Activation of the human posterior parietal cortex by median nerve stimulation

We recorded somatosensory evoked magnetic fields from ten healthy, right-handed subjects with a 122-channel whole-scalp SQUID magnetometer. The stimuli, exceeding the motor threshold, were delivered alternately to the left and right median nerves at the wrists, with interstimulus intervals of 1, 3, and 5 s. The first responses, peaking around 20 and 35 ms, were explained by activation of the contralateral primary somatosensory cortex (SI) hand area. All subjects showed additional deflections which peaked after 85 ms; the source locations agreed with the sites of the secondary somatosensory cortices (SII) in both hemispheres. The SII responses were typically stronger in the left than the right hemisphere. All subjects had an additional source, not previously reported in human evoked response data, in the contralateral parietal cortex. This source was posterior and medial to the SI hand area, and evidently in the wall of the postcentral sulcus. It was most active at 70–110 ms.     

Association between regularity in dapsone (DDS) treatment and development of deformity

The existence of an association between regularity in dapsone intake and the development of deformity was investigated in 5746 leprosy patients under treatment in South India. The incidence of deformity, year by year over a 5-year period, increased significantly with increasing levels of drug collection. The excess incidence in "more regular" patients was significant at all ages and in both sexes in nonlepromatous (N) cases. The same was true in intermediate (N?L) cases except in patients under 15 years of age. The evidence in lepromatous (L) cases was not so consistent. Independent confirmation of the presence of the association was sought through a matched case-control type of analysis with 140 N, 48 N?L, and 81 L cases, matching being undertaken with respect to sex, age, type of leprosy, year of starting treatment, and observation period. This showed that the mean regularity in cases (deformed patients) before the development of deformity was significantly higher than the mean regularity in the corresponding matched controls, the differences being particularly large among the N and N?L types. These findings raise the possibility of a causal link between regular dapsone intake and the development of deformity.     

The concurrence of multiple sclerosis and amyotrophic lateral sclerosis

We report the clinical and pathological findings of the unusual combination of two idiopathic central nervous system diseases, multiple sclerosis and amyotrophic lateral sclerosis in a 56 year old physician with a twenty-seven year history of a disease initially characterized by relapses and remissions, followed by an eight year quiescent period. During the last year of life there was rapid deterioration with development of generalized weakness, atrophy, weight loss and fasciculations of body and tongue, and associated difficulty with swallowing and sudden respiratory failure. The autopsy confirmed characteristic "burned out" plaques of multiple sclerosis and anterior horn cell and axonal degeneration of amyotrophic lateral sclerosis.     

Effect of dihydroergosine (DHESN) on the serotoninergic system and behaviour: Is DHESN a new antidepressive agent?

Acute (50.0 mg/kg) and repeated (0.1–10.0 mg/kg) administration of dihydroergosine (DHESN) to rats over 5 days lowered the concentration of 5-HIAA in the brain. DHESN given acutely increased the brain 5-HT in p-CPA-treated animals and diminished the probenecid-induced increase in brain 5-HIAA. In pargyline-treated rats DHESN enhanced the 5-HT/5-HIAA ratio. DHESN administered to rats repeatedly over 5 days decreased the level of 5-HT in blood platelets, and in vitro at concentrations of 10^-4 M and 10^-3 M inhibited the uptake of [¹⁴C]-5-HT in platelets. DHESN (10.0–100.0 mg/kg) potentiated the 5-HT syndrome produced in rats by pargyline and 5-HTP. This potentiation was blocked with cyproheptadine but not with haloperidol. DHESN (1.0 and 10.0 mg/kg) lowered the locomotor activity of rats and 10.0 mg/kg DHESN also reduced the duration of immobility in rats forced to swim in a restricted space. The results indicate that DHESN, like antidepressants, decreases the turnover of serotonin in the brain and potentiates the 5-HT-mediated behaviour. This might suggest that the drug should be further investigated for its potential antidepressive properties.     

What is the Level of Evidence Substantiating Commercial Payers’ Coverage Policies for Total Joint Arthroplasty?

BackgroundThe prevalence of total joint arthroplasty (TJA) in the United States has drawn the attention of health care stakeholders. The payers have also used a variety of strategies to regulate the medical necessity of these procedures. The purpose of this study was to examine the level of evidence of the coverage policies being used by commercial payers in the United States.MethodsThe references of the coverage policies of four commercial insurance companies were reviewed for type of document, level of evidence, applicability to a TJA population, and success of nonoperative treatment in patients with severe degenerative joint disease.Results282 documents were reviewed. 45.8% were primary journal articles, 14.2% were level I or II, 41.2% were applicable to patients who were candidates for TJA, and 9.9% discussed the success of nonoperative treatment in patients who would be candidates for TJA.ConclusionMost of the references cited by commercial payers are of a lower level of scientific evidence and not applicable to patients considered to be candidates for TJA. This is relatively uniform across the reviewed payers. The dearth of high-quality literature cited by commercial payers reflects the lack of evidence and difficulty in conducting high level studies on the outcomes of nonoperative versus operative treatment for patients with severe, symptomatic osteoarthritis. Patients, surgeons, and payers would all benefit from such studies and we encourage professional societies to strive toward that end through multicenter collaboration.     

Migraine-like headaches associated with nickel allergy requiring removal of atrial septal defect closure device

There is a deficit of literature regarding the association between nickel allergy–induced symptoms and implanted devices. This report describes a case of nickel allergy causing debilitating migraine-like symptoms, failing to resolve with medical therapy, requiring surgical removal of the device and repair of the defect.     

Elevated neutrophil to lymphocyte ratio is associated with poor long-term survival and graft failure after lung transplantation

PurposeWe aimed to assess the prognostic value of Neutrophil to Lymphocyte Ratio (NLR) on long-term outcomes and graft dysfunction after lung transplantation.MethodsWe retrospectively reviewed all patients receiving a lung transplant at our institution from 2011 to 2014. The primary exposure was elevated NLR at the time of transplant, defined by NLR>4. The primary outcomes were graft failure and three-year all-cause mortality. Multivariate logistic regression and Kaplan-Meier survival analysis were used to analyze outcomes.Results95 patients were included. 40 patients (42%) had an elevated NLR. Elevated NLR was associated with graft failure (OR: 4.7 [1.2–18.8], p = 0.02), and three-year mortality (OR: 5.4 [1.3–23.2], p = 0.03) on multivariate logistic regression. Patients with elevated NLR demonstrated significantly lower survival on Kaplan-Meier analysis (50% versus 74%, p = 0.02). The c-statistic for our multivariate model was 0.91.ConclusionElevated neutrophil to lymphocyte ratio is associated with poor long-term survival and graft failure after lung transplantation.     

The role of bone marrow microRNA (miR) in erythropoietic dysfunction after severe trauma

BackgroundPrevious data has shown that severe traumatic injury is associated with bone marrow dysfunction, which manifests as persistent injury-associated anemia. This study sought to identify whether the expression of erythropoiesis-related microRNAs were altered in the bone marrow of trauma patients to determine if these microRNAs play a role in persistent injury-associated anemia.MethodsBone marrow was collected from severely injured trauma patients who underwent fracture fixation as well as patients who underwent elective hip replacement. There were 27 trauma patients and 10 controls analyzed. Total RNA and microRNA were isolated from CD34-positive cells using the RNeasy Plus Mini kit, and genome-wide microRNA expression patterns were assayed. Genes with significant expression differences were found using BRB-ArrayTools with a significance of P < .01.ResultsThere were marked differences in expression of 108 microRNAs in the trauma group when compared with hip replacement patients. Four of these microRNAs play a role in regulating erythropoiesis: microRNA-150, microRNA-223, microRNA15a, and microRNA-24. These microRNAs were all upregulated significantly, with trauma/hip replacement fold changes of 1.7, 1.8, 1.2, and 1.2 respectively, and all act to suppress or regulate erythropoiesis.ConclusionAssessment of the bone marrow microRNA profile in trauma patients compared to those undergoing elective hip replacement revealed the differential expression of microRNA-150, microRNA-223, microRNA-15a, and microRNA-24. These microRNAs all play a role in decreased erythroid progenitor cell growth and provide important insight to the erythropoietic dysfunction seen after trauma.     

Higher mortality rates associated with rheumatoid arthritis in Saskatchewan,Canada, 2001–2019

ObjectivesTo estimate provincial all-cause mortality rates of Saskatchewan people with rheumatoid arthritis (RA) for comparison with the general population over time and between different geographic regions.MethodsSaskatchewan provincial administrative health databases (2001–2019) were utilized as data sources. Two RA case definitions were employed: (1) ≥ 3 physician billing diagnoses, at least 1 from a specialist (rheumatologist, general internist or orthopaedic surgeon) within 2 years; (2) ≥ 1 hospitalization diagnosis (ICD-9 code 714, and ICD-10-CA codes M05, M06). Data from these definitions were combined to create an administrative data RA cohort. All-cause mortality rates across geographic regions, between rural/urban residences and between sexes were examined.ResultsOver an 18-year span, between fiscal-year 2001–2002 and fiscal-year 2018–2019, age- and sex-adjusted mortality rates ranged from 17.10 to 21.04 (95% CI 14.77, 19.44; 18.03, 24.05)/1000 RA person-years, compared with mortality rates for the general Saskatchewan population without RA, which ranged from 9.37 to 10.88 (95% CI 9.23, 9.51; 10.72, 11.05)/1000 person-years. Fiscal-year mortality rate ratios ranged from 1.82 to 2.13 (95% CI 1.56, 2.13; 1.83, 2.46). Provincial mortality rates were higher in men than in women for both general and RA populations. Northern Saskatchewan mortality rates were significantly higher in the general population but did not achieve significance compared with other provincial regions for the RA population. Regression analysis identified age, male sex, RA and geographic region as factors contributing to increased mortality. A trend towards lower mortality rates over time was observed.ConclusionHigher mortality rates were observed in the RA population overall. Men had higher mortality rates, as did residents of Northern Saskatchewan compared with residents of other regions for the general population.