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Biomedical subjects

F Hoffmann

Publications and source records attributed to F Hoffmann.

At least 73 records · Page 4Linked to original sources
PubMed1995

Delay in corneal allograft rejection due to anti-CD4 antibody given alone and in combination with cyclosporin A and leflunomide.

Anti-CD4 monoclonal antibodies (mAbs) have been shown to inhibit in vitro T-cell activation and proliferation to both antigens and mitogens. Animals studies have demonstrated the immunosuppressive potency of anti-CD4 mAbs given in vivo for therapy of autoimmune disease and following allografting. Similarly, leflunomide (LF), a new potent immunosuppressive, has been shown to be effective in preventing autoimmune disorders and reactions leading to organ transplant rejection. LF is thought to antagonize cytokine activity, thereby interfering with T-helper-cell-dependent B- and T-lymphocyte proliferation. A new anti-CD4 antibody (RIB 5/2) was investigated alone and in combination with cyclosporin A (CsA) and LF for the treatment of corneal allograft rejection in the rat. Corneal buttons were grafted from Lewis/Brown Norway rats to Lewis recipients. Animals were randomly assigned to the following treatment groups: (1) untreated; (2) CsA at 1.5 mg/kg; (3) RIB 5/2 at 2.5 mg/kg; (4) RIB 5/2 at 2.5 mg/kg and CsA at 1.5 mg/kg; (5) RIB 5/2 at 2.5 mg/kg, CsA at 1.5 mg/kg and LF at 10 mg/kg; (6) RIB 5/2 at 4 mg/kg; (7) RIB 5/2 at 4 mg/kg and CsA at 1.5 mg/kg; and (8) RIB 5/2 at 4 mg/kg, CsA at 1.5 mg/kg, and LF at 10 mg/kg. RIB 5/2 was given intraperitoneally at 24 h before surgery, on the day of grafting, and on postoperative day 1 and was continued every 2nd day until the rat had received ten doses in all (postoperative day 15).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Hydrolase participation in allograft rejection in rat penetrating keratoplasty.

BACKGROUND: A rat model of orthotopic corneal graft rejection was used to investigate the alterations in hydrolase activity within the corneal graft or within cellular infiltrates during acute rejection. METHODS: The distribution of the lysosomal enzymes [acid phosphatase (AP), N-acetyl-beta-D-glucosaminidase (NAG), beta-glucuronidase (beta-Gluc), beta-galactosidase (beta-Gal), dipeptidylpeptidase II (DPPII)] and of the membrane-bound proteases [aminopeptidase M (APM), aminopeptidase A (APA), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), dipeptidylpeptidase IV (DP-PIV)] were investigated by histochemical methods in the grafts at 3, 5, 8, 10 and 12 days following allogeneic transplantation. Serial sections of the grafts were also examined for RT1b, CD4, CD4+, CD8, CD11b/c and CD45, in order to determine hydrolase activity within infiltrating cells. RESULTS: Allogeneic grafts were invaded by macrophages, CD4- and CD8-positive lymphocytes. In contrast, syngeneic grafts, performed as a control, contained occasional lymphocytes and focal aggregations of macrophages around suture sites. The allogeneic cellular infiltrate stained intensely for AP and ALP; moderately for beta-Gluc, NAG and beta-Gal; and mildly for GGT, DPPII and APM in grafts at all postoperative times. Serial sectioning indicated that the majority of the lysosomal hydrolases were located in macrophages; AP, APM and GGT were, however, observed in lymphocytes. Vessel ingrowth could be observed with enzyme staining for AP, beta-Gluc, NAG, ALP, APA and APM. Hydrolase activity in the corneal endothelium served as an indicator of endothelial function during the rejection process. CONCLUSION: Changes in normal hydrolase activities in corneal grafts in the rat model indicate decreasing corneal function during the rejection process. Hydrolases released from infiltrating cells contribute to the morphological disruption and, possibly, to graft rejection.

Animals↗
PubMed1994

Leflunomide therapy following penetrating keratoplasty in the rat.

BACKGROUND: The isoxal derivative, leflunomide (LF), is a new potent immunosuppressive which has been shown to be effective in preventing autoimmune disorders and reactions leading to organ transplantation rejection. LF is thought to antagonise cytokine activity and thereby to interfere with T-helper-cell-dependent B- and T-lymphocyte proliferation. METHODS: We used LF to treat corneal allograft rejection in the rat, comparing its effect with that of cyclosporin A (CSA). Corneal buttons were grafted from Lewis/Brown Norway rats to Lewis recipients. Animals were randomly assigned to the following treatment groups: I, untreated; II, CSA (10 mg/kg i.m.); III, LF (2.5 mg/kg p.o.); IV, LF (5 mg/kg p.o.); V, LF (10 mg/kg p.o.); VI, combined therapy (LF 10 mg/kg p.o. and CSA 10 mg/kg i.m). Treatment began on the first postoperative day and was continued until rejection occurred. RESULTS: The mean graft rejection time in the untreated allogeneic group was 12 days. A significant delay in graft rejection was observed in all treatment groups compared with group I (P < 0.001). Further, the delay in graft rejection resulting from combined therapy (group VI) was statistically significant compared with all other groups (P < 0.001). CONCLUSION: These results suggest that (a) LF when used alone is as effective as CSA in treating corneal allograft rejection in the rat, and (b) when LF and CSA are combined they are more effective than either drug alone in the prolongation of allograft survival.

Administration, Oral↗
PubMed1994

[Ginkgo extract EGb 761 (tenobin)/HAES versus naftidrofuryl (Dusodril)/HAES. A randomized study of therapy of sudden deafness].

80 patients with idiopathic sudden hearing loss existing no longer than 10 days were included in a randomised reference-controlled study. The therapeutic value of Ginkgo EGb 761 (Tebonin) + HAES was compared to that of Naftidrofuryl (Dusodril)+HAES. The main mechanisms of action of EGb 761 are a vasoregulating activity (increased blood flow), the platelet activating factor antagonism and a prevention of membrane damage caused by free radicals. Naftidrofuryl has antiserotonergic and therefore vasodilatory properties. The statistical analysis of the audiometric data was performed in measuring the relative hearing gain as described by Eibach 1979. After one week of observation, 40% of the patients in each group showed a complete remission of hearing loss. This was also observed by other authors who had compared other drugs. Therefore, in these cases, it is most likely that spontaneous recovery is the most important factor. After two and three weeks of observation, measuring the relative hearing gain, there was a significant borderline benefit of EGb 761 (p = 0.06) without any side effects. Some patients of the reference group developed side effects such as orthostatic dysregulation or headache or sleep disturbances. Minimising side effects should be one of the most important goals in therapy of sudden hearing loss until the efficiency of infusion therapy is proved.

Adult↗
PubMed1994

Interleukin-2 receptor--targeted therapy by monoclonal antibodies in the rat corneal graft.

A possible selective therapeutic approach to corneal graft rejection will aim at IL-2 receptor-bearing antigen-activated T-lymphocytes with monoclonal anti IL-2R antibodies. In a rat penetrating keratoplasty model (Lewis x Lewis-BN) comparing to controls (median, 8 days), a significant delay of the allograft reaction was achieved by applying a therapeutic dose (15 mg/kg bw) of cyclosporin A (median, 18 days; p < 0.01), an intraperitoneal (1.0 mg/kg bw) (median, 13.5 days; p < 0.05) or a subconjunctival injection of IL-2R mab (0.5 mg/kg bw ART-18) (median, 16 days; p < 0.01) with low-dose Cyclosporin A (1.5 mg/kg bw). In pharmacokinetic experiments, the corneal radioactivity 24 h after intraperitoneal injection of 125I-labeled ART-18 was < 1% (p < 0.01) of the values obtained by subconjunctival injection, whereas the serum radioactivity values (p > 0.05) were in the same range. The above results suggest that the onset of an allograft reaction in perforating keratoplasty seems to depend on the locally achievable antibody concentration and can be delayed with a high level of IL-2 R mab present in the immediate surrounding of the foreign antigen-expressing cells.

Animals↗
PubMed1994

Immunohistochemistry study of the glaucomatous and normal human trabecular meshwork.

Although class II-expressing cells have been reported previously in the human trabecular meshwork (HTM), the exact identity of these cells and their possible role in the normal and the pathological state remains unclear. Preliminary results suggest increased human leucocyte antigen (HLA)-DR expression in the glaucomatous TM. To investigate this possibility, 20 trabeculectomy specimens obtained from patients with primary open-angle glaucoma (POAG) were examined immunohistochemically for HLA-DR, leucocyte common antigen (LCA; CD45) and a macrophage marker (CD68). The patients varied in age from 42 to 86 years (average, 69 years). The degree of antibody staining in the TM was compared with that of 20 human control eyes obtained from an eye bank less than 24 h after death. The donors varied in age from 47 to 91 years (average, 69 years); there was no known history of eye disease amongst the control group. Evaluation of specimen was performed by two observers using a grading system ranging from negative (0) to strongly positive (3) and by computer-aided optic densitometry. HLA-DR-positive cells were present in both the normal and the glaucomatous TM. Occasional cells stained for LCA and CD68 in the TM of both groups. Subpopulations of the HLA-DR-staining cells were apparent on serial sectioning. An age effect on antigen staining was not observed; postmortem delay of greater than 48 h resulted in decreased specimen antigenicity. Both evaluation techniques failed to reveal a significant difference in HLA-DR, LCA or CD68 staining between the glaucomatous and the normal TM.

Adult↗
PubMed1994

HLA-B and -DR match reduces the allograft reaction after keratoplasty.

Since 1983, corneal grafts have been routinely obtained from multiorgan donors and allocated to the patient with the greatest HLA compatibility. At follow-ups in 248 primarily clear corneal grafts, grouping according to the HLA mismatch rate revealed that the incidence of allograft reactions did not differ significantly for HLA-A but certainly did for HLA-B (P < 0.01) and, in patients with a poor prognosis, for HLA-DR as well (P < 0.05). Grouping the patients according to the mismatch rate of the total of four HLA-B and -DR antigens disclosed the incidence of allograft reactions to be markedly increased by a mismatch of more than two antigens (P < 0.05). The relative risk of an allograft reaction is increased by factors of 5.1 in patients with a good prognosis and 5.5 in those with a poor prognosis. The adverse influence of a postoperative inflammation on the occurrence of an allograft reaction as seen in nonmatched donor material is no longer present in matched donor material if the prognosis is good and no longer significant if it is poor (P < 0.09). The inflammation-promoted expression of HLA antigens is of less importance for graft survival if the difference in the HLA antigens is reduced by the match.

Cornea↗
PubMed1993

[Spontaneous dislocation of a silicone disk lens 4 months postoperative into the vitreous body].

We report on a patient who experienced an acute deterioration in visual acuity at night four months after implantation of a silicon-disc lens into the capsular bag. On examination, the artificial lens was localized preretinally. The capsular equator was fibrous, but had retained its circular shape. The posterior capsule was ruptured. The rupture may be explained by tension in the posterior capsule, which is only 1-4 microns thick, within the shrunken capsular bag, and by an acute increase of intraocular pressure caused by rubbing of the eyes during sleep.

Aged↗
PubMed1993

Mechanical methods in refractive corneal surgery.

Keratorefractive surgery has developed rapidly over the past decade. For patients with aphakia, however, posterior chamber lenses are safer and more predictable than refractive corneal surgery; myopia is the greatest challenge to this type of surgery. No technique as yet has an accuracy that is adequate for the general treatment of myopia. Keratotomy is the most common procedure currently performed for the correction of mild myopia and astigmatism. Results are less accurate and less stable with myopic than with aphakic epikeratoplasty. Although it is technically more difficult, keratomileusis seems to be more predictable than epikeratophakia. Nonfreeze lamellar corneal surgery accelerates wound healing. Synthetic lenses and ring-shaped implants are also being developed to modify corneal refraction. Current research is directed toward laser stromal keratomileusis on discs that are removed from the cornea using a microkeratome.

Corneal Stroma↗
PubMed1993

Increased hydrolase activities in the human trabecular meshwork of glaucomatous eyes.

Alterations in the metabolic functions of trabecular meshwork (TM) cells are thought to be involved in the pathogenesis of primary open-angle glaucoma (POAG). In an investigation of this possibility, 30 trabeculectomy specimens from patients with POAG were examined histochemically for 11 lysosomal and membrane-bound enzymes. The patients ranged from 48 to 87 years in age. The degree of enzyme staining was compared with that of 15 age-matched controls obtained from an eye bank at less than 24 h after death. There was no history of eye disease in the controls. The enzymes examined were: dipeptidylpeptidases II and IV (DPPII and IV); beta-glucuronidase (beta-GLUC); acid-beta-galactosidase (s beta-GAL); N-acetyl-beta-D-glucosaminidase (NAG); nonspecific esterase (UE); acid phosphatase (SP); alkaline phosphatase (ALP); gamma-glutamyltransferase (GGT); and aminopeptidase A and M (APA and APM). Evaluation of the specimens was performed by two observers and by computer-aided optic densitometry. Results showed increased staining of SP, UE, GGT and APM in the pathological specimens as compared with the controls. SP and UE indicate phagocytic activity, APM is involved in collagen turnover and GGT participates in both drug detoxification and the breakdown of glutathione in the gamma-glutamyl cycle. Our observations show different hydrolase activities in the TM cells of human glaucomatous eyes as compared with normal values, suggesting that such metabolic differences may be related to the pathogenesis of POAG.

Aged↗
PubMed1993

Comparison of corneal lenticules produced for keratokyphosis and keratophakia.

Apart from the original freezing technique, there are three non-freeze keratomileusis procedures, in which the cornea is first deformed before a tissue lens is severed from the side. Two measuring procedures were used to measure corneal lamellae separated from pig eyes by means of the microkeratome. The following parameters were determined: the size of the severed lamellae, given as the two diameters in the feed direction of the microkeratome and perpendicular to it, and the profiles of the axial sections of these lamellae as determined by means of the universal measuring microscope (UMM). Both measuring procedures had a precision of +/- 3 microns. The results obtained with different blade types were compared, and an optimized blade was developed. The corneal lamellae separated parallel to the surface using the optimized blade were of higher quality than those cut with the Barraquer microkeratome. The variation coefficient was 0.9% for the Berlin microkeratome and 6.0% for the Barraquer microkeratome. The profile studies demonstrated that rotationally symmetrical tissue sections can be obtained with the Berlin microkeratome. The lens-shaped tissue sections separated from pig cornea showed an undercorrection. Further studies are needed to determine whether a higher refraction precision can be achieved in lamellae cut from human donor cornea.

Animals↗
PubMed1993

[Subablative gentamycin therapy in Menière's disease].

We have treated 20 patients suffering from unilateral Morbus Meniere (2 x 12 mg gentamicin for 7 days). These patients were controlled for 24 months. In 95% we regarded a complete or substantial control of definitive spells ("American Committee on Hearing and Equilibrium guidelines for reporting treatment results in Meniere's disease", Otolaryngol. Head and Neck Surg. 10/19-85). Only 1 patient with pretherapeutic equal caloric response showed a post-therapeutic destroyed vestibular apparatus on the treated ear. In the other 7 patients (35%), who had a loss of vestibular function after therapy, there was an already pretherapeutic more or less noticeable caloric hypoexcitability. It is possible to induce an only subablative damage with a clinical success in 95%.

Audiometry, Pure-Tone↗
PubMed1992

Acetylcholinesterase. Two types of modifications confer resistance to insecticide.

Quantitative and qualitative changes in acetylcholinesterase confer resistance to insecticides. We have constructed several Drosophila melanogaster strains producing various amounts of enzyme by P-mediated transformation. Toxicological analysis of these strains demonstrates that resistance to organophosphorus insecticides is correlated with the amount of acetylcholinesterase in the central nervous system. Resistance may also be qualitatively determined. Comparison of the Drosophila acetylcholinesterase gene between a resistant strain caught in the wild and a wild type susceptible strain only revealed one nucleotide transition resulting in the replacement of a phenylalanine by a tyrosine. Flies mutant for acetylcholinesterase and rescued with a minigene mutagenized for this same transition produced an altered enzyme which renders flies resistant to pesticides.

Acetylcholinesterase↗
PubMed1992

Minigene rescues acetylcholinesterase lethal mutations in Drosophila melanogaster.

The gene encoding acetylcholinesterase in Drosophila melanogaster is over 34,000 base-pairs long. We have constructed a 5800 base-pair minigene containing 1500 base-pairs of genomic sequence upstream from the transcription start spliced to the coding sequence, but lacking the nine introns. After germline genetic transformation, this minigene rescues acetylcholinesterase lethal mutants. Tissue-specific distribution appears normal. This allows us to test site-directed mutations of acetylcholinesterase. In a first effort, deletion of most of the unusual 1000 bases leader and its intriguing short open reading frames showed no effect on gene expression. The way is open to study in vivo the structure-function relationships of acetylcholinesterase and insecticide resistance.

Acetylcholinesterase↗
PubMed1992

Prediction of phenotype for acetylation and for debrisoquine hydroxylation by DNA-tests in healthy human volunteers.

The debrisoquine/sparteine-type polymorphism of drug oxidation and the polymorphism for acetylation are two common inherited variations in human drug metabolism. The phenotypes for hydroxylation and acetylation can be predicted be newly developed methods based on mutation-specific amplification of DNA by the polymerase chain reaction (PCR), which also allow for identification of heterozygous carriers of one mutant allele. In the present study, the results of genotyping of 81 healthy European volunteers were compared with the phenotype obtained by the classical biochemical approach using debrisoquine and caffeine as probe drugs. Genotyping correctly predicted all 73 extensive metabolisers (EMs) and 6 out of 8 poor metabolisers (PMs) of debrisoquine. All 48 rapid acetylators and 33 of 35 slow acetylators were predicted. Overall, the DNA analysis result matched the in vivo phenotype in 97.5% of individuals.

Acetylation↗
PubMed1992

[Capsulorhexis using an ultrasound-controlled cannula].

Every cataract surgeon performing phacoemulsification has unintentionally damaged the posterior capsule. Thus he knows that the device is suitable for cutting the lens capsule. In recent years, I have performed various modifications of capsulorhexis with the aid of an ultrasound-guided cannula in all patients undergoing phacoemulsification. The following method proved to be practicable: The ultrasound-guided cannula is pressed on the lens capsule at 12 o'clock, thus opening the anterior capsule; the cannula is consecutively guided in two semicircular movements from 12 o'clock to 6 o'clock, and the anterior capsula is torn and cut open by directing the opening of the cannula toward the center of the pupil and simultaneously on the anterior capsula and away from the iris, thus making it possible to cut directly at the pupillary margin without damaging the iris. The anterior capsular tear has a smooth circular edge at the intersection of the two semicircles of the capsulorhexis, while a triangular flap directed towards the center of the pupil is often formed at 12 o'clock. At the end of phacoemulsification, the flap is aspirated with the suction rinsing device and cut off with a sharp cannula. This procedure simplifies and accelerates phacoemulsification.

Cataract Extraction↗
PubMed1991

[The development of methods for the objective assessment of occlusal parameters].

For reasons of different data in literature on occlusal parameters and their metric registration, at the beginning of the 80's two methods independent of each other were developed--the capacity measuring method and the quasiplanimetry method to register the total occlusal contact area and the number of occlusal surfaces of contact at dental casts. The results obtained independently from each other showed a high degree of correspondence. That's why the method of quasiplanimetry was further developed and used for the direct analysis of enorally obtained wafers of different characteristic. The method is improved now with a modern system of digital analysis. The results obtained up to now admit the conclusion that the occlusion of the teeth represents an individual condition of high variability. With the reproducible method used individual occlusal parameters can be numerically registered.

Dental Occlusion↗