Influence of neonatal treatment with the pyrethroid insecticide cypermethrin on the development of dopamine receptors in the rat kidney.

The influence of neonatal treatment with the pyrethroid insecticide cypermethrin ((R,S)alpha-cyano-3-phenoxybenzyl (1R,S)-cis-trans-3-(2,2-dichloro-vinyl)-2,2-dimethylcyclopropane carboxylate) on postnatal development of renal dopamine receptors was investigated by radioligand binding assay techniques. Treatment with cypermethrin was made on rats from the 10th to the 16th day after birth. Dopamine D1- and D2-like receptors were assayed in frozen sections of kidney of 21-, 30-, 60- and 90-day-old rats using as ligands of dopamine D1- and D2-like receptors [3H]([R](+)-(chloro-2,3,4,5,-tetrahydro-5-phenyl-1,4,-benzazepinal hemimaleate) (SCH 23390) and [3H]spiperone, respectively. Treatment with cypermethrin was without effect on the affinity (Kd value) or the density (Bmax value) of dopamine D1- and D2-like receptors of rats of 21 days of age. In older groups, treatment with the compound reduced the affinity and increased the density of dopamine D1-like receptors, whereas it was without effect on the affinity of dopamine D2-like receptors and decreased their density. These findings indicate that neonatal treatment with the pyrethroid insecticide cypermethrin induces long-lasting impairment of renal dopamine D1- and D2-like receptors and that kidney is a target of the toxic action of the compound. Renal dopamine receptor changes caused by cypermethrin are consistent with possible alterations of renal tubular function and of sympathetic neuroeffector modulation. The above data suggest also that, different from the adult, neonatal exposure to pyrethroid insecticides may induce toxic effects.

Synthesis and pharmacological characterization of enantiomerically pure muscarinic agonists: difluoromuscarines.

The four homochiral 4-deoxy-4,4-difluoromuscarine stereoisomers (difluoromuscarines) were prepared in very high enantiomeric excess. A convenient sequence based on the use of natural as well as "unnatural" ethyl lactate allowed the synthesis of target compounds, whose absolute configuration is dictated by that of the starting synthon. Quaternary ammonium salts (+)-5, (-)-5, (-)-6, and (+)-6 were tested in vitro on guinea pig tissues, and their muscarinic potency was evaluated at M2 (heart) and M3 (ileum and bladder) muscarinic receptor subtypes. The eutomer (+)-5 and distomer (-)-5 were also tested in vivo on pithed rat, and their muscarinic activity at the M1 receptor subtype was compared with those of racemic muscarine [(+/-)-1] and (2S,4R,5S)-4-deoxy-4-fluoromuscarine [(+)-4]. Further pharmacological parameters such as affinity, relative efficacy, and enantioselectivity have been determined for compounds (+)-5 and (-)-5 at M2 (heart force and rate) and M3 (ileum and bladder) receptors in order to investigate muscarinic receptor heterogeneity. The four homochiral difluoromuscarines behave as muscarinic agonists in all the tests with a potency trend which is different from that previously observed with the 4-deoxy-4-fluoromuscarines and (+/-)-1, thus indicating the intervention of the second fluorine atom on the receptor-ligand interaction. Moreover, the second fluorine atom produces significant differences in the affinity and relative efficacy values of compounds (+)-5 and (-)-5 at M2 and M3 subtypes, which could be attributed to a heterogeneity between the muscarinic receptors mediating heart rate and heart force and those involved in the contraction of ileum and bladder.

Cypermethrin-induced alteration of thymocyte distribution and functions in prenatally-exposed rats.

The synthetic pyrethroid insecticide, cypermethrin (50 mg/kg) was given during gestation to pregnant rats by gavage in corn oil. Prenatal cypermethrin exposure induced a significant decrease in the absolute number of all thymocyte subsets during the first 30 days after birth, being the double negative CD4-CD8-, single positive CD4 and CD8 T cells preferentially affected. Later on day 60 and 90 double positive CD4+CD8+ and single positive thymocytes gradually recovered, while the total number of CD4 CD8 cells was increased. Moreover, thymocytes from rats prenatally exposed to cypermethrin showed an impaired ability to proliferate in response to different doses of Concanavalin A (ConA) and human recombinant interleukin-2 (hrIL-2) and to produce and/or release IL-2. Overall, our results indicate that cypermethrin administered during prenatal period can affect multiple steps in thymocyte differentiation pathways resulting in an altered cell subset distribution and an impairment of thymocyte functions.

Clinical characteristics associated to atrial fibrillation in chronic hemodialysis patients.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia diagnosed in non-uremic patients and its prevalence increases in older subjects, however, information concerning AF in dialysis patients is scarce. Therefore, we carried out a prospective cross-sectional study from September 1996 to December 1996 in order to evaluate the prevalence and some of the clinical characteristics associated to AF in hemodialysis (HD) patients. SUBJECTS AND METHODS: 316 HD patients (age 63 +/- 12 years, dialysis duration 69 +/- 71 months) treated in three different hospital-based units were studied. Standard 12-lead electrocardiograms (ECGs) carried out in the interdialytic day during the study period were reviewed. Data concerning age, history of ischemic heart disease (IHD), cerebrovascular disease (CVD), peripheral vascular disease (PVD), presence of diabetes, smoking history and antihypertensive therapy were collected. Systolic and diastolic blood pressure, fasting cholesterol and triglycerides, albumin and hemoglobin were also derived from the clinical records. Performance status was assessed by Karnofsky index (Ki). RESULTS: 74 patients (23.4%) had persistent AF, i.e. presence of AF in all (at least two) ECGs performed in the study time. Patients with AF were older (age 69 +/- 10 vs 62 +/- 12 years, p < 0.001), had lower Ki (54 +/- 20 vs 68 +/- 17, p < 0.01), cholesterol (182 +/- 46 vs 198 +/- 52 mg/dl, p < 0.01) and albumin (3.9 +/- 0.5 vs 4.1 +/- 0.5 g/dl, p < 0.001) compared to those with no AF. Prevalence of IHD (44.5% vs 19%, p < 0.05) and PVD (23% vs 11%, p < 0.05) was higher among AF patients. Logistic regression analysis showed that IHD (p < 0.001) and Ki (p < 0.01) were independently associated to AF. CONCLUSION: We conclude that AF is a frequent arrhythmia in HD patients treated in hospital-based dialysis units, especially in those with low performance status. It appears to be associated to the atherosclerotic damage of coronary arterial tree. Prospective studies are necessary to assess whether it could contribute to cardiovascular morbidity and mortality in end-stage renal disease.

Recurrent respiratory tract infections in pediatric age: a population-based survey of the therapeutic role of macrolides.

In order to evaluate the efficacy of macrolides in pediatric patients with recurrent respiratory tract infections (RRTIs), we enrolled 1,706 children (783 females) aged between 6 months and 14 years (median: 4 years) with an acute respiratory infection and a history of RRTIs (> or = 8 episodes per year if aged < 3 years; > or = 6 episodes per year if aged > or = 3 years). The therapies were chosen by the primary care pediatricians and their effects on respiratory relapses were blindly analyzed. Regardless of age and clinical diagnosis, the children treated with macrolides showed a significantly higher rate of short- and long-term clinical success than those receiving beta-lactams (p<0.0001) or symptomatics alone (p<0.0001). These data show that macrolide therapy of acute respiratory infections influences the natural history of RRTIs, probably because of their elective activity on atypical bacteria. They also suggest the possible importance of these pathogens in causing recurrences of respiratory infections in children and show that the infections they cause may have a more complicated course unless treated with adequate antibacterial drugs.

Risk factors of ischemic cardiac disease in patients on continuous ambulatory peritoneal dialysis.

Elevated plasma levels of fibrinogen, factor VII coagulant activity (F VIIc), and plasminogen activator inhibitor (PAI-1) have been reported to be strictly associated with thrombotic events and are considered to be important risk markers of atherothrombotic cardiovascular disease. Therefore, we evaluated in 15 patients on continuous ambulatory peritoneal dialysis (CAPD) the plasma levels of these coagulation factors, basal insulin values, and the lipid pattern in comparison with 33 hemodialysis (HD) patients and 59 healthy subjects. In CAPD the total cholesterol and triglyceride results were significantly increased, but no difference was found in HDL cholesterol. Fibrinogen and F VIIc results were significantly higher in CAPD and HD than in the control group, probably due to an increased hepatic synthesis as a nonspecific response to the peritoneal protein loss. Elevated F VIIc activity may be caused by the presence of large negatively charged lipoproteins, in vivo thrombin formation, or reduced hepatic clearance. Both PAI 1 and t-PA results were higher in CAPD, probably due to an increased synthesis by endothelial cells activated by glucose peritoneal absorption and hypertonic dialysis solutions. The contemporary elevation of fibrinogen, F VIIc, PAI-1, and t-PA suggests that CAPD patients present a hypercoagulability and hypofibrinolysis condition, which may promote the development of atherothrombotic events.

The self-locating catheter: clinical evaluation and comparison with the Tenckhoff catheter.

BACKGROUND: Peritoneal catheter displacement appears to be related to various causes including omental attachment, bowel contractions, peritoneal adhesions, and the catheter floating in the dialysis fluid. In order to prevent this complication, which can impair peritoneal dialysis efficacy, Di Paolo et al. designed a "self-locating catheter" (SLC) that is similar to the Tenckhoff catheter (TC) and includes a small tungsten cylinder (weight 12 g) at the distal end (Di Paolo N, et al. The self positioning catheter. Proceedings of the VII Italian Congress on Peritoneal Dialysis. Milan: Wichtig Editore, 1993:539-42). The weight of the tip prevents the catheter from floating and migrating by gravitation toward the Douglas cavity. OBJECTIVE: Starting in 1996, we implanted SLC in 15 continuous ambulatory peritoneal dialysis patients. The aim of our study was to compare the ratio of migration and other catheter-related complications between patients with SLC (196 patient-months) and 13 patients with conventional straight TC (295 patient-months). RESULTS: Peritonitis ratio, catheter complication rate, dialysate inflow and outflow, and weekly creatinine clearance were similar in the two groups of patients. The incidence of catheter displacement was significantly higher (p = 0.0349) in theTC group than in the SLC group (4 vs 0). CONCLUSION: In our experience, the SLC seems to be useful in preventing catheter migration by continuous gravitation of its extremity toward the pelvic cavity.

Macroporous calcium phosphate ceramic: a prospective study of 106 cases in lumbar spinal fusion.

Macroporous biphasic calcium phosphate (MBCP, Triosite) is well known for its safety, absence of allergenicity, and excellent bone-bonding capacity, and it has been widely used as a bone graft substitute in orthopaedic, ENT, and dental surgery. This study investigates the clinical performance of this synthetic porous ceramic in a series of 106 patients, mainly with degenerative spine aetiologies (95/106) and with a minimum follow-up of 2 years. All patients were treated with posterior correction involving the semi-rigid New Orleans instrumentation. Spinal fusion was always performed using MBCP granules mixed with autogenous bone chips and bone marrow obtained from the local spine. Fusion of the spine was confirmed for 100 patients, and 6 non-unions were observed (3 resulting from primary spondylolisthesis). This study shows that MBCP provides suitable results in spinal fusion involving a semi-rigid instrumentation. Because the indication of degenerative spine is not very favorable to fusion, this technique appears to be a good alternative to autografts and could decrease patient morbidity resulting from iliac bone grafting.

[Correction of architectural defects by femoral osteotomy and/or shelf procedure in the treatment of secondary coxarthrosis in adult]. / La correction des vices architecturaux par ostéotomie fémorale et/ou butée dans le traitement des coxarthroses secondaires de l'adulte.

One hundred and forty-nine cases of secondary osteoarthritis of the hip have been analysed. Twenty-eight were treated by a simple shelf operation, 60 by a varus upper femoral osteotomy with or without derotation and 61 by a combination of the two, in an attempt to re-establish the anatomy of the hip to as near normal as possible. The consequences of the operations and their morbidity were analysed for the whole series. Thirty-four patients, only five of whom were operated on both sides were reviewed after a 10 year follow-up or more with 30 good results in 39 hips. The results seem to depend above all on the quality of the articular congruence and the acetabular cover. These procedures are intended, in general, for young adults between 20 and 45 years of age. They can equally be considered up to the age of sixty as an alternative to total hip arthroplasty when the clinical and radiological condition makes it possible.

[Autoclaved tumoral autografts. Apropos of 12 cases, 6 of which highly malignant]. / Autogreffes tumorales autoclavées. A propos de 12 cas dont 6 tumeurs à haut grade de malignité.

Twelve patients presenting with a bone tumor were operated on using autoclaved bone autografts for reconstruction following carcinologic resection. According to the Enneking grading system, 6 were high malignancy tumors (3 osteosarcomas and 3 grade 2 chondrosarcomas), 4 were low grade tumors (1 paraosteal sarcoma, 1 chondrosarcoma, 1 secondary chondrosarcoma, 1 liposarcoma). One was a metastasis from a kidney tumor. The last patient had a femoral osteoid osteoma. Six local recurrences were responsible for 4 reoperations: 2 disarticulations and 2 iterative resections. With a 1-6 years range of follow-up (average follow-up 2.5 years), osseointegration of autoclaved grafts was studied. Fusion at the host/graft junction was roentgenographically observed. In three cases, proximal resorption of the humeral graft occurred. Five biopsies were obtained during reoperation after 1 year, which showed partial revascularization of autoclaved bone autografts. The authors conclude that autoclaved tumoral bone grafts, are reliable and discuss indications. They point out the main contraindication, represented by chemosensitive bone tumors, in which conservation of the removed tumor is necessary to quantify the response to chemotherapy.

Degenerative lumbar spondylolisthesis: cohort of 670 patients, and proposal of a new classification.

Degenerative spondylolisthesis is common in adults. No consensus is available about the analysis or surgical treatment of degenerative spondylolisthesis. In 2013, the French Society for Spine Surgery (Societe francaise de chirurgie du rachis) held a round table discussion to develop a classification system and assess the outcomes of the main surgical treatments. A multicentre study was conducted in nine centres located throughout France and Luxembourg. We established a database on a prospective cohort of 260 patients included between July 2011 and July 2012 and a retrospective cohort of 410 patients included in personal databases between 2009 and 2013. For patients in the prospective cohort clinical assessments were performed before and after surgery using the self-administered functional impact questionnaire AQS, SF12, and Oswestry Disability Index (ODI). Type of treatment and complications were recorded. Antero-posterior and lateral full-length radiographs were used to measure lumbar lordosis (LL), segmental lordosis (SL), pelvic incidence (PI), pelvic tilt (PT), sagittal vertical axis (SVA), and percentage of vertebral slippage. Mean follow-up was 10 months. We started a randomised clinical trial comparing posterior fusion of degenerative spondylolisthesis with versus without an inter-body cage. 60 patients were included, 30 underwent 180° fusion and 30 underwent 360° fusion using an inter-body cage implanted via a transforaminal approach. We evaluated the quality of neural decompression achieved by minimally invasive fusion technique. In a subgroup of 24 patients computed tomography (CT) was performed before and after the procedure and then compared. Mean age was 67 years and 73% of degenerative spondylolisthesis were located at L4-L5 level. The many surgical procedures performed in the prospective cohort were posterior fusion (39%), posterior fusion combined with inter-body fusion (36%), dynamic stabilization (15%), anterior lumbar fusion (8%), and postero-lateral fusion without exogenous material (2%). Peri-operative complications of any severity occurred in 17% of patients. The AQS, ODI and SF12 scores were improved significantly at follow-up. We found no differences in clinical improvements across surgical procedure types. Circumferential fusion (360°) was associated with greater relief of nerve root pain and better lordosis recovery after 1 year compared to postero-lateral fusion (180°). Post-operative CT images showed effective decompression of nervous structures after minimally invasive fusion. Longer follow-up of our patients is needed to assess the stability of the results of the various surgical procedures. Based on a radiological analysis, the authors propose a new classification with five types of degenerative spondylolisthesis: type 1, SL>5° and LL>PI-10°; type 2, SL<5° and LL>PI-10°; type 3, LL25°; and type 5, sagittal imbalance with SVA>4 cm. PROOF LEVEL: IV Observational cohort study. Retrospective review of prospectively collected outcome data.

Applications in spinal imbalance.

The pelvis may be seen as a single vertebra, between the spine and the femurs. The anatomy of this pelvic vertebra has changed with the evolution of species, notably with the transition to bipedalism, with the consequent appearance of lumbar lordosis. The lumbosacral angle, almost non-existent in other mammals, is at its greatest in humans. Pelvic and spinal radiological parameters reflect the sagittal balance of the spine in bipedal humanity. Applications in the management of spinal imbalance are numerous. Arthrogenic or degenerative kyphosis is the stereotypic example of spinal aging. Postoperative flat back following spine surgery is hard to prevent. Scoliosis surgery in adults should now take greater account of the patient's individual sagittal balance, by analyzing the pelvic and spinal parameters. The extent of arthrodeses performed during adolescence to manage idiopathic scoliosis may also induce problems of balance in adulthood if these elements are not taken into account.

[Results of the surgical treatment of fractures of the tibial plateau (apropos of 110 cases)]. / Résultats du traitement opératoire des fractures des plateaux tibiaux (à propos de 110 cas).

Operation was carried out on 110 fractures of the tibial plateau. Fractures of a single condyle were the most common. Associated ligamentous injury was present in 12.7% of the patients and a meniscal lesion was seen in 15.5%. The meniscus was preserved if possible. Satisfactory results were obtained in 79% of cases, with good correlation between the clinical result and the radiological appearance at review. The late complications and technical difficulties are discussed and the difference in prognosis between simple and complex fractures is emphasised.

Emerging role of Mycoplasma pneumoniae in children with acute pharyngitis.

In order to define the role, the risk factors, and the clinical and laboratory characteristics of Mycoplasma pneumoniae infection in children with pharyngitis, 184 patients with acute non-streptococcal pharyngitis (102 males; median age, 5.33 years) were studied. Acute Mycoplasma pneumoniae infection was demonstrated in 44 (23.9%) patients. A history of recurrent episodes of pharyngitis (defined as at least 3 acute episodes of pharyngitis in the 6 months preceding enrollment) appeared to be the more useful parameter for differentiating Mycoplasma pneumoniae pharyngitis from non-streptococcal non- Mycoplasma pneumoniae pharyngitis ( P<0.05 in multivariate analysis). These data, which highlight the emerging role of Mycoplasma pneumoniae in acute pharyngitis, must be taken into account in the diagnosis and treatment of this clinical manifestation in children.

Cementless fixation of hip prostheses in dogs.

Fixation of smooth cementless femoral prostheses was studied in 16 dogs which were killed 2, 3 and 4 months after operation. Rotational stability, examined by hand, was good in 9 cases and all stable prostheses could be extracted. Five out of 6 dogs, who did not bear weight after the operation, had a stable prosthesis compared with 4 out of 10 who walked early. Histology showed close bone apposition in 4, tight fibrous encapsulation in 4 and lack of tissue apposition in 8 which were loose. Bone remodelling in radiographs reflected the histological appearances; narrow radiolucent spaces were associated with dense well organised fibrous tissue, and wide radiolucent spaces with loose connective tissue. Prostheses with stems which fill the femoral canal should improve the fixation of smooth cementless prostheses.