Renal pericytes: multifunctional cells of the kidneys

Pericytes have become a hot topic in renal biology. They play a critical physiological role in vessel development, maintenance and remodelling through active communication with their vascular partners—endothelial cells—and modulation of extracellular matrix proteins. Multiple functions for renal pericytes have been described; specialised perivascular populations participate in glomerular filtration, regulate medullary blood flow and contribute to kidney fibrosis by differentiation into collagen-generating myofibroblasts. Interestingly, the origin of renin-producing cells of the juxtaglomerular region is attributed to the perivascular cell lineage; we have observed the coincidence of renin and pericyte marker expression during human kidney development. Finally, pericytes have been shown to share features with mesenchymal stem cells, which places them as potential renal progenitor cell candidates. Since renal diseases are often associated with microvascular complications, renal pericytes may emerge as new targets for the treatment of kidney disease.     

Evaluation of the efficacy and safety of pamapimod,a p38 MAP kinase inhibitor,in a double‐blind,methotrexate‐controlled study of patients with active rheumatoid arthritis

Objective

To determine the efficacy and safety of pamapimod (a selective inhibitor of the α‐isoform of p38 MAP kinase) as monotherapy in comparison with methotrexate (MTX) treatment in adult patients with active rheumatoid arthritis (RA).

Methods

Patients were randomly assigned to 1 of 4 treatment groups and received 12 weeks of double‐blind treatment. One group received MTX (7.5 mg/week with planned escalation to 20 mg/week), and 3 groups received pamapimod (50, 150, or 300 mg) once daily. The primary efficacy end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at 12 weeks. Secondary end points included ACR50 and ACR70 responses, change from baseline in the Disease Activity Score in 28 joints (DAS28), categorical analyses of DAS28/European League Against Rheumatism response, and change from baseline in each parameter of the ACR core set of measures. Safety monitoring included recording of adverse events (AEs), laboratory testing, immunology assessments, administration of electrocardiograms, and assessment of vital signs.

Results

Patients assigned to receive MTX and pamapimod had similar demographics and baseline characteristics. At week 12, fewer patients taking pamapimod had an ACR20 response (23%, 18%, and 31% in the 50‐, 150‐, and 300‐mg groups, respectively) compared with patients taking MTX (45%). Secondary efficacy end points showed a similar pattern. AEs were typically characterized as mild and included infections, skin disorders, and dizziness. Pamapimod was generally well tolerated, but the 300‐mg dose appeared to be more toxic than either the 2 lower doses or MTX.

Conclusion

The present results showed that pamapimod was not as effective as MTX in the treatment of active RA.

     

Tratamiento médico del embarazo ectópico instersticial: descripción de un caso clínico

Traditional management of interstitial pregnancy involves laparotomy with cornual resection. Recent advances in transvaginal ultrasonography and sensitive beta-hCG assays have led to earlier diagnosis of these cases. We report a case of interstitial pregnancy successfully treated with parenteral methotrexate. Prompt recognition of interstitial pregnancy allows conservative approachment and systemic methotrexate presents as an effective and safe option.     

Electromyographic thresholds after thoracic screw stimulation depend on the distance of the screw from the spinal cord and not on pedicle cortex integrity

Background contextPresent studies concerning the safety and reliability of neurophysiological monitoring during thoracic pedicle screw placement remain inconclusive, and therefore, universally validated threshold levels that confirm osseous breakage of the instrumented pedicles have not been properly established.PurposeThe objective of this work was to analyze whether electromyographic (EMG) thresholds, after stimulation of the thoracic pedicle screw, depend on the distance between the neural structures and the screws. The modifier effect of different interposed tissues between a breached pedicle and neural structures was also investigated.Study designThis experimental study uses a domestic pig model.MethodsElectromyographic thresholds were recorded after the stimulation of 18 thoracic pedicle screws that had been inserted into five experimental animals using varying distances between each screw and the spinal cord (8 and 2 mm). Electromyographic thresholds were also registered after the medial pedicle cortex was broken and after different biological tissues were interposed (blood, muscle, fat, and bone) between the screw and the spinal cord.ResultsMean EMG thresholds increased to 14.1±5.5 mA for screws with pedicle cortex integrity that were placed 8 mm away from the dural sac. After the medial pedicle cortex was broken and without varying the distance of the screw to the dural sac, the mean EMG thresholds were not appreciably changed (13.6±6.3 mA). After repositioning the screw at a distance of 2 mm from the spinal cord and after medial cortical breach of the pedicle, the mean threshold significantly slowed to 7.4±3.4 mA (p<.001). When the screw was placed in contact with the spinal dural sac, even lower EMG thresholds were registered (4.9±1.9, p<.001). Medial pedicle cortex rupture and the interposition of different biological tissues in experimental animals did not alter the stimulation thresholds of the thoracic pedicle screws.ConclusionsIn the experimental animals, the observed electrical impedance depended on the distance of screws from the neural structures and not on the integrity of the pedicle cortex. The screw-triggered EMG technique did not reliably discriminate the presence or absence of bone integrity after pedicle screw placement. The response intensity was not related to the type of interposed tissue.     

Comparison of C0 and C2 cyclosporine monitoring in long-term renal transplant recipients

Recent data show that monitoring cyclosporine A (CsA) concentrations with 2-hour postdose levels (C2) correlates with the incidence of rejection and graft outcome in de novo renal transplant patients. The purpose of the present work was to evaluate the advantage of C2 monitoring after the first year of kidney transplantation. We studied 161 patients, 96 on CsA-prednisone and 65 on triple therapy (Aza or MMF) who had been transplanted for a mean of 103+/-44 months. Mean serum creatinine (SCr) was 1.65+/-0.69 mg/dL, mean C0 was 174+/-44, and C2 was 667+/-194 ng/mL. Patients were classified according to C2 values: >850 (n=29), between 850 and 450 (n=109), and <450 (n=23) ng/mL. Patients with C2 <450 ng/mL displayed higher SCr values (1.97+/-0.99; 1.59+/-0.51; 1.52+/-0.4 mg/dL; P<.001), received lower CsA doses (172+/-54; 207+/-54; 227+/-56 mg/d, P<.01), showed lower C0 levels (155+/-48; 172+/-41; 199+/-45 ng/mL; P< .001), and included more patients on triple therapy (54.5%; 44%; 17.2%; P<.05). We found weak correlations between C0 and C2 (r=0.37), between C2 and CsA dose (r=0.36), and between C0 and SCr (r=-0.37). Among 117 patients followed up for 1 year with several C0 and C2 measurements, the coefficient of variation of C0 was 17% and of C2 was 21%. Graft functional deterioration occurred in 16 patients independent of the differences among the C2 groups, but 7 recipients (43.7%) had C0 <150 ng/mL and C2/C0 >5. We conclude that C2 in monitoring stable patients needs further evaluation.     

Prognostic significance of terminal transferase activity in childhood acute lymphoblastic leukemia: a prospective analysis of 164 patients

Whether the level of terminal deoxynucleotidyl transferase (TdT) activity in mononuclear cells from bone marrow and peripheral blood has prognostic significance has been analyzed prospectively in 164 children with T and non-T, non-B marked acute lymphoblastic leukemia (ALL). TdT was measured at diagnosis to assess its value as a predictor of duration of remission and length of survival. It was measured repeatedly during remission to assess whether it could predict relapse. Ninety-seven percent of the children achieved a complete remission of their disease, and 40% relapsed during the study. The level of TdT activity in blasts at diagnosis varied 1000-fold from patient to patient. There was no statistically significant relationship between TdT activity in cells at diagnosis and the achievement of complete remission, the duration of remission, or length of survival. TdT activity was significantly increased in the bone marrow of 65% of patients at the time of marrow morphological relapse, but was rarely increased in marrow from patients with isolated testicular or central nervous system relapse. Wide fluctuations in TdT activity were characteristically seen in mononuclear cells from the marrow and peripheral blood of patients with ALL at all stages of their disease. An isolated high value of TdT activity in the bone marrow or peripheral blood cannot be taken as evidence of impending relapse. Quantitative measurements of TdT activity alone on mononuclear cells from bone marrow and peripheral blood are helpful in differential diagnosis, but cannot guide therapy of children with ALL.