Nephrotoxicity and Efficacy Assessment of Polymyxin Use in 92 Transplant Patients

Polymyxins are old antimicrobials, discontinued for many years because of nephrotoxicity and neurotoxicity reports and reintroduced recently due to the increasing frequency of multiresistant Gram-negative bacterial infections. There are very few data related to toxicity and efficacy from transplanted patients, the major subjects of this study. All solid-organ-transplanted patients from our institution during January 2001 to December 2007 who used polymyxins were retrospectively assessed for nephrotoxicity and treatment efficacy. Microbiological and clinical cure rates were 100% and 77.2%, respectively. Only transplant patients subjected to at least 72 h of intravenous polymyxin were entered in the study. Overall, 92 transplant patients were included, and the nephrotoxicity rate was 32.6%. Multivariate analysis showed a statistically significant association between duration of polymyxin treatment (P = 0.037; odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00 to 1.12) and significant renal dysfunction. Polymyxin use is associated with very high rates of significant decrease in renal function; therefore, polymyxin must be used only when no other option is available and for as briefly as possible in the solid organ transplant setting.     

Aging-related Decrease of Human ASC Angiogenic Potential Is Reversed by Hypoxia Preconditioning Through ROS Production

Adipose stroma/stem cells (ASC) represent an ideal source of autologous cells for cell-based therapy. Their transplantation enhances neovascularization after experimental ischemic injury. Aging is associated with a progressive decrease in the regenerative potential of mesenchymal stem cells (MSCs) from bone marrow. This work aims to determine the aging effect on human ASC capacities. First, we show that aging impairs angiogenic capacities of human ASC (hASC) in a mouse ischemic hindlimb model. Although no change in hASC number, phenotype, and proliferation was observed with aging, several mechanisms involved in the adverse effects of aging have been identified in vitro combining a concomitant decrease in (i) ASC ability to differentiate towards endothelial cells, (ii) secretion of proangiogenic and pro-survival factors, and (iii) oxidative stress. These effects were counteracted by a hypoxic preconditioning that improved in vivo angiogenic capacities of hASC from older donors, while hASC from young donors that have a strong ability to manage hypoxic stress were not. Finally, we identified reactive oxygen species (ROS) generation as a key signal of hypoxia on hASC angiogenic capacities. This study demonstrates for the first time that age of donor impaired angiogenic capacities of hASC in ischemic muscle and change in ROS generation by hypoxic preconditioning reverse the adverse effect of aging.     

Severe hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with fluoxetine: case report

Hyponatremia is a significant complication of treatment with serotonin selective reuptake inhibitors (SSRI). We describe a case of a 53-year-old woman that was started on fluoxetine 20 mg/day for depression. Nine days later, the patient started with weakness, nausea, progressing to confusion, inappetence and vomit. Three hours later she became unresponsive and had a generalized seizure. She was brought to our emergency service. On admission, the patient was normovolemic, without focal motor deficits, but had mild generalized muscle rigidity and Babinski's sign bilaterally. Serum sodium was 105 mmol/L, serum osmolality, 220 mmol/L, and urinary osmolality, 400 mmol/L. The other laboratory exams, chest X-ray, cerebrospinal fluid and cranium tomography were normal. She was found to have fluoxetine-induced SIADH and it was discontinued. We started the hyponatremia correction and, in 5 days, the mental status of the patient gradually returned to a normal baseline, paralleling the resolution of her hyponatremia, without recurrence. Hyponatremia and SIADH should be considered if a patient experiences deterioration in his or her clinical condition while taking SSRI. The use of SSRI antidepressants should be remembered in the differential diagnosis of drug-induced hyponatremia.     

Calcified cysticercotic lesions and intractable epilepsy: a cross sectional study of 512 patients

Background

Neurocysticercosis is a major cause of epilepsy in developing countries and is endemic in Brazil. To test the hypothesis that the aetiological profile of patients with intractable epilepsy in Brazil includes neurocysticercosis, we conducted a cross sectional study investigating the aetiology of intractable epilepsy.

Methods

A total of 512 patients evaluated at the outpatient clinic for intractable epilepsy at the Ribeirão Preto School of Medicine were included in the survey. Medical intractability was determined on the basis of seizure incidence and severity, and response to appropriate epilepsy management. Neuroimaging included brain CT with non‐contrasted and contrasted phases and high resolution MRI. Patients were divided into neurocysticercosis and non‐neurocysticercosis groups according to previous diagnostic criteria.

Results

The most common epileptogenic lesions were mesial temporal sclerosis (MTS; 56.0%), malformations of cortical development (12.1%), and brain tumours (9.9%). Neuroimaging was normal in 8.7% of patients. Calcifications were found in 27% of patients and were significantly more common in patients with MTS than in those without MTS (p<0.001). Isolated neurocysticercosis was found in only eight patients (1.56%).

Conclusions

These data suggest that neurocysticercosis is an uncommon cause of intractable epilepsy, even in an endemic region such as Brazil, and that it may only represent a coexistent pathology. However, an analysis of our findings reveals that neurocysticercosis was more common in patients with MTS. This finding could suggest either that there is a cause‐effect relationship between MTS and neurocysticercosis, or that MTS and neurocysticercosis co‐vary with a missing variable, such as socio‐economic status.     

Utrophin is a calpain substrate in muscle cells

Calpains are Ca2+ -dependent cytosolic cysteine proteases that participate in the pathology of Duchenne muscular dystrophy (DMD). Utrophin is a functional homolog of dystrophin that partially compensates for dystrophin deficiency in myofibers of mdx mice. In this study, we investigated the susceptibility of utrophin to cleavage by calpain in vitro and in muscle cells. We found that utrophin is a direct in vitro substrate of purified calpain I and II. Cleavage of utrophin by calpain I or II generates specific degradation products that are also found in cultured control and DMD myotubes under conditions with elevated intracellular Ca2+ levels. In addition, we showed that activation of cellular calpains by Ca2+ ionophore treatment reduces utrophin protein levels in muscle cells and that calpain inhibition prevents this Ca2+ -induced reduction in utrophin levels. These observations suggest that, beside its known effect on general muscle protein degradation, calpain contributes to DMD pathology by specifically degrading the compensatory protein utrophin.     

Improving Functional Performance and Muscle Power 4-to-6 Months After Anterior Cruciate Ligament Reconstruction

The purpose of this study was to examine the effects of 8-week retraining programs, with either two or three training sessions per week, on measures of functional performance and muscular power in athletes with anterior cruciate ligament reconstruction (ACLR). Sixteen male athletes were randomly assigned to two groups after ACLR: a functional training group (FTG, n = 8) training 2 intense sessions per week (4hrs/week), and a control group (CG, n = 8) training 3 sessions per week with moderate intensity (6hrs/week). The two groups were assessed at four and six months post-ACLR and the effects of retraining were measured using the following assessments: the functional and the muscular power tests, and the agility T-test. After retraining, the FTG had improved more than the CG in the operated leg in the single leg hop test (+34.64% vs. +10.92%; large effect), the five jump test (+8.87% vs. +5.03%; medium effect), and single leg triple jump (+32.15% vs. +16.05%; medium effect). For the agility T-test, the FTG had larger improvements (+17.26% vs. +13.03%, medium effect) as compared to the CG. For the bilateral power tests, no significant training effects were shown for the two groups in the squat jump (SJ), the counter movement jump (CMJ) and the free arms CMJ (Arm CMJ). On the other hand, the unilateral CMJ test with the injured and the uninjured legs showed a significant increase for the FTG with respect to CG (p < 0.05). The present study introduces a new training modality in rehabilitation after ACLR that results in good recovery of the operated limb along with the contra-lateral leg. This may allow the athletes to reach good functional and strength performance with only two physical training sessions per week, better preparing them for a return to sport activity at 6 months post- ACLR and eventually sparing time for a possible progressive introduction of the sport specific technical training.

Key points

• Functional training (plyometrics, neuromuscular, proprioceptive and agility exercises) in athletes during 4th to 6th months post-ACLR further improved functional outcomes, compared to a conventional rehabilitation program.
• The former program was more time-efficient compared to the latter one as indicated by the weekly training duration (4hrs/week vs. 6hrs/week).
• This study provides evidence of the functional training in knee rehabilitation and provides important information that is highly relevant to clinicians, physiotherapists, coaches and trainers who are in charge of the injured athletes during the later phase of the rehabilitation after ACLR.

Key words: ACL reconstruction, knee injury, retraining, agility, strength testing, power testing     

Quality of life of pediatric patients with lower urinary tract dysfunction and their caregivers

The interest in quality of life (QoL) studies has increased as they are useful instruments to evaluate and compare medical care delivery and the impact of health interventions. The perception of QoL differs among individuals. Its characterization is especially difficult in the pediatric age group as each developmental stage presents specific demands. The prevalence of congenital lower urinary dysfunction is high and their management changes the daily routine of the patients and their families. In a cross-sectional study, we evaluated the QoL of 28 children and adolescents with urinary malformations and their caregivers using the Autoquestionnaire Qualité de Vie Enfant Imagé (AUQUEI) and Short-Form 36 (SF-36), respectively, and compared the results with 38 healthy control age-paired children/caregivers. Four questions were added to patients' questionnaire to evaluate issues related to their urological management. Our results show lower AUQUEI total scoring in the patients’ group (p < 0.0213, Fisher’s exact test), who also present problems in dealing with social aspects, such as being at classroom, manifest negative feelings in relation to diurnal urinary losses but seem to be well adapted to intermittent urethral catheterization. A tendency for worse QoL scores in the patients’ group caregivers was detected in the SF-36 pain and physical limitation domains.     

Low pretreatment total testosterone (< 3 ng/mL) predicts extraprostatic disease in prostatectomy specimens from patients with preoperative localized prostate cancer

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

• ? To investigate the relationship between pretreatment testosterone levels and pathological specimen characteristics, by prospectively examining serum androgen concentrations in a well‐studied cohort of patients who underwent radical prostatectomy (RP) for localized prostate cancer.

PATIENTS AND METHODS

• ? A total of 107 patients with clinically localized prostate cancer had an assay of total testosterone before laparoscopic RP at our institution.
• ? The results were classified into two groups based on the total serum testosterone: group1, <3 ng/mL; group 2, ≥3 ng/mL.
• ? Student’s t‐test was used to compare continuous variables, and Fisher’s exact test or the chi‐squared test was used to compare categorical variables.
• ? Survival curves were established using the Kaplan–Meier method and compared using the log‐rank test. In all tests, P < 0.05 was considered to indicate statistical significance.

RESULTS

• ? All patients had localized prostate cancer based on digital rectal examination (DRE) and preoperative magnetic resonance imaging (MRI). Groups 1 and 2 were similar in terms of age, body mass index, preoperative co‐morbidities (cardiovascular and diabetes mellitus), clinical stage of prostate cancer and preoperative PSA levels.
• ? In pathological specimens, low total testosterone (<3 ng/mL) was an independent risk factor for high Gleason score (>7) and for locally advanced pathological stage (pT3 and pT4).
• ? Higher preoperative testosterone correlated with disease confined to the gland.
• ? There was no association between serum testosterone levels and surgical margin status, on the one hand, and biochemical recurrence on the other.

CONCLUSION

• ? Low serum testosterone appears to be predictive of aggressive disease (Gleason score >7 and extraprostatic disease, pathological stage >pT2) in patients who underwent RP for localized prostate cancer.

     

Osteoblastoma in the skeletally immature

BACKGROUND: Osteoblastoma is a rare benign and sometimes locally aggressive tumor with peak incidence in the second decade. None of the available series addresses specifically the differences in presentation, management, and outcome between the pediatric and adult patient populations. METHODS: The medical records and radiographs of all children diagnosed with osteoblastoma during a 17-year period were reviewed. We recorded demographic information, time until diagnosis, location, clinical and radiographic characteristics, treatment, complications, and outcome at a minimum 2-year follow-up (range, 2-5 years). RESULTS: Seventeen children met the inclusion criteria. There were 10 boys and 7 girls, with an average age at diagnosis of 11 years (range, 20 months-15 years). The average time delay between onset of symptoms and diagnosis was 6.5 months (range, 2 months-2 years). There were 7 lesions in the lower extremity, 5 in the spine, 4 in the upper extremity, and 1 in the sternum. Pain at the tumor site was present in all cases. Two of the 5 patients with spine lesion had scoliosis. All patients underwent open incisional biopsy with intraoperative frozen section. In 16 cases, this was followed by a 4-step approach (extended curettage, high-speed burring, electrocauterization of cavity wall, and phenol 5% solution). Four of the 5 patients with spine lesions had instrumented posterior spine fusion after tumor removal. Two patients were referred to our institution with recurrent lesion after surgery elsewhere. Only 1 (6%) of 15 children initially treated at our institution had recurrence. All recurrences occurred in children younger than 6 years; all were successfully treated with a 4-step approach. CONCLUSIONS: Osteoblastomas can be successfully treated with a 4-step approach. Children younger than 6 years may have a higher likelihood of recurrence.