The Effect of Doxycycline on Achilles Tendon Repair in a Rat Model

@#Introduction: Doxycycline is a commonly used antibiotic that is also a potent inhibitor of matrix metalloproteinase (MMPs). The use of doxycycline in repairing tendon lesions has been previously investigated and conflicting findings have been reported on its effectiveness. In this study, we sought to evaluate the effects of exposure to doxycycline on Achilles tendon repair. Materials and Methods: Twenty healthy rats of the same breed and gender were randomly assigned to two groups of sham, and Doxycycline group therapy. The rats underwent a surgical intervention in which a 2mm incision was performed on the lateral sides of the right Achilles tendons. The treatment group received oral gavage administrations of 50mg/kg/day of doxycycline for 30 days. After this duration, tissue samples were taken from the site of the injuries, which were then histologically evaluated for alignment of the collagen fibres, inflammation reaction, cellular density, and fibroblastic activity. Results: The histological assessment of the tissue samples, revealed significant changes in the repaired tissues of the treatment group in comparison to the sham group; namely more irregularity in the alignment of the collagen fibres, increased cellular density, and increased fibroblastic activity. However, only the alignment of the collagen fibres reached the statistical significance. Conclusion: The results of this study indicate that exposure to doxycycline may result in the improvement of repair of the Achilles tendon injuries, especially collagen filament integrity

The Effect of Doxycycline on Achilles Tendon Repair in a Rat Model.

INTRODUCTION: Doxycycline is a commonly used antibiotic that is also a potent inhibitor of matrix metalloproteinase (MMPs). The use of doxycycline in repairing tendon lesions has been previously investigated and conflicting findings have been reported on its effectiveness. In this study, we sought to evaluate the effects of exposure to doxycycline on Achilles tendon repair. MATERIALS AND METHODS: Twenty healthy rats of the same breed and gender were randomly assigned to two groups of sham, and Doxycycline group therapy. The rats underwent a surgical intervention in which a 2mm incision was performed on the lateral sides of the right Achilles tendons. The treatment group received oral gavage administrations of 50mg/kg/day of doxycycline for 30 days. After this duration, tissue samples were taken from the site of the injuries, which were then histologically evaluated for alignment of the collagen fibres, inflammation reaction, cellular density, and fibroblastic activity. RESULTS: The histological assessment of the tissue samples, revealed significant changes in the repaired tissues of the treatment group in comparison to the sham group; namely more irregularity in the alignment of the collagen fibres, increased cellular density, and increased fibroblastic activity. However, only the alignment of the collagen fibres reached the statistical significance. CONCLUSION: The results of this study indicate that exposure to doxycycline may result in the improvement of repair of the Achilles tendon injuries, especially collagen filament integrity.

Beta-interferon exposure and onset of secondary progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Beta-interferons (IFNß) are the most widely prescribed drugs for patients with multiple sclerosis (MS). However, whether or not treatment with IFNß can delay secondary progressive MS (SPMS) onset remains unknown. Our aim was to examine the association between IFNß exposure and SPMS onset in patients with relapsing-remitting MS (RRMS). METHODS: A retrospective cohort study using British Columbia (Canada) population-based clinical and health administrative data (1985-2008) was conducted. RRMS patients treated with IFNß (n = 794) were compared with untreated contemporary (n = 933) and historical (n = 837) controls. Cohort entry was the first clinic visit during which patients became eligible for IFNß treatment (baseline). The outcome was time from baseline to SPMS onset. Cox regression models with IFNß as a time-dependent exposure were adjusted for sex, and baseline age, disease duration, disability, *socioeconomic status and *comorbidities (*available for the contemporary cohorts only). Additional analyses included propensity score adjustment. RESULTS: The median follow-up for the IFNß-treated, untreated contemporary and historical controls were 5.7, 3.7 and 7.3 years, and the proportions of patients reaching SPMS were 9.2%, 11.8% and 32.9%, respectively. After adjustment for confounders, IFNß exposure was not associated with the risk of reaching SPMS when either the contemporary or the historical untreated cohorts were considered (hazard ratio 1.07; 95% confidence interval 0.93-1.48, and hazard ratio 1.04; 95% confidence interval 0.74-1.46, respectively). Further adjustments and the propensity score yielded results consistent with the main analysis. CONCLUSIONS: Amongst patients with RRMS, use of IFNß was not associated with a delayed onset of SPMS.

Investigation of heterogeneity in the association between interferon beta and disability progression in multiple sclerosis: an observational study.

BACKGROUND AND PURPOSE: It was recently reported that there was no significant overall association between interferon beta exposure and disability progression in relapsing-remitting multiple sclerosis (RRMS) patients in an observational study from Canada. In the current study, the potential for heterogeneity in the association between exposure to interferon beta and disability progression across patients' baseline characteristics was investigated. METHODS: RRMS patients treated with interferon beta (n = 868) and two cohorts of untreated patients (829 contemporary and 959 historical controls) were included. The main outcome was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained Expanded Disability Status Scale (EDSS) score 6 using a multivariable Cox model, with treatment as a time-varying predictor, testing interaction effects for five pre-specified baseline characteristics: sex, age, disease duration, EDSS and annualized relapse rate (ARR) based on the previous 2 years. RESULTS: Significant heterogeneity was found in the association of interferon beta exposure and disability progression only across ARR, and only when treated patients were compared with historical controls (P = 0.005 at a Bonferroni-adjusted alpha of 0.01). For patients with ARR>1, treatment-exposed time was associated with a hazard ratio of 0.38 (95%CI 0.20-0.75) for disability progression compared with the unexposed time. CONCLUSIONS: RRMS patients with more frequent relapses at baseline may be more likely to benefit from interferon beta treatment with respect to long-term disability progression.

Relative mortality and survival in multiple sclerosis: findings from British Columbia, Canada.

OBJECTIVE: To examine mortality and factors associated with survival in a population based multiple sclerosis (MS) cohort. METHODS: Clinical and demographic data of MS patients registered with the British Columbia MS clinics (1980-2004) were linked to provincial death data, and patients were followed until death, emigration or study end (31 December 2007). Absolute survival and the influence of patient characteristics (sex, disease course (primary progressive (PPMS) vs relapsing onset (R-MS)) and onset age) were estimated by Kaplan-Meier analyses (from birth and disease onset). Mortality relative to the general population was examined using standardised mortality ratios. Excess mortality associated with patient characteristics and time period of cohort entry was assessed by relative survival modelling. RESULTS: Of 6917 patients, 1025 died. Median survival age was 78.6 years (95% CI 77.5 to 79.7) for women and 74.3 years (95% CI 73.1 to 75.4) for men. Survival from onset was longer for R-MS (49.7 years; 95% CI 47.9 to 51.5) than for PPMS (32.5 years; 95% CI 29.5 to 35.7); however, survival age was similar. The overall standardised mortality ratios was 2.89 (95% CI 2.71 to 3.07), and patients survived approximately 6 years less than expected, relative to the general population. PPMS had a higher relative mortality risk compared with R-MS (relative mortality ratio (RMR) 1.52; 95% CI 1.30 to 1.80). Women with PPMS had a relative survival disadvantage compared with men with PPMS (RMR 1.55; 95% CI 1.19 to 2.01). Relative survival within 10 years of cohort entry was similar between time periods. CONCLUSIONS: Some of the longest MS survival times are reported here but the risk of death was still greater than in the age, sex and calendar year matched general population. No evidence of increased survival over time was found when improved survival in the general population was taken into consideration.

Outcomes and recurrence rates in chronic subdural haematoma.

The object of this study was to determine the relationship between outcome (assessed by Glasgow Outcome Scale) and recurrence in chronic subdural haematoma (CSDH). Eighty-two consecutive patients who underwent surgery for CSDH were included in this study. The relationship between the following variables and CSDH recurrence was studied: sex; age; history of trauma; Glasgow Coma Scale (GCS) at the time of admission (stage 1: GCS>12, stage 2: GCS: 8 - 12, stage 3: GCS<8); interval between head injury (when a history of trauma was present) and surgery; presence of a midline shift on CT scans; presence of intracranial air 7 days after surgery; haematoma density; haematoma width; presence of brain atrophy; and Glasgow Outcome Scale (GOS, both quantitative and non-quantitative) at the time of discharge. Throughout the analysis, p<0.05 was considered statistically significant. The results showed lower GCS (p<0.001), higher GOS (p<0.001), presence of intracranial air 7 days after surgery (p=0.002), and a high density haematoma (p<0.001) were significantly associated with recurrence of CSDH. It was concluded that GOS is related with recurrence in CSDH.

Effect of early interferon beta-1a therapy on conversion to multiple sclerosis in Iranian patients with a first demyelinating event.

BACKGROUND: A new treatment approach to multiple sclerosis (MS) is the initiation of interferon therapy in the early phase of the disease when a patient presents with clinically isolated syndrome. AIMS OF THE STUDY: The goal of this study was to assess the effect of early treatment on the risk of conversion to clinically definite MS in Iranian patients. METHODS: Eligible patients had presented with a first episode of neurological dysfunction suggesting MS within the previous 3 months and had abnormal brain magnetic resonance imaging (MRI). Patients were randomly assigned to receive intramuscular interferon beta 1a 30 mug or placebo once a week for 3 years. RESULTS: Of the 217 patients randomized, 202 patients completed the study; 104 received Avonex and 98 received placebo. Fewer patients converted to clinically definite multiple sclerosis in the treated group than in the placebo group during the study (36.6% vs 58.2%, P < 0.003). The number of active T2-weighted MRI lesions was significantly lower in the treated group. CONCLUSIONS: The results of our study, which are consistent with those from western studies, show that treatment at an early stage of MS delays conversion to definite MS and has positive effects on MRI outcomes.

Phosphate enema toxicosis in a pygmy goat wether.

Phosphate enema toxicity was diagnosed in a 7-month-old, castrated male, pygmy goat. On presentation, clinical findings included mild depression, tachycardia, tachypnea, rumen stasis, muscle tremors, hypocalcemia, hypokalemia, hypochloremia, hyperphosphatemia, azotemia, and metabolic acidosis. Fluid diuresis and parenteral antimicrobial therapy resulted in recovery after 3 d of treatment.