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Biomedical subjects

M Wyss

Publications and source records attributed to M Wyss.

At least 55 records · Page 3Linked to original sources

Lymphomatoid papulosis--treatment with recombinant interferon alfa-2a and etretinate.

Lymphomatoid papulosis is a rare cutaneous lymphoproliferative disorder with nodular, papulonecrotic or plaque-like lesions. Although it is clinically benign, the histology shows large, atypical lymphoid cells that display antigenic markers of activated T-helper lymphocytes and express CD30. There is a close relationship to Hodgkin's disease and to Ki-1-positive anaplastic large-cell lymphoma of the skin. For therapy, various modalities such as PUVA, steroids and acyclovir have been used. We report on a patient with a 10-year history of disease. Treatment with interferon alfa-2a, 3 MU 3 times/week for 4 weeks, and etretinate, 50 mg/day for 5 months, was initially successful, but lesions further relapsed 5 months after cessation of the therapy.

Adult↗

Right atrial thrombosis associated with central venous catheters in children with cancer.

Right atrial thrombosis (RAT) is infrequently diagnosed in children with cancer. Once RAT is documented, medical fibrinolysis or surgical thrombectomy is recommended. A RAT was documented in a child with lymphoma and was successfully lysed with recombinant tissue-type plasminogen activator. The case is presented and therapeutic options reviewed.

Antineoplastic Agents↗

Hypersensitivity to molybdenum as a possible trigger of ANA-negative systemic lupus erythematosus.

After implantation of two metal plates a 24 year old woman developed fever of unknown origin and successively more symptoms of an ANA-negative systemic lupus erythematosus (SLE). These symptoms resolved after removal of the plates and recurred during patch testing of the metal components, which showed a reaction to molybdenum. A lymphocyte transformation test indicated a delayed-type hypersensitivity to molybdenum. Subsequent progressive flare ups of SLE appeared without molybdenum reexposure. This is the first report suggesting the existence of a hypersensitivity to molybdenum, which may act as another environmental trigger for SLE.

Adult↗

Limited proteolysis of creatine kinase. Implications for three-dimensional structure and for conformational substrates.

Proteinase K, subtilisin, pronase E, elastase, bactotrypsin, and thermolysin are all shown here to cleave native mitochondrial creatine kinase from chicken heart (Mib-CK) very specifically at a single site, either before or after Ala-323. In analogy with hen egg ovalbumin, where the same proteases all cleaved the polypeptide chain very specifically around Ala-352, Ala-323 of Mib-CK may be located in an exposed surface loop that is sensitive to protease attack. Gel permeation chromatography demonstrated that the two proteolytic fragments of Mib-CK with M(r)'s of approximately 37,000 and approximately 6000 remain associated with each other. Proteinase K cleavage did not influence the octamer to dimer ratio of Mib-CK, indicating that selective cleavage after Ala-323 has no direct effect on dimer-dimer interfaces within the octamer. However, upon addition of MgADP plus creatine and nitrate to induce a transition-state analogue complex of the enzyme, native Mib-CK dissociated much more readily into dimers than proteinase K-digested Mib-CK. Furthermore, proteinase K cleavage of Mib-CK resulted in 2-11-fold decreases in the Vmax values, as well as in 6-23-fold increases in the Km values for phosphocreatine, creatine, and MgATP, whereas the Kd values for both MgATP and creatine were unaffected. Consequently, proteinase K cleavage of Mib-CK does not affect substrate binding per se, but interferes with substrate-induced conformational changes which are essential for catalysis and which mediate the synergism in substrate binding as it is observed with the unmodified enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Selective labelling and inactivation of creatine kinase isoenzymes by the thyroid hormone derivative N-bromoacetyl-3,3',5-tri-iodo-L-thyronine.

Besides their well-known regulation of transcription by binding to nuclear receptors, thyroid hormones have been suggested to have direct effects on mitochondria. In a previous study, incubation of rat heart mitochondria with 125I-labelled N-bromoacetyl-3,3',5-tri-iodo-L-thyronine (BrAcT3), a thyroid hormone derivative with an alkylating side chain, resulted in the selective labelling of a protein doublet around M(r) 45,000 on SDS/polyacrylamide gels [Rasmussen, Köhrle, Rokos and Hesch (1989) FEBS Lett. 255, 385-390]. Now, this protein doublet has been identified as mitochondrial creatine kinase (Mi-CK). Immunoblotting experiments with the cytoplasmic and mitochondrial fractions of rat heart, brain and liver, as well as inactivation studies with the purified chicken CK isoenzymes have further demonstrated that all four CK isoenzymes (Mia-, Mib-, M- and B-CK) are indeed selectively labelled by BrAcT3. However, in contrast with their bromoalkyl derivatives, thyroid hormones themselves did not compete for CK labelling, suggesting that not the thyroid hormone moiety but rather the bromoacetyl-driven alkylation of the highly reactive 'essential' thiol group of CK accounts for this selective labelling. Therefore the assumption that CK isoenzymes are thyroid-hormone-binding proteins has to be dismissed. Instead, bromoacetyl-based reagents may allow a very specific covalent modification and inactivation of CK isoenzymes in vitro and in vivo.

Affinity Labels↗

[Latex allergy--an increasing problem in clinical practice].

In the last few years the allergenic potential of rubber has been receiving more and more attention. Its widespread application in medical devices and everyday objects has increased exposure to this allergen. The central role of rubber in the prevention of HIV infection has certainly played a part in this development. Latex allergy manifests itself as immediate type allergy (type I), delayed type allergy (type IV) or as a combination of both types of hypersensitivity. In this review the different types of latex allergy are illustrated by means of selected case reports. Immediate type allergy to latex leads to contact urticaria, but it may also cause generalized urticaria, bronchial asthma or even anaphylactic reactions (contact urticaria syndrome). Hence, not only dermatologists and allergologists are confronted with latex allergy. Immediate type hypersensitivity can be proven by skin prick test and RAST (radio allergosorbent test). Contact dermatitis in patients using rubber gloves is generally due to delayed type hypersensitivity to rubber additives. However, a recently observed case suggests the possibility of isolated delayed type hypersensitivity to natural latex.

Adolescent↗

The Zurich Study. XVIII. Obsessive-compulsive disorders and syndromes in the general population.

The cross-sectional and longitudinal association between obsessive-compulsive syndrome (OCS) and other psychiatric problems and the course over 11 years was examined in a Swiss cohort of young adults. As the prevalence of obsessive-compulsive disorders, defined according to the DSM-III was very low (n = 5), we applied a lower diagnostic threshold based on obsessive-compulsive symptoms and social impairment, to define an OCS. The weighted lifetime prevalence rate for OCS at age 30 years was 5.5%. The mean age of onset was 17.1 +/- 4.9 years for males, and 19.1 +/- 5.1 year for females. OCS was associated with all subtypes of depressive disorders as well as with social phobia and agoraphobia. Although the longitudinal analysis showed no stability at the diagnostical level, there was some stability on the symptom level. Perhaps subjects with OCS learned in time to cope and to live with their symptoms without suffering.

Adaptation, Psychological↗

Immunotherapy with aluminum hydroxide adsorbed insect venom extracts (Alutard SQ): immunologic and clinical results of a prospective study over 3 years.

This prospective study over 3 years investigated the safety, immunogenicity, and effectiveness of immunotherapy (IT) with aluminum hydroxide adsorbed insect venom extracts (Alutard SQ, ALK Laboratories) in patients with previous, severe, systemic, IgE-mediated, anaphylactic reactions to Hymenoptera stings. Seventeen patients were treated with honeybee venom (BV), 13 with yellow-jacket venom (YJV), and 5 with both. No severe reactions to IT were noted. Only 3 BV-allergic patients experienced mild systemic reactions of grades I or II (1 per 139 injections) during the increase phase. As for the immunologic data, there was a significant decrease in specific IgE antibodies after 1 year, and a significant increase in specific IgG and IgG4 antibodies on reaching the maintenance dose, with a further rise after 1, 2, and 3 years. Moreover, a significant decrease in anti-IgE autoantibodies was observed in the BV group. Out of the 11 patients that were occasionally restung by the relevant insect (totaling 19 stings in all), only one patient developed mild systemic allergic symptoms after a third sting. In view of these results, we consider IT with aluminum hydroxide adsorbed insect venom extracts to be safe, immunogenic, and effective. The low rate of side-effects may be due to the slow release of the venom in the aluminum hydroxide adsorbed form.

Adolescent↗

Allergic contact dermatitis from natural latex without contact urticaria.

During the last decade, there have been many reports of immediate-type hypersensitivity to natural latex, resulting in contact urticaria, generalized allergic reactions such as urticaria and Quincke's edema, and asthmatic or anaphylactic reactions. Moreover, delayed-type hypersensitivity to rubber additives such as thiuram and carbamate derivatives is acknowledged to be the main cause of dermatitis in patients working with rubber gloves. We here report on a patient who developed severe dermatitis on his hands and forearms 3 months after he had started working with rubber gloves. Patch tests with rubber additives, skin prick tests and RAST to natural latex were negative. However, a delayed type of hypersensitivity to latex could be shown by a positive patch test. To our knowledge this is the 1st case reported of an isolated contact dermatitis from natural latex without contact urticaria to latex or hypersensitivity to rubber additives. We therefore propose that not only patch tests with rubber additives, but also skin prick and patch tests with latex should be performed in contact dermatitis patients working with rubber gloves.

Adult↗

Conditioning the leukemic patient before allogeneic BMT: value of intensifying immunosuppression in the context of different levels of T lymphocyte depletion of the graft.

We have studied the value of additional immune suppression in BMT conditioning regimens in 45 patients with leukemia and 4 with myelodysplastic syndrome allografted between 1984 and 1991. A dose of 6 Gy total lymphoid irradiation (TLI) was delivered to 12 of 24 and 15 of 25 patients conditioned with 10 Gy and 12 Gy total body irradiation (TBI), respectively. Thirteen patients also received methylprednisolone (MP) before BMT to enhance immunosuppression. Differences in immunosuppression between the TBI with or without TLI or MP regimens and the influence of different levels of graft T cell depletion were measured in terms of transplant rejection, and complete versus mixed chimerism. The treatment-related complications were evaluated in terms of GVHD and incidence of pneumonitis. The overall transplant rejection rate was 6% (3 of 49). Complete chimerism was not significantly modified by increasing the TBI dose or by additional TLI (p > 0.10) but was more often seen in patients receiving MP given as pre-transplant immunosuppressor booster (p = 0.01). The incidence of GVHD was only influenced by the level of T cell depletion (p = 0.003). All 49 patients received a TBI lung dose in the range 9.5-10 Gy. A crude pneumonitis range of 19% (9 of 47 evaluable patients) was found. Neither the addition of TLI, MP nor the T cell depletion influenced the lung toxicity rate (p > 0.10) but pneumonitis was more frequent in patients with GVHD (p = 0.005).

Adolescent↗

Adoptive immunotherapy for recurrent CML after BMT.

Three patients with CML who relapsed after transplantation with T-depleted BM from their HLA-identical siblings were treated with transfusions of donor peripheral blood mononuclear cells, in combination with (short) IFN alpha 2 therapy. CML was successfully controlled as shown by the complete disappearance of Philadelphia-positive metaphases within 90 days of treatment. This treatment appears to be very effective as neither bcr-abl transcripts nor markers specific for hematological cells of recipient origin could be detected by very sensitive PCR techniques. Two patients treated in chronic phase are without evidence of disease 300 and 360 days after treatment. The third patient, treated in accelerated phase, died with BM aplasia, 39 days following PBMC infusions. Failure to detect residual donor-derived granulocytes, as was the case in this patient prior to initiating adoptive immunotherapy, may indicate loss of donor-derived BM activity. This may help predict and possibly prevent the occurrence of life-threatening aplasia after successful clearance of malignant hematopoiesis.

Acute Disease↗

[Swiss Register for unrelated bone marrow donors: preliminary results].

Bone marrow transplantation from the unrelated volunteer donor is today a realistic possibility for patients lacking an HLA-identical family donor. In 1988, the Swiss Unrelated Bone Marrow Donor Registry was founded to coordinate such bone marrow transplants and create the Swiss volunteer donor registry. Thus for a search has been initiated for 71 patients and 16 transplants have been performed. Donor and recipient were HLA-A-, -B- identical by serology and HLA-Dr-identical by DNA-oligotyping. 10 of the 16 patients are alive without signs of basic disease 2 weeks to 2 years and 4 months after the transplant. These results illustrate that unrelated donor transplantation, using careful selection criteria, is a realistic new therapeutic modality.

Adolescent↗

Recombinant human erythropoietin in the treatment of infants with anaemia of prematurity.

Recombinant human erythropoietin (rHuEPO) was administered subcutaneously three times a week to 18 infants with the anaemia of prematurity at doses of 75, 150, 300, or 600 units/kg per week for 4 weeks, starting at 3-4 weeks of postnatal age. A significant and dose-dependent increase in reticulocyte count was observed from a mean baseline value of 71 x 10(9)/l to 200 x 10(9)/l after 3 weeks of therapy, compared with a change from 69 to 97 x 10(9)/l in 66 historical controls. The haematocrit value remained unchanged during rHuEPO treatment, whereas it steadily declined until 9 weeks of postnatal age in the controls. These effects were accompanied by a marked reduction in serum iron concentration and transferrin saturation in patients receiving standard-dose iron supplements, but not in those given larger doses. Only 3 of 18 patients required a red blood cell transfusion. These infants were among the most anaemic at entry into the study and 2 of them were unable to complete rHuEPO therapy, while the third developed iron deficiency anaemia. These data indicate that rHuEPO with appropriate iron supplementation may accelerate the recovery from anaemia of prematurity. Larger scale placebo-controlled studies are now needed to confirm these findings and verify their impact on transfusion requirements of premature infants.

Anemia, Neonatal↗

Comparison of totally implanted and external catheters in paediatric oncology patients.

From June 1982 until December 1989, 93 permanent central venous catheters [59 external catheters (ECs) and 34 implanted catheters (ICs)] were placed in 69 patients. The median age of these patients at placement was 5.6 years for ECs and 8.8 years for ICs (P less than 0.05). Follow-up evaluation was possible on 86 catheters (58 ECs and 28 ICs). The median time of insertion was 236 days and 316 days for ECs and ICs, respectively (P less than 0.05). The median number of open days was 58 for ECs and 66 for ICs (not significant). 17 catheters (6 ECs and 11 ICs) were transiently obstructed (P less than 0.005). 30 episodes of bacteraemia were documented in 20 patients. The incidence of catheter sepsis and bacteraemia of unknown source was one in 278 and 283 open days for ECs and ICs, respectively (not significant). In this retrospective study, ECs appeared to be as safe as ICs when infection was correlated with use of the catheter, but this finding should be confirmed in a randomised design.

Bacteremia↗