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Biomedical subjects

M Kunkel

Publications and source records attributed to M Kunkel.

At least 19 recordsLinked to original sources
PubMed2006

Infected osteoradionecrosis of the mandible: follow-up study suggests deterioration in outcome for patients with Actinomyces-positive bone biopsies.

Infected osteoradionecrosis (IORN) is one of the major complications of oral cancer radiotherapy. Recent studies showed a high prevalence of Actinomyces in IORN. In this study, the clinical follow up of IORN patients (n=25; 20 male, 5 female) with regard to Actinomyces detection in the mandible was analyzed. Within 1.6-119 months of follow up, disease control was achieved in almost 90% of the patients with Actinomyces-negative bone biopsies, but only in 25% of the Actinomyces-positive group. The presence of Actinomyces was associated with a significantly higher risk of treatment failure (P=0.004; Fisher's exact test). This held true when the data were controlled for 'extent of bone destruction', 'type of surgery' and 'soft-tissue closure' in a logistic regression analysis (P=0.018; Wald test). Since Actinomyces was detected in a significant number of patients with non-healing mucosal defects, this microbe may promote the persistence of chronic non-healing inflammatory processes. Actinomyces positivity defines a subpopulation with a clinically deteriorated course of mandibular IORN.

Actinomyces↗
PubMed2006

Abscess of the orbit arising 48 h after root canal treatment of a maxillary first molar.

AIM: To discuss a rare, but severe complication arising following routine root canal treatment. SUMMARY: An orbital abscess is reported that occurred following routine root canal treatment. A young, healthy female patient, with no history of chronic paranasal infection had undergone root canal treatment of the right maxillary first molar. On hospital admission, she presented with extensive periorbital swelling and discreet diplopia. Computed tomography imaging identified massive purulent sinusitis and subsequent involvement of the orbit via the inferior and medial orbital wall within 48 h after completion of root canal treatment. Immediate surgical drainage of the maxillary sinus and the orbit was established and a high dose of perioperative antibiotics (Amoxicillin/Clavulanic acid, Gentamycin, Metronidazole) were administered. Vision remained undisturbed and mobility of the globe recovered within 10 days. KEY LEARNING POINTS: Rapid exacerbation of a periapical inflammation may occur following root canal treatment and may even involve the orbit. A typical speed of disease progression or ophthalmic symptoms should alert the clinician to at least consider unusual early orbital spread of odontogenic infection. When extra-alveolar spread and especially orbital spread is suspected, immediate referral to a maxillofacial or other specialized unit is mandatory.

Abscess↗
PubMed2004

[Chronic cutaneous infiltration with abscess and fistula formation. A type of clinical course in atypical mycobacteriosis].

BACKGROUND: Cutaneous lesions of atypical mycobacteriosis are very rare in Western Europe. Both the slow disease progression and the rather unspecific clinical appearance of the chronic infiltration render cutaneous mycobacteriosis a diagnostic challenge. In this communication, we present an uncommon, biphasic course of a cutaneous atypical mycobacteriosis. CASE REPORT: A 3-year-old child was referred to our institution due to submandibular cutaneous infiltration together with subcutaneous abscess formation. There was no carious lesion or other odontogenic potential source of infection. First-line therapy was incision of the abscess and local curettage to obtain a specimen for histologic and microbiologic evaluation, which revealed atypical mycobacteria. In spite of local curettage, only partial remission of the cutaneous infiltration was achieved. When the child was readmitted 9 months later, the lesion had progressed to a scrofulosis-like appearance even though specific antibiotic treatment had been administered. Complete surgical excision of the affected skin and extirpation of the respective lymph node and fistula was performed as second-line therapy. Complete remission was achieved without further adjuvant treatment. DISCUSSION: Our case demonstrates the problems that may arise with this rare type of mycobacterial infection. In all probability, scratch artifacts due to atopic dermatitis provided the source/entry of the infection in this specific case. Both histopathologic findings and clinical appearance were suggestive of classic cutaneous tuberculosis (tuberculosis cutis colliquativa), although it was in fact an atypical mycobacteriosis. Furthermore, obstinate persistence after minor surgical intervention and even after specific (triple) antibiotic treatment illustrates the difficulties of limited, minimally invasive treatment.

Abscess↗
PubMed2002

[Acral ischemia as a rare paraneoplastic syndrome in the terminal phase of mouth floor carcinoma].

BACKGROUND: The term "paraneoplastic syndrome" describes a clinically apparent disease associated with a malignant neoplasm, which is not a direct consequence of invasive tumor growth. Acral ischemia and digital necrosis of multiple fingertips have been occasionally described as a paraneoplastic syndrome. However, the exact mechanisms of this phenomenon are still not adequately known. CASE REPORT: This paper describes a 72-year-old male patient with severe acral ischemia and multiple necroses on several fingertips. Symptoms evolved under palliative chemotherapy with gemcitabine for inoperable metachronous squamous cell carcinoma of the tonsil following a history of two simultaneous carcinomas of the alveolar crest. Digital ischemia was combined with severe pain, similar to Raynaud's syndrome, which required therapeutic intervention. The treatment objective is to improve perfusion and simultaneously reduce pain. A combination of iloprost, an analog of prostacyclin (50 micrograms intravenous Ilomedin once daily), and a CT-guided thoracic sympathectomy achieved a continuous positive effect on the intensity of acral ischemia and alleviated the pain.

Aged↗
PubMed2001

Surgically assisted rapid palatal expansion. An acoustic rhinometric, morphometric and sonographic investigation.

This study aimed to evaluate the effect of surgically assisted rapid palatal expansion on the skeletal structures of the midface. Ten patients (mean age 28.5 years) were investigated by means of acoustic rhinometry, study model analysis and sonography before and after the procedure of surgically assisted rapid palatal expansion. The measurements revealed that surgically assisted rapid palatal expansion not only resulted in transverse expansion of the maxilla, providing dental arch space for lining up the teeth; the procedure also caused a substantial enlargement of the maxillary apical base and of the palatal vault, providing space for the tongue for correct swallowing and thus preventing relapse. There was a distinct subjective improvement in nasal breathing associated with enlargement of the nasal valve towards normal values and with an increase of nasal volume in all compartments. The measurements showed a marked influence of surgically assisted rapid palatal expansion on the skeletal structures of the midface. The significant widening can be demonstrated by non-invasive examination. Success of the osteotomy procedure can be readily monitored by sonographic examination of the expansion and the subsequent ossification, which allows individually adjusted retention periods and avoids frequent radiation exposure.

Acoustic Impedance Tests↗
PubMed2001

[Therapy monitoring with 2-(18F)-FDG positron emission tomography after neoadjuvant radiation treatment of mouth carcinoma].

BACKGROUND: Combined protocols of radiation therapy and surgical resection, as applied in advanced oral cancer, rely on objective and early assessment of treatment response to radiation therapy. Non-responders require immediate radical salvage surgery even in spite of substantial operative risks, while complete or subtotal response may give reasons for continuing the conservative approach. Therefore, we investigated radiation response by FDG-PET for early monitoring of oral cancer. PATIENTS AND METHODS: In 30 patients with advanced stages of oral cancer (Table 1), FDG-PET (Siemens, ECAT EXACT 922) was performed within 4 weeks after completion of preoperative radiation therapy (36 Gy). SUV of tumor regions were compared to the histologic degree of tumor regression in complete resection specimens. Statistic evaluation included correlation analysis of SUV vs tumor regression and ROC analysis for SUV cut-off values. RESULTS: While low FDG accumulation was found in tumors with histological complete remission (2.3 +/- 0.4) as well as in cases of residual tumor (3.4 +/- 1.8), high FDG uptake was a rather specific indicator of vital tumor tissue (Figure 2). Significant correlation (p = 0.045) between postradiotherapeutic FDG-uptake and histological tumor regression was recognized. A SUV > 2.75 as a clinically practicable threshold value for the identification of residual vital tumor resulted in a specificity of 88%, sensitivity of 68%, a positive predictive value of 94% and a negative predictive value of 50% (Figure 3). Based on our actual follow-up data we could not confirm a significant correlation between postradiotherapeutic SUV and patients' survival. CONCLUSION: Within a standardized protocol, FDG-PET recognize treatment response to radiation therapy in oral squamous cell carcinoma with a reasonable specificity and thus provides a basis for further therapeutic decisions. An increased SUV (> 2.75) may be the rational to justify an aggressive surgical approach even when patients face substantial surgical or anesthesiological risk. However, the posttherapeutic pattern of glucose uptake varies with the applied treatment modalities and has to be explored for the protocol applied.

Adult↗
PubMed2001

Evolution tunes the excitability of individual neurons.

The relationship between the genome and the evolution of the nervous system may differ between an animal like C. elegans with 302 neurons, and mammals with tens of billions of neurons. Here we report that a class of nonconserved potassium channels highly expanded in C. elegans may play a special role in the evolution of its nervous system. The C. elegans genome contains an extended gene family of potassium channels whose members fall into two evolutionary divergent classes. One class constitutes an ancient conserved "set" of K+ channels with orthologues in both humans and Drosophila and a second larger class made up of rapidly evolving genes unique to C. elegans. Chief among this second class are novel potassium channels having four transmembrane domains per subunit that function as regulated leak conductances to modulate cell electrical excitability. This inventory of novel potassium channels is far larger in C. elegans than in humans or Drosophila. We found that, unlike conserved channel genes, the majority of these genes are expressed in very few cells. We also identified DNA enhancer elements associated with these genes that direct gene expression to individual neurons. We conclude that C. elegans may maintain an exceptionally large inventory of these channels (as well as ligand-gated channels) as an adaptive mechanism to "fine tune" individual neurons, making the most of its limited circuitry.

Adaptation, Physiological↗
PubMed2001

Structure-activity relationship of aza-steroids as PI-PLC inhibitors.

A number of aza-steroids were synthesized as potent phosphatidylinositol phospholipase C (PI-PLC) inhibitors. The epimeric mixtures 22,25-diazacholesterol (8a) and 3beta-hydroxy-22,25-diazacholestane (8b) were among the most active of these inhibitors, with IC(50) values of 7.4 and 7.5 microM, respectively. The 20alpha epimer, 8a2 (IC(50)=0.64 microM), whose stereochemistry at C-20 coincides with that of cholesterol, was found 50 times more potent than the 20beta epimer, 8a1 (IC(50)=32.2 microM). In diaza-estrone derivatives, the 3-methoxy group on the aromatic A-ring of 23 exhibited moderate PI-PLC inhibitory activity (IC(50)=19.7 microM), while compound with a free hydroxyl group (21) was inactive. However, in diaza-pregnane derivatives, epimers with a 3-hydroxyl group (8a, IC(50)=7.4 microM) exhibited more potent PI-PLC inhibitory activity than their counterparts with 3-methoxyl group on the non-aromatic A-ring (26, IC(50)=17.4 microM). We have illustrated in our previous publication that 3-hydroxyl-6-aza steroids are potent PI-PLC inhibitors.(3) However, simultaneous presence of the 6-aza and 22,25-diaza moieties in one molecule as in 13, led to loss of activity. Epimeric mixture 8a showed selective growth inhibition effects in the NCI in vitro tumor cell screen with a mean GI(50) value (MG-MID) of 5.75 microM for 54 tumors.

Azacosterol↗
PubMed2001

Residue mass plot and abundance plot: detection of isobaric interferences in DE-MALDI-TOF-mass spectra of complex polymer mixtures.

Mass spectra of complex polymer mixtures often disturbed by overlapping homologue peak series have been interpreted by means of the novel techniques of the residue mass plot and the abundance plot. The model substance used for the investigations is so far poorly characterized non-ionic emulsifier Cremophor EL (polyoxyl 35 castor oil) (CrEL), a heterogeneous polyethoxylate mixture. Because of its high amount of hydrophobic and hydrophilic components, CrEL was separated into two fractions, aqueous and methanolic, by cation exchange (CCaEx) chromatography. CrEL was then subjected to delayed extraction matrix-assisted laser desorption/ionization time of flight mass spectrometry (DE-MALDI-TOF-MS). Evaluation of the mass spectra was performed by comparing the residue masses of the homologue peak series with the calculated residue masses of potential components of the excipient cationized with Na+ and K+. A number of these series are overlapping because they differ in their theoretical residue masses by about 0.05 Da. The detection of these isobaric interferences was the basic requirement for our analysis method. This goal was achieved by high mass accuracy of the measurements (obtained by internal calibration) in combination with two newly developed evaluation methods, the residue mass plot and the abundance plot. Using this combined technique, generally applicable for complex polymer mixtures, it was shown that the aqueous CCaEx fraction contains hydrophobic components such as di- and triesters of ricinoleic acid and polyethylene glycol as well as glycerol polyoxyethylene di- and triricinoleates, whereas the methanolic fraction contains hydrophilic components, mainly polyethylene glycol (PEG) and glycerol polyoxyethylene ether. Moreover, free PEG was shown to consist of PEG 800 in contrast to the value of 600 Da described so far in literature.

Chromatography, Ion Exchange↗
PubMed2001

Self-assembly of nucleocapsid-like particles from recombinant hepatitis C virus core protein.

Little is known about the assembly pathway and structure of hepatitis C virus (HCV) since insufficient quantities of purified virus are available for detailed biophysical and structural studies. Here, we show that bacterially expressed HCV core proteins can efficiently self-assemble in vitro into nucleocapsid-like particles. These particles have a regular, spherical morphology with a modal distribution of diameters of approximately 60 nm. Self-assembly of nucleocapsid-like particles requires structured RNA molecules. The 124 N-terminal residues of the core protein are sufficient for self-assembly into nucleocapsid-like particles. Inclusion of the carboxy-terminal domain of the core protein modifies the core assembly pathway such that the resultant particles have an irregular outline. However, these particles are similar in size and shape to those assembled from the 124 N-terminal residues of the core protein. These results provide novel opportunities to delineate protein-protein and protein-RNA interactions critical for HCV assembly, to study the molecular details of HCV assembly, and for performing high-throughput screening of assembly inhibitors.

Amino Acid Sequence↗
PubMed2000

[(18F)-2-fluorodeoxyglucose PET. Prospects for secondary prevention of mouth cavity carcinoma].

AIMS: The predominant cause of death due to oral cancer is the failure to control local tumor due to regional tumor recurrence. The sequelae of surgical resection and high-dose irradiation cause substantial changes in head and neck anatomy, leading to considerable problems in the early morphological detection of recurrent disease. Therefore, this study evaluates the verification of cancer recurrence by means of its pathologic glucose metabolism. MATERIALS AND METHODS: We reviewed a total of 50 [18F]-2-fluordeoxyglucose positron emission tomography (18FDG-PET) investigations performed in 44 patients who had undergone surgical resection of oral cancer. In 23 cases, re-staging (group A) was indicated due to suspicion of recurrent or secondary tumor manifestation. In 27 cases, PET served as a screening procedure (group B). Statistic evaluation included sensitivity, specificity, positive/negative predictive value and accuracy of 18FDG-PET for the detection of tumor manifestation. RESULTS: 18FDG-PET correctly identified 23 of 26 tumor sites (88%) in the re-staging group and 9 of 10 tumor sites (90%) in the screening group. We encountered a total number of 16 false-positive foci with an increased 18FDG-uptake. In six patients, 18FDG-PET detected tumor recurrence several months before a morphological correlative could be identified. In 5 of these 6 patients, the PET findings for the latter tumor sites determined the patient's fate. Specificity was 63% for local recurrence, 97% for secondary lymph node involvement and 90% for distant metastasis. CONCLUSION: According to these data, 18FDG-PET is the most effective diagnostic tool in the follow-up of oral cancer patients to date. Due to the high prevalence of recurrent disease in the follow-up of oral cancer, either the detection of early recurrence or the identification of additional, incurable tumors may add substantially to a rational therapeutic management. We therefore recommend 18FDG-PET for screening and re-staging of recurrent oral cancer.

Blood Glucose↗
PubMed2000

3Beta-hydroxy-6-aza-cholestane and related analogues as phosphatidylinositol specific phospholipase C (PI-PLC) inhibitors with antitumor activity.

6-Aza steroid analogues were synthesized as PI-PLC inhibitors. The most active compound, 3beta-hydroxy-6-aza-cholestane (1) showed potent PI-PLC inhibition (IC50 = 1.8 microM), similar to that of the commercially available steroid analogue U73122 (IC50 = 1-2.1 microM). Compound 1 exhibited significant growth inhibition effects (IC50 = 1.3 microM in each case) against MCF-7 and HT-29 cancer cells in in vitro cell culture. Compound 1 also inhibited the in vitro adhesion and transmigration of HT-1080 fibrosarcoma cells at 2.5 and 5.0 microM, respectively. In vivo, compound 1, at 1 mg/kg/day, reduced the volume of MCF-7 tumors in xenograft models, without weight loss in mice. Structure activity relationships of this series of compounds revealed that a hydrophobic cholesteryl side chain, 3beta-hydroxy group and a C-6 nitrogen containing a hydrogen atom at position-6 are crucial for activity. N-Maleic amidoacid derivative 11 also exhibited weak inhibition (IC50 = 16.2 microM).

Animals↗
PubMed1999

[The maxilla--a poor implant site?].

In the maxilla, it is sometimes necessary to use implants to achieve a good prosthetic result. However, an increased failure rate of maxillary implants seems to be a common clinical experience. This experience was investigated in a retrospective statistical analysis. In a retrospective study of 665 patients between 1987 and 1997, 2484 implants were examined. The implants in the upper jaw were compared to those in the lower jaw. Implants with and without autogenous bone grafts and fixtures in patients with alveolar ridge atrophy, tumor, or trauma were explored. In particular, the data obtained from the orthopantomograms after completion of the prosthetic superstructures were controlled for peri-implantary bone loss evaluation. A total of 40% of the fixtures were placed in the maxilla, and 30% of these implants were combined with a local or an iliac bone graft. Out of 2484 implants, 207 were lost, largely during the healing period. The failure rates in the groups of patients with alveolar ridge atrophy, tumor, and trauma were between 6 and 27.5%, and the differences between these groups were higher than the difference between the upper and the lower jaw. Especially in the maxilla and after osteoplasty, horizontal peri-implantary bone loss was increased, with some cases of dramatic bone loss and decrease of the osseous integration of the fixtures. There was no statistic evidence of a significantly higher failure rate in the upper jaw than in the lower jaw. However, besides the rate of implant loss, additional markers should also be considered for adequate evaluation of implant prognosis in the maxilla.

Alveolar Bone Loss↗
PubMed1999

[Changes in the nasal airway by transverse distraction of the maxilla].

OBJECTIVE: To investigate nasal airway changes through transverse maxillary distraction osteogenesis by means of an objective, reliable, noninvasive investigation technique with special attention to nasal valve changes and widening of the posterior maxilla. PATIENTS AND INTERVENTION: Eight patients with a severe maxillary transversal deficit underwent surgically assisted rapid palatal expansion in local or general anesthesia. Before and after the distraction process, a transnasal series of acoustic measurements of nasal airway profile was performed under topical decongestion. Nasal volume was calculated by integration of the area profile. The cross-sectional area of the nasal valve was also determined. RESULTS: A significant enlargement of nasal volume was recorded in all patients (P < 0.01: Wilcoxon signed rank test). The average increase measured 5 cm3 (23%). The increase in volume was recorded in all parts of the nasal cavity, indicating complete maxillary expansion even in the posterior segment. The nasal valve area raised from 0.56 to 0.70 cm2 (P < 0.01). Six out of eight patients reported striking improvement of nasal patency after maxillary distraction. CONCLUSION: Besides correction of the maxillary arch deformity, rapid palatal expansion contributes to improved nasal patency by resolving nasal valve constriction. Significant widening of the posterior nasal cavity was achieved, indicating a translational pattern of maxillary movement, although the pterygomaxillary junction was not touched in the osteotomy.

Adult↗
PubMed1999

[Roentgen spectrometry comparison of currently available bone substitutes].

INTRODUCTION: The crystalline structure of hydroxyapatite (HA) and tricalciumphosphate (TCP) used as bone regeneration materials affects their physical and probably also their biological properties. Varying velocities of the HA solution process seem to be correlated to different results in powder diffraction analysis (RDX) [1], a validated, routine procedure in minerology [2, 6] to analyse crystallized materials. As far we know there are no comparative RDX analyses for the TCP materials in clinical use. GOALS: The dimension and quality of the crystallization of several bone regeneration materials are analysed by RDX. MATERIAL AND METHODS: The materials analysed were divided in different groups: hydroxyapatite, tricalciumphosphate and bioglass. The materials are characterized by the specific intensity curve measurements. RESULTS: The HA products, with the exception of Algipore, seem to be monophasic. Ceros80 and Endobone were the only ones which seem to be totally crystallized. The TCP products Biobase and Cerasorb are nearly monophasic, whereas Ceros82 seems to contain a mixture of 30% HA and 70% beta-TCP. All TCPs show a high crystallization. The bioglasses did--as suspected--not show crystalline structures. DISCUSSION: There are many possible causes for inhomogeneous crystallization of the investigated materials, as they are composites of different foreign ions, extremely small crystals or abnormal (deficient) apatites. How this affects the biological behaviour is not known. SUMMARY: We found differences between the examined materials; how this affects the biological behaviour is unknown. Further investigations are necessary to correlate the characteristics of the materials to the clinical outcome.

Bone Substitutes↗
PubMed1999

[Tissue damage and regeneration after laser surgery using different scanning systems].

INTRODUCTION: Laser systems are frequently used in dentistry. New laser scanner technologies are promising more homogeneous ablation of pathological ablations of the skin and mucosa. The theoretical advantages of these systems have not yet been sufficiently evaluated by histological findings. For this reason, we compared two laser scanners with different scanning patterns in this study (Silktouch and Swiftlase, by Sharplan, Germany). MATERIALS AND METHODS: In this animal study (79 male Osborn-Mendel rats), skin defects of 3-mm diameter were lasered on to the backs of the animals, one for each method mentioned above (defocused laser, Swiftlase, and Silktouch). The histological investigations were conducted, depending on the time after surgery (9 h, 1, 2, 3, 4, 5, 6, 7, 9, 11, or 13 days). On the clinical site, we evaluated the visible ablation rate, homogeneity and morphology of the wound surface and the degree of carbonization. In the histomorphological investigations, we determined the degree of thermal damage as well as the morphology of the necrotic area and reepithelization pattern of the surface. RESULTS: The Silktouch scanner clinically showed a homogeneous ablation rate with less carbonization than the Swiftlase scanner. In the histological specimen, this correlated with an increase in the tissue ablation rate and decreasing thermal damage to the surrounding tissue. Especially in the early wound-healing period, there was a more rapid reepithelization after the use of the Silktouch scanner. These differences could not be evaluated in the later wound-healing period. Compared to the defocused laser ablation, both scanning systems seem to have benefits within these parameters. CONCLUSIONS: The results of this study seem to show a diminished perifocal damage and reduced clinical postoperative morbidity achieved by using laser scanning systems. Compared to the Swiftlase laser, the Silktouch seems to deliver better results.

Animals↗