A case report and review of the locked metacarpophalangeal joint

A 59-year-old female with metacarpal joint locking is presented. The successful closed manipulation is described with a review of the literature.     

Receptor occupancy of nonpeptide corticotropin-releasing factor 1 antagonist DMP696: correlation with drug exposure and anxiolytic efficacy

4-(1,3-Dimethoxyprop-2-ylamine)-2,7-dimethyl-8-(2,4-dichlorophenyl)-pyrazolo[1,5-a]-1,3,5-triazine (DMP696) is a highly selective and potent, nonpeptide corticotropin-releasing factor 1 (CRF(1)) antagonist. In this study, we measured in vivo CRF(1) receptor occupancy of DMP696 by using ex vivo ligand binding and quantitative autoradiography and explored the relationship of receptor occupancy with plasma and brain exposure and behavioral efficacy. In vitro affinity (IC(50)) of DMP696 to brain CRF(1) receptors measured using the brain section binding autoradiography in this study is similar to that assessed using homogenized cell membrane assays previously. The ex vivo binding assay was validated by demonstrating that potential underestimation of receptor occupancy with this procedure could be minimized by identifying an appropriate in vitro incubation time (40 min) based upon the dissociation kinetics of DMP696. Orally administrated DMP696 dose dependently occupied CRF(1) receptors in the brain, with ~60% occupancy at 3 mg/kg. In the defensive withdrawal test of anxiety, this dose of DMP696 produced approximately 50% reduction in the exit latency. The time course of plasma and brain drug levels paralleled that of receptor occupancy, with peak exposure at 90 min after dosing. The plasma-free concentration of DMP696 corresponding to 50% CRF(1) receptor occupancy (in vivo IC(50), 1.22 nM) was similar to the in vitro IC(50) (~1.0 nM). Brain concentrations of DMP696 were over 150-fold higher than the plasma-free levels. In conclusion, doses of DMP696 occupying over 50% brain CRF(1) receptors are consistent with doses producing anxiolytic efficacy in the defense withdrawal test of anxiety, and the IC(50) value estimated in vivo based on plasma-free drug concentrations is consistent with the in vitro IC(50) value.     

Results of a phase I/II trial of recombinant human granulocyte- macrophage colony-stimulating factor in very low birthweight neonates: significant induction of circulatory neutrophils, monocytes, platelets, and bone marrow neutrophils

Neonates, especially those of very low birthweight (VLBW), have an increased risk of nosocomial infections secondary to deficiencies in development. We previously demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) production and mRNA expression from stimulated neonatal mononuclear cells are significantly less than that from adult cells. Recombinant murine GM-CSF administration to neonatal rats has resulted in neutrophilia, increased neutrophil production, and increased survival of pups during experimental Staphylococcus aureus sepsis. In the present study, we sought to determine the safety and biologic response of recombinant human (rhu) GM-CSF in VLBW neonates. Twenty VLBW neonates (500 to 1,500 g), aged < 72 hours, were randomized to receive either placebo (n = 5) or rhuGM-CSF at 5.0 micrograms/kg once per day (n = 5), 5.0 micrograms/kg twice per day (n = 5), or 10 micrograms/kg once per day (n = 5) given via 2-hour intravenous infusion for 7 days. Complete blood counts, differential, and platelet counts were obtained, and tibial bone marrow aspirate was performed on day 8. Neutrophil C3bi receptor expression was measured at 0 and 24 hours. GM-CSF levels were measured by a sandwich enzyme-linked immunosorbent assay at 2, 4, 6, 12, and 24 hours after the first dose of rhuGM-CSF. At all doses, rhuGM-CSF was well tolerated, and there was no evidence of grade III or IV toxicity. Within 48 hours of administration, there was a significant increase in the circulating absolute neutrophil count (ANC) at 5.0 micrograms/kg twice per day and 10.0 micrograms/kg once per day, which continued for at least 24 hours after discontinuation of rhuGM-CSF. When the ANC was normalized for each patient's first ANC, there was a significant increase in the ANC on days 6 and 7 at each dose level. By day 7, all tested doses of rhuGM- CSF resulted in an increase in the absolute monocyte count (AMC) compared with placebo-treated neonates. In those receiving rhuGM-CSF 5.0 micrograms/kg twice per day, there was additionally a significant increase in the day 7 and 8 platelet count. Tibial bone marrow aspirates demonstrated a significant increase in the bone marrow neutrophil storage pool (BM NSP) at 5.0 micrograms/kg twice per day and 10.0 micrograms/kg once per day. Neutrophil C3bi receptor expression was significantly increased 24 hours after the first dose of rhuGM-CSF at 5.0 micrograms/kg once per day. The elimination half-life (T1/2) of rhuGM-CSF was 1.4 +/- 0.8 to 3.9 +/- 2.8 hours.(ABSTRACT TRUNCATED AT 400 WORDS)     

Molecular analysis of relapse in chronic myeloid leukemia after allogeneic bone marrow transplantation

Four patients with Philadelphia (Ph') positive chronic myeloid leukemia (CML) were studied before, after, and on relapse following allogeneic bone marrow transplantation (BMT). Southern analysis of DNA from cells collected before and at relapse after BMT was performed in order to investigate the origin of the leukemia at relapse. Using minisatellite probes we showed that the relapse occurred in cells of host origin in all four patients and this was confirmed with a Y chromosome specific probe in two male patients who had a female donor. Furthermore, using two probes for the breakpoint cluster region (bcr) on chromosome 22, we showed that leukemic cells at relapse bore identical rearrangements to those in the disease at time of presentation of each patient. We conclude that relapse in all four patients is due to re-emergence of the original leukemic clone.     

Microlaryngeal surgery on a day case basis

The aim of this study was to assess the clinical safety of performing microlaryngeal surgery (MLS) under general anaesthesia in selected patients in the ambulatory setting. Twenty-two adult patients were scheduled to have tissue specimens of the larynx taken by biopsy (54%), for vocal cord polypectomy (41%) or for vocal cord cyst excision (5%). Twenty-one ASA I and II patients (95%) were discharged home the same day of the procedure. Two of them presented with laryngospasm after extubation of the trachea. One ASA III patient (5%) had to be admitted overnight because of severe laryngospasm and bronchospasm, but was discharged the day after the operation. None of the patients had significant complications after leaving the recovery room (mean stay 85 min). There were no re-admissions to the hospital. Our data suggests that microlaryngeal surgery in selected patients can be safely performed on a day case basis.     

Intra-rater Reliability of a Qualitative Landing Scale for the Single-Hop Test: A Pilot Study

BackgroundThe test battery classically used for return-to-sport (RTS) decision-making after anterior cruciate ligament (ACL) reconstruction (ACLR) may not be sufficient, as it does not include a qualitative analysis of movement. Therefore, the Landing Error Scoring System (LESS) scale was adapted to a primary functional test in the typical RTS test battery: the single leg hop for distance (SHD).Hypothesis/ PurposeThe aim of this study was to determine the intra-rater reliability of the LESS scale adapted to the SHD (SHD-LESS scale) in healthy young athletes.Study DesignReliability analysisMethodsNineteen healthy individuals (14 men, 5 women; mean age: 22.4 years) participated in the study. Participants performed the SHD tasks on both limbs (dominant and non-dominant) using a standardized protocol in two sessions that were one week apart (single reviewer; 2-dimensional video). Intra-class correlation coefficients (ICC2,1) were used to measure the reproducibility of the scale in the dominant (dom) and non-dominant (nondom) limbs. Additionally, limb data (dom and nondom) were pooled and evaluated collectively with intra-class correlation coefficients. The Kappa coefficient was used to assess the reproducibility of each individual item of SHD-LESS scale.ResultsThe intra-rater reliability was good (ICCdom = 0.77; ICCnondom = 0.87; ICCpooled = 0.87) for the overall SHD-LESS scale scores. Agreement of SHD-LESS individual items ranged from 62% to 100%. Dorsiflexion at initial contact (97% agreement; kappa value=0.79) and knee valgus after landing (88% agreement; kappa value=0.65) had excellent agreement and kappa values.ConclusionThe newly-adapted SHD-LESS scale showed good intra-rater reliability overall. Further studies should evaluate the impact of using the SHD-LESS scale within the RTS test battery on outcomes in patients after ACLR.Level of Evidence3     

Microbiome and pediatric atopic dermatitis

Atopic dermatitis is a chronic inflammatory skin condition with drastic impacts on pediatric health. The pathogenesis of this common disease is not well understood, and the complex role of the skin microbiome in the pathogenesis and progression of atopic dermatitis is being elucidated. Skin commensal organisms promote normal immune system functions and prevent the colonization of pathogens. Alterations in the skin microbiome may lead to increased Staphylococcus aureus colonization and atopic dermatitis progression. Despite the evidence for their important role, probiotics have not been deemed efficacious for the treatment of atopic dermatitis, although studies suggest that probiotics may be effective at preventing the development of atopic dermatitis when given to young infants. This review will cover the most recent published work on the microbiome and pediatric atopic dermatitis.