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PubMed2001

Development and characteristics of a synovial-like interface membrane around cemented tibial hemiarthroplasties in a novel rat model of aseptic prosthesis loosening.

OBJECTIVE: Aseptic prosthesis loosening (APL) is related to the formation and aggressive growth of a synovial-like interface membrane (SLIM) between prosthesis and bone. However, investigation of the early phases of SLIM development in humans presents major difficulties. This study was undertaken to develop and characterize the usefulness of a novel animal model of APL that is based on an established model of defined exercise in a running wheel by Wistar rats that have been subjected to intracranial self-stimulation (ICSS). METHODS: Cemented tibial hemiarthroplasties were implanted into the left knees of 7 male Wistar rats. After 2 weeks, exercise in a running wheel was started in all rats, with a running-load of 2 hours/day for 5 days/week. Six months postoperatively, the knee joints were removed, decalcified, and embedded in paraffin. Histologic evaluation on hematoxylin and eosin-stained sections was performed to investigate the development of a SLIM and the presence of cement debris particles. To characterize the SLIM on a molecular level and investigate growth-regulating factors, the expression of transforming growth factor beta (TGFbeta) and the anti-apoptotic molecule Bcl-2 was analyzed by immunohistochemistry. RESULTS: Although the prostheses appeared mechanically stable after 6 months, the development of SLIM with areas of bone resorption was seen in all samples. Resembling human SLIM, these membranes consisted of loose fibrous tissue, with cement debris particles located particularly at sites originally attached to the prostheses. Immunohistochemistry studies revealed the expression of TGFbeta and Bcl-2 in all specimens. Interestingly, staining for TGFbeta and Bcl-2 was restricted to areas where the SLIM were attached to bone. In contrast, there was only negligible expression of both proteins at sites adjacent to the prostheses. CONCLUSION: Our findings demonstrate that the ICSS Wistar rat model constitutes a feasible tool for studying early stages of APL, and specifically the effect of defined running exercise on SLIM formation. The results further suggest that both cellular proliferation, as stimulated by TGFbeta, and altered apoptosis contribute to early stages of SLIM formation. The expression patterns of TGFbeta and Bcl-2 indicate that the growth of the SLIM is initiated and promoted from the bone rather than from the prosthesis.

Animals↗
PubMedDate not supplied

The association of propofol usage with postoperative wound infection rate in clean wounds: a retrospective study.

OBJECTIVE: To determine if the use of propofol influences the postoperative infection rate of clean surgical wounds in dogs and cats. STUDY DESIGN: Retrospective study. SAMPLE POPULATION: 863 dogs and cats undergoing clean surgical procedures. METHODS: Medical and anesthetic records of surgical cases used as part of a previously described epidemiologic study on postoperative wound infection rates were reviewed. The records of all animals with clean surgical wounds were reviewed to determine if propofol had been used for anesthetic induction or maintenance during the procedure. To determine the effect of propofol use on wound infection rate, data were analyzed using Fisher's exact test, followed by multiple logistic regression to adjust for various factors, including surgery time, time from clipping to surgery, antibiotic usage, coexisting distant infection, endocrine disease, and the use of immunosuppressive drugs in the perioperative period. RESULTS AND CONCLUSIONS: Of 863 dogs and cats with clean surgical wounds, 46 received propofol as part of the anesthetic protocol. A total of 6 of 46 animals (13%) receiving propofol developed postoperative wound infections, compared with 33 of 817 animals (4%) not receiving propofol (P = .014; % difference = 9%; 95% CI = 0.5% to 24%). Adjusting for all other factors evaluated, animals receiving propofol were 3.8 times more likely to develop postoperative wound infections compared to animals not given propofol (95% CI = 1.5-9.9). CLINICAL IMPLICATIONS: Propofol is a lipid-based emulsion capable of supporting microbial growth. Administration of a potentially contaminated solution may contribute to surgical wound infection or other patient morbidity or mortality. Strict aseptic technique in the preparation of the solution and prompt disposal of unused drug are imperative to curtail the potential for extrinsic contamination.

Anesthetics, Intravenous↗
PubMed1982

Neurotoxicologic effects of the nonionic contrast agent iopamidol on the leptomeninges of the dog.

The effect of iopamidol on the leptomeninges was tested and compared with that of metrizamide and normal saline solution in 18 dogs. Pathologic and clinical effects were evaluated at 24 hours and 14 days after cisternal injection of iopamidol, metrizamide, or normal saline solution. Pathologic changes were evaluated by microscopic examination of serial CSF samples and of sections of brain and spinal cord with the leptomeninges intact. Clinical changes were subjectively evaluated. Electromyograms and EEG were performed on each dog after physical and neurologic examination. There were no changes seen in neurologic status, electromyogram, or EEG in any of the dogs immediately after subarachnoid injection nor at 24 hours or 14 days later. Pathologic changes were limited to mild, moderate, or severe patchy hemorrhagic leptomeningitis seen at 24 hours after iopamidol or metrizamide was injected. The severity of changes were judged to be similar with both these agents. The CSF analysis and histologic evaluation of brain and spinal cord sections revealed a neutrophilic response to iopamidol and a mononuclear response to metrizamide. These findings indicate that iopamidol has minimal neurotoxicologic effect on the leptomeninges and therefore has merit as a myelographic agent.

Animals↗
PubMed2004

Intrathecal levels of matrix metalloproteinases in systemic lupus erythematosus with central nervous system engagement.

Symptoms originating from the central nervous system (CNS) occur frequently in patients with systemic lupus erythematosus (SLE), and CNS involvement in lupus is associated with increased morbidity and mortality. We recently showed that neurones and astrocytes are continuously damaged during the course of CNS lupus. The matrix metalloproteinases (MMPs) are a group of tissue degrading enzymes that may be involved in this ongoing brain destruction. The aim of this study was to examine endogenous levels of free, enzymatically active MMP-2 and MMP-9 in cerebrospinal fluid from patients with SLE. A total of 123 patients with SLE were evaluated clinically, with magnetic resonance imaging of brain and cerebrospinal fluid (CSF) analyses. Levels of free MMP-2 and MMP-9 were determined in CSF using an enzymatic activity assay. CSF samples from another 22 cerebrally healthy individuals were used as a control. Intrathecal MMP-9 levels were significantly increased in patients with neuropsychiatric SLE as compared with SLE patients without CNS involvement (P < 0.05) and healthy control individuals (P = 0.0012). Interestingly, significant correlations between MMP-9 and intrathecal levels of neuronal and glial degradation products were noted, indicating ongoing intrathecal degeneration in the brains of lupus patients expressing MMP-9. In addition, intrathecal levels of IL-6 and IL-8--two cytokines that are known to upregulate MMP-9--both exhibited significant correlation with MMP-9 levels in CSF (P < 0.0001), suggesting a potential MMP-9 activation pathway. Our findings suggest that proinflammatory cytokine induced MMP-9 production leads to brain damage in patients with CNS lupus.

Adolescent↗
PubMed1995

Production of matrix metalloproteinases at the bone-implant interface in loose total hip replacements.

BACKGROUND: Incidence of aseptic loosening of hip prostheses is increasing in recent years. Previous studies suggested involvement of proteinases and cytokines in the accelerated bone lysis associated with loosening. EXPERIMENTAL DESIGN: To investigate the role of matrix metalloproteinases (MMPs) in the loosening we immunolocalized MMP-1 (tissue collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin-1), MMP-9 (gelatinase B) and their common inhibitors, tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), in the bone-prosthesis interface membranes. In situ hybridization was performed for the detection of MMP-9 mRNA in the membranes. The amounts of these MMPs and TIMPs in the tissue were measured by the sandwich enzyme immunoassays and enzyme activities assayed using radiolabeled collagen, gelatin, and carboxymethylated transferrin substrates. We also examined the ability of the cells from interface membranes to resorb mouse calvaria bone. RESULTS: The membranes obtained from the loose bone-implant interface were composed of fibrous granulation tissue containing numerous multinucleated giant cells with high density polyethylene debris. Immunohistochemical examination revealed that the giant cells were strongly positive for MMP-9 and weakly for MMP-1. Expression of MMP-9 mRNA in the cells was demonstrated by in situ hybridization. MMP-2 and TIMP-2 were immunolocalized mainly in the fibroblasts. TIMP-1 was localized in the endothelial cells of the blood vessels and weakly in fibroblasts. However, MMP-3 was almost negative in the membrane tissue. Sandwich enzyme immunoassays showed that MMP-9 levels are significantly higher in both homogenates and culture media of the cup and stem interface membranes than the control pseudocapsule. Gelatinolytic activity was also remarkably higher in the membrane samples than the control. The cells isolated from the membranes had no ability to resorb calvaria bone. CONCLUSIONS: These data demonstrate that MMP-9 is produced by the multinucleated giant cells appeared by the reaction to polyethylene debris in the interface membranes. This proteinase may play a role in degradation of the extracellular matrix macromolecules present around and on the surface of the bone trabeculae, facilitating the osteoclastic bone resorption.

Adult↗
PubMed2004

Revision of total hip arthroplasty using an anterior cortical window, extensive strut allografts, and an impaction graft: follow-up study.

PURPOSE: To report the outcome of revised total hip arthroplasty procedures involving an anterior cortical window, extensive strut allografts, and an Exeter impaction graft. METHOD: Eight patients (9 hips) with a mean age of 58 years underwent revision of total hip arthroplasty using the Exeter hip impaction graft system and strut allografts between 1995 and 1998. An extensile anterior approach was used, and an anterior cortical window was created in the femur, to remove the old implant. External strut allografts were attached by wires to provide cortical support. The mean follow-up duration was 74 months. Indications for surgery were aseptic loosening of previous implants in 8 hips and infection of one hip that had previously undergone total arthroplasty. RESULTS: 19 Dall Miles cables, 4 ordinary cerclage wires, and 8 cerclage wires tightened with the clincher knot technique were used to secure the allograft to the host bone. The strut grafts were found to be incorporated in all cases. No wires became loose. One patient developed 20 degrees of angulation at the allograft-host bone junction. Using the method of Fowler and Gie, we found that one femoral implant had subsided 2 mm within the cement mantle. Two other implants had 1 mm of subsidence at the cement bone interface, and one patient had a major subsidence of 15 mm that required revision. CONCLUSION: Using an anterior cortical window in the femur to remove the old implant does not predispose to failure of the allograft to incorporate into the host bone.

Adult↗
PubMed1995

Multivariate approach to differential diagnosis of acute meningitis.

A previously reported statistical model based on a combination of four parameters (total polymorphonuclear cell count in cerebrospinal fluid (CSF), CSF/blood glucose ratio, age and month of onset) appeared effective in differentiating acute viral meningitis (AVM) from acute bacterial meningitis (ABM). The objectives of this study were to validate this model on a large independent sample of patients with acute meningitis and to build and validate a new model based on this sample. Of 500 consecutive cases of community-acquired meningitis reviewed retrospectively, 115 were ABM, 283 were AVM and 102 were of uncertain etiology. For each of the ABM and AVM cases, the probability of ABM versus AVM (pABM) was calculated for both models. Sensitivity, specificity and predictive values as well as areas under the receiver operating characteristic (ROC) curves were calculated for both models. The original model proved an accurate and reliable diagnostic test. Its area under the ROC curve was 0.981. For pABM = 0.1, its negative and positive predictive values were 0.99 and 0.68, respectively. The new model retained four slightly different independent variables: CSF protein level, total CSF polymorphonuclear cell count, blood glucose level and leukocyte count. Its area under the ROC curve was 0.991 and, for pABM = 0.1, its negative and positive predictive values were 0.99 and 0.85, respectively. In conclusion, both models provide a valuable aid in differentiating AVM from ABM. They should be further evaluated in a prospective appraisal of their contribution to therapeutic decision making.

Acute Disease↗
PubMedDate not supplied

Pennsylvania dental hygienists' knowledge, attitudes, and infection control practices in relation to AIDS and AIDS patients.

PURPOSE: Limited documentation is found on dental hygienists' attitudes toward acquired immunodeficiency syndrome (AIDS) patients and their knowledge and practice of clinical infection control to prevent disease transmission to themselves and their patients. The purpose of this paper was to survey practicing Pennsylvania dental hygienists to document 1) their infection control practices; 2) their attitudes towards AIDS patients; and 3) their knowledge of clinical infection control practices. METHODS: A self-administered survey questionnaire, with fixed-alternative responses, was mailed in January 1991 to a random sample (N = 300) of licensed, practicing Pennsylvania dental hygienists. The questionnaire comprised eight multiple-choice questions for demographic purposes and 89 Likert-type questions eliciting information in five areas: AIDS-related knowledge, attitudes toward AIDS patients, knowledge of recommended Centers for Disease Control and Prevention (CDC) infection control measures, individual infection control measures, and individual laboratory infection control measures. Means and modes for individual questions and for specific categories were determined and analyzed utilizing Spearman rho correlation coefficients (p < .05). Mean scores were also tabulated for actual operator/laboratory infection control practices for both a routine patient and an AIDS patient. Those scores were analyzed utilizing the Wilcoxen signed-ranks test. RESULTS: Two hundred twenty questionnaires were returned for a 73.3% initial response rate. One hundred fifty-four of those returned were usable, for a 64% response rate. Results indicated that 94.2% of surveyed dental hygienists had comprehensive knowledge about AIDS and 92% had comprehensive knowledge of CDC-recommended infection control procedures. Eighty-five percent of respondents possessed a moderate or high feeling of worry concerning treatment of AIDS patients. The majority of surveyed dental hygienists routinely practiced the use of glasses, masks, and gloves; the use of disposable items; and surface disinfection of light handles, instrument bracket trays, and patient chair switches. Knowledge of recommended infection control procedures for dentistry was found to be associated (r = .22) with adherence to recommended infection control practices. Accurate knowledge about AIDS showed a weak (r = -.088) and nonsignificant relationship with dental hygienists' attitudes toward AIDS patients. Use of recommended infection control practices was found to be associated (r = -.20) with less fear concerning the treatment of AIDS patients. In addition, dental hygienists' infection control practices varied according to their perception of patient HIV status. CONCLUSIONS: Since Pennsylvania dental hygienists, within the limitations of this study, appear not to follow CDC guidelines on proper and responsible operatory/laboratory aseptic techniques stringently, and to differentiate infection control procedures based on perceived patient HIV status, recommendations are that 1) the Commonwealth of Pennsylvania should mandate that all Pennsylvania-licensed dental hygienists take at least one state-approved course on operatory/laboratory infection control every two years to qualify for relicensure; 2) all dental and dental hygiene education institutions and professional organizations should place more emphasis on strict adherence to the various agency recommended clinical guidelines for infection control; and 3) all dental hygienists should continually strive to update their own knowledge of current infection control practices.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Interferon gamma quantification in cerebrospinal fluid compared with PCR for the diagnosis of tuberculous meningitis.

PURPOSE: To assess the utility of interferon gamma (INF-gamma) levels in cerebrospinal fluid (CSF), for the diagnosis of tuberculous meningitis (TBM), and compare these results with aPCR technique. METHODS: We studied CSF samples from patients with proven or probable TBM and a control group, composed by patients with other causes of meningitis and without meningitis. INFgamma levels were measured by radioimmunoassay. A PCR technique was performed using IS6110 primers. RESULTS: Of the 127 patients studied, 20 (15.6%) had TBM, 59 (46%) had meningitis of another aetiology and 49 (38.4%) had were HIV and non-HIV patients with normal CSF. The area below the ROC curve for interferon gamma levels in the diagnosis of TBM was 0.94. A cut-off of 6.4 IU/mL yielded a sensitivity of 70% and a specificity of 94%. False positive results were observed in 7 of the 59 patients (11.8%) with non-TB meningitis, (patients with herpetic meningoencephalitis and meningitis due to intracellular microorganisms). INF-gamma sensitivity was higher than PCR (70% vs. 65%). Both tests performed together showed higher sensitivity (80%) and specificity (92.6%). CONCLUSION: CSF INF-gamma levels (> 6.4 IU/mL) are very valuable in TBM diagnosis. PCR and INF-gamma could be simultaneously used to increase the diagnostic yield.

Adolescent↗
PubMed1994

Detection of enterovirus-specific total and polymeric IgA antibodies in serum using a synthetic peptide or heated virion antigen in ELISA.

The presence of enterovirus-specific total and polymeric IgA antibodies was assessed in serum from different groups of patients and healthy controls by indirect ELISA using heated virions and synthetic peptide, both enteroviral broad reactive antigens. Total IgA antibody response against a synthetic peptide, representing an enterovirus group-common epitope, was detected in 52% of the patients with an acute enterovirus infection and in 12% of the patients with other infections (P = 0.02). We also found a significant difference (P = 0.005) in the prevalence of peptide IgA antibodies between serum samples collected from blood donors during summer (20%), the prevalent season of enterovirus infections, and winter (6%). A polymeric IgA activity against the peptide was detected in only three patients with an enterovirus infection. In contrast, when a heated coxsackie B5 (coxB5) virus antigen was used, the prevalence of total serum IgA antibodies was not significantly different between patients with an acute enterovirus infection and patients with other infections (71% vs. 53% respectively; P = 0.3). Also no difference was found between the two groups of blood donors (47% in summer vs. 51% in winter; P = 0.7). However, the prevalence of serum polymeric IgA antibodies against coxsackie B5 antigen was significantly greater (P = 0.02) in patients with an acute enterovirus infection (57%) than in patients with other infections (18%). These findings suggest that the presence (18%). These findings suggest that the presence of total peptide-IgA or of polymeric coxsackie B5-IgA in serum is a specific marker of acute enterovirus infection. Finally, we show that the total peptide-IgA- and polymeric coxsackie B5-ELISAs may have a diagnostic value for the serodiagnosis of enterovirus infections when they are used in combination with enteroviral IgG-ELISA.

Amino Acid Sequence↗
PubMed2006

Detection of 65 kD heat shock protein in cerebrospinal fluid of tuberculous meningitis patients.

BACKGROUND: Diagnosis of tuberculous meningitis (TBM) is difficult. Rapid confirmatory diagnosis is essential to initiate required therapy. There are very few published reports about the diagnostic significance of 65 kD heat shock protein (hsp) in TBM patients, which is present in a wide range of Mycobacterium tuberculosis species and elicits a cellular and humoral immune response. In the present study we have conducted a prospective evaluation for the demonstration of 65 kD hsp antigen in cerebrospinal fluid (CSF) of TBM patients, by indirect ELISA method using monoclonal antibodies (mAb) against the 65 kD hsp antigen, for the diagnosis of TBM. METHODS: A total of 160 CSF samples of different groups of patients (confirmed TBM {n = 18}, clinically suspected TBM {n = 62}, non TBM infectious meningitis {n = 35} and non-infectious neurological diseases {n = 45}) were analyzed by indirect ELISA method using mAb to 65 kD hsp antigen. The Kruskal Wallis test (Non-Parametric ANOVA) with the Dunnett post test was used for statistical analysis. RESULTS: The indirect ELISA method yielded 84% sensitivity and 90% specificity for the diagnosis of TBM using mAb to 65 kD hsp antigen. The mean absorbance value of 65 kD hsp antigen in TBM patients was [0.70 +/- 0.23 (0.23-1.29)], significantly higher than the non-TBM infectious meningitis group [0.32 +/- 0.14 (0.12-0.78), P < 0.001] and also higher than the non-infectious neurological disorders group [0.32 +/- 0.13 (0.20-0.78), P < 0.001]. A significant difference in the mean absorbance of 65 kD hsp antigen was noted in the CSF of culture-positive TBM patients [0.94 +/- 0.18 (0.54-1.29)] when compared with clinically suspected TBM patients [0.64 +/- 0.20 (0.23-0.98), P < 0.05]. CONCLUSION: The presence of 65 kD hsp antigen in the CSF of confirmed and suspected cases of TBM would indicate that the selected protein is specific to M. tuberculosis and could be considered as a diagnostic marker for TBM.

Bacterial Proteins↗
PubMed1983

Effects of dorsal root section on spinocervical tract neurones in the cat.

1. In nine cats, dorsal roots L(6) and L(7) were sectioned under pentobarbitone anaesthesia using strict aseptic precautions. In two cats all lumbosacral roots except L(6) were sectioned under similar conditions. 27-75 days after the dorsal rhizotomies, under chloralose anaesthesia, neurones of the spinocervical tract (s.c.t.) were recorded electrophysiologically both extracellularly and intracellularly, their response properties and receptive fields were analysed, and they were injected with horseradish peroxidase (HRP). Twenty-five cells were recorded extracellularly and twenty were recorded intracellularly and stained with the enzyme.2. Of the twenty neurones stained with HRP, one was located in caudal L(5), eleven in L(6) and eight in L(7). Five cells had no receptive field, either before or after current injection, two cells had no field before injection but after current injection responded to either electrical stimulation of peripheral nerve or to brusque tapping on the limb; six neurones responded only to tapping before current injection and two of these showed a more clearly defined receptive field after current injection; six neurones had a receptive field and responded with impulses to hair movement and/or pressure within a well-defined area but this area was surrounded by skin from which excitatory post-synaptic potentials could be elicited; only one neurone had an apparently normal receptive field.3. Of the twenty-five neurones recorded extracellularly, eleven had no receptive field, four responded only to tapping on the limb, three had receptive fields consisting of an area of low threshold plus an area responding to brusque or noxious mechanical stimulation, and seven neurones had apparently normal receptive fields.4. Neurones with no observable receptive fields were either silent with no resting activity, or had very low rates of background activity consisting of isolated single impulses or short bursts of impulses. No neurones in de-afferented segments had high rates of background activity.5. There were no alterations in the normal somatotopy of the dorsal horn. All fifteen s.c.t. neurones injected with HRP and which had a localizable receptive field had fields appropriately located in the somatotopic map. There were no electro-physiological signs of inappropriate connexions.6. The dendritic trees of fifteen neurones injected with HRP were reconstructed. With the exception of one cell which appeared grossly disorganized (but which was the one cell with an apparently normal receptive field), there were no obvious differences between the dendritic trees of de-afferented cells and normal cells from the same and other cats. Their dendritic trees had similar rostro-caudal, medio-lateral and dorso-ventral extents to normal cells, and appeared to exhibit similar degrees of branching. There was a suggestion that de-afferented neurones had rather more of their dorsally-directed distal dendrites invading lamina II than normal cells, but the sample size was too small to make this more than a possibility.7. It is concluded that after dorsal rhizotomy, s.c.t. neurones lose part or all of their afferent input and that within 75 days do not show any signs of new or inappropriate connexions.

Action Potentials↗
PubMed1996

Changes in cerebrospinal fluid and cerebrovascular endothelin concentrations during hypotension and hypertension in newborn piglets with induced sterile meningitis.

The effects of sterile meningitis on endothelin-1 (ET-1) and big ET-1 concentrations during hypotension and hypertension were studied in the cerebrospinal fluid and plasma of newborn piglets. Cerebrospinal fluid was obtained via cisterna magna puncture, and blood was obtained from the sagittal sinus vein and left subclavian artery. The study group consisted of 14 newborn piglets injected with 0.5 mL heat-killed group B streptococcus (GBS) (10(9) colony forming unit (cfu) equivalents), into the right cerebral lateral ventricle; the control group consisted of 10 newborn piglets injected with sterile normal saline, in a similar fashion. Hypotension (mean arterial blood pressure (MABP) 20-59 mmHg; 1 mmHg = 133.3 Pa) and hypertension (MABP 110-140 mmHg) were induced 1.5-2 h apart in random sequence in each animal, by inflating balloon-tipped catheters placed at the aortic root and descending aorta, respectively. Cerebral blood flow (CBF) was measured using radiolabeled microspheres, 15 min before and after injection of GBS or saline (normotension), during the hypotension and hypertension episodes, and during recovery normotension, immediately prior to cerebrospinal fluid and blood sampling. ET-1 and big ET-1 concentrations (pg/mL) were measured using radioimmunoassay kits. The combined effect of induced sterile meningitis and induced hypotension resulted in a significant rise in the concentration of cerebrospinal fluid ET-1 (control, 5.1 +/- 0.1; GBS, 9.3 +/- 0.2 pg/mL; p < 0.01), cerebrospinal fluid big ET-1 (control, 0; GBS, 18.1 +/- 2.7 pg/mL; p < 0.01), and sagittal sinus (cerebrovascular) big ET-1 (control, 15.5 +/- 4.2; GBS, 47.5 +/- 9.6 pg/mL; p < 0.01). In contrast, the combined effect of induced sterile meningitis and induced hypertension resulted in a marked elevation in cerebrovascular ET-1 concentrations (control, 9.5 +/- 0.9; GBS, 28.5 +/- 6.1 pg/mL; p < 0.01), with no significant change in cerebrospinal fluid concentrations. In addition, cerebrovascular production of ET-1 increased dramatically during hypertension in the GBS group (control, 0; GBS, 161.7 +/- 13.2 pg.min-1.100 g-1; p < 0.001), and was maintained during the recovery period (133.7 +/- 10.8 pg.min-1.100 g-1). Cerebrovascular ET-1 concentrations correlated significantly with total CBF and MABP in both groups of animals (control, r = 0.49, p < 0.002; GBS, r = 0.64, p < 0.0001), but the response was of a much greater magnitude in the GBS group. There was an inverse relationship between cerebrovascular big ET-1 concentrations and total CBF (r = -0.53, p < 0.0001) and MABP (r = -0.71, p < 0.0001) in the GBS group. In the MABP range of 60-110 mmHg a positive relationship was observed between cerebrovascular ET-1 concentrations and cerebral vascular resistance, in the control group only (r = 0.59, p < 0.002). The combined insult of induced sterile meningitis and induced hypotension or hypertension may be associated with increased cerebrovascular ET-1 and (or) big ET-1 concentrations. Changes in these vasoactive agents may contribute to pressure passivity of CBF in the newborn with meningitis.

Animals↗