Chronic lower extremity ischemia: a human model of ischemic tolerance.

BACKGROUND: Ischemic preconditioning (IPC) has been found in animals to have a protective effect against future ischemic injury to muscle tissue. Such injury is unavoidable during some surgical procedures. To determine whether chronic ischemia in the lower extremities would imitate IPC and reduce ischemic injury during vascular surgery, we designed a controlled clinical study. PATIENTS AND METHODS: Two groups of patients at a university-affiliated medical centre with chronic lower-extremity ischemia served as models of IPC: 6 patients awaiting femoral distal bypass (FDB) and 4 scheduled for aortobifemoral (ABF) bypass grafting for aortoiliac occlusive disease. Seven patients undergoing elective open repair of an infrarenal abdominal aortic aneurysm (AAA) were chosen as non-IPC controls. Three hematologic indicators of skeletal-muscle injury, lactate dehydrogenase (LDH), creatine kinase (CK) and myoglobin, were measured before placement of the proximal clamp, during surgical ischemia, immediately upon reperfusion, 15 minutes after and 1 hour after reperfusion, and during the first, second and third postoperative days. RESULTS: Baseline markers of skeletal-muscle injury were similar in all groups. In postreperfusion samples, concentrations of muscle-injury markers were significantly lower in the 2 PC groups than in the control group. For example, at day 2, LDH levels were increased by about 30% over baseline measures in the elective AAA (control) group, whereas levels in the FDB and ABF groups remained statistically unchanged from baseline. Myoglobin in controls had increased by 977%, but only by 160% in the FDB and 528% in the ABF groups. CK levels, in a similar trend, were 1432% higher in the control group and only 111% (FDB) and 1029% (ABF) in the study groups. Taken together, these data represent a significant level of protection. CONCLUSIONS: Patients with chronic lower-extremity ischemia suffered less severe ischemic injury after a period of acute ischemia than those with acute ischemia alone. Ischemic preconditioning is one proposed mechanism to help explain this protective effect.     

Stromal progenitor cell therapy corrects the wound-healing defect in the ischemic rabbit ear model of chronic wound repair

Chronic wounds create a formidable clinical problem resulting in considerable morbidity and healthcare expenditure. The etiology for wound healing impairment appears to be multifactorial; however, ischemia is a common factor in most types of chronic wounds. Ideal therapy for such wounds would be to correct deficiencies in growth factors and matrix components and provide cellular precursors required for timely wound closure. We hypothesized that stromal progenitor cell (SPC) therapy could correct the ischemic wound-healing defect through both direct and indirect mechanisms. To test this hypothesis, we used the ischemic rabbit ear model of chronic wound healing. We found that treatment of the wounds with SPCs was able to reverse the ischemic wound-healing impairment, with improved granulation tissue formation and reepithelialization compared with vehicle or bone marrow mononuclear cell controls. In vitro, SPCs were found to produce factors involved in angiogenesis and reepithelialization, and extracellular matrix components, providing evidence for both direct and indirect mechanisms for the observed correction of the healing impairment in these wounds. Treatment of ischemic wounds with SPCs can dramatically improve wound healing and provides a rationale for further studies focused on SPCs as a potential cellular therapy in impaired wound healing.     

Autonomy and modernisation: the management of change in an English primary care trust

Recent New Labour policy for the ‘modernisation’ of Government places a good deal of emphasis on decentralisation. This emphasis is particularly marked in relation to the organisation of primary care. However, like hospitals and other National Health Service institutions, primary care trusts (PCTs) are subject to a substantial raft of centrally established performance targets and indicators, including those which contribute to the public award of between zero and three performance ‘stars’. This raises questions about the extent to which employees can exercise autonomy in the context of rigid top‐down directives. This paper presents findings from a study using participant observation and interviews to examine the impact of a training course aimed ostensibly at increasing employee autonomy in an English PCT. The suggestion is that attempts to make employees more autonomous can be seen as a strategy for increasing central control based upon the internalisation by the employees of centrally promulgated values. The attraction of such strategies is that they may be potentially more effective and less costly than alternative strategies of direct control. However, the study suggests that the outcome of attempts by such methods as programmes to increase employee autonomy may be very different from those intended.     

Four-Year Follow-up on Endovascular Radiofrequency Obliteration of Great Saphenous Reflux

BACKGROUND: Endovascular radiofrequency obliteration has been used since 1998 as an alternative to conventional vein stripping surgery for elimination of saphenous vein insufficiency. OBJECTIVE: To demonstrate the long-term efficacy of this treatment modality. METHODS: Data were prospectively collected in a multicenter ongoing registry. Only great saphenous vein above-knee treatments were included in this study. Eight hundred ninety patients (1,078 limbs) were treated prior to November 2003 at 32 centers. Clinical and duplex ultrasound follow-up was performed at 1 week, 6 months, and 1, 2, 3, and 4 years. RESULTS: Among 1,078 limbs treated, 858 were available for follow-up within 1 week, 446 at 6 months, 384 at 1 year, 210 at 2 years, 114 at 3 years, and 98 at 4 years. The vein occlusion rates were 91.0%, 88.8%, 86.2%, 84.2%, and 88.8%, respectively; the reflux-free rates were 91.0%, 89.3%, 86.2%, 86.0%, and 85.7%, respectively; and the varicose vein recurrence rates were 7.2%, 13.5%, 17.1%, 14.0%, and 21.4%, respectively, at each follow-up time point at 6 months, and 1, 2, 3, and 4 years. Patient symptom improvement persisted over 4 years. CONCLUSIONS: Endovascular temperature-controlled radiofrequency obliteration of saphenous vein reflux exhibits an enduring treatment efficacy clinically, anatomically, and hemodynamically up to 4 years following treatment.     

It's all about sex: gender, lung development and lung disease.

Accumulating evidence suggests that gender affects the incidence, susceptibility and severity of several lung diseases. Gender also influences lung development and physiology. Data from both human and animal studies indicate that sex hormones might contribute to disease pathogenesis or serve as protective factors, depending on the disease involved. In this review, the influence of gender and sex hormones on lung development and pathology will be discussed, with specific emphasis on pulmonary fibrosis, asthma and cancer.     

Pretransplant bilateral hand-assisted laparoscopic nephrectomy in adult patients with polycystic kidney disease.

Laparoscopic procedures continue to gain popularity over traditional open procedures for a number of abdominal and pelvic surgeries. With increasing experience, the application of this technique is rising because it provides an alternative, less invasive, approach to various surgical procedures. Herein, we report our experience with adult patients with polycystic kidney disease, requiring bilateral laparoscopic nephrectomy before renal transplantation.     

Technetium-99m RBC scintigraphy in the evaluation of small bowel leiomyoma

Hypervascularity and persistent uptake were demonstrated in a small bowel leiomyoma not actively bleeding at the time of Tc-99m RBC scintigraphy. The potential value of Tc-99m RBC scanning in the evaluation of benign small bowel tumors is discussed.     

Guidelines for Trials of Behavioral Treatments for Recurrent Headache, First Edition: American Headache Society Behavioral Clinical Trials Workgroup

Guidelines for design of clinical trials evaluating behavioral headache treatments were developed to facilitate production of quality research evaluating behavioral therapies for management of primary headache disorders. These guidelines were produced by a Workgroup of headache researchers under auspices of the American Headache Society. The guidelines are complementary to and modeled after guidelines for pharmacological trials published by the International Headache Society, but they address methodologic considerations unique to behavioral and other nonpharmacological treatments. Explicit guidelines for evaluating behavioral headache therapies are needed as the optimal methodology for behavioral (and other nonpharmacologic) trials necessarily differs from the preferred methodology for drug trials. In addition, trials comparing and integrating drug and behavioral therapies present methodological challenges not addressed by guidelines for pharmacologic research. These guidelines address patient selection, trial design for behavioral treatments and for comparisons across multiple treatment modalities (eg, behavioral vs pharmacologic), evaluation of results, and research ethics. Although developed specifically for behavioral therapies, the guidelines may apply to the design of clinical trials evaluating many forms of nonpharmacologic therapies for headache.