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Biomedical subjects

M Winter

Publications and source records attributed to M Winter.

At least 73 records · Page 4Linked to original sources

Antibodies to factor XII associated with lupus anticoagulant.

Falsely low levels of factor XII (FXII) have been documented in patients who are lupus anticoagulant positive (LA+). In addition, we have previously noted a surprisingly high incidence (20.9%) of apparently true FXII deficiency in patients who were LA+. We have hypothesised that this may be partly due to the presence of antibodies to FXII. The aim of the present study was to investigate whether LA+ patient plasmas contain antibodies directed either against FXII or FXII in association with phospholipids. Plasma samples from 60 blood donors, all LA negative, and 51 LA+ patients were tested using ELISA assays employing purified FXII, phosphatidylserine (PS) and phosphatidylethanolamine (PE). We have identified seven patients whose plasma contained either IgG or IgM that reacted with purified FXII in the absence of PS or PE. When PS was included in the assay system four additional patient plasmas were shown to contain either IgG or IgM that reacted with FXII. The plasma of one patient contained IgG that reacted with FXII both in the presence and absence of PS. There was no reactivity to FXII with either IgG or IgM when PE was included in the assay system. Affinity purified IgG from three patients whose plasma reacted with FXII in the ELISA assay in the absence of PS, gave a positive reaction in an immunoblot assay. These results suggest that FXII antibodies are present in a significant proportion of LA+ patients and may lead to an erroneous diagnosis of FXII deficiency.

Antibody Specificity↗

[Depth of lamellar keratoplasty with the guided trephine system for transplantation of full-thickness donor sections].

BACKGROUND: Despite the fact that deep lamellar keratoplasty (DLKP) is less invasive than to penetrating keratoplasty (PKP), this procedure is rarely performed. We therefore investigated whether or not the DLKP technique we employed can achieve stable improvement of visual acuity. MATERIALS AND METHODS: Thirty-three eyes underwent TLKP for treatment of superficial corneal pathology. The donor tissue transplanted was suitable for PKP. The donor lenticule was obtained on the artificial chamber of the guided trephine system (GTS). The recipient cornea was trephined with the same trephine to a depth of 680 microns. Manual dissection was performed with a bevel-up blade. The donor lenticule with the endothelium peeled off was then sutured in with a 10 x 0 nylon double-running antitorque suture. Cortisone-antibiotic eye drops were administered postoperatively. RESULTS: Throughout the series no complications occurred. The mean best corrected visual acuity (BSCVA) over glasses was 0.29 (+/- 0.21) preoperatively, 0.1 (+/- 0.11) at 1 week, 0.33 (+/- 0.14) at 1 month, 0.5 (+/- 0.13) at 6 months, 0.61 (+/- 0.16) at 1 year and 0.63 (+/- 0.15) at 2 years. Clinically, we observed two subpopulations. In the first group of 87% of the cases, mean BSCVA was 0.67 (+/- 0.07) at 6 months. The remaining cases (BSCVA < or = 0.25 at 6 months) achieved a mean BSCVA of only 0.2 (+/- 0.04) at 1 year. Mean corneal astigmatism measured 2.93 D (+/- 1.62) preoperatively, 2.69 D (+/- 1.18) at 1 month, 2.09 D (+/- 1.07) at 1 year, and 2.22 D (+/- 1.11) at 2 years. We did not observe any graft rejection. CONCLUSION: The technique reported for DLKP provides excellent matching of donor lenticule and recipient bed. Separation of donor and recipient stroma prevents interface healing. DLKP appears to be a safe procedure for the surgical treatment of superficial corneal pathology and may offer a clinically applicable alternative to PKP.

Adolescent↗

Scanning electron microscopic findings on intraocular metallic foreign bodies.

BACKGROUND: The study reported here was performed to investigate morphologic intraocular reactions on the surface of metallic intraocular foreign bodies (IOFB) with scanning electron microscopy. METHODS: Twenty-seven extracted IOFB were investigated. Of these, 22 were situated in the vitreous body; 19 had contact with the retina. Five IOFB had been removed from the anterior segment (control group). The duration of intraocular retention was 6 h to 24 days. Immediately after microsurgical removal the IOFB were fixed, dehydrated, dried, sputter-coated and investigated with a scanning electron microscope. Two IOFB from the vitreous were treated for collagen preservation. RESULTS: Eighteen of 20 intravitreal IOFB showed fibers of fibrin on its surface; 11 of 20 were covered with a homogeneous layer. Within this layer a net of collagen fibers was detectable. A major cellular reaction was observed only on IOFB that injured the retina, pigment epithelium and choroid. CONCLUSIONS: This morphologic study shows that: (1) a fibrin net develops in the vitreous around intravitreal IOFB; (2) depositions of amorphous material into the spaces of this net lead to dense coverage of the IOFB; (3) cellular reactions are not condition for the development of this coverage; (4) laceration of the retina induces a fibrocellular response.

Adolescent↗

Antigastric autoantibodies and gastric secretory function in Helicobacter pylori-infected patients with duodenal ulcer and non-ulcer dyspepsia.

BACKGROUND: Autoantibodies against epitopes located at the canaliculi of human parietal cells occur in about 30% of Helicobacter pylori-infected patients. This has led to the hypothesis that gastric secretory function could be inhibited by anticanalicular autoantibodies in H. pylori gastritis. METHODS: Forty-four H. pylori-infected patients with and without duodenal ulcers were screened for anticanalicular autoantibodies by means of immunohistochemistry. Plasma gastrin levels and basal and maximal gastric acid output were determined. RESULTS: Fasting gastrin levels were significantly increased in the group with anticanalicular autoantibodies. In the group of patients with non-ulcer dyspepsia the presence of anticanalicular autoantibodies was significantly correlated with an impaired basal acid secretion. CONCLUSIONS: Antigastric autoimmunity in H. pylori gastritis seems to be relevant for gastric hyposecretion either directly by inhibiting the proton pump or indirectly through the development of gastric mucosa atrophy.

Adult↗

An automated chromogenic peptide substrate assay for coagulation factor XII.

We have developed an automated chromogenic peptide substrate assay for factor XII (FXIIcs) on a Cobas Mira S Plus clinical chemistry analyser using a new commercially available kit. This was used to determine factor XII (FXII) levels in plasma samples from 320 blood donors, 206 patients with a history of venous thrombosis and 74 lupus anticoagulant positive (LA+) patients. Results were compared with those obtained in a clotting assay for FXII (FXIIct) and an immunochemical assay (FXIIag). A satisfactory correlation coefficient of 0.92 and a regression line equation of y = 7.898 + 0.871x was obtained between FXIIcs and FXIIct in the 320 blood donors. Levels of FXII below the calculated normal range were found in nine blood donors (2.8%) and 16 venous thrombosis patients (7.8%). The blood donors and patients with venous thrombosis with low FXIIcs values had FXII levels below our lower limits of normal for both FXIIct and FXIIag; all were lupus anticoagulant negative. When FXII levels were determined in the 74 LA+ patients, 27 (36.5%) gave markedly lower FXII values in the FXIIct when compared with the FXIIcs. FXIIag levels corresponded with FXIIcs. The automated FXIIcs assay is therefore lupus anticoagulant insensitive and allows us to measure FXII levels accurately and routinely in large numbers of patient samples.

Autoanalysis↗

Transient deafness due to temperature-sensitive auditory neuropathy.

OBJECTIVE: To define mechanisms accounting for transient deafness in three children (two siblings, ages 3 and 6, and an unrelated child, age 15) when they become febrile. DESIGN: Audiometric tests (pure-tone audiometry, speech and sentence comprehension), tympanometry, middle ear muscle reflex thresholds, otoacoustic emissions (OAEs), and electrophysiological methods (auditory brain stem responses [ABRs], sensory evoked potentials, peripheral nerve conduction velocities) were used to test the children when they were afebrile and febrile. RESULTS: ABRs, when afebrile, were abnormal with a profound delay of the IV-V and absence of waves I-III. The ABR in one of the children, tested when febrile, showed no ABR components. Measures of cochlear receptor function using OAEs were normal in both febrile and afebrile states. Cochlear microphonic potentials were present in the three children, and a summating potential was likely present in two. When afebrile, there was a mild threshold elevation for all frequencies in the 15-yr-old and a mild elevation of thresholds for just low frequencies in the two siblings. Speech comprehension in quiet was normal but impaired in noise. One of the siblings tested when febrile had a profound elevation (>80 dB) of pure-tone thresholds and speech comprehension was absent. Acoustic reflexes subserving middle ear muscles and olivocochlear bundle were absent when febrile and when afebrile. No other peripheral or cranial nerve abnormalities were found in any of the children. Sensory nerve action potentials from median nerve in one of the children showed no abnormalities on warming of the hand to 39 degrees C. CONCLUSION: These children have an auditory neuropathy manifested by a disorder of auditory nerve function in the presence of normal cochlear outer hair cell functions. They develop a conduction block of the auditory nerves when their core body temperature rises due, most likely, to a demyelinating disorder of the auditory nerve. The auditory neuropathy in the two affected siblings is likely to be inherited as a recessive disorder.

Acoustic Impedance Tests↗

Factor XII determinations in the presence and absence of phospholipid antibodies.

Factor XII (FXII) levels were determined in plasma samples from 29 normal donors, 10 patients with inherited FXII deficiency (all lupus anticoagulant [LA] negative) and 67 LA positive patients, using clotting (FXIIct), chromogenic substrate (FXIIcs) and immunochemical (FXIIag) assays. Excellent correlations were obtained in the three FXII assays with the LA negative samples and between the FXIIcs and FXIIag assays in the LA positive samples. Correlations between both the FXIIcs and FXIIag with FXIIct in the LA positive patients were poor. Of 67 LA positive samples studied, 25 (37.3%) showed lower values in the FXIIct assay; 13 (19.4%) of these patients were pseudo FXII deficient with values of FXII below the lower limit of normal. These results indicate that a diagnosis of FXII deficiency can be made inappropriately in the presence of phospholipid antibodies and that such a diagnosis should not be made by FXIIct assay alone.

Antibodies, Antiphospholipid↗

CD8+,CD38+ lymphocyte percent: a useful immunological marker for monitoring HIV-1-infected patients.

We investigated the relationship between three prognostic markers, CD4 lymphocyte count, serum beta2-microglobulin (beta2M) levels, and CD8+,CD38+ lymphocyte percent, and the association with the rate of development of AIDS. The markers were measured regularly throughout follow-up in 224 patients. The risk of developing AIDS during follow-up was investigated using Cox proportional hazards models. Time-updated values of the prognostic markers were used, which modelled the risk of AIDS according to the latest measurement of the marker rather than using a single value of the marker at baseline. During a median follow-up period of 13.6 months (range 0.5-31.9 months), 34 cases of AIDS occurred. In a univariate analysis, all three markers predicted the development of AIDS; a 10% increase in the percentage of CD8+ T cells expressing CD38+ resulted in an 88% increase in the risk of AIDS (95% confidence interval: 53-130%; p < 0.0001). After adjustment for the current CD4 count and beta2M, a 10% increase in the CD8+,CD38+ population was associated with a 37% increase in the risk of AIDS (95% confidence interval: 4-81%; p = 0.02). Thus, the percentage CD8+,CD38+ level predicts the development of AIDS independently of the latest CD4 count and beta2M. This assay is therefore potentially useful in conjunction with blood CD4 counts and serum beta2M levels in patient management and clinical trial design.

ADP-ribosyl Cyclase↗

Preclinical safety assessment of the recombinant TNF receptor-immunoglobulin fusion protein.

The tumor necrosis factor (TNF) is now recognized as one of the most pleiotropic mediators of host defense, immune regulation, and inflammatory response. Due to its broad spectrum of effects, TNF has been implicated as a key mediator in the pathogenesis of acute and chronic inflammatory conditions. The inhibition of bioactive TNF could therefore provide a substantial therapeutic benefit. One approach to a potent TNF antagonist is to use recombinant protein technology in the design of a molecule in which the heavy-chain sequences of an immunoglobulin are fused with the ligand-binding region of the TNF receptor. This paper describes some aspects of the preclinical safety evaluation of the recombinant human TNF receptor-immunoglobulin fusion protein (TENEFUSE). Specific emphasis was placed on transgenic and gene-deleted mice models as central sources of information in the safety evaluation of this TNF antagonist.

Animals↗

[Radiologic performance in night and emergency care].

This report deals with radiologic examinations outside official working hours in a German university hospital and the influence of new government regulations. A total of 65,113 radiologic examinations were requested and performed outside official working hours between 1 July 1990 and 30 Juni 1994. The data were analyzed according to the age and sex of this patient population compared with the entire population studied within this 4-year period. Further analysis included the time of the study, the organ systems investigated, and the radiologic technique. About one-third of requests occurred between 16.00 and 20.00 hours on normal working days and, thus, could be taken care of by late shifts. Another third covers the time between 20.00 and 08.00 hours in the morning, which requires inhouse staff (medical and technical). The remainder of the requests occurred during holidays and weekends in the daytime. The most common request in this analysis was for portable chest examination. About 50% of all portable chest examinations were performed outside regular working hours. In all, 17.2% of all requests involved CT and MRT studies. Government regulation did not change the number, technique, and frequency of radiologic examinations outside official working hours.

Adolescent↗

[Pharmacologic intolerance reaction after intravenous injection of pethidine].

We report on anaphylactoid reactions (urticae at the injection site and along the injection vein) after intravenous injections of pethidine in two patients. Skin tests with pethidine were negative, but intravenous challenge showed urticae. These results indicate that the reactions were due to a non-immunological mechanism resembling pharmacological intolerance. Retrospective analysis revealed a 5.6% incidence of pharmacological intolerance reactions to intravenous pethidine in 519 patients.

Adjuvants, Anesthesia↗

Impaired motor cortex inhibition in patients with amyotrophic lateral sclerosis. Evidence from paired transcranial magnetic stimulation.

We investigated 14 patients with amyotrophic lateral sclerosis (ALS) by paired conditioning-test transcranial magnetic stimulation to test the hypothesis that the motor cortex is hyperexcitable in ALS. Intracortical (corticocortical) inhibition was significantly less in the ALS group than in an age-matched healthy control group (85.3 +/- 27.0% versus 45.2 +/- 15.5%, respectively; p < 0.0001). In contrast, intracortical facilitation, motor threshold, and cortical silent period duration in the ALS patients were not different from the control group. We suggest that the selective abnormality of intracortical inhibition is best compatible with an impaired function of inhibitory interneuronal circuits in the motor cortex that in turn renders the corticomotoneuron hyperexcitable.

Aged↗

[ORBIT-NET. Discussion forum on orbitology on the internet].

INTRODUCTION: A basic service in the public network "Internet" is electronic mail (e-mail). E-mail makes the participation in discussion groups possible by mailing contributions to the discussion to all members electronically. To complement the existing list of ophthalmologic discussion groups ORBIT-NET was introduced. It offers experts in research, clinic, diagnostic and therapy of orbital diseases the opportunity to make queries or present interesting casuistries and to ask for comments, differential diagnosis or advice on therapy. Other participants can be made aware of new scientific results, actual publications or meetings. MATERIAL AND METHODS: For participation a computer, a modem, an Internet-Provider and special software are required. Registration is made either by e-mail or regular mail. A verification is necessary to limit the list of participants to experts. RESULTS: Since the introduction of ORBIT-NET on November 9th, 1996, there have been no technical problems. ORBIT-NET has been effective as a platform. CONCLUSIONS: The international, interdisciplinary platform ORBIT-NET is an addition to the existing ophthalmologic discussion groups. ORBIT-NET offers orbitologists an international discussion of results and diagnosis, supports further training and can give encouragement to further research.

Computer Communication Networks↗