The efficacy of immediate versus delayed antibiotic administration on bacterial growth and biofilm production of selected strains of uropathogenic Escherichia coli and Pseudomonas aeruginosa

Purpose

The treatment of urinary tract infections (UTI) with antibiotics is commonly used, but recurrence and antibiotic resistance have been growing and concerning clinicians. We studied whether the rapid onset of a protective biofilm may be responsible for the lack of effectiveness of antibiotics against selected bacteria.

Materials and Methods

Two established uropathogenic Escherichia coli strains, UTI89 and CFT073, and two Pseudomonas aeruginosa strains, PA01 and Boston-41501, were studied to establish a reliable biofilm formation process. Bacterial growth (BG) was determined by optical density at 600 nm (OD 600) using a spectrophotometer, while biofilm formation (BF) using crystal violet staining was measured at OD 550. Next, these bacterial strains were treated with clinically relevant antibiotics, ciprofloxacin HCl (200 ng/mL and 2 μg/mL), nitrofurantoin (20 μg/mL and 40 μg/mL) and ampicillin (50 μg/mL) at time points of 0 (T0) or after 6 hours of culture (T6). All measurements, including controls (bacteria -1% DMSO), were done in triplicates and repeated three times for consistency.

Results

The tested antibiotics effectively inhibited both BG and BF when administered at T0 for UPEC strains, but not when the antibiotic administration started 6 hours later. For Pseudomonas strains, only Ciprofloxacin was able to significantly inhibit bacterial growth at T0 but only at the higher concentration of 2 μg/mL for T6.

Conclusion

When established UPEC and Pseudomonas bacteria were allowed to culture for 6 hours before initialization of treatment, the therapeutic effect of selected antibiotics was greatly suppressed when compared to immediate treatment, probably as a result of the protective nature of the biofilm.     

Prevalence of hepatitis B and C viruses in HIV-positive patients in China: a cross-sectional study

Introduction

Liver disease related to hepatitis B (HBV) and hepatitis C (HCV) may temper the success of antiretroviral therapy (ART) in China. Limited data exist on their prevalence in HIV-positive Chinese. A multi-centre, cross-sectional study was carried out to determine the prevalence and disease characteristics of HBV and HCV co-infection in HIV-positive patients across 12 provinces.

Methods

HIV-positive ART-naïve patients were recruited from two parent cohorts established during November 2008–January 2010 and August 2012–September 2014. Hepatitis B surface antigen (HBsAg), hepatitis B e antigen and HCV antibody (anti-HCV) status were retrieved from parent databases at the visit prior to ART initiation. HBV DNA was then determined in HBsAg+ patients. HCV RNA was quantified in anti-HCV+ patients. Aspartate aminotransferase-to-platelet ratio index (APRI) and the fibrosis-4 (FIB4) were calculated. Chi-square test, Kruskal–Wallis test and logistic regression were used for statistical analysis, as appropriate.

Results

Of 1944 HIV-positive patients, 186 (9.5%) were HIV–HBV co-infected and 161 (8.3%) were HIV–HCV co-infected. The highest HIV–HBV prevalence (14.5%) was in Eastern China while the highest HIV–HCV prevalence was in the Central region (28.2%). HIV–HBV patients had lower median CD4 + T cell count (205 cells/μL) than either HIV monoinfected (242 cells/μL, P=0.01) or HIV–HCV patients (274 cells/μL, P=0.001). Moderate-to-significant liver disease was present in >65% of the HIV–HCV, ~35% of the HIV–HBV and ~20% of the HIV monoinfected patients. Independent associations with moderate-to-significant liver disease based on APRI included HBV (Odds ratio, OR 2.37, P < 0.001), HCV (OR 9.64, P<0.001), CD4 count≤200 cells/μL (OR 2.55, P<0.001) and age ≥30 years (OR 1.80, P=0.001).

Conclusions

HBV and HCV prevalence is high in HIV-positive Chinese and differs by geographic region. HBV and HCV co-infection and HIV monoinfection are risks for moderate-to-significant liver disease. Only HIV–HBV is associated with greater HIV-related immunosuppression. Incorporating screening and management of hepatitis virus infections into Chinese HIV programmes is needed.     

Clinical and Neurophysiologic Assessment of Strength and Spasticity During Intrathecal Baclofen Titration in Incomplete Spinal Cord Injury: Single-Subject Design

Background/Objective:

Spasticity after spinal cord injury (SCI) is commonly managed with oral and intrathecal baclofen (ITB), with less attention to the effects on voluntary motor control. Studies combining clinical and neurophysiologic assessments during dose optimization are rare. Study aims (a) systematically evaluate effects of varied doses of oral and ITB on clinical and neurophysiologic measures of strength and spasticity and (b) relate clinical and neurophysiologic findings.

Methods:

A 41-year-old man with an incomplete T11-ASIA D SCI was studied during ITB titration. Spasticity and strength in the lower extremities were assessed clinically and neurophysiologically at 5 different daily dosages of baclofen: (a) 80 mg oral, (b) 80 mg oral/50 μg ITB, (c) 80 mg oral/125 μg ITB, (d) 30 mg oral/125 μg ITB, and (e) 125 μg ITB only.

Results:

A dose-dependent change in the Ashworth score and lower limb motor score was observed during titration of oral and ITB. Whereas the Hoffman (H)-reflex was abolished after the introduction of ITB, the flexion withdrawal reflex approximated a dose-dependent pattern. Changes in the motor score and EMG during voluntary muscle activation were proportionally smaller than the corresponding changes in clinical and neurophysiologic measures of spasticity. Neurophysiologic assessment largely paralleled clinical findings.

Conclusions:

This single-subject study shows that the control of spasticity can be achieved without detrimental effects on strength in incomplete SCI and suggests the need for including strength testing in comprehensive clinical assessment of spasticity. The study shows convergent validity between clinical and neurophysiologic assessments during ITB dose titration. Adding neurophysiologic assessment to clinical assessment may provide objectivity and sensitivity and facilitate decision-making during ITB titration.     

Accuracy of medical models made by consumer-grade fused deposition modelling printers

BACKGROUND:

Additive manufacturing using fused deposition modelling (FDM) has become widely available with the development of consumer-grade three-dimensional printers. To be useful in maxillofacial surgery, models created by these printers must accurately reproduce the craniofacial skeleton.

OBJECTIVE:

To determine the accuracy of consumer-grade FDM printers in the production of medical models compared with industrial selective laser sintering (SLS) printers.

METHODS:

Computed tomography images of a dry skull were manipulated using OsiriX (OsiriX, Switzerland) and ZBrush (Pixologic, USA) software. Models were fabricated using a consumer-grade FDM printer at 100 μm, 250 μm and 500 μm layer heights and an industrial SLS printer. Seven linear measurements were made on the models and compared with the corresponding dry skull measurements using an electronic caliper.

RESULTS:

A dimensional error of 0.30% was observed for the SLS models and 0.44%, 0.52% and 1.1% for the 100 μm, 250 μm and 500 μm FDM models, respectively.

CONCLUSION:

Consumer-grade FDM printers can produce medical models with sufficient dimensional accuracy for use in maxillofacial surgery. With this technology, surgeons can independently produce low-cost maxillofacial models in an office setting.     

High-risk human papillomavirus infection in HIV-positive African women living in Europe

Introduction

Cervical infection with high-risk human papillomavirus (HRHPV) induces cervical cancer and is present in 14% of women in Europe. We assessed the prevalence and incidence of cervical HRHPV in a cohort of HIV-positive women living in Belgium.

Methods

Prospective observational program of screening and follow up of HRHPV cervical infection performed by Hybrid Capture in 825 HIV-positive women between 2002 and 2011. Women without normal cervix at baseline were excluded.

Results

The final analysis included 652 women: median age 38 years, African origin (81%), median HIV follow-up (66 months), median CD4 count (426 cells/μL) and 79% on antiretroviral therapy (cART). At baseline, HRHPV prevalence was 43% and decreased significantly as both age and CD4 cell count increased: highest prevalence (100%) in women <30 years and <200 CD4/μL and lowest (19%) in women >40 years and >500 CD4/μL (p<0.0001, multivariate analysis). The relative risk (RR) to carry HRHPV at baseline decreases proportionally by 11% for each 5 years-age increase and by 11% for each 100 CD4 cells/μL rise (RR=0.89, 95% CI: 0.85-0.93; p<0.0001, Poisson regression for both). During follow-up, incidence rate of HRHPV was 13.4 per 100 women-years.

Conclusions

We found a high HRHPV prevalence of 43% and an incidence rate of 13 per 100 women-years in this cohort of HIV-positive women living in Europe and on cART. Women under 40 years-age had the highest prevalence even with CD4 count >350 cells/μL. The magnitude of HRHPV epidemiology should prompt to evaluate the clinical efficacy of vaccines against HPV in HIV-infected women.     

Lower-Dose Mepivacaine Plus Fentanyl May Improve Spinal Anesthesia for Knee Arthroscopy

Background

Previous work indicates that 30 mg isobaric mepivacaine 1.5% plus 10 μg fentanyl produces reliable anesthesia for knee arthroscopy with a more rapid recovery profile than 45 mg mepivacaine.

Questions/Purposes

This randomized controlled trial compared plain mepivacaine to three reduced doses of mepivacaine with 10 μg fentanyl for spinal anesthesia.

Methods

Following written informed consent, subjects undergoing outpatient knee arthroscopy were prospectively randomized into one of four groups: mepivacaine 37.5 mg (M37.5); mepivacaine 30 mg plus fentanyl 10 μg (M30/F10); mepivacaine 27 mg plus fentanyl 10 μg (M27/F10); and mepivacaine 24 mg plus fentanyl 10 μg (M24/F10). The spinal was evaluated by the blinded anesthetist and surgeon. In the post-anesthesia care unit, sensory and motor block resolution was assessed. Subjects rated their satisfaction with the overall experience.

Results

Group M30/F10 (n = 6) had two “fair” anesthetics, and group M27/F10 (n = 10) had one “fair” and one “inadequate” anesthetic. Both groups were eliminated from further enrollment per study protocol. The recovery profiles showed little difference between groups M37.5 and M30/F10, except for motor block resolution (median (25th percentile, 75th percentile): 171 (135, 195) and 128 (120, 135), respectively). Groups M27/F10 and M24/F10 demonstrated recovery profiles that were faster than group M37.5. Patient satisfaction was 10/10 for all groups.

Conclusions

Adding fentanyl 10 μg to a lower dose of mepivacaine 1.5% can lead to quicker recovery profiles. However, this advantage of a quicker recovery must be weighed against the likelihood of an incomplete anesthetic.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-015-9454-8) contains supplementary material, which is available to authorized users.     

Delayed-type hypersensitivity (DTH) test anergy does not impact CD4 reconstitution or normalization of DTH responses during antiretroviral therapy

Introduction

Delayed-type hypersensitivity (DTH) testing is an in vivo assessment of cell-mediated immunity. Although highly active antiretroviral therapy (HAART) improves immunologic parameters, the relationship between DTH responsiveness and CD4 gains on HAART is not completely understood. We investigated CD4 reconstitution and the change in DTH responses from treatment baseline through 24 months of viral load (VL)-suppressive HAART in the U.S. Military HIV Natural History Study.

Methods

Treatment-naïve subjects with VL <400 copies/mL after ≥24 months on HAART were included (n=302). DTH testing consisted of ≥3 recall antigens, and responses were classified by the number of positive skin tests: anergic (0–1) or non-anergic (≥2). Pre-HAART DTH results were compared for the outcome of CD4 reconstitution at 24 months of HAART. Improvement in DTH responses was also analyzed for those anergic before HAART initiation.

Results

Non-anergic responses were observed in 216 (72%) participants, while 86 (28%) individuals were anergic prior to HAART initiation. Demographically there were similar distributions of age at HIV diagnosis and HAART initiation, as well as gender and race or ethnicity. There were no significant differences between non-anergic and anergic participants in pre-HAART CD4 count (409 cells/μL, interquartile range (IQR) 315–517 vs. 373 cells/μL, IQR 228–487; p=0.104) and VL (4.3 log₁₀ copies/mL, IQR 3.4–4.9 vs. 4.4 log₁₀ copies/mL, IQR 3.6–5.0; p=0.292). Median CD4 gains 24 months after HAART initiation were similar between the non-anergic (220 cells/μL, IQR 115–358) and anergic groups (246 cells/μL, IQR 136–358; p=0.498). For individuals anergic before HAART initiation, DTH normalization occurred at 24 months post-HAART in the majority of participants (51 of 86, 59%). Normalization of DTH responses was not associated with CD4 count at HAART initiation (OR 0.73, 95% CI 0.47, 1.09 per 100 cells; p=0.129) nor with AIDS diagnoses prior to HAART (OR 0.34, 95% CI 0.04, 2.51; p=0.283).

Conclusions

DTH responsiveness has been shown to predict HIV disease progression independent of CD4 count in untreated individuals. In the setting of HAART, pre-HAART anergy does not appear to impact CD4 gains or the ability to normalize DTH responses after 24 months of VL-suppressive HAART.     

Liposomal Formulation Decreases Toxicity of Amphotericin B In Vitro and In Vivo

Background

Liposomal amphotericin B is locally delivered to treat fungal orthopaedic infections but little is known about local tissue toxicity, if any, that might be associated with local delivery.

Questions/purposes

(1) Is liposomal amphotericin B cytotoxic in vitro? (2) Is locally delivered liposomal amphotericin B toxic to tissue in vivo?

Methods

Mouse fibroblasts (BA LB/3T3 A31) and osteoblasts (MC3T3) were exposed to two formulations of amphotericin B (liposomal and deoxycholate) at concentrations of 0, 1, 5, 10, 100, 500, and 1000 μg/mL. Cell viability was determined by MTT assay after 1, 3, and 5 hours of exposure and a proliferation assay after 1, 4, and 7 days of exposure and then after 3 recovery days without drug. Tissue exposure occurred by local delivery of liposomal amphotericin B, 200 or 800 mg/batch antifungal-loaded bone cement (ALBC), or amphotericin B deoxycholate, 800 mg/batch ALBC in rat paraspinal muscles. White blood cell count (WBC) and serum amphotericin B levels were obtained on Days 1 and 3. Rats were euthanized at 2 and 4 weeks and semiqualitative histopathology was performed.

Results

Liposomal amphotericin B is cytotoxic in vitro but not toxic to tissues in vivo. All cells survived concentrations up to 1000 μg/mL for 5 hours, 100% ± 0%, but none survived ≥ 100 μg/mL for 7 days, 0% ± 0%. Fibrosis was seen adjacent to ALBC without inflammation or necrosis, indistinguishable from controls for both liposomal amphotericin B doses. Amphotericin B serum levels were all less than 1 µg/mL and WBC counts were all normal.

Conclusions

In vitro cytotoxicity to liposomal amphotericin B occurred but no adverse tissue reaction was seen in vivo.

Clinical Relevance

Local delivery of liposomal amphotericin B in ALBC was well tolerated by mouse tissue; however, clinical studies are needed to confirm this finding in humans.     

Solid and hollow pedicle screws affect the electrical resistance: A potential source of error with stimulus-evoked electromyography

Background:

Although stimulus evoked electromyography (EMG) is commonly used to confirm the accuracy of pedicle screw placement. There are no studies to differentiate between solid screws and hollow screws to the electrical resistance of pedicle screws. We speculate that the electrical resistance of the solid and hollow pedicle screws may be different and then a potential source of error with stimulus-evoked EMG may happen.

Materials and Methods:

Resistance measurements were obtained from 12 pedicle screw varieties (6 screws of each manufacturer) across the screw shank based on known constant current and measured voltage. The voltage was measured 5 times at each site.

Results:

Resistance of all solid screws ranged from 0.084 Ω to 0.151 Ω (mean =0.118 ± 0.024 Ω) and hollow screws ranged from 0.148 Ω to 0.402 Ω (mean = 0.285 ± 0.081 Ω). There was a significant difference of resistance between the solid screws and hollow screws (P < 0.05). The screw with the largest diameter no matter solid screws or hollow screws had lower resistance than screws with other diameters. No matter in solid screws group or hollow screws group, there were significant differences (P < 0.05) between the 5.0 mm screws and 6.0 mm screws, 6.0 mm screws and 7.0 mm screws, 5.0 mm screws and 7.0 mm screws, 4.5 mm screws and 5.5 mm screws, 5.5 mm screws and 6.5 mm screws, 4.5 mm screws and 6.5 mm screws. The resistance of hollow screws was much larger than the solid screws in the same diameter group (P < 0.05).

Conclusions:

Hollow pedicle screws have the potential for high electrical resistance compared to the solid pedicle screws and therefore may affect the EMG response during stimulus-evoked EMG testing in pedicle screw fixation especially in minimally invasive percutaneous pedical screw fixation surgery.     

Renal and functional outcomes following cystectomy and neobladder reconstruction

Background:

Orthotopic reconstruction following cystectomy has evolved in an attempt to restore anatomy and function to as close as possible to the preoperative state. We review the renal and functional outcomes of patients who underwent cystectomy and neobladder reconstruction at our institution.

Methods:

Between December 2003 and October 2007, 31 patients underwent cystectomy with Studer neobladder reconstruction at the Ottawa Hospital, Ottawa, Ontario, Canada. Follow-up data were obtained regarding renal function (serum creatinine, μmol/L), continence, urinary flow rates and post-void residual (PVR) at 3, 6 and 12 months after surgery. Change in creatinine from preoperative baseline was calculated and analyzed by student t-test to determine if there was a significant rise in creatinine.

Results:

There was a statistically significant increase in creatinine from preoperative baseline, with an average increase of 17.3 μmol/L, 21.8 μmol/L and 26.3 μmol/L at 3, 6 and 12 months, respectively. Six patients developed hydronephrosis. Excluding patients with hydronephrosis, there continued to be a statistically significant rise in creatinine with an average increase of 11.9 μmol/L, 14.7 μmol/L and 19.4 μmol/L at 3, 6 and 12 months, respectively. At 1 year, daytime continence was achieved by 89% of patients; 70% were continent at night.

Interpretation:

Orthotopic neobladders have excellent functional outcomes with low rates of incontinence, which improved throughout follow-up. A significant proportion of patients developed hydronephrosis, highlighting the need for close follow-up to prevent reversible renal deterioration. Creatinine increased during follow-up irrespective of the development of hydronephrosis, but the clinical significance is unknown.     

Dietary habits and prostate cancer detection: a case–control study

Background

Many studies have suggested that nutritional factors may affect prostate cancer development. The aim of our study was to evaluate the relationship between dietary habits and prostate cancer detection.

Methods

We studied 917 patients who planned to have transrectal ultrasonography–guided prostatic biopsy based on an elevated serum prostate-specific antigen (PSA) level, a rising serum PSA level or an abnormal digital rectal examination. Before receiving the results of their biopsy, all patients answered a self-administered food frequency questionnaire. In combination with pathology data we performed univariable and multivariable logistic regression analyses for the predictors of cancer and its aggressiveness.

Results

Prostate cancer was found in 42% (386/917) of patients. The mean patient age was 64.5 (standard deviation [SD] 8.3) years and the mean serum PSA level for prostate cancer and benign cases, respectively, was 13.4 (SD 28.2) μg/L and 7.3 (SD 4.9) μg/L. Multivariable analysis revealed that a meat diet (e.g., red meat, ham, sausages) was associated with an increased risk of prostate cancer (odds ratio [OR] 2.91, 95% confidence interval [CI] 1.55–4.87, p = 0.027) and a fish diet was associated with less prostate cancer (OR 0.54, 95% CI 0.32–0.89, p = 0.017). Aggressive tumours were defined by Gleason score (≥ 7), serum PSA level (≥ 10 μg/L) and the number of positive cancer cores (≥ 3). None of the tested dietary components were found to be associated with prostate cancer aggressivity.

Conclusion

Fish diets appear to be associated with less risk of prostate cancer detection, and meat diets appear to be associated with a 3-fold increased risk of prostate cancer. These observations add to the growing body of evidence suggesting a relationship between diet and prostate cancer risk.     

Bony defect repair in rabbit using hybrid rapid prototyping polylactic-co-glycolic acid/β-tricalciumphosphate collagen I/apatite scaffold and bone marrow mesenchymal stem cells

Background:

In bone tissue engineering, extracellular matrix exerts critical influence on cellular interaction with porous biomaterial and the apatite playing an important role in the bonding process of biomaterial to bone tissue. The aim of this study was to observe the therapeutic effects of hybrid rapid prototyping (RP) scaffolds comprising polylactic-co-glycolic acid (PLGA), β-tricalciumphosphate (β-TCP), collagen I and apatite (PLGA/β-TCP-collagen I/apatite) on segmental bone defects in conjunction with combination with bone marrow mesenchymal stem cells (BMSCs).

Materials and Methods:

BMSCs were seeded into the hybrid RP scaffolds to repair 15 mm defect in the radius of rabbits. Radiograph, microcomputed tomography and histology were used to evaluate new bone formation.

Results:

Radiographic analysis done from 12 to 36 weeks postoperative period demonstrated that new bone formed at the radial defect site and continues to increase until the medullary cavity is recanalized and remodelling is complete. The bone defect remained unconnected in the original RP scaffolds (PLGA/β-TCP) during the whole study. Histological observations conformed to the radiographic images. In hybrid RP scaffold group, woven bone united the radial defect at 12 weeks and consecutively remodeled into lamellar bone 24 weeks postoperation and finally matured into cortical bone with normal marrow cavity after another 12 weeks. No bone formation but connective tissue has been detected in RP scaffold at the same time.

Conclusion:

Collagen I/apatite sponge composite coating could improve new bone formation in vivo. The hybrid RP scaffold of PLGA/β-TCP skeleton with collagen I/apatite sponge composite coating is a promising candidate for bone tissue engineering.     

Comparison of the cheese-wiring effects among three sutures used in rotator cuff repair

Purpose:

The goal of this study was to compare the cheese-wiring effects of three sutures with different coefficients of friction.

Materials and Methods:

Sixteen human cadaveric shoulders were dissected to expose the distal supraspinatus and infraspinatus muscle tendons. Three sutures were stitched through the tendons: #2 Orthocord^™ suture (reference #223114, DePuy Mitek, Inc., Raynham, MA), #2 ETHIBOND* EXCEL Suture, and #2 FiberWire^® suture (FiberWire^®, Arthrex, Naples, FL). The sutures were pulled by cyclic axial forces from 10 to 70 N at 1 Hz for 1000 cycles through a MTS machine. The cut-through distance on the tendon was measured with a digital caliper.

Results:

The cut-through distance in the supraspinatus tendons (mean ± standard deviation, n = 12) were 2.9 ± 0.6 mm for #2 Orthocord^™ suture, 3.2 ± 1.2 mm for #2 ETHIBOND* suture, and 4.2 ± 1.7 mm for #2 FiberWire^® suture. The differences were statistically significant analyzing with analysis of variance (P = 0.047) and two-tailed Student''s t-test, which showed significance between Orthocord^™ and FiberWire^® sutures (P = 0.026), but not significant between Orthocord^™ and ETHIBOND* sutures (P = 0.607) or between ETHIBOND* and FiberWire^® sutures (P = 0.103).

Conclusion:

The cheese-wiring effect is less in the Orthocord^™ suture than in the FiberWire^® suture in human cadaveric supraspinatus tendons.

Clinical Relevance:

Identification of sutures that cause high levels of tendon cheese-wiring after rotator cuff repair can lead to better suture selection.     

Asymptomatic cryptococcal antigenemia is associated with mortality among HIV-positive patients in Indonesia

Introduction

Previous studies, mostly from Africa, have shown that serum cryptococcal antigenemia may precede the development of cryptococcal meningitis and early death among patients with advanced HIV infection. We examined cryptococcal antigenemia as a risk factor for HIV-associated mortality in Indonesia, which is experiencing a rapidly growing HIV epidemic.

Methods

We included ART-naïve HIV patients with a CD4 cell count below 100 cells/μL and no signs of meningitis in an outpatient HIV clinic in Bandung, West Java, Indonesia. Baseline clinical data and follow-up were retrieved from a prospective database, and cryptococcal antigen was measured in stored serum samples using a semiquantitative lateral flow assay. Cox regression analysis was used to identify factors related to mortality.

Results

Among 810 patients (median CD4 cell count 22), 58 (7.1%) had a positive cryptococcal antigen test with a median titre of 1:80 (range: 1:1 to 1:2560). Cryptococcal antigenemia at baseline was strongly associated with the development of cryptococcal meningitis and early death and loss to follow-up. After one year, both death (22.4% vs. 11.6%; p=0.016; adjusted HR 2.19; 95% CI 1.78–4.06) and the combined endpoint of death or loss to follow-up (67.2% vs. 40.4%; p<0.001; adjusted HR 1.57; 95% CI 1.12–2.20) were significantly higher among patients with a positive cryptococcal antigen test.

Conclusions

Cryptococcal antigenemia is common and clinically relevant among patients with advanced HIV in this setting. Routine screening for cryptococcal antigen followed by lumbar puncture and pre-emptive antifungal treatment for those who are positive may help in reducing early mortality.     

Limited adequacy of thyroid cancer patient follow-up at a Canadian tertiary care centre

Background

We sought to evaluate the adequacy of follow-up of thyroid cancer patients at a Canadian centre.

Methods

We mailed a survey to the family physicians of thyroid cancer patients and analyzed the findings relative to follow-up guidelines published by the American Thyroid Association (ATA). Statistical significance between early and late follow-up patterns was analyzed using the χ² test.

Results

Our survey response rate was 56.2% (91 of 162). The time from operation ranged from 1.24–7.13 (mean 3.96) years, and 87.9% of patients had undergone a physical exam within the previous year. Only 37.4% and 14% of patients had a serum thyroglobulin measurement within 6 and between 6 and 12 months before the survey, respectively. Thyroid simulating hormone (TSH) levels were measured within the prior 6 months in 67% of patients and between 6 and 12 months in 13.2%. The TSH levels were suppressed (< 0.1 μIU/L) in 24.2% of patients, 0.1–2 μIU/L in 44% and greater than 2 μIU/L in 17.6%. Ultrasonography was the most common imaging test performed.

Conclusion

There is significant variation in the follow-up patterns of patients with thyroid cancer, and there is considerable deviation from current ATA guidelines.     

Microfracture of chondral lesions of the glenohumeral joint

Objective:

To determine if microfracture is successful in treating chondral lesions of the shoulder.

Design:

Case series.

Setting:

Tertiary referral practice.

Patients:

From June 2005 to November 2006, eight patients underwent shoulder arthroscopy with arthroscopic microfracture to treat full-thickness chondral lesions of less than 4 cm² size. The study group consisted of six men and two women. The mean age at surgery was 37 years (range: 27–55 years).One patient (12.5%) had an isolated chondral defect and seven patients (87.5%) had associated conditions treated simultaneously: two patients had arthroscopic subacromial decompressions, two had capsular plications for multidirectional instability, and three had anterior stabilization done (one with an associated superior labrum anterior to posterior repair and one with repair of a small rotator cuff tear). Five patients had humeral head defects and three had glenoid defects.

Intervention:

Microfracture.

Main outcome measures:

Constant score and Oxford score.

Results:

The mean follow-up period was 15.4 months, with a range of 12–27 months. The mean preoperative Constant score was 43.88 (range: 28–70) and at final follow-up the mean Constant score was 90.25 (range: 85–100); this difference was significant (P<0.005). The mean preoperative Oxford score was 25.75 (range: 12–37) and the mean postoperative Oxford score at final follow-up was 17 (range: 11–27); the difference was significant (P<0.005).There were no complications. Two patients underwent reoperation which allowed assessment of the lesion; in both cases the lesions showed good filling with fibrocartilage.

Conclusion:

Microfracture has been shown to be a reliable method of treatment for chondral lesions within the knee. We believe that this technique may also be applied to the shoulder; however, further study is required to assess its efficacy in this joint.

Level of evidence:

IV     

Pravastatin suppresses matrix metalloproteinase expression and activity in human articular chondrocytes stimulated by interleukin-1β

Background

Matrix metalloproteinases are catabolic enzymes that play a key role in the articular cartilage degeneration evident in degenerative and inflammatory conditions of articular cartilage. The aim of this study is to assess the ability of pravastatin to modify matrix metalloproteinase (MMP) messenger RNA (mRNA) expression and enzyme activity in a culture of normal human chondrocytes stimulated by interleukin-1β.

Materials and methods

Normal human chondrocytes were stimulated with interleukin (IL)-1β for 6 h to induce MMP expression, simulating a catabolic state, and then treated with pravastatin (1, 5 and 10 μM) for a further 18 h before cell lysates and supernatants were harvested. Cells stimulated with IL-1β but not treated with pravastatin served as controls. Real-time polymerase chain reaction (PCR) was used to assess expression of MMP-3 and MMP-9 mRNA. MMP enzyme activity was assessed using a fluorescent MMP-specific substrate. Statistical analysis was performed using analysis of variance (ANOVA).

Results

MMP-3 and MMP-9 mRNA expression was reduced at all concentrations tested with statistically significant trends in reduction (p = 0.002 and <0.001, respectively). Analysis of culture supernatants revealed that pravastatin treatment led to a reduction in total MMP activity but not to a statistically significant degree (p = 0.07).

Conclusions

Treatment with pravastatin of stimulated human chondrocytes leads to significant down-regulation of selected MMP genes and a non-significant reduction in MMP enzyme activity. Our results provide further evidence that statins may have a role to play in future treatment of disease affecting articular chondrocytes.     

Single nucleotide polymorphism of bone morphogenetic protein 4 gene: A risk factor of non-syndromic cleft lip with or without palate

Background:

The bone morphogenetic protein (BMP) signalling pathway is crucial in a number of developmental processes and is critical in the formation of variety of craniofacial elements including cranial neural crest, facial primordium, tooth, lip and palate. It is an important mediator in regulation of lip and palate fusion, cartilage and bone formation.

Aim:

To study the role of mutation of BMP4 genes in the aetiology of non-syndromic cleft lip with or without palate (NSCL ± P) and identify it directly from human analyses.

Materials and Methods:

A case-control study was done to evaluate whether BMP4T538C polymorphism, resulting in an amino acid change of Val=Ala (V152A) in the polypeptide, is associated with NSCL ± P in an Indian paediatric population. Genotypes of 100 patients with NSCL ± P and 100 controls (in whom absence of CL ± P was confirmed in three generations) were detected using a polymerase chain reaction-restriction fragment length polymorphism strategy. Logistic regression was performed to evaluate allele and genotype association with NSCLP.

Results:

Results showed significant association between homozygous CC genotype with CL ± P (odds ratio [OR]-5.59 and 95% confidence interval [CI] = 2.85-10.99). The 538C allele carriers showed an increased risk of NSCL ± P as compared with 538 T allele (OR - 4.2% CI = 2.75-6.41).

Conclusion:

This study suggests an association between SNP of BMP4 gene among carriers of the C allele and increased risk for NSCLP in an Indian Population. Further studies on this aspect can scale large heights in preventive strategies for NSCLP that may soon become a reality.KEY WORDS: Aetiology of non-syndromic cleft lip and palate, bone morphogenetic protein 4 gene, bone morphogenetic protein gene     

Effect of intrathecal baclofen concentration on spasticity control: case series

Background/Objective:

Intrathecal baclofen (ITB) has been shown to be an effective treatment for severe spasticity of spinal or cerebral origin. Although most patients respond well to an ITB trial, there are often difficulties in achieving and/or maintaining such effectiveness with ITB pump treatment. There are few published guidelines for dosing efficacy and no studies looking at the effect of concentration of ITB on spasticity management.

Methods:

Case series of 3 adults with severe spasticity treated with ITB pump: a 44-year-old man with C7 tetraplegia using a 40-mL Medtronic SynchroMed II pump with 500-μg/mL concentration; a 35-year-old woman with traumatic brain injury with right spastic hemiplegia using a 18-mL Medtronic SynchroMed EL pump with 2,000-μg/mL concentration; and a 43-year-old woman with spastic diplegic cerebral palsy using a 40-mL Medtronic SynchroMed II pump with 2,000-μg/mL concentration.

Results:

After reducing ITB concentrations in the pump, either as part of a standard protocol for dye study to assess the integrity of pump and catheter system or secondary to plateau in therapeutic efficacy, patients experienced temporary, significant reduction in spasticity based on range of motion, Modified Ashworth scores, and verbal feedback.

Conclusions:

Decreasing the concentration of ITB seems to affect spasticity control. Further research in this area is needed for those patients with refractory spasticity to optimize efficacy of ITB therapy.