[Hollow organ injury and multiple trauma: treatment, course and outcome - an organ-specific evaluation of 1127 patients from the trauma registry of the DGU]. / Inzidenz von Hohlorganverletzungen nach Trauma: Behandlung, Verlauf und Outcome - eine organspezifische Auswertung von 1127 Patienten des Traumaregisters der DGU.

BACKGROUND: The relevance of hollow organ trauma in severely injured patients within a large collective has not been thoroughly reviewed as yet. This study aimed at assessing the prevalence of hollow organ trauma in relation to the outcome and the currently established method of treatment. PATIENTS AND METHODS: Altogether data of all patients of the Trauma Register of the German Society of Trauma Surgery (DGU) (1993 - 2009) were interpreted retrospectively. All patients with an "Injury Severity Score" (ISS) ≥ 16, direct admission to a trauma centre and an age of ≥ 16 years were included. All patients with abdominal trauma (AISabdomen ≥ 2) were compared with patients with hollow organ trauma (AIShollow organ ≥ 2). The following organs were attributed to the hollow organs: stomach, small intestine (duodenum, jejunum / ileum), colon, gall bladder and urinary bladder. RESULTS: From 9268 patients with abdominal injuries 1127 (12.2 %) additionally showed a hollow organ injury (AISabdomen ≥ 2, AIShollow organ 2 - 5) and were analysed in dependence on the classification of the "American Association for the Surgery of Trauma" (AAST) organ severity score. AAST-hollow organ: II°: 4.6 %, III°: 5.3 %, IV°: 2.1 %, V°: 0.2 %. Patients with leading hollow organ injury (grades IV and V) thereby showed a significant increase of lethality (IV°: 32.7 % and V°: 31.3 %). With an increasing grade of hollow organ injury, however, the ISS increased as well. Lethality was not increased over the expected lethality rate (RISC score) due to the additional hollow organ injury though. CONCLUSION: The results presented here show the prevalence and the outcome of hollow organ injury in a large collective within the Trauma Register of the DGU for the first time.

Genotype List String: a grammar for describing HLA and KIR genotyping results in a text string.

Knowledge of an individual's human leukocyte antigen (HLA) genotype is essential for modern medical genetics, and is crucial for hematopoietic stem cell and solid-organ transplantation. However, the high levels of polymorphism known for the HLA genes make it difficult to generate an HLA genotype that unambiguously identifies the alleles that are present at a given HLA locus in an individual. For the last 20 years, the histocompatibility and immunogenetics community has recorded this HLA genotyping ambiguity using allele codes developed by the National Marrow Donor Program (NMDP). While these allele codes may have been effective for recording an HLA genotyping result when initially developed, their use today results in increased ambiguity in an HLA genotype, and they are no longer suitable in the era of rapid allele discovery and ultra-high allele polymorphism. Here, we present a text string format capable of fully representing HLA genotyping results. This Genotype List (GL) String format is an extension of a proposed standard for reporting killer-cell immunoglobulin-like receptor (KIR) genotype data that can be applied to any genetic data that use a standard nomenclature for identifying variants. The GL String format uses a hierarchical set of operators to describe the relationships between alleles, lists of possible alleles, phased alleles, genotypes, lists of possible genotypes, and multilocus unphased genotypes, without losing typing information or increasing typing ambiguity. When used in concert with appropriate tools to create, exchange, and parse these strings, we anticipate that GL Strings will replace NMDP allele codes for reporting HLA genotypes.

[Disposition for organ donation: analysis of a survey and trial of 974 respondents]. / Organspendebereitschaft: Interventionsstudie bei 974 Befragten.

BACKGROUND: Due to the lack of donor organs many patients cannot be helped in time with the necessary transplantation in Germany. At the same time, there is an organ donor potential that is not being exploited. A high refusal rate with a low rate of organ donor card holders remains problematic. The objective of this study was to collect the rate of holders of organ donor cards in a collective and to evaluate the collective according to other attributes in the context of a targeted trial. METHODS: In 2009, a three-part questionnaire including an educational text regarding the topic of "organ donation" was sent out to the employees of the Sparkasse Essen (a savings bank). RESULTS: Altogether, 974 out of 1480 (65.8 %) completely answered questionnaires were evaluated. 21.3 % of the respondents had an organ donor card at the time the survey was carried out. A statistically significant association between gender (p value, 0.0438), age (p value, 0.0267) and the possession of a donor card could be determined. 22.1 % of the respondents who participated in sports regularly or donated blood (p value, < 0.0049), were holding an organ donor card. 60 % of the respondents found the brief information to be sufficient, 22.6 % could imagine acquiring an organ donor card for them based on the presented information alone. CONCLUSION: The spread of information and transparency in transplant medicine are essential for the facilitation of "willingness to donate organs". In the framework of this trial, besides data analysis, also fundamental information on "organ donation" could be conveyed. After all, 95.3 % of the respondents have read the information material and hence document the success of the study.

[Kidney injury and multiple trauma: outcome, course and treatment algorithm. An organ-specific evaluation of 835 patients from the trauma register of the DGU]. / Nierenverletzung und Polytrauma: Outcome, Verlauf und Behandlungsalgorithmus. Eine organspezifische Auswertung von 835 Patienten des TraumaRegisters der DGU.

BACKGROUND: The relevance of renal trauma in severely injured patients within a large collective has not yet been thoroughly reviewed. This study aimed at assessing the prevalence of renal trauma in relation to the outcome and the currently established method of treatment. PATIENTS AND METHODS: Altogether data of 35,664 patients of the TraumaRegister of the German Society of Trauma Surgery (DGU) (1996-2007) were interpreted retrospectively. All patients with an injury severity score (ISS) ≥16, direct admission to a trauma center and an age of ≥16 years were included. All patients with abdominal trauma (AIS(Abdomen) ≥2) were compared with patients with abdominal and renal trauma (AIS(Kidney) ≥2). RESULTS: A total of 18,416 patients fulfilled the inclusion criteria of which 6,218 (34.1%) had abdominal injuries. Of these patients with abdominal injury 835 (13.3%) additionally showed a kidney injury (AIS(Abdomen) ≥2, AIS(Kidney) 2-5) and were analyzed according to the classification of the American Association for the Surgery of Trauma (AAST) organ-severity-score. AAST kidney: II°: 45.5%, III°: 31.1%, IV°: 15.6%, V°: 7.8%. Patients with leading kidney injury (grade IV and V) thereby showed a significant increase in mortality (IV: 32.3% and V: 40.0%) and an increase in the need for surgical intervention (IV: 61.5 and V: 81.5%). With an increasing grade of renal injury, however, the ISS is also increased but mortality was not increased over the expected mortality rate (RISC score) due to the additional renal injury. Dialysis rate in the surviving patients showed an increased rate depending on the degree of the kidney injury (II: 5.5%, III: 7.6%, IV: 18.8%, V: 8.3%). CONCLUSION: The results presented here show the prevalence and the outcome of kidney injury in a large collective within the TraumaRegister of the DGU for the first time. Based on the current literature and the findings a treatment algorithm has been developed.

No further incidence of sepsis after splenectomy for severe trauma: a multi-institutional experience of The trauma registry of the DGU with 1,630 patients.

OBJECTIVE: Non-operative management of blunt splenic injury in adults has been applied increasingly at the end of the last century. Therefore, the lifelong risk of overwhelming post-splenectomy infection has been the major impetus for preservation of the spleen. However, the prevalence of posttraumatic infection after splenectomy in contrast to a conservative management is still unknown. Objective was to determine if splenectomy is an independent risk factor for the development of posttraumatic sepsis and multi-organ failure. METHODS: 13,433 patients from 113 hospitals were prospective collected from 1993 to 2005. Patients with an injury severity score >16, no isolated head injury, primary admission to a trauma center and splenic injury were included. Data were allocated according to the operative management into 2 groups (splenectomy (I) and conservative managed patients (II)). RESULTS: From 1,630 patients with splenic injury 758 patients undergoing splenectomy compared with 872 non-splenectomized patients. 96 (18.3%) of the patients with splenectomy and 102 (18.5%) without splenectomy had apparent infection after operation. Additionally, there was no difference in mortality (24.8% versus 22.2%) in both groups. After massive transfusion of red blood cells (>10) non-splenectomy patients showed a significant increase of multi-organ failure (46% vs. 40%) and sepsis (38% vs. 25%). CONCLUSIONS: Non-operative management leads to lower systemic infection rates and mortality in adult patients with moderate blunt splenic injury (grade 1-3) and should therefore be advocated. Patients with grade 4 and 5 injury, patients with massive transfusion of red blood cells and unstable patients should be managed operatively.

Use of marginal organs in kidney transplantation for marginal recipients: too close to the margins of safety?

OBJECTIVE: Due to organ shortage, average waiting time for a kidney in Germany is about 4 years after start of dialysis. Number of kidney grafts recovered can only be maintained by accepting older and expanded criteria donors. The aim of this study was to analyse the impact of donor and recipient risk on kidney long-term function. METHODS: All deceased kidney transplantations were considered. We retrospectively studied 332 patients between 2002 and 2006; divided in 4 groups reflecting donor and recipient risk. RESULTS: Non-marginal recipients were less likely to receive a marginal organ (69 of 207, 33%) as compared to marginal recipients, of whom two-thirds received a marginal organ (p<0.0001). Graft function significantly differed between the groups, but detrimental effect of marginal recipient status on eGFR after 12 months (-6 ml/min/1.73qm, 95% CI -2 to -9) was clearly smaller than the effect of marginal donor status (-10 ml/min/1.73qm, 95% CI -7 to -14). CONCLUSIONS: As we were able to show expanded criteria donor has a far bigger effect on long-term graft function than the "extra risk" recipient. Although there have been attempts to define groups of recipients who should be offered ECD kidneys primarily the discussion is still ongoing.

Tumor markers as a diagnostic key for hilar cholangiocarcinoma.

OBJECTIVE: Hilar cholangiocarcinoma is the fourth most common gastrointestinal malignancy. CA19-9 and CEA are helpful devices in the management of gastrointestinal malignancies and belong to clinical routine in surgical oncology. But the validity of these parameters in terms of tumor extension and prognosis of bile duct malignancies still remains unclear. METHODS: From 1998 to 2008, we obtained preoperative CA19-9 and CEA serum levels in 136 patients with hilar cholangiocarcinoma. We correlated tumor stage, resectability rate and survival with preoperative CA 19-9 and CEA serum levels. RESULTS: CA19-9 (UICC I: 253 ± 561U/ml; UICC II: 742 ± 1572 U/ml; UICC III: 906 ± 1708 U/ml; UICC IV: 1707 ± 3053U/ml) and CEA levels (UICC I: 2.9 ± 3.8U/ml; UICC II: 4.6 ± 6.5 U/ml; UICC III: 18.1 ± 29.6 U/ml; UICC IV: 22.7 ± 53.9 U/ml) increase significantly with rising tumor stage. Patients with pre?operative serum levels of CA19-9 (>1000U/ml) and CEA (>14.4ng/ml) showed a significant poorer resectability rate and survival than patients with lower CA19-9 and CEA serum levels respectively. CONCLUSION: CA19-9 and CEA serum levels are associated with the tumor stage. If preoperatively obtained CA19-9 and CEA serum levels are highly elevated patients have an even worse survival and the frequency of irresectability is significantly higher.

Liver transplantation in swine without venovenous bypass.

INTRODUCTION: A model of orthotopic liver transplantation in swine was developed to investigate an advanced reperfusion approach. Thereby, we consciously disclaim otherwise commonly practiced venovenous bypass during the recipient operation. MATERIAL AND METHODS: Ten liver transplantations were performed according to the described technique without using venovenous bypass. In each swine the observation period was 48 h. RESULTS: All transplantations were carried out after a median cold ischemic time of 307.5 min (295-340); the median warm ischemic time in these cases was 25 min (20-32). Eight of 10 swine survived 48 h after the operation. CONCLUSION: Orthotopic liver transplantations in the recipient swine are feasible even without using venovenous bypass.

BioJava: an open-source framework for bioinformatics.

SUMMARY: BioJava is a mature open-source project that provides a framework for processing of biological data. BioJava contains powerful analysis and statistical routines, tools for parsing common file formats and packages for manipulating sequences and 3D structures. It enables rapid bioinformatics application development in the Java programming language. AVAILABILITY: BioJava is an open-source project distributed under the Lesser GPL (LGPL). BioJava can be downloaded from the BioJava website (http://www.biojava.org). BioJava requires Java 1.5 or higher. All queries should be directed to the BioJava mailing lists. Details are available at http://biojava.org/wiki/BioJava:MailingLists.

Effect of low-dose rapamycin on tumor growth in two human hepatocellular cancer cell lines.

AIM: Liver transplantation is the best treatment for patients with early hepatocellular carcinoma (HCC) and cirrhosis. A limiting factor for long-term survival remains posttransplant tumor recurrence. Thus, there is widespread discussion about the role of various immunosuppressive agents. The newly developed immunosuppressive drug rapamycin may aid to lower recurrence rates. We investigated the efficiency of rapamycin as compared with previous immunosuppressants in a tumor cell model. METHODS: We studied two HCC cell lines for cell-cycle and proliferation analyses after treatment with rapamycin or other immunosuppressants. To elucidate the underlying molecular signaling pathway, we performed Western blotting for phosphorylated p70 S6 kinase protein expression. RESULTS: Low-dose rapamycin inhibited tumor cell growth at doses of 1, 5, and 10 ng/mL, while standard immunosuppressants stimulated growth. A rapamycin dose of 20 ng/mL showed a marked decrease in the growth inhibition of both HCC cell lines compared to low-dose administration. CONCLUSION: Rapamycin in low doses inhibited the growth of two HCC cell lines in vitro. Inhibition of tumor cell growth was observed with a high dose of rapamycin (20 ng/mL), which appears to be the dividing line between growth and inhibition. We postulated that at higher doses the immunosuppressive effect of rapamycin is overrode by its antitumor effects.

[CA19-9 in intrahepatic cholangiocarcinoma : A diagnostic and prognostic armamentarium?] / CA19-9 beim intrahepatischen Cholangiokarzinom : Ein diagnostisches und prognostisches Armamentarium?

BACKGROUND: Intrahepatic cholangiocarcinomas are the second most common malignant tumors of the liver with an unfavorable prognosis. The role of CA19-9 in terms of patient prognosis is still under debate in the literature. OBJECTIVE: The aim of the present study was to investigate the prognostic value of preoperatively assessed CA19-9 levels in patients with intrahepatic cholangiocarcinoma after surgery. MATERIAL AND METHODS: A total of 63 patients suffering from intrahepatic cholangiocarcinoma underwent surgery between March 2001 and February 2013 at the West German Cancer Center in Essen, Germany. The follow-up ended in December 2017. The UICC stages, clinicopathological parameters and postoperative tumor-specific survival rates were analyzed with respect to preoperatively measured CA19-9 serum levels. RESULTS: Increased CA19-9 serum levels correlated with higher UICC tumor stages and other unfavorable clinicopathological parameters. Moreover, patients with preoperative elevated CA19-9 serum levels displayed significantly reduced overall survival rates (especially >1000 U/ml vs. ≤1000 U/ml; median overall survival: 14.05 months vs. 42.40 months; p = 0.0003). CONCLUSION: Preoperatively assessed CA19-9 levels >1000 U/ml are a strong negative prognostic factor of postoperative disease-specific survival in patients suffering from intrahepatic cholangiocarcinoma. Future studies are necessary to evaluate if patients with highly elevated CA19-9 serum levels should be considered for modified treatment strategies (e. g. neoadjuvant or adjuvant therapy).

[Laparoscopic liver resection : A retrospective analysis of 94 clinical cases]. / Laparoskopische Leberresektion : Eine retrospektive Analyse von 94 klinischen Fällen.

BACKGROUND: Since the introduction of minimally invasive surgery its use in liver resections is controversial. The importance of laparoscopic liver surgery within a large collective has been studied insufficiently to date. OBJECTIVES: In this article we report our experiences with minimally invasive liver resections. METHODS: A retrospective analysis was conducted looking at all patients in our clinic where a laparoscopic liver resection was performed between 01 January 2000 and 30 April 2013. RESULTS: In total, we performed 94 laparoscopic liver resections in 90 patients (female n = 44, 46.8 %, male n = 50, 53.2 %) with 28 primary and 63 secondary liver tumors and 3 tumors remaining unclear. Of these 62 were atypical or wedge resections, 19 segmental resections, 8, left lateral and 3 right lateral resections as well as 1 hemihepatectomy left and 1 right. Switching to an open resection intraoperatively was necessary in eight cases. Postoperative complications were observed in two patients, one patient experienced a postoperative cerebral artery stroke and one patient died on postoperative day 13 from sepsis in multiorgan failure. The average operative time was 145 ± 82.34 min (range 10-430 min) and the average hospital stay 7 days. In 79 patients an R0 resection was achieved. CONCLUSIONS: Laparoscopic liver resection can be considered a safe procedure for the treatment of liver tumors. The accurate selection of patients and appropriate expertise of the attending team in minimally invasive surgery are essential to the outcome.

Generation of mature dendritic cells from human blood. An improved method with special regard to clinical applicability.

Two methods to generate human dendritic cells from hematopoietic precursor cells in peripheral blood have recently been published. One approach utilizes the rare CD34+ precursors and GM-CSF plus TNF-alpha. The other method makes use of the more abundant CD34- precursor population and GM-CSF plus IL-4. Here we report a method that is based on the latter approach. However, the GM-CSF and IL-4 treated cells are not stable mature dendritic cells, e.g., the characteristic morphology and nonadherence of dendritic cells is lost if the cytokines are removed. We describe the need for a monocyte-conditioned medium to generate fully mature and stable dendritic cells. This is achieved by adding a 3 day 'maturation culture' to the initial 6-7 day culture in the presence of GM-CSF and IL-4. Macrophage-conditioned medium contains the critical maturation factors. Mature dendritic cells are defined by their pronounced display of motile cytoplasmic processes ('veils'), their high capacity to induce proliferative responses in resting T cells, particularly in naive umbilical cord T cells, their down-regulated antigen processing ability, and their characteristic phenotype: expression of CD83, high levels of MHC molecules and CD86, lack of CD115 and perinuclear dot-like CD68 staining. These features are stable for at least 3 days upon withdrawal of cytokines and conditioned media. IL-4 can be replaced by IL-13. When CD34+ progenitors are depleted from blood, there is only a minor reduction in the yield of dendritic cells by this method. We have adapted the method to consider several variables that are pertinent to clinical use, including a change from fetal calf serum to human plasma and to media approved for clinical use like X-VIVO or AIM-V. 1% plasma and RPMI 1640 are currently optimal. Additional reagents used for cell culture (Ig. cytokines) and cell separation (immunomagnetic beads) are approved for or already used in clinical applications. For 40 ml blood, the yield is 0.8-3.3 x 10(6) mature dendritic cells as defined by the expression of the new dendritic cell-restricted marker CD83. CD83+ cells constitute between 30 and 80% of all cells recovered at the end of the culture period. Yields can be enhanced up to six-fold if the blood donors are pretreated with G-CSF. Stable, mature dendritic cells generated by this method should be a powerful tool for active immunotherapy.

Generation of large numbers of fully mature and stable dendritic cells from leukapheresis products for clinical application.

Dendritic Cell (DC)-based vaccination approaches in man require a reproducible DC generation method that can be performed in conformity with GMP (Good Manufacturing Practice) guidelines and that circumvents the need for multiple blood drawings to generate DC. To this end we modified our previously described method to generate mature DC from CD14 + monocytes by a two step method (priming in GM-SF + IL-4 followed by maturation in monocyte conditioned medium) for use with leukapheresis products as a starting population. Several adaptations were necessary. We established, for example, a modified adherence step to reliably enrich CD14 + DC precursors from apheresis mononuclear cells. The addition of GM-CSF + IL-4 at the onset of culture proved disadvantageous and was, therefore, delayed for 24 h. DC development from apheresis cells occurred faster than from fresh blood or buffy coat, and was complete after 7 days. Monocyte conditioned medium when added on day 6 resulted in fully mature and stable DC (veiled, highly migratory and T cell sensitizing cells with a characteristic phenotype such as 85% CD83 + , p55/fascin + , CD115/M-CSF-R - , CD86 + ) already after 24 h. The mature DC progeny were shown to remain stable and viable if cultured for another 1-2 days in the absence of cytokines, and to be resistant to inhibitory effects of IL-10. Freezing conditions were established to generate DC from frozen aliquots of PBMC or to freeze mature DC themselves for later use. The approach yields large numbers of standardized DC (5-10 x 10(8) mature CD83 + DC/leukapheresis) that are suitable for performing sound DC-based vaccination trials that can be compared with each other.

Auranofin: a unique oral chrysotherapeutic agent.

Auranofin is a chemically unique gold coordination complex with demonstrated antiarthritic properties on oral administration. Its pharmacokinetic and immunologic profiles are distinct from injectable gold compounds. When auranofin is added to a regimen of salicylates and/or a nonsteroidal antiinflammatory drug for the treatment of RA, significant additional therapeutic benefit is observed. Published studies indicate that auranofin given 6 mg per day approaches the efficacy of parenteral gold salts in the treatment of rheumatoid disease. Noticeable improvement in clinical and laboratory parameters of disease activity has been observed by the third month of auranofin therapy. Further benefit occurs in some patients during the remainder of the first year of treatment. In the more than 3,000 patients treated with auranofin, the most frequently reported side effects were gastrointestinal (mainly diarrhea) and mucocutaneous. Most side effects were mild in nature and the withdrawal rate due to all adverse reactions averaged 11%. Auranofin differs from injectable gold by producing more gastrointestinal but fewer mucocutaneous reactions. The severity of these reactions is less with auranofin and causes fewer withdrawals from therapy.

Composition and mechanical properties of gutta-percha endodontic points.

Gutta-percha endodontic filling points were found to contain approximately 20% gutta-percha (matrix), 66% zinc oxide (filler), 11% heavy metal sulfates (radiopacifier), and 3% waxes and/or resins (plasticizer). The mechanical properties were indicative of a partially crystalline viscoelastic polymeric material. They were found to obey Hooke's law and displayed a prominent upper and lower yield point when stressed beyond the proportional limit. The essential differences in mechanical properties of individual brands were found to be a function of the gutta-percha and zinc oxide concentration.

Different cytokine mRNA profiles in Graves' disease, Hashimoto's thyroiditis, and nonautoimmune thyroid disorders determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR).

Intrathyroidal lymphocytes are a source of cytokines thought to stimulate or maintain the immune process within the thyroid in Graves' disease (GD) and Hashimoto's thyroiditis (HT). Quantitative assessment of the cytokine profile may provide important clues as to the Th1/Th2 balance prevailing in these diseases. We analyzed cytokine mRNA expression levels in thyroid tissue samples from 13 patients with GD, 2 with HT, 5 with nontoxic multinodular goiter (NTG), and 4 with thyroid autonomy (nodular = TAnod and perinodular = TAperi tissue) using multispecific competitor fragments with primer sequences for IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IFN-gamma, CD25, and CD3 delta-chain mRNA. Patients with GD were subdivided into two groups according to their serum levels of antibodies to thyroperoxidase (anti-TPO; GDhigh > 4000 U/mL, GDlow < or = 200 U/mL). These levels correlated positively with the CD3 delta-chain mRNA levels (r = 0.83) and with the T cell infiltration (r = 0.71) as determined by immunohistochemistry. Patients with GDhigh demonstrated 2- to 4-fold higher IL-4 mRNA levels (as compared to all other investigated groups) and significantly higher IL-10 mRNA levels as compared to HT, GDlow, and TAnod patients. Patients with GDhigh also had significantly higher levels of IFN-gamma, IL-1 beta, IL-8, and CD25 mRNA as compared to GDlow. The highest IFN-gamma, IL-2, and CD25 mRNA levels were found in HT. The lowest mRNA levels of all the investigated groups were detected in TAnod. No significant differences in IL-6 and IL-8 mRNA levels were found between most of the patient groups. In summary, patients with GDhigh showed a shift to a more Th2-driven cytokine pattern. In contrast, the increase mRNA levels of Th1-related cytokines found in HT indicate predominantly T cell-mediated cytotoxic processes.

Determination and relationship of C-reactive protein in human dental pulps and in serum.

C-reactive protein (CRP), an acute phase protein synthesized by the liver, increases in serum as much as 3000 times above its normal level in response to acute inflammation. The purpose of this study was to determine whether CRP levels in dental pulps could be correlated with the histological disease status of the pulp and with systemic blood levels of CRP. Inflamed and necrotic pulps were extirpated during routine endodontic therapy. Normal pulps were removed from extracted, intact third molars. One half of each pulp specimen was placed in formalin for histological study; the other half was frozen for immunological study. A serum sample was obtained from each patient at the end of the dental visit. CRP levels were determined by the enzyme-linked immunosorbent assay. Pulps were categorized histologically as normal, inflamed, inflamed/necrotic, or necrotic. The correlation between CRP levels of pulp and serum was not significant. CRP levels of normal pulps differed significantly only from inflamed pulps (p less than 0.05, Dunnett). This increase in CRP appears to be a local phenomenon resulting from the interaction of CRP with various inflammatory mediators in the pulp.

Natural modifiers of the inflammatory process in the human dental pulp.

Concentrations of the protease inhibitors alpha 1-antitrypsin and alpha 2-macroglobulin were determined in normal and inflamed human dental pulps. Carious pulpal exposure which is associated with polymorphonuclear leukocyte infiltration and release of lysosomal enzymes was chosen as the point of verifiable inflammatory activity in the pulp. Normal samples were collected from nondiseased third molar teeth treatment planned for extraction and inflamed human pulps were collected from teeth with deep carious lesions. One half of each sample was assayed for concentration of protease inhibitors by enzyme-linked immunosorbent assay and the remaining half was examined histologically to verify the clinical diagnosis and categorize the extent of the inflammatory process. alpha 1-Antitrypsin and alpha 2-macroglobulin were detected in normal and inflamed human dental pulps in the nanogram per milliliter range. Statistically significant differences were found in the concentrations of alpha 2-macroglobulin (p less than 0.01) in moderate to severe inflammation versus normal pulp categories and between mildly inflamed pulps and moderate to severely inflamed pulps (p less than 0.05). Although differences in concentrations of alpha 1-antitrypsin were seen between inflamed and normal pulps, the differences were not statistically significant. The presence of these two protease inhibitors in the human dental pulp tissue and the increase in their concentration in acute inflammation indicates that these proteins play a role in the pathogenesis of pulpal inflammatory disease.