Biomedical subjects

J A Patel

Publications and source records attributed to J A Patel.

At least 19 recordsLinked to original sources

PubMed2004

Accurate axillary nodal staging can be achieved after neoadjuvant therapy for locally advanced breast cancer.

Lymph node status remains the most important prognostic indicator for breast cancer. Recent reports have established that the accuracy of assessing lymph node status is proportional to the number of nodes dissected. The accuracy of axillary staging following neoadjuvant chemotherapy has been cited as a technical concern due to limited node retrieval. The current study attempts to evaluate the ability to perform sentinel node biopsy (SNB) and formal axillary node dissection (AND) following neoadjuvant chemotherapy and to compare these results with non-neoadjuvant patients. One hundred sixteen consecutive patients undergoing SNB with simultaneous AND were retrospectively reviewed. Forty-two of these patients were treated with neoadjuvant chemotherapy prior to AND. Overall success rate in performing SNB in the neoadjuvant group was 95 per cent, and no false negatives have been noted to date. The overall SNB success rate in the non-neoadjuvant group was also 95 per cent with a false negative rate of 3 per cent. After AND in each group, a mean of 21 nodes were retrieved in the neoadjuvant group and 17.9 nodes in the non-neoadjuvant group (P = 0.018). In the neoadjuvant group, there were 19 node positive patients (42%) and 21 patients (28%) in the non-neoadjuvant group (P = 0.16). The mean number of positive nodes per patient was also similar between the two groups (2.9 in the neoadjuvant group vs 1.67 in the non-neoadjuvant group, P = 0.10). Following neoadjuvant therapy, accurate evaluation of the axilla is feasible. In this study, the mean number of nodes is significantly different in favor of the neoadjuvant group, but there is no significant difference in the number of node positive patients identified or in the mean number of positive nodes identified per patient. SNB is technically feasible with accuracy similar to that seen in patients with no history of neoadjuvant therapy. Neoadjuvant chemotherapy extends the use of breast-conserving therapy without sacrificing the ability to accurately stage the axilla either by use of standard axillary dissection or SNB.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Neoadjuvant chemotherapy for locally advanced breast cancer results in alterations in preoperative tumor marker status.

Neoadjuvant therapy followed by breast-conserving surgery has become an acceptable option for patients with locally advanced breast cancer. Although a distinct survival benefit has not been demonstrated using this approach, several questions have been raised following such therapy including its effects on receptor status and tumor markers. The current study retrospectively reviews estrogen receptor (ER), progesterone receptor (PR), and HER2-neu status in 55 consecutive patients treated by neoadjuvant chemotherapy. Preoperative and postoperative tumor markers were available for 43 of the 55 patients (78%). The pathologic complete tumor response rate (pCR) for this group was 19 per cent (8/43). Of those patients who did not achieve a pCR (n = 35), a change in tumor markers was seen in 25.7 per cent (9/35) of patients. When compared to a control group not undergoing neoadjuvant therapy, a significantly higher percent change in marker expression was noted in the neoadjuvant group (25.7% vs 5.9%, P = 0.046). ER, PR, and HER2-neu status remain important prognostic indicators for breast cancer. Tumor markers are useful in planning adjuvant therapy regimens. In this review, nearly 19 per cent of patients achieved a pCR. In patients not achieving a pCR, one in four patients had at least one change in tumor marker status. This study demonstrates the importance of establishing receptor and marker status prior to neoadjuvant therapy, as many patients will achieve a pCR and make tumor analysis impossible. Postoperative marker studies should be performed given the possibility of a change in status. The clinical relevance of this data will require further long-term follow-up. Until such data becomes available, caution should be considered when basing adjuvant therapy regimens on preoperative tumor marker studies alone.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Comparison of 3 vancomycin dosage regimens during hemodialysis with cellulose triacetate dialyzers: post-dialysis versus intradialytic administration.

AIMS: Traditionally, vancomycin is administered following dialysis to minimize drug loss when high-flux membranes are employed. Unfortunately, this approach is extremely inconvenient for patients and staff, requiring the patients to remain in the unit for at least 1 hour following dialysis. This study was designed to evaluate the feasibility of administering vancomycin during hemodialysis. Specifically, this study was designed to compare the pharmacokinetics of vancomycin when administered during the last 1-2 hours of dialysis (i.e. intra-dialytic administration) to that administered after completion of dialysis. MATERIALS AND METHODS: In a randomized, 3-way crossover trial, the pharmacokinetics of vancomycin were evaluated in 9 hemodialysis patients, comparing vancomycin 15 mg/kg following dialysis (Phase I), vancomycin 15 mg/kg during the last hour of hemodialysis (Phase II) or vancomycin 30 mg/kg during the last 2 hours of hemodialysis (Phase III). Vancomycin plasma concentrations were obtained over an 8-day period and subsequent comparisons between the treatment approaches were made with paired t-tests or ANOVA, as appropriate. Dialysate vancomycin concentrations determined on Day 1 and Day 3 of Phases II and III were used to calculate the fraction of vancomycin dose removed, and were compared to plasma data using paired t-tests. RESULTS: Vancomycin was significantly removed (33.4 to 39.5%) during a 3- to 4-hour high-flux dialysis session occurring on Day 3 after vancomycin administration. Mean serum concentrations immediately following intradialytic vancomycin administration of 15 mg/kg over the last hour of dialysis or 30 mg/kg over the last 2 hours of dialysis were initially high (77.7 and 95.5 mcg/ml respectively), but fell to 25.9 and 40.5 mcg/ml, respectively, by 4 hours post-dialysis. Predialysis concentrations on Days 3, 5 and 8 were similar for vancomycin 30 mg/kg administered over the last 2 hours of dialysis as compared with a 15 mg/kg dose given after dialysis. Vancomycin 15 mg/kg over the last hour of dialysis resulted in significantly lower subsequent predialysis concentrations than the other dosing schemes. CONCLUSIONS: Vancomycin administration of 30 mg/kg over the last 2 hours of dialysis achieves serum concentrations similar to conventional dosing of 15 mg/kg after dialysis and would allow dosing on a weekly basis.

Adult↗

PubMed2001

Dexamethasone affects cytokine-mediated adhesion of HL-60 human promyelocytic leukemia cells to cultured dermal microvascular endothelial cells.

Leukocyte endothelial adhesion (LEA) is the prelude to a complex cascade of reactions following an immunological challenge. Recently, LEA has been implicated in the molecular basis of several dermatological disorders. While the role of proinflammatory cytokines, such as interleukin-1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), in LEA has been investigated using nondermal models, limited data exist regarding their effects on LEA in dermal models. This study shows that cotreatment of cultured human dermal endothelial cells (CADMEC) with IL-1beta and TNF-alpha resulted in a marked increase in the adherence of human promyelocytic leukemia (HL-60) cells to CADMEC and an increase in expression of intercellular adhesion molecule-1 and E-selectin. Pretreatment of CADMEC with dexamethasone, a long-lasting glucocorticoid, resulted in a decrease in both HL-60 cell adhesion to CADMEC and adhesion molecule expression. Taken together, these data demonstrate that LEA may play a role in inflammatory skin conditions and in the mechanisms underlying the potential use of glucocorticoids as a treatment option.

Cell Adhesion↗

PubMed2001

Clinical manifestations and management of pediatric HIV infection.

HIV infection has emerged as a colossal problem with epidemic proportions. According to an estimate from UNAIDS about 36.1 million people all over the world are infected at present. In India about 3.5 million people are infected. The infection has evolved into phase II process of disease evolution, spreading from high-risk population to the general population. The antenatal HIV seropositivity has shown a steady increase from 0.1% to 2% in some tertiary care hospitals in Mumbai. Pediatric HIV infection presents with diverse clinical manifestations. In developing countries like India, diagnosis of infection during first year of life in perinatally exposed infants poses a problem due to lack of easy accessibility and increased cost of diagnostic facilities like HIV-PCR, CD4/CD8 counts and viral cultures. Moreover, lack of adequate drugs and exorbitant cost of sustaining antiretroviral therapy complicates the management issues. An assortment of antiretovirals is available in USA and other developed countries. In India drugs like zidovudine, lamivudine, stavudine, nevirapine and indinavir are available and are used in symptomatic patients. CDC has defined definite treatment guidelines for pediatric population recently. These guidelines need to be modified in our set up. At the present juncture in India the emphasis remains on the prevention and treatment of opportunistic infections like tuberculosis and pneumocystis carinii and on prevention of perinatal transmission with zidovudine. This brief review deals with various clinical manifestations as relevant in a developing country like India and recent advances in antiretroviral therapy.

AIDS-Related Opportunistic Infections↗

PubMed2001

Mother-to-child transmission of the human immunodeficiency virus in Texas.

BACKGROUND: The Pediatric Spectrum of HIV Diseases (PSD) project has been collecting data on HIV-exposed children in Texas since 1989. These data have now been analyzed to describe mother-to-child transmission in Texas and to provide much needed information on the magnitude of the pediatric HIV epidemic in the state. METHODS: We examined trends in the numbers of perinatally exposed children and perinatally acquired cases of HIV in the Texas PSD cohort. We calculated transmission rates and relative risks for 656 children born from January, 1995, to July, 1998, that received all or part of the ACTG 076 regimen. RESULTS: Only a small proportion (38%) of pairs of an HIV-infected mother and her HIV-exposed child received the full AIDS Clinical Trial Group 076 (ACTG 076) regimen; only 73% of the mothers received at least some prenatal care. In recent years, however, the numbers of perinatally exposed children and perinatally acquired cases of HIV have decreased in Texas. Univariate analyses showed that a reduction in the vertical transmission of HIV was associated with receipt of a full ACTG 076 regimen, receipt of a partial ACTG 076 regimen and residence in Dallas County. CONCLUSIONS: Findings identify a gap in meeting the health care needs of pregnant HIV-infected women and suggest missed opportunities to prevent mother-to-child transmission of HIV. At the same time this study confirms progress in prevention efforts to reduce mother-to-child transmission of HIV in Texas.

Anti-HIV Agents↗

PubMed1999

Subjective assessment of fork-lift truck seats under laboratory conditions.

A subjective assessment of fork-lift truck seats has been carried out to assess the range of preferred seat dimensions and the acceptability of different seat adjustments to fork-lift truck drivers. Twelve fork-lift truck seats fitted to a fixed bench were assessed by twelve fork-lift truck drivers. For each seat, each driver completed a questionnaire that covered the following areas: eleven seat dimensions, four seat adjustments and other features (arm rests, safety belts and safety wings). The drivers assessed the dimensions of a seat chosen at random, before moving to the adjacent seat in either a clockwise or anticlockwise direction. Before each assessment, they were asked to look forward and backward in the seat as though they were driving a fork-lift truck. In general, significant correlations were obtained between the subjective assessments and objective measurements of the seat dimensions. This enabled preferred seat dimension ranges to be defined. Fork-lift truck drivers ranked the forward-backward and the backrest inclination adjustments as most important. The results showed that although the drivers had previous experience in the use of suspension seats, they did not understand the purpose of the weight adjustment. All adjustments should be easy to find, accessible, easy to move and they should enable a range of adjustments. In addition, clear and simple information on the seat is needed, especially for the weight adjustment. The most recently designed seats generally had dimensions within the preferred ranges compared with the older generation seats, mainly because they had more adjustments. However, the results show that adjustments on fork-lift truck seats could be improved further. Some tentative conclusions are made for the preferred fork-lift truck seat dimensions and adjustment ranges which are based on the evidence from this restricted sample of fork-lift truck drivers. They may be useful for seat and truck designers in the preparation of a standard on fork-lift truck seat dimensions.

Adult↗

PubMed1999

Fimbria-mediated enhanced attachment of nontypeable Haemophilus influenzae to respiratory syncytial virus-infected respiratory epithelial cells.

Respiratory syncytial virus (RSV) infection is known to predispose children to otitis media and sinusitis due to bacteria such as nontypeable Haemophilus influenzae (NTHI). In this study, we investigated the role of NTHI surface outer membrane protein P5-homologous fimbriae (P5-fimbriae) in attachment to RSV-exposed A549 epithelial cells. Analysis by fluorescence flow cytometry showed that a live P5-fimbriated NTHI strain (NTHIF+) attached to a higher proportion of RSV-exposed A549 cells than to control cells (mean, 68% for RSV versus 29% for control; P = 0.008), while attachment of the P5-fimbriae-deficient isogenic mutant strain (NTHIF-) was significantly lower than in control cells and rose only slightly following RSV exposure (mean, 17% for RSV versus 10% for control, P = 0.229). Attachment of NTHIF+ did not correlate with the amount of RSV antigen expressed by A549 cells. Furthermore, paraformaldehyde-fixed NTHIF+ also demonstrated an enhanced binding to RSV-exposed cells. Observations by transmission electronic microscopy showed that the mean number of bacteria attached per 100 RSV-exposed A549 cells was higher for NTHIF+ than NTHIF- (99 versus 18; P < 0.001). No intracellular bacteria were identified. UV-irradiated conditioned supernatants collected from RSV-infected A549 cultures (UV-cRSV) also enhanced the attachment of NTHIF+ to A549, suggesting the presence of a preformed soluble mediator(s) in UV-cRSV that enhances the expression of receptors for P5-fimbriae on A549 cells. In summary, RSV infection significantly enhances NTHI attachment to respiratory epithelial cells. P5-fimbria is the critical appendage of NTHI that participates in this attachment. In clinical settings, blocking of the P5-fimbria-mediated attachment of NTHIF+ by passive or active immunity may reduce the morbidity due to NTHI during RSV infection.

Antigens, Viral↗

PubMed1998

Arachidonylethanolamide (AEA) activation of FOS proto-oncogene protein immunoreactivity in the rat brain.

It is thought that the physiological actions of endogenous cannabinoid arachidonylethanolamide (AEA), as well as exogenous cannabinoids such as Delta9-tetrahydrocannabinol (THC), are mediated by two subtypes of cannabinoid receptors, CB1 and CB2, which have recently been characterized. Injection of AEA leads to alterations in motor behavior and endocrine function. While these phenomena have been well characterized, the neuronal substrate of AEA's actions remains undetermined. In this study, FOS immunoreactivity (FOSir) was used to map rat brain nuclei that are responsive to a single intracerebroventricular injection of AEA. The results showed that FOSir was induced in several nuclei including the bed nucleus of the stria terminalis (BNST), paraventricular nucleus of the hypothalamus (PVN), central nucleus of the amygdala (Ce), periaqueductal gray area (PAG), dentate gyrus in the hippocampus (Dg), paraventricular nucleus of the thalamus (PVA), median preoptic nucleus (MnPO), periventricular nucleus (Pe), caudate putamen (CPU) and the ependymal lining of the ventricles. The pattern of activation identified correlates, in part, with the distribution of CB receptors. At the same time, a new subset of nuclei, without demonstrable CB receptors, have been shown to respond to an AEA challenge. Activation of these nuclei is consistent with the physiological effects of AEA. These findings provide valuable information on the response to AEA at the level of neuronal activation and provide the basis for a broader understanding of the possible role of CB receptors in the modulation of motor and endocrine function associated with the use of exogenous cannabinoids, such as marijuana.

Animals↗

PubMed1998

Cytokine modulation of human corneal epithelial cell ICAM-1 (CD54) expression.

To determine whether pro-inflammatory cytokines modulate intercellular adhesion molecule-1 (ICAM-1; CD54) expression on cultured primary human corneal epithelial cells (HCEs), confluent HCEs were treated with various concentrations of interferon-gamma(IFN-gamma), interleukin-1alpha(IL-1alpha), IL-1beta, IL-4, tumor necrosis factor-alpha (TNF-alpha), or combinations over time. ICAM-1 expression was measured by flow cytometry and/or a cell-based ELISA using a monoclonal mouse anti-human CD54 antibody. The apparent MW of ICAM-1 protein was determined by immunoprecipitation of biotinylated HCEs. RT-PCR was used to detect ICAM-1 RNA. The mature cell surface form of HCE ICAM-1 was approximately 110 kDa as determined by immunoprecipitation. IFN-gammaand TNF-alpha induced both dose- and time-dependent increases in ICAM-1 expression. An approximately 20-fold increase in ICAM-1 was seen at 50-100 U IFN-gamma ml-1. ICAM-1 specific mRNA accumulated approximately 4.5-fold after IFN-gammatreatment. TNF-alpha(100 U ml-1) induced a consistent approximately 6.0-fold increase in ICAM-1 expression. When IFN-gammaand TNF-alpha were mixed, at sub-optimal concentrations of each, a synergistic effect on ICAM-1 expression was not detected. Neither IL-4, IL-1alpha nor IL-1beta affected ICAM-1 expression in a consistent fashion. In summary, ICAM-1 was modulated on primary human corneal epithelial cells by the cytokines IFN-gamma and TNF-alpha in a dose- and time-dependent fashion. Cytokine modulation of corneal epithelial cell ICAM-1 during inflammation may contribute to corneal epithelial cell injury by aiding the attachment of inflammatory cells such as eosinophils which express the receptor for ICAM-1, the beta2 integrins (CD11a,b,c/CD18).

Cell Culture Techniques↗

PubMed1998

Autocrine regulation of interleukin-8 by interleukin-1alpha in respiratory syncytial virus-infected pulmonary epithelial cells in vitro.

Respiratory epithelial cells infected with respiratory syncytial virus (RSV) produce interleukin-8 (IL-8); however, the mechanisms of RSV-induced regulation of IL-8 are poorly understood. In the present study, the regulation of IL-8 by RSV was evaluated using pulmonary type II-like epithelials (A549). Live purified RSV (pRSV) induced a significant increase in IL-8 after 8 hr of exposure, while conditioned supernatants from pRSV-infected A549 cells (cRSV) induced IL-8 production in fresh A549 cultures within 4 hr of infection. Furthermore, cRSV that had been rendered non-infectious by ultraviolet-irradiation (UV-cRSV) or ribavirin treatment also induced an increased production of IL-8 in fresh A549 cells, suggesting that RSV induced the synthesis of a soluble mediator(s) which in turn enhanced the synthesis of IL-8. We have previously shown that RSV-infected A549 cells produce IL-1alpha, IL-1-beta and tumour necrosis factor-alpha (TNF-alpha), which by themselves are known to induce the synthesis of IL-8. Preincubation of UV-cRSV or simultaneous incubation of pRSV with recombinant IL-1 receptor antagonist almost completely blocked (95-98%) the production of IL-8 by A549 cells. Furthermore, incubation with neutralizing antibodies against IL-1alpha, IL-1beta and TNF-alpha showed that IL-1alpha was the predominant soluble mediator that enhanced the mRNA expression and synthesis of IL-8. IL-1beta and TNF-alpha induced the synthesis of IL-8 at 24 hr, but partially inhibited the synthesis at 48 hr. In summary, these experiments provide direct evidence for an autocrine mechanism of enhanced IL-8 production in RSV-infected epithelial cells that is primarily mediated by IL-1alpha. In clinical settings, inhibitors of IL-1alpha may be useful in suppressing inflammation due to IL-1alpha as well as IL-8.

Antibodies, Monoclonal↗

PubMed1998

Autocrine regulation and experimental modulation of interleukin-6 expression by human pulmonary epithelial cells infected with respiratory syncytial virus.

The mechanisms of regulation of interleukin-6 (IL-6) production in respiratory syncytial virus (RSV)-infected respiratory epithelial cells were evaluated in A549 cell cultures. Incubation with purified RSV resulted in significant production of IL-1alpha, IL-1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha). Addition of saturating concentrations of neutralizing antibodies against IL-1alpha, IL-1beta, or TNF-alpha into purified RSV-infected cell cultures resulted in a significant inhibition of IL-6 production, although anti-IL-1alpha antibody had the most predominant effect (80% inhibition). Anti-IL-1alpha antibody also almost completely blocked the expression of mRNA for IL-6. Addition of therapeutic concentrations of dexamethasone (1 microM) or ribavirin (90 microg/ml), an antiviral agent, also significantly inhibited the synthesis of IL-6. Hence, in clinical settings, pharmacological agents such as the specific antagonists of IL-6-inducing cytokines, as well as dexamethasone and ribavirin, could be used to modulate IL-6 production.

Antiviral Agents↗

PubMed1997

Chronic exposure to morphine, but not ethanol, attenuates the expression of interleukin-1 beta converting enzyme in rat spleen.

IL-1 beta converting enzyme (ICE), a proteolytic enzyme that converts the inactive precursor of interleukin-1 beta (IL-1 beta) to its mature active form, has been abundantly detected in the IL-1 beta producing cells in the spleen. Since IL-1 beta is a potent neuro-endocrine-immuno modulator, alterations in the production of IL-1 beta by an exogenous factor, such as morphine or ethanol, may have deleterious effects on the system as a whole. In this study, we examined the expression of ICE in the spleens of rats given chronic treatment with morphine versus ethanol using reverse transcriptase-polymerase chain reaction (RT-PCR). The expression of ICE in the spleen of rats given chronic morphine was clearly less than that of the animals given placebo, however, it was similar for both rats on ethanol and control diets. These data suggest that chronic use of morphine, but not ethanol, attenuates the expression of ICE in the spleen.

Animals↗

PubMed1997

Transcription of genes encoding iron and heme acquisition proteins of Haemophilus influenzae during acute otitis media.

Unencapsulated Haemophilus influenzae is the second most common etiologic agent of otitis media in children. H. influenzae requires heme for aerobic growth in vitro and is able to utilize hemoglobin and complexes of heme-hemopexin, heme-albumin, and hemoglobin-haptoglobin and ferritransferrin as sources of iron and heme in vitro. Several of the acquisition mechanisms have been characterized and been shown to be heme repressible in vitro. However, little is known about the expression of heme and/or iron acquisition mechanisms during infections in the middle ear. This study was performed to determine if the genes encoding heme and iron acquisition proteins are transcribed during in vivo growth and to compare these findings with those for samples grown in vitro. Reverse transcriptase PCR (RT-PCR) was used to analyze total RNA fractions derived from in vitro- and in vivo-grown H. influenzae. Genes encoding the transferrin-binding proteins TbpA and TbpB, the 100-kDa hemopexin-binding protein HxuA, and the hemoglobin-binding protein HgpA were transcribed during otitis media. Twelve middle ear fluid samples were analyzed by blind RT-PCR to determine the transcriptional status of these genes in H. influenzae during otitis media. Five isolates had transcripts corresponding to tbpA, tbpB, and hxuA. The presence of hgpA transcripts was variable, depending on the presence of hgpA in the genome of the H. influenzae isolate. Samples without H. influenzae gene transcripts contained other etiologic agents commonly causing otitis media. These data demonstrate that H. influenzae iron and/or heme acquisition genes are transcribed during otitis media and suggest that the microenvironment during acute otitis media starves H. influenzae of heme.

Acute Disease↗

PubMed1996

Role of leukotriene B4 and interleukin-8 in acute bacterial and viral otitis media.

In order to evaluate the role of polymorphonuclear leukocytes (PMNs) in acute otitis media (AOM), levels of leukotriene B4 (LTB4), a potent inflammatory product of PMNs, and interleukin-8 (IL-8), a PMN chemotactic cytokine, were measured in 271 middle ear fluid (MEF) samples from 106 children with AOM. Forty-two percent of the patients had evidence of respiratory viral infection. At the time of diagnosis, levels of both LTB4 and IL-8 were higher in the MEFs from patients with AOM associated with bacterial or bacterial and viral infection than those MEFs containing no pathogen (p < .05). Antibiotic treatment was not associated with a significant change in levels of LTB4 or IL-8 in the MEFs obtained 2 to 5 days into treatment, compared to those obtained at diagnosis. Bacteriologic failure after 2 to 5 days of treatment was associated with high LTB4 levels in the initial MEFs (p = .05). Recurrence of AOM within 1 month was associated with high IL-8 levels in the initial MEF (p = .04). Our findings suggest that LTB4 and IL-8 are produced during acute infection of the middle ear, and these PMN-related inflammatory substances may play an important role in delaying recovery or in recurrence of AOM. Effective treatment of AOM may require eradication of bacteria by antibiotics, as well as pharmacologic agents that modulate PMN functions.

Bacterial Infections↗

PubMed1996

Effects of a pH 7.4, lactate-based and a pH 7.4, bicarbonate-based peritoneal dialysis solutions on neutrophil superoxide generation.

Neutrophil superoxide formation was similar when cells were incubated in self-made, non-autoclaved pH 7.4, lactate-based peritoneal dialysis solutions or in their self-made, non-autoclaved, pH 7.4, bicarbonate-based counterparts. On the other hand, commercially available, autoclaved, pH 7.4, lactate-based peritoneal dialysis solutions resulted in inhibition of superoxide production when compared to their self-made, non-autoclaved, pH 7.4, lactate-based or bicarbonate-based counterparts. The cause for this inhibition of superoxide generation is at present unknown.

Adult↗

PubMed1995

Bacteriologic failure of amoxicillin-clavulanate in treatment of acute otitis media caused by nontypeable Haemophilus influenzae.

OBJECTIVE: To evaluate the rate of bacteriologic failure of amoxicillin-clavulanate in the treatment of acute otitis media (AOM) and to identify the risk factors associated with failure. METHODS: Ninety-nine subjects (mean age, 21.4 months) with AOM were treated with amoxicillin-clavulanate in two prospective study trials that compared efficacy of two experimental antibiotics with amoxicillin-clavulanate. Tympanocentesis for microbiologic studies was performed in all subjects at enrollment; at 3 to 6 days, during amoxicillin-clavulanate therapy; and at other times when clinically indicated. The subjects were followed up for 1 month. Clinical, bacteriologic, and virologic characteristics of the subjects were analyzed. RESULTS: Bacteriologic failure of treatment occurred in none of 39 subjects (0%) with Streptococcus pneumoniae, two of 25 (8%) with Moraxella catarrhalis, and 11 of 29 (38%) with nontypeable Haemophilus influenzae (NTHi) infection. The failure rate for NTHi was higher than that for other pathogens (p = 0.0007) and was increased when compared with the preceding study period (p = 0.017). Bacteriologic failure was also associated with clinical failure (p = 0.041). In subjects with AOM caused by NTHi the rates of adequate drug compliance were comparable in both success and failure groups. Antimicrobial susceptibility testing by minimum inhibitory concentration and minimum bactericidal concentration (MIC/MBC) assays showed that amoxicillin-clavulanate resistance was not significantly associated with bacteriologic failure of treatment. However, in two subjects, MIC/MBC of the NTHi isolates during therapy were higher than MIC/MBC of the isolates before therapy; these strains of isolates pretherapy and during therapy were discordant as determined by outer membrane protein analysis. The bacteriologic failure rate was higher in nonwhite boys (p = 0.026) and in subjects with a history of three or more previous episodes of AOM (p = 0.008). Other factors such as age, bilaterality of disease, polymicrobial infection, and biotype pattern of NTHi were not associated with treatment failure. When children with adequate drug compliance were analyzed separately, only those with concomitant viral infection of the nasopharynx or middle ear were found to be at an increased risk of bacteriologic failure of treatment (p = 0.04). CONCLUSIONS: The bacteriologic failure rate of amoxicillin-clavulanate therapy for AOM caused by NTHi was higher in the current study period than in the preceding period. Factors contributing to treatment failure were race, gender, proneness to otitis, and concomitant viral infection.

Acute Disease↗

PubMed1995

Interleukin-1 alpha mediates the enhanced expression of intercellular adhesion molecule-1 in pulmonary epithelial cells infected with respiratory syncytial virus.

The mechanisms of virus-induced enhancement of intercellular adhesion molecule-1 (ICAM-1) expression in epithelial cells are unknown. In the present study, the effect of respiratory syncytial virus (RSV) infection on the expression of ICAM-1 in human pulmonary type II-like epithelial (A549) cells was evaluated. Conditioned RSV media (cRSV) produced from growth of RSV in A549 cells induced a significant increase in the expression of ICAM-1. Treatment of the cells with noninfectious cRSV prepared by ultraviolet (UV) irradiation (UV-cRSV) or ribavirin treatment resulted in the expression of ICAM-1 to a similar extent as infectious cRSV. These results suggested that RSV induces the synthesis of a soluble mediator(s) that regulates the expression of ICAM-1. Cytokine analysis by immunoassay and polymerase chain reaction showed that RSV induces the synthesis of interleukin (IL)-1 alpha and -beta, and tumor necrosis factor alpha (TNF-alpha). Preincubation of UV-cRSV with soluble IL-1 receptor (sIL-1r) almost completely blocked the enhancement of ICAM-1 expression. Furthermore, simultaneous incubation of infectious purified RSV with sIL-1r resulted in a significant reduction in enhancement of ICAM-1 expression. Preincubation with neutralizing antibodies to IL-1 alpha and -beta, and TNF-alpha showed that the predominant ICAM-1 enhancing soluble mediator in UV-cRSV was IL-1 alpha. These experiments provide direct evidence for an autocrine mechanism of enhanced ICAM-1 expression in RSV-infected epithelial cells that is mediated primarily by IL-1 alpha. Pulmonary epithelial cells may play an important immunoregulatory role in the microenvironment of the lower respiratory tract infected with RSV.

Cell Adhesion↗