Low molecular weight heparin-induced skin necrosis occurring distant from injection sites and without thrombocytopenia

Tietge UJF, Schmidt HH-J, Jäckel E, Trautwein C, Manns MP (Medizinische Hochschule Hannover, Hannover, Germany). Low molecular weight heparin-induced skin necrosis occurring distant from injection sites and without thrombocytopenia (Case Report). J Intern Med 1998; 243 : 313–15. In this paper we report a case of 76-year-old white male patient with skin necrosis induced by subcutaneous prophylactic administration of low-molecular-weight heparin (LMWH). Skin necrosis occured distant from heparin injection sites and without concomitant thrombocytopenia. This is the first reported case presenting these clinical findings.     

Learning the lessons of antitumour necrosis factor therapy-associated psoriasis

Psoriasis or psoriasiform skin lesions, as an adverse effect of treatment with antitumor necrosis factor antibody therapy, have been described relatively recently. Patients with these lesions have no personal or family history of psoriasis. In a small number of cases, an association with Chlamydia has been suggested. The skin lesions may disappear on discontinuation of therapy or, in the majority of cases, even if antitumor necrosis factor antibody therapy is continued. Therefore, withdrawal of therapy is generally not required for this adverse effect but referral to a dermatologist may be desirable for confirmation of diagnosis and treatment.     

Diagnosis of Gaucher's disease in cultured skin fibroblasts and leucocytes

Washing skin fibroblasts or leucocytes in 0.25 mol/l sucrose increases the activity of-glucosidase at acid pH. This effect is primarily due to removal of low levels of sodium chloride, which inhibit acid-glucosidase. A secondary factor for skin fibroblasts is the removal of residual phosphate buffer pH 7.3 used to wash the cells following trypsinization. As the-glucosidase activity of water-lysed leucocytes is higher at acid pH than that of a saline suspension of leucocytes, the former are better for the diagnosis of Gaucher's disease. However, more reliable results still may be obtained by assay of this enzyme in cultured skin fibroblasts.     

Regression of atypical lymphoid hyperplasia after eradication ofHelicobacter pylori

A rare case of endescopic and histological regression of a gastric lymphoid mucosal lesion after eradication ofHelicobacter pylori is reported. A 72-year-old man was suspected of having a low-grade B-cell gastric mucosa-associated lymphoid tissue (MALT) lymphoma by endoscopic and histological findings. Histology of biopsy specimens showed massive infiltration of atypical lymphocytes and lymphoepithelial lesions. Immunohistochemical staining revealed kappa light chain expression in the infiltrated atypical lymphocytes to be twofold that of lambda light chain. The above diagnosis was thus highly suspected but not confirmed. Antibiotic therapy was given on the basis of evidence ofH. pylori infection. Successful eradication ofH. pylori resulted in remarkable improvement of endoscopic and histological findings. Follow-up studies were carried out 8 months after eradication, with no evidence of relapse. The eradication ofH. pylori appears to be an effective alternative therapy for B-cell lymphoproliferative disease, although longer follow-up and further studies are needed before this treatment can be establisted.     

Neutrophil dysfunction in a family with a SAPHO syndrome–like phenotype

SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis) is an inflammatory disorder of the bone, skin, and joints. We describe a family with multiple affected members who segregate a SAPHO syndrome–like phenotype, and we report the results of neutrophil studies and candidate gene analysis. We obtained written informed consent and a family history and reviewed medical records. We collected DNA and sequenced candidate genes, and we performed functional studies on neutrophils isolated from the proband and her mother. The pedigree segregated chronic osteomyelitis and cutaneous inflammation in a pattern that suggested an autosomal‐dominant disorder. No coding sequence mutations were detected in PSTPIP1, PSTPIP2, LPIN2, SH3BP2, or NCF4. Analysis of neutrophil function in the proband, including nitroblue tetrazolium tests, myeloperoxidase assays, neutrophil chemotaxis, and neutrophil chemotaxis assays, revealed no identifiable abnormalities. However, an abnormality in the luminol, but not the isoluminol, respiratory burst assays following stimulation with phorbol myristate acetate (PMA) was detected in neutrophils isolated from the affected proband. Internal oxidant production was also reduced in the proband and her mother when neutrophils were treated with fMLP with or without platelet‐activating factor, PMA alone, or tumor necrosis factor α alone. This family segregates a disorder characterized by chronic inflammation of the skin and bone. Functional differences in neutrophils exist between affected individuals and controls. The biologic significance of this defect remains unknown. Identification of the gene defect will help identify an immunologic pathway that, when dysregulated, causes inflammation of the skin and bone.     

Comparison of fecal granulocyte excretion in ulcerative colitis and Crohn's colitis

Impaired granulocyte migration has been suggested to be present in Crohn's disease on the basis ofin vitro granulocyte function tests andin vivo skin window studies. This idea is supported by the impression histologically that the acute inflammatory infiltrate in diseased bowel is less in Crohn's disease than ulcerative colitis. We have developed a method of quantitating the acute inflammatory infiltrate in inflamed bowel by measuring fecal indium-111 granulocyte excretion and have compared this assessment in patients with ulcerative colitis and Crohn's colitis matched for disease activity. For equivalent disease groups in ulcerative colitis and Crohn's colitis, there was no significant difference between fecal granulocyte excretion. These findings provide no support for the contention that there is a reduced granulocyte infiltration in Crohn's disease.     

Unusual cause of fever and diarrhea in a patient with AIDS

Summary Penicillium marneffei is an opportunistic pathogen predominantly found in Southeast Asia. Systemic infection ofPenicillium marneffei has protean manifestations including fever, weight loss, anaemia, skin lesions, and lymphadenopathy. We report a rare case of penicillium colitis in an AIDS patient who responded successfully to a course of amphotericin B therapy.     

The role of beta-lactamase-producing-bacteria in mixed infections

Beta-lactamase-producing bacteria (BLPB) can play an important role in polymicrobial infections. They can have a direct pathogenic impact in causing the infection as well as an indirect effect through their ability to produce the enzyme beta-lactamase. BLPB may not only survive penicillin therapy but can also, as was demonstrated in in vitro and in vivo studies, protect other penicillin-susceptible bacteria from penicillin by releasing the free enzyme into their environment. This phenomenon occurs in upper respiratory tract, skin, soft tissue, surgical and other infections. The clinical, in vitro, and in vivo evidence supporting the role of these organisms in the increased failure rate of penicillin in eradication of these infections and the implication of that increased rate on the management of infections is discussed.     

Late-onset warfarin-induced skin necrosis: case report and review of the literature

Warfarin-induced skin necrosis is a rare complication of therapy with warfarin or other coumarin derivatives. When it occurs it usually appears 3 to 6 days after initiation of therapy and almost always between days 1 and 10. We report a case of late-onset (16 days after initiation of therapy) warfarin-induced skin necrosis and review the literature on this rarely reported variant of warfarin-induced skin necrosis. The skin lesion in our patient was not associated with either deficiency of protein C or resistance to activated protein C. Am. J. Hematol. 57:233–237, 1998. © 1998 Wiley-Liss, Inc.     

An experimentally-induced acute hepatic failure model in various strains of mice

When BALB/cAJcl mice are intravenously injected with heat-killedPropionibacterium acnes (P. acnes) followed by an intravenous injection of lipopolysaccharide (LPS) 7 days later, massive necrosis is induced in the liver tissue and most of the mice die within 24 hours of LPS injection. Using this experimental model, acute hepatic failure was induced in various strains of mice and the difference in the response was studied. As a result, as in BALB/cAJcl mice, acut hepatic failure was also induced in BALB/ cAJcl-nu, AKR/J, C3H/HeNJcl, C57BL/6NJcl and DDy mice. However, as an exception, hepatic cell necrosis was hardly seen and the survival rate was remarkable high in C3H/HeJ mice, which genetically do not respond to LPS stimulation. These results indicate that for this experimental induction of acute hepatic failure, macrophages must be activated by the two-step stimulation ofP. acnes and LPS.     

IgA1 protease production by bacteria colonizing the upper respiratory tract

Summary Thirty-eight clinical isolates ofHaemophilus influenzae and ten clinical isolates ofStreptococcus pneumoniae were examined for IgA1 protease production. A suspension of surface material of each individual strain was incubated with human secretory IgA; IgA1 cleavage products were detected by SDS-PAGE and immunoblotting. The high incidence of IgA1 protease-positive strains (68.4% of the examinedH. influenzae and 100% of the examinedS. pneumoniae strains) confirms that IgA1 protease activity is a frequent characteristic of these two species. Yet the presence of this enzyme is, if at all, only a minor decisive factor for the induction of symptomatic infections of the upper respiratory tract by IgA1 protease-positive bacteria.     

High frequency ofYersinia antibodies in healthy populations in Finland and Germany

Sera from 94 healthy Finnish and 100 healthy German blood donors were studied forYersinia enterocolitica antibodies by two different techniques, enzyme immunoassay and immunoblotting, to compare the frequency ofYersinia infections in Finnish and German populations. The prevalence ofYersinia antibodies in Finland (19% and 31% by enzyme immunoassay and immunoblotting, respectively) and in Germany (33%, 43%) is relatively high and may indicate many subclinicalYersinia infections in healthy populations. Postinfectious complications, such as reactive arthritis, may follow also such subclinical infection; sensitive serological tests are important in their diagnosis.     

The Cathlocator: A novel non-radiological method for the localization of enteral tubes

Safe placement of nasogastric tubes requires reliable positioning of the tip of the tube within the stomach. Radiology and aspiration are currently used to confirm tube position, but suffer from significant problems of cost and efficacy, respectively. We have developed a novel method to locate the position of a catheter tip within the body, using the detection of a low energy electromagnetic field generated in a coil located in the catheter with an external hand-held unit (Cathlocator). In vitro, the unit detected the distance of the coil from the detector with an accuracy of 0.1 cm over a range of 4–12 cm. In vivo studies were performed in 11 healthy volunteers using a purpose-built manometric assembly that incorporated the signal generating coil in its tip. In all subjects the Cathlocator showed the position of the signal generating coil to be cranial to the xiphisternum when manometric and transmucosal potential difference criteria showed it to be located above the lower oesophageal sphincter. When the coil was within the stomach, the Cathlocator identified its position within the epigastric, umbilical and left hypochondrial regions of the abdomen. The distance of the coil from the surface was significantly greater when in the duodenum mean (±s.e.m. 7.6±0.3 cm; P<0.001) and oesophagus (8.6±0.2 cm; P<0.002) than the stomach (5.0±0.4 cm). In one subject studied twice there was a close correlation between the location and depth measured by the device on each occasion. The Cathlocator is a novel non-radiological device that has the potential to be useful in the placement of gastrointestinal catheters.     

CerebralDermabacter hominis abscess

Summary Dermabacter species are commonly isolated from the skin and other body sites but rarely show pathogenicity in humans. A case ofDermabacter hominis cerebral abscess is reported which presented as a contrast-enhancing intracranial mass in a renal tranplant patient.     

Circulating N‐cadherin levels are a negative prognostic indicator in patients with multiple myeloma

N‐cadherin (cadherin 2, type 1, N‐cadherin (neuronal); CDN2) is a homotypic adhesion molecule that is upregulated in breast, prostate and bladder cancer. Here we investigated the prognostic significance of upregulated N‐cadherin expression in multiple myeloma (MM). Our results indicate that N‐cadherin protein and gene expression is abnormally increased in trephine biopsies and CD38⁺⁺/CD138⁺ plasma cells from MM patients, when compared with those of normal donors. In addition, levels of circulating N‐cadherin were elevated in a subset of patients with MM (n = 81; mean: 14·50 ng/ml, range: 0–146·78 ng/ml), relative to age‐matched controls (n = 27; mean: 2·66 ng/ml, range: 0–5·96 ng/ml), although this did not reach statistical significance. Notably, patients with abnormally high levels of N‐cadherin (>6 ng/ml) had decreased progression‐free survival (P = 0·036; hazard ratio: 1·94) and overall survival (P = 0·002; hazard ratio: 3·15), when compared with patients with normal N‐cadherin levels (≤6 ng/ml). Furthermore, multivariate analyses revealed that the combination of N‐cadherin levels and International Staging System (ISS) was a more powerful prognostic indicator than using ISS alone. Collectively, our studies demonstrate that circulating N‐cadherin levels are a viable prognostic marker for high‐risk MM patients.     

Erythropoietin as an adjunctive treatment for methanol-induced toxic optic neuropathy

Background: Methanol-induced optic neuropathy (MTON) is frequently seen in countries where alcohol consumption is banned or poorly regulated. MTON frequently results in blindness and there is no empirically validated treatment. Objective: To evaluate the effect of erythropoietin (EPO) as an adjunctive treatment for MTON. Methods: In this nonrandomized interventional comparative study, all participants were diagnosed with MTON and received the steroid methylprednisolone. Eleven participants received intravenous EPO (10000 IU twice a day) for three days as an adjuvant to methylprednisolone (EPO group); 11 participants in a historical control group received methylprednisolone only (control group). Main outcomes were best-corrected visual acuity (BCVA), peripapillary retinal nerve fiber layer thickness (PRNFLT), and visual field mean deviation (MD). Results: Mean BCVA improved significantly in both groups: from 2.93 ± 0.55 to 1.75 ± 1.16 LogMAR at month 3 (p < 0.001) in the EPO group, and from 2.65 ± 0.68 to 2.19 ± 0.75 at final visit in the control group (p = 0.001). The final BCVA was significantly better in the EPO group (p = 0.012). The mean PRNFLT decreased in both groups. However, at the final follow-up, PRNFLT was significantly thinner in the control group (53 ± 6 vs. 77 ± 26 microns, respectively; p < 0.001). Conclusion: Intravenous EPO plus high-dose intravenous steroid may be an effective combination therapy for the patients with MTON.     

Identification of the stereoisomeric configurations of methylcitric acid produced bysi-citrate synthase and methylcitrate synthase using capillary gas chromatography-mass spectrometry

Summary The absolute separation of the four stereoisomeric configurations of methylcitric acid can be achieved on a nonchiral stationary phase SE30 capillary column using the correspondingO-acetylated (tri-(–)-2-butyl ester derivatives. Identification of the separated isomers was done using methylcitric acid produced bysi-citrate synthase and methylcitrate synthase ofCandida lipolitica. si-Citrate synthase produces the (2S,3S)-, (2S,3R)- and a small amount of the (2R,3S)-isomers. Methylcitrate synthase produces the (2R,3S)-isomer, indicating that this enzyme is more stereospecific than the animal citrate synthase enzyme. The (2R,3R)-isomer may act as an inhibitor of aconitase.     

Molecular typing ofHelicobacter pylori: Differences in pathogenicity among diverse strains

Helicobacter pylori appears to be a species with strain diversity, according to studies carried out using various molecular biological techniques. Differences in pathogenicity caused by the strain diversity ofH. pylori were therefore investigated. Two hundred and thirty strains were divided into four types by polymerase chain reaction-restriction fragment length polymorphism, and their relationship to endoscopic diagnosis, ammonia concentration of gastric juice, and urease activity were assessed. With regard to incidence by type, patients infected with type 1, type 2, and type 3 exhibited the highest incidences of gastric ulcer, duodenal ulcer, and gastritis, respectively. The urease activity of type 2 was significantly lower than that of types 1 and 3 (P<0.05). These observations suggest differences in pathogenicity due to the strain diversity ofH. pylori. However, the diversity of diseases related toH. pylori is also presumed to be caused by both the diversity ofH. pylori strains and differences in the host immunological reaction. Future studies should be directed toward clarifying the entire pathogenic mechanism ofH. pylori infection.Part of this study was presented at the 36th Annual Meeting of The Japanese Society of Gastroenterology, Sendai, Japan, 1994     

Intra‐Arterial Treatment for Massive Subcutaneous Hemorrhage in Hemodialysis Patients

The incidence of acute massive hemorrhage in hemodialysis (HD) patients is thought to be higher than in healthy individuals, and a large, expanding subcutaneous hematoma can result in necrosis of the overlying skin. We evaluated the efficacy of intra‐arterial treatment for acute massive subcutaneous hemorrhage in HD patients. Seven HD patients with subcutaneous hemorrhage following minor blunt trauma were treated using superselective transarterial embolization, between July 2005 and October 2012. After examining the site of the hemorrhage using contrast‐enhanced computed tomography (CT), embolizations were performed using microcoils, gelatin sponges, or N‐butyl cyanoacrylate. Hematoma evacuation or skin grafting was performed as needed. Four men and three women with a mean age of 70 years (range, 63–82 years) comprised the study population. Sites of bleeding were as follows: lower leg (N = 3), upper leg (N = 1), buttock (N = 1), precordia (N = 1), and forearm (N = 1). Blood transfusions were administered to five cases. All patients were successfully salvaged using transarterial embolization. Six patients underwent hematoma evacuation after transarterial embolization, and two patients underwent split‐thickness skin grafting for skin necrosis. We established a treatment strategy for HD patients with acute subcutaneous hemorrhage. Immediate confirmation of the site and the degree of bleeding with contrast‐enhanced CT and early treatment using the transarterial embolization and as needed, hematoma evacuation are effective for preventing skin necrosis in HD patients with acute subcutaneous hemorrhage.