Intensive cytotoxic therapy followed by autologous bone marrow transplantation for non-Hodgkin's lymphoma of high-grade malignancy

Fourteen patients with non-Hodgkin's lymphoma (NHL) of high-grade malignancy were treated with cyclophosphamide and total body irradiation followed by autologous bone marrow transplantation (ABMT). All patients were pretreated with conventional chemotherapy. Three of four patients with drug-resistant disease achieved complete remission (CR), but relapse occurred within six months. Four patients in partial remission (PR) achieved CR; one died because of sepsis, two relapsed within six months, and one is still in CR 28+ months later. Six were treated in CR, five in first CR, and one in second CR. From these six patients (who received this treatment as consolidation therapy), five are in unmaintained CR seven to 31+ months after ABMT (one patient died of a secondary illness). There were two therapy-related deaths, both in patients with a poor clinical condition. Toxicity of this treatment was mild for those receiving transplants who were in better condition. These preliminary results suggest that intensive cytoreductive therapy followed by ABMT may improve disease-free survival in patients in NHL of high-grade malignancy in CR.     

Platelet-dependent primary hemostasis promotes selectin- and integrin- mediated neutrophil adhesion to damaged endothelium under flow conditions

Co-localization of blood platelets and granulocytes at sites of hemostasis and inflammation has triggered an intense interest in possible interactions between these cellular processes and induction of vessel wall injury. Leukocyte adhesion to endothelial cells decreases with increasing shear and is dependent on an initial rolling phase mediated by selectins. We hypothesized that flow-dependent platelet adhesion at an injured vessel wall will lead to P-selectin expression by platelets, thus mediating leukocyte co-localization. A perfusion chamber was used in which flowing whole blood induced platelet adhesion to a subendothelial matrix (ECM) of cultured human umbilical vein endothelial cells (HUVEC). We compared neutrophil (polymorphonuclear leukocyte [PMN]) interactions with HUVEC and their ECM with and without adhered platelets. PMNs adhered predominantly to ECM-adhered platelets and not to endothelial cells. ECM alone did not support PMN adhesion under flow conditions. PMN adhesion to unstimulated HUVEC was only substantial at low shear (up to 200 cells/mm2 at shear stress 80 mPa). In marked contrast, PMN adhesion to ECM-adhered platelets was dramatically increased, and adhesion was demonstrated at much higher shear stress (up to 640 mPa). Studies with specific antibodies showed that the platelet-dependent neutrophil adhesion was selectin-mediated. Inhibition of P-selectin caused a marked inhibition of adhesion at high shear stress, whereas the role of leukocyte L-selectin was less pronounced. beta2-Integrin-blocking antibodies inhibited static neutrophil adhesion. fMLP induced L-selectin shedding from leukocytes, resulting in decreased leukocyte adhesion. In conclusion, platelet- dependent hemostasis at the ECM appears to be a powerful intermediate in neutrophil-vessel wall interactions at shear stresses that normally do not allow neutrophil adhesion to intact endothelium.     

High prevalence of vitamin D deficiency in elderly patients with advanced osteoarthritis scheduled for total knee replacement associated with poorer preoperative functional state

Vitamin D deficiency has been reported previously in patients with osteoarthritis undergoing total hip arthroplasty. We found a high prevalence of vitamin D deficiency in elderly patients with advanced knee osteoarthritis scheduled for total knee replacement and also a significant association with a lower preoperative functional state. A review of the literature is given on vitamin D deficiency in patients with knee osteoarthritis and the association with lower outcome scores after arthroplasty is discussed.     

Preoperative C-reactive protein predicts the severity and likelihood of complications following appendicectomy

Introduction

Diagnostic laparoscopy with appendicectomy (LA) has become the accepted method of investigation and treatment of appendicitis. However, concerns remain in cases of complicated appendicitis when many advocate conversion to an open procedure (LCOA) owing to the risk of complications. The aim of this study was to look for factors that could predict complications occurring in patients undergoing appendicectomy.

Methods

Data inclusive of all consecutive appendicectomies over a two-year period were retrieved from the computerised theatre database. Clinical details including admission inflammatory markers, complications, severity (final pathology) and length of stay were collected from the discharge letter. Readmissions were identified as those hospital identifiers had a second set of admission dates and/or a second discharge letter.

Results

During the 2-year study period, 517 appendicectomies were performed. Of these, 429 patients (83%) had LA and the remaining 88 (17%) had LCOA. The LA group had a mean age of 28 years (range: 2–86 years) and a mean C-reactive protein (CRP) level of 71mg/l (range: 0–480mg/l) while the LCOA group had a mean age of 46 years (range: 11–92 years) and a mean CRP level of 162mg/l (range: 3–404mg/l). These differences in age and CRP were significant (p<0.001). LA patients were less likely to have complications overall (22% vs 52%, p=0.015). Complications were independently more than twice as common with established inflammation with a CRP level of >150mg/l (p<0.05).

Conclusions

A high preoperative CRP level predicts an increased rate of postoperative complication due to established inflammation and/or infection. This raises the question of whether we should be offering primary open appendicectomies to patients with a CRP level of >150mg/l.     

Insulin‐like growth factor‐II is produced by,signals to and is an important survival factor for the mature podocyte in man and mouse

Podocytes are crucial for preventing the passage of albumin into the urine and, when lost, are associated with the development of albuminuria, renal failure and cardiovascular disease. Podocytes have limited capacity to regenerate, therefore pro‐survival mechanisms are critically important. Insulin‐like growth factor‐II (IGF‐II) is a potent survival and growth factor; however, its major function is thought to be in prenatal development, when circulating levels are high. IGF‐II has only previously been reported to continue to be expressed in discrete regions of the brain into adulthood in rodents, with systemic levels being undetectable. Using conditionally immortalized human and ex vivo adult mouse cells of the glomerulus, we demonstrated the podocyte to be the major glomerular source and target of IGF‐II; it signals to this cell via the IGF‐I receptor via the PI3 kinase and MAPK pathways. Functionally, a reduction in IGF signalling causes podocyte cell death in vitro and glomerular disease in vivo in an aged IGF‐II transgenic mouse that produces approximately 60% of IGF‐II due to a lack of the P2 promoter of this gene. Collectively, this work reveals the fundamental importance of IGF‐II in the mature podocyte for glomerular health across mammalian species. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Laparoscopic adrenalectomy for functioning and non-functioning adrenal tumors: Analysis of surgical aspects based on histological types

BACKGROUND: The aim of this study was to evaluate whether hormonal functions of the tumor influence the operative results of laparoscopic adrenalectomy, and to analyse the clinical outcomes in patients with various hormonally active adrenal tumors. METHODS: Clinical and pathological records of 68 patients were reviewed. The average age of patients was 40 years (range 20-75); 39 were women and 29 men. For the comparison, patients were divided into the non-functioning tumor group (n = 22) and the functioning tumor group (n = 46). RESULTS: All laparoscopic adrenalectomies were finished successfully, and no open surgery was necessary. The median operative time and blood loss in the two groups were similar; however, in subgroup analysis, operative time for pheochromocytoma was significantly longer than that for non-functioning tumor (P = 0.044). No difference was noted in intra- and postoperative data between the groups. Of the 22 patients with aldosteronoma, 18 (81.8%) became normotensive and no longer required postoperative blood pressure medications. Adrenalectomy led to an overall reduction in the median number of antihypertensive medications (P < 0.001). All patients with Cushing adenoma had resolution or improvement of the signs and symptoms during follow-up periods. There was no evidence of biochemical or clinical recurrence in any patient with pheochromocytoma. CONCLUSION: The results of this retrospective review document that laparoscopic adrenalectomy is a safe and effective treatment for functioning as well as non-functioning adrenal tumors, although endocrinologic features may play a significant role.