Does neck pain as chief complaint influence the outcome of cervical total disc replacement?

PURPOSE: We investigated whether outcomes after cervical total disc replacement (cTDR) are influenced by preoperative neck pain as the chief complaint. METHODS: This was a retrospective study using data in our local spine surgery outcomes database, linked to EUROSPINE Spine Tango Registry. Patients completed questionnaires at baseline enquiring about the "chief complaint" [neck pain (NP), arm/shoulder pain (AP) or neurological deficits (ND)] and including the Core Outcome Measures Index (COMI); these were completed again at 24 months postoperatively, along with a rating of "global treatment outcome" (on a five-point scale, later dichotomized as "good" or "poor"). Differences in outcomes between the groups were examined using ANOVA. Multivariable regression analysis examined the effect of the chief pain location on 24-month outcomes, controlling for age, gender, comorbidity, baseline pain and COMI scores. RESULTS: One hundred and fifty-nine consecutive patients were included, with a chief complaint of NP in 31%, AP in 38% and ND in 31%. The chief complaint groups did not differ in relation to their baseline COMI scores or their reductions in score from before surgery to 24 months after surgery (reduction: NP group, 4.4 ± 2.9 points; AP group, 4.7 ± 2.7; ND group, 4.3 ± 2.9; p = 0.78). Similarly, the percentage of patients reporting a "good global treatment outcome" at 24 months postoperatively did not differ between the groups (NP, 79%; AP, 77%; ND, 85%; p = 0.64). The findings were consistent when controlling for possible confounders in multiple regression. CONCLUSIONS: Having neck pain as opposed to arm pain or neurological deficits as preoperative chief complaint had no significant impact on clinical outcome after cTDR. These slides can be retrieved under Electronic Supplementary Material.

How does patient-rated outcome change over time following the surgical treatment of degenerative disorders of the thoracolumbar spine?

PURPOSE: Patient-rated measures are considered the gold standard for assessing the outcome of spine surgery, but there is no consensus on the appropriate timing of follow-up. Journals often demand a minimum 2-year follow-up, but the indiscriminate application of this principle may not be warranted. We examined the course of change in patient outcomes up to 5 years after surgery for degenerative spinal disorders. METHODS: The data were evaluated from 4287 consecutive patients (2287 women, 2000 men; aged 62 ± 15 years) with degenerative disorders of the thoracolumbar spine, undergoing first-time surgery at the given level between 01/01/2005 and 31/12/2011. The Core Outcome Measures Index (COMI; scored 0-10) was completed by 4012 (94%) patients preoperatively, 4008 (93%) at 3-month follow-up, 3897 (91%) at 1-year follow-up, 3736 (87%) at 2-year follow-up, and 3387 (79%) at 5-year follow-up. 2959 (69%) completed the COMI at all five time-points. RESULTS: The individual COMI change scores from preoperatively to the various follow-up time-points showed significant correlations ranging from r = 0.50 (for change scores at the earliest vs the latest follow-up) to r = 0.75 (for change scores after 12- vs 24-month follow-up). Concordance with respect to whether the minimum clinically important change score was achieved at consecutive time-points was also good (70-82%). COMI decreased significantly (p < 0.05) from preop to 3 months (by 3.6 ± 2.8 points) and from 3 to 12 months (by 0.3 ± 2.4 points), then levelled off up to 5 years (0.04-0.05 point change; p > 0.05). The course of change up to 12 months differed slightly (p < 0.05) depending on pathology/whether fusion was carried out. For patients undergoing simple decompression, 3-month follow-up was sufficient; those undergoing fusion continued to show further slight but significant change up to 12 months. CONCLUSIONS: Stable group mean COMI scores were observed for all patients from 12 months postoperatively onwards. The early postoperative results appeared to herald the longer term outcome. As such, a 'wait and see policy' in patients with a poor initial outcome at 3 months is not advocated. The insistence on a 2-year follow-up could result in a failure to intervene early to achieve better long-term outcomes.

A novel use of the Spine Tango registry to evaluate selection bias in patient recruitment into clinical studies: an analysis of patients participating in the Lumbar Spinal Stenosis Outcome Study (LSOS).

PURPOSE: Patients enrolled in clinical studies typically represent a sub-set of all who are eligible, and selection bias may compromise the generalizability of the findings. Using Registry data, we evaluated whether surgical patients recruited by one of the referring centres into the Lumbar Spinal Stenosis Outcome Study (LSOS; a large-scale, multicentre prospective observational study to determine the probability of clinical benefit after surgery) differed in any significant way from those who were eligible but not enrolled. METHODS: Data were extracted for all patients with lumbar spinal stenosis registered in our in-house database (interfaced to Eurospine's Spine Tango Registry) from 2011 to 2013. Patient records and imaging were evaluated in relation to the admission criteria for LSOS to identify those who would have been eligible for participation but were not enrolled (non-LSOS). The Tango surgery data and Core Outcome Measures Index (COMI) data at baseline and 3 and 12 months after surgery were analysed to evaluate the factors associated with LSOS enrolment or not. RESULTS: 514 potentially eligible patients were identified, of which 94 (18%) were enrolled into LSOS (range 2-48% for the 6 spine surgeons involved in recruiting patients) and 420 (82%) were not; the vast majority of the latter were due to non-referral to the study by the surgeon, with only 5% actually refusing participation. There was no significant difference in gender, age, BMI, smoking status, or ASA score between the two groups (p ≥ 0.18). Baseline COMI was significantly (p = 0.002) worse in the non-LSOS group (7.4 ± 1.9) than the LSOS group (6.7 ± 1.9). There were no significant group differences in any Tango surgery parameters (additional spine patholothegies, operation time, blood loss, complications, etc.) although significantly more patients in the non-LSOS group had a fusion procedure (38 vs 18% in LSOS; p = 0.0004). Postoperatively, neither the COMI nor its subdomain scores differed significantly between the groups (p > 0.05). Multiple logistic regression revealed that worse baseline COMI (p = 0.021), surgeon (p = 0.003), and having fusion (p = 0.014) predicted non-enrolment in LSOS. CONCLUSION: A high proportion of eligible patients were not enrolled in the study. Non-enrolment was explained in part by the specific surgeon, worse baseline COMI status, and having a fusion. The findings may reflect a tendency of the referring surgeon not to overburden more disabled patients and those undergoing more extensive surgery with the commitments of a study. Beyond these factors, non-enrolment appeared to be somewhat arbitrary, and was likely related to surgeon forgetfulness, time constraints, and administrative errors. Researchers should be aware of potential selection bias in their clinical studies, measure it (where possible) and discuss its implications for the interpretation of the study's findings.

Development of appropriateness criteria for the surgical treatment of symptomatic lumbar degenerative spondylolisthesis (LDS).

PURPOSE: Spine surgery rates are increasing worldwide. Treatment failures are often attributed to poor patient selection and inappropriate treatment, but for many spinal disorders there is little consensus on the precise indications for surgery. With an aging population, more patients with lumbar degenerative spondylolisthesis (LDS) will present for surgery. The aim of this study was to develop criteria for the appropriateness of surgery in symptomatic LDS. METHODS: A systematic review was carried out to summarize the current level of evidence for the treatment of LDS. Clinical scenarios were generated comprising combinations of signs and symptoms in LDS and other relevant variables. Based on the systematic review and their own clinical experience, twelve multidisciplinary international experts rated each scenario on a 9-point scale (1 highly inappropriate, 9 highly appropriate) with respect to performing decompression only, fusion, and instrumented fusion. Surgery for each theoretical scenario was classified as appropriate, inappropriate, or uncertain based on the median ratings and disagreement in the ratings. RESULTS: 744 hypothetical scenarios were generated; overall, surgery (of some type) was rated appropriate in 27%, uncertain in 41% and inappropriate in 31%. Frank panel disagreement was low (7% scenarios). Face validity was shown by the logical relationship between each variable's subcategories and the appropriateness ratings, e.g., no/mild disability had a mean appropriateness rating of 2.3 ± 1.5, whereas the rating for moderate disability was 5.0 ± 1.6 and for severe disability, 6.6 ± 1.6. Similarly, the average rating for no/minimal neurological abnormality was 2.3 ± 1.5, increasing to 4.3 ± 2.4 for moderate and 5.9 ± 1.7 for severe abnormality. The three variables most likely (p < 0.0001) to be components of scenarios rated "appropriate" were: severe disability, no yellow flags, and severe neurological deficit. CONCLUSION: This is the first study to report criteria for determining candidacy for surgery in LDS developed by a multidisciplinary international panel using a validated method (RAM). The panel ratings followed logical clinical rationale, indicating good face validity. The work refines clinical classification and the phenotype of degenerative spondylolisthesis. The predictive validity of the criteria should be evaluated prospectively to examine whether patients treated "appropriately" have better clinical outcomes.

Surgery in lumbar degenerative spondylolisthesis: indications, outcomes and complications. A systematic review.

PURPOSE: This systematic review summarises the literature on patient selection, decision-making, effectiveness and outcomes in the surgical treatment of lumbar degenerative spondylolisthesis (LDS). INTRODUCTION: In daily practice, decision-making in the treatment of LDS is challenging. There is little consensus on either the precise indications or prognostic factors for any specific therapy (operative or non-operative). METHODS: We searched for LDS trials published between 01.01.1990 and 16.11.2011 in Medline, Embase, Cochrane Library and Cinahl. Two independent reviewers selected studies according to the inclusion criteria. Data were then extracted by two of the authors. Quality assessment was performed using the Downs and Black list for the clinical trials/studies and AMSTAR for the reviews. DATA SYNTHESIS: 21 papers met the inclusion criteria (2 studies comprising both a RCT and a concurrent observational analysis, 1 RCT, 6 prospective studies, 8 retrospective studies, 3 reviews, 1 review guideline). The quality of the clinical studies was on average "fair" [mean score 15.6 points (range 10-19) out of 24 points (Downs and Black)]. The quality of the reviews ranged from 1 to 7 out of 11 points with an average of 5 points (AMSTAR). The study outcomes could not be subject to meta-analysis due to heterogeneity of study design and variable measure used. CONCLUSIONS: Despite there being many articles describing and/or comparing different surgical options for LDS, there was insufficient evidence to draw conclusions concerning clear indications for specific types of surgical treatment, predictors of outcome or complication rates. There remains a need to establish a decision-making tool to facilitate daily clinical practice and to assure appropriate treatment for patients with LDS.

Safe cycling: how do risk perceptions compare with observed risk?

OBJECTIVE: Safety concerns deter cycling. The Bicyclists' Injuries and the Cycling Environment (BICE) study quantified the injury risk associated with 14 route types, from off-road paths to major streets. However, when it comes to injury risk, there may be discordance between empirical evidence and perceptions. If so, even if protective infrastructure is built people may not feel safe enough to cycle. This paper reports on the relationship between perceived and observed injury risk. METHODS: The BICE study is a case-crossover study that recruited 690 injured adult cyclists who visited emergency departments in Toronto and Vancouver. Observed risk was calculated by comparing route types at the injury sites with those at randomly selected control sites along the same route. The perceived risk was the mean response of study participants to the question "How safe do you think this site was for cyclists on that trip?", with responses scored from +1 (very safe) to -1 (very dangerous). Perceived risk scores were only calculated for non-injury control sites, to reduce bias by the injury event. RESULTS: The route type with the greatest perceived risk was major streets with shared lanes and no parked cars (mean score = -0.21, 95% confidence interval [CI]: -0.54-0.11), followed by major streets without bicycle infrastructure (-0.07, CI -0.14-0.00). The safest perceived routes were paved multi-use paths (0.66, CI 0.43-0.89), residential streets (0.44, CI 0.37-0.51), bike paths (0.42, CI 0.25-0.60) and residential streets marked as bike routes with traffic calming (0.41, CI 0.32-0.51). Most route types that were perceived as higher risk were found to be so in our injury study; similarly, most route types perceived as safer were also found to be so. Discrepancies were observed for cycle tracks (perceived as less safe than observed) and for multiuse paths (perceived as safer than observed). CONCLUSIONS: Route choices and decisions to cycle are affected by perceptions of safety, and we found that perceptions usually corresponded with observed safety. However, perceptions about certain separated route types did not align well. Education programs and social media may be ways to ensure that public perceptions of route safety reflect the evidence.

[First responder defibrillation in the LAGO-die Therme--results and experiences]. / Frühdefibrillation im LAGO-die Therme- Ergebnisse und Erfahrungen.

The use of automated external defibrillator (AED) by persons other than paramedics and emergency medical technicians is advocated by several US- and European organizations. However, at the present time it is still unclear to identify public places with a high incidence of out-of-hospital cardiac arrest. There are few data on the potential impact of public access defibrillators on survival after out-of-hospital cardiac arrest in sporting arenas or water parks. Therefore, we studied prospectively incidence of out-of-hospital cardiac arrest in the LAGO-die Therme in Herne. This is one of the most important swimming parks in Europe and member of the European Waterpark Association EWA. Eight AEDs were placed in the waterpark LAGO-die Therme. The locations where the defibrillators were stored were chosen to make possible a target interval of 60 seconds from collapse to first defibrillation. Twenty waterpark officers were instructed in cardiopulmonary resuscitation and in the use of the AED. During November 16, 2001 and December 31, 2004, 2.05 Mio. visitors were counted in the LAGO. Out-of-hospital cardiac arrest occurred in none of them. AED were used in two visitors with non arrhythmogenic syncope, no shock was delivered. Questionaires were done in 588 visitors (336 males, 252 females, mean age 38+21 years) in 2002 and in 579 visitors (322 males, 257 females, mean age 37+/-25 years) in 2004. In 2002, 77% of the visitors noticed the AED and, therefore, 49% performed more sporting activities. In addition, in 2004, AED was noticed by 480 visitors (83%) and 277 visitors (48%) did more sporting activities. There were no significant differences between 2002 and 2004 (p=ns). Despite no out-of-hospital cardiac arrest in the waterpark during the 3 year follow- up, it seems reasonable to install AED in sporting places with thousands of visitors per year.

[Recommendations for statin therapy in the elderly]. / Empfehlungen zur Statintherapie im AlterDaten und Konsensus.

Elderly patients are significantly less likely to receive statins than younger patients possibly because of doubts regarding compliance or concerns regarding the increased likelihood of adverse events and drug interactions. Poor compliance can be expected especially in patients suffering from dementia or depression as well as those whose stage of cardiovascular disease exhibits few symptoms. On the other hand, the clinical significance of CHD events is high in the elderly, and 80% of coronary deaths occur in patients aged over 65 years. The average statistical life expectancy of elderly and old patients is often underestimated. The HPS and PROSPER studies showed that statins reduce mortality and morbidity even in very elderly individuals with a high global cardiovascular risk and/or CAD. Patients up to the age of 79 years should be treated according to the same guidelines as younger patients. Statin therapy should only be considered for patients aged 80 years and older who are at a very high risk for cardiovascular events.

Who's wired and who's not: children's access to and use of computer technology.

As computer technology becomes increasingly prevalent throughout society, concerns have been raised about an emerging "digital divide" between those children who are benefitting and those who are being left behind. This article presents results from new analyses of national survey data describing children's differential access to computers in school and at home, and the varying conditions that affect how children experience computers. For example, responses from a nationwide survey of teachers suggest that, as of 1998, more than 75% of students had access to computers at school. In fact, those teaching lower-income students reported weekly use of computers more often than those teaching higher-income students. But the nature of children's experiences using computers in school varied greatly by subject and teacher objectives, and the data suggest that lower-income students use computers more often for repetitive practice, whereas higher-income students use computers more often for more sophisticated, intellectually complex applications. Differences between low-income and high-income children's access to home computers were far less subtle. Survey data indicate that only about 22% of children in families with annual incomes of less than $20,000 had access to a home computer, compared to 91% of those in families with annual incomes of more than $75,000. And among children with access, those in low-income families were reported to use the computer less than those in high-income families, perhaps because most low-income families with computers lacked a connection to the Internet. The two most predictive factors of children's use of home computers were the child's age and the computer's capabilities. The author concludes that home access to computers will be a continued area of inequality in American society, and that schools must play a critical role in ensuring equal opportunity for less-advantaged children to access the benefits of the more intellectually powerful uses of computer technology.

[Biodegradable miniplates (lactosorb) in cranio-osteoplasty--experimental results with the rapidly maturing, juvenile minipig]. / Biodegradierbare Miniplatten (Lactosorb) bei Kranioosteoplastik--experimentelle Ergebnisse am schnell wachsenden, juvenilen Miniaturschwein.

As a passive intracranial transmission (PIT- effect) has been described for metallic osteosyntheses materials in the infant growing skull. Thereby the use of resorbable plates and screws might be an alernative fixation device in infant craniofacial surgery. For evaluating the biological behaviour, craniotomies were performed in the frontoorbital region of four infant minipigs, six weeks of age and 6.1 kg of weight. After turning and orthotopical repositioning the full thickness bone graft were fixed with resorbable plates and screws made of LactoSorb on the left side after epiperiosteal, on the right side after subperiosteal preparation. The animals were sacrificed after 3, 6, 9 and 18 months. Histologically, a PIT- effect was detected similar to metallic microplates and screws being significant diminished after epiperiosteal preparation and plate positioning. The biodegradation was not affected by intraosseous translocation. Even in case of intrasinuidal transmission no inflammatory reactions werde observed. No contraindications for the clinical use of this specific PLLA-PGA copolymer could be found when implanted in the rapidly growing craniofacial bone surfaces.

The resorbable miniplate system Lactosorb in a growing cranio-osteoplasty animal model.

In the surgical treatment of craniosynostosis and craniofacial dysostosis in the growing child, passive intraosseous translocation (PIT effect) with intracranial displacement of metal plates and screws may be a problem. In an animal experiment, a possible PIT effect using resorbable PLA/PGA miniplates (Lactosorb, W. Lorenz, FL, USA) following cranio-osteoplasty were investigated in four young Göttingen minipigs. In addition to the mechanical properties, the processes of degradation and of sub- vs supraperiosteal application of the miniplates were evaluated. During degradation the resorbable PLA/PGA miniplates performed like metal plates as they also displayed passive intraosseous translocation in the growing animal model. However, in the experimental PLA/PGA miniplating the internal calvarial bone was not affected. Degradation took 12-18 months and was not delayed by bony incorporation. Mechanical properties proved to be sufficient in craniofacial surgery. Supraperiosteal plating delayed the PIT effect during the first 3 months after surgery. In the growing skull resorbable plates seem to be a promising therapeutic approach. However, prior to a general recommendation results of long-term clinical studies have to be evaluated.

Feasibility and sensing thresholds of temporary single-lead VDD pacing in intensive care.

Long-term pacemaker treatment of patients with a high-degree atrioventricular (AV) block routinely uses AV synchronous pacing because of its hemodynamic advantages compared with VVI pacing. In cases of temporary pacing, however, the limitations inherent in attempting to reliably position a temporary atrial lead generally influences the use of VVI pacing. We therefore tested the use of temporary single-lead VDD pacing, making AV pacing possible with only 1 lead, in 22 patients requiring temporary pacing due to a high-degree AV block. AV synchronous stimulation was achieved in all patients using a quadripolar lead with an atrial dipole with the atrial rings spaced 30 mm apart. During follow-up (14.1 +/- 12.5 hours) intermittent undersensing was detected in 4 of the 22 patients. We initially evaluated the atrial sensing threshold by decreasing the pacemaker device sensitivity stepwise in all patients (1.54 +/- 1.08 mV; n = 22). In 15 patients an intra-atrial electrocardiogram was recorded. During the breathing cycle, the maximum P-wave amplitude was significantly different from the minimum P-wave amplitude (2.19 +/- 1.00 mV vs 1.25 +/- 0.65 mV, p < 0.005). The atrial signal detected by the single lead was further analyzed in 10 of 15 patients using various filters. A mean signal loss of 45% was observed, increasing the lower bandpass frequency from 0.1 to 40 Hz (1.73 +/- 0.71 mV vs 0.92 +/- 0.51 mV, p < 0.02). Lowering the upper filter range from 1,000 Hz down to 100 Hz did not significantly influence the atrial signal (1.73 +/- 0.71 mV vs 1.61 +/- 0.75 mV, NS). Single-lead VDD pacing, even on a temporary basis, is a reliable means of achieving AV synchronous pacing. Due to the floating atrial dipole, the system is characterized by a high degree of variability in the atrial signal with intermittent lower values. A significant signal loss must be expected when a lower bandpass frequency of 40 Hz is used.

[Significance of periosteum in profile and contour improving osteotomies of the growing skull. Animal experiment studies with the juvenile minipig]. / Bedeutung des Periosts bei profil- und konturverbessernden Osteotomien am wachsenden Schädel. Tierexperimentelle Untersuchungen am juvenilen Minipig.

Passive intracranial translocation of plates and screws (PIT effect), which has been described in the literature, is one of the undesirable outcomes in infant craniofacial surgery. Therefore, we investigated the hypothesis of whether epiperiosteal placement of plates and screws causes the periosteum to act as a "limiting membrane", possibly preventing or delaying passive intracranial translocation of hardware. In two different experimental models of the fast-growing skull of juvenile minipigs (16 or 7 weeks old) on one side of the skull a typical, standard galeaperiosteal flap was raised. On the contralateral side, the periosteum was left attached to the bone and after performing the osteotomies, plates and screws were placed on top of the periosteum. This technique showed that the periosteum acts as a "limiting membrane" and prevents early covering of the hardware by appositional bone growth. Thus, plates and screws could easily be identified if removal was intended. In contrast to this, on the subperiosteal side (conventional technique of raising a galeaperiosteal flap), plates and screws were already completely covered by appositional bone formation 8 weeks postoperatively. The posterior bone gaps that resulted from fronto-orbital advancements showed significant delay in reossification when the epiperiosteal technique was used. This may be advantageous for the growth of the skull following fronto-orbital advancements. In contrast, the posterior bone gap showed early reossification when the standard subperiosteal technique was used. Thus, in infant craniofacial surgery, the epiperiosteal technique and placing the plates and screws on top of periosteum seem to have some advantages compared to the standard subperiosteal technique.

Effect of neurotensin on pancreatic growth and pancreatic polyamine metabolism in rats.

The neuropeptide neurotensin is known to play a role in the regulation of exocrine pancreatic secretion, but actually there are conflicting results as to whether or not neurotensin exerts a trophic response on the pancreas and there are no data concerning its effect on pancreatic polyamine metabolism. In the present study, acute and long-term effects of various intraperitoneal dosages of neurotensin that resulted in mildly supraphysiological and even unphysiological high plasma concentrations of neurotensin were studied. Furthermore, neurotensin was simultaneously administered with cholecystokinin (1 microgram CCK-8/kg body wt ip every 8 h) for five days. The administration of neurotensin resulted in an acute significant decrease of pancreatic amylase and trypsinogen concentrations (p < 0.001), which indirectly confirms the potent effect of neurotensin on pancreatic exocrine secretion. In contrast to that, neither during the short-term study (100 micrograms neurotensin/kg body wt ip every 8 h for 2, 4, 6, 8, 16, and 24 h) nor during the long-term study (1 microgram, 100 micrograms, or 200 micrograms neurotensin/kg body wt ip three or eight times daily for 10 d) did neurotensin administration result in any increase of the various parameters of pancreatic growth and polyamine metabolism. Simultaneous administration of neurotensin and CCK failed to alter or further increase the known stimulatory effect of CCK on pancreatic polyamine metabolism and pancreatic growth after 5 d of treatment. These data indicate that neither alone nor in combination with cholecystokinin did various dosages of neurotensin exert any significant stimulation on pancreatic growth or the parameters of pancreatic polyamine metabolism.

[Atrial sensing by a new VDD pacemaker]. / Atriale Wahrnehmung bei einem neuen VDD-Schrittmacher.

VDD stimulation is an alternative to DDD pacing due to the possibility of p-wave synchronous ventricular pacing without the need of an atrial lead. Mainly, the reliability of the system depends on the atrial sensing. In 22 patients the intraoperative atrial amplitude and, postoperatively, the atrial sensing threshold were measured. Furthermore, the stability of the atrial sensing threshold during follow-up was proven. The mean atrial amplitude was intraoperative by 2.4 +/- 1.2 (1.0-6.8) mV. The measurement of the atrial sensing threshold in the first 5 postoperative days showed a mean value of 1.02 +/- 0.49 (0.3-1.6) mV. The measurements of the mean atrial sensing threshold after 30, 90, and 180 days showed no statistical differences. Intraindividual variance was shown in 17/20 patients (0.55 +/- 0,42; 0.15-1.05 mV). Seventeen of the 22 patients were programmed with an atrial sensing threshold of 0.3 mV. In five patients the atrial sensing threshold was programmed at less than 0.3 mV in order to reach a twofold atrial sensitivity. Despite a programmed atrial sensitivity of 0.1 mV and isometric conditions no atrial oversensing occurred. The postoperative atrial sensing thresholds of the VDD system investigated were significantly lower than the intraoperatively measured atrial amplitudes. The mean atrial sensing threshold did not change during the follow-up period. The variation which did occur was within individual variation at different return visits.

Detection of human papillomavirus DNA sequences in leucocytes: a new approach to identify hematological markers of HPV infection in patients with oral SCC.

Squamous cell carcinoma of oral mucosa was shown to be associated with human papillomavirus (HPV) infection. The aim of this study was to find a hematological marker for HPV infection in patients with extensive HPV positive squamous cell carcinoma of the anterior oral cavity. In forty patients, referred to our clinic, suffering from histopathologically confirmed squamous cell carcinoma of the oral cavity with a tumor index T3/N2/M0 preoperative blood probes were taken. Human leucocytes were gained by FACS-lysis centrifugation. Paraffin-embedded sections of tumor tissue were deparaffinized and proteolytically digested to expose fixed target DNA. For detection of human papillomavirus, DNA sequences 6, 11, 16, 18, 31 and 33 a nonradioactive in situ hybridization technique was used (Biohid). For the first time we demonstrated HPV DNA sequences in leucocytes of patients with HPV positive oral SCC. Furthermore we found a correlation in type between HPV DNA sequences in tumor tissue and in leucocytes. This might lead to HPV as a hematological marker for follow up of patients with oral SCC and have consequences on therapy.