Biomedical subjects
Publications and source records attributed to R Feldmann.
Diabetes mellitus is a common disease, and the cutaneous manifestations of it are frequently encountered. Some skin diseases have a strong association with diabetes, as necrobiosis lipoidica and diabetic bullae. They can be regarded as a cutaneous marker for diabetes. Other disorders--for example shin spots--also occur in the nondiabetic population. Cutaneous infections may be a sign of poorly controlled diabetes.
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Antimalarials are the first line in the treatment of chronic and subacute cutaneous lupus erythematosus (LE). However, some patients show either no or only minor improvement on antimalarial monotherapy. We treated 14 patients (9 with chronic LE and 5 with subacute cutaneous LE) who had poorly responded to chloroquine or hydroxychloroquine with an association of chloroquine and quinacrine. The initial dose was: chloroquine 100 mg 3x/day and quinacrine 65 mg 3x/day. The skin lesions improved significantly or cleared totally in 5 of the 9 patients with chronic LE and in all the 5 patients with subacute cutaneous LE. These findings suggest that a chloroquine-quinacrine combination may sometimes be superior to the usual antimalarial monotherapy, especially for subacute LE. If chloroquine or hydroxychloroquine fails to control chronic or subacute cutaneous LE, chloroquine-quinacrine is worthy to be tried.
We previously described an acute dermatosis characterized by pruritic erythematous and slightly papular lesions on the hands and feet in a 'gloves and socks' distribution associated with oral aphthoid lesions and fever (papular-purpuric 'gloves and socks' syndrome = PPGSS). We strongly suspected a viral origin, but serologic tests for a large panel of viruses remained negative. Subsequently, 2 cases of PPGSS with serologic evidence of a parvovirus B19 infection have been reported in the literature. Since then we observed 5 additional patients with a PPGSS. Parvovirus B19 infection could be confirmed in only 2 cases. Our findings suggest that the PPGSS can be another, yet undescribed manifestation of parvovirus infection. However, this cannot be shown in all the cases. As the papular acrodermatitis of childhood, this syndrome may be caused by various viral agents.
In congestive heart failure, down-regulation of myocardial beta-adrenoceptors (beta-AR) due to an elevated sympathetic tone is well known. In infancy and childhood, heart failure is usually related to congenital heart disease (CHD). Therefore, 71 samples of right atrial tissue of infants and children with CHD undergoing cardiac surgery were studied for beta-adrenoceptor density and distribution of the beta 1-/beta 2-AR subtypes. In 49 cases, the coupling of the beta-AR to the adenylate cyclase (AC) was examined. In a further study of 19 myocardial samples, AC was selectively stimulated with beta 1- or beta 2-AR whereas the other subtype was blocked by an antagonist. The following results were obtained: (1) Infants and children with severe acyanotic or cyanotic CHD had severely reduced beta-AR densities. (2) In most of the cases, the beta-AR down regulation is beta 1-subtype selective, but in critically ill newborns with congenital aortic valve stenosis or transposition of the great arteries, there is additional significant beta 2-AR down-regulation. In Fallot patients treated with the beta-antagonist propranolol, a significant increased beta-AR number compared with untreated Fallot patients was found. (3) beta-Adrenoceptor reduction in CHD is correlated with elevated noradrenaline plasma levels, thus proving a sympathetic dysregulation. (4) In CHD with moderate hemodynamic load, beta 2-AR coupling to AC was markedly more efficient than beta 1-AR coupling. The small number of myocardial beta 2-AR produced most of the cyclic adenosine monophosphate. (5) In severe acyanotic and cyanotic CHD, a partial decoupling of the beta 2-AR to the AC occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
A case of primary autonomic failure (AF) with uncomplicated Parkinson's disease is presented with clinical and neurophysiological data. Special emphasis is placed on new methods of examining impairment of unmyelinated sympathetic and afferent C-fibres. Sympathetic vasoconstrictor responses in the skin induced by deep inspiration were examined quantitatively with laser Doppler flowmetry. The vasoconstriction was markedly depressed in primary AF compared with healthy controls and similar to secondary forms of AF. Peripheral nociceptive C-fibre function was quantitatively assessed by measurement of axon reflex vasodilatation induced by histamine iontophoresis. The axon reflex vasodilatation was completely intact in primary AF in contrast to patients with secondary peripheral small fibre neuropathy. The results indicate that sympathetic C-fibres are considerably affected by the degenerative disease, whereas the afferent C-fibres seem to be totally preserved. Modern neurophysiological methods of testing sympathetic and afferent small fibre function in combination with other neurophysiological tests, e.g. brain-stem auditory evoked potentials, might help to diagnose and differentiate primary AF in early stages and make it easier to distinguish between secondary autonomic neuropathies of unknown origin that often also involve unmyelinated afferent fibres.
The influence of childhood pertussis infection and of purified pertussis toxin on histamine release from human basophil leucocytes was investigated. Three different stimuli, the peptide N-formyl-Met-Phe (NFMP), anti-IgE, and the calciumionophore A23187 were used to challenge the cells. When NFMP was the stimulus, histamine release in the control group (age 0.5-17 years) increased in an age-dependent fashion, whereas anti-IgE and A23187 stimulated release did not vary with age. During the convulsive state of pertussis infection there was a significant reduction of histamine release in response to 10 microM NFMP (from 9.5 +/- 1.4 [n = 21] to 6.7 +/- 1.5 [n = 19], P < 0.05) and in response to 800 and 80 U/ml anti-IgE (from 28.5 +/- 5 [n = 19] to 16.3 +/- 5 [n = 13], P < 0.05, and from 6.9 +/- 1.7 [n = 16] to 2 +/- 0.8 [n = 13], P < 0.01), whereas histamine release stimulated by A23187 was unchanged compared to release in control children. In vitro pretreatment of basophils from healthy children and adults with pertussis toxin also inhibited histamine release. When NFMP was the stimulus, release was completely blocked by pertussis toxin with an IC50 of about 11 ng/ml, whereas anti-IgE stimulated release was only inhibited by 20%-30% and release induced by A23187 was reduced to 40%-50% by toxin treatment. In conclusion we have demonstrated a functional impairment of histamine release during the convulsive state of pertussis and that this inhibition is likely to be mediated by pertussis toxin.
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We report on a 41-year-old female patient who presented with a 3-year history of multiple filiform hyperkeratoses on the trunk. The family history revealed that her uncle had similar skin lesions. Another patient presented with filiform hyperkeratoses only on the palms of the hands and soles of the feet. This condition, referred to in English as multiple minute digitate hyperkeratoses, is a rare, mostly hereditary, disorder of cornification. As yet there is no official name for this dermatosis in German; we propose "multiple filiforme Hyperkeratosen".
Paraffinoma is a well-recognized complication of paraffin injection. We describe a 44-year-old man who had an ethmoidectomy for chronic sinusitis. A communicating fracture of the ethmoid bone into the orbit occurred intraoperatively. The nasal cavity was subsequently packed with gauze containing a petrolatum-based antibiotic ointment. Bilateral, periocular swelling developed 1 week later. Optical and electron microscopic studies revealed a paraffinoma.
We report a 66-year-old woman with a 3-year history of intensely pruritic follicular papules in the axillar, pubic and inguinal areas. Previous treatment with topical fusidic acid and gentamicin sulfate was ineffective. The clinical and histological examination was consistent with Fox-Fordyce disease. Application of clindamycin in an alcoholic propylene glycol solution led to the clearing of the lesions within 1 month. Nine months later, the treatment was stopped, and no recurrence was observed.
The protein C system is a physiological inhibitor of coagulation and is important for the regulation of hemostasis. Protein C deficiencies can be inherited or acquired, and they lead to enhanced thrombophilia. A number of clinical entities that are also of interest to dermatologists have been related to protein C deficiency. Inherited protein C deficiency can become manifest in various ways, e.g. as purpura fulminans neonatalis, as recurrent episodes of thrombosis and as coumarin necrosis. Acquired protein C deficiency can be observed in the course of purpura fulminans, disseminated intravascular coagulation, hepatic failure or in the presence of antiphospholipid antibodies. The clinical features, the possible pathogenesis and the therapy of these manifestations are briefly discussed.
A review of lichen sclerosus et atrophicus is presented in this article. Clinical manifestations, possible complications and histology are described. Particular emphasis is given to the aetiological hypotheses, which include genetic, autoimmune, hormonal and infectious mechanisms. Finally, the various treatments are discussed.
We report five cases of an acute, self-limiting dermatosis that has not been previously described. It consists of a pruritic edema and erythema of the hands and feet in a gloves-and-socks distribution and is associated with oral lesions and fever. The clinical course is characterized by the rapid development of petechial purpura and clearing of lesions within 1 to 2 weeks. The disease appears to affect only young and otherwise healthy persons and occurs mostly during the spring. The etiology is unknown but might be of infectious origin.
In order to study the dynamics of protein and nucleic acid conformations, a molecular folding-unfolding system (FUS written in Lisp) has been developed. Secondary structure features of protein and nucleic acids are graphically represented by cubes in a modified 'Blocks World' paradigm. Modeling of protein and nucleic acid unfolding (denaturation) and folding of their three-dimensional structure is possible by the use of high level 'block' operators which allow displacement of these structural features in space. Due to the flexible nature of this program, FUS is a useful tool for the rapid evaluation of user-defined rules governing conformational changes. The use of FUS to unfold three common proteins (prealbumin, flavodoxin and triose phosphate isomerase) and a tRNA is presented.
A regular family support group was established within an outpatient clinic for demented elderly patients. At the outset of the group, the relatives knew little about the disease and about the available resources of help, but some were highly experienced in the management of dementia. The group provided information, exchange of experience, practical problem-solving, support in emotional difficulties, and clarification of interpersonal conflicts in the family. The effect of the group showed in decreased feelings of burden and tension in most participants. The present observations suggest that family support groups should be long-termed and that the experts' primary task is to activate and amplify the self-help potential of the caregivers.
The defective parvovirus Adeno-associated virus (AAV) is absolutely dependent upon coinfection with either Adenovirus or Herpes Simplex Virus (HSV) for its multiplication. We have compared the terminal repeats of HSV-1F strain DNA with the terminal 200 nucleotides of AAV DNA. Our findings demonstrate similarities between portions of the HSV inverted repeats found at the L/S junction and the termini of AAV. By computer analysis we have determined potential secondary folding patterns for both genomes. The following points can be made about the a, b, and c repeats in HSV: (1) Regions b and c are complementary over a significant portion of their length. (2) The ends of a can fold back on themselves to form large secondary structures. Moreover, when the b and c homology is used to align the ends of a, the b/a and c/a junctions are within 1 base of each other. (3) The short direct repeats within a are essentially a large loop with little secondary structure. The potential implications of this structure are discussed and a model for HSV DNA replication is presented.
The architecture of the 48-meric hemocyanin of the horseshoe crab Limulus polyphemus has been determined from electron micrographs of whole (48-mer) molecules and half- (24-mer) molecules. The assembly of hexamers of kidney-shaped subunits can produce two dodecameric enantiomorphs, designated as right and left. The assembly of 24-mers can again result in two enantiomorphs. By taking into account the rocking effect described by Van Heel and Frank [Van Heel, M., & Frank, J. (1981) Ultramicroscopy 6, 187-194], we deduced that the 24-meric half-molecule is made up of two copies of the left dodecameric enantiomorph. In addition, the two constituent dodecamers of the half-molecule are shifted with respect to a symmetric head-to-tail arrangement, which makes it possible to distinguish two different faces of the 24-mer, termed flip and flop. A model of the whole molecule was built from two copies of the 24-meric half-molecule. This model presents the four distinct views observed in the electron microscope (pentagon, ring, cross, and bowtie). In addition, the model shows the pentagonal view to exist in two varieties: symmetric and asymmetric. An analysis of electron micrographs presenting the pentagonal view by image processing using the statistical technique of correspondence analysis confirmed the existence of two types of pentagonal view, representing projections of a molecule built from two copies of the left 24-meric enantiomorph. In addition, the best fit between the averaged molecule images and the possible models was observed with a flop-flop inter 24-mer contact. The final model is shown in a series of stereo views produced by computer graphical techniques.