Effect of long-term calcitonin administration on steroid-induced osteoporosis after cardiac transplantation.

BACKGROUND: Early, rapid bone loss and fractures after cardiac transplantation are well-documented complications of steroid administration; therefore, we undertook this study on the effects of long-term calcitonin on steroid-induced osteoporosis. METHODS: Twenty-three heart transplant recipients on maintenance immunosuppression with cyclosporine, mycophenolate mofetil and prednisone were retrospectively studied. All patients received long-term prophylactic treatment with elemental calcium and vitamin D. Twelve (52.2%) patients also received long-term intranasal salmon calcitonin, whereas 11 (47.8%) received none. Bone mineral density and vertebral fractures were assessed at yearly intervals. Statistical comparisons between each group's bone loss during the first year and in the early (1 to 3 years), intermediate (4 to 6 years) and late (7+ years) post-transplantation periods were done. RESULTS: Lumbar spine bone loss was significant during the early follow-up period in the group not receiving calcitonin (0.744 +/- 0.114 g/cm(2) vs 0.978 +/- 0.094 g/cm(2) [p = 0.002]). The calcitonin group showed bone mineral density (BMD) levels within normal average values throughout the study period. BMD increased in the no-calcitonin group during the intermediate (4 to 6 years) and late (7+ years) follow-up periods, with values approaching normal average and no significant difference between the 2 groups (0.988 +/- 0.184 g/cm(2) vs 0.982 +/- 0.088 g/cm(2) [p = 0.944] and 0.89 +/- 0.09 g/cm(2) vs 1.048 +/- 0.239 g/cm(2) [p = 0.474], respectively). CONCLUSIONS: Prophylactic treatment with intranasal salmon calcitonin prevents rapid bone loss associated with high-dose steroids early after cardiac transplantation. Long-term administration does not seem warranted in re-establishing BMD.     

Conservative management of thoracolumbar burst spine fractures using Gertzbein and Load Shearing classification

. The purpose of this prospective study was to assess the efficacy of the Gertzbein classification and the Load Shearing classification in the conservative treatment of thoracolumbar burst spinal fractures. From 1997 to 1999, 30 consecutive patients with single-level thoracolumbar spinal injury with no neurological impairment were classified according to the Gertzbein classification and the Load Shearing scoring, and were treated conservatively. A custom-made thoracolumbosacral orthosis was worn in all patients for 6 months and several radiologic parameters were evaluated, while the Denis Pain and Work Scale were used to assess the clinical outcome. The average follow-up period was 24 months (range 12-39 months). During this period radiograms showed no improvement of any radiologic parameter. However, the clinical outcome was satisfactory in 28 of 30 patients with neither pseudarthrosis, nor any complications recorded on completion of treatment. This study showed that thoracolumbar burst fractures Gertzbein A3 with a load shearing score 6 or less can be successfully treated conservatively. Patient selection is a fundamental component in clinical success for these classification systems. Résumé. Cette étude a pour objectif de classer les fractures comminutives du segment thoraco-lombaire de la colonne vertébrale qui ont été traitées de manière conservatrice, conformément à la classification de Gertzbein et à la classification de la répartition des contraintes. Depuis 1997 à 1999, trente malades présentant une fracture comminutive dans le segment thoraco-lombaire de la colonne vertébrale, sans dommages neurologiques, ont été traités de manière conservatoire, conformément aux classifications de Gertzbein et à la notation de la répartition des charges. Les patients ont porté une orthèse thoraco-lombaire pendant 6 mois et on a procédé à une évaluation des paramètres radiographiques. L'échelle de la douleur et du travail de Dennis a été utilisée pour évaluer les résultats. La durée moyenne d'observation des malades a été de 24 mois (de 12 à 39 mois). Bien que les paramètres radiologiques, pendant cette période, n'aient manifesté aucune amélioration, le résultat clinique de ces patients a été satisfaisant pour 93.33% d' entre eux. L'on n'a pas constaté de complications ni de pseudarthroses. La classification de Gertzbein associe le type de fracture au degré d'instabilité mécanique et au dommage neurologique. La classification de la répartition des contraintes relie l'écrasement et le déplacement de la fracture à la stabilité mécanique. Les fractures explosives du segment lombaire de la colonne vertébrale de type A3, selon Gertzbein, degré 6 ou inférieur à 6, selon la classification des contraintes, peuvent être traitées avec succès de manière conservatrice. Le choix judicieux des patients est important pour le succès clinique de cette méthode de classification.     

Autologous whole plasma fibrin gel. Intraoperative procurement.

Fibrin glue is a relatively recent addition to the armamentarium of hemostatic agents for surgical use. Its efficacy has been repeatedly demonstrated in almost all surgical disciplines and subspecialties. Its use in the United States has been limited because of the risk of viral transmission associated with the use of human plasma. Previous authors have described techniques that limit this risk, but they are frequently impractical, expensive, or cumbersome. We describe the use of patients' own fresh plasma to make fibrin gel at the operative field. It provided hemostasis at least as good as that from heterologous plasma glue in 40 cardiac surgical patients. Autologous whole plasma fibrin gel is inexpensive and safe and eliminates the risk of viral transmission associated with glue derived from heterologous donor plasma.     

A unique property of a plasma proteoglycan, the C1q inhibitor. An anticoagulant state resulting from its binding to fibrinogen.

The C1q inhibitor, C1qI, an approximately 30-kD circulating chondroitin-4 sulfate proteoglycan, displayed concentration-dependent prolongation of plasma and fibrinogen solution clotting times. Under factor XIIIa catalyzed cross-linking conditions and maximum C1qI concentrations, minor amounts of clot formed displaying complete gamma-gamma dimer formation but virtually no alpha-polymer formation. The anticoagulant effect was undiminished by its binding to C1q, by increased ionic strength, and by CaCl2, but was abolished by incubation of C1qI with chondroitinase ABC. 125I-labeled C1qI bound to immobilized fibrinogen, fibrin monomer, fibrinogen plasmic fragments D1 and E, and fibrin polymers. Occupancy on the E domain required uncleaved fibrinopeptides together with another structure(s), and it did not decrease binding of thrombin to fibrinogen. Occupancy on the D domain did not decrease the fibrinogen binding to fibrin monomer. We conclude that the E domain occupancy impaired fibrinopeptide cleavage, and occupancy on the D domain impaired polymerization, both steric hindrance effects. C1qI binding to fibrinogen explains at least in part the well-known fibrin(ogen) presence in immune complex-related lesions, and the fibrinogen presence in vascular basement membranes and atheromata. We postulate that fibrin binding by resident basement membrane proteoglycans provides dense anchoring of thrombus, substantially enhancing its hemostatic function.     

Ontogeny of intrinsic innervation in the human kidney

We aimed to define, for the first time, the ontogeny of intrarenal innervation and to assess the distribution and nature of parenchymal nerves in the human fetal kidney. Our material consisted of routinely-processed renal tissue sections from 17 human fetuses, six of 20–24 gestational weeks (gw) and 11 of 25–40 gw, and three adults. We used immunohistochemistry with antibodies to the pan-neural markers neuron-specific enolase (NSE), neurofilaments (NF), PGP9.5, S100, and the adrenergic marker tyrosine hydroxylase (TH). NSE-, NF-, S100-, and PGP9.5-positive nerves, associated with arterial and venous vasculature, were identified in the renal cortex from 20 gw onwards, and their density appeared to increase with gestation, reaching adult levels at 28 gw. Most of the intrarenal nerves were TH-positive. Nerve fibers extended from the corticomedullary region to the outer cortex, reaching the renal capsule in the 3rd trimester. In detail, NSE-, NF-, S100-, PGP9.5-, and TH-immunoreactive fibers were observed in close apposition to the renal artery and its branches, occasionally reaching the afferent and efferent arteriole (3rd trimester). Nerve fibers were detected in close apposition to the juxtaglomerular apparatus in the 2nd and 3rd trimesters. In the renal medulla, NSE-, PGP9.5-, S100-, and TH-positive nerve fibers were detected close to tubular cells as early as 20 gw. However, their density gradually decreased during the 3rd trimester, and they were not observed in the medulla of the adult kidney. In conclusion, the human fetal kidney appears richly innervated during the 2nd and 3rd trimesters. There is a progressive increase in the density of parenchymal nerve fibers towards term from the corticomedullary region to the cortex. Most intrarenal nerves are adrenergic and have a predominant perivascular distribution, implying that renal innervation plays an important functional role during intrauterine life.     

Apolipoprotein(a) phenotypes are reliable biomarkers for familial aggregation of coronary heart disease

Lipoprotein(a) [Lp(a)] is an atherogenic and prothrombotic molecule formed by the covalent binding of the highly polymorphic apolipoprotein(a) [apo(a)] to apoprotein B-100 of LDL. High Lp(a) concentrations are a recognized genetic risk factor for coronary heart disease (CHD) and have been shown to be related with a familial clustering of ischemic cardiac events. Nevertheless, the association between apolipoprotein(a) isoforms and a positive familial history of CHD has received far less attention. In this report, we explored the distribution of apo(a) phenotypes in 127 CHD subjects with a family history of coronary events and in 92 CHD patients without such a history. Twenty-two apo(a) isoforms were detected by a high-resolution immunoblotting method. In univariate analysis, the percentage of subjects with at least one small sized apo(a) isoform was significantly higher in CHD patients with a positive family history than in those without (P<0.01). Multivariate analysis showed that apo(a) isoforms of low molecular weight were the best predictors of familial aggregation of cardiac ischemia. We conclude that apo(a) size polymorphism is strongly associated with a familial history of CHD and is more efficient than Lp(a) plasma concentrations in predicting the familial clustering of coronary disease. When detected by high-resolution techniques, apo(a) phenotypes are objective laboratory markers that can substitute for a knowledge of a positive family history of CHD and should be used, together with Lp(a) levels, to better assess the familial predisposition to coronary events.     

Evaluation of ciprofloxacin in the treatment ofPseudomonas aeruginosa infections

The efficacy and safety of ciprofloxacin in the treatment ofPseudomonas aeruginosa infections was evaluated in 72 patients suffering from upper urinary tract infection (19 patients), deep soft tissue infection (16), chronic osteomyelitis (12), abscess (7), chronic otitis media (6), otitis externa (3) and bronchopneumonia (9). Forty-eight patients received an oral dose of 500 mg or 750 mg b.i.d. and five patients an i.v. dose of 200 mg b.i.d., while 19 patients were given both oral and parenteral doses. The duration of therapy ranged from seven days to more than four months. The MICs of ciprofloxacin for thePseudomonas aeruginosa strains isolated were in the range < 0.06–2 mg/l; 36% of the strains were resistant to all other available antibiotics. At follow-up after a minimum of six months the clinical success rate was 75% and the infecting organism was permanently eradicated in 49% of the patients. In nine patients the organism developed resistance, particularly when the initial MIC was higher than 0.5 mg/l. No significant adverse reactions were observed. Ciprofloxacin is the first antipseudomonal antimicrobial agent which can be administered orally and therefore fulfills a need in chemotherapy.     

TLR8 and TLR7 are involved in the host's immune response to human parechovirus 1

Toll-like receptors (TLR) have a key role in regulating immunity against microbial agents. Engagement of TLR by bacterial, viral or fungal components leads to the production and release of inflammatory cytokines. In this study we show that mainly TLR8 and also TLR7 act as the host sensors for human parechovirus 1, a single-stranded RNA (ssRNA) virus. Furthermore, we see that the viral ssRNA genome is detected in endosomal compartments by these TLR, which activate signalling that lead to the synthesis of pro-inflammatory molecules by the host.     

Integrin expression in correlation to clinicopathological features and prognosis of prostate cancer: A systematic review and meta-analysis

Background: The prompt identification of patients with poor prognosis is essential in order to improve the treatment outcomes in prostate cancer (CaP); as a novel approach, several molecular markers, including integrins, have been discussed as prognostic biomarkers. Our aim was to comprehensively examine aberrant expression of integrins in correlation with clinicopathological features and prognosis in CaP by synthesizing all available evidence, in a systematic review and meta-analysis. Methods: A systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Scientific literature databases (Pubmed, Embase, and Scopus) were systematically searched until May 10, 2020. Random-effects (DerSimonian-Laird) models were used to estimate pooled odds ratios (ORs) for cross-sectional correlations with clinicopathological characteristics and relative risks for longitudinal associations with prognosis. Results: Fourteen studies were included with a total number of 3,194 CaP cases examined (13 cross-sectional and four longitudinal cohort study arms). Correlation of low expression of α₆ (pooled OR = 0.10, 95% confidence interval [CI]: 0.04–0.28, P < 0.001) and β₁ (pooled OR = 0.45; 95% CI: 0.21–1.00, P = 0.049) integrin with high Gleason score was noted. A borderline trend between reduced expression of α₆ integrin and an advanced clinical stage of CaP (pooled OR = 0.48; 95% CI: 0.22-1.03, P = 0.06) was observed. No associations with biochemical recurrence and survival were documented. Conclusions: Evidence on the association of low expression of integrins α₆ and β₁ and more advanced CaP exist, whereas significant results on survival were not documented; further studies are warranted.     

Arthrodesis of the first metatarsophalangeal joint: The “when and how”

Arthrodesis of the first metatarsophalangeal (MTP) joint has been established as the “gold standard” for the treatment of several first ray disorders, due to its perceived efficacy and the consistently reported good results in the literature. Arthrodesis is a commonly performed procedure for the treatment of end stage arthritis, rheumatoid arthritis with severe deformity, selected cases of severe hallux valgus (with or without signs of degenerative joint disease), as well as a salvage procedure after failed previous operation of the first ray. The goals of a successful 1^st MTP arthrodesis are pain alleviation and deformity correction in order to restore a comfortable gait pattern and to improve shoe wear. Several techniques have been reported with several proposals regarding the preparation of the articular surfaces and the method of definitive fixation. As with any given surgical procedure, various complications may occur after arthrodesis of the 1^st MTP joint, namely delayed union, nonunion, malunion, irritating hardware, etc.