Can pre-operative contrast-enhanced dynamic MR imaging for prostate cancer predict microvessel density in prostatectomy specimens?

The aim of this study was to correlate quantitative dynamic contrast-enhanced MRI (DCE MRI) parameters with microvessel density (MVD) in prostate carcinoma. Twenty-eight patients with biopsy-proven prostate carcinoma were examined by endorectal MRI including multiplanar T2- and T1-weighted spin-echo and dynamic T1-weighted turbo-FLASH MRI during and after intravenous Gd-DTPA administration. Microvessels were stained on surgical specimens using a CD31 monoclonal antibody. The MVD was quantified in hot spots by counting (MVC) and determining the area fraction by morphometry (MVAF). The DCE MRI data were analyzed using an open pharmacokinetic two-compartment model. In corresponding anatomic locations the time shift (t) between the beginning of signal enhancement of cancer and adjacent normal prostatic tissue, the degree of contrast enhancement and the contrast exchange rate constant (k₂₁) were calculated. The MVC and MVAF were elevated in carcinoma (p<0.001 and p=0.002, respectively) and correlated to k₂₁ (r=0.62, p<0.001 and r=0.80, p<0.001, respectively). k₂₁-values of carcinoma were significantly higher compared with normal peripheral but not central zone tissue. t was longer in high compared with low-grade tumors (p=0.025). The DCE MRI can provide important information about individual MVD in prostate cancer, which may be helpful for guiding biopsy and assessing individual prognosis.     

Differences in the rehabilitation period following two methods of anterior cruciate ligament replacement: semitendinosus/gracilis tendon vs. ligamentum patellae

This study compared patient outcome during the early rehabilitation phase following two different methods of anterior cruciate ligament (ACL) reconstruction: ligamentum patellae (LP) and semitendinosus/gracilis tendon (SG) based reconstruction. The study included 50 consecutive patients treated by each method, examined 6 weeks and 3, 6 and 12 months after surgery. Patients in the SG group showed significantly better Lysholm scores at 6 and 12 months, Tegner Activity Scale scores at 3 months, and pain profile assessments at 6 weeks and 3 months than those in the LP group. Significant advantages were observed in LP group in the Overall Knee Score at 6 weeks and in range-of-motion at 6 weeks and 3 and 6 months post-surgery. Stability tests revealed no significant differences between patients in the two groups. SG-based reconstruction of the ACL thus demonstrates advantages over LP-based reconstruction regarding pain and function, while LP-based reconstruction was associated with an earlier return of motion.     

Calculated DNA damage from gadolinium Auger electrons and relation to dose distributions in a head phantom

PURPOSE: To calculate the number of 157Gadolinium (157Gd) neutron capture induced DNA double strand breaks (DSB) in tumor cells resulting from epithermal neutron irradiation of a human head when the peak tissue dose is 10 Gy. To assess the lethality of these Gd induced DSB. MATRIALS AND METHODS: DNA single and double strand breaks from Auger electrons emitted during 157Gd(n,gamma) events were calculated using an atomistic model of B-DNA with higher-order structure. When combined with gadolinium neutron capture reaction rates and neutron and photon physical dose rates calculated from the radiation transport through a model of the human head with explicit tumors, peak tissue dose can be related to the number of Auger electron induced DSB in tumor cell DNA. The lethality of these DNA DSB were assessed through a comparison with incorporated 125I decay cell survival curves and second comparison with the number of DSB resulting from neutron and photon interactions. RESULTS: These calculations on a molecular scale (microscopic calculations) indicate that for incorporated 157Gd, each neutron capture reaction results in an average of 1.56 +/- 0.16 DNA single strand breaks (SSB) and 0.21 +/- 0.04 DBS in the immediate vicinity (approximately 40 nm) of the neutron capture. In an example case of Gd Neutron Capture Therapy (GdNCT), a 1 cm radius midline tumor, peak normal tissue dose of 10 Gy, and a tumor concentration of 1000 ppm Gd, result in a maximum of 140 +/- 27 DSBs per tumor cell. CONCLUSIONS: The number of DSB from the background radiation components is one order of magnitude lower than the Gd Auger electron induced DSB. The cell survival of mammalian cell lines with a similar amount of complex DSB induced from incorporated 125I decay yield one to two magnitudes of cell killing. These two points indicate that gadolinium auger electrons could significantly contribute to cell killing in GdNCT.     

The potential of gene therapy for the treatment of disc degeneration

Research in biologic methods of treating disc degeneration is still in its infancy. Many different strategies are being evaluated, but the gene therapy strategy stands out because of its potential for long-term efficacy. Choosing the correct gene for use in gene therapy is critically important. Of the many different classes of potentially therapeutic genes, the regulatory genes hold the most promise. Of the different gene therapy delivery methods, the most work has been performed with viral vectors, either ex vivo or in vivo. Current research now is turning toward in vivo experiments in rabbits. Efficacy and safety will be demonstrated first with smaller animal models. Beyond that, nonhuman primate experiments demonstrating efficacy and safety will be the penultimate step before initiation of human studies.     

Ventral cardiac denervation reduces the incidence of atrial fibrillation after coronary artery bypass grafting

OBJECTIVES: Because the autonomic nervous system is an important determinant in the appearance of atrial fibrillation, we have assessed the role of ventral cardiac denervation for its prevention. METHODS: Patients undergoing low-risk coronary artery surgery were enrolled. No routine antiarrhythmic drugs were administered before or after the operation. Ventral cardiac denervation was performed in 207 patients, and 219 patients were used as control subjects. Denervation was performed before cardiopulmonary bypass. The groups were comparable regarding demographic, clinical, and operative variables. RESULTS: The additional time for the denervation was 5 +/- 2 minutes, and there were no associated complications. Postoperative atrial fibrillation was present in 15 (7%) patients undergoing ventral cardiac denervation (95% confidence interval, 4%-12%) and in 56 (27%) control subjects (95% confidence interval, 18%-35%). Patients submitted to ventral cardiac denervation had fewer and less severe episodes of atrial fibrillation, and no patient had atrial fibrillation after discharge. Ventral cardiac denervation was the most significant predictor of postoperative atrial fibrillation (odds ratio, 0.42; confidence interval, 0.23-0.78; P =.006). Age of greater than 65 years (odds ratio, 1.67; confidence interval, 0.96-2.9; P =.067) was a highly suggestive predictor. The analysis of the effect of ventral cardiac denervation correlated with the patient's age showed a more pronounced effect in patients younger than 70 years (odds ratio, 0.43; confidence interval, 0.22-0.86; P =.022) CONCLUSIONS: Ventral cardiac denervation is a fast and low-risk procedure. Its use significantly reduces the incidence and severity of atrial fibrillation after routine coronary artery bypass surgery. Patients younger than 70 years of age are expected to have a higher success rate than those older than 70 years.     

Monitoring systemic donor lymphocyte macrochimerism to aid the diagnosis of graft-versus-host disease after liver transplantation

BACKGROUND: The diagnosis of graft-versus-host disease (GvHD) after liver transplantation can be difficult because early symptoms are often nonspecific. In this study, the presence of donor lymphocyte macrochimerism in recipient peripheral blood was examined as a diagnostic aid for GvHD after cadaveric donor liver transplantation. METHODS: Between 1996 and 2002, 33 liver transplant recipients with a clinical suspicion of GvHD (skin rash, diarrhea, pyrexia, pancytopenia, or anemia, without an obvious alternative cause) were investigated for peripheral blood donor lymphocyte macrochimerism. Donor macrochimerism was determined at the time of first clinical presentation by a low-sensitivity polymerase chain reaction (PCR) to detect donor human leukocyte antigen (HLA) alleles using genomic DNA extracted from recipient peripheral blood. Where donor HLA alleles were detected, the percentage of donor T cells was quantified by two-color flow cytometric analysis using antibodies specific for mismatched donor and recipient HLA alleles. The relationship between the presence or absence of donor lymphocyte macrochimerism and final diagnoses based on clinical and histological criteria was examined. RESULTS: Seven of the 33 patients were PCR positive for donor HLA alleles. All had macrochimerism, with donor T lymphocyte levels ranging from 4% to 50% of circulating lymphocytes. All seven patients had normal liver function tests, skin rash, and diagnosis of GvHD histologically confirmed by skin or gut biopsies. Twenty-six patients were PCR negative, and, in 23, an alternative diagnosis was eventually established. The remaining three patients made a rapid and spontaneous recovery with no further symptoms suggestive of GvHD. CONCLUSIONS: Donor lymphocyte macrochimerism was present in all patients in whom the diagnosis of GvHD was confirmed. In patients with symptoms consistent with GvHD and a negative PCR for donor HLA, an alternative diagnosis was eventually established or the patients recovered spontaneously. Detection of donor HLA alleles in recipient peripheral blood by PCR is a useful diagnostic tool for GvHD after liver transplantation.     

Infection studies on human cell lines with porcine circovirus type 1 and porcine circovirus type 2

Abstract: Background: The lack of human donor organs in allotransplantation has led to a proposal for the use of porcine tissues and organs as alternative therapeutic material for humans. Besides immunological problems like graft rejection, one of the major concerns is the transmission of porcine microorganisms as viruses, bacteria and fungi to a human recipient. Methods: Human cell lines have been infected with porcine circovirus type 1 (PCV1) and porcine circovirus type 2 (PCV2) to investigate whether PCV can infect and replicate in human epithelial cells and lymphocytes. Infection of PCV1 was observed with 293, Hela and Chang liver cells, infection with PCV2 only in Rd cells. In addition, religated viral DNA of PCV1 and PCV2 has been used to transfect adherent human cell lines. Results: PCV1 persisted in most cell lines without causing any visible changes, while PCV2‐transfected cells showed a cytopathogenic effect. Presence of PCV DNA was detected in cells and supernatant by PCR, expression of viral proteins by an indirect immune fluorescence assay. A replication assay showed that the replication of PCV DNA was initiated at the origin of replication. When virus‐free cells were inoculated with the supernatant of PCV‐infected human cells, the infection was not passed. Conclusion: Although PCV gene expression and replication took place in human cells, the infection is non‐productive. Alteration of protein localization suggests that protein targeting may be disturbed in human cells.     

The Influence of Vibration on Muscle Activation and Rate of Force Development during Maximal Isometric Contractions

At present there appears to be a need for research conducted on the effects of vibration on the contractile ability of skeletal muscle tissue. The aim of this study was to address this issue by examining the effects of a superimposed muscle/tendon vibration at 50.42±1.16 Hz (acceleration 13.24 ± 0.18ms^-2: displacement ≈5mm) on muscular activation and maximal isometric contraction. Sixteen participants with a mean age, body mass, and height of 22 ± 4.4 years, 73.2 ± 11.7 kg and 173.1 ± 9.7 cms, respectively, were recruited for this study. Electromyography and accelerometry from the rectus femoris, and maximal isometric force data characteristics were collected from the dominant limb under conditions of vibration, and no-vibration. A superimposed 50 Hz vibration was used during the contraction phase for the maximal isometric leg extension for the condition of vibration. A one-way ANOVA revealed no significant (p > 0.05) differences between the vibration and no-vibration conditions for peak normalized EMG_RMS (84.74% Vs 88.1%) values. An ANOVA revealed significant (p > 0.05) differences between the peak fundamental frequencies of the FFT between the conditions vibration (27.1 ± 12.2 Hz) and no-vibration (9.8 ± 3.5 Hz). Peak isometric force, peak rate of force development, rate of force development at times 0.05, 0.01, 0.1, 0.5 seconds, and rate of force development at 50, 75, and 90% of peak force were not significantly different. The results of this study suggest that the application of vibration stimulation at 50 Hz during the contraction does not contribute to muscle activation, or enhance force production for maximal isometric contractions.

Key Points

• The application of a vibratory stimulation to the human body increases the normal acceleration resulting in an increase in force and a change in performance
• This study was to address this issue by examining the effects of a direct superimposed muscle/tendon vibration at 50 Hz on isometric strength characteristics
• No improvement or change in isometric force or rate of force development
• No changes to peak normalized EMG_RMS values

Key words: Strength, oscillations, isometric, peak, muscle activation