[Hypersensitivity reactions to implantable cardiac pacemakers and defibrillators]. / Unverträglichkeitsreaktionen auf implantierbare Herzschrittmacher und Defibrillatoren.

Nowadays, for modern electrotherapy of cardiac arrhythmias different pacemaker systems are used. Antibradycardia pacing systems (e. g. single-chamber, two-chamber, three-chamber systems, frequency-adapted pacemaker) can be distinguished from antitachycardia pacing systems like implantable or portable cardioverter defibrillators and combined antibradycardia/antitachycardia systems. Cutaneous reactions overlying a pacemaker or defibrillator are often termed "pacemaker dermatitis". In terms of the differential diagnostic workup, these cutaneous reactions can have various causes. After exclusion of infection by analyzing clinical and laboratory-chemical results, "pressure dermatitis" or the often clinically asymptomatic "reticular telangiectatic erythema" (synonym "postimplantation erythema") must be considered. Histological examination of the affected skin can contribute to the diagnosis. In case of suspected contact hypersensitivity to implant material, allergological exploration should be realized. In addition to patch testing with commercially available contact allergens, product-related material metal alloy discs are often available from the pacemaker manufacturer for epicutaneous testing. Due to the lack of additional benefit compared to standardized patch testing, a clear recommendation for such metal alloy discs cannot be given. In selected cases of suspected hypersensitivity reaction, sensitization can eventually be analyzed by the lymphocyte transformation test. Positive reactions must always be critically interpreted taking into consideration the corresponding clinical signs. Depending on the cause, cutaneous reactions are occasionally self-limiting. In many cases, however, removal of the pacemaker is inevitable.

[Acquired reactive perforating collagenosis associated with diabetes mellitus and renal insufficiency requiring dialysis]. / Erworbene reaktiv perforierende Kollagenose bei Diabetes mellitus und dialysepflichtiger Niereninsuffizienz.

HISTORY: A 60-year-old man with diabetes mellitus and chronic renal insufficiency needing hemodialysis was admitted with a 3 months history of multiple hyperkeratotic papules on the trunk and extremities partly ulcerated with a keratotic central plug. INVESTIGATIONS: Laboratory tests revealed elevated levels of blood urea nitrogen, creatinine, and HbA (1c). Histopathology showed vertical strands of collagen perforating from the ulcerated lesions. COURSE, DIAGNOSIS AND TREATMENT: The biopsy specimen was consistent with acquired reactive perforating collagenosis. The progression was stopped and secondary wound healing was initiated after two weeks of therapy with allopurinol and PUVA. CONCLUSION: Acquired reactive perforating collagenosis should be considered when ulcera with oystershell-like keratotic plugs are found especially in patients with predisposing diseases like diabetes and renal insufficiency. A good interdisciplinary cooperation between internist and dermatologist is crucial for the early recognition by histopathology and the immediate treatment.

Effect of cytochrome P450 induction on phosphorus metabolites and proton relaxation times measured by in vivo 31P-magnetic resonance spectroscopy and 1H-magnetic resonance relaxometry in human liver.

Experimental and clinical studies have led to the hypothesis that the phosphodiester signal obtained by 31P magnetic resonance (MR) spectroscopy may be a specific marker for the hepatic induction of oxidative metabolism (P450 induction) by phenobarbitone or ethanol. Systematic studies in humans are lacking. Therefore, we studied 10 volunteers who received rifampin (600 mg/d) for 6 days, resulting in a documented induction of oxidative metabolism as measured by an increase in urinary 6-beta-hydroxycortisol output in all volunteers (P = .0004). 31P-MR spectroscopy and 1H-MR relaxometry were performed before and after hepatic P450 induction. As shown by 31P-MR spectroscopy, the median phosphomonoester concentration (PME) relative to nucleoside triphosphate (NTP) increased by 21% from 0.63 (range, 0.40-0.89) before induction to 0.76 (0.49-1.67) after induction (P = .0451). The median level of phosphodiesters (PDE) relative to NTP increased by 28% from 4.82 (3.41-6.67) before induction to 6.18 (4.63-11.63) after induction (P = .0091). An increase in the level of inorganic phosphates (Pi) relative to NTP was observed, but changes were not significant. As shown by 1H-MR relaxometry, a nonsignificant trend of the liver parenchyma to shorter relaxation times was observed after P-450 induction. In conclusion, both PME/NTP and PDE/NTP ratios (measured by in vivo 31P-MR spectroscopy) increased significantly after hepatic induction with rifampin. Further clinical studies with 31P-MR spectroscopy must take into account the potential effects of P450-inducing agents.

LI-cadherin-mediated cell-cell adhesion does not require cytoplasmic interactions.

The adhesive function of classical cadherins depends on the association with cytoplasmic proteins, termed catenins, which serve as a link between cadherins and the actin cytoskeleton. LI-cadherin, a structurally different member of the cadherin family, mediates Ca2+-dependent cell-cell adhesion, although its markedly short cytoplasmic domain exhibits no homology to this highly conserved region of classical cadherins. We now examined whether the adhesive function of LI-cadherin depends on the interaction with catenins, the actin cytoskeleton or other cytoplasmic components. In contrast to classical cadherins, LI-cadherin, when expressed in mouse L cells, was neither associated with catenins nor did it induce an upregulation of beta-catenin. Consistent with these findings, LI-cadherin was not resistant to detergent extraction and did not induce a reorganization of the actin cytoskeleton. However, LI-cadherin was still able to mediate Ca2+-dependent cell-cell adhesion. To analyze whether this function requires any interaction with proteins other than catenins, a glycosyl phosphatidylinositol-anchored form of LI-cadherin (LI-cadherin(GPI)) was constructed and expressed in Drosophila S2 cells. The mutant protein was able to induce Ca2+-dependent, homophilic cell-cell adhesion, and its adhesive properties were indistinguishable from those of wild type LI-cadherin. These findings indicate that the adhesive function of LI-cadherin is independent of any interaction with cytoplasmic components, and consequently should not be sensitive to regulatory mechanisms affecting the binding of classical cadherins to catenins and to the cytoskeleton. Thus, we postulate that the adhesive function of LI-cadherin is complementary to that of coexpressed classical cadherins ensuring cell-cell contacts even under conditions that downregulate the function of classical cadherins.

Subdural hemorrhage as an initial sign of glutaric aciduria type 1: a diagnostic pitfall.

The case of a 9-month-old girl with glutaric aciduria type 1 (GA 1) is reported. On initial presentation at 6 months of age, the patient demonstrated bilateral subdural hemorrhages and widening of the basal cisterns. After neurosurgical intervention the subdural effusions regressed; their etiology remained unclear. At the age of 9 months the patient presented again because of progressive loss of psychomotor abilities and a dystonic movement disorder. Cerebral MRI revealed regressive subdural hematoma, but marked frontotemporal atrophy as well. Because of a suspected metabolic disorder, urinary analysis of organic acids was performed. This repeatedly showed marked excretion of glutaric acid, 3-hydroxyglutaric acid and glutaconic acid, indicating a diagnosis of GA 1. Considering our patient's history, we recommend the inclusion of GA 1 in the differential diagnosis of patients with unexplained subdural hematoma and neurological deficits.

Liver-intestine cadherin: molecular cloning and characterization of a novel Ca(2+)-dependent cell adhesion molecule expressed in liver and intestine.

A novel member of the cadherin family of cell adhesion molecules has been characterized by cloning from rat liver, sequencing of the corresponding cDNA, and functional analysis after heterologous expression in nonadhesive S2 cells. cDNA clones were isolated using a polyclonal antibody inhibiting Ca(2+)-dependent intercellular adhesion of hepatoma cells. As inferred from the deduced amino acid sequence, the novel molecule has homologies with E-, P-, and N-cadherins, but differs from these classical cadherins in four characteristics. Its extracellular domain is composed of five homologous repeated domains instead of four characteristic for the classical cadherins. Four of the five domains are characterized by the sequence motifs DXNDN and DXD or modifications thereof representing putative Ca(2+)-binding sites of classical cadherins. In its NH2-terminal region, this cadherin lacks both the precursor segment and the endogenous protease cleavage site RXKR found in classical cadherins. In the extracellular EC1 domain, the novel cadherin contains an AAL sequence in place of the HAV sequence motif representing the common cell adhesion recognition sequence of E-, P-, and N-cadherin. In contrast to the conserved cytoplasmic domain of classical cadherins with a length of 150-160 amino acid residues, that of the novel cadherin has only 18 amino acids. Examination of transfected S2 cells showed that despite these structural differences, this cadherin mediates intercellular adhesion in a Ca(2+)-dependent manner. The novel cadherin is solely expressed in liver and intestine and was, hence, assigned the name LI-cadherin. In these tissues, LI-cadherin is localized to the basolateral domain of hepatocytes and enterocytes. These results suggest that LI-cadherin represents a new cadherin subtype and may have a role in the morphological organization of liver and intestine.