The influence of diabetes on free flap transfer: I. Flap survival and microvascular healing.

Although recent clinical case presentations suggest that diabetes does not predispose free tissue transfers to increased risk of failure, this remains an open question. The present study used a syngeneic rat strain (Lewis) for free groin flap transplantations between normal rats and streptozotocin-induced diabetic rats (2 months' duration of symptoms), to investigate the influence of diabetes on flap transfer. Flap survival at 1 week, vascular patency, flap histology and ultrastructure, and scanning electron microscopy of anastomotic sites and of corrosion casts of flap vasculature were used as bases for comparison. No differences were found in comparisons of flap survival between any groups of transfer combinations (normal flap onto normal recipient, diabetic flap onto normal recipient, normal flap onto diabetic recipient, and diabetic flap onto diabetic recipient); 100% success was achieved in each group. No differences were found in histology or corrosion casts. Transmission electron microscopy revealed a thickening of the capillary basement membrane in rat diabetic skin after only 8 weeks of symptoms. This ultrastructural finding is consistent with similar capillary basement membrane thickening seen in many other tissues of short- and long-term diabetic animals and humans. Re-endothelialization across the arterial anastomosis at 2 weeks postoperatively was significantly faster in normal versus diabetic animals (p less than 0.05). The predominantly negative findings of this study support the application of free flap transfers in diabetic patients. It is concluded that reconstructive efforts involving free tissue transfer may not be contraindicated in diabetic patients.     

Cancer of the colon in an egg donor: policy repercussions for donor recruitment

This paper describes the tragic case of a young woman who died of cancer of the colon after successfully donating eggs to her younger sister. Although there is no direct link between her operation and the subsequent development of bowel carcinoma, this case imparts a feeling of unease when seen in conjunction with other cases reported during the last few years. It is a reminder that little is known of the long-term consequences of some aspects of assisted conception. Women undergoing ovarian stimulation for themselves or a matched recipient have the right to be advised, in an agreed format, that there is some concern about unproven potential risks from the stimulatory drugs. The safety of egg donors must assume priority over all other considerations, including lack of donors or any moral position. The recent decision by the Human Fertilisation and Embryology Authority (HFEA) to withdraw any form of payment or recompense to egg donors does not seem to us to be based on a balance of scientific advances, patient needs and the ethics of gamete supply. They state that the intention to withdraw payments was implicit in the 1990 Human Fertilisation and Embryology (HFE) Act. However the Act was based on the Warnock report made 6 years earlier. Even in 1990 ovum donation was uncommon and fertility drugs had not yet caused any unease. The Act provided the HFEA with discretionary powers to issue directions so that the future policies would be consistent with any emerging new medical evidence. It is imperative that the HFEA provide convincing evidence on how the current policy of payment to donors harms society, donors or recipients, and how in the UK the new policy will improve medical practice in assisted conception. Successful pilot studies must precede the implementation of any new policy. Failure to do this could cause irreversible harm to the practice of assisted conception using donor gametes, which will ultimately be against the basic aims of the 1990 HFE Act.      

Muscle mass effect on arterial desaturation after maximal exercise.

We measured arterial oxygen saturation before and immediately after randomly allocated 6 min of "all-out" maximal arm cranking, treadmill running, and ergometer rowing in 10 men and women with a median maximal oxygen uptake of 4.47 (range 3.22-5.34) 1.min-1. Arterial saturation for oxygen was unaltered after arm cranking, but decreased 1.7 (-2.5-6.0) % (P less than 0.05) after running, and 2.2 (1.0-8.7) % (P less than 0.01) after rowing. Arterial saturation was inversely related to capillary blood lactate, which reached 11.8 (7.4-14.0), 12.6 (8.9-18 2), and 14.3 (12.0-19.3) mmol.l-1 (P less than 0.01), respectively, and arterial bicarbonate fell to 15.0 (13.0-23.6), 12.4 (7.2-20.4), and 10.8 (0.0-12.5) mmol.l-1 (P less than 0.01). Thus, pH decreased to 7.25 (7.22-7.40), 7.17 (6.95-7.35), and 7.09 (6.84-7.19) (P less than 0.01). When measured immediately post-exercise, arterial oxygen tension was unchanged or elevated from rest, eliminating the possibility that the arterial desaturation was caused by a pulmonary diffusion limitation. The results of this investigation show that arterial desaturation associated with maximal exercise takes place in proportion to the involved muscle mass, as do deviations in blood lactate, bicarbonate, and hydrogen concentrations.     

Investigation of three new mouse mammary tumor cell lines as models for transforming growth factor (TGF)-β and Neu pathway signaling studies: identification of a novel model for TGF-β-induced epithelial-to-mesenchymal transition

Introduction  

This report describes the isolation and characterization of three new murine mammary epithelial cell lines derived from mammary tumors from MMTV (mouse mammary tumor virus)/activated Neu + TβRII-AS (transforming growth factor [TGF]-β type II receptor antisense RNA) bigenic mice (BRI-JM01 and BRI-JM05 cell lines) and MMTV/activated Neu transgenic mice (BRI-JM04 cell line).     

"Early-peak" carbon monoxide production in certain erythropoietic disorders

The "early-labeled" peak (ELP) of 14CO excretion following injection of glycine-2-14C was used to study erythropoiesis in a patient with sideroblastic anemia and in four subjects with myeloproliferative disorders. The ELP was greatly enlarged in all patients, as compared with a normal volunteer. The contour of the peaks from the hematologically abnormal subjects suggested the presence of increased erythroid heme degradation. In the patient with sideroblastic anemia, all hours of the early peak were significantly reduced after transfusion. This was interpreted to mean that even the earliest or "nonerythroid" phase of the peak is influenced by erythropoietic activity, at least under conditions of erythropoietic stress.     

Safety of Intraventricular Hemorrhage (IVH) Thrombolysis Based on CT Localization of External Ventricular Drain (EVD) Fenestrations and Analysis of EVD Tract Hemorrhage

Background

The purpose of the study is to review the CT findings associated with ventriculostomy placement in regards to the safety of an EVD plus recombinant tissue plasminogen activator (rt-PA) for IVH.

Methods

A retrospective review was conducted for patients receiving intraventricular rt-PA for IVH from January 2004 to September 2009. Safety was assessed by the presence of EVD tract hemorrhage by CT at baseline after EVD placement, worsening hemorrhage after rt-PA, and CSF infection. IVH volumetrics were assessed by the Le Roux score and outcomes by Glasgow Outcome Scale and modified Rankin Scale.

Results

Twenty-seven patients received rt-PA for IVH. Median dose was 2 mg (range 0.3–8) and a median of two doses (range 1–17) were given. Worsening EVD catheter tract hemorrhage after rt-PA was 46.7 %, with a significantly higher incidence of worsening tract hemorrhage seen with incorrectly placed EVDs (p = 0.04). IVH hematoma burden decreased by a median Le Roux score of 10 (range 3–16) prior to rt-PA to 4 (range 0–16) after rt-PA. There were no central nervous system bacterial infections.

Conclusion

Intraventricular rt-PA appears to be relatively safe especially when all EVD fenestrations are within the ventricle and reduces IVH burden similar to other studies. We describe a CT-based EVD tract hemorrhage grading scale to evaluate EVD tract hemorrhage before and after thrombolysis, and a bone-window technique to evaluate EVD fenestrations prior to IVH thrombolysis. Further research is needed evaluating these imaging techniques in regard to intraventricular thrombolytic safety and EVD tract hemorrhage.     

Relationship of Height to Site‐Specific Fracture Risk in Postmenopausal Women

Height has been associated with increased risk of fracture of the neck of femur. However, information on the association of height with fractures at other sites is limited and conflicting. A total of 796,081 postmenopausal women, who reported on health and lifestyle factors including a history of previous fractures and osteoporosis, were followed for 8 years for incident fracture at various sites by record linkage to National Health Service hospital admission data. Adjusted relative risks of fracture at different sites per 10‐cm increase in height were estimated using Cox regression. Numbers with site‐specific fractures were: humerus (3036 cases), radius and/or ulna (1775), wrist (9684), neck of femur (5734), femur (not neck) (713), patella (649), tibia and/or fibula (1811), ankle (5523), and clavicle/spine/rib (2174). The risk of fracture of the neck of femur increased with increasing height (relative risk [RR] = 1.48 per 10‐cm increase, 99% confidence interval [CI] 1.39–1.57) and the proportional increase in risk was significantly greater than for all other fracture sites (p_{heterogeneity} < 0.001). For the other sites, fracture risk also increased with height (RR = 1.15 per 10 cm, CI 1.12–1.18), but there was only very weak evidence of a possible difference in risk between the sites (p_{heterogeneity} = 0.03). In conclusion, taller women are at increased risk of fracture, especially of the neck of femur. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).     

Genetic marking shows that Ph+ cells present in autologous transplants of chronic myelogenous leukemia (CML) contribute to relapse after autologous bone marrow in CML

Relapse after autologous bone marrow transplantation for chronic myelogenous leukemia (CML) can be due either to the persistence of leukemia cells in systemic tissues following preparative therapy, or due to the persistence of leukemia cells in the autologous marrow used to restore marrow function after intensive therapy. To help distinguish between these two possible causes of relapse, we used safety-modified retroviruses, which contain the bacterial resistance gene NEO, to mark autologous marrow cells that had been collected from patients early in the phase of hematopoietic recovery after in vivo chemotherapy. The cells were then subjected to ex vivo CD34 selection following collection and 30% of the bone marrow were exposed to a safety-modified virus. This marrow was infused after delivery of systemic therapy, which consisted of total body irradiation (1,020 cGy), cyclophosphamide (120 mg/kg), and VP-16 (750 mg/m2). RT PCR assays specific for the bacterial NEO mRNA, which was coded for by the virus, and the bcr-abl mRNA showed that in two evaluable CML patients transplanted with marked cells, sufficient numbers of leukemia cells remained in the infused marrow to contribute to systemic relapse. In addition, both normal and leukemic cells positive for the retroviral transgenome persisted in the systemic circulation of the patients for at least 280 days posttransplant showing that the infused marrow was responsible for the return of hematopoiesis following the preparative therapy. This observation shows that it is possible to use a replication-incompetent safety-modified retrovirus in order to introduce DNA sequences into the hematopoietic cells of patients undergoing autologous bone marrow transplantation. Moreover, this data suggested that additional fractionation procedures will be necessary to reduce the probability of relapse after bone marrow transplantation in at least the advanced stages of the disease in CML patients undergoing autologous bone marrow transplantation procedures.