Biochemical alterations associated with ALS

Our objective was to identify metabolic pathways affected by ALS using non-targeted metabolomics in plasma, comparing samples from healthy volunteers to those from ALS patients. This discovery could become the basis for the identification of therapeutic targets and diagnostic biomarkers of ALS. Two distinct cross-sectional studies were conducted. Plasma was collected from 62 (Study 1) and 99 (Study 2) participants meeting El Escorial criteria for possible, probable, or definite ALS; 69 (Study 1) and 48 (Study 2) healthy controls samples were collected. Global metabolic profiling was used to detect and evaluate biochemical signatures of ALS. Twenty-three metabolites were significantly altered in plasma from ALS patients in both studies. These metabolites include biochemicals in pathways associated with neuronal change, hypermetabolism, oxidative damage, and mitochondrial dysfunction, all of which are proposed disease mechanisms in ALS. The data also suggest possible hepatic dysfunction associated with ALS. In conclusion, the data presented here provide insight into the pathophysiology of ALS while suggesting promising areas of focus for future studies. The metabolomics approach can generate novel hypotheses regarding ALS disease mechanisms with the potential to identify therapeutic targets and novel diagnostic biomarkers.     

Humanitarianism in surgery

Purpose

Humanitarianism is by definition a moral of kindness, benevolence and sympathy extended to all human beings. In our view as surgeons working in underserved countries, humanitarianism means performing the best operation in the best possible circumstances with high income country (HIC) results and training in-country surgeons to do the same. Hernia Repair for the Underserved (HRFU), a not for profit organization, is developing a long term public health initiative for hernia surgery in Western Hemisphere countries. We report the progress of HRFUs methods to render humanitarian care.

Methods

In a collaborative effort, Creighton University and the Institute for Latin American Concern developed an outpatient surgery site for hernia surgery in Santiago, Dominican Republic. Based on this experience, we developed a sustainable care model by recruiting American and European Hernia Society expert surgeons, staff members they recommended, building relationships with local and industry partners, and selecting local surgeons to be trained in mesh hernioplasty. HRFU then extended the care model to other Western Hemisphere countries.

Results

Between 2004 and 2015, the HRFU elective hernia morbidity and mortality rates for 2052 hernia operations were 0.7 and 0%, respectively. This is consistent with outcomes from HICs and confirms the feasibility of a public health initiative based on the principles of the Preferential Option for the Poor.

Conclusions

HRFU has recorded HIC morbidity and mortality rates for hernia surgery in low and middle income countries and has initiated a new surgical training model for sustainability of effect.

     

The thermal effect on the blood flow response to electrical stimulation.

BACKGROUND: Wounds, especially in the elderly, can be life threatening. One modality which allegedly increases blood flow (BF) as an aid to heal chronic wounds is electrical stimulation. This technique applies electrical current (ES) across wounds. However, while many studies show positive findings, others do not. The purpose of this investigation was to investigate some of this inconsistency in results by determining the effect of environmental temperature on the circulation of the skin which may negate the effects of electrical stimulation in a clinical setting. MATERIAL/METHODS: Ten people with no wounds, controls (C), and 12 people with wounds (W) were examined in a thermally neutral or cool room (20 degrees C) and a warm room (34 degrees C) to observe the effect of reducing sympathetic vasoconstrictor activity on the response to 5 and 15 mA sine wave biphasic ES delivered by 2x2 cm surface electrodes. RESULTS: C and W subjects showed a greater BF in the skin in a warm room. In group C, after 30 minutes of stimulation at a current of 15 milliamps, BF increased significantly (p<0.05) but by an average of only 4 flux in the cool room. In the warm environment, BF increased significantly (p<0.01) by 19.3+/-7 flux and increased further during the 60 minute recovery phase. In the W group, BF during ES increased much more during stimulation in a warm room compared to a cool room. CONCLUSIONS: The results show that local vasoconstriction due to exposure to a warm global temperature greatly increases the response of the skin the ES.     

Improved diagnostic effectiveness with a sequential diagnostic paradigm in idiopathic pediatric sensorineural hearing loss.

OBJECTIVES: To determine whether a stepwise diagnostic paradigm is more diagnostically efficient and cost-effective than a simultaneous testing approach in the evaluation of idiopathic pediatric sensorineural hearing loss (SNHL). DESIGN: Prospective prevalence study. SETTING: Tertiary referral children's hospital. PATIENTS: Consecutive children (n = 150) presenting with idiopathic SNHL in the last 2 years. INTERVENTIONS: All children were evaluated with full diagnostic evaluations including GJB2 screens, temporal bone computed tomography scans, and laboratory investigations. MAIN OUTCOME MEASURES: 1) Diagnostic yields of GJB2 screens, imaging, and laboratory results per SNHL category; 2) Cost analysis comparing a sequential versus a simultaneous testing approach. RESULTS: Overall, 12.0% of patients had biallelic mutations in the GJB2 gene, whereas 30% of patients had an abnormality on temporal bone scan. Laboratory testing did not reveal the SNHL etiology in any patient. While maintaining diagnostic accuracy, significant cost savings were inferred by using a sequential diagnostic algorithm. Our data show children with severe to profound SNHL should first be tested with a GJB2 screen, as opposed to those with milder SNHL, who should undergo imaging as the initial testing step. In patients with initially positive GJB2 or imaging screens, logistic regression analysis significantly predicted negative results on further testing. CONCLUSIONS: A stepwise diagnostic paradigm tailored to the level of the hearing loss in children with bilateral SNHL is more diagnostically efficient and cost effective than the more commonly used full, simultaneous testing approach. Laboratory investigation should not be routine but based on clinical history.     

Re-operation for recurrent coronary artery and graft disease. A review of 73 patients in a group of 2573 consecutive first operations

Between January 1980 and December 1986, 2573 patients underwent simple first time coronary artery bypass grafting, of whom 73 (65 males and 8 females) aged 34-69 years (mean 51.3 yrs) had repeat bypass grafts at Wythenshawe Hospital, Manchester. Of these 73 patients, 15 had a previous myocardial infarction, 5 hyperlipidaemia, 4 systemic hypertension, and 12 had a strong family history of ischemic heart disease. There was an overall deterioration of left ventricular function at the time of reoperation. The interval between the two operations was 5-131 months (mean 34.2 mths); recurrence of angina occurred earlier (mean 18.4 mths). Vessels grafted at the first operation were LAD (59), RCA (46), circumflex (41) and diagonal (13). The corresponding data at reoperation were LAD (55), RCA (46), circumflex (28) and diagonal (10). Blocked grafts were seen in 67 patients and new lesions noticed in 29. Reoperation was done using saphenous vein (129), internal mammary artery (5), arm veins (2) and tubular Gortex grafts (2). One patient had concurrent excision of a left ventricular aneurysm. Coronary anastomoses were performed with elective ventricular fibrillation (47) or cardioplegic arrest (91). Aortic cross clamp time varied from 0-92 minutes. Seven patients required intra-aortic balloon support. These patients died in the first 30 days, an operative mortality rate of 4.1%, and two 18 months after surgery. Sixty-eight percent of patients seen at 1 year were totally symptom free. We conclude that reoperation for coronary artery disease can be done with a low mortality and good immediate relief of symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)     

Type IIB Tampa: a variant of von Willebrand disease with chronic thrombocytopenia, circulating platelet aggregates, and spontaneous platelet aggregation

Type IIB von Willebrand disease is characterized by enhanced ristocetin- induced platelet aggregation and absence of large von Willebrand factor multimers from plasma. An alteration of the von Willebrand factor molecule resulting in increased reactivity with platelets appears to be the basis for these abnormalities. We have now identified a new variant of type IIB von Willebrand disease in a family in which the four affected members also have chronic thrombocytopenia, in vivo platelet aggregate formation, and spontaneous platelet aggregation in vitro. In spite of repeatedly prolonged bleeding times and persistent thrombocytopenia, their bleeding diathesis is only moderate.     

Splanchnic artery aneurysms and pseudoaneurysms: transcatheter embolization

Over the past 7 years, eight patients with splanchnic artery aneurysms and pseudoaneurysms were studied and treated. Transcatheter embolization resulted in occlusion of the lesions in all eight patients. Potentially risky and difficult surgery was avoided completely in four patients. Three patients had elective surgery at a later date when their condition was more stable. The remaining patient had definitive surgery after embolization. Transcatheter embolization should be the initial treatment of choice in splanchnic artery aneurysms and pseudoaneurysms.