Spinal cord stimulation for refractory angina pectoris: a retrospective analysis of efficacy and cost-benefit

BACKGROUND: Patients with refractory angina pectoris have severe symptoms despite optimal medication, but are not suitable for revascularisation. Spinal cord stimulation (SCS) has been used for treating refractory angina pectoris since 1985. The efficacy of SCS has been proven by randomised controlled trials and follow-up studies have shown that SCS is a safe treatment. The objective of the current study was to retrospectively analyse the clinical outcomes and cost-benefit of SCS in patients with refractory angina pectoris. METHODS: Eighteen months after SCS implantation, the effects on Canadian Cardiovascular Society (CCS) functional level and acute symptom relief of 24 patients with permanent SCS were analysed by review of medical records. Nineteen of these 24 patients were able to report their anginal frequency, nitroglycerin consumption and subjective perception on physical activity and quality of life. RESULTS: Angina frequency decreased from a median of 14.0 to 2.3 attacks/week (p < 0.01). Nitroglycerin intake decreased from a median of 27.5 to 1.5 doses/week (p < 0.01). Canadian Cardiovascular Society angina class improved from a median of three to two (p < 0.001). During a three-year period before SCS implantation, the hospitalisation rate and duration related to coronary artery disease increased progressively. The duration of hospitalisation increased from a median of three to 10 days/patient/year. In the year after SCS implantation the duration of hospitalisation decreased to a median of 0 day/patient/year (p < 0.001). The cost of hospital care due to coronary artery disease decreased significantly thereafter. The total cost of SCS procedure was recovered within 16 months after implantation, which is less than 40% of the device life span. CONCLUSIONS: This retrospective study indicates that SCS treatment alleviates angina symptoms and improves quality of life. The treatment is also effective in preventing hospitalisations and saving costs in hospital care. A prospective study is warranted to confirm the current observations.     

D-14 Monoclonal antibody to carcinoembryonic antigen: immunohistochemical analysis of formalin-fixed,paraffin-embedded human colorectal carcinoma,tumors of non-colorectal origin and normal tissues

Summary The reactivity of D-14 monoclonal antibody (mAb) to a specific epitope of carcinoembryonic antigen (CEA) was evaluated on formalin-fixed, paraffin-embedded tissues. A total of 52 normal tissues, 90 colorectal carcinomas and 127 non-colorectal neoplasms were tested using the peroxidase/antiperoxidase technique. D-14 mAb did not react with normal tissues apart from producing a weak staining of normal colonic glands immediately adjacent to the neoplastic structures. All 61 primary and 29 metastatic colorectal carcinomas expressed the carcinoembryonic antigen. However, there was considerable heterogeneity in cellular antigen expression in both primary and metastatic colorectal carcinomas with 10%–99% of tumor cells staining. Of 22 stomach adenocarcinomas, 14 were also immunoreactive, as were 2 of 5 pancreatic carcinomas. Only 6 of 100 neoplasms of non-gastrointestinal origin expressed weak to moderate immunoreactivity. In 7 cases, colorectal micrometastases not recognized in conventional hematoxylin and eosin slides could be identified with D-14 mAb. The specificity of this antibody could be used in differentiating colorectal carcinomas from other types of tumors, including adenocarcinoma from other sites.This paper was presented at the 1989 Annual Meeting of the American Association for Cancer Research Inc., San Francisco, California     

The role of intramyocellular lipids during hypoglycemia in patients with intensively treated type 1 diabetes

CONTEXT: Endocrine defensive mechanisms provide for energy supply during hypoglycemia. Intramyocellular lipids (IMCL) were recently shown to contribute to energy supply during exercise. OBJECTIVE: The objective of this study was to assess the contribution of IMCL compared with lipolysis and endogenous glucose production (EGP) to insulin-mediated hypoglycemia counterregulation in patients with type 1 diabetes mellitus (T1DM). DESIGN AND SETTING: This was a prospective explorative study performed in a university research facility. PARTICIPANTS: Six well-controlled T1DM (age, 29 +/- 4 yr; body mass index, 23.4 +/- 1.0 kg/m2; hemoglobin A1c, 6.3 +/- 0.1%) and six nondiabetic humans (controls; age, 28 +/- 2 yr; body mass index, 23.4 +/- 1.0 kg/m2; hemoglobin A1c, 5.1 +/- 0.1%) were studied. INTERVENTIONS: We performed 240-min hypoglycemic (approximately 3 mM)-hyperinsulinemic (0.8 mU/kg x min) clamps on separate days to measure: 1) systemic lipolysis ([2H5]glycerol turnover), EGP ([6,6-(2)H2]glucose), and local lipolysis in abdominal s.c. adipose tissue and gastrocnemius muscle (microdialysis); and 2) IMCL (by 1H nuclear magnetic resonance spectroscopy) in soleus and tibialis anterior muscle. MAIN OUTCOME MEASURES: The main outcome measures were changes in IMCL during prolonged hypoglycemia. RESULTS: At baseline, EGP, glycerol turnover, and IMCL were not different between the groups. During hypoglycemia, hormonal counterregulation was blunted in T1DM (peak: glucagon, 68 +/- 4 vs. 170 +/- 37 pg/ml; cortisol, 16 +/- 2 vs. 24 +/- 2 microg/dl; epinephrine, 274 +/- 84 vs. 597 +/- 212 pg/ml; all P < 0.05 vs. control). T1DM had approximately 50% lower EGP (4.6 +/- 0.6 vs. 10.9 +/- 0.5 micromol/kg x min; P < 0.005), but approximately 40% higher glycerol turnover (374 +/- 21 vs. 272 +/- 19 micromol/kg x min; P < 0.01). Glycerol concentrations in muscle (T1DM, 302 +/- 22 control, 346 +/- 17 micromol/liter) and adipose tissue (264 +/- 25 vs. 318 +/- 25 micromol/liter) did not differ between groups. IMCL in soleus and tibialis anterior muscle did not change from baseline during hypoglycemia. CONCLUSIONS: In well-controlled T1DM, impaired hypoglycemia counterregulation is associated with decreased glucose production and augmented whole body lipolysis, which cannot be explained by either hydrolysis of muscle triglycerides or increased abdominal s.c. adipose tissue lipolysis.     

Attenuation of flightless I improves wound healing and enhances angiogenesis in a murine model of type 1 diabetes

Aims/hypothesis

Skin lesions and ulcerations are severe complications of diabetes that often result in leg amputations. In this study we investigated the function of the cytoskeletal protein flightless I (FLII) in diabetic wound healing. We hypothesised that overexpression of FLII would have a negative effect on diabetic wound closure and modulation of this protein using specific FLII-neutralising antibodies (FnAb) would enhance cellular proliferation, migration and angiogenesis within the diabetic wound.

Methods

Using a streptozotocin-induced model of diabetes we investigated the effect of altered FLII levels through Flii genetic knockdown, overexpression or treatment with FnAb on wound healing. Diabetic wounds were assessed using histology, immunohistochemistry and biochemical analysis. In vitro and in vivo assays of angiogenesis were used to assess the angiogenic response.

Results

FLII levels were elevated in the wounds of both diabetic mice and humans. Reduction in the level of FLII improved healing of murine diabetic wounds and promoted a robust pro-angiogenic response with significantly elevated von Willebrand factor (vWF) and vascular endothelial growth factor (VEGF)-positive endothelial cell infiltration. Diabetic mouse wounds treated intradermally with FnAb showed improved healing and a significantly increased rate of re-epithelialisation. FnAb improved the angiogenic response through enhanced formation of capillary tubes and functional neovasculature. Reducing the level of FLII led to increased numbers of mature blood vessels, increased recruitment of smooth muscle actin-α-positive cells and improved tight junction formation.

Conclusions/interpretation

Reducing the level of FLII in a wound may be a potential therapeutic approach for the treatment of diabetic foot ulcers.     

Aerosolized clindamycin is superior to aerosolized dexamethasone or clindamycin-dexamethasone combination in the treatment of severe Porphyromonas gingivalis aspiration pneumonia in an experimental murine model

Adjunctive corticosteroid treatment to reduce excessive local inflammatory response in pneumonia is controversial. To study the effects of an early local adjunct dexamethasone treatment on the course of pneumonia and inflammatory/cytokine response, mice were intratracheally inoculated with live Porphyromonas gingivalis and treated with either clindamycin (C), dexamethasone (D), C+D combination, or were not treated (Pg). Six mice from each group were euthanized at 6, 24, 72, and 168 hours after inoculation. Levels of tumor necrosis factor (TNF)-α, soluble TNF-α receptors (sTNFR1 and sTNFR2), interleukin (IL)-1β, and IL-6 in the serum and lung-homogenate supernatant were determined. Lung samples were histopathologically assessed and all findings compared to those found in 24 sham-inoculated mice (phosphate-buffered saline [PBS]). Severe P. gingivalis-induced bronchopneumonia progressed from 24 hours, peaked at 72 hours, and resolved after 168 hours with changes in local and systemic cytokine levels. Clindamycin-treated mice developed only mild bronchopneumonia that resolved fast (72 hours) with an early (6-24 hours) normalization of local and systemic cytokine levels. Similar course of pneumonia and cytokine level changes were observed in mice treated with C+D, but later. Early (6-24 hours) local elevation of sTNFRs was observed in C and C+D groups of mice, whereas nontreated (Pg) mice had increased systemic sTNFRs. Severe bronchopneumonia with delayed resolution was observed in D-group mice, with an early local and systemic decrease in sTNFR1 and persistent elevation of local TNF-α. Clindamycin or a clindamycin-dexamethasone combination treatment significantly improves the course of P. gingivalis-aspiration pneumonia, but more so if clindamycin alone is used. A favorable course of pneumonia seems to be associated with an early elevation of sTNFRs and normalization of TNF-α.     

Learning from UJAMBO: Perspectives on Gynecologic Care in African Immigrant and Refugee Women in Boston,Massachusetts

African-born immigrant women, and particularly refugees and asylum seekers, are at risk for reproductive health disparities but inadequately use relevant gynecologic services. We sought to elucidate perspectives on gynecologic care in a population of Congolese and Somali immigrants. We conducted a secondary qualitative analysis of focus group data using a grounded theory approach and the Integrated Behavioral Model as our theoretical framework. Thirty one women participated in six focus groups. Participant beliefs included the states of pregnancy and/or pain as triggers for care, preferences included having female providers and those with familiarity with female genital cutting. Barriers included stigma, lack of partner support, and lack of resources to access care. Experiential attitudes, normative beliefs, and environmental constraints significantly mediated care preferences for/barriers to gynecologic health service utilization in this population. Centering of patient perspectives to adapt delivery of gynecologic care to immigrants and refugees may improve utilization and reduce disparities.     

The diabetes-obesity-hypertension nexus in Qatar: evidence from the World Health Survey

Background

As countries develop economically, an “epidemiological transition” occurs whereby a set of chronic diseases increasingly becomes a country’s health challenge. Against this background, this paper examines the most common conditions associated with the prevalence of diabetes in Qatar, with a specific focus on the diabetes-obesity-hypertension nexus.

Methods

We analyzed data from the World Health Organization’s World Health Survey conducted in the State of Qatar in 2006. The survey included demographic, anthropometric, and blood chemistry measurements. Using multivariate logistical regression analysis, we assessed the most common conditions associated with diabetes, using both objective and subjective measures of diabetes. The objective measures relied on random blood sugar tests, and the subjective measure included respondents who affirmatively answered the question on diabetes diagnosis. We repeated our analysis on respondents who had blood glucose levels high enough to be considered diabetic/glucose intolerant but did not answer affirmatively on the question of diabetes diagnosis.

Results

When using the objective measure of diabetes, the following conditions appeared significant: obesity (OR?=?1.5, 95% CI?=?1.2 – 1.9), higher income (OR?=?1.4, 95% CI?=?1.0 – 1.9), high cholesterol (OR?=?1.4, 95% CI?=?1.0 – 1.9), having Qatari origin (OR?=?1.3, 95% CI?=?1.0 – 1.7), and increasing systolic blood pressure (SBP) 120–139 mmHg (OR?=?1.5, 95% CI?=?1.2 – 2.0), SBP 140–159 mmHg (OR?=?2.2, 95% CI?=?1.6 – 3.1), SBP?>?160 mmHg (OR?=?3.2, 95% CI?=?2.0 – 5.3). Similar results were obtained using the subjective measure of diabetes as a dependent variable. When applied to the group of respondents that included pre-diabetics and those who did not know they were diabetic, obesity and hypertension appeared as the only statistically significant explanatory variables.

Conclusion

High prevalence of diabetes, hypertension, and especially obesity is documented among residents of Qatar. Further steps are required to tackle the most common conditions associated with the rising diabetes epidemic in the country, which might also pose significant fiscal challenges in the future.

     

Thoracic Aortic Frontier: Review of Current Applications and Directions of Thoracic Endovascular Aortic Repair (TEVAR)

Thoracic endovascular aortic repair, a minimally invasive technique is replacing the maximally invasive gold standard of thoracotomy and replacement of the descending thoracic aorta. With experience, indications have expanded to encroach on the arch and even ascending aorta. This review highlights the current state of technology, discusses controversies, and takes the perspective of a forward-thinking review to describe novel, innovative techniques that might make the entire thoracic aorta amenable to minimally invasive repair.