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Psoriasis is a common chronic disease in childhood of yet unclear etiology. Thirty per cent of psoriatic patients experience onset of their disease before 15 years of age. Psoriasis is exceptionally congenital but may present in infancy as a napkin dermatitis. There are specific pediatric clinical forms, but at the beginning the eruption is usually discrete, and the diagnosis can be difficult. Pustular, erythrodermic and arthropathic forms are rare. Treatment must weigh the advantages and disadvantages of the possible therapies and be kept to the minimum compatible with asymptomatic control.

Purpose: The aim of the authors was to report their experience with living related liver transplantation (LRLT) in children, particularly focusing on the safety of the two-center "Parisian" strategy., Methods: The records of donors and recipients of 26 pediatric living-related donor liver transplantations performed between November 1994 and March 1998 were reviewed retrospectively. Donors were assessed 1 year after transplantation for medical and overall status., Results: Indications for LRLT included biliary atresia (n = 18), Byler's disease (n = 5), alpha-1-antitrypsin deficiency (n = 1), Alagille syndrome (n = 1), and undefined cirrhosis (n = 1). Liver harvesting consisted of either a complete left hepatectomy (n = 14) or left lateral hepatectomy (n = 12) without vascular clamping. The recipient procedure essentially was the same as in split liver transplantation. Mean overall cold ischemia time averaged 140 minutes (range, 90 to 230 minutes). Twenty-four of 26 patients had end-to-end vascular anastomoses without interposition. Biliary reconstruction consisted of a Roux-en-Y choledochojejunostomy in all patients. All recipients except one received cyclosporine A (CSA). Mean donor hospitalization was 8 days (range, 6 to 13) with normalization of all liver function assays by the time of discharge. There were no donor deaths and two postoperative complications (perihepatic fluid collection and bleeding from the wound). One year after donation, the initial 19 donors had resumed their pretransplant status. Two of the children who underwent transplant died. Thirteen of the recipients required reoperation for hepatic artery thrombosis (n = 2), portal vein thrombosis (n = 2), biliary complications (n = 6), fluid collection (n = 3), small bowel perforation (n = 1), and plication for diaphragmatic eventration (n = 1). With mean follow-up of 2 years, 24 of 26 patients are alive and well (patient and graft survival rate, 92%)., Conclusions: LRLT is still controversial, even with minimal and decreasing donor risk. The "Parisian" strategy consists of harvesting the liver in an adult unit by an adult hepatic surgery team. The transplantation is then performed in a pediatric hospital by the pediatric liver transplantation team. The two steps of the procedure allow units specialized in adult surgery, on one hand, and pediatric liver transplantation, on the other hand, to dedicate themselves completely to their respective procedures, improving the safety of the harvest, and alleviating stress for both the medical staff and the families.

Purpose: The aim of the authors was to report an up-to-date review of their experience with 26 intestinal transplantations in children since 1987., Methods: A retrospective study was conducted of 26 patients with a mean age of 5 years (range, 0.3 to 14 years). Three groups were isolated. In group A (1987 to 1990), seven patients received nine isolated intestinal transplants for short bowel syndrome. Immunosuppression therapy consisted of cyclosporine, aziathioprine, and corticosteroids. In group B (1994-current), nine patients received nine isolated intestinal transplants for short bowel syndrom (n = 2), intestinal pseudoobstruction (n = 2), neonatal intractable diarrhea (n = 3), and Hirschsprung' disease (n = 1); hepatic biopsy results showed weak cholestasis or fibrosis. In group C (1994-current), 10 patients received 10 combined liver-small bowel transplants for short bowel syndrome (n = 3), neonatal intractable diarrhea (n = 4), and Hirschsprung' disease (n = 3); hepatic cirrhosis related to total parenteral nutrition (TPN) was shown in all cases. Groups B and C received immunosupressive treatment consisting of tacrolimus, aziathioprine, and corticosteroids. Posttransplant follow-up included intestinal biopsies of the small bowel twice a week and more frequently or combined with liver biopsy if rejection was suspected., Results: Overall patient survival (PS) and graft survival (GS) are 61% (16 of 26) and 50% (13 of 26), respectively. In group A, severe intestinal allograft rejection occurred in six patients leading to graft removal (GS, 11%). Five patients died of TPN complications after graft removal (PS, 28%). One survivor is off TPN, and one currently is waiting for a second graft. In group B, six patients survived (PS, 66%). Causes of death include hepatic failure (n = 1), renal and liver failure (n = 1), and systemic infection (n = 1). Severe intestinal allograft rejection occurred in five patients, which neccessitated aggressive immunosuppression (antilymphocyte serum) leading to an incomplete functional recovery of the graft. Only two patients currently are off TPN. In group C, eight patients survived (PS, 80%) all of which are currently off TPN. One patient died during the procedure, and one died of severe systemic infection. Intestinal graft rejection occurred in six patients; rejection of the liver allograft occurred in five patients, yet all rejections were weak and successfully treated by corticosteroids (GS, 80%)., Conclusions: Intestinal transplantation is a valid therapeutic option for children with definitive intestinal failure and not only for short bowel syndrome. Tacrolimus improves graft and patient survival (group A v group B). The lower severity of graft rejection in combined liver-small bowel transplantation improves functional results of intestinal transplantation in children without additional mortality or morbidity (group B vgroup C).

The aim of this study was to report the presentation and outcome of 22 consecutive children (13 female) who presented with a syndrome of chronic intestinal pseudo-obstruction with or without urinary tract involvement. We analyse the main clinical and histopathological features and discuss therapeutic management. Ten patients had signs of intestinal obstruction at birth, in which 6 presented antenatally with megacystis on ultrasound. Six children presented with constipation and/or obstruction between 1 and 6 months of age and in 6 other patients diagnosis was made between the ages of 1 and 12 years. There was a family history in 4 patients. Investigations showed diffusely dilated gut on x-ray with slow transit on small bowel follow through. Absent or abnormal motor migrating complex with low amplitude contractions were demonstrated on duodeno-jejunal manometry in 12/13. Megacystis occurred in 15/21 and megaureter in 2/21. Full thickness biopsies (n = 22) revealed involvement of muscle layers in 8, and abnormal myenteric plexus on histochemistry in 13. In 1, the biopsies were inconclusive. Recurrent urinary tract infections occurred in all with structural urinary tract abnormality and most had bacterial overgrowth. Severe recurrent episodes of obstruction which required parenteral nutrition (PN) occurred in all patients. Drugs were unhelpful and decompression ileostomies or colostomies were performed in 20/22. Five children died from sepsis (n = 3) or sudden death. Eleven patients remain partially or totally dependent on PN despite decompression ileostomy in 10/11. Six patients underwent colectomy and ileorectal pull-through, 2 of which remain on long-term PN, while the others are totally orally fed. Despite careful histological study pointing to 2 main forms, myopathy and neuropathy, the etiology of primary intestinal pseudoobstruction syndromes remains unknown. It may present antenatally while most of the time the gut and the urinary tract are diffusely involved. The condition has a high morbidity with a percentage requiring long-term PN. Although the mortality rate is high (23%), careful treatment of urinary tract infections and bacterial overgrowth, decompression surgery and judicious use of PN allows survival to adult life.

A 26-year-old pregnant woman was hospitalized in an emergency setting for a skin eruption. She had developed pustules distributed on round patch-like areas of rash localized at the umbilicus and the larger skin folds. She was given calcitriol and calcium with good results. Systemic steroids are usually given for exanthematic pustulosis of pregnancy but with variable efficacy. Few cases of successful treatment with calcium and vitamin D have been reported. We suggest this alternative treatment could be useful in other cases.

Congenital pigmented nevi are found in approximately 1% of newborn infants. Two main factors determine their management: 1) the risk of malignancy (melanoma); 2) the aesthetic consequences, these factors being themselves dependent upon the size and the localization of the nevi. Thus, if the systematic resection of small nevi is not required, early treatment of giant nevi which carry a high risk of malignancy before the age of ten years, is highly recommended. Main methods of treatment are surgical resection (with the help of skin grafts, or cutaneous expansion or mobilization, in giant nevi), dermabrasion and curettage.

Objective: This study was undertaken to determine whether certain criteria could be used to select among asbestos-exposed subjects those who could benefit from computed tomography screening., Materials and Methods: Search for criteria enabling the selection of patients who should undergo a CT screening exam after occupational exposure to asbestos was conducted in 150 subjects. All subjects were explored with selected high-resolution CT scans. Studied parameters were age, exposure data, pulmonary function test results., Results: None of the exposure data or pulmonary function test results suggested with certainty the presence or absence of asbestos-related pleural and parenchymal lung disease. The studied parameters could not be used to select patients who could benefit from CT screening., Conclusion: None of the studied parameters enabled a selection of asbestos-exposed subjects who should undergo chest CT screening.

The management of patients with intestinal failure has benefited from progress in parenteral nutrition (PN), especially home-based parental nutrition. Intestinal transplantation is now possible and in some conditions, constitutes the logical treatment option. Since 1985, more than 300 small-bowel grafts have been performed, involving the isolated small bowel with or without the colon (45%), the liver + small bowel (40%) or several organs (15%). 2/3 of recipients were under 20 years of age, and indications were short-bowel syndrome (64%), severe intractable diarrhea (13%), abdominal cancer (13%), or chronic intestinal pseudo-obstruction syndrome (8%). 51% of patients survived > 2 years after the graft. Patient and graft survival depends on the type of immunosuppression, i.e. Cyclosporine or FK 506. The results must be interpreted carefully as they represent the first experience in numerous centers using different immuno-suppressive protocols, without any randomization. The results from the largest of these centers more closely reflect the current situation and may exceed a 70% 2-year survival rate. Functional grafts lead to gastrointestinal autonomy (weaning of PN) while maintaining satisfactory nutritional status and normal growth in childhood. Intestinal transplantation is theoretically indicated for all patients permanently or persistently dependent on PN. However, as PN is generally well tolerated, even for long periods, each indication for transplantation must be carefully weighed up in terms of the iatrogenic risk and quality of life. When PN has reached its limits, especially those associated with vascular, infectious, hepatic or metabolic complications, intestinal transplantation must be undertaken. Transplantation of the small bowel alone remains the first option, as combined liver-small bowel grafting is only indicated in case of life-threatening progressive cirrhogenic liver disease.

Background/purpose: The development of thoracoscopic surgery has made many procedures possible, including the treatment of mediastinal cysts in children. The authors report their experience with this procedure between 1992 and 1997., Methods: Surgery was performed on 22 children aged from 1 month to 9 years (median, 27 months), weighing 5 to 49 kg (median, 12.5 kg). Diagnosis was made by antenatal ultrasound scan in six cases (27%), with a chest x-ray performed for respiratory symptoms in 14 cases, and with a chest x-ray performed for positive tuberculin intradermoreaction in two cases. Decision to resect the cyst was determined by thoracoscopy in 21 of the 22 cases, and by open surgery in one case only (subcarinal compressive cyst with left lung distension and a mediastinal shift)., Results: Eighteen of the 21 (86%) cases were treated successfully by thoracoscopy. In three cases of bronchogenic cysts, we performed an associated thoracotomy because the dissection was too difficult and dangerous. In three cases, a small part of a common wall between the cyst and the bronchus was not removed. The pathological diagnosis was bronchogenic cysts in 15 cases (71%), pleuropericardiat cysts in three cases (14%), esophageal duplication in two cases (10%), and cystic hygroma in one case (5%). Two postoperative complications were observed: one esophageal wound and a case of recurrent pneumothorax after chest tube removal. Patients were discharged after 2 to 11 days (median, 3 days). Follow-up was uneventful., Conclusions: Treatment of mediastinal cyst by thoracoscopy is feasible in most cases. Compressive cysts with lung distension and mediastinal shift remain a contraindication. If the cysts have a common wall with the bronchus or esophagus, or if they are subcarinal, the dissection may be difficult and dangerous, and thoracotomy may be preferable.

Background: Keratosis punctata of the palmar creases is a variant of punctata palmoplantar keratoderma., Case Report: Keratosis punctata of the palmar creases was observed in a 53 year-old North African male. The lesions presented as small keratotic papules confined exclusively to the flexion creases of the palms and digits, with a bilateral localization on the soles. The lesions were sensitive to pressure. The proband's 19 year-old son had similar lesions., Discussion: Keratosis punctata of the palmar creases is characterized by the development of small round keratotic papules, electively and exclusively found in the palmar, digital, and uncommonly soles creases. The etiology is unknown. The frequency is higher in the black population. Although considered as an hereditary palmoplantar keratoderma with autosomal dominant transmission, familial cases with localizations on the soles is uncommon.

Have been selected for this review: 1) the recent and impressive development of high-resolution and spiral CT scan in pediatric thoracic imaging; 2) the emerging of new and promising therapies for asthma (long acting inhaled beta 2-agonists, leukotriene antagonists, anti-IgE monoclonal antibodies); 3) the multifactorial origin of asthma in childhood; 4) the development of thoracoscopic surgery, a minimal-invasive approach beneficial in numerous circumstances.

Intrapulmonary lymph nodes are rare lesions, usually appearing as small subpleural nodule (coin lesion), at or under the height of the carina. Computed tomography (CT) is very accurate in their detection. Three observations are reported.

Lichenoid eruptions are represented by lichen planus and lichen striatus. They are characterized clinically by a papulous eruption, and histogically by a dermal superficial infiltrate of lymphocytic cells and a cytotoxic reaction directed against basal keratinocytes. The main differential diagnosis is hamartoma, the differentiation being important because of the possible association of haemartoma with malformations.

The acronym CHARGE refers to a syndrome of unknown cause. Here we report on 47 CHARGE patients evaluated for the frequency of major anomalies, namely coloboma (79%), heart malformation (85%), choanal atresia (57%), growth and/or mental retardation (100%), genital anomalies (34%), ear anomalies (91%), and/or deafness (62%). In addition, we comment on anomalies observed very frequently in neonates and infants with the CHARGE syndrome, including, minor facial anomalies, neonatal brain stem dysfunction with cranial nerve palsy, and, mostly, internal ear anomalies such as semicircular canal hypoplasia that were found in each patient that could be tested. We propose several criteria for poor survival including male gender, central nervous system and/or oesophageal malformations, and bilateral choanal atresia. No predictive factor regarding developmental prognosis could be identified in our series. A significantly higher mean paternal age at conception together with concordance in monozygotic twins and the existence of rare familial cases support the role of genetic factors such as de novo mutation of a dominant gene or subtle sub-microscopic chromosome rearrangement. Finally, the combination of malformations in CHARGE syndrome strongly supports the view that this multiple congenital anomalies/mental retardation syndrome is a polytopic developmental field defect involving the neural tube and the neural crests cells.

Infection by group B streptococci (GBS) is an important cause of bacterial disease in neonates. Alpha C protein is a protective cell surface-associated protein of GBS. This protein contains a repeat region flanked by N and C termini. Variable expression of tandem repeating units of alpha C proteins had been found among clinical isolates of GBS. We examined the effect of the number of repeats on the immunogenicity of the alpha C protein and its ability to elicit protection from GBS infection in a neonatal mouse model. Mice were immunized with purified alpha C proteins of constructs containing various numbers of repeats (n = 1, 2, 9, and 16) and the N- and C-terminal regions. Both the N-terminal and the repeat regions contain protective and opsonic epitopes. Antibody responses to the alpha C protein constructs with various numbers of repeats were tested with enzyme-linked immunosorbent assay plates coated with either native, nine-repeat alpha C protein or "repeatless" N-terminal antigen. An inverse relationship was found between the number of repeats and the immunogenicity of the alpha C protein; this effect was most pronounced on titers of antibody to the N-terminal region. An inverse relationship was also observed between the number of repeats and protective efficacy, i.e., mouse dams immunized with 5 microg of one- or nine-repeat alpha C protein transferred protective immunity to 65 or 11% of their pups, respectively (P < 0.0001). Thus, the presence of multiple repeats appears to lessen the antibody response to the complete alpha C protein, and especially the antibody response to its N-terminal region, and suggests a mechanism whereby repeat elements contribute to the evasion of host immunity.

The alpha C protein of group B Streptococcus (GBS) is a major surface-associated antigen. Although its role in the biology and virulence of GBS has not been defined, it is opsonic and capable of eliciting protective immunity. The alpha C protein is widely distributed among clinical isolates and is a potential protein carrier and antigen in conjugate vaccines to prevent GBS infections. The structural gene for the alpha C protein, bca, has been cloned and sequenced. The protein encoded by bca is related to a class of surface-associated proteins of gram-positive cocci involved in virulence and immunity. To investigate the potential roles of the alpha C protein, bca null mutants were generated in which the bca gene was replaced with a kanamycin resistance cassette via homologous recombination using a novel shuttle/suicide vector. Studies of lethality in neonatal mice showed that the virulence of the bca null mutants was attenuated 5- to 7-fold when compared with the isogenic wild-type strain A909. Significant differences in mortality occurred in the first 24 h, suggesting that the role of the alpha antigen is important in the initial stages of the infection. In contrast to A909, bca mutants were no longer killed by polymorphonuclear leukocytes in the presence of alpha-specific antibodies in an in vitro opsonophagocytic assay. In contrast to previous studies, alpha antigen expression does not appear to play a role in resistance to opsonophagocytosis in the absence of alpha-specific antibodies. In addition, antibodies to the alpha C protein did not passively protect neonatal mice from lethal challenge with bca mutants, suggesting that these epitopes are uniquely present within the alpha antigen as expressed from the bca gene. Therefore, the alpha C protein is important in the pathogenesis of GBS infection and is a target for protective immunity in the development of GBS vaccines.

Maple syrup urine disease results in accumulation of leucine and its metabolites, which may lead in the long term to neurological dysfunction. In acute neonatal crises, large amounts of leucine may be removed by continuous venovenous haemofiltration. This extracorporeal technique has its risks and hazards, which increase with duration of treatment. We report three neonates in life-threatening conditions due to maple syrup urine disease, treated for not more than 12 h with various continuous venovenous techniques: continuous haemofiltration, haemodiafiltration and haemodialysis. The efficiency of and tolerance to these techniques was evaluated. For all three patients, plasma leucine levels decreased dramatically from 2186, 3818 and 2536 mumol/L to 1131, 1275 and 488 mumol/L, respectively. Leucine clearance obtained was 4.28 ml/min in haemodiafiltration. Their patients' neurological status improved rapidly and they have a normal developmental quotient at 22 months, 13 months, and 11 months of age, respectively. Tolerance was good except for hypothermia and drop in haematocrit in all cases. Haemodiafiltration management was more cumbersome and time consuming because it required continual adjustment of the substitution fluid flow rate to precisely balance inflow and outflow rates. We recommend continuous venovenous haemodialysis as the therapy of choice. It might be anticipated that improvement of this technique, by increasing dialysate flow rate and blood flow rate, will allow leucine concentration to be decreased below 1000 mumol/L within 6-8 h, whatever the initial level.

Esophageal bronchus is the most common congenital bronchopulmonary foregut malformation. Current surgical treatment is resection of anomalous pulmonary tissue, which is often hypoplastic and destroyed by infection. The authors report two cases of bronchotracheal reconstruction. The diagnosis was early, before 15 days of age. The anomalous pulmonary tissue had a pulmonary arterial supply and venous drainage as assessed by angiography and a good functional capacity on selective ventilation. Bronchotracheal anastomosis was successful in both cases: a right main bronchus at 25 days of age and a left main bronchus at 13 days of age. One child underwent reoperation 1 year later for bronchomalacia of the reimplanted bronchus. Both children are well with normal growth 3 and 7 years after surgery. Chest roentgenograms showed normal and symmetrical lung aeration. Tracheal reimplantation may be preferred to pulmonary resection when the anomalous pulmonary tissue is not destroyed. The pulmonary functional capacity is increased and the complications of pneumonectomy avoided.

Group B Streptococcus (GBS) is a major cause of neonatal sepsis, meningitis in early infancy, postpartum endometritis, and serious invasive infections in adults in the United States. We previously cloned, sequenced, and characterized the alpha antigen gene, bca, and showed that the alpha C protein of GBS is a trypsin-resistant, surface-associated polypeptide that contains a signal sequence, a unique N terminus, nine identical tandem repeats, and a C-terminal membrane anchor structure. Polyclonal antiserum raised to the recombinant alpha C protein and an opsonic monoclonal antibody, 4G8, raised to the native protein from GBS have been shown to be protective in a mouse model. The binding site of 4G8 has now been localized to the tandem repeat region of the alpha C protein. To determine whether the N terminus of the alpha C protein contains additional opsonic and/or protective epitopes, the sequence corresponding to the alpha C protein N terminus was subcloned into a pET vector, the expressed peptide from Escherichia coli was purified by Ni2+ affinity chromatography, and rabbit polyclonal antibodies were raised to the purified recombinant peptide. Antibodies to the alpha C protein N terminus were shown to be opsonic by an in vitro opsonophagocytosis assay. In addition, 69% of newborn mouse pups from mothers passively immunized with the antiserum to the recombinant N-terminal polypeptide of the alpha C protein were protected against lethal challenge with GBS A909. These data indicate that at least two distinct regions of the alpha C protein, the N terminus and the tandem repeat region, contain opsonic and protective epitopes.

Plain radiograms are insufficient to evaluate the integrity of a graft used to replace acetabular tissue loss in reoperations for total hip replacement. The aim of this work was to compare radiographic, computed tomographic and magnetic resonance imaging findings. Two groups of patients including 12 hip joints in each were evaluated 5 years after undergoing reoperation for annular support. Allografts (5 cases) or xenografts (7 cases) were used in one group. Plain radiograms. CT-scan and MRI were performed in each patient. The graft-receiver bone borders were visible on the CT-scans but were not distinguishable on the radiograms. Bone and graft density and structure in contact with the implant could be determined on the CT-scan. MRI was difficult to interpret in most cases due to implant-induced artefacts and is not recommended in this type of reconstruction.

Background: Eccrine angiomatous hamartoma is an uncommon skin disease with vascular and sudoral components: less than thirty cases have been reported in the literature., Case Report: A 3.5 month-old female infant developed a painful angiomatous plaque on the abdomen which was first seen 15 days after birth. Histology showed numerous vessels and eccrine sudoral glands in the dermis. Exeresis could not be complete and was followed for 15 years. There has been a slight hyperpigmentation with localized hyperhidrosis over the plaque. This hypersudation confirms the diagnosis which could not be confirmed on the initial biopsies., Discussion: This case of congenital eccrine angiomatous hamartoma could only be diagnosed late in the clinical course. This is the first case report on the abdomen, 80 p. 100 of the previous reports were on the limbs. After a 15 year follow-up, there was no progression of the hamartoma and pain regressed gradually. Without secondary development of localized hyperhidrosis, the diagnosis could not have been made. Careful comparison of pathology findings and clinical expression are essential for the diagnosis of eccrine angiomatous hamartoma.

The accessory soleus muscle is a supernumerary leg muscle that is rare and usually clinically silent. The best diagnostic strategy is not agreed on. We report two cases in which magnetic resonance imaging contributed significantly to the diagnosis and to the pretreatment evaluation.

We examined the utility of a PCR-based method termed cleaved amplified polymorphic sequences (CAPS) to type 35 well-characterized isolates of Staphylococcus epidermidis. The results were compared with detailed epidemiologic information and typing obtained by using pulsed-field gel electrophoresis (PFGE). To identify CAPS markers for this study, eight pairs of oligonucleotide primers corresponding to five previously sequenced S. epidermidis genes were synthesized and then used to amplify DNA sequences from the S. epidermidis strains by using PCR. Amplified products were reproducibly obtained for seven of eight primer pairs from chromosomal DNA of 33 of the 35 isolates. Seven restriction site polymorphisms were found in five of the amplified products when they were subjected to digestion with a panel of restriction endonucleases. Each fragment-enzyme combination that was polymorphic demonstrated only two alleles in the 33 S. epidermidis isolates analyzed, corresponding to the presence or absence of a single restriction site. Overall, five distinct combinations of alleles were detected and were designated CAPS types A through E. There was a close correlation between the CAPS grouping, the epidemiologic information for the strains, and grouping by PFGE following SmaI digestion of chromosomal DNA. Although PFGE analysis was more discriminatory than typing based on the limited number of CAPS markers used in this study (isolates from the same CAPS group were sometimes distributed into more than one PFGE group), no isolates from the same PFGE group were found in more than one CAPS group. The CAPS procedure was highly reproducible, in contrast to published experience with arbitrarily primed PCR. These preliminary data suggest that CAPS represents a PCR-based technique for strain typing that is highly reproducible, rapid, utilizes widely available technologies, and provides results that are relatively easy to interpret and express.

Variable expression of repeating units of the protective alpha C proteins among clinical isolates of group B streptococci (GBS) may have implications for vaccine development. In this study, alpha C protein genes containing various numbers of repeats (1,2,9, and 16) were cloned in a T7 overexpression vector in Escherichia coli. Expression was induced by isopropyl-beta-D-thiogalactopyranoside, and proteins were purified by anion-exchange, gel filtration, or affinity chromatography or by isoelectric focusing. Rabbits were immunized with purified 1-,2-,9-, or 16-repeat proteins. All proteins appeared to be highly immunogenic. Enzyme-linked immunosorbent assay inhibition with 9-repeat protein as the coating antigen and 9-repeat-antigen-elicited antiserum showed that a 200-fold-higher concentration of 1-repeat antigen than of 9- or 16-repeat antigen was required for 50% inhibition of antibody-antigen binding. The concentration of 2-repeat antigen required for 50% inhibition was intermediate relative to the concentrations of 1- and 9-repeat antigens. These results suggested that antibodies to 9-repeat antigen recognized predominantly a conformational epitope(s) contained in proteins with higher numbers of repeats (9 or 16) but lost considerable binding affinities for an epitope(s) contained in alpha C proteins with fewer repeats (1 or 2). Similar results were obtained with antiserum to 16-repeat antigen. However, antibodies to 1- and 2-repeat antigens recognized 1-,2-,9-,and 16-repeat antigens with equal binding affinities. This finding suggested that 1- and 2-repeat-elicited antibodies recognized an epitope(s) on individual repeats. Loss of repeating units from the alpha C proteins may result in decreased protection because the loss of epitopes (including conformational epitopes) gives the microorganisms the opportunity to escape host antibodies. If 1- and 2-repeat-elicited antibodies bind all alpha C proteins with equal affinity, regardless of their repeat number, they may prevent GBS strains with fewer repeats from escaping host immunity. Protection data obtained with antisera to the proteins with different repeat numbers support this hypothesis: mouse pups challenged with GBS strain A909 were better protected when immunized with 1- or 2-repeat-elicited antiserum (76 and 75%, respectively) than when immunized with 9- or 16-repeat-elicited antiserum (41 and 48%, respectively).

Group B streptococci (GBS) are the most common cause of neonatal sepsis, pneumonia, and meningitis. The alpha C protein is a surface-associated antigen; the gene (bca) for this protein contains a series of tandem repeats (each encoding 82 aa) that are identical at the nucleotide level and express a protective epitope. We previously reported that GBS isolates from two of 14 human maternal and neonatal pairs differed in the number of repeats contained in their alpha C protein; in both pairs, the alpha C protein of the neonatal isolate was smaller in molecular size. We now demonstrate by PCR that the neonatal isolates contain fewer tandem repeats. Maternal isolates were susceptible to opsonophagocytic killing in the presence of alpha C protein-specific antiserum, whereas the discrepant neonatal isolates proliferated. An animal model was developed to further study this phenomenon. Adult mice passively immunized with antiserum to the alpha C protein were challenged with an alpha C protein-expressing strain of GBS. Splenic isolates of GBS from these mice showed a high frequency of mutation in bca--most commonly a decrease in repeat number. Isolates from non-immune mice were not altered. Spontaneous deletions in the repeat region were observed at a much lower frequency (6 x 10(-4)); thus, deletions in that region are selected for under specific antibody pressure and appear to lower the organism's susceptibility to killing by antibody specific to the alpha C protein. This mechanism of antigenic variation may provide a means whereby GBS evade host immunity.

Introduction: Skin cancers are more frequent and more aggressive in immunosuppressed patients., Case Report: A 58-year-old man was seen in January 1994 for squamous cell carcinoma of the right shoulder which had grown to 7 x 7 cm in the last 5 months. The patient had a past history of surgical exeresis of 5 squamous cell carcinomas and 3 basal cell carcinomas. Despite complete exeresis, the disease spread to localized then diffuse skin metastases. Acitretine and alpha-interferon were uneffective. Polychemotherapy stabilized the situation but several bronchopulmonary infections with atypical germs led to death (in February 1995). The patient had CD4 lymphocytopenia with a count < 100/mm3 in January 1994 of unknown origin (viral infection was eliminated)., Discussion: Our patient had idiopathic CD4 lymphocytopenia. In 40 p. 100 of the cases CD4 lymphocytopenia is caused by AIDS and in 53 p. 100 by other diseases, especially skin diseases including Kaposi syndrome, mycosis fungoides, squamous cell or basal cell carcinoma. The cutaneous carcinomas which often develop in AIDS patients with low CD4 counts are usually less aggressive than in our patient. Certain neoplasia could be the cause of the lymphopenia. CD4 counts are usually more variable and lymphopenia of shorter duration in other etiologies.

Introduction: Human papilloma virus is highly prevalent, but rarely localized in the conjunctiva., Case Report: A 19-year-old man with no past history of skin or mucosal disease consulted for tumefaction of the conjunctiva. Exeresis revealed a viral papilloma. In situ hybridization was positive for human papilloma virus 6/11., Discussion: Conjunctival lesions of human papilloma virus are often located in the caroncula as in our patient. The papillomatous aspect of the tumour may suggest squamous cell carcinoma (sometimes induced by human papillomavirus 16/18). Contamination may be manual or occur at birth via the maternal genital mucosa. Treatment usually is based on wide exeresis with cryo-application although spontaneous regression is possible.

The cDNA for human ferrochelatase, the enzyme that is defective in the rare genetic disease erythropoietic protoporphyria (EPP), was tested for its ability to allow the expression of ferrochelatase in mammalian cells. The cDNA was ligated to the plasmid expression vectors pCD and pED6 and transfected into COS-1 and CHO-DUKX cells, respectively. In each case, ferrochelatase activity increased. The cDNA was also ligated into the retroviral vector pLXSN, and virus-packaging cells were produced. Supernatants from these cells were used to infect fibroblasts in vitro from a patient with EPP. We found that the infected cells containing the ferrochelatase cDNA had enzyme levels in the range of normal fibroblasts and that they did not accumulate protoporphyrin when grown in the presence of delta-aminolevulinic acid. We conclude that introducing the cDNA for normal ferrochelatase into fibroblasts from an EPP patient restores ferrochelatase enzyme activity to the normal range. These experiments suggest potential for genetic therapy in EPP.

Bronchial schwannomas are rare tumours. We report a case of an endo and exobronchial schwannoma which presented with dyspnoea and left pulmonary atelectasis. This was treated by complete resection of the tumour with a resection and anastomosis of the left bronchial stump flush with the lobar bifurcation. This tumour is most often benign and a conservative approach should be taken each time that this is permissible anatomically.

The only curative treatment for enzymatic deficiency such as Ornithine transcarbamylase (OTC) deficiency is liver transplantation. We have studied hepatocyte transplantation as alternative therapy in spfash mouse, the animal mode of OTC deficiency. Hepatocytes were obtained from C57BL/6J strain mice (normal OTC activity). About 2 x 10(6) hepatocytes in 0.1 ml were injected in the spleen of recipient mouse. We then studied: ammonemia, urinary orotate, spleen OTC activity, liver OTC activity, histological presence of hepatocytes in the spleen, immunohistochemical OTC staining in liver and spleen hepatocytes. In syngeneic hepatocyte transplantation (C57 > C57) functional transplanted hepatocytes were found in the spleen over 5 months after transplantation. In allogeneic transplantation (C57 > spfash) without immunosuppression, hepatocytes were rejected in 3 days. With cyclosporine immunosuppression, hepatocyte survived 12 days and showed OTC activity. A few transplanted hepatocytes with OTC activity migrated from spleen of liver. Metabolic disorder were not corrected. This technically easy method (compared to whole liver transplantation) demonstrated 2 problems: reject in allogeneic transplantation and the small amount of injected enzyme.

Group B streptococci (GBS) cause the majority of cases of neonatal sepsis and meningitis in the United States. Immunization of women of childbearing age is one strategy under consideration for the prevention of neonatal disease. The beta C protein, a 130-kDa antigen present in many clinical isolates of GBS, was purified from GBS by extraction into sodium dodecyl sulfate (SDS)-containing buffer, preparative SDS-polyacrylamide gel electrophoresis, and electroelution. Purified beta C protein antigen (25 micrograms) with Freund's adjuvant was used to immunize rabbits. Rabbits developed enzyme-linked immunosorbent assay titers of > 1:1.6 x 10(6), and sera from immunized rabbits were administered to pregnant mice. Their neonatal pups were then challenged with a strain of GBS expressing beta C protein; 68% of these pups were protected by immune antiserum, whereas no controls were protected (P < 0.001). The immune serum (diluted 1:100) facilitated opsonophagocytic killing of GBS strains expressing the beta C protein but not those that do not express the antigen (mean log kill +/- standard deviation = 0.71 +/- 0.8 log10 CFU for beta+ strains and 0.09 +/- 0.2 for beta- strains; P = 0.02). In subsequent experiments, adult female mice were actively immunized with two doses of 2, 5, or 10 micrograms of beta C protein 2 months prior to mating. One- to two-day-old offspring of these dams were challenged with GBS and were protected in a dose-dependent manner, with 96% survival in the high-dose (10-micrograms) group and 20% survival in a sham-immunized control group (P < 0.001). Thus, active immunization of mice with the GBS beta C protein confers protection against lethal infection with beta+ GBS to their offspring.

Group B Streptococcus (GBS) is the leading cause of neonatal sepsis and meningitis in the United States. The surface-associated C protein alpha antigen of GBS is thought to have a role in both virulence and immunity. We previously cloned the C protein alpha antigen structural gene (named bca for group B, C protein, alpha) into Escherichia coli. Western blots of both the native alpha antigen and the cloned gene product demonstrate a regularly laddered pattern of heterogeneous polypeptides. The nucleotide sequence of the bca locus reveals an open reading frame of 3060 nucleotides encoding a precursor protein of 108,705 Da. Cleavage of a putative signal sequence of 41 amino acids yields a mature protein of 104,106 Da. The 20,417-Da N-terminal region of the alpha antigen shows no homology to previously described protein sequences and is followed by a series of nine tandem repeating units that make up 74% of the mature protein. Each repeating unit is identical and consists of 82 amino acids with a molecular mass of 8665 Da, which is encoded by 246 nucleotides. The size of the repeating units corresponds to the observed size differences in the heterogeneous ladder of alpha C proteins expressed by GBS. The C-terminal region of the alpha antigen contains a membrane anchor domain motif that is shared by a number of Gram-positive surface proteins. The large region of identical repeating units in bca defines protective epitopes and may play a role in generating phenotypic and genotypic diversity of the alpha antigen.

The authors report a new case of hemangiopericytoma in an elderly man. An asymptomatic mediastinal mass was found on a routine chest film. C.T. guided fine-needle biopsy was diagnostic. These rare lesions are clinically and radiologically aspecific and require pathologic proof. The value of percutaneous biopsy before therapeutic decision is emphasized.

Closed traumatic rupture of the esophagus is uncommon, usually located in the upper third of the esophagus. We report a case occurring in the lower third. This diagnosis must be envisaged when faced with delayed clinical and radiological signs. The prognosis is severe and the therapeutic decisions are controversial.

Group B streptococci (GBS) is the leading cause of neonatal sepsis and meningitis. C proteins are an immunologically important group of surface-associated antigens in GBS that remain incompletely characterized. Two C proteins have been designated alpha and beta on the basis of protease susceptibility. We recently used a monoclonal antibody to describe a protective epitope of the GBS alpha (or trypsin-resistant) C protein in the prototype Ia/c GBS strain. In the present study, we examined 51 GBS isolates for expression of C-protein alpha and beta antigens. The alpha antigen, as detected with monoclonal antibody in sodium dodecyl sulfate (SDS) extracts, appears as a heterogeneous series of proteins spaced 8 kDa apart on SDS-polyacrylamide gel electrophoresis, but has a maximum molecular mass that varies among strains from 62.5 to 167 kDa. By immunoblotting with human immunoglobulin A, polyclonal antiserum, or monoclonal antibody, the beta antigen, in contrast, appears as a single protein of molecular mass between 124 and 134 kDa. The amount of alpha antigen expressed by each strain was quantified by enzyme immunoassay inhibition and was found to vary markedly from strain to strain. The susceptibility of strains of GBS to opsonization and killing by human polymorphonuclear leukocytes in the presence of either complement alone or complement with alpha-specific monoclonal antibody was examined. Strains expressing the alpha antigen were less readily killed in the absence of specific antibody than were alpha-negative strains. Killing in the presence of alpha-specific monoclonal antibody was found to correlate directly with the maximum molecular mass of the alpha antigen and with the quantity of antigen on the bacterial cell surface. Isolates of GBS that express the alpha C protein vary widely in the quantity and molecular mass of the alpha antigen produced, and this heterogeneity appears to have biologic importance.