transplant recipients who received a solid organ transplant when younger than 21 years old. The analysis includes kidney, liver, liver-kidney, heart, and lung recipients. No recipients in the registry received a pancreas-kidney or heart-lung transplant before age 21. To date, the NTPR has not received report of a pregnancy in a small bowel recipient. This article also reviews immunosuppressive medications with regard to pregnancy safety.     

Change in neoadjuvant chemotherapy could alter the prognosis of patients with pancreatic adenocarcinoma: A case report

BACKGROUNDNeoadjuvant treatment has become a standard of care for borderline or locally advanced pancreatic cancer and is increasingly considered even for up-front resectable disease. The aim of this article is to present the case of a 62-year-old patient with locally advanced pancreatic adenocarcinoma who was successfully treated with gemcitabine plus nab-paclitaxel after the failure of the first line treatment.CASE SUMMARYComputerized tomography scan and magnetic resonance imaging demonstrated a nodular lesion of ill-defined limits in the body of the pancreas, measuring approximately 4.2 cm × 2.7 cm, with an infiltrative aspect. The tumor had contact with the superior mesenteric vein, splenomesenteric junction and the proximal segment of the splenic artery, causing focal reduction of its lumens. Due to vascular involvement, neoadjuvant chemotherapy treatment with eight cycles of “folinic acid, 5-fluorouracil, irinotecan and oxaliplatine” (FOLFIRINOX) were performed. At the end of the cycles, surgery was performed, but the procedure was interrupted due to finding of lesions suspected of metastasis. Gemcitabine plus nab-paclitaxel was then successfully used for neoadjuvant treatment with subsequent R0 surgical resection.CONCLUSIONGemcitabine plus nab-paclitaxel may be effective as an alternative regimen when FOLFIRINOX fails as the first line of treatment, suggesting the need for further studies to identify which patients would benefit from each type of therapeutic approach.     

Spontaneity as predictive factor for well-being

The study discusses the construct of spontaneity and its causal relationship with psychological well-being. It develops a preview phase of validation of the SAI-R and its correlation with the Clinical Outcomes for Routine Evaluation-Outcome Measure (CORE-OM) and the Beck Depression Inventory (BDI-II) and assumes the hypothesis that a high level of spontaneity is correlated negatively with low level of well-being and positively with depression. The research involved Italian and Austrian participants, consisting of 166 Italian and 146 Austrian university students. The findings suggested a causal relationship between low spontaneity and psychological suffering. The results obtained confirm the hypothesized model, showing significant negative causal relationship. The verification of this theoretical model on non-clinical samples allows us to set the ground for future use in clinical samples. Furthermore, this result encourages the development of further research into the use of SAI-R.     

EFFECT OF EXERCISE ON GLUTAMINE SYNTHESIS AND TRANSPORT IN SKELETAL MUSCLE FROM RATS

• 1 Reductions in plasma glutamine are observed after prolonged exercise. Three hypotheses can explain such a decrease: (i) high demand by the liver and kidney; (ii) impaired release from muscles; and (iii) decreased synthesis in skeletal muscle. The present study investigated the effects of exercise on glutamine synthesis and transport in rat skeletal muscle.
• 2 Rats were divided into three groups: (i) sedentary (SED; n = 12); (ii) rats killed 1 h after the last exercise bout (EX‐1; n = 15); and (iii) rats killed 24 h after the last exercise bout (EX‐24; n = 15). Rats in the trained groups swam 1 h/day, 5 days/week for 6 weeks with a load equivalent to 5.5% of their bodyweight.
• 3 Plasma glutamine and insulin were lower and corticosterone was higher in EX‐1 compared with SED rats (P < 0.05 and P < 0.01, respectively). Twenty‐four hours after exercise (EX‐24), plasma glutamine was restored to levels seen in SED rats, whereas insulin levels were higher (P < 0.001) and costicosterone levels were lower (P < 0.01) than in EX‐1. In the soleus, ammonia levels were lower in EX‐1 than in SED rats (P < 0.001). After 24 h, glutamine, glutamate and ammonia levels were lower in EX‐24 than in SED and EX‐1 rats (P < 0.001). Soleus glutamine synthetase (GS) activity was increased in EX‐1 and was decreased in EX‐24 compared with SED rats (both P < 0.001).
• 4 The decrease in plasma glutamine concentration in EX‐1 is not mediated by GS or glutamine transport in skeletal muscle. However, 24 h after exercise, lower GS may contribute to the decrease in glutamine concentration in muscle.

     

Pregnancy after transplantation

The National Transplantation Pregnancy Registry (NTPR) was established in 1991 to study the outcomes of pregnancies in female transplant recipients and pregnancies fathered by male transplant recipients. Data from the NTPR have helped to endorse the reassurances from publications of smaller experiences that successful pregnancies are possible in the transplant population. In our last review for this journal (2000), we noted that important future issues would include the reassessment of prepregnancy guidelines, gestational and organ-specific problems, the role of new immunosuppressive drugs, and the long-term effects of pregnancy on both graft and child. Data collected by the NTPR over the last 7 years have addressed these issues, thus providing additional information for health care providers of transplant recipients of childbearing age. There has been some refinement of prepregnancy guidelines, but there is a need for additional data collection so that organ-specific outcomes and risks can further be identified. To date, the outcomes of the children followed have been encouraging, and specific remote effects have not been identified, but continued surveillance is still vital. Of special concern are the new immunosuppressive drugs, specifically for mycophenolate mofetil (CellCept, Roche Laboratories Inc., Nutley, New Jersey), where data reported to the NTPR and through postmarketing surveillance have shown an increased incidence of nonviable outcomes and a specific pattern and increased incidence of malformation in the newborn, which has resulted in a pregnancy category change. Newer information points to an increased need for vigilance among centers and continued monitoring of pregnancy outcomes in this population. As the first reported pregnancy after transplantation occurred in a kidney recipient 50 years ago, in March 1958, this review also highlights the first reported pregnancies in other solid organ recipients.