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H J Schmitz

Publications and source records attributed to H J Schmitz.

At least 19 recordsLinked to original sources
PubMed2003

Efficacy and safety of inhaled recombinant interleukin-2 in high-risk renal cell cancer patients compared with systemic interleukin-2: an outcome study.

Systemic IL-2 is an effective treatment for low to intermediate risk mRCC patients, its efficacy is marginal in high-risk cases. Therefore, other treatment approaches are required for this population. Ninety-four high-risk patients with RCC and pulmonary metastases were treated with inhaled plus concomitant low-dose subcutaneous rhIL-2. Clinical response, survival and safety were compared with those from IL-2 given systemically at the registered dose and schedule in 103 comparable historical controls. In the rhIL-2 INH group, treatment consisted of 6.5 MIU rhIL-2 nebulized 5x/day and 3.3 MIU rhIL-2 SC once daily. The rhIL-2 SYS group received treatment which consisted of intravenous infusion of 18.0 MIU/m2/day rhIL-2 or SC injection of 3.6-18.0 MIU rhIL-2. Some patients in both groups also received IFNalpha. Mean treatment durations were 43 weeks rhIL-2 INH and 15 weeks rhIL-2 SYS. Significantly longer overall survival and progression-free survival durations were observed in the rhIL-2 INH group. The probability of survival at 5 years was 21% for the rhIL-2 INH group. No patients survived 5 years in the rhIL-2 SYS group. A multivariate analysis of overall survival adjusting for differences in baseline characteristics between the two treatment groups resulted in a risk ratio of 0.43 (95% CI 0.30-0.63; P < 0.0001). The data suggested an association between the response (SD or better) and survival, especially in the rhIL-2 INH group. The inhalation regimen was well tolerated. This outcome study suggests that administration of rhIL-2 by inhalation is efficacious and safe in high-risk mRCC patients with pulmonary metastases, who have no other treatment option available.

Administration, Inhalation↗
PubMed2001

Malassezin--A novel agonist of the arylhydrocarbon receptor from the yeast Malassezia furfur.

The yeast Malassezia furfur converts tryptophan into several indole compounds. One of these, malassezin, was identified as 2-(1H-indol-3-ylmethyl)-1H-indole-3-carbaldehyde (1). It was synthesized from N-Boc-indole-3-carbaldehyde in five steps with 12% overall yield. The compound easily cyclizes to indolo[3,2-b]carbazole (7) which is known to interact with the arylhydrocarbon receptor (AHR). Similarly, malassezin was found to induce cytochrome P450 as an agonist of AHR (EC50 = 1.57 microM) in rat hepatocytes.

Animals↗
PubMed2001

Inhibition of apoptosis in rat hepatocytes treated with 'non-dioxin-like' polychlorinated biphenyls.

Polychlorinated biphenyls (PCBs) are among the most prominent persistent environmental pollutants exhibiting neurotoxic, teratogenic and tumour-promoting effects in experimental animals. 'Dioxin-like' properties have been assigned to a number of PCBs whereas other PCBs have been classified as 'non-dioxin-like'. Many of the latter congeners are inducers of cytochrome P450 (CYP) 2B1 and 2B2 similar to the liver tumour promoter phenobarbital. In contrast, 'dioxin-like' PCBs induce CYP1A isozymes, and other congeners have been classified as 'mixed-type' inducers. Inhibition of apoptosis of pre-neoplastic hepatocytes is thought to play a central role in tumour promotion in rat liver. We have used the inhibition of UV-induced apoptosis in rat hepatocytes in primary culture as an in vitro model for mechanistic studies on the inhibition of apoptosis. It could be shown that phenobarbital, and the 'non-dioxin-like' PCBs 28, 101 and 187 completely inhibit UV-induced apoptosis. The concentration-response curves and EC(50) values for this effect, however, were different from those of induction of CYP2B1/2B2-catalysed 7-pentoxyresorufine O-dealkylase or CYP1A-catalysed 7-ethoxyresorufine O-deethylase activities. The PCBs and phenobarbital did not affect the spontaneous incidence of apoptotic nuclei. In conclusion, 'non-dioxin-like' PCBs are likely to promote liver carcinogenesis via the suppression of apoptosis. The signaling events in rat hepatocytes leading to induction of 2B1/2B2 activity by the compounds investigated are assumed to differ from those leading to inhibition of apoptosis.

Animals↗
PubMed2001

Inducing effects of dioxin-like polychlorinated biphenyls on CYP1A in the human hepatoblastoma cell line HepG2, the rat hepatoma cell line H4IIE, and rat primary hepatocytes: comparison of relative potencies.

Polychlorinated biphenyls (PCBs) are a group of widespread environmental pollutants. Some non-ortho-substituted congeners with a high likelihood of coplanarity of both aromatic rings have been shown to act like 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as agonists of the aryl hydrocarbon receptor (AhR) subsequently leading to adverse effects, such as immunosuppression and tumor promotion. Although there is a broad base of experimental data concerning the toxicity of PCBs in laboratory animals and animal-derived primary cells and cell lines, only few experimental data are available for cells of human origin. As a parameter of AhR activation, induction of CYP1A-mediated 7-ethoxyresorufin O-deethylase (EROD) activity was determined in the human hepatoblastoma cell line HepG2 treated with the PCBs IUPAC Nos. 77, 81, 105, 114, 118, 123, 126, 156, 157, 167, 169, and 189, and with TCDD as a positive control. Compared with results in rat primary hepatocytes and the rat hepatoma cell line H4IIE, treated HepG2 cells showed lower specific EROD activities maximally inducible by TCDD and PCBs, and EC50 values were shifted to higher concentrations. Furthermore, relative potency factors (REPs) for some congeners such as PCBs 81, 126, and 169 greatly differed from those observed in cells derived from rats. Northern blot analyses showed that EROD activities run parallel to changes in CYP1A-specific mRNA contents. The considerable differences in EROD-derived REPs between cells of human and rat origin indicate the need for further investigations in experimental models from different species including humans in order to extend the database of biochemical and toxic responses to PCBs.

Animals↗
PubMed1999

Potency of various polycyclic aromatic hydrocarbons as inducers of CYP1A1 in rat hepatocyte cultures.

A number of highly toxic environmental pollutants including certain polychlorinated dibenzo-p-dioxins (PCDD), polychlorinated dibenzofurans (PCDF), and 'dioxin-like' polychlorinated biphenyls (PCB) are among the most potent agonists of the aryl hydrocarbon receptor (AHR). Induction of cytochrome P4501A1 (CYP1A1) in mammalian cell culture is widely used as a functional parameter for AHR activation providing an estimate for 'dioxin-like' inducing equivalents in extracts from environmental samples. Since a number of polycyclic aromatic hydrocarbons (PAHs) also act as AHR-agonists, the CYP1A1-inducing potencies, measured as induction of 7-ethoxyresorufin O-deethylase (EROD) activity in rat hepatocyte cultures were analyzed for 16 PAHs frequently present in environmental samples. Among these, seven PAHs including benzo[a]pyrene were relatively potent inducers allowing the determination of Induction Equivalency Factors (IEF). For three PAHs including benzo[k]fluoranthene which acted as weak inducers, IEFs were estimated, while six PAHs including acenaphthylene were classified as inactive. Based on different efficacies the concentration-response characteristics of CYP1A1 induction were analyzed in more detail for benzo[a]pyrene, benzo[k]fluoranthene, and acenaphthylene. Benzo[k]fluoranthene was markedly less effective than benzo[a]pyrene as inducer of EROD activity but even more effective than benzo[a]pyrene as inducer of CYP1A1 protein and mRNA. Acenaphthylene was highly more effective on the level of mRNA than on the levels of protein or EROD activity. Further analysis revealed that the low efficacy of acenaphthylene as inducer of CYP1A1 protein and EROD activity is due to its marked cytotoxicity while no clear-cut explanation was found for the differences in efficacy between benzo[k]fluoranthene and benzo[a]pyrene. The EROD-inducing potency of a mixture of 16 PAH was about 2-fold higher than that calculated on the basis of IEFs of the individual constituents of the mixture.

Animals↗
PubMed1997

[Animal experiments for testing a hydroxyapatite ceramic coating under vacuum conditions].

Implants that were coated with hydroxyapatite ceramic (H-A.C.) under atmospheric condition in vivo often showed local areas of delamination. By applying the H-A.C. coating using the vacuum plasma spraying (VPS) technique, the mechanical characteristics of the coating was decidedly improved. We used a standardized rabbit model to compare a coating produced by this new technique with an implant conventionally plasma sprayed under atmospheric condition (APS). Cylindrical implants, 6 x 4 mm in size with a region flattened to a depth of 800 microns, were inserted into distal rabbit femurs underneath the patella. The flattened surfaces were coated with either a 150-micron APS-H-A.C. layer or a 150-micron VPS-H-A.C. layer plasma sprayed on an underlying 50-micron porous titanium layer. The animals were killed after 84 or 365 days. After 84 days histomorphologic evaluation revealed that more than 86% of each surface was covered with mature bone, while the VPS-H-A.C. coating demonstrated an almost two times greater tensile strength than the APS-H-A.C. coating. After 365 days both coatings showed a bony coverage of more than 94%. Again the tensile strength testing revealed much higher values for the VPS-H-A.C. coating. This study demonstrates that after 84 days as well as after 365 days in vivo, the VPS-H-A.C. coating had a significantly greater load capacity than an H-A.C. coating applied under atmospheric condition, and an equal affinity for bone.

Animals↗
PubMed1997

Metabolic degradation, inducing potency, and metabolites of fluorinated and chlorinated-fluorinated dibenzodioxins and dibenzofurans.

The metabolic degradation of fluorinated, chlorinated-fluorinated and chlorinated congeners was measured in liver homogenate of NMRI mice. While in the time period between 0 and 240 min no degradation of the 2,3,7,8-TCDD/TCDF could be detected, for all fluorinated congeners a perceptible degradation was found, even for the 2,3,7,8-TFDD. Stepwise chlorination of the 2,3,7,8-fluorinated congeners leads to a decrease of the degradation rate. In the EROD test, the exchange of chloro- with fluorosubstituents in the 2,3,7,8-TCDF leads to a decrease of induction potency. 3,7-Dichloro-2,8-difluorodibenzofuran was about 1/1000th as potent as 2,3,7,8-TCDF, while 2,3,7,8-TFDF was complete inactive. Comparison of the metabolic rates of different TCDD with those of the analogous TFDD demonstrates that the order of enzymatic degradation of different TCDD and the analogous TFDD is identical. The TFDD are degraded slightly faster than the corresponding TCDD. Surprisingly 1,4,6,9-TXDD showed the second slowest metabolic rate of the fluorinated and chlorinated TXDD after 2,3,7,8-TXDD although none of the 2,3,7,8-positions were substituted. Judging from 2,3,7,8-TFDD and 1,7-dichloro-2,8-difluorodibenzofuran the metabolic pathway of fluorinated and chlorinated-fluorinated congeners seem to be comparable to the chlorinated congeners.

Animals↗
PubMed1996

Osteoplastic frontal sinusotomy and extradural microsurgical repair of frontobasal cerebrospinal fluid fistulas.

The choice of the surgical approach and operative technique for the management of cerebrospinal fluid (CSF) fistulas of the anterior cranial fossa are still a controversially discussed topic. Although "extracranial" approaches through the paranasal sinuses are becoming increasingly more popular among otolaryngologists and maxillo-facial surgeons, most neurosurgeons traditionally prefer the "intracranial" repair of CSF fistulas by a craniotomy. We present an approach through the frontal sinus for the repair of dural defects behind the posterior wall of the frontal sinus and at the floor of the anterior cranial fossa. The operative procedure comprises the following main steps: 1) exposure of the anterior wall of the frontal sinus by a bicoronal incision; 2) excision of the anterior wall without frontal burr holes; 3) bilateral removal of the posterior wall of the frontal sinus; 4) extradural inspection of the dura behind the frontal sinus and above the cribriform plate, ethmoidal roof, and orbital roof bilaterally; 5) closure of dural tears by direct suture and a periosteal graft; 6) reinsertion of the anterior wall of the frontal sinus and fixation with titanium micro plates. Twenty-five patients operated upon using this technique are described. The aetiology of the frontobasal lesion was traumatic in 23, and an ethmoid carcinoma in two. In all patients, the dural fistulas were successfully repaired during the initial procedure. One patient died from sudden circulatory arrest after an uneventful postoperative course of nine days. Otherwise, there were no postoperative complications. This technique affords atraumatic extradural inspection and repair of dural fistulas bilaterally behind the frontal sinus, and above the cribriform plate and the ethmoidal and orbital roofs with none or minimal brain retraction. It therefore allows early repair of CSF fistulas also in patients with severe brain injury. Although we consider the extradural closure of fistulas the method of choice, this approach also allows for a combined extradural-intradural procedure, thus enabling the surgeon to treat associated intradural pathologies, such as traumatic lesions or tumours of the frontal cranial base.

Adolescent↗
PubMed1996

Influence of vessel dilatation on restenosis after successful percutaneous transluminal coronary angioplasty.

The aim of this study was to evaluate the influence of vessel dilation on restenosis after successful percutaneous transluminal coronary angioplasty (PTCA) on the basis of quantitative angiographic analysis. To have the best comparison possible, we restrospectively studied a homogenous series of patients from the early 1980s treated according to a standardized PTCA procedure. The study group consisted of 86 patients with stable angina pectoris and single-vessel disease, all of whom underwent successful PTCA for a short concentric lesion in proximal vessel parts. The overall restenosis rate was 27%. Angiographically measured balloon size remained below specifications. The size of the inflated balloon at the site of minimal lumen diameter averaged 2.6 +/- 0.5 mm, and nominal balloon size was 3.3 +/- 0.4 mm (p < 0.001). In 22 patients with an oversized balloon (mean balloon/artery ratio 1.1 +/- 0.16) the restenosis rate was 5% compared with 34% in the corresponding group (p = 0.02). Minimal lumen diameters that were similar after the procedure (2.4 +/- 0.3 vs 2.3 +/- 0.4, NS) were 2.3 +/- 0.4 mm and 1.8 +/- 0.7 mm, respectively, at follow-up (p = 0.002). Multivariate analysis revealed balloon/vessel size ratio (p < 0.001), postprocedure diameter stenosis (p = 0.02), and percentage diameter increase produced by PTCA (p = 0.04) as independent correlates of the late outcome. Postangioplasty minimal lumen diameter was not related to restenosis. The strongest and most significant predictor of late PTCA outcome both by univariate and multivariate analysis was balloon/vessel size ratio, especially when balloon expansion at the site of minimal lumen diameter was regarded. In patients with continued success at follow-up, the ratio was 0.81 +/- 0.15 compared with 0.60 +/- 0.11 in patients with restenosis (p < 0.001). Our results suggest that the late angiographic outcome of PTCA is strongly influenced by procedural factors. It appears that in a selected group of patients, an increased balloon/artery ratio, supposedly associated with increased vessel wall stretch, favorably affects the restenosis process.

Aged↗
PubMed1996

Healing of apical periodontitis in dogs after apicoectomy and retrofilling with various filling materials.

OBJECTIVE: To histologically assess the efficacy of various retrofilling materials in apical surgery. STUDY DESIGN: The pulps of mandibular premolars in seven beagle dogs were infected; this resulted in periapical lesions. Apical surgery was performed without disinfection of the root canals. Super EBA (Harry J. Bosworth Co., Skokie, III.), two formulations of glass ionomer cement, amalgam with varnish, IRM,(Caulk Co., Ltd., Densply International, Milford, Del.) and a light-cured composite resin were the retrofilling materials used. Roots infected and apicoectomized without retrofilling were positive controls. After 6 months the dogs were killed. The experimental roots and surrounding apical tissues were prepared and histologically examined and relative percentages of bone and inflammation were calculated. RESULTS: Super EBA was consistently the best. In overall periapical condition, Super EBA was statistically superior to all materials except IRM. IRM was superior to the glass ionomer cements but not the other materials. As to percentage of bone, Super EBA was the best overall; it was superior to glass ionomer, composite resin, and the positive control but not different from amalgam or IRM. When comparing remaining numbers of inflammatory cells, Super EBA was superior with the lowest number of inflammatory cells present. CONCLUSION: Although not statistically different from IRM, Super EBA was consistently the best retrofilling material tested when compared with all retrofilling materials studied.

Alveolar Process↗
PubMed1995

Potency of mixtures of polychlorinated biphenyls as inducers of dioxin receptor-regulated CYP1A activity in rat hepatocytes and H4IIE cells.

Among the polychlorinated biphenyls (PCBs), a family of widespread environmental pollutants, the most toxic non-ortho-substituted coplanar (non-ortho coplanar) congeners are thought to act as strong dioxin (aryl hydrocarbon) receptor agonists leading to adverse effects, such as body weight loss, immunosuppression, thymic atrophy, hepatotoxicity, tumor promotion, and disturbances of steroid hormone action. Since PCBs are present in environmental and tissue samples as complex mixtures, we investigated the possible interaction of non-ortho coplanar congeners with other major PCBs, which are less active or inactive as dioxin receptor agonists. As a parameter for dioxin receptor activation, induction of CYP1A-catalyzed 7-ethoxyresorufin O-deethylase (EROD) was determined in rat hepatocytes in primary culture and in the rat hepatoma cell line H4IIE. In rat hepatocytes, individual EC50-values and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalency factors (TEFs) for the non-ortho and mono-ortho coplanar PCBs 126, 169, 105, 118 and 156, were in good agreement with published data from in vivo experiments, while in H4IIE cells coincidence was lower. However, in both cell systems TEFs for PCB 77 were significantly higher than reported from experiments in rats. In an approximately equipotent mixture the six potent PCB congeners showed perfect additive behaviour in both cell systems. In contrast, addition of a tenfold surplus of abundant mono- and di-ortho PCBs (28, 52, 101, 138, 153 and 180) led to an almost threefold higher TEF than predicted. This finding suggests a moderate synergistic enhancement of the inducing potency of potent PCBs by less potent congeners, present in abundance in environmental and tissue samples.

Animals↗
PubMed1995

Polyfluorinated dibenzodioxins and dibenzofurans--synthesis, analysis, formation and toxicology.

The 75 congeners of the polyfluorinated dibenzodioxins (PFDDs) and about half of the 135 polyfluorinated dibenzofurans (PFDFs) have been synthesized by pyrolysis of fluorophenols and fluorobenzenes. The individual congeners were characterized by GC/MS. 2,3,7,8-TFDD was also characterized by 1H-, 13C- and 19F-NMR spectroscopy. The retention behaviour of PFDDs and PFDFs during gaschromatographic separation is entirely different from that of PCDDs/PCDFs or PBDDs/PBDFs. The PFDDs/PFDFs elute earlier than the PCDDs/PCDFs and the order of the elution is not governed by the degree of substitution, O8FDD eluting e.g. much earlier than the M1FDDs. A preliminary toxicological evaluation of 2,3,7,8-TFDD was carried out. The elimination of 2,3,7,8-TFDD from mice after a single i.p. injection is biphasic with a very rapid elimination half-life of 5 minutes and a slower phase of 165 minutes. This means a dramatically reduced half-life compared to 2,3,7,8-TCDD with 8.5 d. In liver the TFDD level reaches a maximum 30 minutes after injection and also declined in a biphasic manner. In rat hepatocytes a primary culture induction of CYP4501A1-catalyzed EROD activity could be demonstrated, indicating that 2,3,7,8-TFDD activates the dioxin receptor. In rat hepatocyte cultures similar EC50 values were found for 2,3,7,8-TCDD and 2,3,7,8-TFDD. So far no de novo synthesis of PFDD/PFDF could be detected under conditions were PCDDs/PCDFs are formed. Also, formation of PFDDs/PFDFs could not be detected during thermal treatment of fluorotrichloromethane or Teflon.

Animals↗
PubMed1995

Treatment of exposed implant threads using a synthetic bone graft.

The aim of this study was to evaluate clinically and histologically the use of a synthetic bone graft (Ionogran) alone and in combination with guided bone regeneration (GBR) to facilitate bone regeneration and augmentation around exposed implant threads. Five male Beagle dogs were used in this investigation. Prior to the study all 3rd and 4th premolars were extracted. After 3 months, a flap was elevated and two Brånemark implants were inserted in each quadrant in such a way that two-three threads remained exposed over the alveolar bone. On the control sites the synthetic bone graft was then placed around the exposed threads and the flaps were repositioned and sutured. On the test sites, the same procedure was performed, but an expanded polytetrafluoroethylene barrier was placed to cover the bone graft and implants. Three months after implant placement, the barriers on the test sites were removed, healing abutments were inserted on all implants, and a thrice weekly plaque control regime was initiated. The following clinical parameters were measured at 1, 2, and 3 months: Plaque Index, Gingival Index, Probing Depth and Clinical Attachment Level. Three months after abutment connection the animals were killed and specimens were obtained for histological evaluation. Clinical parameters revealed a significant improvement on the experimental sites compared to control sites during the 3 month loading phase. Histological analyses, however, could not determine a difference in the nature of the implant/tissue interphase between experimental and control sites.

Aluminum Silicates↗
PubMed1994

Cytogenetic findings in squamous cell carcinoma of the oral cavity.

A case of squamous cell carcinoma (SCC) of the oral cavity is presented which, in addition to normal metaphases, cytogenetically displayed two cell clones with chromosomal aberrations: 46,XY,1+del(5)(q13),der(18)t(5;18)(q13;p11),-5 and 49,XY,+5,+7,+10 After a review of the literature of the few cytogenetically analyzed cases, the findings confirm the multiclonal origin of oral SCC and also the commonly seen aberrations of chromosome 5.

Aged↗
PubMed1994

Bone augmentation using a synthetic bone graft in dogs.

The aim of this investigation was to evaluate clinically and histologically the use of a synthetic bone graft (Ionogran) alone and in combination with guided bone regeneration (GBR) for alveolar ridge augmentation. Five beagle dogs were used in this study. Prior to the augmentation procedure the maxillary and mandibular second, third and fourth premolars were extracted. Three months after the extractions, impressions from the area of the ridges were taken. Particles of Ionogran were then placed under mucoperiosteal flaps in each quadrant. On the experimental sites, an expanded polytetrafluoroethylene barrier was placed between the flap and the particles. Impressions were retaken at 1 and 3 months after surgery. Three months after surgery, the animals were sacrificed and specimens were prepared for histological evaluation. Computer-assisted volumetric analyses from the casts revealed an increase in ridge volume from baseline in both groups at 1 and 3 months. There was no difference in the height of the augmentation between the test and control sites. The histological results of this study indicate that this new synthetic bone graft appears to be a safe biocompatible grafting material. There were no apparent histological differences between the graft alone and graft/GBR sites. In both groups, however, graft particles were surrounded by dense fibrous connective tissue and bone formation was limited to the graft bone interface.

Aluminum Silicates↗
PubMed1993

[Titanium implant as an alternative possibility in fusion of the cervical vertebrae--initial clinical experiences].

We report on our experience with the use of titanium for disc replacement in the cervical spine. In 52 patients a total of 55 titanium grafts were implanted. Follow-up examinations were available in 48 patients with an observation time of 14 month on average. Results of clinical-neurological examinations were excellent or good in 37 patients (77%), moderate in 9 cases (19%), while two patients (4%) showed poor outcome. Radiological follow-up examinations showed a correct position in 47 of the 48 patients. Incorrect position as observed in 1 case made operative revision necessary. According to our results, titanium grafts seem to be a useful alternative method as compared to conventional techniques of fusion. Essential advantages are simple handling, biocompatibility of the material as well as the solid bond achieved by the special qualities of the graft with respect to surface and form. Availability of different graft sizes allows tailored fusion.

Adult↗