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Biomedical subjects

R Neumann

Publications and source records attributed to R Neumann.

At least 19 recordsLinked to original sources
PubMed1992

Micropharmacology of monoclonal antibodies in solid tumors: direct experimental evidence for a binding site barrier.

Monoclonal antibodies (MAbs) often distribute nonuniformly in tumors. In part, that observation reflects intrinsic heterogeneity within the tumor; in part, it reflects poor penetration through tumor substance. Several years ago, we proposed the "binding site barrier" hypothesis (J.N. Weinstein, R.R. Eger, D.G. Covell, C.D.V. Black, J. Mulshine, J.A. Carrasquillo, S.M. Larson, and A.M. Keenan, Ann. NY Acad. Sci., 507: 199-210, 1987; K. Fujimori, D.C. Covell, J.E. Fletcher, and J.N. Weinstein, Cancer Res., 49: 5656-5663, 1989), the idea that antibodies (and other ligands) could be prevented from penetrating tumors by the very fact of their successful binding to target antigen. Calculations suggested that this might be a significant factor in the therapy of even microscopic nodules. The higher the affinity and the higher the antigen density, the greater the barrier. Here, we provide direct experimental evidence of such a barrier to the percolation of D3 MAb through intradermally implanted line 10 carcinoma of guinea pigs. After affinity purification using glutaraldehyde-fixed line 10 cells, the D3 had an average immunoreactivity of 88%, a binding constant of 1.6 +/- 0.3 (SEM) x 10(10) M-1, and saturation binding of 355,000 +/- 15,000 molecules/cell. Using a combination of double-label autoradiography and double-chromagen immunohistochemistry, we determined simultaneously the distribution of (a) i.v. injected D3 MAb; (b) coinjected isotype-matched control IgG (BL3); (c) D3 antigen; (d) blood vessels. The previously developed mathematical models aided in the design of these experiments. Double immunochemical staining of the tumors showed antigen-rich patches 100-800 microns across, surrounded by blood vessels. At a low MAb dose (30 micrograms), binding to antigen severely hindered penetration into antigenic patches as small as 200 microns, even at 72 h. Explanation of this finding by a physical barrier was ruled out by the observation that BL3 distributed uniformly in the same patches. At a higher dose (1000 micrograms), the binding site barrier could be partially overcome. The same general principles of micropharmacology may apply to biological ligands other than antibodies, including those secreted by genetically modified cells.

Adenoma, Bile Duct↗
PubMed1992

A long-term follow-up of metallic intraocular foreign bodies, employing diagnostic x-ray spectrometry.

We describe 10 eyes harboring metallic intraocular foreign bodies (IOFBs) for 9 to 46 years that had undergone diagnostic x-ray spectrometry to measure metal dissolution 9 years before this study. Findings from the present clinical and laboratory examinations, including perimetry, electroretinography, electrooculography, and diagnostic x-ray spectrometry examinations are reported. Deterioration in visual acuity consequent to metal dissolution of the IOFB was found in only one eye. Visual fields and electrophysiologic performances deteriorated in two other eyes for reasons that were probably unrelated to IOFB dissolution. Visual functions remained stable during the follow-up period in seven eyes, although excess copper levels were demonstrated in one of them. Eight of 10 eyes retained visual acuity of 6/24 or better. Diagnostic x-ray spectrometry confirmed siderosis in one patient and ruled out metallosis in the two patients with deteriorated vision for reasons that were unrelated to metallosis. The favorable outcome of this series of patients may influence one to consider a more conservative approach in the decision to remove IOFBs. A careful, life-long follow-up might be considered with periodic electroretinographic and diagnostic x-ray spectrometry examinations; the IOFB should be promptly removed if and when metallosis with damage to visual functions is demonstrated.

Adult↗
PubMed1992

Long-term results of systemic chemotherapy for ocular cicatricial pemphigoid.

Ocular cicatricial pemphigoid (OCP) is a chronic, progressive, blinding, autoimmune disease that scars mucous membranes. We studied the long-term outcome in 104 consecutive patients (average follow-up: 4 years) to determine whether complete remission could be achieved following a course of treatment with immunosuppressive drugs. We found that prolonged periods of remission off therapy are maintained in about one third of OCP patients. Follow-up must be continued for life as relapse occurs in approximately one third of cases. Those who relapsed regained disease control readily upon reinstitution of therapy and did not deteriorate to more advanced cicatrization. Sex, age, initial degree of inflammation and the incidence of extraocular involvement did not bear a prognostic significance. The mechanism which underlies the differing responses to therapy is not yet known.

Adult↗
PubMed1992

Distribution of the 72-kd type IV collagenase in nonneoplastic and neoplastic thyroid tissue.

The 72-kd type IV collagenase (matrix metalloproteinase-2 [MMP-2]) is a neutral metalloproteinase that initiates the degradation of type IV collagen in basement membranes. Its production by tumor cells has been correlated with the invasive and metastatic potential of neoplasms. Two recently developed affinity-purified antibodies against synthetic peptides from the amino terminus (H1) and an internal domain (Ab48) of the molecule were used to investigate immunohistochemically the distribution of this enzyme in a variety of thyroid tissues. All primary carcinomas (20 papillary, seven follicular, and three medullary) as well as nine of 11 metastases were positive, with the more aggressive tumors (tall cell variant of papillary carcinomas and invasive follicular carcinomas) tending to be more reactive than the low-grade tumors (classic and microinvasive papillary carcinomas and minimally invasive follicular tumors). Negative or minimal positivity was found in six cases of normal thyroid, one goiter, and two cases of Graves' disease. Immunoreactive follicular cells were seen focally in areas of inflammation, fibrosis, and distortion of normal follicles, and in Hashimoto's thyroiditis (four cases). Five of nine adenomas showed positive cells, but this could be related to previous trauma to the area. We conclude that there is increased production of the 72-kd type IV collagenase (MMP-2) in thyroid cancer; however, this enzyme also is elevated in benign conditions that are undergoing remodeling and repair.

Adenocarcinoma↗
PubMed1992

Treatment of traumatic tattoos with various sterile brushes.

BACKGROUND: Various types of brushes are efficient for the removal of foreign material accidentally projected into the skin by explosive or abrasive trauma. OBJECTIVE: To evaluate how different times between injury and treatment influenced esthetic results, we retrospectively evaluated 14 patients subjected to the brushing technique. METHODS: Two groups were identified. Group I had been treated within 24 hours of injury. In group II debridement had been performed later. RESULTS: Cosmetic results were strikingly better in group I. CONCLUSION: Our results demonstrate that debridement of traumatic tattoos should be carried out as soon as possible to achieve favorable cosmetic results.

Adult↗
PubMed1992

Demonstration of Epstein-Barr viral DNA in paraffin-embedded specimens of lymphoproliferative syndrome. Evidence for a productive infection comparable to lymphoblastoid cell lines.

B-cell lymphoproliferative syndromes (LPS) occurring in immunodeficient subjects are frequently associated with EBV infections. Histology as well as EBV-related serology are not diagnostic, but demonstration of EBV DNA in LPS suspected lesions might be useful for diagnosis. We studied four autopsied cases of LPS that developed in the setting of bone marrow transplantation, with proliferations ranging from poly- to monoclonal. Our protocol of DNA extraction allowed detection of EBV DNA in formalin-fixed, paraffin-embedded tissue specimens of all four cases. In dot blot hybridization the sensitivity in these specimens was 10% as compared to fresh frozen material, but still sufficient for a biotinylated probe. Southern blotting with the former DNA was not successful due to extensive degradation. In situ hybridization resulted in positive signals in all cases, using either 35S or 3H labeled probes. The labeling pattern suggested virus replication in B cells of LPS. By this, LPS resembles productively infected lymphoblastoid cell lines rather than latently EBV-infected Burkitt's lymphoma (BL). These findings strengthen the concept of LPS as a distinct clinicopathologic entity, differing from monoclonal, latently EBV-infected BL, as well as from polyclonal infectious mononucleosis, and the more common EBV-negative Non-Hodgkin lymphomas of the immunocompetent host.

Adult↗
PubMed1992

[Polymorphous photodermatitis. Morphology and temporal course].

From 1985 to 1990 we saw 318 patients with polymorphous light eruption (PLE). Papular (47.4%) and papular-vesicular (27.2%) skin lesions were predominant. A monomorphous picture was seen in 31%. The first lesions appeared within a median period of 19 h after sun exposure, and in 38% of cases within 5 h. In most patients (78.7%) the skin eruptions faded within 1 week of appearance (median 4 days). There seems to be a correlation between the course of light exposure and the resulting clinical morphology. Terminological and methodical problems in the classification of PLE are discussed.

Diagnosis, Differential↗
PubMed1992

Cryosurgery of lentigo maligna.

Lentigo maligna denotes flat, pigmented lesions predominantly in areas of actinic damage that have the propensity to become malignant. More than 10 years may pass before lentigo maligna evolves into an invasive neoplasma. As an invasive process, it is termed lentigo maligna melanoma (LMM), and it has the potential for both lymphatic and hematogenic metastases. Because of the size and location of the lesions, cosmetically unsatisfactory scars may result from conventional surgery. Therefore, alternative means of treatment, including cryosurgery, have been employed. We report on 12 patients suffering from lentigo maligna who had been treated successfully by cryosurgery between 1984 and 1990. The average follow-up period was 51.4 months, and the recurrence rate was 8.3 percent. Knowing that microinvasive components can be demonstrated in 15 percent of lentigo maligna lesions, we retrospectively reassessed our patients by immunohistochemical procedures with S-100 protein. Although intradermal microinvasion could be confirmed in one patient, no recurrence had been observed within 61 months of follow-up. Provided that patients are selected properly and extension of cryonecrosis is monitored, cryosurgery may prove an efficient alternative to conventional surgery in the treatment of lentigo maligna.

Aged↗
PubMed1991

Principles and recent advances in human DNA fingerprinting.

Since 1985, DNA typing systems have played an increasingly important role in many aspects of human genetics, most notably in forensic and legal medicine. This article reviews the development of multilocus and single locus minisatellite DNA probes, and more recently the use of PCR to amplify hypervariable DNA loci, as well as discussing the biological properties of the unstable regions of DNA which form the basis of almost all DNA fingerprinting systems.

Base Sequence↗
PubMed1991

The influence of cosmetic additives on the acceptability of alcohol-based hand disinfectants.

A prospective, randomized double-blind study with intra-individual comparison of the results was undertaken with 20 volunteers to assess the influence of cosmetic additives on the acceptability of a mixture of n-propanol (50% v/v) and isopropanol (30% v/v) for hand disinfection. Three to 5 ml of antiseptic was rubbed into the hands until dry 15 times a day, 5 days a week and for 2 weeks per preparation. For self-assessment the parameters 'appearance', 'intactness', 'turgor' and 'sensation' were evaluated weekly by visual analogue; for assessment by a dermatologist the same parameters except 'sensation' were used. Each score was compared before and after treatment. The antimicrobial efficacy of the alcoholic mixture was equivalent to or better than the standard (isopropanol 60% v/v, 1 min). The frequent application of these antiseptic preparations caused a slight but significant deterioration of the skin condition as judged by both self-assessment and dermatologist; however, this was significantly less when the antiseptic contained cosmetic additives. It is concluded that the addition of suitable emollients can significantly increase the acceptability of alcoholic disinfectants.

1-Propanol↗
PubMed1991

Remission and recurrence after withdrawal of therapy for ocular cicatricial pemphigoid.

Ocular cicatricial pemphigoid (OCP) is a chronic, progressive, autoimmune disease that scars mucus membranes and may lead to blindness. The authors studied the long-term effects of OCP in 104 consecutive patients (average follow-up, 4 years) to determine whether complete remission could be achieved after a course of treatment with immunosuppressive drugs. Prolonged periods of remission while not undergoing therapy were maintained in approximately one third of patients with OCP. Follow-up must be continued for life, as relapse occurred in 22% of those who were in remission and not undergoing therapy. Those who relapsed regained disease control readily upon reinstitution of therapy and did not deteriorate to more advanced cicatrization. Sex, age, initial degree of inflammation, and the incidence of extraocular involvement did not have a prognostic significance on outcome. Mechanisms that underlie the differing responses to therapy are not yet known.

Adult↗
PubMed1991

[Supplemental infection therapy with i.v. immunoglobulins (polyvalent IgG and Pseudomonas IgG)--results of an observational case study with 163 patients].

The impact of i.v. immunoglobulin (IVIG) therapy on the survival of adult septic patients cannot yet be considered either proved or disproved. To define optimal criteria for a large multicenter placebo-controlled trial, a multicenter observational study was carried out in 163 medical and surgical patients exhibiting a total of 173 episodes of sepsis and septic shock [Elebute (El) sepsis score; 19 +/- 0.5). The effects of supplemental IVIG treatment (unmodified polyvalent IgG, pH 4.25, n = 123; for Pseudomonas sepsis, n = 50, Pseudomonas IgG) on multiple-organ failure (MOF) were investigated according to changes in the APACHE II score (AP) (pretreatment value 23.7 +/- 0.6). In 44% of the cases ("responders"), a prompt improvement in AP (defined as a decrease of greater than or equal to 4) was evident from day 0 to day 4 after the onset of therapy, thus showing a close temporal relationship to IVIG administration. This improvement, associated with an improved prognosis (mortality, 24% vs 55%), was found in all subgroups, most importantly, polyvalent IgG vs Pseudomonas IgG treatment; medical vs surgical patients; moderate vs severe MOF; and gram-positive vs gram-negative septicemia. Thus, all of these patients should be included in future placebo-controlled, randomized IVIG trials.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

[The pathology and pathogenesis of experimental Mycoplasma hyorhinis infection of piglets with and without thermomotoric stress. 1. Pathologico-anatomic, histologic and immunomorphologic study results].

The effect of an experimental Mycoplasma (M.) hyorhinis infection (3 times intranasal instillation of 3-5 ml bouillon with 10(7) Colony forming units [CFU]/ml) in combination with a standard thermomotoric stress (swim-test) was studied in piglets using pathomorphological, immunomorphological and microbiological methods. The 92 piglets were divided into the following 5 groups: swimmers with infection (S-I; n = 19); swimmers without infection (S; n = 19); control piglets with infection (K-I; n = 21); controls without infection, but direct (K1; n = 16) or indirect contact (K2; n = 17) with experimentally infected animals. The experimental or spontaneous infection (direct or aerogenous infection) with M. hyorhinis caused in 30.4% of the piglets an acute or subacute, catarrhal-purulent bronchopneumonia with an interstitial component. Incidence and intensity of pneumonia were significantly higher in the groups with thermomotoric stress (independent from the mode of infection) than in the non-stressed groups. The M. hyorhinis pneumonia was characterized by a limited expansion and a trend to restitution. The causal agent (M. hyorhinis) was demonstrated with immunomorphological methods (immunofluorescence and PAP) in the ciliary zone of the nasal, tracheal and especially on the bronchial mucosa, and occasionally in the bronchioles and alveoli.

Animals↗
PubMed1991

[The pathology and pathogenesis of experimental Mycoplasma hyorhinis infection of piglets with and without thermomotor stress. 2. Electron microscopic study results].

Electron microscopic investigations on the respiratory tract of piglets with and without Mycoplasma hyorhinis infection (10th day of life) partly combined with swim stress (15 degrees C water temperature) (n = 20/20) yielded the following results: colonization of Mycoplasma hyorhinis in the ciliary zone of trachea and bronchi in 15 out of 40 piglets (37.5%); the evidence rate of Mycoplasma hyorhinis in pneumonic lungs (8 out of 12 = 66.7%) was significantly higher than in nonpneumonic lungs (7 out of 28 = 25.0%) and highest in experimentally infected piglets with swim stress (9 out of 16 = 56.2%). Ultrastructural lesions: loss of cilia; bleb-formation; hydropic degeneration and desquamation of ciliary cells; the occurrence of cilia-free and immature epithelial cells; alveolar collapse; microatelectasis; oedematous swelling of pneumocyte I; accumulation of surfactant in the alveoli; hyperplasia of pneumocyte II; exudation of mononuclear macrophages and neutrophils with numerous digestion vacuoles; several lymphocytes and plasma cells, only a little lymphohistiocytic interstitial and peribronchial infiltration. Phagocytized mycoplasmas were found within the resorption vacuoles of neutrophils in the tracheobronchial area, for this once in alveoli, not (more) against in alveolar macrophages. The results were discussed with regard to etiology and pathogenicity of enzootic pneumonia in pigs.

Animals↗
PubMed1991

[The patient with polymorphous light dermatosis. Skin type, hardening and other light-associated markers].

From 1985 to 1989 we interviewed 312 patients suffering from polymorphous light eruption (PLE). The interviews were based on a questionnaire dealing with the various light-dependent factors that exacerbate the disease. Of 90 patients who were tested with artificial UV-A and UV-B irradiation sources, 60 reacted with typical PLE lesions: (a) 27 patients to UV-A alone, (b) 12 to UV-B alone, and (c) 21 to both UV-A and UV-B. Using UV-A provocation tests we were able to determine the anamnestic criteria indicating a possible UV-A induction of PLE, e.g. occurrence in the shade, no protection from window glass, no benefit from conventional sunscreens, and occurrence in solaria. The period from experimental irradiation to induction of skin lesions was shorter in skin types I and II than in skin type III and IV. Hardening phenomenon was reported by 37% of our patients. Of the UV-A-positive patients, 38% showed the first presentation of PLE lesions at the height of summer, as against 64% of the total number of patients questioned. Additional lesions at non-irradiated skin sites occurred in 25% of our patients, the frequency rising with increasing duration of the tendency to PLE.

Adult↗
PubMed1991

[Acute uncomplicated anterior knee instability. 2-5 year follow-up of surgical treatment].

A retrospective review of 158 acute anterior cruciate ligament injuries without additional ligamentous lesions was conducted. The follow-up study included 127 patients (80%), 109 of whom were personally examined 2-5 years after surgery. In the largest group proximal ruptures were found and treated with reinsertion. The other group had intraligamentary ruptures which were augmented with semitendinosus tendon. A modified Ellison procedure was routinely performed. Postoperative treatment was cast-free and included immediate physiotherapy using a functional brace. Examination at follow-up included Lysholm score, Tegner activity scale, instrumented testing with a KT-100 arthrometer and measurement of isometric leg muscle strength in four different positions. Among other clinical manoeuvres, the Lachman test and pivot shift testing were performed. No significant differences were found between the two groups in subjective evaluation, stability, consecutive meniscal lesions or patella symptoms. The average anterior dislocation difference at 89 N was 2 mm in both groups. Pivot shift was definitely absent in 88% of one group and 90% of the other. Almost no meniscal problems were noted, but 15% of the patients complained of patellofemoral pain.

Adolescent↗