Intravenous pamidronate as treatment for osteoporosis after heart transplantation: a prospective study.

Fractures due to osteoporosis are one of the major complications after heart transplantation, occurring mostly during the first 6 months after the graft, with an incidence ranging from 18% to 50% for vertebral fractures. Bone mineral density (BMD) decreases dramatically following the graft, at trabecular sites as well as cortical sites. This is explained by the relatively high doses of glucocorticoids used during the months following the graft, and by a long-term increase of bone turnover which is probably due to cyclosporine. There is some evidence for a beneficial effect on BMD of antiresorptive treatments after heart transplantation. The aim of this study was to assess prospectively the effect on BMD of a 3-year treatment of quarterly infusions of 60 mg of pamidronate, combined with 1 g calcium and 1000 U vitamin D per day, in osteoporotic heart transplant recipients, and that of a treatment with calcium and vitamin D in heart transplant recipients with no osteoporosis. BMD of the lumbar spine and the femoral neck was measured by dual-energy X-ray absorptiometry in all patients every 6 months for 2 years and after 3 years. Seventeen patients, (1 woman, 16 men) aged 46+/-4 years (mean +/- SEM) received only calcium and vitamin D. A significant decrease in BMD was observed after 6 months following the graft, at the lumbar spine (- 6.6%) as well as at the femoral neck (-7.8%). After 2 years, BMD tended to recover at the lumbar spine, whereas the loss persisted after 3 years at the femoral neck. Eleven patients (1 woman and 10 men) aged 46+/-4 years (mean +/- SEM) started treatment with pamidronate on average 6 months after the graft, because they had osteoporosis of the lumbar spine and/or femoral neck (BMD T-score below -2.5 SD). Over the whole treatment period, a continuous increase in BMD at the lumbar spine was noticed, reaching 18.3% after 3 years (14.3% compared with the BMD at the time of the graft). BMD at the femoral neck was lowered in the first year by -3.4%, but recovered totally after 3 years of treatment. In conclusion, a 3-year study of treatment with pamidronate given every 3 months to patients with existing osteoporosis led to a significant increase in lumbar spine BMD and prevented loss at the femoral neck. However, since some of these patients were treated up to 14 months after the transplant, they may already have passed through the phase of most rapid bone loss. In patients who were not osteoporotic at baseline, treatment with calcium and vitamin D alone was not able to prevent the rapid bone loss that occurs immediately after transplantation.

Monostotic fibrous dysplasia: a 23-year follow-up of a patient with spontaneous bone remodeling

Fibrous dysplasia is a benign fibro-osseous disease that affects one or more bones. Although its etiology has been defined, the mechanism of spontaneous resolution is still unclear. There is strong evidence indicating the occurrence of stabilization when bone maturation is completed. Deformities that lead to esthetic and functional disorders are observed in almost all cases. Plastic surgery is often recommended when the maxilla and mandible are involved. In the case of mild deformities, careful follow-up during skeletal growth is recommended. We describe here the 23-year follow-up of a patient with monostotic fibrous dysplasia whose disease had stabilized by 13 years of follow-up. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 107: 229-234)

Treatment of symphysitis pubis with one unique iv injection of Ibandronate: report of two cases

Objective: Osteitis pubis is a noninfectious painful inflammatorydisorder of the symphysis pubis. Etiologic factors are numerous, themost common are: osseous extension of adductor, enthesis due tosport overuse, irritation after urological and abdominal procedures,and systemic inflammatory disorders in particularspondylarthropathies. Many cases are idiopathic. The symptomsconsist of regional chronic mechanical and sometime nocturnal pain.Diagnosis is usually confirmed by either bone scintigraphy or by MRI.There are no standard treatments but conservative approachesincluding rest and NSAIDS are generally recommended. In 2001, agood clinical and radiological response of three refractory cases with3 to 6 monthly perfusions of pamidronate was reported [1].Ibandronate is a much more powerful and long-lasting bisphosphonatethan pamidronate, and has not yet been reported in literature to ourknowledge in this indication.Patients and Methods: We present two cases of idiopathic origin:one woman (63 years old) and one man (36 years old).The symptomswere present >3 months in the first patient and one year in the second.The diagnosis was confirmed by MRI which showed bone edemaon both sizes of symphysis and in the second case bony erosionsadjacent to the joint were seen. Both cases failed to respond toconservative measures. Both patients received one single direct ivInjection of 3 mg of Ibandronate.Results: The injections resulted in a rapid (within a few days)resolution of pain that lasted more than 6 months in both patients.No side effects were observed. In the first case, an isotope bone scanperformed 4 months after the injection showed no residual uptake. Thesecond patient had a repeated MRI after 6 months. It demonstrated anattenuation of bone edema compared to the first MRI.Conclusion: IV Ibandronate may constitute a safe and effectivetreatment option for patients with refractory osteitis pubis.References1 Maksymowych WP, Aaron SL, Russell AS. Treatment of refractorysymphysitis pubis with intravenous pamidronate. J Rheumatol.2001;28(12):2754, 2001.

Impacto funcional con el uso de clavo telescopico tipo Fassier Duval en pacientes con osteogénesis imperfecta

Introducción: la osteogénesis es una patología de origen genético caracterizada por fragilidad ósea, en su curso natural los pacientes que la padecen se enfrentan a múltiples fracturas y múltiples intervenciones quirúrgicas, este tipo de pacientes por ser de alto riesgo necesitan técnicas quirúrgicas que aumenten el tiempo entre cada intervención y que demuestren un mayor impacto en el estado funcional. Objetivo: Determinar el impacto en el estado funcional de los pacientes con osteogénesis imperfecta llevados a tratamiento quirúrgico con clavos telescopados tipo Fassier Duval. Diseño: Estudio descriptivo prospectivo en el que se incluyeron 8 pacientes con diagnóstico de osteogénesis imperfecta, llevados a tratamiento quirúrgico con clavos telescopados tipo Fassier Duval desde el 2009 al 2013 a los cuales se les realizó seguimiento menor de 1 año del post operatorio. Resultados: La respuesta encontrada fue satisfactoria en la mayoría de los pacientes analizados 6 de 8, con cercanía a un estado funcional normal; un riesgo de caída bajo, incorporación y deambulación adecuada y una valoración funcional motora gruesa con valores cercanos al 100% identificando un buen nivel de independencia funcional. Se pudo demostrar que existieron cambios en los valores de la escala y que estos fueron estadísticamente significativos con p=0,028 indicando que el aumento dichos valores en el posoperatorio están relacionados con el procedimiento quirúrgico al utilizado en este grupo de pacientes. Conclusión: El tratamiento quirúrgico con el clavo telescopado de Fassier Duval en nuestra experiencia demostró tener una mejoría en el estado funcional de los pacientes del presente estudio, por lo tanto se sugiere la posibilidad de implementar su uso según este indicado con el fin de obtener un mejor resultado quirúrgico y funcional. Palabras clave: Osteogénesis Imperfecta, Clavo de Fassier Duval, Valoración Funcional Motora

Pharmacokinetics of tetracycline in plasma, synovial fluid and milk using single intravenous and single intravenous regional doses in dairy cattle with papillomatous digital dermatitis

The purpose of this study was to compare the pharmacokinetics of tetracycline in plasma, synovial fluid, and milk following either a single systemic intravenous (i.v.) injection or a single i.v. regional antibiosis (IVRA) administration of tetracycline hydrochloride to dairy cattle with papillomatous digital dermatitis (PDD). To this end, plasma and synovial fluid tetracycline concentrations were compared with the minimal inhibitory concentration (MIC) values of the major bacteria, which are known to cause digital diseases and thus assess its efficacy in PDD. Residual tetracycline concentrations in milk from cows treated by both methods were also determined. Twelve Holstein cows with various stages of PDD were randomly assigned to two groups of six animals. Group 1 received a single systemic i.v. injection of 10 mg/kg of tetracycline hydrochloride. Group 2 received 1000 mg of tetracycline hydrochloride by IVRA of the affected limb. Blood, synovial fluid and milk samples were taken prior to tetracycline administration (time 0 control), and then at 22, 45 and 82 min, and 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h following drug administration. Tetracycline concentrations were determined by high-performance liquid chromatography. Mean tetracycline plasma and milk concentrations in Group 1 were higher than Group 2. The opposite was observed for synovial fluid concentrations. Group 2 synovial fluid concentrations were higher than the MIC value over 24 h for the bacteria most frequently responsible for claw disease. Compared with i.v. administration, IVRA administration of tetracycline produced very high synovial fluid and low plasma and milk concentrations.

Apparent insensitivity of the hotplate latency test for detection of antinociception following intraperitoneal, intravenous or intracerebroventricular M6G administration to rats

Although morphine-6-glucuronide (M6G) has been shown to be analgesically active, the relative involvement of spinal and supraspinal structures in mediating M6G's pain-relieving effects following central and systemic administration to rats is unclear. As the tail flick and hotplate latency tests are reported to quantify antinociception mediated primarily by spinal and supraspinal mechanisms respectively, these methods were used to determine the comparative apparent levels of antinociception (expressed as percentage maximum possible effect, % MPE) achieved after M6G or morphine administration. Following i.v. or i.p. M6G (1.9-5.4 mu mol) dosing or i.p. morphine (10 mu mol) dosing, high levels of antinociception (>50% MPE) were achieved using the tail flick test whereas base-line levels of antinociception were observed 30 sec later in the same rats using the hotplate test. By contrast, antinociception evoked by i.v. morphine (10 mu mol) exceeded 50% MPE using both the hotplate and tail flick tests although the apparent potency was approximately 2.5 times greater using the tail flick test. After i.c.v. dosing, M6G (0.22-3.3 nmol) was significantly (P < .05) more potent when assessed using the tail flick compared with the hotplate test. Taken together, these data strongly indicate that following central and systemic administration, M6G's antinociceptive effects are mediated primarily by spinal structures whereas both spinal and supraspinal mechanisms contribute to systemic morphine's antinociceptive effects.

Systemic coadministration of chloramphenicol with intravenous but not intracerebroventricular morphine markedly increases morphine antinociception and delays development of antinociceptive tolerance in rats

Chloramphenicol, an in vitro inhibitor of the glucuronidation of morphine to its putative antianalgesic metabolite, morphine-3-glucuronide (M3G), was coadministered with morphine in adult male Sprague-Dawley rats to determine whether it inhibited the in vivo metabolism of morphine to M3G, thereby enhancing morphine antinociception and/or delaying the development of antinociceptive tolerance. Parenteral chloramphenicol was given acutely (3-h studies) or chronically (48-h studies). Morphine was administered by the i.v. or i.c.v. route. Control rats received chloramphenicol and/or vehicle. Antinociception was quantified using the hotplate latency test. Coadministration of chloramphenicol with i.v. but not i.cv. morphine increased the extent and duration of morphine antinociception by approximate to 5.5-fold relative to rats that received i.v. morphine alone. Thus, the mechanism through which chloramphenicol enhances i.v. morphine antinociception in the rat does not directly involve supraspinal opioid receptors. Acutely, parenteral coadministration of chloramphenicol and morphine resulted in an approximate to 75% increase in the mean area under the serum morphine concentration-time curve but for chronic dosing there was no significant change in this curve, indicating that factors other than morphine concentrations contribute significantly to antinociception. Antinociceptive tolerance to morphine developed more slowly in rats coadministered chloramphenicol, consistent with our proposal that in vivo inhibition of M3G formation would result in increased antinociception and delayed development of tolerance. However, our data also indicate that chloramphenicol inhibited the biliary secretion of M3G. Whether chloramphenicol altered the passage of M3G and morphine across the blood-brain barrier remains to be investigated.

Intermittent heparinised saline flushes for maintaining indwelling peripheral and central intravenous catheters in diabetic dogs

Intermittent low-dose heparinised saline flushes were found to be efficacious for maintaining patency of indwelling peripheral and central intravenous catheters in diabetic dogs. The catheters were flushed with 1 mL of 1 U/mL heparinised saline every two hours immediately following blood sample collection, or every 12 hours when not being used for sampling. Central catheters were flushed with saline solution first to clear the line before instillation of the heparinised saline. Patency of 54/57 (95%) of the peripheral catheters and 30/32 (94%) of the central catheters was achieved for up to 36 hours and five days, respectively. No phlebitis, or local or systemic infections were observed and, in each case, catheter failure was attributable to obstruction or extravasation. It is unlikely that there will be any contraindications to this flushing technique and its introduction may improve intravenous catheter survival and reduce catheter-associated complications in hospitalised dogs.

Adult-onset Still`s Disease with Pulmonary and Cardiac Involvement and Response to Intravenous Immunoglobulin

Cardiopulmonary manifestations of adult-onset Still`s disease (AOSD) include pericarditis, pleural effusion, transient pulmonary infiltrates, pulmonary interstitial disease and myocarditis. Serositis are common but pneumonitis and myocarditis are not and bring elevated risk of mortality. They may manifest on disease onset or flares. Previously reported cases were treated with high-dose glucocorticoids and immunosupressants and, when refractory, intravenous immunoglobulin (IVIG). We report an AOSD patient whose flare presented with severe pleupneumonitis and myopericarditis and, following nonresponse to a methylprednisolone pulse, high dose of prednisone and cyclosporine A, recovered after a 2-day 1g/kg/day IVIG infusion.

Outpatient treatment with intravenous antimicrobial therapy and oral levofloxacin in patients with febrile neutropenia and hematological malignancies

The purpose of this study was to evaluate outcomes such as success of the initial therapy, failure of outpatient treatment, and death in outpatient treatment during intravenous antimicrobial therapy in patients with febrile neutropenia (FN) and hematological malignancies. In addition, clinical and laboratory data and the Multinational Association for Supportive Care of Cancer index (MASCC) were compared with failure of outpatient treatment and death. In a retrospective study, we evaluated FN following chemotherapy events that were treated initially with cefepime, with or without teicoplanin and replaced by levofloxacin after 48 h of defervescence in patients with good general conditions and ANC > 500/mm(3). Of the 178 FN episodes occurred in 126 patients, we observed success of the initial therapy in 63.5% of the events, failure of outpatient treatment in 20.8%, and death in 6.2%. The success rate of oral levofloxacin after defervescence was 99% (95 out of 96). Using multivariate analysis, significant risks of failure of outpatient treatment were found to be smoking (odds ratio (OR) 3.14, confidence interval (CI) 1.14-8.66; p = 0.027) and serum creatinine levels > 1.2 mg/dL (OR 7.97, CI 2.19-28.95; p = 0.002). With regard to death, the risk found was oxygen saturation by pulse oximetry < 95% (OR 5.8, IC 1.50-22.56; p = 0.011). Using the MASCC index, 165 events were classified as low risk and 13 as high risk. Failure of outpatient treatment was reported in seven (53.8%) high-risk and 30 (18.2%) low-risk episodes (p = 0.006). In addition, death occurred in seven (4.2%) low-risk and four (30.8%) high-risk events (p = 0.004). Ours results show that MASCC index was able to identify patients with high risk. In addition, non-smoking, serum creatinine levels a parts per thousand currency sign1.2 mg/dL, and oxygen saturation by pulse oximetry a parts per thousand yen95% were protection factors.

Intravenous glutamine decreases lung and distal organ injury in an experimental model of abdominal sepsis

Introduction The protective effect of glutamine, as a pharmacological agent against lung injury, has been reported in experimental sepsis; however, its efficacy at improving oxygenation and lung mechanics, attenuating diaphragm and distal organ injury has to be better elucidated. In the present study, we tested the hypothesis that a single early intravenous dose of glutamine was associated not only with the improvement of lung morpho-function, but also the reduction of the inflammatory process and epithelial cell apoptosis in kidney, liver, and intestine villi. Methods Seventy-two Wistar rats were randomly assigned into four groups. Sepsis was induced by cecal ligation and puncture surgery (CLP), while a sham operated group was used as control (C). One hour after surgery, C and CLP groups were further randomized into subgroups receiving intravenous saline (1 ml, SAL) or glutamine (0.75 g/kg, Gln). At 48 hours, animals were anesthetized, and the following parameters were measured: arterial oxygenation, pulmonary mechanics, and diaphragm, lung, kidney, liver, and small intestine villi histology. At 18 and 48 hours, Cytokine-Induced Neutrophil Chemoattractant (CINC)-1, interleukin (IL)-6 and 10 were quantified in bronchoalveolar and peritoneal lavage fluids (BALF and PLF, respectively). Results CLP induced: a) deterioration of lung mechanics and gas exchange; b) ultrastructural changes of lung parenchyma and diaphragm; and c) lung and distal organ epithelial cell apoptosis. Glutamine improved survival rate, oxygenation and lung mechanics, minimized pulmonary and diaphragmatic changes, attenuating lung and distal organ epithelial cell apoptosis. Glutamine increased IL-10 in peritoneal lavage fluid at 18 hours and bronchoalveolar lavage fluid at 48 hours, but decreased CINC-1 and IL-6 in BALF and PLF only at 18 hours. Conclusions In an experimental model of abdominal sepsis, a single intravenous dose of glutamine administered after sepsis induction may modulate the inflammatory process reducing not only the risk of lung injury, but also distal organ impairment. These results suggest that intravenous glutamine may be a potentially beneficial therapy for abdominal sepsis.

Sildenafil improves the beneficial haemodynamic effects of intravenous nitrite infusion during acute pulmonary embolism

Acute pulmonary embolism produces acute pulmonary hypertension, which can be counteracted by activating the nitric oxide-cyclic guanosine 3`,5`-monophosphate (cGMP) pathway. While previous studies have shown that sildenafil (an inhibitor of cGMP-specific phosphodiesterase type 5) or nitrite (a storage molecule for nitric oxide) produces beneficial effects during acute pulmonary embolism, no previous study has examined whether the combination of these drugs can produce additive effects. Here, we expand previous findings and examine whether sildenafil enhances the beneficial haemodynamic effects produced by a low-dose infusion of nitrite in a dog model of acute pulmonary embolism. Haemodynamic and arterial blood gas evaluations were performed in non-embolized dogs treated with saline (n = 4), and in embolized dogs (intravenous injections of microspheres) that received nitrite (6.75 mu mol/kg intravenously over 15 min. followed by 0.28 mu mol/kg/min.) and sildenafil (0.25 mg/kg over 30 min.; n = 8), or nitrite followed by saline (n = 8), or saline followed by sildenafil (n = 7), or only saline (n = 8). Plasma thiobarbituric acid-reactive substances (TBARS) concentrations were determined using a fluorometric method. Acute pulmonary embolism increased pulmonary artery pressure by similar to 24 mmHg. While the infusion of nitrite or sildenafil infusions reversed this increase by similar to 42% (both P < 0.05), the combined infusion of both drugs reversed this increase by similar to 58% (P < 0.05). Similar effects were seen on the pulmonary vascular resistance index. Nitrite or sildenafil alone produced no significant hypotension. However, the combined infusion of both drugs caused transient hypotension (P < 0.05). Both dugs, either alone or combined, blunted the increase in TBARS concentrations caused by acute pulmonary embolism (all P < 0.05). These results suggest that sildenafil improves the beneficial haemodynamic effects of nitrite during acute pulmonary embolism.

Cardiopulmonary and isoflurane-sparing effects of epidural or intravenous infusion of dexmedetomidine in cats undergoing surgery with epidural lidocaine

Objective To compare the cardiorespiratory, anesthetic-sparing effects and quality of anesthetic recovery after epidural and constant rate intravenous (IV) infusion of dexmedetomidine (DEX) in cats given a low dose of epidural lidocaine under propofol-isoflurane anesthesia and submitted to elective ovariohysterectomy. Study design Randomized, blinded clinical trial. Animals Twenty-one adult female cats ( mean body weight: 3.1 +/- 0.4 kg). Methods Cats received DEX (4 mu g kg(-1), IM). Fifteen minutes later, anesthesia was induced with propofol and maintained with isoflurane. Cats were divided into three groups. In GI cats received epidural lidocaine (1 mg kg(-1), n = 7), in GII cats were given epidural lidocaine (1 mg kg(-1)) + DEX (4 mu g kg(-1), n = 7), and in GIII cats were given epidural lidocaine (1 mg kg(-1)) + IV constant rate infusion (CRI) of DEX (0.25 mu g kg(-1) minute(-1), n = 7). Variables evaluated included heart rate (HR), respiratory rate (f(R)), systemic arterial pressures, rectal temperature (RT), end-tidal CO(2), end-tidal isoflurane concentration (E`ISO), arterial blood gases, and muscle tone. Anesthetic recovery was compared among groups by evaluation of times to recovery, HR, f(R), RT, and degree of analgesia. A paired t-test was used to evaluate pre-medication variables and blood gases within groups. ANOVA was used to compare parametric data, whereas Friedman test was used to compare muscle relaxation. Results Epidural and CRI of DEX reduced HR during anesthesia maintenance. Mean +/- SD E/ISO ranged from 0.86 +/- 0.28% to 1.91 +/- 0.63% in GI, from 0.70 +/- 0.12% to 0.97 +/- 0.20% in GII, and from 0.69 +/- 0.12% to 1.17 +/- 0.25% in GIII. Cats in GII and GIII had longer recovery periods than in GI. Conclusions and clinical relevance Epidural and CRI of DEX significantly decreased isoflurane consumption and resulted in recovery of better quality and longer duration, despite bradycardia, without changes in systemic blood pressure.