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Biomedical subjects

A Ulmer

Publications and source records attributed to A Ulmer.

At least 19 recordsLinked to original sources

Low-dose prednisolone has a CD4-stabilizing effect in pre-treated HIV-patients during structured therapy interruptions (STI).

BACKGROUND: A favorable development of CD4+ T cells was firstly noticed in therapy-naive HIV-patients without antiretroviral therapy (ART) taking 5 mg prednisolone daily. This observation led to the prescription of prednisolone during structured therapy interruptions (STI). OBJECTIVE: To evaluate the effect of low dose prednisolone on pre-treated patients during STI. METHODS: A retrospective analysis including all pre-treated patients with prednisolone therapy for > or =6 months during STI has been conducted. The patients with prednisolone onset right at the beginning of STI (n = 95) were compared with all patients without prednisolone therapy during their first 6 months of STI (n = 49). Patients with prednisolone were divided into two subgroups: the ongoing STI-group and the patients with ART-restart. Additionally, the development of all 33 patients from the control group having started prednisolone later during STI was documented. Irrespective of the time of initiation of prednisolone therapy during STI, the development of CD4+ T cells in all patients with prednisolone for >12 months during STI was analyzed (n = 108). RESULTS: The mean daily CD4+ T cell decrease during STI was significantly less pronounced in the prednisolone-group (-0.50 vs. -0.74 cells/day; p = 0.0361). The daily CD4+ T cell decline of the 33 patients from the control subgroup including patients with a later onset of prednisolone therapy was only -0.11 during a mean time of 715 days under prednisolone. The CD4+ T cell count of the STI-patients treated with prednisolone for >12 months (n = 108; mean: 837 days +/- 64.6 (366-1,756 days)) decreased from 677/microl to 504/microl. - 51 of 81 patients (63%) included in 2-year-analysis showed stable CD4+ T cell counts (mean daily CD4+ T cell decrease: 0.08) and continued ART interruption. CONCLUSION: This retrospective evaluation provides evidence that low dose corticosteroids are associated with less decrease of CD4+ T cell count in pre-treated HIV patients resulting in prolongation of the potential time of structured treatment interruptions for many HIV patients.

AIDS-Related Opportunistic Infections↗

Long-term consequences of treatment interruptions in chronically HIV-1-infected patients.

OBJECTIVE: To evaluate the long-term effects of antiretroviral treatment (ART) interruptions on metabolic, immunological, virological and clinical outcomes in chronically HIV-1 infected patients. METHODS: Multi-centric, prospective, controlled 24-month cohort study in HIV-1 infected patients interrupting ART once or several times and for at least two weeks. Patients were compared to a frequency-matched control group continuing on ART. RESULTS: A total of 399 HIV-1 infected patients were included, among them 133 patients with treatment interruption (TI) and 266 control patients. Baseline characteristics were well matched. Median baseline CD4 cell count was 379/microl in TI-patients and 410/microl in control patients (p = ns). Median duration of the first TI was 1.1 months, and 37 % of patients had two or further TI's. Whereas CD4 cell count in control patients had increased significantly by a median of 67/microl at month 24 (p<0.0001), median CD4 cell count at month 24 in the TI-patients did not differ significantly from baseline. However, two-year AIDS-free survival was not significantly different between TI- and control patients. Liver enzymes and blood lipids improved significantly during TI. CONCLUSION: TI was associated with a significant immunological disadvantage at 24-month follow-up compared to continued ART. In this relatively immunocompetent cohort, however, TI's did not lead to an increased risk of disease progression within two years of follow-up.

Adult↗

Successful treatment of subacute cutaneous lupus erythematosus with mycophenolate mofetil.

Mycophenolate mofetil (MMF) is an immunosuppressive agent that has been shown to be effective in transplant patients. Some case reports and pilot studies have suggested efficacy against systemic lupus erythematosus (LE), particularly in the case of lupus nephritis. Reports on MMF treatment of skin manifestations of LE are still anecdotal. We report two cases with extensive skin lesions owing to subacute cutaneous LE (SCLE). Both patients had been treated with azathioprine and antimalarials without effect. Finally both patients were given highly dosed glucocorticosteroids, which were also ineffective but led to vertebral fractures because of long-term steroid treatment in one patient and steroid-induced psychosis in the other. MMF 2 g daily caused the skin manifestations to disappear within a few weeks in both patients. One patient was followed up for more than 24 months, and showed good toleration of MMF treatment. The skin remained stable over this period when at least 1 g MMF per day was administered. In conclusion, MMF appears to be an attractive treatment option in skin manifestations of SCLE, and seems to be beneficial for patients with steroid-refractory lesions that are also resistant to treatment with immunosuppressants or antimalarials. The observations suggest that further evaluation of this route in randomized controlled trials is warranted.

Dermatologic Agents↗

Successful palliation of stenosing anorectal melanoma by intratumoral injections with natural interferon-beta.

Anorectal malignant melanoma is an uncommon tumour. Unlike for cutaneous melanoma, there are few guidelines for its optimal management. In particular, very few palliative treatment strategies have been described for patients with advanced disease. We report on an 80 year old patient with locally advanced anorectal melanoma nearly completely blocking the anal orifice and disseminated metastases. Complete regression of the primary tumour and partial remission of the metastases was achieved with intratumoral injections of natural interferon-beta and systemic administration of dacarbazine. The quality of life in this patient was improved markedly by providing relief from severe rectal pain and bleeding. We propose that conservative treatment strategies such as intratumoral injections with interferon-beta should be considered as a palliative treatment option for stenosing anorectal melanoma before an abdominoperineal resection is recommended.

Aged↗

[Initial effects of the 1998 revised narcotic law in substitute drug treatment of narcotic dependent patients--results of a physician survey].

UNLABELLED: To study the consequences of the last revision of the German narcotics act (1998, which forbids prescribing codeines as substitutes), a survey was carried out several months after implementation with 639 physicians, who gave substitution treatment. It could be determined how far codeine patients were ready to change their substitute, how content physicians said their patients were after changing the substitute and which were the attitudes of physicians to the revision in question. RESULTS: The majority of patients (70%) who were formerly substituted by means of codeine accepted methadone as a substitute. After the method of substitution had been changed, 51% of patients had been classified as "very content" and 35% as "reasonably content". Especially those physicians who prescribed codeines in the past, unlike physicians who used methadone for substitution treatment only, criticised the revision in question and feared that many patients should be without medical care as a consequence of the new situation.

Attitude of Health Personnel↗

[Scleredema adultorum Buschke. Case report and review of the literature].

Scleredema adultorum of Buschke is a rare disorder of unknown aetiology. It is characterized by diffuse, non-pitting swelling and induration of the skin. Skin biopsies reveal marked thickening of the dermis due to collagenous replacement of the subcutis and deposition of hyaluronic acid between the collagen fibers. The disease classically only affects the skin. In 24 cases an associated monoclonal gammopathy has been detected. A 75-year-old patient had a 19-year history of scleredema adultorum. In addition to a monoclonal gammopathy the patient suffered from involvement of the tongue, pharynx and upper esophagus. Furthermore a polyneuropathy, ocular involvement with restricted eye movements and a sicca syndrome were present. The simultaneous occurrence of cutaneous scleredema with any one of the above mentioned symptoms has been reported before. The wide variety of extracutaneous manifestations of scleredema as found in our patient is amazing and has not been previously described.

Aged↗

Increased activity of cathepsin B in fibroblasts isolated from primary melanoma in comparison to fibroblasts from normal skin.

We determined activity of cathepsin B in early-passage fibroblasts isolated from primary melanoma and in fibroblasts from normal skin. Our results show an up to 5-fold increase in activity of cathepsin B in the tumor-derived fibroblasts in comparison to the fibroblasts from normal skin. We conclude that fibroblasts isolated from melanoma tissue are altered with regard to their specific activity of cathepsin B and preserve this elevated activity in early-passage cell culture. The data support the idea that stromal cells are not passive elements of the peritumoral environment but actively participate in the production of proteolytic enzymes.

Cathepsin B↗

[Amelanotic melanoma of the vulva simulating lichen sclerosus et atrophicus].

Malignant melanoma of the vulva is an uncommon disease. The amelanotic subtype is only rarely mentioned. We report a 60-year-old patient with a 6 month history of vulvar pruritus. Ivory lesions combined with erosions and fine "cigarette paper'-like wrinkling were suspicious for lichen sclerosus et atrophicus. Histologically the diagnosis of an amelanotic malignant melanoma was made. Amelanotic melanoma may present with a wide variety of clinical features. Even in the uncommon location of the vulva, amelanotic melanoma should be suspected in any nonhealing nonpigmented lesion.

Biopsy↗

Pharmacodynamics of recombinant IFN-beta during long-term treatment of malignant melanoma.

The pharmacodynamics and biologic activities of recombinant human interferon-beta (rHuIFN-beta) derived from chinese hamster ovary (CHO) cells were examined during long-term therapy in 7 melanoma patients. The CHO-derived rHuIFN-beta was given s.c. in a dose of 3 x 10(6) U three times per week for 24 weeks. Serum levels of IFN could not be detected before and 48 h after the s.c. injections. 2'-5'-Oligoadenylate synthetase (2-5 OAS), beta 2-microglobulin, and neopterin levels increased significantly 48 h after application, with a maximum after 96 h. Subsequently, the values decreased and remained only slightly elevated during the long-term therapy. Natural killer (NK) cell activity increased in the first 96 h significantly and fell below pretreatment values after 4 weeks. The decrease of biologic response could not be attributed to the occurrence of anti-IFN-beta antibodies because only 2 of the 7 patients developed neutralizing antibodies after 16 and 24 weeks of treatment, respectively. This trial confirms the biologic potency of CHO-derived rHuIFN-beta. However, the selected parameters demonstrate that immunostimulation is only possible over a short treatment period.

2',5'-Oligoadenylate Synthetase↗

Accumulation of macrophages in the arterial vessel wall following experimental balloon angioplasty.

Smooth muscle cell (SMC) proliferation is a key event in the development of restenosis after balloon angioplasty, and it is thought that macrophages play an important role in the complex process of activation of SMCs after vascular injury induced by balloon angioplasty. The study was designed to determine the time course of the accumulation of macrophages in the intimal layer following experimental balloon angioplasty. To determine the extent and time course of the accumulation of macrophages after experimental balloon angioplasty, an intimal atheroma was produced by repeated weak electrical stimulation of the right carotid artery of 45 male New Zealand White rabbits. Additionally, the animals received an 0.5% cholesterol diet during the 28 days of plaque development. Transluminal balloon angioplasty was subsequently performed. At 3, 7, 14, 21, 28 and 42 days after balloon treatment the vessels from at least five animals from each group were excised and analysed for the presence of macrophages using immunocytochemical techniques. In one group of five animals plaque development occurred without subsequent balloon angioplasty; the animals were killed after 21 days (sham group). SMCs were identified by immunohistological staining of alpha-actin. Intimal thickening increased after dilatation from 137 +/- 62 microns (control group without balloon treatment) to 244 +/- 47 microns in the 42 days after angioplasty (P < 0.05). The percentage of macrophages in the intimal layer displayed a significant increase (P < 0.01) at 14 days after angioplasty (9.1 +/- 4.3% vs 2.0 +/- 1.7% in the control group).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗

Intraperitoneal injection of synthetic bacterial lipopeptides does not cause a rise in circulating inflammatory cytokines.

The production of TNF-alpha, IL-1 and IL-6 was measured in mice after i.p. injections of the synthetic bacterial lipopeptide Pam3Cys-Ala-Gly, a potent macrophage and B cell activator in vitro. Only minor amounts of IL-6 and no TNF-alpha were detectable in the serum of mice injected with 10 or 100 micrograms of Pam3Cys-Ala-Gly. Lipopeptide concentrations up to 1000 micrograms failed to induce IL-1, and TNF-alpha production and serum IL-6 levels were only slightly elevated. In contrast to Pam3Cys-Ala-Gly, i.p. injections of LPS were accompanied by high levels of the inflammatory cytokines TNF-alpha, IL-1 and IL-6 suggesting fundamental differences of the mode of action of these two substances when applied in vivo.

Amino Acid Sequence↗

Season of birth of schizophrenics in Mississippi, USA.

Prior reviews indicate that schizophrenics tend to be born in the winter, relative to non-psychiatric controls. This conclusion has been criticized, however, as the association between birth seasonality and schizophrenia may be the result of a statistical artifact, the age-incidence effect. To examine this possibility, we studied the birth seasonality of 2892 schizophrenics, controlling for the age-incidence effect. Both before and after instituting these controls, we found excesses for the months of December and March. We conclude that the age-incidence hypothesis does not provide any general explanation of the season-of-birth effect in schizophrenia.

Adolescent↗