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K Wolff

Publications and source records attributed to K Wolff.

At least 163 records · Page 9Linked to original sources
PubMed1992

Stereologic estimation of volume-weighted mean nuclear volume as a predictor of prognosis in "thin" malignant melanoma.

At present, tumor invasion represents the most reliable prognostic factor for primary malignant melanoma. The 10-year survival rate of "thin" melanomas (Breslow less than 0.76 mm) is more than 95%, but approximately 5% of these low-risk tumors do metastasize. In an attempt to determine prognostic markers for "thin" melanomas we investigated the volume-weighted mean nuclear volume (Vv) of primary melanomas with tumor invasions below 0.76 mm in 32 patients. Ten of these patients had developed melanoma metastases within a mean follow-up period of 49 months; 22 patients who had not developed metastases and who were comparable with regard to clinical and histologic criteria as well as to follow-up period were selected as a comparison group. Vv was determined by computer-assisted image analysis (IBAS 20, Kontron, Germany) on hematoxylin-eosin-stained sections employing stereologic estimation of the volume-weighted mean nuclear volume. In addition, two-dimensional morphometric parameters (nuclear area and shape factors) as well as clinical (sex, age, location) and histologic characteristics (Breslow's thickness, Clark's level, and growth patterns) were recorded. The mean Vv (+/- SD) of primary melanomas with subsequent metastatic course was 273 microns 3 (+/- 81.3), whereas primary melanoma lesions without subsequent metastases exhibited a significantly lower Vv of 154 microns 3 (+/- 25.3) (p = 0.0008). On the other hand, two-dimensional morphometric and clinical and histologic parameters did not correlate with prognosis. Vv thus seems to represent a powerful and independent prognostic marker for "thin" primary melanomas. Assessment of Vv may provide a valuable tool in selecting patients with high-risk stage I, Breslow less than 0.76 mm, melanoma for adjuvant therapy.

Adult↗
PubMed1992

Necrobiosis lipoidica: treatment with systemic corticosteroids.

In an attempt to find an effective therapy for necrobiosis lipoidica, we have treated six patients with this disease with a 5-week course of systemic corticosteroids. This treatment resulted in complete cessation of disease activity in all patients and no recurrence in a mean follow-up period of 7 months; however, restitution of atrophic skin lesions could not be achieved. The therapy was well tolerated and did not pose problems, even in diabetic patients. These results strongly suggest that short-course therapy of necrobiosis lipoidica with corticosteroids is of lasting benefit to these patients and should probably be considered early in the course of their skin disease.

Administration, Oral↗
PubMed1992

Consensus conference on cyclosporin A for psoriasis February 1992.

Human studies using oral cyclosporin A (CyA; Sandimmun) therapy for psoriasis have been in progress for nearly 9 years. Cumulative data of the clinical effects of this therapy in 1000 patients have been collected, and are derived from multiple open and controlled studies. The efficacy of this treatment in psoriasis is well recognized, and the relative safety of up to 2 years of therapy is also established, provided that the guidelines are observed. However, there is concern regarding the long-term safety of CyA treatment of psoriasis as experience is still limited. Careful monitoring of all CyA-treated patients is therefore mandatory, and CyA should only be used by dermatologists who have expertise in its use. During treatment, co-operation with an experienced nephrologist is strongly recommended.

Cyclosporine↗
PubMed1992

Effects of cyclosporin A on resident and passenger immune cells of normal human skin and UV-induced erythema reactions.

Cyclosporin A (CyA) has proved effective in various dermatological diseases, but its mechanisms of action within the skin are still ill-defined. In order to characterize more clearly the cellular targets of CyA we examined its effects on skin immune cells in normal and UVB- and PUVA-irradiated skin by means of a three-step immunoperoxidase reaction and immunofluorescence double-labelling technique. The CyA-induced depletion of epidermal Langerhans cells equals that seen with UVB or PUVA alone. CyA alone has no effect on the number and distribution of dermal cells. CyA modulates the UV irradiation-induced changes by: (i) inhibiting the UVB- and PUVA-induced ICAM-1 expression by keratinocytes and (ii) suppressing the PUVA-induced upregulation of CD11a expression by macrophages (72 +/- 12% of Ki-M8+ macrophages express CD11a with PUVA, compared with 20 +/- 5% with CyA + PUVA, P < 0.001). Neither treatment affected ICAM-1 expression by endothelial cells. In addition, CyA increases PUVA minimal phototoxicity dose from 10 +/- 2.6 J/cm2 (PUVA alone) to 15.3 +/- 3.1 J/cm2 (CyA + PUVA), (P < 0.001). In conclusion, the effects of CyA on the skin include a down-modulation of the PUVA-erythema reaction, associated with a direct or indirect modulation of adhesion molecule expression.

Adult↗
PubMed1992

Plasma methadone measurements and their role in methadone detoxification programs.

We monitored eight patients who were receiving a decreasing dose of methadone for treatment for opioid addiction (detoxification). Patients with plasma concentrations of methadone less than 0.05 mg/L experienced withdrawal symptoms, relapsed, and re-abused illicit drugs. Four patients took extra methadone (illicitly obtained) during detoxification. None of the eight patients in our study were successfully weaned off methadone: all left the methadone detoxification program before the completion of treatment. Two patients subsequently returned to a fixed methadone program elsewhere, and four relapsed and returned to illicit drug misuse. Plasma measurements may help clinicians assess patients during methadone detoxification.

Adult↗
PubMed1991

The class 3 outer membrane protein (PorB) of Neisseria meningitidis: gene sequence and homology to the gonococcal porin PIA.

The class 3 protein (PorB) is an important component of the meningococcal outer membrane. The structural gene (porB) encoding the class 3 protein has been cloned using primers suitable for the amplification of the corresponding chromosomal fragment by the polymerase chain reaction (PCR). The complete nucleotide sequence was determined and predicts a mature protein of 310 amino acids, preceded by a signal peptide of 19 residues. The predicted protein sequence of the class 3 protein exhibits essential structural homology to the gonococcal porin PIA. The class 3 protein encoding gene was expressed in Escherichia coli under the control of an inducible promoter.

Amino Acid Sequence↗
PubMed1991

Measuring compliance in methadone maintenance patients: use of a pharmacologic indicator to "estimate" methadone plasma levels.

A quantitative indicator of compliance is not available for methadone--the drug of choice for the treatment of opioid addiction. We successfully used low-dose phenobarbital (a valid pharmacologic indicator) to measure compliance by incorporating the drug into the methadone medication of patients attending an addiction unit. Plasma phenobarbital and methadone concentrations were measured in 20 (11 clinic-based and 9 community-based) patients receiving long-term treatment with the phenobarbital level-to-dose ratio, together with interviews, to validate methadone measurements and to monitor compliance. Patients attending the unit on a daily basis and who consumed their medication in the clinic were substantially more compliant than community-based patients. Laboratory measurements of phenobarbital and methadone helped to identify the use of illicit methadone, as well as incorrect self-administration, such as the consumption of several days' dosage at one time.

Adult↗
PubMed1991

Cyclosporin A suppresses ICAM-1 expression by papillary endothelium in healing psoriatic plaques.

To analyze the mode of action of Cyclosporin A (CsA) in psoriasis, we examined the phenotypic profile of resident and passenger skin cells in seven psoriatic patients before and after 2 weeks of CsA treatment using a large panel of monoclonal antibodies in a three-step immunoperoxidase technique. For comparison, skin biopsies from psoriatic patients receiving psoralen + UVA (PUVA) therapy were examined. Although both treatment protocols were equally effective in inducing resolution of psoriatic lesions, the phenotypic changes induced by CsA differed greatly from those seen after PUVA. In CsA-treated patients there was a dramatic reduction in the ICAM-1 expression by papillary endothelial cells, but density, pattern, and phenotype of infiltrating inflammatory cells remained essentially unchanged. In contrast, PUVA therapy had no visible effect on ICAM-1 expression by papillary endothelial cells, but resulted in a significant reduction of the hemopoietic resident and infiltrating mononuclear cells within the epidermis. These results favor, but do not prove, the assumption that the CsA regimen chosen in this study exerts its anti-psoriatic effect primarily at the level of the keratinocyte, i.e., by inhibiting events leading to keratinocyte proliferation as well as by interfering with the secretion of mediators responsible for ICAM-1 expression by papillary endothelial cells.

Adult↗
PubMed1991

Upper keratinocytes of psoriatic skin lesions express high levels of NAP-1/IL-8 mRNA in situ.

In order to better understand the factors regulating disease promotion and activity in psoriasis (PS), we searched for the in situ expression of mRNA for various cytokines in long-standing PS skin lesions. Specific hybridization with a NAP-1/IL-8 anti-sense RNA probe was keratinocyte associated and yielded strong and specific signals exclusively in the upper layers of the lesional epidermis, but not in uninvolved skin from psoriatic patients or normal skin from non-psoriatics. Interestingly, NAP-1/IL-8 transcripts were focally clustered in a spotty pattern predominantly between the tips of elongated papillae, but were absent in the lower epidermal region and the dermal compartment. We consistently failed to detect appreciable numbers of TNF-alpha and/or IL-6 mRNA-containing cells in psoriatic lesions. These results support the notion that IL-8, rather than IL-6, is an important disease-promoting cytokine in PS. In view of the known in vitro and in vivo effects of IL-8, it is conceivable that this substance greatly contributes to the major pathologic changes seen in psoriatic skin, i.e., keratinocyte hyperproliferation and leucocyte infiltration. In this case, local pharmacologic down-regulation of NAP-1/IL-8 activity could be a promising therapeutic strategy in PS.

Cell Adhesion Molecules↗
PubMed1991

Serological (Em2-ELISA) and parasitological examinations of fox populations for Echinococcus multilocularis infections.

Serum or body fluid samples of 1,006 foxes were investigated in an ELISA for antibodies against a highly sensitive and specific antigen (Em2-antigen) of Echinococcus multilocularis. Parasitological examinations of the intestines and simultaneous serological examinations were carried out in 505 foxes: A group of 98 blue foxes (Alopex lagopus) from Norwegian fox farms did not contain intestinal stages of E. multilocularis and was clearly sero-negative in Em2-ELISA. On the other hand in red foxes (Vulpes vulpes) originating from European areas known to be endemic for E. multilocularis the following average prevalence rates were found: 244 foxes from Southern Germany, E. multilocularis prevalence 55% and sero-prevalence 60%; 139 foxes from Austria, E. multilocularis prevalence 4% and sero-prevalence 12%. Serological identification of individual foxes with or without intestinal E. multilocularis infection was not possible. Only serological (no parasitological) examination in 402 foxes originating from endemic areas in Switzerland resulted in a sero-prevalence rate of 37%. Sero-prevalence was only 6% and 4% in 54 and 26 other foxes, respectively, originating from Swiss and German areas where E. multilocularis has not yet been reported. Negative control Norwegian (farmed) silver foxes (n = 43) were all sero-negative. The specificity of the Em2-ELISA was confirmed by negative Em2-serologies with sera from dogs infected with intestinal and tissue dwelling helminth species (with the exception of two from 24 dogs infected with E. granulosus).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Endothelin--a potent constrictor of small myometrial arteries of term pregnant women.

This study was performed to evaluate the in vitro effects of a new polypeptide, endothelin-1 (ET-1) on small intramyometrial vessels in comparison with the action of noradrenalin (NA). In connection with cesarean section, myometrial biopsies were obtained and small arteries (100-500 microns in diameter) were excised. Cylindrical segments of these vessels were used for registration of contractile activity after administration of ET-1 and NA. ET produced vasoconstriction and was approximately three times as powerful and 70-fold as potent as NA. It is suggested that ET may be involved in the regulation of human utero-placental blood flow.

Adult↗
PubMed1991

High-dose methadone and the need for drug measurements in plasma.

We report a case of high-dose methadone prescribed to a heroin addict for pain control. The patient was prescribed methadone during convalescence from surgery and subsequently for maintenance treatment. Dosing was started at 360 mg of methadone per day and reduced over 12 days to an 80 mg/day maintenance dose. Although the patient was drowsy on the initial dose, his recovery was uneventful. However, there were complaints of pain and withdrawal discomfort when the plasma concentration decreased to less than 1 mg/L. Measurements of methadone in plasma were helpful for monitoring the recovery of this patient after surgery and are likely to prove useful in similar cases.

Adult↗
PubMed1991

Recombinant human interleukin 3 induces proliferation of inflammatory cells and keratinocytes in vivo.

In this preclinical study we investigated the effect(s) of recombinant human (rh) interleukin 3 (IL-3) on hemopoietic differentiation and attempted to evaluate possible clinical side effects of this hemopoietic growth factor. Rh IL-3, derived from either Escherichia coli or Chinese hamster ovary, was administered subcutaneously to 16 rhesus monkeys (by pairs) at different doses (11, 33, and 100 micrograms/kg/day) for 14 days. During the 2nd week of administration white blood cell counts increased 2- to 3-fold mainly because of a dose-dependent elevation of basophils (up to 40% of white blood cells) and eosinophils. In addition, moderate to marked elevations of plasma histamine levels were measured. Transient diarrhea and an erythematous skin rash with generalized cutaneous lesions that was not restricted to the injection sites were present in 3 of 6 animals treated with E. coli-derived rh IL-3 (1 of 2 animals that received 33 micrograms/kg and 2 of 2 that received 100 micrograms/kg) and 2 of 6 monkeys treated with Chinese hamster ovary-derived rh IL-3 (1 of 2 that received 33 micrograms/kg and 1 of 2 that received 100 micrograms/kg), respectively. Histopathologic and immunohistologic evaluation of skin specimens revealed a perivascular mononuclear cell infiltrate interspersed with numerous mast cells. Signs of vasculitis were absent. The density of the perivascular infiltrate correlated not only with the dose of IL-3 but also with the duration of the skin eruption. Moreover, hyperproliferation of basal keratinocytes resulting in acanthosis was observed in lesions persisting for 1 and 4 days as also evidenced by a significant (p less than 0.01) increase in Ki-67 (a proliferation-associated marker)-positive basal keratinocytes.

Animals↗
PubMed1991

Methadone in saliva.

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Chromatography, High Pressure Liquid↗