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Biomedical subjects

M Hoffmann

Publications and source records attributed to M Hoffmann.

At least 163 records · Page 9Linked to original sources

Efficacy of skin barrier creams (I). The repetitive irritation test (RIT) in the guinea pig.

An animal model for the evaluation of skin protective creams against chemical irritants is described. The irritants were applied daily for 2 weeks to shaved back skin of young guinea pigs: sodium lauryl sulphate (5% aq.; 30 min), sodium hydroxide (0.5% aq.; 2 min), and toluene (20% eth.; 2 min). The barrier cream was applied 2 h prior to and immediately after exposure to the irritant. Control animals were treated with the irritant only. The irritant reaction was scored on a 4-point scale for erythema and quantified with regard to transepidermal water loss (TEWL) by evaporimetry and skin blood flow volume (BFV) by laser Doppler velocimetry. A total of 90 guinea pigs, consisting of individual panels of 5 to 10 animals, was tested. While one barrier cream (Stokoderm) significantly suppressed the irritation due to sodium lauryl sulphate and toluene, the other (Contra-Alkali) failed to do so and even aggravated the response, which was particularly evident with sodium hydroxide. This model may be useful in developing more effective barrier creams.

Animals↗

Efficacy of skin barrier creams (II). Ineffectiveness of a popular "skin protector" against various irritants in the repetitive irritation test in the guinea pig.

A popular "skin protector" consisting of an emulsion-like foam of lipophilic and hydrophilic substances (Marly skin) was evaluated in a previously described repetitive irritation guinea pig model. The product failed to inhibit the irritation due to sodium lauryl sulphate and toluene. In striking contrast to the recommended use, the irritant response of sodium hydroxide was aggravated, as demonstrated by significant differences for all test parameters (clinical score for erythema and scaling, transepidermal water loss, blood flow volume). The results show that protection against chemical irritants may be quite specific and that some formulations may actually be harmful.

Administration, Topical↗

Noninvasive detection of vertebral artery dissection.

BACKGROUND AND PURPOSE: We sought to identify the use of duplex and transcranial Doppler sonography in the noninvasive diagnosis of vertebral dissection. METHODS: Ten patients with a diagnosis of symptomatic vertebral artery dissection confirmed by cerebral angiography were retrospectively analyzed. RESULTS: Computed tomographic scanning and magnetic resonance imaging together delineated lateral medullary or cerebellar infarcts in 7 patients. Angiography documented a total of 21 vertebral artery lesions (16 stenoses and 5 occlusions), with 7 of 10 patients having multiple sites of vertebral artery dissection. Vertebral Doppler was abnormal in 8 of the 10 patients. A high resistance signal in the relevant vertebral artery was found in 6 patients, no flow in a well-imaged vertebral artery in 1, and bilateral retrograde vertebral artery flow in 1 patient. Transcranial Doppler was abnormal in only 2 patients, with reduced pulsatility index in 1 and high resistance vertebral signal in another. A hyperintense intramural signal of the affected vertebral artery by magnetic resonance imaging was documented in 1 patient in whom Doppler sonography was nondiagnostic. CONCLUSIONS: Vertebral artery dissection can be detected and monitored by noninvasive vertebral Doppler and magnetic resonance imaging in the setting of a clinically suggestive presentation.

Adult↗

Cytogenetic studies in lymphocytes of patients with rectal cancer.

Spontaneous and clastogen-induced chromosomal instability in a high-risk group (i.e, 33 patients with rectal carcinomas) was investigated using peripheral blood lymphocytes as target cells. In addition to the analysis of spontaneous and clastogen-induced chromosome aberrations, this study also included classical karyotype analysis and scoring of sister chromatid exchanges (SCE) in some of the patients. Diepoxybutane (DEB), 4-nitroquinoline-1-oxide (NQO), and bleomycin were used as standard clastogens. Lymphocytes of healthy control individuals were studied in parallel with each cancer patient. While only slight but significant differences could be detected of the average spontaneous, DEB- and bleomycin (G2)-induced chromosome breakage between patient and control lymphocytes, individual patients and two of the control individuals showed a more distinct increase in the frequency of the studied end points. These increases were documented by a variegated mosaicism of karyotypic changes and by an increased breakage rate induced by the clastogens. Neither the bleomycin-exposure in the G1 phase nor SCE was capable of detecting differences between the patients and controls. Of particular interest in the sense of high-risk individuals were seven patients and two control persons whose lymphocytes exhibited increased chromosomal sensitivity under more than one of the studied experimental conditions.

4-Nitroquinoline-1-oxide↗

[Local vascular complications in heart catheter studies].

Over a period of 30 months (1. 1. 89-30. 6. 91) 3516 patients who had either a diagnostic (2718) or therapeutic (798) heart catheterization were followed for local vascular complications. 774 patients were investigated prospectively. The following complications were observed in declining frequency: 1. relevant haematoma, 2. pseudoaneurysm, 3. arteriovenous fistula, 4. arterial thrombosis/dissection, 5. venous thrombosis, 6. rupture of the vessel, 7. local infection. The total complication rate was 2.22%. With prospective investigation it was significantly higher (3.23%) than with retrospective investigation (1.93%). The complication rate was also significantly higher in therapeutical procedures (3.76%) than in diagnostic catheterizations (1.76%). Factors associated with a significantly higher incidence of local vascular complications were age (p < 0.01), female gender (p < 0.025), manifest arterial hypertension (p < 0.005), aortic regurgitation (p < 0.1), peri-interventional medication with acetylsalicylic acid and full dose heparin (p < 0.001), full dose heparin alone (p < 0.001) or fibrinolysis-therapy (p < 0.025). Relevant technical factors were: duration of the procedure, duration of the placement of the catheter-sheath, French size of the catheter, left femoral access, arterial and venous access at one extremity. In about half of the cases the treatment of the complications was conservative, in the other half it was surgical (51%). In relation to all surgically treated patients the percentage of emergency operations was 25%, the percentage of reoperations was 15%.

Adult↗

A simplified method for the determination of nitric oxide in biological solutions.

A new simplified procedure for determination of nitric oxide (NO) in biological solutions is described utilizing a new reducing system of nitric oxide prior to chemiluminescence. Advantages of the new method makes heating of the reducing solution unnecessary and avoids cooling and condensation of generated vapors. Only traces of acid with a high boiling point are used. The method permits analysis of small sample volumes (200 microL). The basal production of nitric oxide by freshly harvested endothelial cells ranged from 100 to 880 picomoles.

Animals↗

Analysis of the promoter of the cytochrome P-450 2B2 gene in the rat.

About 3 kb of the promoter region of the gene encoding cytochrome P-450 2B2 (CYP2B2) in the rat were sequenced and searched for potential cis-acting elements. Apart from putative binding sites for (liver-specific) protein factors, a region showing homology with the LINE 1 retrotransposon element was also found. Three proximal promoter fragments, encompassing nucleotides -579 to -372, -372 to -211, and -211 to +1, respectively, were shown to contain binding sites for multiple protein factors by bandshift analyses. The strongest protein-binding element, designated BRE (basic regulatory element), occurs between -103 to -66. Its structure is very similar to a negative control element in the murine cmyc promoter and displays a composite feature having a tandemly repeated sequence homology with the BTE (basic transcription element; Yanagida et al., 1990) separated by a CCAAA-box. The use of a deletion series of this template in in vitro transcription assays, provided evidence that the BRE serves as a major cis-acting element in the (regulated) transcription activation of the CYP2B2 gene.

Animals↗

[Mercury concentration in blood and urine--before and after the placement of dental amalgam fillings].

70 patients of dentist's surgery were given MOD amalgam fillings (non-gamma-2 amalgam) for molars. They were allocated for comparison to four groups defined by their treatment, i.e. the number of old and new restorations and whether a rubber dam was used. Blood and urine samples were collected at regular intervals before and during a 14-day period after treatment and tested for mercury concentration (Hg). Over the observation period the groups with the highest exposure (1-2 old restorations replaced by new ones) showed a tendency, in contrast to the less exposed groups (1 new filling with or without dam), towards increases (p less than 0.10) in group average Hg values of approx. 0.2 microgram/L (blood) and 0.3 microgram/g creatinine (urine) as acute treatment effects. The highest values recorded before and after the treatment, 3.3 micrograms/L (blood) and 16.5 micrograms/L (urine) are higher than normal but do not indicate any increase in the risk to health especially if they are not persistent.

Creatinine↗

[The importance of estradiol treatment by the transdermal route in preventing postmenopausal osteoporosis].

The authors selected 18 women in surgical menopause in order to evaluate the validity of estrogen treatment for the prevention of postmenopausal osteoporosis. Ten of these patients were given transdermal estradiol continuously for 12 months while the remaining eight served as untreated controls. Urinary hydroxyproline and bone density were assessed before and at previously determined intervals during treatment: the results showed the importance of estrogen replacement therapy for the prevention of postmenopausal osteoporosis.

Administration, Cutaneous↗

Fibrin degradation product D-dimer in the diagnosis of pulmonary embolism.

The study objective was to determine the specificity and sensitivity of plasma concentrations of D-dimer, a fibrin degradation product, as a marker for ongoing thrombotic and thrombolytic events in pulmonary embolism. A prospective study was performed in 74 patients with suspected pulmonary embolism who appeared in the emergency room with dyspnea and/or chest pain. The presence of pulmonary embolism was established by positive findings either in pulmonary angiography or lung scan. D-dimer concentrations were determined in all patients. In 11 patients with positive pulmonary angiography, D-dimer concentrations were monitored for 6-12 days. D-dimer concentrations were determined by a quantitative enzyme-linked immunoassay. Plasma probes of 26 patients (16 with/10 without positive pulmonary angiography) were re-assayed with a semiquantitative latex agglutination assay. D-dimer levels were significantly higher in patients with pulmonary embolism (greater than 1000 ng/mL in 41 out of 43) than in those without (less than 1000 ng/mL in all 21 patients) (p less than 0.01). The sensitivity and specificity for the ELISA were found to be 95% and 100%, respectively, for establishing the diagnosis of pulmonary embolism. In the latex assay the values were 81% and 60%, respectively. It is concluded that in patients with dyspnea and/or chest pain, determination of D-dimer in plasma by ELISA adds a valuable tool to the noninvasive diagnostic procedure for pulmonary embolism. From the time-course of D-dimer values we conclude that this assay might be valuable up to at least 6 days after symptom onset. The assay, however, is unreliable in malignancies or after surgery.

Adult↗

Spinal cord schistosomiasis. A clinical, laboratory and radiological study, with a note on therapeutic aspects.

Fourteen patients with schistosomiasis of the spinal cord are described. They fall into two groups: 7 patients had clinical and computer-assisted myelographic evidence of lesions in the conus medullaris or cauda equina, or both. The clinical picture in the remaining 7 patients was usually that of acute or subacute transverse myelitis with normal or equivocal CT myelographic appearances. Granulomas containing bilharzial ova were found in 2 female patients with conus swelling subjected to laminectomy and biopsy. In 1 of these the ova were identified as S. haematobium while in the second, unidentified bilharzial ova were found. A presumptive diagnosis of spinal cord schistosomiasis was made in the remaining 12 patients based on characteristic clinical and investigative profiles. All 13 patients tested showed evidence of bilharzial infection based on positive blood serology or the detection of bilharzial ova, or both. All but 1 patient showed at least one of the following abnormalities on CSF examination: pleocytosis, an elevated protein content and as indicated by the presence of oligoclonal IgG bands, an elevated IgG index and an increased CSF IgG synthesis rate. A CSF bilharzia enzyme-linked immunosorbent assay (ELISA) test, developed to indicate the presence of schistosomal infection within the theca, was found to be sensitive although not entirely specific for the diagnosis of spinal cord schistosomiasis. Eleven of the 14 patients showed rapid clinical improvement, 8 after praziquantel and corticosteroid treatment, 2 after operation and 1 spontaneously. Significant reductions in the CSF cell count, protein concentration and bilharzia ELISA titre, and in intrathecal antibody production, occurred following praziquantel and corticosteroid therapy. The CSF sugar level showed a significant rise. A reduction in conus size was observed in 3 patients when CT myelography was repeated after medical therapy. The normalization of most of the laboratory parameters after combined medical treatment with praziquantel and corticosteroids, together with clinical and radiological improvement, strengthened the presumptive diagnosis of cord schistosomiasis and supports the policy of early intensive medical treatment (as opposed to surgical therapy) for this condition when diagnosed on indirect evidence.

Adolescent↗

A transgenic approach to the study of peripheral T-cell tolerance.

There is now convincing evidence for the imposition of self tolerance by means of the clonal deletion of self-reactive T cells operating within the thymus. Since not all self components may be encountered there, the question must be asked whether tolerance can occur post-thymically. To test this, we and other investigators have used transgenic technology to direct expression of a known "nonself" gene to a given extrathymic tissue. No lymphocytic infiltration was ever seen in transgene-expressing tissues, even if the mice were given normal syngeneic (nontransgenic) spleen cells intravenously or were stimulated with H-2Kb spleen cells. Infiltration did, however, occur in irradiated transgenic recipients of H-2Kb immune spleen cells. In MET-Kb mice, this infiltrate diminished with time, raising the possibility that peripheral tolerance may even have been induced in immune cells. H-2Kb-bearing skin was accepted in young RIP-Kb mice but rejected in older mice, which had lost more than 75% of their beta cells as a result of the overexpression of H-2Kb. This loss of tolerance thus occurred when the concentration of the tolerogen, H-2Kb, fell below some critical threshold. Following in vitro stimulation, spleen cells from young RIP-Kb mice could not kill H-2Kb-bearing targets, but could respond to third party targets. Thymus cells, on the other hand, could be stimulated to kill both targets, clearly indicating that tolerance was not imposed intrathymically. Spleen cells from older RIP-Kb mice (those that had lost most of their beta cells) killed both targets, which is in agreement with the in vivo data. Reactivity to H-2Kb was restored to young spleen cells by providing them with IL-2. Two hypotheses were proposed to account for the above findings: tolerance results either from the deletion or functional silencing of high-affinity effector cells or of regulatory, IL-2-producing helper T cells. As it is difficult to distinguish between these, we have produced a second series of transgenic mice (F3+) with rearranged TCR genes encoding an anti-H-2Kb TCR and derived "double-transgenic" (F3+RIP+) offspring by mating these mice with RIP-Kb mice. The transgenic TCR utilized the V beta 11 segment which can be detected by a monoclonal antibody. There were in the thymus very few CD4+ and very few CD4+8+ cells in both F3+ and F3+RIP+ mice and, in the double-transgenic mice, there was no evidence of deletion of CD8+V beta 11+ cells in the periphery although they showed tolerance to H-2Kb-bearing skin.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Does interleukin-1 save B cells from paralysis? Studies with pre-B cells and antigen-reactive B cells.

The role of the second messenger cAMP in the differentiation of the pre-B cell line 70Z/3 and in the initial phase of the immune response of B cells, IgM antibody production is examined. Our data indicate that in these B cells, the elevation of intracellular cAMP levels can have two fundamentally different effects: it may dedifferentiate B cells and cause their disintegration (catabolic pathway) or it may induce their differentiation and maturation (anabolic pathway). The switch that determines which pathway B cells enter is set by interleukin-1. Our experiments indicate that intracellular cAMP levels rise in B cells when they interact with helper T cells in a cognate interaction. Given the dual effect that cAMP may have on the fate of B cells, activation or destruction, our data may be taken to suggest that helper T cells may direct B cells into catabolic or anabolic responses, depending on the availability of a costimulatory signal mediated by interleukin-1.

Animals↗

[The ruminal nitrogen metabolism in calves and sheep. 1. Studies in calves].

In a model experiment with calves supplied with duodenal re-entrant and rumen fistula resp. rations were tested that were energetically different (535 and 585 EFU cattle/kg DM) due to changing quotas of wheat starch and straw resp., dry matter intake being equal, and in which 45% of the crude protein came from soybean oil meal or urea resp. Due to the N-equivalent exchange of soybean oil meal by urea in rations for ruminating calves (130th day of life) the ammonia-N content in the rumen fluid, the quota of bacteria-N in the duodenal non-ammonia N (NAN) as well as the fermentation of crude plant protein in the ration were clearly increased. The iso-acid content in the rumen fluid and the utilization of the N available for bacteria N synthesis (N intake minus not degraded feed N in the duodenum) were reduced. An influence on duodenal NAN passage, on the apparent fermentation of the organic matter, on postruminal NAN digestibility and on the content of amino acid nitrogen as well as the amino acid composition of duodenal NAN could not be proved. A ca. 20% higher energy intake by ruminating calves did not have a clear influence on other parameters, with the exception of the reduction of the molar quota of acetic acid in favour of the quota of propionic acid in the rumen fluid.

Amino Acids↗

[The ruminal nitrogen metabolism in calves and sheep. 2. Studies in wethers].

Energetically differing rations which received ca. 45% of their crude protein from a supplement of soybean oil meal or urea were tested in a model experiment with adult wethers fitted with duodenal re-entrant cannulae or rumen cannulae resp. The N-equivalent exchange of soybean oil meal by urea in wethers resulted in a distinct increase of the NH3-N content of the rumen fluid, an increase of irreversible N losses and thus a worsening of the utilization of the available N for bacterial N-efficiency. A significant influence on duodenal NAN passage, on the apparent fermentation of the organic matter, on postruminal NAN digestibility and on the content of amino acid nitrogen as well as the amino acid composition of the duodenal NAN could not be detected. The increase of the energy level of the rations did not have a significant influence on the parameters of the ruminal N metabolism in the wethers. The studies with calves and adult wethers showed that a transposition of the parameters of ruminal N metabolism obtained to calves is not possible under the conditions given.

Amino Acids↗

A murine model of NK cell mediated resorption.

There is increasing evidence that some models of immunologically mediated murine embryo demise involve nonspecific lytic effector cells. In this paper, we use two double stranded synthetic RNAs, known as potent interferon inducers and NK cell activators, the Poly (I). Poly (C) and the less toxic Poly (I). Poly (C12U). These polynucleotides enhance fetal resorption rates in both resorption prone and none-resorption prone strains of mice. We have studied the kinetics of the phenomenon, and observed an anti-implantation-like effect of early injection during early pregnancy. The abortifacient effects can be adoptively transferred to naive recipients by spleen cells from Ds RNA injected donors. Such effects are abrogated if the cells are pretreated with anti-NK cell antiserum. The relevance of these findings to the survival of the conceptus is suggested.

Animals↗