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Biomedical subjects

N Haas

Publications and source records attributed to N Haas.

At least 73 records · Page 4Linked to original sources

Enhanced P-selectin expression in chronic and dermographic urticaria.

In both chronic and dermographic urticaria, superficial perivascular leukocytic infiltrations are seen histologically in lesional skin. We have therefore investigated the role of endothelial adhesion molecule expression in these diseases. E-selectin, P-selectin, ICAM-1 and VCAM-1 expression was examined immunohistologically, and the serum levels of the soluble forms of these adhesion molecules were determined by EIA in patients with chronic urticaria, dermographic urticaria as well as in healthy controls (n = 8 in each group) and subjects with symptomatic allergic rhinitis (n = 7) for comparison. A significant increase (p<0.01) was observed for soluble P-selectin in dermographic urticaria (mean 487+/-44 ng/ml) and chronic urticaria (mean 464+/-74 ng/ml) compared to healthy controls (mean 149+/-15 ng/ml) and rhinitis subjects (mean 177+/-30 ng/ml). In contrast, the other adhesion molecules were not significantly elevated in both urticaria groups. Immunohistologically, a strong expression of P-selectin was found in superficial vessels of lesional and nonlesional skin in dermographic urticaria with only a mild increase of the other adhesion molecules studied, supporting the findings observed with the soluble forms in the patients' sera. Since an alteration of soluble P-selectin was not seen in symptomatic allergic rhinitis, an unspecific effect due to inflammation appears to be unlikely. These results therefore point to a potentially relevant role of the endothelial P-selectin expression in the evolution of urticarial whealing.

Case-Control Studies↗

Fastest reduction of posttraumatic edema: continuous cryotherapy or intermittent impulse compression?

Sixty patients with foot or ankle trauma were randomized and treated in three groups. In intermittent impulse compression, an air pad under the foot was inflated every 20 seconds, thus activating the venous foot pump. In continuous cryotherapy, ice water circulates between the ice box and the cold pad. The ice water was changed once per day. In standard therapy, the injured extremity was treated with cool packs, which were changed 4 times per day. Beginning at admission, every 24 hours the circumference was measured around the ankle, midfoot, and forefoot. After 24 hours of treatment, there was a 47% reduction in swelling with the A-V impulse System, 33% with continuous cryotherapy, and 17% with cool packs. After 4 days of postoperative treatment, the A-V impulse System reduced the swelling by 74% versus 70% with continuous cryotherapy and 45% with cool packs. Both new methods are preferable to cool packs. Because of the better preoperative results, the A-V impulse System proved to be the most effective device.

Adult↗

Phase II trial of 96-hour paclitaxel plus oral estramustine phosphate in metastatic hormone-refractory prostate cancer.

PURPOSE: To evaluate the antitumor activity of 96-hour paclitaxel and daily oral estramustine phosphate (EMP) in patients with metastatic hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: Thirty-four patients with adenocarcinoma of the prostate that progressed after one or more hormonal therapies and a trial of antiandrogen withdrawal were enrolled onto this phase II trial. Patients received paclitaxel 120 mg/m2 by 96-hour intravenous (i.v.) infusion on days 1 through 4 of each 21-day cycle, together with daily oral EMP 600 mg/m2/d, continuously. RESULTS: Four of nine patients with measurable disease had objective responses (one complete response [CR] and three partial responses [PRs]) in liver (two patients) or nodes (two patients) of 2, 6, 8, and 20 months' duration. Of 25 assessable patients with metastases limited to bone, 14 had a > or = 50% decline in pretreatment prostate-specific antigen (PSA) level sustained for at least 6 weeks and seven had a > or = 80% decline. Overall, 17 of 32 patients (53.1%) with elevated pretreatment PSA levels had a > or = 50% decline of PSA and nine (28.1%) had a > or = 80% decrease. The main toxicities (> or = grade 2) were nausea, fluid retention, and fatigue, which occurred in 33%, 33%, and 24.2% of patients. Median time to progression, based on increasing PSA level and other clinical criteria, was 22.5 weeks. The estimated median overall survival time is 69 weeks. CONCLUSION: The combination of EMP and 96-hour paclitaxel is an active regimen for patients with HRPC. These results further support the therapeutic strategy of combining agents that impair microtubule function by complementary mechanisms.

Adenocarcinoma↗

Immunopathological events of adverse cutaneous reactions to coumarin and heparin.

We here describe a female patient with thromboembolic disease, who exhibited allergic reactions to heparin and who developed a large necrotic area on the abdomen when coumarin treatment was instituted. On immunohistology of the necrotic lesion, tumour necrosis factor alpha was markedly expressed, with decreasing intensity towards the central necrotic part of the lesion. Furthermore, endothelial cell adhesion molecule expression was upregulated, particularly in the haemorrhagic zone at the periphery of the lesion. These findings suggest that the pathology of coumarin necrosis is mediated via tumour necrosis factor alpha-associated inflammatory events, after activation of the coagulation pathway due to an inherited or transiently induced, acquired protein C-deficiency. In view of these findings, we propose that patients be treated in the future with tumour necrosis factor alpha antagonists such as pentoxifylline.

Coumarins↗

Clinical experiences with magnetic drug targeting: a phase I study with 4'-epidoxorubicin in 14 patients with advanced solid tumors.

Anticancer drugs reversibly bound to magnetic fluids (ferrofluids) could be concentrated in locally advanced tumors by magnetic fields that are arranged at the tumor surface outside of the organism. If certain requirements are met, systemic toxicity might be minimized, and local tumor efficacy might be increased. We have conducted a Phase I clinical trial using this approach in patients with advanced and unsuccessfully pretreated cancers or sarcomas. Nine such patients received two treatment courses, 3 patients received one course, and 2 patients received three courses of magnetic drug targeting consisting of the infusion of epirubicin in increasing doses (from 5 to 100 mg/m2) that had been chemically bound to a magnetic fluid and the application of magnetic fields to the tumors for 60-120 min. In 2 of 14 patients, the same dose of epirubicin not bound to a magnetic fluid was administered systemically 3 weeks after drug targeting for intraindividual comparisons. Magnetic drug targeting with epirubicin was well tolerated. In one case, a planned second treatment was withdrawn, because of an episode of chills 130 min after infusion of the magnetic drug. Two patients received a third treatment because of good responses after the first two therapies. Based on magnetic resonance tomographic techniques, pharmacokinetics, and the histological detection of magnetites, it was shown that the ferrofluid could be successfully directed to the tumors in about one-half of the patients. Organ toxicity did not increase with the treatment, but epirubicin-associated toxicity appeared at doses greater than 50 mg/m2. Although treatment with magnetic drug targeting seems safe, improvements are necessary to make it more effective and independent of patient- or disease-related problems. A study design to compare conventional treatments with the new treatment form within one patient seems crucial to eliminate interindividual differences.

Adolescent↗

[Value of dental treatment in interdisciplinary management of a child with epidermolysis bullosa dystrophica hereditaria (Hallopeau-Siemens)].

Severe dystrophic epidermolysis bullosa with oral involvement often leads to dental destruction and restricted food intake, resulting in malnutrition and maldevelopment. The patients become handicapped and have a poor prognosis. We report on a now 13-year-old Turkish child with normal secondary dentition who had severely damaged primary dentition. The teeth were treated surgically and then by continuous dental hygiene measures over the next 7 years. This care also resulted in an improvement in the nutritional state, associated anemia and the incidence of skin infections. Although cutaneous blistering and scarring has been progressive, with resulting mutilation of the fingers, the child is socially well adjusted in school and family. Its clinical course demonstrates that the fate of patients with severe dystrophic epidermolysis bullosa can be improved through multidisciplinary management.

Adolescent↗

[Plasmapheresis and immunopathogenetic aspects of toxic epidermal necrolysis].

Drug-induced toxic epidermal necrolysis (TEN) is a rare but frequently lethal disease of the skin and mucosa of unknown etiology. Toxic metabolic and immunologic products in the serum have been discussed as possible causes. For this reason we have performed plasmapheresis on these patients for many years. Results regarding survival and healing of the lesions are quite favorable, as exemplified with two patients described here who benefited from the procedure despite their old age. In order to gain insight into possible disease mechanisms that would explain the beneficial effect of plasmapheresis, we did immunohistochemical studies on these patients before and in one case after the procedure. In dermis and epidermis, there was a striking increase of macrophages and a relative increase of CD8-positive lymphocytes which might act as cytotoxic effector cells; these findings can be interpreted as the result of an immunological reaction. An increased staining of lesional epidermis with TNF alpha, as previously noted by other authors, should be interpreted with caution since necrotic cells are involved. On the basis of the clinical results, the pathogenetic considerations, and in view of the lack of specific treatment modalities, clinical studies concerning plasmapheresis for the treatment of toxic epidermal necrolysis are recommended, particularly since this procedure is widely available and generally well tolerated.

Aged↗

MHC class II antigen expression is increased in different forms of urticaria.

Urticarial reactions encompass a variety of inflammatory and immunological reactions. In order to clarify specific aspects of these processes, we analyzed the distribution and sequential expression of major histocompatibility complex II (MHC class II) molecules in tissue sections from different types of whealing reactions. Using immunohistochemical techniques and monoclonal antibodies, expression of HLA-DR, HLA-DP, and HLA-DQ was examined on resident and infiltrating cells in different skin cell compartments, comparing early with longer-lasting wheals and lesional with uninvolved skin. Sequential biopsies were studied in cold urticaria (CU). No increase of MHC class II molecule expression was found in early prick test wheals to common inhalant allergens. In CU, however, sequential biopsies demonstrated an up-regulation of MHC class II molecules within 30 min after elicitation. This was more pronounced in longer-lasting urticaria lesions of acute, chronic recurrent and delayed pressure urticaria, with HLA-DR and, to a lesser degree, HLA-DP and HLA-DQ being noted on cell infiltrates, on vascular endothelia and around nerves and sweat glands. Nonelesional skin in these types of urticaria also showed increased MHC class II expression. Longer-lasting urticarial wheals are thus associated with up-regulation of MHC class II molecules on resident and infiltrating cells, suggesting an involvement of these molecules in the pathomechanisms of these types of urticarial lesions.

Acute Disease↗

Neutrophil respiratory burst in term and preterm neonates without signs of infection and in those with increased levels of C-reactive protein.

Developmental immaturities in neonatal host defense predispose the neonates to an increased mortality rate during bacterial infections. Early diagnosis is of great clinical importance, but, especially in neonates, is sometimes very difficult. The ability to generate reactive oxygen species, the so-called respiratory burst, is essential for neutrophils to kill infectious microorganisms. Therefore, changes of respiratory burst may reflect increased susceptibility of neonates to infections and may be useful for the early detection of infections. Superoxide anion production was determined by a flow cytometric method using dihydrorhodamine 123 (DHR) as an oxidative probe after priming of neutrophils with PBS buffer (spontaneous burst), with N-formyl-methionyl-leucyl-phenylalanine (fMLP), or with Escherichia coli. During the study period, the spontaneous percentage of activated cells in whole blood as well as the percentage of activated cells in stimulation with fMLP was lower in adults (n = 100; PBS, 1.0 +/- 0.1%; fMLP, 8.3 +/- 0.9%) compared with neonates without signs of infection (n = 143). Among the latter, the percentage of activated cells (PBS and fMLP assay) varied with respect to gestational age and hours of life: lowest values were measured in preterm newborns with gestational age less than 32 wk and between 25 and 120 h of life. The same correlation to gestational age was true for total neutrophil cell counts. In neonates with increased levels of C-reactive protein during the first 5 d of life (n = 43), the percentages of activated cells after PBS and fMLP incubation were higher than those of neonates without signs of infection. The relationship of neutrophil respiratory burst and neutrophil cell counts to gestational age might reflect at least in part a reason for the increased susceptibility of neonates to infections. Furthermore, determination of respiratory burst may prove to be a new laboratory parameter of neonatal infection.

Adult↗

Psychiatric comorbidity: prevalence in methadone maintenance treatment.

This study examines prevalence rates for DSM-III-R anxiety and affective disorders in three follow-up samples of opioid addicts who were treated with methadone maintenance. At least one anxiety disorder was diagnosed in 55% of the total sample. Affective disorders were found in 58%. At least one anxiety disorder coexisted with at least one affective disorder in 36% of the sample. The research demonstrates that opiate addiction in this sample is most often associated with other comorbid psychopathology. It suggests a need for thorough assessment for general psychopathology in opioid addicts entering addiction treatment, especially assessment for anxiety and affective disorders. It also suggests the need for treatment that focuses on diagnosed mental disorders in addition to drug counseling for the substance abuse disorder.

Adult↗

Clinical experience with two types of pelvic C-clamps for unstable pelvic ring injuries.

The emergency stabilization of unstable pelvic injuries, in particular, injuries to the posterior pelvic ring, can be achieved following reduction by application of the pelvic C-clamp. This and other procedures contribute to controlling what is almost always a life-threatening blood loss. The pelvic C-clamp is a temporary measure preceding definitive treatment of the injury. If this procedure is to have an optimal and lasting effect, the clamp must be applied correctly, provide adequate compression and stability, and be easy to handle. In one year, we applied the AO and ACE pelvic clamps in 9 clinical cases. Satisfactory primary compression and stability were achieved for unstable injuries with both clamps. It was more difficult to achieve good rotational stability as required for subsequent treatment with the ACE clamp due to its construction design.

External Fixators↗

[Intermittent impulse compression. An alternative in therapy of post-traumatic and postoperative edema].

In patients with foot and ankle trauma, surgery and postoperative mobilization are often delayed because of swelling. The aim of this study was to assess if intermittent impulse compression of the foot is better than the standard therapy of applying cool packs at intervals. For intermittent impulse compression the AV impulse device was used (Novamedix Inc.). From May to November 1993, 40 patients (20 ankle fractures, 8 ruptured ligaments, 6 calcaneal fractures, 4 distal tibial fractures, 1 talus fracture, 1 subtalar dislocation) were prospectively assigned at random to the two groups and treated. After 24 h of treatment, the patients with intermittent impulse compression of the foot showed an average reduction of swelling of 47% around the ankle, midfoot and forefoot. With cryotherapy it was 17%. After 4 days of treatment in the postoperative course the swelling subsided at a rate of 74% with impulse compression and 45% with cryotherapy. Intermittent impulse compression of the foot proved to be a highly effective method of treating post-traumatic and postoperative edema. It seems preferable to the standard therapy using cold packs.

Adult↗

Phenotypic characterization of skin lesions in urticaria pigmentosa and mastocytomas.

In order to identify possible cellular abnormalities in human mastocytosis, sections from 13 urticaria pigmentosa lesions and 5 mastocytomas were compared with 5 normal skin specimens using histochemical, enzyme histochemical and immunohistochemical techniques. All toluidine blue-positive mast cells also reacted with Fc epsilon RI and c-kit antibodies, almost all stained for tryptase, many for chymase and the myeloid workshop mast cell antibodies, few for Fc epsilon RII and none for the proliferation marker Ki-67. Urticaria pigmentosa lesions contained fewer epidermal Langerhans cells and a lower percentage of avidin-positive mast cells than mastocytomas and normal skin. Mastocytomas exhibited generally weaker staining for mast cell markers and mostly lacked Fc epsilon RI-bound IgE on mast cells and Langerhans cells, although the receptor was able to bind IgE in tissue sections. Most of the mast cell antibodies also reacted with other cell types. Only toluidine blue, avidin, tryptase and chymase stains were mast cell specific. Mast cells in mastocytosis thus differed only to a minor degree from normal mast cells, although distinct pathomechanisms may play a role in urticaria pigmentosa and mastocytosis.

Adolescent↗

Comparative immunoreactivity of the eosinophil constituents MBP and ECP in different types of urticaria.

In order to elucidate the role of eosinophil constituents in urticaria, we investigated major basic protein expression immunohistologically in comparison with that of eosinophilic cationic protein and the low-affinity IgE receptor in lesional and uninvolved skin of different types of urticaria. Eosinophil activation was studied with the markers EG1 and EG2. Different eosinophil constituents were found in all urticarial lesions except those of urticaria pigmentosa. MBP staining tended to be distributed diffusely throughout the tissue, whereas EG1 and EG2 antibodies were located at or close to individual cells. Staining with the low affinity IgE receptor antibody was rare. In uninvolved skin, major basic protein and particularly eosinophilic cationic protein reactivity was found in chronic recurrent urticaria, delayed pressure urticaria and, to a minor degree, in cholinergic urticaria. No correlation was found between antibody reactivity and eosinophil counts. Reactivity with either of the eosinophil constituents is thus a better marker for eosinophil involvement than routine H&E staining of the cells. The demonstration of eosinophil constituents in non-lesional skin of some urticaria patients suggests generalized eosinophil activation in certain subtypes of the disease.

Biopsy↗