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Human herpes virus type 7 DNA in the cerebrospinal fluid of children with central nervous system diseases.

UNLABELLED: Human herpes virus type 7 (HHV-7) has been associated with unspecific febrile syndrome, exanthem subitum (ES), viral rashes and Epstein-Barr virus (EBV) like syndrome. Neurological complications such as hemiplegia or seizures have been described in a few children with ES. Whether HHV-7 may also affect the CNS in the absence of ES is unknown. In this study, we investigated CSF samples from children with different neurological diseases for the presence of HHV-7 specific DNA. A HHV-7 specific nested polymerase chain reaction (PCR) was established amplifying a 478 bp DNA sequence of the glycoprotein U23 of HHV-7 strain SB. 68 children with CNS diseases with inflammatory CSF findings (n = 24), CNS diseases without inflammatory CSF findings (n = 18) and febrile seizures (n = 26) were examined. A total of 26 children with infectious diseases in the absence of neurological disease and 11 children without signs of a peripheral infection and without neurological disease served as controls. The CSF samples of six children from the study groups were HHV-7 PCR positive, but none from the controls. These children were diagnosed with aseptic meningitis (n = 1), viral encephalitis/meningoencephalitis (n = 2), facial palsy (n = 1), vestibular neuritis (n = 1) and febrile seizure (n = 1). CONCLUSION: These results indicate that human herpes virus type 7 infection is associated with central nervous system disease in children and should be considered in children whether inflammation in the cerebrospinal fluid is present or not.

Adolescent↗

Impact of central venous catheter type and methods on catheter-related colonization and bacteraemia.

A prospective, randomized, controlled, multi-centre clinical trial was performed to test the effectiveness of an antimicrobial central venous catheter (CVC) made of polyurethane integrated with silver, platinum and carbon black (Vantex). Adults expected to require a CVC for more than 60 h were eligible, and were randomized to receive the test or control catheter. All CVCs were inserted with new venipunctures using full aseptic technique. Following catheter removal, the distal tip and an intracutaneous segment were removed and cultured using semiquantitative and quantitative methods. Peripheral blood samples were obtained and cultured to confirm cases of catheter-related bloodstream infection (CRBSI). Bacterial and fungal organisms were identified by standard microbiological methods. Catheter placement was performed primarily in the intensive care unit (50%) or operating theatre (42%). Complete data could be evaluated for 539 patients (77%). The mean duration of CVC placement was 149.3h (six days). There were no significant differences in colonization or bacteraemia rates between the test and control catheters. The overall colonization rate was not particularly low (24.5%), and yet CVC-related bacteraemia occurred in only 1.4% of patients, and CRBSI occurred in only one patient from the control group (0.2%). Insertion site and dressing change frequency were significantly associated with the colonization rate. Although CVCs with antimicrobial features have been associated with a decrease in catheter-related colonization and bacteraemia, this study demonstrated that infection rates may depend more on non-catheter-related factors, such as adherence to infection control standards, selection of insertion site, duration of CVC placement, and dressing change frequency. As microbial resistance increases, clinicians should make maximal use of these processes to reduce catheter-related infections.

Adult↗

Preliminary results of uncemented metal on metal stemmed and resurfacing hip replacement arthroplasty.

Seventy uncemented stemmed total hip replacements and 35 uncemented surface replacements with all metal Metasul articulating surfaces were followed up in a prospective study. There was no evidence that this metal on metal articulation causes new problems or complications that were not known already from other polyethylene-aluminum oxide ceramic articulating combinations. The results of 64 of 70 patients could be assessed as excellent and good. When tissue samples obtained during 2 reoperations for ectopic ossification were examined histologically, there was no light microscopic evidence of metal particles. In these cases, aseptic loosening seemed to be due to the lack of initial fixation with the original femoral component design, and was not related to the use of the Metasul bearing. The metal on metal articulation reduces the production of particles considerably according to experience to date. It is therefore hoped that foreign body reactions due to wear particles will be significantly reduced. The results support the continued investigation of metal on metal joint replacements for younger, active patients.

Adolescent↗

Observations on the endemicity of plague in Karatu and Ngorongoro, northern Tanzania.

Commensal and field rodents and wild small carnivores were live-trapped in five villages of Karatu district and one settlement in the Ngorongoro Conservation Area in Ngorongoro district in Tanzania. Blood samples were taken and serologically tested for plague, using the Blocking ELISA technique. Some domestic dogs and cats in the Karatu villages were aseptically bled and similarly tested for plague. Fleas were collected from the examined animals and from randomly selected residential houses. A total of 241 rodents, 1 Crocidura spp, 43 dogs, 12 cats and 4 slender mongooses were involved in the survey. Of the rodents, 14.5% were infested with fleas, which comprised of Xenopsylla brasiliensis (45.8%) and Dinopsyllus lypusus (54.2%), with an overall population density of 0.2 fleas/animal. Thirty one (72.1%) of the dogs were infested with fleas, all of which were Ctenocephalides spp. Thirty five (63.3%) houses were infested with fleas whose population was composed of Ctenocephalides spp, Pulex irritans, Tunga penetrans and Echinophaga gallinacea. Infected rodents were found in all the villages while the infected dog was found at Rhotia-Kati. Nineteen (11%) of the rodents and one (2%) dog harboured specific plague antibodies. It was broadly concluded that sylvatic plague was endemic in Karatu district and Ngorongoro Conservation Area and that outbreaks of the disease can occur in the area any time if and when relevant conditions become favourable. Prompt application of appropriate preventive and control measures and survey for substantiating the status in the Lake Manyara National Park, which is adjacent to some of the infected villages, are recommended.

Animals↗

Leptin in cerebrospinal fluid from children: correlation with plasma leptin, sexual dimorphism, and lack of protein binding.

BACKGROUND: Previous studies in adults have established that leptin is present at very low concentrations in cerebrospinal fluid (CSF), but few data exist concerning CSF leptin in children. Current evidence suggests that CSF leptin concentrations interact with hypothalamic centers controlling food intake. Serum leptin concentrations manifest a sexual dimorphism that arises during puberty. METHODS: Leptin concentrations were determined in CSF from 42 pre- and postpubertal children who had been objectively classified into non-neurological disease or aseptic meningitis groups. Multivariate analysis of the dependence of CSF leptin on gender, pubertal state, body mass index (BMI), presence of aseptic meningitis, and CSF protein concentration was performed. RESULTS: CSF leptin concentrations correlated with log-transformed plasma leptin concentrations in concomitantly collected samples (r = 0.582; P = 0.029). BMI and gender were significant determinants of CSF leptin in postpubertal children, but only BMI was significant in prepubertal children. Analysis with HPLC to separate protein-bound and free forms of leptin found only free leptin in CSF. CONCLUSIONS: CSF leptin concentrations in children reflect plasma leptin concentrations, including the advent of sexual dimorphism at puberty. Only free leptin is detectable in CSF, suggesting that it is the biologically active form.

Adolescent↗

Cerebrospinal fluid interleukin-6, interleukin-8, and tumor necrosis factor-alpha in children with central nervous system infections.

Concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) in cerebrospinal (CSF) samples were determined from 11 control and 42 children with central nervous system infections including 11 patients with bacterial meningitis, 20 patients with aseptic meningitis, 11 patients with encephalitis. The CSF IL-6, IL-8 and TNF-alpha concentrations in patients with bacterial meningitis were significantly higher than those with aseptic meningitis, encephalitis and the control groups. CSF IL-6, IL-8 and TNF-alpha levels in patients with aseptic meningitis were also significantly higher than those in the control group. There was no significant increase of CSF IL-6, IL-8 and TNF-alpha concentrations in patients with encephalitis compared to the control group. CSF IL-6 and TNF-alpha concentrations were decreased in patients with bacterial meningitis after treatment. CSF IL-8 levels were significantly decreased in both bacterial and aseptic meningitis groups at recovery period. There were no correlation between CSF IL-6, IL-8 and TNF-alpha levels and other parameters including CSF leukocytes, protein, sugar, IgG levels and IgG indexes in patients with bacterial meningitis. These results suggest that IL-6, IL-8 and TNF-alpha are important mediators in the meningeal inflammatory process in patients with meningitis. The levels of these mediators are good indicators for the extent of the meningeal inflammation.

Adolescent↗

Human herpesvirus 7-associated meningitis and optic neuritis in a patient after allogeneic stem cell transplantation.

A 9-year-old boy who received allogeneic stem cell transplantation began to vomit from day 10 after transplantation. In addition to vomiting, the patient had a fever (from day 26) and severe headache (from day 34). His cerebrospinal fluid (CSF) (day 41) demonstrated pleocytosis with an absence of leukemic cells. Although the patient's symptoms were resolved with further supportive care, abrupt onset of bilateral decreased vision occurred at day 54. He was diagnosed with bilateral optic neuritis, due to the presence of disc edema and redness. Concomitant with the occurrence of aseptic meningitis, the human herpesvirus 7 (HHV-7) antibody titer increased significantly in this patient. Although neither HHV-6 nor cytomegalovirus (CMV) DNA was detected in CSF collected at day 41, HHV-7 DNA was detected in the sample. Viral DNA was not detected in CSF collected at day 93.

Antibodies, Viral↗

[Serous meningitis associated with primary genital herpes infection].

Aseptic meningitis is not an uncommon complication to primary genital herpes infection caused by herpes simplex virus type 2 (HSV-2). Compared with other types of viral meningitis, HSV-2-meningitis is associated with a significant rate of neurological complications in the acute stage. In addition, some patients will suffer from recurrent aseptic meningitis (Mollaret's meningitis) later. We describe six patients, five women and one man, age 26-35 years, with aseptic meningitis caused by HSV-2. All the patients showed serological evidence of primary herpes infection (negative HSV-IgG and/or positive HSV-IgM in serum samples). Polymerase chain reaction detected HSV-2 in cerebrospinal fluid in all five of five cases, while virus cultures were positive in two of the six cases. Only three patients showed clinical signs of simultaneous genital herpes infection. One patient, a 28-year-old female, developed transient autonomic nervous system dysfunction with urinary retention, constipation, and neuralgic pain in the buttocks, perineum and lower limbs. 13 months later she was hospitalised for a genital herpes infection with headache, parestesia and fever, but spinal fluid examination showed no abnormality.

Adult↗

Do infusions of midazolam and propofol pose an infection risk to critically ill patients?

In order to investigate bacterial contamination of i.v. anaesthetic agents, given by infusion to critically ill patients, we have cultured residual infusion fluid from infusion syringes, 50 containing midazolam and 50 propofol. The infusions had been prepared with routine aseptic precautions and had been running for between 0.75 and 21.25 h. Only scanty growths of Staphylococcus epidermidis were isolated from seven syringes (four midazolam and three propofol). Small volume samples were more likely to produce bacterial growth than large volume specimens. Midazolam infusions made up in 5% glucose were more likely to be contaminated than those made up in 0.9% saline. Antibacterial activity was detected in 18 midazolam and one propofol filtrate. Midazolam infusions inhibited the growth of all seven of the S. epidermidis isolates, whereas propofol supported similar rates of multiplication to that obtained with control broth medium. The results of this study imply that contamination of the infusions probably occurred after they were disconnected from the patient. Despite the ability of propofol to support microbial multiplication, we have no evidence to suggest that this is clinically significant when infusions are prepared with conventional aseptic precautions.

Bacterial Infections↗

[Effects of disease modifying antirheumatic drugs (DMARDs) and DEX on IL-1 beta and IL-6 production by IL-1 beta stimulated synovial culture cells].

UNLABELLED: To investigate the effects of disease modifying antirheumatic drugs (DMARDs) and DEX on production of IL-1 beta, IL-6 and TNF-alpha, synovial cells were observed after IL-1 beta administration in vitro. MATERIALS AND METHODS: Synovial tissue was obtained aseptically from 8 rheumatoid arthritis patients during joint surgery. The dissected tissue was treated with collagenase and adherent cells were passaged before using as samples. They were stimulated with IL-1 beta (1 ng/ml) and cultured with DMARDs and DEX in serum-free media. After 24 hours' incubation, the production of IL-1 beta, IL-6 and TNF-alpha in the supernatants was measured. RESULTS: DEX inhibited the production of IL-6. GST inhibited the production of IL-1 beta and IL-6. CONCLUSION: DEX and GST may modulate the disease activity by inhibiting the cytokine production from synovial cells.

Anti-Inflammatory Agents↗

The gene expression profile in refractory periodontitis patients.

BACKGROUND: There are no specific bacterial profiles or diagnostic tests capable of identifying refractory periodontitis patients before a treatment regimen is initiated. Therefore, in this high-risk cohort of patients who do not respond appropriately, host factors that might be partly under genetic control may play a crucial role in their susceptibility. Specifically, we tested the hypothesis that patients with refractory periodontitis have multiple upregulated and/or downregulated genes that might be important in influencing clinical risk. METHODS: Oral subepithelial connective tissues were harvested aseptically from seven refractory periodontitis and seven periodontally well-maintained patients. An RNA isolation kit was used to isolate total RNA from tissue samples that had been stabilized in the RNA stabilizing reagent. The isolated total RNA was then subjected to gene expression profiling using the microarray to measure gene expression levels. The retrieved data were analyzed with a computer program for the differential analysis of gene expression microarray experiments. In addition, real-time polymerase chain reaction (PCR) analysis was performed on selected samples to confirm the microarray data's gene expression patterns. RESULTS: A total of 68 upregulated and six downregulated genes were identified that were differentially expressed at least two-fold out of 22,283 genes we analyzed. The selected model provided a 93% intrinsic validation along with a 93% extrinsic validation. To validate the microarray data, five upregulated genes (lactotransferrin [LTF], matrix metalloproteinase-1 [MMP-1], MMP-3, interferon induced-15 [IFI-15], and Homo sapiens hypothetical protein MGC5566) and two downregulated genes (keratin 2A [KRT2A] and desmocollin-1 [DSC-1]) were randomly selected for further analysis by real-time PCR. The relative RNA expression level of these genes measured by real-time PCR was similar to those measured by microarrays. CONCLUSION: The combined use of microarray technology with the computer program for the differential analysis of gene expression microarray experiments provided a set of candidate genes that may serve as novel therapeutic intervention points and improved diagnostic and screening procedures for high-risk individuals.

Aged↗

Effect of prechill fecal contamination on numbers of bacteria recovered from broiler chicken carcasses before and after immersion chilling.

Paired carcass halves were used to test whether fecal contamination of skin during processing of broiler chickens can be detected by increased bacterial counts in samples taken before and after immersion chilling. In each of three trials, six freshly defeathered and eviscerated carcasses were cut in half, and a rectangle (3 by 5 cm) was marked with dots of ink on the breast skin of each half. One half of each pair was chosen randomly, and 0.1 g of freshly collected feces was spread over the rectangle with a spatula. After 10 min, both halves were sprayed with tap water for 10 to 15 s until feces could no longer be seen in the marked area. Both halves were sampled with a 1-min carcass rinse and were then put in a paddle chiller with other eviscerated carcasses for 45 min to simulate industrial immersion chilling. Immediately after chilling, each carcass half was subjected to another 1-min rinse, after which the skin within the rectangle was aseptically removed from the carcass halves and stomached. Rinses of fecally contaminated halves had significantly higher Enterobacteriaceae immediately before chilling, but there were no differences in coliform and Escherichia coli counts. After chilling, there were no differences in Enterobacteriaceae, coliform, and E. coli counts in rinse or skin samples from the paired carcass halves. Correlations were generally poor between counts in rinse and skin samples but were significant between prechill and postchill rinses for both control and fecally contaminated halves. Correlations were also significant between counts in rinses of control and contaminated halves of the same carcass after chilling. Bacterial counts in postchill carcass rinses did not indicate that fecal contamination occurred before chilling.

Animals↗

An outbreak of echovirus meningitis in children.

An outbreak of aseptic meningitis in children as evidenced by increase in the number of admissions in a tertiary care hospital is described. Clinical data and stool samples were collected from 25 hospitalized infants and young children. The stool samples were subjected to virological investigations. Fever and vomiting were the commonest symptoms. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis in majority of cases. Of the 25 stool samples, 14 showed an enterovirus specific cytopathogenic effect (CPE) in rhabdomyosarcoma (RD) cell line. All the 14 samples were positive for enterovirus RNA by reverse transcription-polymerase chain reaction (RT-PCR). Partial sequencing of the Virion protein 1 (VPI) region of the enterovirus genome carried out on the first 7 isolates revealed 5 isolates to be echovirus serotype 4 and one each to be echovirus serotypes 3 and 30. All children showed a rapid recovery and were discharged within 3 days of admission.

Child↗

Blood-brain barrier damage in children with central nervous system infections.

The blood-brain barrier (BBB) function in childhood central nervous system (CNS) infections was evaluated, using cerebrospinal fluid (CSF) and paired serum samples from 30 controls and 74 patients aged from 1 to 15 years with various CNS infections. The 74 patients included 34 cases of aseptic meningitis, 24 of encephalitis and 16 of purulent meningitis. The degree of BBB damage was graded by CSF/serum albumin ratio, and IgG production by IgG index (IgG ratio/albumin ratio of CSF to serum). In the acute stage, patients with purulent meningitis had greater elevation of the albumin ratio than other study groups. The patients with encephalitis, especially chronic encephalitis, had a selectively elevated IgG index compared to other groups. Most patients with aseptic meningitis showed little or no elevation of albumin ratio and IgG index. This study demonstrated the nature of various degrees of BBB damage and intra-BBB IgG production in different infectious CNS diseases in children. BBB damage is most severe in cases of purulent meningitis, while the intrathecal IgG production is greatest in chronic encephalitis. These abnormalities disappear as the inflammatory processes subside.

Adolescent↗

Evaluation of febrile infants under 3 months of age: is routine lumbar puncture warranted?

Fever may be the sole clinically evident presentation of serious bacterial infection (SBI) in a very young infant, and therefore lumbar puncture is still widely regarded as a mandatory procedure in the sepsis workup of febrile infants under 2 months of age. In this retrospective study, we evaluated the frequency and the diagnostic value of cerebrospinal fluid examination in 492 infants aged less than 3 months who were hospitalized because of fever during 1988-1994. The patients were categorized as being at "high risk" or "low risk" for SBI according to current clinical and laboratory criteria. Among the 492 infants, 196 (40%) were identified as "high-risk" for SBI, and 296 (60%) were at low risk. Among the overall series of infants, 60 babies (12%) were subsequently proven with bacterial infection. Among the 196 "high-risk" babies, 26% had bacterial infection, compared to only 3% of the 296 infants at low risk (p < 0.0001), denoting a sensitivity of 85% and a specificity of 65% of the clinical classification criteria. Lumbar puncture was done to 186 (46%) infants upon hospital admission; 176 punctures yielded satisfactory samples of cerebrospinal fluid (CSF). Sixteen (3%) patients had abnormal CSF findings: 2 of them had positive bacterial cultures and 14 were compatible with aseptic meningitis. The 2 patients with purulent meningitis were clinically very ill and were immediately recognized as deserving a lumbar puncture. Of the 14 patients with aseptic meningitis, 13 were initially screened as being at high risk for serious infection, and therefore underwent a lumbar puncture. Over the years of this survey, a declining trend for performing lumbar puncture in "low-risk" young febrile infants became evident: during 1988-1992, evaluation of sepsis included a lumbar puncture in 45% of the infants, compared to 27% during the following 2 years (p < 0.0001). Not one instance of purulent meningitis evolved among the infants in whom lumbar puncture was not performed. Our observations suggest that hospitalized young febrile infants may safely be spared a lumbar puncture when they do not meet the proposed criteria for being at high risk, or when their clinical and laboratory picture suggests being at low risk for SBI.

Age Factors↗

Sterility testing of antimicrobial-containing injectable solutions prepared in the pharmacy.

The need for sterility testing of antimicrobial-containing injectable solutions is discussed and specific testing methods are described. Despite their antimicrobial activity, antimicrobial-containing injectable drug products are not necessarily self-sterilizing and can become contaminated. In addition to practicing aseptic technique, pharmacists must perform end-product sterility testing on intravenous solutions to ensure their sterility. The United States Pharmacopeia provides guidelines for the performance and validation of two sterility test methods: membrane filtration and direct transfer to culture media. Membrane filtration is the method of choice for sterility testing of many antimicrobial-containing injectable solutions. After the test article is filtered, the membrane is rinsed with sterile fluid to remove residual antimicrobial agent, cut into two portions, and immersed in two types of culture medium. Visible turbidity of a sample within the appropriate incubation period indicates the presence of a contaminating microorganism. Closed filtration systems minimize false-positive results. In the direct transfer method, samples of the test article are directly inoculated into vessels of culture media, and antimicrobial activity is eliminated by dilution or by deactivation with chemical or enzymatic agents. Sterility testing as well as aseptic technique is needed to ensure the sterility of antimicrobial-containing injectable solutions.

Anti-Infective Agents↗

Mollaret's recurrent aseptic meningitis: relationship to epidermoid cysts. Light microscopic and ultrastructural cytological studies of the cerebrospinal fluid.

Cells, originally called "endothelial" cells, have been described in the cerebrospinal fluid (CSF) of patients developing recurrent aseptic meningitis (Mollaret's meningitis). In an attempt at better establishing their nature, a 6-year-old child was followed for a period of 3 1/2 years. A cytological light microscopic and ultrastructural study was performed on samples of the CSF obtained during 17 attacks. The findings are presented, and the relationship of Mollaret's meningitis to intracranial epidermoid cysts is discussed.

Brain Diseases↗

Sensory nerves in the interface membrane of aseptic loose hip prostheses.

We studied the presence of sensory nerves by immunohistochemistry in the interface membranes of hip prostheses after aseptic loosening. Substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) were analysed as was protein gene product (PGP) 9.5, a general marker for nerve fibres. We identified nerve fibres in all samples but differences in their density were found. SP- and NKA-positive fibres were predominantly non-vascular, forming varicose nerve terminals. CGRP-immunoreactive nerve fibres with varicose terminals were seen mostly close to blood vessels, but also as free nerve endings. Sensory neuropeptides participate not only in nociception but also stimulate immune cells to release cytokines. The presence of sensory nerves in the interface membrane may reflect a pathophysiological response contributing to the aseptic loosening of hip prostheses.

Aged↗