Response After Repeated Ketamine Injections in a Rat Model of Neuropathic Pain.

Ketamine, an N-methyl-D-aspartate antagonist, reduces pain by decreasing central sensitization and pain windup. However, chronic ketamine use can cause tolerance, dependency, impaired consciousness, urinary symptoms, and abdominal pain. This study aimed to investigate the effects of repeated ketamine injections and ketamine readministration after discontinuation in a rat model of neuropathic pain. To induce neuropathic pain, partial sciatic nerve ligation (PSNL) was performed in 15 male Wistar rats, and these animals were divided into three groups: PSNL (control), PSNL + ketamine 5 mg/kg (K5), and PSNL + ketamine 10 mg/kg (K10; n=5 each). Ketamine was injected intraperitoneally daily for 4 weeks, discontinued for 2 weeks, and then readministered for 1 week. Following PSNL, the mechanical withdrawal threshold was determined weekly using the Von Frey. The K10 group showed a significant increase in the mechanical withdrawal threshold, presented here as the target force (in g), at 21 and 28 days compared to the time point before ketamine injection (mean±SE, 276.0±24.0 vs. 21.6±2.7 and 300.0±0.0 vs. 21.6±2.7, respectively; P<0.01) and at 14, 21, and 28 days compared to the control group (108.2±51.2 vs. 2.7±1.3, 276.0±24.0 vs. 2.5±1.5, and 300.0±0.0 vs. 4.0±0.0, respectively; P<0.05). However, in the K10 group, the ketamine effects decreased significantly at 7 days after readministration compared to those after 28 days of repeated injections (P<0.05). In the K10 group, repeated ketamine injections showed a significant increase in antinociceptive effect for >2 weeks, but this ketamine effect decreased after drug readministration.

Blinded vs. unblinded peer review of manuscripts submitted to a dermatology journal: a randomized multi-rater study.

BACKGROUND: Submissions to medical and scientific journals are vetted by peer review, but peer review itself has been poorly studied until recently. One concern has been that manuscript reviews in which the reviewer is unblinded (e.g. knows author identity) may be biased, with an increased likelihood that the evaluation will not be strictly on scientific merits. OBJECTIVES: The purpose of this study was to compare the outcomes of blinded and unblinded reviews of manuscripts submitted to a single dermatology journal via a randomized multi-rater study. MATERIALS AND METHODS: Forty manuscripts submitted to the journal Dermatologic Surgery were assessed by four reviewers, two of whom were randomly selected to be blinded and two unblinded regarding the identities of the manuscripts' authors. The primary outcome measure was the initial score assigned to each manuscript by each reviewer characterized on an ordinal scale of 1-3, with 1 = accept; 2 = revise (i.e. minor or major revisions) and 3 = reject. Subgroup analysis compared the primary outcome measure across manuscripts from U.S. corresponding authors and foreign corresponding authors. The secondary outcome measure was word count of the narrative portion (i.e. comments to editor and comments to authors) of the reviewer forms. RESULTS: There was no significant difference between the scores given to manuscripts by unblinded reviewers and blinded reviewers, both for manuscripts from the U.S. and for foreign submissions. There was also no difference in word count between unblinded and blinded reviews. CONCLUSIONS: It seems, at least in the case of one dermatology journal, that blinding during peer review does not appear to affect the disposition of the manuscript. To the extent that review word count is a proxy for review quality, there appears to be no quality difference associated with blinding.

Acute necrotic stomatitis (noma) associated with methicillin-resistant Staphylococcus aureus infection in a newly acquired rhesus macaque (Macaca mulatta).

BACKGROUND: A newly acquired rhesus macaque was suffering from rapid destruction of the left cheek caused by necrotizing stomatitis. METHODS: To restore reconstructive surgery and intensive care with antibiotics, wound protection, wound healing agents, and debridement were applied. RESULTS: Staphylococcus aureus and Enterococcus faecalis were isolated from the culture of the lesion, and the antibiotic susceptibility test revealed methicillin-resistant Staphylococcus aureus infection. Vancomycin and ampicillin-sulbactam effectively treated the bacterial infections, and reconstructive surgery was performed once the infection was cleared. Topical application of recombinant human epidermal growth factor (rhEGF) was useful to treat exposed wound of the noma lesion. CONCLUSIONS: Simian noma associated with methicillin-resistant Staphylococcus aureus (MRSA) had not previously been reported in non-human primates. Although noma associated with MRSA is hard to cure because of its rapid and destructive progress, the aggressive therapy used in this study led to the successful resolution of an acute necrotic stomatitis lesion in a rhesus macaque.

C4A deficiency due to a 2 bp insertion is increased in patients with systemic lupus erythematosus.

OBJECTIVE: The association of C4A deficiency with systemic lupus erythematosus (SLE) is well documented. In Caucasian populations, the most common cause of C4A deficiency is a large gene deletion in linkage disequilibrium with a conserved MHC haplotype. Because of this linkage disequilibrium, it has been difficult to determine which of the genes constitutes the disease susceptibility allele. Evidence from non-caucasoid populations has supported a role for C4A deficiency in SLE. We investigated whether a specific genetic cause of C4A deficiency, not associated with A1, B8, DR3, is found with increased frequency in SLE compared to controls. METHODS: Polymerase chain reaction was used to identify carriers of a 2 base pair (bp) insertion in exon 29. In total, 188 patients with SLE from the Johns Hopkins lupus cohort and 222 controls were genotyped. RESULTS: The 2 bp insertion was found more frequently in patients with SLE compared to controls and was more common in Caucasian than in African American SLE patients. There were no clinical differences between patients that carried the mutation and those that did not. CONCLUSION: The association of this C4A null allele with SLE supports a role for C4A deficiency independent of other MHC associations in the etiopathogenesis of SLE.

Frequency of the Fc gamma RIIIA-158F allele in African American patients with systemic lupus erythematosus.

OBJECTIVE: Defects in genes involved in immune complex clearance constitute one of the most common gene defects identified in patients with systemic lupus erythematosus (SLE). Defects in early complement components, complement receptors, and Fc receptors have all been implicated in the susceptibility to SLE. Recently, the role of functionally relevant Fc receptor polymorphisms in the etiology of SLE has been investigated. Specifically, a polymorphism of FC gamma RIII, termed Fc gamma RIIIA-158F, has been found to be associated with SLE in 2 largely Caucasian populations and appeared to constitute a risk factor for nephritis. We investigated the association of the Fc gamma RIIIA-158F and Fc gamma RIIIA-131R polymorphisms with SLE in an African American study population. METHODS: Nested polymerase chain reaction (PCR) and allele-specific PCR was used to genotype patients with SLE and controls. RESULTS: There was no difference in Fc gamma RIIIA-158F or Fc gamma RIIA-131R gene frequencies in the SLE populations compared to controls. There was no significant association between Fc gamma RIIIA-158F or Fc gamma RIIA-131R and any specific clinical or laboratory variable. CONCLUSION: In our African American study population, there did not appear to be any association of Fc gamma RIIA-158F or Fc gamma RIIA-131R with SLE.

Possible roles of LFA-1 and Fc gamma receptors on the functional immaturities of cord blood polymorphonuclear leukocytes.

The functional immaturity of PMNs is one of the major causes of overwhelming sepsis in newborns. In this study, we observed functions and surface markers of PMNs to investigate what causes the functional immaturity of PMNs in newborns. As results, the percentage of EA rosette forming PMNs (58.5 +/- 15.5%) and the chemotactic movement (0.14 +/- 0.09 mm) of cord blood PMNs were significantly lower than those of adult peripheral blood PMNs (70.8 +/- 9.9%, 0.60 +/- 0.34 mm). Cord blood PMNs showed decreased glass adherence and ADCC activity. The expression of Fc gamma RII or Fc gamma RIII was a little lower than those of adult peripheral blood PMNs, but the expression of Fc gamma RI (43.1 +/- 26.8%) was significantly higher than that of adult peripheral blood PMNs (3.2 +/- 1.8%). There was a significant difference in LFA-1 expression between EA rosette forming PMNs (92.9 +/- 9.1%) and EA rosette non-forming PMNs (25.6 +/- 22.6%). From these results, it is assumed that neonatal PMNs may consist of heterogeneous populations. And the relatively high percentage of EA rosette non-forming PMNs which express a low level of LFA-1 may be responsible for the functional immaturity of cord blood PMNs.

Steroid effects on minimal lesion nephrotic syndrome with and without immune deposits.

A comparison was done between the two groups of MLNS (minimal lesion nephrotic syndrome) with and without mesangial deposits of immunoglobulin and complement. The subjects were 40 patients with MLNS whose kidney could be obtained by biopsy. No significant differences were found between the two groups in selective protein index, serum cholesterol level, serum albumin level, amount of 24 hour urine protein, hematuria, serum immunoglobulin level and response to steroid therapy. Ig M was deposited in eleven of fourteen patients with MLNS, Ig G three of fourteen, C3 thirteen of fourteen. There was no relationship between serum level and glomerular deposition of immunoglobulin and complement.

[Electrolyte excretion by the rat kidney following intravenous injection of a solution of sodium phosphate]. / Vydelenie élektrolitov pochkoi krysy posle vnutrivennoi in'ektsii rastvora fosfata natriia

In rats, after administration of 0.125 ml/100 g sodium phosphate solution (pH 7.4, 0.05 M concentration), the urinary concentration of phosphate was increased just as in control experiments with administration of 0.15 M sodium chloride. The 0.25-0.75M solutions of sodium phosphate led to the maximal urinary phosphate concentration (200-250 mmol/l). Within 120-150 min of the injection the serum phosphate concentration did not differ from the control level. The renal reabsorption of phosphate was decreased in all the experiments. After administration of sodium phosphate, urinary potassium concentration was increased while that of chloride was decreased; no correlation was found between urinary concentration of these ions. The data obtained indicate presence of a specific system of phosphate transport in the cells of the rat kidney.