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Biomedical subjects

R M Knobler

Publications and source records attributed to R M Knobler.

At least 37 records · Page 2Linked to original sources
PubMed1993

Parenteral administration of 8-methoxypsoralen in photopheresis.

BACKGROUND: Extracorporeal photochemotherapy (EP) is used for the treatment of cutaneous T-cell lymphoma (CTCL), progressive systemic sclerosis (PSS), pemphigus vulgaris, and rheumatoid arthritis. During this procedure, the oral administration of the photoactive drug 8-methoxypsoralen (8-MOP) results in an unpredictable range of serum levels and in side effects limiting its efficacy. OBJECTIVE: To circumvent this limitation, extracorporeally administrable 8-MOP (EX-8-MOP) was developed. It is administered directly to the leukocyte/plasma concentrate in the treatment bag of the EP apparatus before irradiation with UVA light. METHODS: Efficacy, tolerance, and side effects of EX-8-MOP were evaluated in 108 consecutive treatments of 16 patients who had previously been treated with oral 8-MOP (91 treatments). RESULTS: With EX-8-MOP constant drug levels for UV light exposure were obtained; for equivalent levels only a small fraction of the oral dose (1/250 to 1/500) was required with none of the side effects associated with oral 8-MOP. Effective and reproducible inhibition of lymphocyte proliferation and cell viability was attained. No difference in clinical efficacy could be observed. CONCLUSION: EX-8-MOP eliminates the need for premedication and drug level monitoring of 8-MOP and should improve the effectiveness of EP.

Administration, Oral↗
PubMed1992

Gilvocarcin V exhibits both equilibrium DNA binding and UV light induced DNA adduct formation which is sequence context dependent.

The relative degree of both equilibrium binding and of ultraviolet light induced adduct formation for the antitumor antibiotic gilvocarin V with two hexaecamer DNA sequence isomers, d[ATATATAGCTATATAT]2 and d[AAAAAAAGCTTTTTTT]2, was assessed. The experiments reveal that gilvocarin V binds, under equilibrium conditions, and reacts, in the presence of exogenously applied UV light, more efficiently with the alternating purine:pyrimidine sequence hexadecamer than the homopurine:homopyrimidine duplex at identical gilvocarcin V to DNA duplex ratios. DNAse I digests of adduct containing duplexes derived from the d[AAAAAAAGCTTTTTTT]2 duplex, identified and isolated using gel shift assays employing denaturing polyacrylamide gels, confirm that gilvocarcin V adducts can be formed with thymine residues but suggest that adduct formation with either adenine or guanine residues is also possible.

Aminoglycosides↗
PubMed1992

Extracorporeal photochemotherapy for the treatment of systemic lupus erythematosus. A pilot study.

OBJECTIVE: To investigate the effectiveness and feasibility of extracorporeal photochemotherapy (ECP) in the treatment of an autoimmune disease with known cutaneous photosensitivity. METHODS: Ten patients with systemic lupus erythematosus (SLE) were treated with ECP in an open clinical trial. The efficacy of treatment was analyzed by means of established disease activity scores. RESULTS: Eight patients completed the trial. In 7 of the 8, there was a significant response to the treatment, with no or minor side effects. The clinical activity score in the group of 8 patients decreased from a median of 7 (range 4-9) to a median of 1 (range 0-5) (P less than 0.05). Laboratory abnormalities did not change significantly, but were mild at the outset. CONCLUSION: ECP led to clinical improvement of SLE without side effects. The effectiveness of this method should be investigated further in controlled clinical trials.

Adult↗
PubMed1992

Comparative histochemistry of port-wine stains after copper vapor laser (578 nm) and argon laser treatment.

The present study compared the histologic changes occurring 15 min after copper vapor laser (CVL; operating at 578 nm) and argon laser (488/514 nm) treatment of port-wine stains (PWS) over a range of energy densities (8-32 J/cm2) with corresponding pulse widths of 50-200 ms. Frozen tissue sections were stained with nitroblue tetrazolium chloride (NBTC). This histochemical method permits an accurate color differentiation between blue-stained viable and unstained thermally damaged cells. At 8, 10, and 12 J/cm2 the argon-laser injury was confined to epidermal cell layers; none to superficial dermal effects were found. Fluences of at least 15 J/cm2 produced a diffuse NBTC-negative coagulation necrosis. Exposure of PWS skin to 8-12 J/cm2 at 578 nm did not alter the integrity of epidermal cells. In the dermis, damage was confined to blood vessels and surrounding collagen, showing a clear demarcation from adjacent viable structures. The maximum penetration depth achieved with these vessel selective energy densities was 0.44 mm. At 15 J/cm2, besides vascular injury, damage to the basal cell layer also occurred. At fluences of 17-20 J/cm2 a diffuse necrosis similar to that induced by the argon laser was found. Vessel selectivity of the 578 nm wave band was achieved with pulse widths from 50-74 ms, exceeding the estimated "ideal" exposure time (0.1-10.0 ms) for a vascular selective laser effect. The NBTC method allowed identification of subtle laser-induced tissue changes providing accurate quantitative data relating to the extent of vascular injury.

Adult↗
PubMed1992

Human papillomavirus in cervix carcinoma and condylomata acuminata--identification of HPV-DNA by improved dot-blot-hybridization.

Using the benzoylated naphthoylated DEAE cellulose method (BND-method) we have designed a more efficient approach for the detection of human papillomavirus-DNA (HPV-DNA) via dot-blot and hybridization. Biopsy material from anogenital warts (40 patients), invasive carcinoma uteri (12 patients) and normal controls (20 patients) were studied for the presence of HPV-DNA. Phenol extracted DNA from representative lesions was loaded onto a pretreated nitrocellulose filter, was incubated under stringent conditions with 32-P-dCTP labelled HPV-DNA and exposed to a Kodak X-OMAT film. DNA of HPV types 11, 16, 18 were cloned into plasmid vectors. The common, time-consuming caesium-chloride density-gradient centrifugation used for purification of plasmid DNA (20-36 h), was substituted by the BND-method (15 min). Complete HPV genomes were excised using the restriction endonucleases Eco RI and Bam HI. The HPV-DNA fragments obtained were then electroeluted using the 'Bio-Trap' method and subsequently labelled with 32P-dCTP by nick translation. Without resorting to more complex and sensitive technology, such as the polymerase chain reaction, efficiency of specific analysis of large numbers of cervical samples and condylomata was achieved without loss of accuracy or increased costs. The time required for HPV identification from biopsy or sample receipt was shortened considerably (approximately 50%).

Blotting, Southern↗
PubMed1992

Accurate histochemical definition of argon-laser-induced tissue necrosis.

We present a histochemical method using the redox dye nitro blue tetrazolium chloride (NBTC) for the evaluation of argon-laser-induced tissue damage. By this method viable cells are stained blue, devitalized cells not. Our findings suggest that the NBTC staining method is more appropriate for the accurate definition of the necrosis and cell viability after laser treatment than routine histology.

Hemangioma↗
PubMed1991

Histochemical evaluation of the coagulation depth after argon laser impact on a port-wine stain.

A two-step excisional treatment of a port-wine stain (PWS) on the back of a 43-yr-old female patient was performed. Immediately before the first surgical treatment, two corresponding series of argon laser impacts were performed, each on one PWS half. Different laser parameters with irradiances ranging from 95 to 382 W/cm2 and energy fluences ranging from 19 to 114,6 J/cm2 were used. Laser spots on the first part ot be excised were biopsied 10 min after laser treatment and prepared for histochemical analysis by staining with nitro blue tetrazolium chloride (NBTC). Reduction of this redox dye by nicotinamide adenine dinucleotide diaphorase (NADH-diaphorase) leads on frozen tissue sections to an intense blue precipitate. The activity of NADH-diaphorase subsides immediately upon cell damage. All vital epidermal and dermal cells presented a dense blue granular pigment in their cytoplasm, sparing the nuclei. Laser induced arc-shaped epidermal and dermal necrosis did not stain, showing a clear demarcation from surrounding vital tissue. The depth of the thermal injury ranged from 0.28 to 0.45 mm; it did not correlate with the chosen fluences. With these penetration depths, the vast majority of PWS vessels was affected. Assessment of the remaining part of the PWS 8 months later yielded blanching of all laser-treated areas. With the NBTC method, an accurate definition of laser-induced tissue damage is feasible. It could be shown that the exposure time is the most relevant parameter influencing the penetration depth.

Adult↗
PubMed1991

Porokeratoses: immunohistochemical, light and electron microscopic evaluation.

Punch biopsy specimens of 14 patients with porokeratosis of Mibelli (n = 1), disseminated superficial porokeratosis (n = 6), disseminated superficial actinic porokeratosis (n = 4), porokeratosis plantaris, palmaris et disseminata (n = 2), and punctate porokeratosis (n = 1) were obtained for light and electron microscopy for evaluation of possible differences between these clinical variants. Langerhans cells in close contact with early degenerating keratinocytes could be observed in the epidermis. To study the cellular composition of the epidermal inflammatory infiltrate immunohistochemistry was performed. These studies demonstrated that the predominant cell type in these infiltrates are helper T cells, intermingled with Leu-6+ Langerhans cells. Despite the clinical variation and possible different etiologic or triggering mechanisms, the immunohistochemical and morphologic changes in all types of porokeratosis are the same and seem to represent a uniform reaction pattern.

Adult↗
PubMed1991

Treatment of cutaneous T cell lymphoma with a combination of low-dose interferon alfa-2b and retinoids.

In a pilot study the therapeutic effect and side effect profile of low-dose interferon alfa-2b in combination with a retinoid for the treatment of cutaneous T cell lymphoma were evaluated. Seven patients (four women, three men) with histologically confirmed cutaneous T cell lymphoma were included. Four patients had received therapy previously. The treatment schedule consisted of 2 million U of interferon alfa-2b administered subcutaneously three times per week and oral 13-cis-retinoic acid, 1 mg/kg/day, with subsequent dose reduction in case of response. The combination therapy produced two complete and two partial remissions. Responses were maintained by continuous therapy for up to 15 months even after dose reduction of both agents by 50%. Side effects were negligible and did not result in discontinuation of treatment in any patient.

Administration, Oral↗
PubMed1991

Abnormal epidermal changes after argon laser treatment.

A 26-year-old woman with a congenital port-wine stain on the forehead was treated three times at 2-month intervals with an argon laser. Six months after the last treatment, moderate blanching and mild scaling confined to the treated area was observed. A biopsy specimen of the treated area revealed a significant decrease in ectatic vessels. However, epidermal changes similar to those of actinic keratosis with disorganized cell layers and marked cytologic abnormalities were seen. Analysis of peripheral blood lymphocytes for a defect in DNA repair was negative. Multiple, argon laser-induced photothermal effects may be responsible for the changes observed in our case and may lead to premalignant epidermal transformation.

Adult↗
PubMed1991

Enzyme histochemical analysis of cell viability after argon laser-induced coagulation necrosis of the skin.

Reduction of nitroblue tetrazolium chloride, a redox indicator, by nicotinamide adenine dinucleotide diaphorase produces in frozen tissue sections an intense blue cytoplasmic pigment. The activity of this enzyme has been shown to subside immediately upon cell death. Twelve patients with port-wine stains were treated with an argon laser. Frozen tissue sections from biopsy specimens obtained before and 10 minutes, 24 hours, and 48 hours after laser application were processed for nitroblue tetrazolium chloride staining. In normal skin all epidermal and dermal cells displayed dense cytoplasmic blue granular pigment that spared the nuclei. In port-wine stains the laser-induced coagulation necrosis was first seen as an arc-shaped, sharply demarcated, unstained, nitroblue tetrazolium chloride-negative area. Initiation of epidermal repair could be observed in all 48-hour sections. The nitroblue tetrazolium chloride method, when compared with hematoxylin and eosin staining, allowed an easier and more accurate definition of laser injury because of the color difference between damaged and normal tissue.

Adult↗
PubMed1991

Photoelectric quantitative evaluation of argon laser treatment of port wine stains.

Sixty patients with port wine stains were treated with the argon laser and graded visually into four subjective categories for changes in skin colour. For objective quantitative evaluation a photoelectric colorimeter was used. Reproducible definition of the lightness of the lesions into numbers was obtained. Differentials in lightness between normal contralateral skin and the port wine stain before and after treatment were quantified for each individual. The objective evaluation revealed a statistically significant difference between the four categories (P less than 0.05). The best clinical therapeutic effect was found to correlate with only 80-90% blanching. The average lightening obtained was 46.5%. Local heating of port wine stains in 12 patients showed no measurable darkening in the colour of the lesions, whereas the normal contralateral skin reacted with marked reddening. Determination of changes in lightness by photoelectric colorimetry provides an objective, quantitative means to evaluate the effects of laser treatment of port wine stains.

Adolescent↗
PubMed1990

Experimental treatment of chronic lymphocytic leukemia with extracorporeal photochemotherapy. Initial observations.

Based on the encouraging results obtained with extracorporeal photochemotherapy (EP) in the treatment of the exfoliative erythrodermic form of cutaneous T-cell lymphoma (CTCL), leukemic form, as well as other T-cell-mediated diseases we evaluated the therapeutic potential of EP in patients with chronic lymphocytic leukemia (B-CLL). Three patients with B-CLL were treated for a period of 1 year. Two patients showed stabilization of disease, as demonstrated by reduction in their peripheral white blood cell count, with one patient showing lymph-node resolution. A third patient with significant intolerance to previous chemotherapy did not respond within the observed period. No significant side effects of EP were observed. Our observations suggest that EP may have a positive effect on the course of B-CLL in selected patients. Additional clinical trials are warranted to further define the role of EP alone or in combination therapy in the management of B-CLL.

Adult↗
PubMed1990

Xanthoma disseminatum with progressive involvement of the central nervous and hepatobiliary systems.

A rapidly progressive disease with multiple organ involvement and symptoms of polyuria and polydipsia developed in a 32-year-old woman, with an initial presentation of xanthoma disseminatum. Within 6 months increasing visual impairment of the right eye developed; a computed tomographic scan revealed multiple cerebral and cerebellar lesions. Progress of her disease resulted in blindness of the right eye, internal hydrocephalus with involvement of both ventricles, and cerebellar ataxia. Ultrasound examination of the abdomen and a subsequent endoscopic retrograde cholangiopancreatographic examination revealed a xanthomatous gallbladder and liver involvement. The gallbladder and liver showed histologic changes compatible with xanthomatosis. The patient died 4 years after the appearance of skin lesions.

Adult↗
PubMed1990

Long-term adjuvant therapy of high-risk malignant melanoma with interferon alpha 2b.

Fifty-three high-risk melanoma patients in stage I and 15 patients in stage II were treated after standard surgical intervention with adjuvant therapy with recombinant interferon alpha-2b (rIFN alpha 2b) therapy for a total period of 20 months. Concomitant patients (stage I, n = 82; stage II, n = 33) with identical stages and prognostic factors without adjuvant therapy were used to evaluate the efficacy of rIFN alpha 2b therapy. No difference in 5-year relapse incidence and overall survival rates could be detected. However, it appears that patients of both stage I and stage II benefit from long-term adjuvant rIFN alpha 2b therapy, because during the treatment period (20 months), the incidence of relapses was lower in comparison to controls. After stopping treatment the incidence of relapse is equal in treated and control groups. According to the results of our study, we suggest using continuous low-dose rIFN alpha 2b therapy for adjuvant treatment of malignant melanoma.

Adult↗