Cytomegalovirus-Associated CD4(+) CD28(null) Cells in NKG2D-Dependent Glomerular Endothelial Injury and Kidney Allograft Dysfunction.

Emerging data suggest that expansion of a circulating population of atypical, cytotoxic CD4(+) T cells lacking costimulatory CD28 (CD4(+) CD28(null) cells) is associated with latent cytomegalovirus (CMV) infection. The purpose of the current study was to increase the understanding of the relevance of these cells in 100 unselected kidney transplant recipients followed prospectively for a median of 54 months. Multicolor flow cytometry of peripheral blood mononuclear cells before transplantation and serially posttransplantation was undertaken. CD4(+) CD28(null) cells were found predominantly in CMV-seropositive patients and expanded in the posttransplantation period. These cells were predominantly effector-memory phenotype and expressed markers of endothelial homing (CX3CR1) and cytotoxicity (NKG2D and perforin). Isolated CD4(+) CD27(-) CD28(null) cells proliferated in response to peripheral blood mononuclear cells previously exposed to CMV-derived (but not HLA-derived) antigens and following such priming incubation with glomerular endothelium resulted in signs of endothelial damage and apoptosis (release of fractalkine and von Willebrand factor; increased caspase 3 expression). This effect was mitigated by NKG2D-blocking antibody. Increased CD4(+) CD28(null) cell frequencies were associated with delayed graft function and lower estimated glomerular filtration rate at end follow-up. This study suggests an important role for this atypical cytotoxic CD4(+) CD28(null) cell subset in kidney transplantation and points to strategies that may minimize the impact on clinical outcomes.

Biomarkers to enhance accuracy and precision of prediction of short-term and long-term outcome after spontaneous intracerebral haemorrhage: a study protocol for a prospective cohort study.

BACKGROUND: Several studies reported prognostic value of biomarker in intracerebral hemorrhagic (ICH) but they are either preliminary observation or inadequately powered to analyse independent contribution of biomarkers over and above clinical and neuroimaging data. OBJECTIVE: To examine whether the biomarker can significantly add to the predictive accuracy of prognosis of ICH. METHOD/DESIGN: In a multi-centric prospective cohort study, 1020 patients with ICH within 72 hours of onset are being recruited. After obtaining written informed consent from patients/proxy, venous blood sample (10 ml) is being collected and analysed for C-reactive protein (CRP) level, S100B, Glial fibrillary acidic protein (GFAP), Troponin, change in leukocyte count and Copeptin levels. The patients are telephonically followed using stroke scales (Barthel Index and modified Rankin Scale) at 3, 6, 12 months and 2 years after the recruitment. DISCUSSION: This protocol will aim at predicting the short term or long term prognosis with the use of clinical, neuroimaging and biomarkers in order to help clinician to stratify patients for early referral or intervention.

Transitional B lymphocytes are associated with protection from kidney allograft rejection: a prospective study.

Recent cross-sectional studies suggest an important role for transitional B lymphocytes (CD19 + CD24hiCD38hi) in promoting transplant tolerance, and protecting from late antibody-mediated rejection (ABMR). However, prospective studies are lacking. This study enrolled 73 de novo transplant recipients, and collected serial clinical, immunological and biochemical information over 48 ± 6 months. Cell phenotyping was conducted immediately prior to transplantation, and then on five occasions during the first year posttransplantation. When modeled as a time-dependent covariate, transitional B cell frequencies (but not total B cells or "regulatory" T cells) were associated with protection from acute rejection (any Banff grade; HR: 0.60; 95% CI: 0.37-0.95; p = 0.03). No association between transitional B cell proportions and either de novo donor-specific or nondonor-specific antibody (dnDSA; dnNDSA) formation was evident, although preserved transitional B cell proportions were associated with reduced rejection rates in those patients developing dnDSA. Three episodes of ABMR occurred, all in the context of nonadherence, and all associated with in vitro anti-HLA T cell responses in an ELISPOT assay (p = 0.008 versus antibody-positive patients not experiencing ABMR). This prospective study supports the potential relevance of transitional ("regulatory") B cells as a biomarker and therapeutic intervention in transplantation, and highlights relationships between humoral immunity, cellular immunity and nonadherence.

Characterizing dilute combustion instabilities in a multi-cylinder spark-ignited engine using symbolic analysis.

Spark-ignited internal combustion engines have evolved considerably in recent years in response to increasingly stringent regulations for emissions and fuel economy. One new advanced engine strategy ustilizes high levels of exhaust gas recirculation (EGR) to reduce combustion temperatures, thereby increasing thermodynamic efficiency and reducing nitrogen oxide emissions. While this strategy can be highly effective, it also poses major control and design challenges due to the large combustion oscillations that develop at sufficiently high EGR levels. Previous research has documented that combustion instabilities can propagate between successive engine cycles in individual cylinders via self-generated feedback of reactive species and thermal energy in the retained residual exhaust gases. In this work, we use symbolic analysis to characterize multi-cylinder combustion oscillations in an experimental engine operating with external EGR. At low levels of EGR, intra-cylinder oscillations are clearly visible and appear to be associated with brief, intermittent coupling among cylinders. As EGR is increased further, a point is reached where all four cylinders lock almost completely in phase and alternate simultaneously between two distinct bi-stable combustion states. From a practical perspective, it is important to understand the causes of this phenomenon and develop diagnostics that might be applied to ameliorate its effects. We demonstrate here that two approaches for symbolizing the engine combustion measurements can provide useful probes for characterizing these instabilities.

An unusual cause of reversible axonal neuropathy and hypertension in a 10-year-old girl.

A 10-year-old girl, who was referred with refractory epilepsy, had 1.5 years of episodic abnormal behavior. On examination, she also had hypertension and peripheral neuropathy. Hypoglycemia with correspondingly high insulin levels was documented during a confusional episode. MRI of the abdomen revealed an islet cell tumor in the body of the pancreas. One year after tumor excision, both the neuropathy and hypertension showed remarkable improvement. A final diagnosis of insulinoma with hypoglycemic axonal neuropathy and hypertension (reversed with tumor excision) was made. Insulinoma is the commonest cause of hyperinsulinemic hypoglycemia in adults, but is rare in childhood. To our knowledge, distal symmetrical motor-sensory axonal neuropathy has been described in only 40 patients, and hypertension has not been reported with insulinoma.

Chorioamnionitis, not epidural analgesia, is associated with maternal fever during labour.

PURPOSE: Maternal fever is associated with chorioamnionitis and has been linked to labour epidural analgesia (LEA). The purpose of this study was to determine possible associations between LEA and chorioamnionitis, maternal fever, operative delivery rate, and neonatal outcome. METHODS: Data from 14,073 patients were entered into a database over a two-year period. From this database, 62 nulliparous parturients with clinical chorioamnionitis (amnionitis), but without LEA were identified (Group I). Two other groups who received LEA were matched for parity and gestation: Group II - LEA with concomitant amnionitis (n=50) and, Group III - LEA without concomitant amnionitis (n=201). The diagnosis of chorioamnionitis was confirmed by histologic examination. Results are expressed as mean +/- SD and analyzed at P <0.05 using ANOVA or Chi-square. RESULTS: No differences were noted among the groups in the operative delivery rate or Apgar scores at five minutes. The percentage of patients with maternal fever during labour (38.0 degrees C) with amnionitis was significantly less in Group III compared to the other groups (100% in both Groups I and II vs 1.0% in Group III; P=0.000). Likewise, Group III had a lower percentage of neonates with Apgar scores <7 at one minute (35.5% in Group I, 20.0% in Group II, 17.4% in Group III; P=0.010). The percentage of histologic chorioamnionitis was significantly higher in both amnionitis groups compared to Group III (67.7% in Group I, 56.0% in Group II, 4.0% in Group III; P=0.000). CONCLUSION: LEA without chorioamnionitis is not associated with maternal fever (38.0 degrees C), increased operative delivery rates or low Apgar scores.

Epidural labor analgesia and neonatal sepsis evaluation rate: a quality improvement study.

UNLABELLED: Labor epidural analgesia (LEA) is allegedly associated with maternal fever and an increase in the newborn sepsis work-up (SWU) rate. In this study, we evaluated whether LEA causes an increase in the SWU rate compared with a Control group given parenteral narcotics for labor pain. Maternal and neonatal data were collected prospectively for a continuous quality improvement database. Odds ratios were calculated by using multiple logistic regression for various triggers for SWU in the neonate. Of the 1177 primiparous women and their neonates studied, 922 women received LEA and 255 women received parenteral analgesics. A small but statistically significant increase in maternal and neonatal temperatures occurred in parturients receiving LEA. The SWU rates were 7.5% in the LEA group and 9.4% in the Controls (not significant). Triggers identified for SWU were birth weight (odds ratio = 116, P = 0.000), gestational age (odds ratio = 86.6, P = 0.000), meconium aspiration and respiratory distress requiring intubation (odds ratio = 8.6, P = 0.000), hypothermia at birth (odds ratio = 7.1, P = 0.001), maternal Group B beta-hemolytic streptococcal colonization (odds ratio = 6, P = 0.000), and preeclampsia or hypertension (odds ratio = 3.5, P = 0.03). There was no association between LEA and SWU. IMPLICATIONS: Although it has been suggested that epidural analgesia for labor contributes to an increase in neonatal sepsis work-up (SWU), this retrospective analysis shows that epidural analgesia is not associated with an increase in SWU. The factors that were found to contribute to SWU included low birth weight, low gestational age, meconium aspiration or respiratory distress at birth, hypothermia at birth, maternal group B beta-hemolytic colonization, and preeclampsia or hypertension.

Re-emergence of lead poisoning from contaminated flour in a West Bank Palestinian village.

Although contaminated flour was first described as an important source of endemic lead poisoning in the Middle East almost 20 years ago, the use of lead in community flour mills has not been eliminated and continues to represent a significant environmental risk. The authors describe an outbreak of lead poisoning in a West Bank Palestinian family and draw attention to this unusual but important source of lead exposure. All 13 members of the family (two children and 11 adults), were found to have lead poisoning following hospitalization for "gastroenteritis," headache, joint pain, weight loss, and vision difficulties. Seven females had low hemoglobin levels. Blood lead concentrations ranged from 42 to 84 microg/dL. Household flour samples obtained from a stone mill, previously closed because of lead contamination, contained 2,000 ppm lead. Flour from traditional stone mills reinforced with lead joints remains a potential source for lead poisoning.

Blood lead and erythrocyte protoporphyrin levels in Kazakhstan.

A pilot study was conducted to examine the extent of lead exposure and prevalence of iron deficiency in 3 major cities of Kazakhstan. Blood lead (B-Pb.) and erythrocyte protoporphyrin (ZnPP) levels of 475 children, age range 6 months to 7 yeas were measured. The mean B-Pb. levels in the different cities ranged from 4-7 micrograms/dl (minimum 1 to max 29 micrograms/dl) and similarly the mean ZnPP levels ranged from 26-32 micrograms/dl (minimum 12 and maximum 95 micrograms/dl), thus confirming low level lead poisoning of children at some sites. One to four year olds had greater than 10 micrograms/dl B-Pb in 18-27% cases compared with 3-7% cases in five to seven year olds. Prevalence of iron deficiency in 6 months to 4 year old children was the highest ranging from 28-86% compared with 4 to 15% in 4-7 year olds. However, there was remarkably low prevalence (4%) of iron deficiency in a group of 5-6 years olds. This study suggests that a targeted B-Pb and ZnPP monitoring together with an iron supplementation programme in the 3 cities of Kazakhstan is essential. Environmental education appears to have had a positive impact in lowering B-Pb at one site and should thus be expanded nationwide.

Improved bowel function after gynecological surgery with epidural bupivacaine-fentanyl than bupivacaine-morphine infusion.

PURPOSE: To compare postoperative gastrointestinal recovery between continuous epidural bupivacaine-fentanyl and bupivacaine-morphine. METHODS: In a blinded, randomized, prospective trial, 60 women undergoing surgery for gynecologic cancer were studied. Anesthesia was provided by a combined general/epidural (L2-3 catheter) technique without epidural opioids. Postoperative epidural analgesia was by continuous infusion of bupivacaine 0.1% with either morphine 0.05 mg x ml(-1) (BM) or fentanyl 5 microg x ml(-1) (BF). Visual Analogue Scale (VAS) scores for pain at rest and during movement, and the return of bowel function were collected for three days and the duration of hospitalization were noted. RESULTS: On POD-1, 18.5% of patients in the BM group had emesis compared with none in the BF group (P = 0.038) and fewer patients in the BM group tolerated clear oral fluids (11.1% BM vs 40.6% BF, P = 0.025). These differences became insignificant on POD-2 and 3. Median pain scores were comparable at rest and ranged from 10-20 in the BM group vs 0-20 in the BF group over the three days. Similarly, median pain scores with movement respectively ranged from 20-25 and 20-30 in the BF and BM groups. The mean duration of hospitalization was longer in the BM group (5.7 +/- 2.4) vs BF (4.5 +/- 1.2 days), P = 0.017. CONCLUSION: Epidural BM and BF provided equally effective postoperative analgesia at rest and during movement. Compared with BM, epidural BF is associated with less emesis and an increased ability to tolerate oral fluids on POD-1 and an overall shorter hospital stay.

Follow-up screening of lead-poisoned children near an auto battery recycling plant, Haina, Dominican Republic.

In August 1997 we performed a follow-up survey of 146 lead-poisoned children from a community near a previously active auto battery recycling smelter in Haina near Santo Domingo, Dominican Republic. Our follow-up survey confirmed a severe incidence of elevated blood lead (BPb) and erythrocyte protoporphyrin/zinc protoporphyrin (EP-ZnPP) levels. The mean BPb level was 32 micrograms/dL and the mean EP-ZnPP level was 128 micrograms/dL. The frequency distribution of BPb showed that only 9% of the children had BPb levels below the currently acceptable 10 micrograms/dL threshold level, 23% had between 10 and 19 micrograms/dL, 40% had between 20 and 39 micrograms/dL, 27% had between 40 and 99 micrograms/dL, and the remainder had > 100 micrograms/dL. These findings are significantly greater than the mean BPb and EP-ZnPP levels of 14 and 35 micrograms/dL, respectively, in a comparison group of 63 children in Barsequillo, 4 miles away. BPb frequency distributions for these groups were < 10 micrograms/dL (42%), 10-19 micrograms/dL (32%), and 20-39 micrograms/dL (16%); in the remaining 10%, BPb levels were between 40 and 99 micrograms/dL. Similarly, the corresponding frequency distribution of EP-ZnPP levels in Haina children were proportional to the severity of lead poisoning and significantly higher than those of the Barsequillo comparison group. This study reveals that at least 28% of Haina children require immediate treatment; of these, 5% with lead levels > 70 micrograms/dL are also at risk for severe neurologic sequelae, and urgent action is imperative.

Lead exposure and iron deficiency among Jammu and New Delhi children.

In order to examine the prevalence of lead exposure and iron deficiency in Jammu, blood lead (B-Pb) and erythrocyte protoporphyrin (EP-ZnPP) levels were measured in a group of 125 children and compared with B-Pb and EP levels of 46 New Delhi children. The mean B-Pb level of Jammu children was 15 micrograms/dl and ZnPP level 46 micrograms/dl. The frequency distribution of B-Pb in Jammu children according to the 1997 CDC stratification showed that only 33% were below the 10 micrograms/dl "normal" threshold levels and 50.5% were between 10-19 micrograms/dl, an increasing level of concern. The remaining 16.5% were in the medical intervention lead poisoned level between 20-87 micrograms/dl with corresponding EP levels between 29-160 micrograms/dl. The mean B-Pb and ZnPP levels for New Delhi children were 14 micrograms/dl and 55 micrograms/dl respectively. This study on Jammu children shows a modest increase in mean B-Pb and EP levels from those in 1985; the percentage of children with higher levels of B-Pb > 10 micrograms/dl have significantly increased. Moreover, the continued underlying high prevalence of iron deficiency among these children predisposes them to increased lead absorption from various sources thus aggravating further, the detrimental effects of lead. Therefore, a more extensive screening of all children below 10 years of age and an ongoing B-Pb and EP monitoring and iron supplementation programme for Jammu and New Delhi is essential. An environmental assessment of the sources leading to serious lead intoxication problem in Jammu, a rapidly growing and overpopulated city of the state of Jammu and Kashmir is strongly recommended.

Elevated blood lead and erythrocyte protoporphyrin levels of children near a battery-recycling plant in Haina, Dominican Republic.

A survey of children from a community adjacent to an auto-battery-recycling smelter in Haina, the Dominican Republic, revealed alarming elevations of blood lead (B-Pb) and erythrocyte protoporphyrin (EP-ZnPP) compared with controls. The authors recommend follow-up confirmation and treatment of severely lead-poisoned children, shutdown of the plant, controlled disposal of the hazardous waste from the site, and relocation of the community.

Evaluation of repellent activities of Cymbopogon essential oils against mosquito vectors of Malaria, Filariasis and Dengue Fever in India.

Essential oils of four species and two hybrid varieties of Cymbopogon grasses were evaluated for their repellent properties against the major vector mosquitoes, namely, Anopheles stephensi, Culex quinque-fasciatus and Aedes aegypti, both in laboratory and field. The magnitude of repellency in the Cymbopogon essential oils was found to be of moderate to high order. All grass species protected completely from mosquito bites for 4 hrs, whereas C. nardus provided protection for as much as 8-10 hrs overnight.

Manometry of individual segments of the distal esophageal sphincter. Its relation to functional incompetence.

The major components of the lower esophageal sphincter, the pressure it exerts, its total length, and the length of sphincter affected by abdominal pressure are usually expressed as means of several recordings from different radial segments of the sphincter. In segmental manometry, the individual readings for these components in each segment, rather than the mean values, are analyzed. We used segmental manometry to study 50 normal volunteers and 200 patients with symptoms suggestive of gastroesophageal reflux. Of the latter, 100 had increased esophageal acid exposure and 100 did not. An increased number of defective segments was associated with a greater prevalence of increased esophageal acid exposure. Segmental analysis disclosed the same number (52) of defective sphincters (defined as sphincters with two or more defective segments) in the 100 patients with increased acid exposure as did standard analysis. However, the relationship between a defective lower esophageal sphincter and the number of reflux episodes was clearer when a defective sphincter was defined using standard analysis. Segmental analysis of the lower esophageal sphincter has no clear advantage over standard analysis.

Effect of caffeic acid esters on carcinogen-induced mutagenicity and human colon adenocarcinoma cell growth.

Propolis, a honey bee hive product, is thought to exhibit a broad spectrum of activities including antibiotic, antiviral, anti-inflammatory and tumor growth inhibition; some of the observed biological activities may be due to caffeic acid (cinnamic acid) esters that are present in propolis. In the present study we synthesized three caffeic acid esters, namely methyl caffeate (MC), phenylethyl caffeate (PEC) and phenylethyl dimethylcaffeate (PEDMC) and tested them against the 3,2'-dimethyl-4-aminobiphenyl, (DMAB, a colon and mammary carcinogen)-induced mutagenicity in Salmonella typhimurium strains TA 98 and TA 100. Also, the effect of these agents on the growth of human colon adenocarcinoma, HT-29 cells and activities of ornithine decarboxylase (ODC) and protein tyrosine kinase (PTK) was studied. Mutagenicity was induced in Salmonella typhimurium strains TA 98 and TA 100 plus S9 activation using 5 and 10 micrograms DMAB and antimutagenic activities of 0-150 microM MC, 0-60 microM PEC and 0-80 microM PEDMC were determined. The results indicate that MC, PEC and PEDMC were not mutagenic in the Salmonella tester system. DMAB-induced mutagenicity was significantly inhibited with 150 microM MC, 40-60 microM PEC and 40-80 microM PEDMC in both tester systems. Treatment of HT-29 colon adenocarcinoma cells with > 150 microM MC, 30 microM PEC and 20 microM PEDMC significantly inhibited the cell growth and syntheses of RNA, DNA and protein. ODC and PTK activities were also inhibited in HT-29 cells treated with different concentrations of MC, PEC and PEDMC. These results demonstrate that caffeic acid esters which are present in Propolis possess chemopreventive properties when tested in short-term assay systems.

Immunosuppression in patients with Barrett's esophagus.

BACKGROUND: Patients with Barrett's esophagus have a higher incidence of esophageal cancer than has the general population. Local tissue injury and exposure to carcinogens presumably play a role in malignant transformation, but the possibility of altered host immune surveillance must also be considered. METHODS: The level of immunoreactivity was investigated in six healthy control subjects; 14 patients with gastroesophageal reflux, seven with and seven without esophagitis; and nine patients with Barrett's esophagus. Parameters studied were (1) T-cell and B-cell function with mitogen-stimulated lymphocyte blastogenesis, (2) immunosuppressive properties of autologous serum, and (3) interleukin-2 production by peripheral blood mononuclear cells. Nutritional status as a possible cause for immunosuppression was assessed by measurement of serum albumin, transferrin, and prealbumin. RESULTS: Patients with Barrett's esophagus had a significant suppression of all T-cell (p less than 0.01) and B-cell function (p less than 0.01) and interleukin-2 production (p less than 0.001) when they were compared to the controls. Interleukin-2 production was also reduced significantly compared to that in patients with gastroesophageal reflux with and without esophagitis (p less than 0.05). No differences were observed in serum immunosuppression or nutritional factors. CONCLUSIONS: Although the immunosuppression observed in the patients with Barrett's esophagus was milder than that found in other immunocompromised states, it may be sufficient to encourage the malignant transformation of Barrett's mucosa.