Temporo-spatial distribution of blood vessels in human lumbar intervertebral discs

While there is consensus in the literature that blood vessels are confined to the outer anulus fibrosus of normal adult intervertebral disc, debate continues whether there is a vascular in-growths into inner parts of the intervertebral disc during degeneration. We therefore tested the hypothesis that vascular in-growth is not a distinct feature of disc degeneration. The specific endothelial cell marker CD 31 (PECAM) was used to immunohistochemically investigate 42 paraffin-embedded complete mid-sagittal human intervertebral disc sections of various ages (0–86 years) and varying extent of histomorphological degeneration. Additionally, 20 surgical disc samples from individuals (26–69 years) were included in this study. In discs of fetal to infantile age, blood vessels perforated the cartilaginous end plate and extended into the inner and outer anulus fibrosus, but not into the nucleus pulposus. In adolescents and adults, no blood vessels were seen except for the outer zone of the anulus fibrosus adjacent to the insertion to ligaments. The cartilaginous end plate remained free of vessels, except for areas with circumscribed destruction of the end plate. In advanced disc degeneration, no vessels were observed except for those few cases with complete, scar-like disc destruction. However, some rim lesions and occasionally major clefts were surrounded by a small network of capillary blood vessels extending into deeper zones of the anulus fibrosus. A subsequent morphometric analysis, revealed slightly “deeper” blood vessel extension in juvenile/adolescent discs when compared to young, mature and senile adult individuals with significantly “deeper” extension in the posterior than anterior anulus. The analysis of the surgical specimens showed that only sparse capillary blood vessels which did not extend into the nucleus pulposus even in major disc disruption. Our results show that vascular invasion deeper than the periphery was not observed during disc degeneration, which supports the hypothesis that vascular in-growth is not a distinct feature of disc degeneration. This study was supported by a grant from the AO/ASIF Foundation Switzerland (00-B72) and a grant from the AO Spine (SRN 02/103).     

CD4+CD25+FoxP3+ T lymphocytes fail to suppress myelin basic protein-induced proliferation in patients with multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disorder directed against self antigens of the central nervous system. CD4⁺CD25⁺FoxP3⁺ regulatory T cell (T_reg) mediated suppression is an essential mechanism of self-tolerance. We studied whether changes in the suppressive function of a mixture of CD25^high and CD25^intemediate expressing T_reg cells in myelin basic protein (MBP)-induced proliferation occurred in untreated MS patients. Suppression of MBP-induced proliferation was observed in 13 out of 29 (45%) MS patients; this was significantly (p < 0.05) less compared with 17 out of 19 (89%) healthy individuals. Relative T_reg counts was significantly increased in MS patients (mean ± S.D.; 20 ± 8%) compared with healthy individuals (15 ± 5%). These findings suggest that impaired T_reg function may be involved in pathogenesis of MS.     

F-18 Fluorodeoxyglucose (FDG) and C-Reactive Protein (CRP)

This study was done to evaluate if the accuracy of FDG-PET concerning the differentiation of benign and malignant pancreatic masses differs for patients with and without elevated C-Reactive Protein (CRP). Three hundred-four patients (165 neoplasms, 98 chronic pancreatitis, and 41 benign lesions) received FDG-PET of the abdomen prior to planned resective surgery. CRP was unknown, normal, and elevated with 211, 71, and 22 patients, respectively. For differentiation of benign and malignant lesions, specificity was 87% for patients with unknown or normal CRP, and it was 40% for patients with elevated CRP (P < 0.01). Thirty-five percent of those patients with both a positive PET and elevated CRP were false positive. On the contrary, sensitivity was slightly higher in the group with elevated CRP (92% vs. 80%, NS). FDG-PET is a sensitive and specific test for patients with normal CRP, however, FDG-PET may be false positive if CRP is elevated. Proper patient selection is therefore important. CRP or other parameters indicative of active inflammation appear useful adjuncts for the interpretation of increased FDG-accumulation.     

Autologous in vivo adipose tissue engineering in hyaluronan-based gels--a pilot study

BACKGROUND: There is a major clinical need for strategies for adequately reconstructing the soft tissue defects found after deep burns, tumor resection, or trauma. A promising solution is adipose tissue engineering with preadipocytes, stem-cell derived precursors of the adipose tissue, implanted within biomaterials. This pilot study evaluated hyaluronan gels mixed with autologous undifferentiated preadipocytes in a pig model for their potency to generate new fat. MATERIALS AND METHODS: Preadipocytes were isolated from intra-abdominal pig fat by collagenase digestion, plated on fibronectin-coated culture dishes in Dulbecco's modified Eagle medium/Ham's F12 (Biochrom, Berlin, Germany) combined with 10% pig serum, expanded, and mixed with hyaluronan gel. Two types of gels with varying degrees of amidation of the carboxyl groups were tested (HYADD3, HYADD4). Cell-loaded gels and unseeded controls were injected subcutaneously into the ears of three pigs, explanted at 6 wk, and analyzed histologically. RESULTS: Both cell-loaded specimens were detected macroscopically. They demonstrated a slight volume effect with limited stability after 6 wk. Unloaded HYADD3 and HYADD4 controls could not be identified at the time of explantation. Histology of HYADD3 revealed islets of mature adipocytes and vessels embedded in fat tissue surrounded by gel. In contrast, no fat formation was found in HYADD4 gels when implanted in the ear. CONCLUSIONS: Histological findings demonstrate that HYADD3 is a promising gel for generating adipose tissue. Even though HYADD3 might be a potential material for the reconstruction of small tissue defects, the question remains as to whether the adipose tissue within the gel is attributable to preadipocyte maturation or ingrowth from neighboring tissue.     

Noninvasive grading of untreated gliomas: a comparative study of MR imaging and 3-(iodine 123)-L-alpha-methyltyrosine SPECT

PURPOSE: To compare the accuracy of magnetic resonance (MR) imaging scores with that of 3-(iodine 123)-L-alpha-methyltyrosine ((123)I-IMT) single photon emission computed tomography (SPECT) in the noninvasive grading of untreated gliomas. MATERIALS AND METHODS: The study comprised 15 patients with low-grade gliomas (grades I-II, according to World Health Organization criteria) and 33 patients with high-grade gliomas (grades III-IV). The lesions were evaluated by using an MR imaging score based on nine criteria. The (123)I-IMT uptake was quantified as the ratio between the amino acid uptake in the tumor and that in the contralateral hemisphere. To test for potentially significant differences in diagnostic performance between contrast material-enhanced MR imaging and (123)I-IMT SPECT, binormal receiver operating characteristic curves were fitted to the data and compared by using the area test. RESULTS: The accuracy of MR imaging in the noninvasive grading of untreated gliomas was higher than that of (123)I-IMT SPECT (88% vs 79%). However, the difference in diagnostic performance was not significant on the basis of findings at receiver operating characteristic analysis (P >.2). Neither MR imaging nor (123)I-IMT SPECT allowed differentiation between high-grade gliomas (grades III and IV). CONCLUSION: Although (123)I-IMT uptake is significantly higher in high-grade gliomas than in low-grade gliomas, the performance of (123)I-IMT SPECT adds little to the accuracy of determining tumor grade when MR imaging is performed.     

Measurement of skeletal muscle motion in vivo with phase-contrast MR imaging

The ability to measure skeletal muscle motion with phase-contrast magnetic resonance (MR) imaging was tested with a motion phantom that simulated muscle activity. Quantitative analytic data on unidimensional, bidirectional skeletal muscle motion measured in vivo was obtained in four healthy volunteers. MR images of the subjectss' forearms were obtained during flexion and extension of the fingers and of the anterior and posterior muscle compartments of the lower leg with various resistances to ankle dorsiflexion and plantar flexion. It was necessary to correct the data for the effects of eddy currents. In vitro evaluation of the technique was done by studying through-plane sinusoidal motion of solid objects. The largest error was underestimation of the peak excursion of 11.5 mm by 0.09 mm (the root mean square error for the cycle was 0.04 mm) In vivo experiments demonstrated the contraction of muscles in relation to each other. Data acquisition and analysis techniques must be refined, but measuring skeletal muscle motion with phase-contrast MR imaging should enhance the understanding of bioengineering fundamentals and muscular changes in disease and adaptation.     

Radical Resection of Giant Congenital Melanocytic Nevus and Reconstruction With Meek-Graft Covered Integra Dermal Template

BACKGROUND: Giant congenital melanocytic nevi represent a surgical challenge, particularly in cases in which the size of the nevus exceeds certain extend and malignant transformations have to be considered. OBJECTIVE: To discuss through case report considerable surgical options when extensive giant congenital melanocytic nevi with malignant transformation are encountered. METHODS: We present an unusual case of a giant congenital melanocytic nevi of the entire back of a 44-year-old patient. To achieve radical resection with direct appropriate wound closure and acceptable outcome, the integument of the entire back was excised and covered with Integra, followed by split-thickness skin grafting after stable integration of the matrix. RESULTS: The approach resulted in a complete excision of the tumor and acceptable cosmetic and excellent biomechanical outcome. CONCLUSION: The introduced practice demonstrates a useful alternative to established methods, particularly if tumor excision in large areas and subsequent wound closure might be achieved in one procedure.     

The ryanodine contracture test may help diagnose susceptiblity to malignant hyperthermia

PURPOSE: The ryanodine contracture test (RCT) using the plant alkaloid ryanodine as the triggering agent has been proposed to reduce equivocal results of the in vitro caffeine-halothane-contracture test (IVCT), which is the accepted and standardized procedure to diagnose malignant hyperthermia (MH). However, the response of skeletal muscle of non-MH affected patients (controls) to ryanodine has not yet been characterized. METHODS: Skeletal muscle biopsies were studied in 33 controls and in six patients with a history of fulminant MH. Following the IVCT, the RCT was performed in all specimens using ryanodine 1 micro M. Onset time of contracture and time to reach a contracture level of 10 mN above lowest resting tension and above predrug tension were calculated. RESULTS: With the standard IVCT, all controls were labelled MH non-susceptible; all clinically diagnosed MH patients were labelled MH susceptible. With ryanodine, control muscle differed from MH susceptible muscle regarding onset time of contracture (26 vs 3.8 min, P < 0.05) and time to reach a contracture of 10 mN (49 vs 12.5 min, P < 0.05; all median). Tissue viability and patient's age significantly influenced contracture times. CONCLUSIONS: Despite the highly specific binding of ryanodine at the myocytic sarcoplasmic reticulum, the wide range of contracture times of the controls points toward heterogeneity of ryanodine receptors within physiologic limits. This may also be caused in part by tissue viability and the patients' age. The ryanodine contracture test performed in addition to the IVCT may add clarity into diagnosing a patient as MH-susceptible or not.     

Outcome in a post-cardiac surgery population with acute renal failure requiring dialysis: does age make a difference?

BACKGROUND: Acute renal failure (ARF), requiring dialysis (ARF-d), develops in 1-5% of patients undergoing cardiac surgery and is associated with higher in-hospital mortality. Age is one of the known risk factors for the development of ARF. As the ageing population is increasing, the nephrologist will be faced with a large population of elderly patients requiring dialysis following cardiac surgery. The aim of our study was to evaluate the influence of age on and the risk factors for in-hospital mortality. METHODS: Eighty-two patients with ARF following cardiac surgery and requiring dialysis between January 1997 and October 2001 were included. Two groups of patients were studied: the younger population (<70 years, 42 patients, mean age 59+/-10) and an elderly population (>/=70 years, 40 patients, mean age 76+/-4). Severity of disease was evaluated using the SAPS (Simplified Acute Physiology Score), the Liano score and the SHARF (Stuivenberg Hospital Acute Renal Failure) score. RESULTS: Overall mortality in the population with ARF-d was 56.1%. No difference in mortality rate was found between the younger (61.9%) and elderly patient group (50.0%). The two groups were very similar in baseline and procedural characteristics with exception of body weight (P=0.02) and preoperative glomerular filtration rate (P=0.0001). No significant difference was found in the scoring systems between the old and the young (SAPS P=0.52; Liano P=0.96; SHARF T0 P=0.06; SHARF T48 P=0.15). Mortality in the elderly was significantly correlated with hypotension before starting renal replacement therapy (RRT) (P=0.002), mechanical ventilation (P=0.002), presence of multiorgan failure (MOF) (P=0.0001) and higher scores in the severity models (SAPS: P=0.01; Liano: P<0.0001 and SHARF: P<0.0001). CONCLUSION: The outcome in the elderly requiring dialysis due to ARF post-cardiac surgery is comparable with the outcome in a younger population. No significant difference was found in severity of disease between the elderly and the younger. Variables predicting mortality in the elderly are the presence of MOF, mechanical ventilation and hypotension 24 h before starting RRT. These findings indicate that at the time the nephrologist is called for an elderly patient requiring dialysis due to ARF following cardiac surgery, age per se is not a reason to withhold RRT.     

Echocardiographic monitoring during induction of general anesthesia with a miniaturized esophageal probe

Standard transesophageal echocardiography (TEE) does not allow cardiac monitoring during the induction of anesthesia because standard probes would limit the oropharyngeal space and impair mask ventilation and tracheal intubation. We hypothesized that a prototype, miniaturized TEE probe could be safely introduced transnasally in awake patients and that mask ventilation and orotracheal intubation could be performed while continuously monitoring left ventricular (LV) function during the induction of anesthesia. Forty-five patients were studied prospectively. The transnasal TEE probe was introduced through one of the nares and advanced until a transverse plane image of the LV at the level of the papillary muscles was seen. Anesthesia was induced, and the patients were ventilated with a mask that had previously been threaded over the TEE probe via a central perforation. Probe insertion was successful in 12 patients under local anesthesia alone and in an additional 31 patients with a combination of local anesthesia and mild sedation. In two cases, probe placement was unsuccessful. Overall, hemodynamic variables did not change significantly during insertion. No case of significant mucosal bleeding was seen. In one patient, regurgitation of gastric contents occurred without affecting the perioperative outcome. The two-dimensional echocardiogram image quality of the LV during the induction of anesthesia was good or acceptable in 95% of patients. We conclude that transnasal TEE can effectively be used for cardiac monitoring during the induction of general anesthesia. IMPLICATIONS: This study demonstrates that it is feasible and generally safe to introduce a miniaturized transesophageal echocardiography probe transnasally in awake cardiac risk patients to monitor cardiac performance during the induction of general anesthesia.