Cholestasis After Pediatric Liver Transplantation-Recurrence of a Progressive Familial Intrahepatic Cholestasis Phenotype as a Rare Differential Diagnosis: A Case Report.

INTRODUCTION: Nonobstructive cholestasis after pediatric liver transplantation is a common diagnostic and therapeutic dilemma. We describe a girl with neonatal cholestasis because of progressive familial intrahepatic cholestasis 2 (PFIC-2) and presence of a homozygous splice site mutation in the ABCB11 gene. Liver transplantation was performed because of end-stage liver disease at the age of 6. Cholestasis with normal gamma-glutamyl transferase (GGT) developed 8 years after liver transplantation. A liver biopsy showed canalicular cholestasis and giant cell hepatitis without evidence of rejection, mimicking PFIC-2. Immunofluorescence staining of normal human liver sections with patient's serum revealed reactivity toward a canalicular epitope, which could be identified as bile salt export pump (BSEP) using BSEP-yellow fluorescent protein (YFP) transfected cells. Our patient developed a recurrence of a PFIC-2 phenotype due to production of antibodies against BSEP (alloimmune BSEP disease [AIBD]). Intensification of immunosuppressive therapy as well as antibody treatment with plasmapheresis and Rituximab were initiated, leading to stabilization of the clinical condition and depletion of anti-BSEP antibodies in serum. However, after 1 year liver transplantation was necessary again because of end-stage liver insufficiency. Afterward, immunomodulatory treatment consisted of tacrolimus, mycophenolate mofetil, prednisone, immunoadsorption, and high-dose immunoglobulin therapy (1 g/kg/d). CONCLUSION: Cholestasis after liver transplantation may indicate an AIBD with a PFIC-2 phenotype. Besides enhancement of immunosuppressive therapy, an antibody depletion with plasmapheresis, immunoadsorption, immunoglobulins, and B-cell depletion represents a therapeutic option.

Direct association of Bloom's syndrome gene product with the human mismatch repair protein MLH1.

Bloom's syndrome (BS) is a rare genetic disorder characterised by genomic instability and cancer susceptibility. BLM, the gene mutated in BS, encodes a member of the RecQ family of DNA helicases. Here, we identify hMLH1, which is involved in mismatch repair (MMR) and recombination, as a protein that directly interacts with BLM both in vivo and in vitro, and that the two proteins co-localise to discrete nuclear foci. The interaction between BLM and hMLH1 appears to have been evolutionarily conserved, as Sgs1p, the Saccharomyces cerevisiae homologue of BLM, interacts with yeast Mlh1p. However, cell extracts derived from BS patients show no obvious defects in MMR compared to wild-type- and BLM-complemented BS cell extracts. We conclude that the hMLH1-BLM interaction is not essential for post-replicative MMR, but, more likely, is required for some aspect of genetic recombination.

Dual versus triple therapy of Helicobacter pylori infection: results of a multicentre trial.

OBJECTIVE: To compare dual therapy (omeprazole and amoxicillin) with triple therapy (omeprazole, amoxicillin, and clarithromycin) in the treatment of Helicobacter pylori infection. The efficacy of 1 mg/kg/day omeprazole was randomly compared with 2 mg/kg/day. STUDY DESIGN: 252 patients (median age, 11.0 years; range, 3-18) presenting with chronic abdominal pain underwent endoscopy and a 13C-urea breath test. Gastric biopsy specimens were taken for histological examination and for the rapid urease test. Patients were treated for two weeks: group A (n = 63) received amoxicillin (50 mg/kg; maximum, 2 g/day), group B (n = 73) received amoxicillin and clarithromycin (20 mg/kg; maximum, 1 g/day). Both groups were randomly treated with either 1 or 2 mg/kg omeprazole (maximum, 80 mg/day). Diagnostic procedures were repeated four weeks after the end of treatment. RESULTS: 11 patients were excluded; 136 patients were H pylori positive (56%), 105 of whom were re-examined after treatment. Helicobacter pylori was eradicated in 52% of group A and 83% of group B. The dose of omeprazole had no influence on the eradication rate. Specificity and sensitivity of the rapid urease test were 94% and 93%, respectively. Specificity and sensitivity of the 13C-urea breath test were 93% and 95%, respectively. CONCLUSIONS: Dual therapy can no longer be recommended. Triple therapy is more effective than dual therapy in the eradication of H pylori infection. The lower dose of 1 mg/kg omeprazole was as effective as 2 mg/kg.

Nursing management of the child in status asthmaticus and impending respiratory failure.

Asthma is a chronic disease that affects a large number of children. Some children require admission to an intensive care unit for advanced therapies and continuous nursing assessment. Nurses must be knowledgeable about asthma treatment and expected responses. By playing an integral role in caring for the child with status asthmaticus, the nurse can help to maximize a good outcome.

Delivery of trifluridine to human cornea and aqueous using collagen shields.

PURPOSE: We investigated the ability of collagen shields to deliver trifluridine (trifluorothymidine [TFT]) to human cornea and aqueous humor. METHODS: 24-hour porcine collagen shields were soaked in commercially prepared TFT (Viroptic). Patients undergoing penetrating keratoplasty wore a pre-soaked collagen shield for at least 30 minutes preoperatively. Control patients received drops of TFT only. Cornea and aqueous samples were obtained. TFT levels were measured using high performance liquid chromatography. RESULTS: Among the four patients with intact corneal epithelium, TFT was detected in only one patient (0.13 microgram/g in the aqueous). In seven patients with poor epithelium, corneal levels ranged from 0 to 635.34 micrograms/g, and aqueous levels ranged from 0.06 to 11.17 micrograms/g. CONCLUSIONS: Collagen shields do not enhance delivery of TFT to corneas with intact epithelium. In corneas with poor epithelium, drug penetration was higher but variable. The role of collagen shields as a drug delivery system for the treatment of herpes simplex keratitis remains to be determined.

Reducing risk of house dust mite and cockroach allergen exposure in inner-city children with asthma.

Asthma prevalence among disadvantaged and minority children is disproportionately higher in inner-city populations. Environmental allergen exposure, particularly that of house dust mites and cockroaches, is known to contribute to asthma exacerbations in children. Environmental control of these particular triggers is a necessary component of asthma education and should be incorporated into the teaching plan for these children. The costs surrounding environmental control may not be within the means of many families living in urban, inner-city environments; therefore nurses should offer families creative ideas and cost effective suggestions for controlling environmental triggers.

[Sterile eosinophilic pustulosis (Ofuji). A rare entity in Europe]. / Sterile eosinophile Pustulose (Ofuji). Eine in Europa seltene Entität.

This case report refers to a German patient with sterile eosinophilic pustulosis of the Ofuji type (SEP), which is rarely described in non-Japanese humans. The distinctive histomorphology, with intraepidermal eosinophilic abscesses and eosinophilic folliculitis, is complemented in this patient by marked eosinophilia, evident eosinophilic bone marrow reaction and involvement of the oral mucosa with eosinophilic spongiosis, which is a feature that had not previously been reported. Possible transitions between cutaneous and internal hypereosinophilic syndromes are discussed. Despite the initial good effect of topical corticosteroids on the cutaneous changes, long-term follow-up to check for internal involvement is necessary.

[Comparative analysis of narcosis and local anesthesia in surgery of malignant melanoma of the skin]. / Vergleichende Analyse in Narkose und Lokalanästhesie operierter maligner Melanome der Haut.

A nonrandomized trial was performed to compare the survival rate attained in patients with malignant melanoma who underwent their operations under general anaesthesia (g.a.) and in those who underwent surgery with only local anaesthesia (l.a.). All stage I patients were treated and followed up in our hospital exclusively. Data recorded in 190 patients operated on under g.a. from 1972 to 1980 and 376 patients operated on with l.a. from 1981 to 1987 were evaluated by computer. The 5-year survival rates calculated by the Kaplan-Meier method were as follows: Breslow's thickness up to 1.50 mm (pT1 and pT2): g.a. 91.4% l.a. 94.5%; 1.51-3.00 mm (pT3a) g.a. 64.1%, l.a. 84.5% (P less than 0.01); over 3.00 mm (pT3b and pT4) g.a. 57.9%, l.a. 62.2% (P greater than 0.05). Women with pT3a melanoma had more benefit from the operation in l.a. (93.1% to 69.7%) than did men (71.6% to 55.2%). The l.a. does not prejudice the prognosis, whether the l.a. improves the prognosis has to be stated. The available evidence that anaesthetic agents influence host defence could be an explanation for the better results with l.a.

[Results of treatment of malignant melanoma--a computer analysis of 772 patients]. / Behandlungsergebnisse des malignen Melanoms--eine Computeranalyse von 772 Patienten.

The data of 772 patients with malignant melanoma, treated from 1.1.1972 to 30.6.1988 in the Regional Hospital Dresden-Friedrichstadt were analysed by computer. The probability of survival was estimated separately by the method of Kaplan and Meier in dependence on clinical stage in the time of the first treatment, pT and sex. The 10-year survival rate in clinical stage I amounts to pT1 = 100%; pT2 = 82.9% +/- 4.0%; pT3 = 67.1 +/- 4.3% and pT4 = 58.0 +/- 4.7%. There are significantly differences between women and men with melanomas of the category pT2 and pT3 in favour of women (pT2: 88.6%:70.0%; pT3: 75.8%: 53.4%). In the cases of pT4 melanoma there are no differences (61%:53%). The average time of survival from these patients who have died from melanoma shows also marked differences according to pT (pT2 = 46.6 month, pT3 = 36.6 month, pT4 = 30.2 month).

Autoantibody-associated cross-reactive idiotypes expressed at high frequency in chronic lymphocytic leukemia relative to B-cell lymphomas of follicular center cell origin.

Using murine monoclonal antibodies (MoAbs) specific for immunoglobulin (Ig) cross-reactive idiotypes (CRI), we performed immunohistochemical analyses on frozen tissue sections and cytocentrifuge preparations of Ig-expressing malignant cells from patients with chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin's lymphomas (NHL) of follicular center cell origin. Twenty percent (4/20) of the Ig kappa light chain-expressing CLL cells reacted with 17.109, a MoAb against a major CRI on human IgM autoantibodies that is encoded by a conserved Ig variable-region gene (V gene) of the V kappa IIIb sub-subgroup. Another MoAb specific for V kappa IIIb framework determinant(s) reacted exclusively with all the 17.109-reactive CLL cells. Only one of 20 kappa light-chain-expressing CLL cells reacted with 6B6.6, a monoclonal antibody specific for a CRI commonly found on rheumatoid factor (RF) paraproteins with light-chain variable regions of the V kappa IIIa sub-subgroup. Finally, greater than 20% (8/34) of all CLL reacted with G6, a MoAb specific for an Ig heavy chain-associated CRI present on several RF paraproteins. In contrast, these CRIs were expressed at significantly lower frequencies in NHL of follicular center cell origin. Only one of 30 NHL expressing kappa light chains reacted with the 17.109 MoAb. Also, in contrast to the concordance between the 17.109-CRI and V kappa IIIb framework determinant(s) in CLL, two lymphomas in addition to the 17.109-reactive lymphoma were recognized by the anti-V kappa IIIb framework MoAb. None of the NHL reacted with either the 6B6.6 or the G6 MoAbs. These results are the first to demonstrate that CLL and NHL differ with respect to the expression of autoantibody-associated CRIs. The data support the notion that NHL of follicular center cell origin differs from CLL in its utilization and/or somatic mutation of Ig variable-region genes. The physiological and immunotherapeutic implications of these findings are discussed.

[Spontaneous pneumothorax in cystic fibrosis]. / Spontanpneumothorax bei Cystischer Fibrose.

The clinical course of 13 cystic fibrosis patients with a total of 24 episodes of pneumothorax was analysed. The study is based on 488 (273/215) patients seen over 20 respectively 10 years at the University Children's Hospitals Frankfurt/Main and Essen. A pneumothorax was observed with a frequency of 2.7% mainly in adolescents of young adults with advanced pulmonary disease (mean age 17.4 years). It was not seen before the age of 10 years. Thus among 255 patients at risk above 10 years a pneumothorax occurred in 5.1%. Presenting symptoms were acute chest pain (n = 17), dyspnea (n = 17) and irritating cough (n = 8). In two patients pneumothorax was an incidental diagnosis. A tension pneumothorax was seen in 7 (= 30%; 3 initial, 4 recurrences of which 3 were ipsilateral). Out of 11 recurrences (n = 6, ipsi- and n = 5, contralateral) 4 occurred only once, one twice and in one patient five times. Two patients died as a consequence of the event (one initially due to tension pneumothorax, one due to heart failure). The therapeutic approach was conservative. Without specific treatment pneumothorax resolved in 12 cases. Ten patients were treated by chest tube drainage and only one patient by pleurodesis with a sclerosing agent. Though the therapeutic results were favorable in the patients presented, the authors suggest more aggressive treatment in view of the high ipsilateral recurrence rate. Detailed recommendations are given.

[Varicocele and fertility--spermiographic and histologic findings]. / Varikozele und Fertilität--spermiografische und histologische Befunde.

The results of the treatment of 251 patients with varicocele are demonstrated. By means of spermiographic and histologic investigations the fertility-disturbing influence of this vascular disease of the testis shall be proved and the effect of the operative sanation shall be estimated. For many years the high ligature of the testicular vein has been favoured method of operation; since 1984 exclusively the percutaneous transfemoral occlusion of the testicular vein has been performed, when a left-sided varicocele is present. In 61% of the patients examined an improvement of the spermiogram is to be proved, in which case the most conspicuous rate of increase lies at the motility of spermatozoa with 58%. After removal if the varicocele the investigations of the testicular tissue reveal in 42% of the cases an improvement of the findings by decrease of the tubular atrophy and increase of the tubular cell number. Among the number of our patients the rate of conception is 49%. The treatment of varicocele is a fertility-protective measure and therefore should be performed in all adolescents and males at fertile age.

[Vas deferens-obstructive azoospermia following inguinal herniotomy]. / Zur samenleiterobstruktiven Azoospermie nach inguinaler Herniotomie.

Azoospermia due to obstruction of the vas deferens following herniotomy in childhood is rare; its therapy is technically difficult and its prognosis appears unfavourable. The problems are discussed on the basis of 6 of our own patients.