The effect of cephalothin prophylaxis on postoperative ventriculoperitoneal shunt infections.

Postoperative infection is an important complication after insertion of a ventriculoperitoneal (VP) shunt in children with hydrocephalus. A randomized double-blind placebo-controlled study was performed to determine the efficacy of cephalothin in preventing postoperative shunt infection. Sixty-three children who presented for elective VP shunt insertion between January 1982 and December 1985 and who did not have a history of shunt infections were randomly assigned to receive four doses of prophylactic cephalothin, 25 mg/kg (32 patients), or of a multivitamin placebo (31 patients). Postoperative infection developed in 6% of the treatment group, compared with 10% of the placebo group, a difference that was not statistically significant, although a clinical significance may have been masked by the small sample size. A large multicentre trial is needed to determine the efficacy of antibiotic prophylaxis in reducing the incidence of postoperative VP shunt infections.     

Serum proteins and zinc as parameters to monitor the health of children in a rural Tanzanian community

Total protein concentration, zinc, prealbumin, albumin, alpha-1-, alpha-2-, beta- and gammaglobulin concentrations were measured in serum samples collected in three successive years (1982, 1983 and 1984) from children (1 month-15 years) of Kikwawila village, Tanzania. The analysis of a total of 1590 serum samples provided the baseline data for children living in a rural Tanzanian community. The total protein values and the concentrations of betaglobulin were within the range described for Caucasians. Albumin, prealbumin, alpha-1- and alpha-2-globulin concentrations were below these standard values. On the other hand the gammaglobulin concentration was twice as high. The concentrations of total protein, gammaglobulin and prealbumin correlated with age. From 1982 to 1983 a significant decrease of most of the serum components (incl. zinc) was observed, although in children older than 2 years the alpha-1-globulins increased. All values increased again from 1983 to 1984, except for the zinc concentration, which decreased further. The individual fluctuations were analysed by comparing paired values for the children participating in the period 1982-1983, or 1983-1984. The proportion of children showing large fluctuations, sometimes exceeding the selected limits of tolerance, was larger in the period 1982-1983 than 1983-1984. This was consistent with the overall pattern found for all children. The prealbumin level, which has been postulated to be an indicator for malnutrition or borderline malnutrition, was analysed in detail. The values were far below normal values (200-300 mg/l), reaching a plateau with 130 mg/l among 4-6-year-old children. The individual fluctuations indicated a decrease from 1982 to 1983, which was considerable both in terms of the proportion of children showing a decrease (55%) and in the magnitude of the decrease. There was an increase from 1983 to 1984 but this increase did not compensate for the loss in 1983. Prealbumin concentrations showed a slight trend towards decreased values with stunting and wasting. No direct correlation was found between the other biochemical parameters and the parasite or anthropometric data collected at the same time. It was difficult to establish direct relationships between the biochemical parameters, which mainly indicate the health status of the child at the time-point of the survey, and anthropometric parameters which reflect the history of the individual over a long period. No direct correlation could be established between the biochemical parameters and the parasitological data.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pattern of Sequence Variation Across 213 Environmental Response Genes

To promote the clinical and epidemiological studies that improve our understanding of human genetic susceptibility to environmental exposure, the Environmental Genome Project (EGP) has scanned 213 environmental response genes involved in DNA repair, cell cycle regulation, apoptosis, and metabolism for single nucleotide polymorphisms (SNPs). Many of these genes have been implicated by loss-of-function mutations associated with severe diseases attributable to decreased protection of genomic integrity. Therefore, the hypothesis for these studies is that individuals with functionally significant polymorphisms within these genes may be particularly susceptible to genotoxic environmental agents. On average, 20.4 kb of baseline genomic sequence or 86% of each gene, including a substantial amount of introns, all exons, and 1.3 kb upstream and downstream, were scanned for variations in the 90 samples of the Polymorphism Discovery Resource panel. The average nucleotide diversity across the 4.2 MB of these 213 genes is 6.7 × 10^-4, or one SNP every 1500 bp, when two random chromosomes are compared. The average candidate environmental response gene contains 26 PHASE inferred haplotypes, 34 common SNPs, 6.2 coding SNPs (cSNPs), and 2.5 nonsynonymous cSNPs. SIFT and Polyphen analysis of 541 nonsynonymous cSNPs identified 57 potentially deleterious SNPs. An additional eight polymorphisms predict altered protein translation. Because these genes represent 1% of all known human genes, extrapolation from these data predicts the total genomic set of cSNPs, nonsynonymous cSNPs, and potentially deleterious nonsynonymous cSNPs. The implications for the use of these data in direct and indirect association studies of environmentally induced diseases are discussed.     

Molecular and biological analysis of echovirus 9 strain isolated from a diabetic child

The full-length infectious cDNA clone was constructed and sequenced from the strain DM of echovirus 9, which was recently isolated from a 6-week-old child at the clinical onset of type 1 diabetes. Parallel with the isolate DM, the full-length infectious cDNA clone of the prototype strain echovirus 9 Barty (Barty-INF), was constructed and sequenced. Genetic relationships of the sequenced echo 9 viruses to the other members of the human enterovirus type B species were studied by phylogenetic analyses. Comparison of capsid protein sequences showed that the isolate DM was closely related to both prototype strains: Hill and Barty-INF. The only exception was the inner capsid protein VP4 where serotype specificity was not evident and the isolate DM clustered with the strain Hill and the strain Barty-INF with echovirus 30 Bastianni. Likewise, the nonstructural protein coding region, P2P3, of isolate DM was more similar to strain Hill than to strain Barty-INF. However, like echovirus 9 Barty, the isolate DM contained the RGD-motif in the carboxy terminus of capsid protein VP1. By blocking experiments using an RGD-containing peptide and a polyclonal rabbit antiserum to the alpha(v)beta(3)-integrin, it was shown that this molecule works as a cellular receptor for isolate DM. By using primary human islets, it was shown that the isolate DM is capable of infecting insulin-producing beta-cells like the corresponding prototype strains did. However, only isolate DM was clearly cytolytic for beta-cells. The infectious clones that were made allow further investigations of the molecular features responsible for the diabetogenicity of the isolate DM.     

Cell surface membrane antigen phenotype of human gastrointestinal mast cells

BACKGROUND: Mast cells (MC) are important effector cells of allergic and inflammatory reactions in diverse organs. These cells interact with a number of other immune cells and structural cells in the tissues as well as with proinflammatory mediators and cytokines. The various interactions are considered to be mediated through distinct cell surface membrane receptors on MC. METHODS: In the present study, we have established the cell surface membrane phenotype of human gastrointestinal MC (HGMC) using a panel of monoclonal antibodies and indirect immunofluorescence staining techniques. RESULTS: HGMC were found to react with antibodies against CD29, CD33, CD44, CD45, CD47, CD54, CD55, CD58, CD63, CD117, CD147, CD151, CD172a, and CD203c. By contrast, HGMC did not express detectable amounts of CD1, CD2, CD4, CD5, CD14, CD15, CD16, CD22, CD24, CD25, CD26, CD27, CD28, CD31, CD32, CD34, CD35, CD88, or CD116. The alpha-chain of the IL-3 receptor (CD123) was detectable neither in resting HGMC nor in HGMC exposed to stem cell factor and interleukin-4. CONCLUSIONS: HGMC express a unique profile of surface antigens including the receptor for mast cell growth factor, adhesion-related molecules, and activation-linked membrane antigens.     

Indolent systemic mastocytosis with elevated serum tryptase, absence of skin lesions, and recurrent severe anaphylactoid episodes

BACKGROUND: In contrast to aggressive mastocytosis, patients with indolent systemic mastocytosis (ISM) usually present with urticaria pigmentosa-like skin lesions. In those who lack skin lesions, mastocytosis is often overlooked or confused with endocrinologic, allergic, or other internal disorders. CASE REPORT AND RESULTS: We report on a 33-year-old male patient in whom severe hypotensive episodes occurred after contact with ants or yellow jackets. Since no specific IgE was detected, the serum tryptase concentration was measured and found to be clearly elevated (70 ng/ml). Consecutive staging and examination of the bone marrow revealed ISM. The patient was advised to circumvent insect contact, to take antihistamines on demand, and to carry an epinephrine self-injector for emergency events. In a retrospective analysis of 40 patients seen between 1988 and 2003, only 2 had a life-threatening mediator-related episode before ISM was diagnosed. CONCLUSIONS: Our report confirms the diagnostic value of tryptase in patients with suspected mastocytosis. In addition, the report suggests that the lack of typical skin lesions does not exclude an indolent form of mastocytosis even if the serum tryptase is clearly elevated. Finally, our case further shows that mastocytosis can be an important differential diagnosis to be considered in patients with unexplained anaphylactoid or other mediator-related symptoms.     

A role for epithelial gamma delta T cells in tissue repair

Conclusions  A balance between epithelial growth and repair versus inflammation to isolate and contain damage is critical for maintenance of the epithelial microenvironment. Epithelial γδ T cells appear to play an important role in maintaining the integrity of the epithelial tissues they survey. Insult to the epithelium likely leads to the up-regulation of self-associated stress molecules that are recognized by intraepithelial γδ T cells. The limited, and in some cases canonical, repertoire of the epithelial γδ TCRs is certainly consistent with this recognition of damaged self, rather than recognition of the vast array of possible non-self antigens that could invade these epithelial barriers. Furthermore, the cellular context of the various γδ T cell subsets and the types of antigens they engage together may contribute to the distinct requirements of γδ T cells for PTKs in their selection, homing and presumably also in their response to epithelial cell damage.     

Hormone-active intradural spinal metastasis of a prolactinoma — A case report

Summary A 44-year-old woman developed acute severe visual field defects and was operated on a macroprolactinoma. Since complete resection of the tumor was not possible, radiotherapy was performed and in addition to hormone replacement therapy, bromocriptine (up to 60 mg daily) was started without however complete normalization of PRL levels. Four years later PRL levels increased to 10⁵ µU/ml despite continuation of dopamin agonist (mesulergin) treatment. As shown by ophthalmological examination and computer tomography there were no signs of regrowth of the pituitary tumor. At that time the patient complained of severe lumbar pain and myelography revealed a tumor mass in the spinal cord (L₁–L₂). Since the spinal tumor was not removable, laminectomy was performed. Histology and immunohistochemistry demonstrated a metastasis of the prolactinoma. Radiotherapy and bromocriptine in extreme doses (140 mg daily) together with an antiestrogen were not able to improve the neurological deficits (paraparesis) and to lower the PRL levels. This case of a metastasis of a prolactinoma after operation, radiotherapy, and dopamin agonist treatment stresses the importance of close surveillance of patients with prolactinomas without PRL normalization during dopamin agonist therapy and shows for the first time the possibility of ectopic PRL production due to an intradural spinal metastasis.Abbreviations ACTH adrenocorticotropin - FSH folliclestimulating hormone - GH growth hormone - Gy Gray - L lumbar - LH luteinizing hormone - µU/ml microunits per milliliter - mU/ml milliunits per milliliter - PRL prolactin - TBG thyroxine-binding globulin - TSH thyrotropin - T₄ thyroxine - T₃ triiodothyronine