SIGMA-1 Receptor Gene Variants Affect the Somatosensory Phenotype in Neuropathic Pain Patients

Pain sensitivity is characterized by interindividual variability, determined by factors including genetic variation of nociceptive receptors and pathways. The sigma-1 receptor (SIGMAR1) is involved in pain modulation especially under pre-sensitized conditions. However, the contribution of SIGMAR1 genetic variants to pain generation and sensitivity is unknown yet. This study aimed to identify effects of 5 SIGMAR1 variants on the somatosensory phenotype of neuropathic pain patients (n?=?228) characterized by standardized quantitative sensory testing. Principal component analysis revealed that the SIGMAR1 variants ?297G>T (rs10814130) and 5A>C (rs1800866) significantly lowered thermal detection and heat/pressure nociception in particular in neuropathic pain patients with mainly preserved somatosensory function. Compared to wild-type, the variant allele ?297T was associated with loss of warm detection (P?=?.049), lower heat-pain sensitivity (P?=?.027) and wind-up ratio (P?=?.023) as well as increased paradoxical heat sensation (P?=?.020). Likewise for 5A>C the strongest genotype-associated differences observed were reduced peripheral (less heat hyperalgesia; P?=?.026) and central sensitization (lower mechanical pain sensitivity; P?=?.026) in variant compared to wild-type carriers. This study indicates lack of association of SIGMAR1 ?297G>T and 5A>C genetic variants to susceptibility to develop chronic pain, but significant modulation of somatosensory function in neuropathic pain patients.

Marrow transplantation for chronic myeloid leukemia: a randomized study comparing cyclophosphamide and total body irradiation with busulfan and cyclophosphamide

A prospective randomized study was conducted comparing two conditioning regimens for the treatment of patients with chronic myeloid leukemia in chronic phase by marrow transplantation from HLA identical siblings. Sixty-nine patients received 60 mg/kg of cyclophosphamide on each of 2 successive days followed by 6 fractions of total body irradiation each of 2.0 Gy (CY-TBI), and 73 patients received 16 mg/kg of busulfan delivered over 4 days followed by 60 mg/kg CY on each of 2 successive days (BU-CY). There was no significant difference between the CY-TBI and the BU-CY groups in the 3-year probabilities of survival (0.80 for both), relapse (0.13 for both), or event-free survival (CY-TBI, 0.68; BU-CY, 0.71) or in speed of engraftment or incidence of venocclusive disease of the liver. The 4-year probabilities of survival and event- free survival for patients transplanted within 1 year of diagnosis were 0.86 and 0.72, respectively, for each group. Significantly more patients in the CY-TBI group experienced major creatinine elevations. There was significantly more acute graft-versus-host disease in the CY- TBI group. Fever days, positive blood cultures, hospitalizations, and inpatient hospital days were significantly more common in the CY-TBI group than in the BU-CY group. In conclusion, the BU-CY regimen was better tolerated than, and associated with survival and relapse probabilities that compare favorably with, the CY-TBI regimen.     

Repeatability of near visual acuity measurement at high and low contrast

Purpose: The aim of this study was to determine the repeatability of high‐ and low‐contrast visual acuity (VA) measurements at near. Methods: Fifty‐five normal subjects were recruited. Inclusion criteria included visual acuity of at least 0.00 logarithm of minimum angle of resolution (logMAR) on each eye at distance. One eye was selected for this study, either the one with a better acuity or randomly chosen if there was no difference between the two eyes. Near VA was measured in a random order with the PolyU high‐contrast (PolyU‐HC), the PolyU low‐contrast (PolyU‐LC), the Precision high‐contrast (P‐HC) and the Precision low‐contrast (P‐LC) charts at 400 mm. Measurements were repeated after one to two weeks. Repeatability was presented using the 95% limits of agreement between visits. Results: The between‐visit repeatability was ±0.063 logMAR for high‐contrast and ±0.141 for low‐contrast using the PolyU charts. The between‐visit repeatability was ±0.120 logMAR for high‐contrast and ±0.110 for low‐contrast using the Precision charts. Seventeen subjects had high‐contrast VA better than ‐0.10 logMAR using Precision chart, which could not be measured by PolyU chart. The mean difference between high‐ and low‐contrast VA was 0.108 from the Precision charts (median difference of 0.10 or one line). Conclusions: The Precision charts could measure high‐contrast near VA to threshold level. Practitioners should be aware of a VA difference of more than one line in repetitive measurement, at both high and low contrast. A difference in near high‐ and low‐contrast VA of more than one line may warrant further investigation.     

Promoting Father Involvement for Child and Family Health

Paternal involvement in children's lives is associated with a variety of child outcomes, including improved cognition, improved mental health, reduced obesity rates, and asthma exacerbation. Given this evidence, the American Academy of Pediatrics has promoted actions by pediatricians to engage fathers in pediatric care. Despite these recommendations, the mother–child dyad, rather than the mother–father–child triad, remains a frequent focus of care. Furthermore, pediatric care is often leveraged to improve maternal health, such as screening for maternal depression, but paternal health is infrequently addressed even as men tend to exhibit riskier behaviors, poorer primary care utilization, and lower life expectancy. Therefore, increasing efforts by pediatric clinicians to engage fathers may affect the health of both father and child. These efforts to engage fathers are informed by currently used definitions and measures of father involvement, which are discussed here. Factors described in the literature that affect father involvement are also summarized, including culture and context; interpersonal factors; logistics; knowledge and self-efficacy; and attitudes, beliefs, and incentives. Innovative ways to reach fathers both in the clinic and in other settings are currently under investigation, including use of behavior change models, motivational interviewing, mobile technologies, peer support groups, and policy advocacy efforts. These modalities show promise in effectively engaging fathers and improving family health.     

Surgical bacterial infections and antimicrobial susceptibility patterns at Lilongwe Central Hospital

A cross sectional study was done between October 1999 and February 2000 to determine antimicrobial susceptibility patterns of consecutive bacterial isolates of 102 clinical samples among surgical in-patients at Lilongwe Central Hospital (LCH), Malawi. Antimicrobial susceptibility was determined using comparative disc diffusion techniques. 83 (81.4%) samples were culture positive for bacterial growth while 19 (18.6%) grew nothing. Of the 93 culture positive specimens, Staphylococcus aureus was the predominant organism 43(51.8%) followed by Proteus species 8(9.6%) and E. coli 7(8.4%). Overall, 98.6% of all isolates tested against ciprofloxacin were susceptible, and against gentamicin and flucloxacin were 84.8% and 66.7% respectively. 59.3% of isolates tested against chloramphenicol were resistant. We recommend a review on the use of chloramphenicol as first-line antimicrobial therapy among surgical in-patients at Lilongwe Central Hospital. We also recommend restricted use of antimicrobials so as to minimise development of drug resistance. Periodic susceptibility studies are necessary to guide judicious use of antibiotics.     

Transient bone marrow oedema: A variant pattern of sacral insufficiency fractures

A 71-year-old woman presenting with severe low back pain was found to have a large oval area of increased sacral uptake on Tc-99m MDP scan, with corresponding T1-hypointense and T2-hyperintense areas on magnetic resonance (MR) images, highly suggestive of malignancy. Open biopsies showed only callus formation. The patient responded clinically to conservative measures, with twice-repeated follow-up Tc-99m MDP and MR scans documenting resolution of transient bone marrow oedema. We suggest that this form of marrow oedema represents a variant pattern of sacral insufficiency fractures.