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Biomedical subjects

R Hoekzema

Publications and source records attributed to R Hoekzema.

At least 19 recordsLinked to original sources
PubMed2003

Botryomycosis in an HIV-positive subject.

A 28-year-old male AIDS patient with generalized painful skin ulcers, fever and malaise presented to us. The differential diagnosis included varicella zoster infection, herpes simplex infection, actinomycosis, sporotrichosis and botryomycosis. Histopathology revealed clusters of gram-positive coccoid bacteria in the deep dermis, surrounded by a mixed dense inflammatory infiltrate. A bacterial culture grew Staphylococcus aureus. Viral cultures remained negative. Based on these findings botryomycosis was diagnosed. Large lesions were excised surgically and with antimicrobial therapy all skin symptoms disappeared. We discuss this case with reference to a short review of the literature on botryomycosis in relation to HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed2002

Treatment of necrobiosis lipoidica with topical psoralen plus ultraviolet A.

BACKGROUND: Necrobiosis lipoidica (NL) is a rare skin disease, mostly seen on the legs and often occurring in patients with diabetes mellitus. The disease belongs to the idiopathic cutaneous palisading granulomatous dermatitides associated with a degeneration of collagen, thus leading to skin atrophy. Application of topical corticosteroids is the most widely used treatment but the results are not always satisfactory and may worsen skin atrophy. Preliminary studies in patients with NL have shown a clinical response with psoralen plus ultraviolet (UV) A (PUVA). Objectives To study the effect of topical PUVA on NL in a multicentre prospective study. METHODS: Thirty patients (27 women and three men) including 13 with insulin-dependent diabetes mellitus, with a diagnosis of NL proven by histopathology, were included. All patients had been unsuccessfully treated with topical and/or intralesional corticosteroids. Patients were treated twice weekly with an aqueous gel containing 0.005% psoralen followed by irradiation with UVA. Clinical photographs were taken for evaluation. In addition, 20-MHz high-frequency ultrasound analysis was performed in 10 patients to evaluate the thickness and density of the dermis during topical PUVA therapy. RESULTS: Five patients (17%) showed complete clearing (healing of ulceration and disappearance of erythema) after a mean of 22 exposures (range 15-30). Eleven patients (37%) showed improvement, defined as healing of ulceration and/or reduction of erythema, after a mean of 23 exposures (range 11-42). Ten patients (33%) showed no effect and four patients (13%) worsened during topical PUVA therapy. The treatment results of the patients who suffered from diabetes mellitus were not different from those who did not have diabetes mellitus. No difference was seen in mean dermal thickness (1666 vs. 1706 micro m) and density (17 vs. 16 units) before and after topical PUVA therapy. Side-effects were seen in 10 patients: hyperpigmentation (n = 4), blistering (n = 4) and bacterial infection (n = 2). CONCLUSIONS: Topical PUVA may be a useful treatment modality for NL in patients not responding to topical or intralesional corticosteroids.

Adolescent↗
PubMed1999

Treatment of patients with systemic sclerosis with extracorporeal photochemotherapy (photopheresis).

BACKGROUND: Effective treatment modalities for systemic sclerosis, a life-threatening and disabling disease, are still lacking. Possible efficacy of photopheresis has been reported in several studies. Because of the complexity of the treatment, placebo-controlled trials are difficult to perform. OBJECTIVE: We investigated the effect of photopheresis on clinical parameters (skin score and internal organ functions), immunologic parameters, and quality of life. METHODS: Nineteen patients with progressive systemic sclerosis of less than 5 years' duration were randomized into 2 groups. One group (group A) received photopheresis for 1 year, the other group (group B) received no treatment at all. After 1 year the groups switched (crossover design). Photopheresis was performed on 2 consecutive days every 4 weeks; the psoralens were administered parenterally. The main outcome parameter was the skin score after 1 year of treatment compared with that of the control group. RESULTS: The average skin score improved with 5.4% (standard error [SE], 20. 8%) in group A and deteriorated with 4.5% (SE, 13.8%) in group B (not significant; P =.71). Before crossover, the average increase in skin score was 5.3% (means of entire group). No change was observed in other clinical parameters. Approximately 1 year after crossover, the skin score reversed to what would have been expected with an average increase of 5.3% per year. There was also no effect on immunologic parameters. Quality of life did not change during treatment. CONCLUSION: We were not able to show that photopheresis, performed as described above, is an effective treatment in systemic sclerosis. The difference in average skin score was statistically and clinically insignificant. Despite the small sample size, we concluded that the magnitude of the observed changes is too small to justify photopheresis as a regular treatment.

Adult↗
PubMed1998

Adhesion molecule expression in basal cell carcinoma.

Basal cell carcinomas (BCCs) are frequently associated with a peritumoral mononuclear infiltrate. Until now, the function of this inflammatory infiltrate and its possible role in the control of tumor growth is unclear. Mechanisms controlling endothelial and target cell adhesiveness for leukocytes are important features in the development of a specific local immune response. The expression and distribution of the adhesion molecules ICAM-1, VCAM-1 and E-selectin by microvascular endothelial cells and tumor cells, together with their leukocyte receptors LFA-1, VLA-4 and CLA respectively, were studied in 33 BCCs of different histological subtypes. In normal skin, ICAM-1 is expressed by resting endothelial cells, whereas VCAM-1 and E-selectin expression correlates with endothelial activation. The epidermis in normal conditions displays no ICAM-1, VCAM-1, or E-selectin expression. In BCC, endothelial ICAM-1 expression was only slightly increased compared to normal skin, whereas expression of endothelial VCAM-1 and E-selectin was low or absent in all BCCs examined. Peritumoral infiltrates contained mostly LFA-1-expressing lymphocytes, with minimal VLA-4 and CLA positivity. In none of the cases studied was adhesion molecule expression by BCC tumor cells identified. The lack of significant expression of adhesion molecules on peritumoral vascular endothelial cells and BCC tumor cells does not support the idea of specific, cell-mediated immunity being an important mechanism in limiting BCC tumor spread.

Biomarkers, Tumor↗
PubMed1997

Transforming growth factor-beta and bcl-2 distribution patterns distinguish trichoepithelioma from basal cell carcinoma.

BACKGROUND: Trichoepithelioma (TE) and basal cell carcinoma (BCC) have many features in common both clinically and histologically. Despite these many similarities TE and BCC represent different biological entities. OBJECTIVE: Recently, bcl-2 and CD34 have been reported as reliable markers in distinguishing the two types of tumor. Transforming growth factor-beta (TGF-beta), a multifunctional regulator of both cell growth and differentiation, was evaluated in this study. METHODS: The immunohistochemical expression of TGF-beta was compared with the distribution patterns of bcl-2 and CD34 in five BCCs, five TEs, and seven borderline cases. RESULTS: All five TEs showed a diffuse cytoplasmic staining of tumor cells for TGF-beta, whereas four of five BCCs were TGF-beta negative. Of the seven equivocal cases of TE/BCC, five tumors demonstrated TGF-beta positivity in combination with negative bcl-2 staining corresponding to TE. The remaining two cases demonstrated the opposite staining pattern, characteristic for BCC. CONCLUSION: The TGF-beta staining pattern appears to be a helpful additional marker together with bcl-2 in differentiating between TE and BCC. The demonstrated staining differences may relate to the distinct origin and biological behavior of the two tumors and may therefore be of value in subsequent patient management.

Adult↗
PubMed1997

Expression of adhesion molecules in pagetoid reticulosis (Woringer-Kolopp disease).

Cell adhesion molecules play a critical role in lymphocyte migration and homing. They convey tissue-specific homing properties to lymphocyte subsets and regulate the positioning of these subsets in the body. In a patient with pagetoid reticulosis, a rare form of cutaneous T-cell lymphoma characterized by extreme epitheliotropism, we examined the expression of adhesion molecules. The neoplastic T lymphocytes showed a strong expression of cutaneous lymphocyte antigen, a skin-homing receptor which interacts with E-selectin on skin endothelium. alpha E beta 7 an adhesion molecule interacting with E-cadherin on epithelial cells, was also expressed on tumour cells. These findings suggest that adhesion molecules are responsible for the unique growth pattern in pagetoid reticulosis, and for the clinical behaviour of the disorder.

Aged↗
PubMed1996

Quantification of cutaneous sclerosis with a skin elasticity meter in patients with generalized scleroderma.

BACKGROUND: The skin score, a subjective assessment of skin elasticity, is widely used in patients with systemic sclerosis. Although this scoring method is regarded as a validated and accepted tool, the interobserver and intraobserver reproducibility is relatively poor. OBJECTIVE: Our purpose was to investigate whether the recently developed SEM 474 cutometer, which exerts a controlled vacuum force to the skin, can measure skin elasticity more objectively than the skin score. METHODS: Skin elasticity was measured in 74 different body areas in patients with systemic sclerosis and compared with the skin score obtained from the same areas. RESULTS: The cutometer produced quantitative and reproducible data. A large-diameter (8 mm) measuring probe was superior to a small probe. The interobserver intraclass correlation coefficient (ICC) was 0.92; the intraobserver ICC was 0.94. A linear correlation was found with the clinical skin score; the Spearman rank correlation test was 0.69. CONCLUSION: The correlation with the skin score was reasonable, despite the observation that regional differences in skin elasticity were detected by the cutometer but not by the human observer, who automatically compensates for these factors and integrates them into the skin score. The high interobserver and intraobserver ICC makes the cutometer more suitable for quantifying changes in skin thickness than the subjective skin score.

Adult↗
PubMed1995

Inhibiting interleukin-1 and tumor necrosis factor-alpha does not reduce induction of plasminogen activator inhibitor type-1 by endotoxin in rats in vivo.

In experimental animals and humans, intravenous (i.v.) injection of endotoxin induces large increases in circulating plasminogen activator inhibitor type-1 (PAI-1), a major inhibitor of blood fibrinolysis. A similar increase is seen after the injection of interleukin-1 (IL-1) or of tumor necrosis factor-alpha (TNF-alpha), suggesting that these cytokines mediate the induction, by endotoxin, of PAI-1. To test this hypothesis we pretreated rats, before i.v. endotoxin, with compounds that inhibit the formation of cytokines (pentoxifylline; dexamethasone), or with compounds that inhibit the action of these cytokines (anti-TNF antiserum for TNF-alpha; IL-1 receptor antagonist for IL-1). None of these pretreatments affected the induction of PAI-1 synthesis by endotoxin. However, pretreatment did reduce the endotoxin-induced increase in plasma tPA antigen concentration. Thus, the data suggest that, in rats in vivo, TNF-alpha and IL-1 are not significantly involved in the induction of PAI-1 by endotoxin.

Animals↗
PubMed1995

Systemic anti-tumor necrosis factor antibody treatment exacerbates endotoxin-induced uveitis in the rat.

Tumor necrosis factor is released in the circulation and aqueous humor during endotoxin-induced uveitis, and induces acute uveitis when injected intraocularly in rats. To elucidate the role of tumor necrosis factor in the development of endotoxin-induced uveitis we analysed the effect of neutralizing anti-tumor necrosis factor antibodies and of pentoxifylline, a drug that inhibits tumor necrosis factor synthesis. Lewis rats were treated with: (a) a single intracardial injection of polyclonal rabbit anti-murine tumor necrosis factor antiserum prior to foot pad injection of 200 micrograms lipopolysaccharide; (b) an intraperitoneal injection of 10 mg pentoxifylline 1 hr before, at the time of, and 3 hr after foot pad injection of lipopolysaccharide; or (c) an intravitreal injection of 20 to 500 micrograms pentoxifylline together with 1 microgram lipopolysaccharide. The ocular inflammation was examined by slit-lamp and evaluated for the presence of hyperemia, flare, miosis, infiltrating cells or hypopyon. Levels of tumor necrosis factor in serum and aqueous samples were determined using a bioassay. Systemic treatment with either anti-tumor necrosis factor antibodies or pentoxifylline resulted in a significant inhibition, 90 and 70% respectively, of serum tumor necrosis factor activity at 3 to 4 hr after lipopolysaccharide injection. Systemic pentoxifylline treatment had no influence on the severity of uveitis. Anti-tumor necrosis factor antibody treatment, in contrast, caused an exacerbation of endotoxin-induced uveitis at t = 20 hr; mean uveitis score 3.9 vs. 1.4 in controls; P < 0.01. Intraocular administration of pentoxifylline together with lipopolysaccharide also had an aggravating effect on uveitis, that was associated with increased levels of intraocular tumor necrosis factor. The results show that inhibition of serum tumor necrosis factor activity does not block the development of endotoxin-induced uveitis. In fact, anti-tumor necrosis factor antibody treatment exacerbates the intraocular inflammation. These findings suggest that tumor necrosis factor may have other than proinflammatory properties in this uveitis model.

Animals↗
PubMed1995

Tumour necrosis factor-induced uveitis in the Lewis rat is associated with intraocular interleukin 6 production.

Lewis rats were injected with recombinant murine tumour necrosis factor-alpha either intravitreally (0.08-50 ng) or intracardially (1 microgram). The intraocular inflammatory response induced by tumour necrosis factor was examined by slit-lamp and protein extravasation into aqueous humor was determined. The phenotype of the inflammatory cells in the eye was analysed by immunohistochemistry. In addition, the kinetics of intraocular interleukin 6 production were determined. At 24 hr after intravitreal injection, a significant clinical uveitis was observed only in rats injected with 50 ng of tumour necrosis factor, when compared to saline-treated controls (P < 0.05). Maximal clinical uveitis and blood-aqueous barrier breakdown were already present at 4 hr after tumour necrosis factor injection. The uveitis was characterized by a massive cellular infiltrate in the anterior segment, consisting predominantly of polymorphonuclear cells and macrophages/monocytes, and to a lesser extent of T lymphocytes. Intraocular interleukin 6 mRNA expression and elevated levels of interleukin 6 in aqueous humor were detected 1 hr after tumor necrosis factor injection, reached a maximum at 3 to 4 hr after injection, and had declined again at 2 hr. Although intracardial injection of 1 microgram of tumour necrosis factor in Lewis rats induced a rise of circulating interleukin 6, it did not produce uveitis. The results obtained with intravitreally injected tumour necrosis factor indicate that intraocular TNF may play a pivotal role in the induction of uveitis in the rat. The transient intraocular production of interleukin 6 early during tumour necrosis factor-induced uveitis suggests that this cytokine may participate in the response induced by tumour necrosis factor.

Animals↗
PubMed1995

Demodicidosis or rosacea: what did we treat?

We report a 75-year-old man with a fulminant rosacea-like eruption, suggestive of demodicidosis. Multiple Demodex folliculorum mites were found in facial scales and pustules and, on histological examination, in the infundibulum of pilosebaceous follicles and in the dermis. Intradermal mites were surrounded either by polymorphonuclear granulocytes and histiocytes, or by a granulomatous infiltrate containing foreign-body giant cells, which had phagocytosed the parasites. Complete recovery, with disappearance of facial mites, was achieved by treatment with a combination of oral and topical metronidazole, although this drug is not known to be miticidal.

Aged↗
PubMed1994

Circulating cornea-specific antibodies in corneal disease and cornea transplantation.

In order to establish the significance of circulating cornea-specific antibodies, we determined the presence of anti-corneal antibodies in the serum of 100 patients with corneal disease and in 50 healthy controls, and subsequently followed the pattern of antibody reactivity in 46 patients who underwent corneal transplantation. An indirect immunofluorescence test on cryostat sections of rabbit corneas was used for screening. The reactivity against two known bovine corneal epithelial proteins was also tested: a 54-kD protein (BCP 54) and an 11-kD protein (BCP 11/24). No significant difference in the presence and specificity of anti-corneal antibodies was observed between the group of patients with corneal disease, taken as a whole, and the healthy controls. Patients with keratoconus or non-immunological graft failure, however, were significantly more often positive for anti-corneal antibodies. Neither the presence of antibodies prior to corneal transplantation nor their appearance post-transplantation had a predictive value for corneal graft survival.

Aldehyde Dehydrogenase↗
PubMed1994

Kinetics of intraocular tumor necrosis factor and interleukin-6 in endotoxin-induced uveitis in the rat.

PURPOSE: To determine the kinetics of tumor necrosis factor (TNF) and interleukin-6 (IL-6) in serum and aqueous humor of rats with different susceptibilities to endotoxin-induced uveitis (EIU), after footpad injection of lipopolysaccharide (LPS). METHODS: Samples were collected from EIU-susceptible Lewis rats and EIU-resistant Brown Norway (BN) rats for up to 72 hours after LPS injection. Specific bioassays were used to measure TNF and IL-6 activity. Northern blot analysis was used to assess intraocular IL-6 mRNA expression. RESULTS: High levels of TNF and IL-6 were detected in serum of both rat strains early after LPS injection. A second rise in serum TNF was observed at 18 to 20 hours in Lewis rats only. In aqueous humor of Lewis rats, high levels of TNF and IL-6 were observed early after LPS injection (2 to 8 hours) and concomitant with maximal uveitis (18 to 24 hours). Low levels of TNF and IL-6 were found in aqueous humor of BN rats. Ocular IL-6 mRNA was detected at the same time as IL-6 activity was measured in aqueous humor. CONCLUSIONS: The results of this study indicate that both TNF and IL-6 may play a role in the pathogenesis of EIU. The early release of TNF in aqueous humor during EIU suggests that this cytokine may serve as an initial mediator of intraocular inflammation. Furthermore, Northern blot analysis indicates that IL-6 is produced locally during EIU.

Animals↗
PubMed1994

Human corneal extract enhances serum complement activity.

PURPOSE: The concomitant presence of complement-activation products in the cornea during inflammation is well described. The present study was undertaken to analyze the complement activity of normal human corneal tissue and to assess the presence of complement-modulating activities. METHODS: Human corneal tissue was extracted in veronal-buffered saline. The overall complement (C) activity of the human corneal extract (HCE) and the effect of HCE on serum C-activity were investigated using a hemolytic assay. Anion-exchange chromatography and gel filtration were applied for biochemical analysis of HCE. Monoclonal anti-human C3 was used to detect corneal C3 and to remove C3 from HCE by immunoadsorption. RESULTS: It was found that C-activity of HCE was less than 200 U/g tissue. Experiments to test whether HCE exhibited inhibitory activity led to an unexpected result: When added to human serum dilutions, HCE caused a significant, dose-dependent increase of C-activity. Pretreatment of HCE at 56 degrees C abolished the effect. Analysis of HCE by anion-exchange chromatography revealed two C-enhancing peaks. One peak was identified as C3 whereas the identity of the other protein peak remained unknown. CONCLUSIONS: Results indicate that the human cornea contains an as yet unidentified heat sensitive factor(s) able to enhance complement activity of serum. It is postulated that this factor(s) may play an important role in corneal physiology and pathology.

Chromatography, Gel↗
PubMed1992

Analysis of aqueous humour in uveitis by high performance liquid chromatography and sodium dodecyl sulphate-polyacrylamide gel electrophoresis.

Aqueous humour from patients with Fuchs' heterochromic cyclitis (FHC) and other types of uveitis was analysed by high performance liquid chromatography (HPLC) and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Using HPLC, the number of peaks and their respective elution times were similar for the FHC, uveitis and control groups. SDS-PAGE and silver staining showed immunoglobulin G migrating as two to four distinct bands in all non-reduced samples. In the reduced state, 1-5 unidentified low MW bands (10-19 kD) were seen. Two bands at 19 and 10 kD appeared to be specific for the uveitis group, and a band at 11 kD was present in 76% of uveitis and 19% of FHC patients. None of these three bands were detected in any of the control group. As yet the identity of these low MW proteins and their possible significance in the pathogenesis of intraocular inflammation are unknown.

Adult↗