Cyclosporine A plus low-dose steroid treatment in COVID-19 improves clinical outcomes in patients with moderate to severe disease: A pilot study.

BACKGROUND: COVID-19 pandemic causes high global morbidity and mortality and better medical treatments to reduce mortality are needed. OBJECTIVE: To determine the added benefit of cyclosporine A (CsA), to low-dose steroid treatment, in patients with COVID-19. METHODS: Open-label, non randomized pilot study of patients with confirmed infection of SARS-CoV-2 hospitalized from April to May 2020 at a single centre in Puebla, Mexico. Patients were assigned to receive either steroids or CsA plus steroids. Pneumonia severity was assessed by clinical, laboratory, and lung tomography. The death rate was evaluated at 28 days. RESULTS: A total of 209 adult patients were studied, 105 received CsA plus steroids (age 55.3 ± 13.3; 69% men), and 104 steroids alone (age 54.06 ± 13.8; 61% men). All patients received clarithromycin, enoxaparin and methylprednisolone or prednisone up to 10 days. Patient's death was associated with hypertension (RR = 3.5) and diabetes (RR = 2.3). Mortality was 22 and 35% for CsA and control groups (P = 0.02), respectively, for all patients, and 24 and 48.5% for patients with moderate to severe disease (P = 0.001). Higher cumulative clinical improvement was seen for the CsA group (Nelson Aalen curve, P = 0.001, log-rank test) in moderate to severe patients. The Cox proportional hazard analysis showed the highest HR improvement value of 2.15 (1.39-3.34, 95%CI, P = 0.0005) for CsA treatment in moderate to severe patients, and HR = 1.95 (1.35-2.83, 95%CI, P = 0.0003) for all patients. CONCLUSION: CsA used as an adjuvant to steroid treatment for COVID-19 patients showed to improve outcomes and reduce mortality, mainly in those with moderate to severe disease. Further investigation through controlled clinical trials is warranted.

Prolonged breastfeeding and delayed introduction of whole cow's milk into the diet are factors associated with egg sensitization: A matched case-control study.

BACKGROUND: Both breastfeeding and the moment at which introduction to solid food occurs have been associated with food allergy. OBJECTIVE: To evaluate whether prolonged breastfeeding and the delayed introduction of whole cow's milk into an infant's diet are factors that can be associated with egg sensitization. METHODS: This was a hospital-based case-control study, matched by age and sex: each study group comprised 97 atopic children. Additionally, logistic regression was used to identify the factors associated with egg protein sensitization. RESULTS: The most common type of allergic disease among both groups was allergic rhinitis. After adjusting for possible confounding variables, a delayed introduction to whole cow's milk decreased the odds of egg protein sensitization; OR=0.16 (95% CI: 0.07-0.36, p<0.0001). Notably, breastfeeding during the first six months of life, regardless of whether it was the only milk an infant drank, increased the risk for sensitization to chicken eggs; OR=5.54 (95% CI: 2.41-12.7, p<0.0001). CONCLUSION: Prolonged breastfeeding, regardless of whether it was the only milk an infant drank, greatly increased the risk of egg sensitization. Interestingly, a delayed introduction to whole cow's milk was associated with a reduced possibility of becoming sensitized to eggs. Further studies are required to elucidate these findings.

Prevalence of oral allergy syndrome in children with allergic diseases.

INTRODUCTION: The oral allergy syndrome (OAS) is a particular type of food allergy rarely explored in the paediatric population that is already considered an adult problem. OBJECTIVE: Identify the prevalence of OAS, symptoms and pollen species associated with its presence in children affected by allergic diseases. METHODS: A cross-sectional study was conducted. Consecutive sampling included children from 6 to 14 years who needed allergy treatment for the first time. A structured questionnaire was carried out to collect demographic and clinical data and history of OAS. Besides sensitisation to various allergens, the skin prick-by-prick test was performed to corroborate sensitisation to food related to OAS. Prevalence of OAS and its association with pollens was established following the covariate adjusted logistic regression. RESULTS: 267 subjects were included. Overall prevalence of OAS was 8.9% (95%CI 6.1-13.1%). Prevalence of OAS for allergic rhinitis and asthma were 8.8% and 9.1%, respectively. In patients sensitised to pollen, the prevalence ranged from 9.6% to 12.2% depending on the type of pollen. 62.5% of children with OAS were sensitive to pineapple. After adjusting for gender and family history of atopic disease, trees from the Quercus species showed an association with OAS (OR=2.7, 95%CI 1.2-6.2). CONCLUSIONS: OAS is not uncommon in our environment. Pineapple, a typical fruit from the region, was the main food related. Quercus sp., but not birch nor olive, was the pollen associated with this syndrome.

Prevalence and factors associated to peanut allergy in Mexican school children.

BACKGROUND: In our country, the prevalence and the factors associated to peanut allergy are unknown, a health problem that has been emerging worldwide. OBJECTIVE: To establish the prevalence and the factors that are associated to peanut allergy amongst school children. METHODS: This is a population-based cross-sectional study. We included 756 children aged 6-7 years. The children's parents were questioned about their peanut intake habits. A structured questionnaire was applied, it included questions regarding peanut intake; family and personal history of asthma; rhinitis; and atopic dermatitis. Allergic reactions to peanuts were registered as: probable, convincing and systematic. The statistical analyses included logistical regression models to look for associated factors. RESULTS: Males were 356/756 (47.1%). Peanut allergy prevalence: probable reaction: 14/756 (1.8%), convincing reaction: 8/756 (1.1%) and systemic reaction: 3/756 (0.4%). Through multivariate analysis, the presence of symptoms of allergic rhinitis (OR=4.2 95% CI 1.3-13.2) and atopic dermatitis (OR=5.2; 95% CI 1.4-19.5) during the previous year, showed significant association to probable peanut reaction. The former year, the presence of atopic dermatitis was the only variable that was substantially associated to a convincing reaction (OR=7.5; 95% CI 1.4-38.4) and to a systematic reaction (OR=45.1; 95% CI 4.0-510.0), respectively. CONCLUSIONS: The reported prevalence of peanut allergy was consistent with that found in previous studies; symptoms of allergic rhinitis and atopic dermatitis were identified as associated factors to peanut allergy.

[Virulence genes and bacteriocins in Enterococcus faecalis strains isolated from different clinical samples in Maule Region, Chile]. / Genes de virulencia y bacteriocinas en cepas de Enterococcus faecalis aisladas desde diferentes muestras clínicas en la Región del Maule, Chile.

The presence of virulence genes (VG) and bacteriocins from different clinical samples was studied in Enterococcus faecalis isolated from urinary tract infections (UTI), bacteremia and endodontitis and was correlated with haemolysin and gelatinase activity. We evaluated the presence of VG by PCR in 150 strains of E. faecalis including cylA, aggA, efaA, eep, gelE, esp, as-48, bac31, entL50A/B, entA, entP, entB, enlA andentl071. Haemolysin and gelatinase activity was studied. gelE and cylA genes expressed hemolysin and gelatinase, respectively. This activity was observed in some strains of bacteremia, UTI and endodontitis. The highest number of VG was detected in bacteremic strains, being aggA and entA genes the most frequent. efaA, esp, entA, entL50A/B were associated with their clinical origin (p < 0.05). The most common genetic profile was aggA-eep-enlA-entL50A/B. E. faecalis from UTI, bacteremia and endodontitis presented different gene combinations. Some of the genes studied were related to their clinical origin. The results obtained in this study are similar to those reported in other countries.

The percentage of CD39+ monocytes is higher in pregnant COVID-19+ patients than in nonpregnant COVID-19+ patients.

Current medical guidelines consider pregnant women with COVID-19 to be a high-risk group. Since physiological gestation downregulates the immunological response to maintain "maternal-fetal tolerance", SARS-CoV-2 infection may constitute a potentially threatening condition to both the mother and the fetus. To establish the immune profile in pregnant COVID-19+ patients, a cross-sectional study was conducted. Pregnant women with COVID-19 (P-COVID-19+; n = 15) were analyzed and compared with nonpregnant women with COVID-19 (NP-COVID-19+; n = 15) or those with physiological pregnancy (P-COVID-19-; n = 13). Serological cytokine and chemokine concentrations, leucocyte immunophenotypes, and mononuclear leucocyte responses to polyclonal stimuli were analyzed in all groups. Higher concentrations of serological TNF-α, IL-6, MIP1b and IL-4 were observed within the P-COVID-19+ group, while cytokines and chemokines secreted by peripheral leucocytes in response to LPS, IL-6 or PMA-ionomicin were similar among the groups. Immunophenotype analysis showed a lower percentage of HLA-DR+ monocytes in P-COVID-19+ than in P-COVID-19- and a higher percentage of CD39+ monocytes in P-COVID-19+ than in NP-COVID-19+. After whole blood polyclonal stimulation, similar percentages of T cells and TNF+ monocytes between groups were observed. Our results suggest that P-COVID-19+ elicits a strong inflammatory response similar to NP-COVID19+ but also displays an anti-inflammatory response that controls the ATP/adenosine balance and prevents hyperinflammatory damage in COVID-19.

Incidence of the major Brassica pests in northwestern Spain.

Kale (Brassica oleracea L. acephala group) crops are common in northwestern Spain, where they are severely damaged by different insect pests. The damage notably affects the value of this crop because it is freshly consumed and fresh processed. The objective of this work was to determine the abundance and relative importance of the main Lepidoptera pests of Brassica crops for 6 yr at five localities in northwestern Spain and to relate the seasonal changes of larval populations and environmental conditions. Pheromone traps were used as a method of monitoring adults. Larval populations were monitored on kales by counting the larvae for several years and locations at different sample dates. Five species were found: Mamestra brassicae (L.); imported cabbageworm, Pieris rapae (L.); Pieris brassicae (L.); diamondback moth, Plutella xyllostella (L.); and Autographa gamma L. Proportions of each insect fluctuated over the years and in the different locations. M. brassicae was the most abundant (48.5% of the total of Lepidoptera species) followed by P. xyllostella (25%) and P. rapae (15%). The use of pheromone traps combined with plant sampling permitted the detection of two generations of M. brassicae. However, adult counts were not correlated to the number of larvae on plants.

Induction of apoptosis by diethylstilbestrol in hormone-insensitive prostate cancer cells.

BACKGROUND: Diethylstillbestrol (DES) and diethylstilbestrol diphosphate (DESdP) are effective agents for the treatment of advanced prostate cancers. Tumor-inhibiting effects of DES and DESdP are presumed secondary to suppression of androgen production in vivo. Little is known, however, about the direct cellular mechanisms of the tumor inhibition. Estrogens have been reported not only to stimulate growth but also to disrupt microtubule formation in prostate cancer cells. PURPOSE: The study was designed to examine and compare mechanisms of in vitro growth inhibition of DES and DESdP in human androgen-insensitive prostate cancer cells (DU145, 1-LN, and PC-3) and human androgen-sensitive prostate cancer cells (LNCaP) and to examine estrogen receptor modulation of such effects. METHODS: The cytotoxic effects of DES and DESdP were examined in vitro by use of a standard microculture tetrazolium assay to quantitate numbers of viable cells. Immunofluorescence microscopy, DNA fragmentation analysis, and fluorescence flow cytometry were used to investigate microtubules, the induction of apoptosis, and changes in cell cycle distribution. The degree of estrogen receptor positivity of untreated and treated cells was determined by immunohistochemistry and quantitative image analysis. RESULTS: LD50 levels (the dose at which 50% of cells are no longer viable) in the concentration range of 19-25 microM were observed for both DES and DESdP in all cell lines examined. DESdP-induced growth inhibition was found to be dependent on heat-labile phosphatases present in fetal calf serum. DES-induced cytotoxicity was not affected by the presence of 17 beta-estradiol, and it was not dependent on the presence of estrogen receptor. Estrogen receptor-positive cells and estrogen receptor-negative cells were equally responsive to DES. PC-3 cells stained with fluorescent anti-tubulin, phalloidin (actin stain), and 4',6-diamidino-2-phenylindole (DNA stain) showed no inhibition of microtubules or actin filaments but revealed the presence of apoptotic bodies in the nuclei. Fluorescence flow cytometry of nuclear DNA content of propidium iodide-stained nuclei from androgen-insensitive prostate cancer cells treated with 15 or 30 microM DES or DESdP revealed an increase in relative numbers of hypodiploid (apoptotic) nuclei, a depletion of G1- and S-phase cells, and an accumulation of cells in G2/M phase. Conversely, androgen-sensitive cells contained a lower percentage of hypodiploid nuclei but no accumulation of cells in G2/M phase. CONCLUSIONS: Direct cytotoxic effects of DES in prostate cancer cells are estrogen receptor independent and do not involve disruption of microtubule architecture but do involve the promotion of cell cycle arrest and apoptosis. These are the first data confirming direct cytotoxic effects of DES and DESdP in prostate cancer cells via an apoptotic mechanism. IMPLICATIONS. These results suggest that DES and DESdP have potential value as agents against androgen-insensitive prostate neoplasms through induction of an apoptotic cascade.

Suppression of a a carcinogen (1,2-dimethylhydrazine dihydrochloride)-induced increase in mitotic activity in the colonic crypts of rats by addition of dietary cellulose.

Serial injections of the colon carcinogen, 1,2-dimethylhydrazine (DMH), have been reported to increase the proliferative activity in the colonic crypts preceding development of tumors. Can addition of purified cellulose to a fiber-free AIN-76 rat diet be used to suppress this increase in proliferative activity? To answer this question rats were divided into two groups, and one group was given eight weekly injections of the DMH base at 9.5 mg/kg of body weight. Throughout this period and for 2 additional wk the rats were isocalorically fed a defined nutritionally complete diet both with and without different dietary levels of cellulose (0, 5, and 15%). The rats were given injections of colchicine 3 h prior to sacrifice to arrest and to collect dividing cells at metaphase. Analysis of variance was performed on various morphometric parameters obtained from histological sections of midaxial crypts from the descending colon. Our results confirm that DMH induced a significant increase in the mitotic activity as measured by the number of metaphase figures per crypt. The presence of dietary cellulose did cause a significant suppression of the DMH-induced increase in the crypt mitotic activity.

Vasopressin levels and pediatric head trauma.

The syndrome of inappropriate secretion of antidiuretic hormone is associated with head trauma; however, there are no reports concerning vasopressin levels in pediatric patients with head trauma. Urine vasopressin in eight children (mean +/- SEM, age 7.5 +/- 1.6 years, range 1 to 15 years) was measured by radioimmunoassay during their hospitalization for head trauma. Urine vasopressin values for ten healthy children (mean age 5.4 +/- 1.3 years) and for eight children hospitalized for systemic antibiotic treatment of infections (age 5.9 +/- 1.8 years) also were obtained. Urine vasopressin, urine and serum sodium concentration and osmolality, urea nitrogen, creatinine, and fluid intake were measured within 24 hours of admission and daily for the following two days. For the first three days following head trauma, mean urine vasopressin levels in pediatric patients with head trauma were increased (P less than .05) compared with those of healthy children. Despite fluid restriction to 85% of maintenance level, 25% of patients with head trauma exhibited the clinical syndrome of inappropriate secretion of antidiuretic hormone (hyponatremia, increased urinary sodium, diminished serum osmolality, and urine osmolality greater than serum osmolality). Urine osmolality greater than 800 mosm/kg was associated with markedly increased urine vasopressin levels (200 to 1,650 pg/mL); children with this finding may be at particular risk for the syndrome of inappropriate secretion of anti-diuretic hormone without restrictive water intake.

The effect of transport on the rate of severe intraventricular hemorrhage in very low birth weight infants.

OBJECTIVE: To determine the incidence of grade III or IV intraventricular hemorrhage in very low birth weight (VLBW) infants born at level I hospitals and transported to one tertiary center compared with those delivered at the same level III facility. METHODS: We evaluated all newborns admitted to a large tertiary neonatal intensive care unit from June 1, 1992, through December 31, 1995. All live born infants with birth weights of 500-1200 g and at least 24 weeks' gestation were included. Neonatal transports within 24 hours of delivery from 11 level I facilities were compared with those delivered at the same level III center with respect to grade III and IV intraventricular hemorrhage. Various antenatal and neonatal data were collected. RESULTS: Thirty-seven newborns (11%) experienced grade III or IV intraventricular hemorrhages among 329 who met study criteria. There were 27 cases (9%) in the 285 inborn neonates compared with 10 of 44 outborn cases (23%) (P < .02, 95% confidence interval 0.15, 0.87). The mean gestational age of the neonates with grade III or IV intraventricular hemorrhages was significantly lower in the inborn group, which further emphasizes the finding. No other study factors explained the difference. CONCLUSION: We found a higher risk for grade III or IV intraventricular hemorrhage developing in VLBW infants born at level I hospitals and transported to the tertiary care center compared with those born at the level III facility. This data should be considered when analyzing the potential effects of perinatal deregionalization.

Altered expression of oligopeptide-binding protein (OppA) and aminoglycoside resistance in laboratory and clinical Escherichia coli strains.

Oligopeptide-binding protein (OppA) is the periplasmic component of the major oligopeptide transport system of enteric bacteria. Genetic and biochemical evidence suggests that OppA plays a role in the uptake of aminoglycoside antibiotics in Escherichia coli K-12. Forty-six (82%) of 56 aminoglycoside-resistant mutants of E. coli K-12 selected in vitro had reduced or undetectable OppA levels, as compared with their parent strain. Moreover, nine (36%) of 25 aminoglycoside-resistant clinical isolates of E. coli expressed reduced or undetectable levels of OppA. No decrease in OppA expression was observed among aminoglycoside-sensitive E. coli strains from patients. Twenty-three (42%) of 56 aminoglycoside-resistant mutants of E. coli K-12 and six (24%) of 25 clinical isolates also were deficient for expression of ornithine or arginine decarboxylases, or both, and these deficiencies might negatively affect OppA expression by reducing polyamine synthesis. These results support the view that reduced OppA expression is associated with aminoglycoside resistance in E. coli strains.

1-dehydro-melengestrol acetate inhibits the growth and protein kinase C activity of androgen-independent Dunning rat prostatic tumors.

Androgen-independent Dunning R3327-AT3 rat prostate tumors are considered an appropriate model of advanced prostate cancer in humans. We recently reported that the progestational steroid melengestrol acetate (MGA) inhibited growth of these tumors on oral administration but also induced a marked involution of adrenals and androgen target organs (prostate, seminal vesicles, and testes). We report herein that the 1-dehydro derivative of melengestrol acetate (dMGA) fed to rats for 21 days also inhibited the growth of Dunning AT3 tumors by approximately 55% without causing a significant regression of adrenals or androgen-dependent tissues. Thus, tumor-growth inhibition was induced by dMGA in the absence of glucocorticoid activity. Cytosolic AT3 tumor fractions obtained by diethylaminoethyl (DEAE)-Sephacel batch chromatography were assayed for lipid- and Ca(2+)-dependent (PKC) and -independent protein kinase activities. Prostatic cytosols had equivalent activity levels of both types of kinases (approximately 2 nmol gamma-[32P]-adenosine 5'-triphosphate (ATP) incorporated mg protein-1 min-1. The PKC activity recovered from the cytosol of untreated AT3 tumors was approximately 4 times higher. Oral administration of dMGA reduced this activity by > 95%. The relationship between protein-kinase activity levels and dMGA-induced growth inhibition of androgen-independent tumors in this animal model is discussed.

Androgenic suppression of mouse hepatic FAD-containing monooxygenase activity.

Sex-related differences in the activity of hepatic FAD-containing monooxygenase (FAD-M) were found in C3H/St mice. Adult female mice had enzyme activities nearly two-fold greater than male mice and these differences, which were absent in sexually immature mice, became apparent at the onset of puberty. The sex differences in hepatic FAD-M appeared to be mediated through the suppressive effect of testosterone; castration of male mice enhanced enzyme activity, while androgenic replacement returned activities to control levels. Testosterone's suppressive effect was found to be relatively specific for hepatic FAD-M. Treatment of castrated male mice with both the anti-androgen flutamide and testosterone returned enzyme activity to control levels, suggesting that testosterone's regulation of hepatic microsomal FAD-M is receptor-mediated. Female gonadectomy had no effect on this enzyme's activity.

Home care: maintaining quality of life for patient and family.

Cancer affects the family as well as the patient. The home is a primary site of care, which often must be intensive and complex. Attention to home care of the cancer patient is therefore a major concern in maintaining quality of life for both patient and family. The authors explore the major burdens of home care that affect both patient and family and describe four specific interventions that the health care team can initiate to optimize quality of life in these difficult situations.

Psychological aspects of nutrition and cancer.

Cancer and the various treatments employed to combat this disease have an impact on food intake that is psychologic in nature. These psychologic consequences include behavioral responses such as learned food aversions, changes in food preferences, and anticipatory nausea and vomiting. In a second cluster of psychologic consequences are the emotional responses of anxiety and depression. A third type of psychologic consequence is perceptual in nature and is most commonly represented by changes in palatability of foods. A fourth psychologic aspect of food intake and cancer includes attitudinal responses, wherein social, religious, cultural, and other values related to food may change as a consequence of the disease. Studies are needed in this area. Approaches to nutritional care that address the psychologic impact of cancer are described. As a means of maintaining adequate nutritional status, artificial feeding routes may create psychologic problems. In general, cancer and its treatment can exert a negative impact on quality of life. Finally, the ethics of feeding are discussed in terms of care giving versus alimentation.

Gastrointestinal side effects and quality of life in patients receiving radiation therapy.

A sample of 101 patients from four radiation oncology clinics participated in a study to describe the relative impact of gastrointestinal side effects of radiation therapy on the psychological and physical well-being dimensions of quality of life. Stepwise regression analysis showed that 44.2% of the variance in psychological well-being was accounted for by patient-reported gastrointestinal problems (21.5%), tension-anxiety (11.8%), other side effects of radiation (5.4%), and satisfaction with care (5.5%). A similar analysis revealed that 50.7% of the variance in physical well-being was accounted for by patient-reported fatigue (35.5%), gastrointestinal problems (8.8%), other side effects (4%), and willingness to comply (2.4%). Although treatment dose and field size directly impact on the severity of side effects, these results suggest that it is the perception of side effects as problems that impacts on psychological and physical well-being.

Subjective distresses of nasogastric tube feeding.

Health care professionals assume that tube feeding is an unpleasant, distressing experience for patients, which is only partially substantiated by experience. Thirty patients were interviewed via a tube feeding and hospital experience checklist (a 47-item interview schedule). Common experiences were operationally defined as those felt by at least 50%; subjectively distressful experiences were those identified by patients as causing distress. The most common and most distressful experiences of nasogastric tube feeding were: sensory irritations and sensory deprivation. The psychosensory irritation experiences were: thirst, sore nose or throat, dry mouth, runny nose, a tube in the nose, taking food through a tube, breathing through the mouth, breathing with a tube in the nose, taking food in a treatment type container, and taking food with a different texture and smell than usual. The psychosensory deprivation experiences were: an unsatisfied appetite for certain foods, deprivation of tasting, chewing, swallowing food, and drinking liquids, limited mobility, and deprivation of regular food. Except for burping, gastrointestinal symptoms were not common though they were usually distressful. This information has been used to develop teaching programs which are being tested for effectiveness in reducing distress associated with nasogastric tube feeding.

Isolation and characterization of a novel human bladder cancer cell line: BK10.

Molecular studies of bladder carcinomas have aided in determining causative genetic events and the prognosis of cancers endowed with certain abnormalities. In vitro bladder cancer characterization of key cytogenetic alterations is useful for study of molecular changes that may promote oncogenic events. In our laboratory, a novel human bladder cancer cell line, BK10, has been established in vitro and passaged for more than 20 mo. This new bladder cancer cell line (BK10) was derived from bladder tissue containing grade III-IV/IV transitional cell carcinoma. Bladder cancer tissue was obtained at the time of radical cystoprostatectomy extirpation. Cell cultures derived from this surgical sample exhibited an epithelial morphology and expressed epithelial cytokeratins. Immunostains of BK10 were negative for prostate specific antigen (PSA), fibronectin, smooth muscle actin alpha, and desmin. Karyotypic analysis revealed an aneuploid chromosomal content <4n> with many numerical and structural abnormalities previously linked to bladder oncogenesis. Translocations occurred in chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 14, 15, 16, 17, 19, 20, 21, 22, X and Y. G-banding analysis revealed rearrangements involving chromosomes 9q and 17p, and the location of the ab11 oncogene and the p53 gene, respectively. The availability of this bladder cancer cell line will provide a useful tool for the further study of bladder carcinoma oncogenesis and gene therapy.