Timing of oral feeding changes in premature infants who underwent osteopathic manipulative treatment.

BACKGROUND: The delayed transition from gavage-to-nipple feeding is one of the most significant factors that may prolong hospital length of stay (LOS). Osteopathic manipulative treatment (OMT) has been demonstrated to be effective regarding LOS reduction, but no investigations have documented its clinical validity for attaining oral feeding. OBJECTIVES: To assess OMT utility regarding the timing of oral feeding in healthy preterm infants. DESIGN: Preliminary propensity score-matched retrospective cohort study. SETTING: Data were extrapolated from the neonatal intensive care unit (NICU) of Del Ponte Hospital in Varese, Italy, during the period between March 2012 and December 2013. INTERVENTIONS: Two propensity score-matched groups of healthy preterm infants aged 28+0 to 33+6 were compared, observing those supported with OMT until hospital discharge and control subjects. MAIN OUTCOME MEASURES: Days from birth to the attainment of oral feeding was the primary endpoint. Body weight, body length, head circumference and LOS were considered as secondary endpoints. RESULTS: Seventy premature infants were included in the study as the control group (n = 35; body weight (BW) = 1457.9 ± 316.2 g; gestational age (GA) = 31.5 ± 1.73 wk) and the osteopathic group (n = 35; BW = 1509.6 ± 250.8 g; GA = 31.8 ± 1.64 wk). The two groups had analogous characteristics at study entry. In this cohort, we observed a significant reduction in TOF (-5.00 days; p = 0.042) in the osteopathic group with a greater effect in very low birth weight infants. CONCLUSIONS: These data demonstrate the utility and potential efficacy of OMT for the attainment of oral feeding. Further adequately powered clinical trials are recommended.

Osteopathic manipulative treatment in chronic coccydynia: A case series.

BACKGROUND: Coccydynia is a disorder associated with pain/discomfort at the base of the spine. The role of osteopathic manipulative treatment (OMT) in chronic coccydynia as well as for low back pain (LBP) and radicular pain (RP) associated with coccydynia, has not previously been investigated. This study seeks to analyse the effects of OMT on chronic coccydynia compared to physical therapy and pharmacological treatment (PTPT). The secondary objective is to analyse the effect of OMT on LBP and RP associated with coccydynia. METHODS: Clinical records of 50 patients were examined. These patients (aged 39.94 ± 15.34 years, BMI 21.22 ± 3.15) who complained of chronic coccydynia were assessed 3 times: before any treatment (t0), after PTPT (t1) and after OMT (t2). Patients were treated with PTPT during the first 3 months and then referred by physicians to osteopaths to receive 3 sessions of OMT over a period of 5 weeks. The outcome measurements were made by a visual analogue scale (VAS 0-10 cm) and the Oswestry Low Back Pain Disability Questionnaire. RESULTS: Before starting OMT treatment, patients showed a stable condition of coccydynia (mean VAS values from 7.1 to 6.5 p = 0.065) and a slight but significant reduction in disability (mean OD values from 17.7 to 14.5 p = 0.017) after PTPT. After the 3 sessions of OMT, all subjects gained a successful reduction in pain (mean VAS values from 6.5 to 1.2, p ≤ 0.001) and demonstrated a higher significant reduction in disability (mean Oswestry scale values from 14.5 to 2.5, p < 0.001). CONCLUSIONS: This case series shows that OMT elicits a positive benefit for pain relief and reduction in disability in patients complaining of coccydynia (with or without LBP and RP associated with coccydynia). Therefore, OMT could be considered as a valid therapeutic approach for treating chronic coccydynia. Nevertheless, further research is required to test the hypothesis and to better determine the benefits of OMT.

Clinical nodal staging scores for prostate cancer: a proposal for preoperative risk assessment.

BACKGROUND: Pelvic lymph node dissection in patients undergoing radical prostatectomy for clinically localised prostate cancer is not without morbidity and its therapeutical benefit is still a matter of debate. The objective of this study was to develop a model that allows preoperative determination of the minimum number of lymph nodes needed to be removed at radical prostatectomy to ensure true nodal status. METHODS: We analysed data from 4770 patients treated with radical prostatectomy and pelvic lymph node dissection between 2000 and 2011 from eight academic centres. For external validation of our model, we used data from a cohort of 3595 patients who underwent an anatomically defined extended pelvic lymph node dissection. We estimated the sensitivity of pathological nodal staging using a beta-binomial model and developed a novel clinical (preoperative) nodal staging score (cNSS), which represents the probability that a patient has lymph node metastasis as a function of the number of examined nodes. RESULTS: In the development and validation cohorts, the probability of missing a positive lymph node decreases with increase in the number of nodes examined. A 90% cNSS can be achieved in the development and validation cohorts by examining 1-6 nodes in cT1 and 6-8 nodes in cT2 tumours. With 11 nodes examined, patients in the development and validation cohorts achieved a cNSS of 90% and 80% with cT3 tumours, respectively. CONCLUSIONS: Pelvic lymph node dissection is the only reliable technique to ensure accurate nodal staging in patients treated with radical prostatectomy for clinically localised prostate cancer. The minimum number of examined lymph nodes needed for accurate nodal staging may be predictable, being strongly dependent on prostate cancer characteristics at diagnosis.

Whole-mount in situ detection of microRNAs on Arabidopsis tissues using Zip Nucleic Acid probes.

MicroRNAs (miRNAs) affect fundamental processes of development. In plants miRNAs regulate organ development, transition to flowering, and responses to abiotic/biotic stresses. To understand the biological role of miRNAs, in addition to identifying their targeted transcripts, it is necessary to characterize the spatiotemporal regulation of their expression. Many methods have been used to define the set of organ-specific miRNAs by tissue dissection and miRNA profiling but none of them can describe their tissue and cellular distribution at the high resolution provided by in situ hybridization (ISH). This article describes the setup and optimization of a whole-mount ISH protocol to target endogenous miRNAs on intact Arabidopsis seedlings using DIG-labeled Zip Nucleic Acid (ZNA) oligonucleotide probes. Automation of the main steps of the procedure by robotized liquid handling has also been implemented in the protocol for best reproducibility of results, enabling running of ISH experiments at high throughput.

Transcriptome analysis reveals coordinated spatiotemporal regulation of hemoglobin and nitrate reductase in response to nitrate in maize roots.

Given the importance of nitrogen for plant growth and the environmental costs of intense fertilization, an understanding of the molecular mechanisms underlying the root adaptation to nitrogen fluctuations is a primary goal for the development of biotechnological tools for sustainable agriculture. This research aimed to identify the molecular factors involved in the response of maize roots to nitrate. cDNA-amplified fragment length polymorphism was exploited for comprehensive transcript profiling of maize (Zea mays) seedling roots grown with varied nitrate availabilities; 336 primer combinations were tested and 661 differentially regulated transcripts were identified. The expression of selected genes was studied in depth through quantitative real-time polymerase chain reaction and in situ hybridization. Over 50% of the genes identified responded to prolonged nitrate starvation and a few were identified as putatively involved in the early nitrate signaling mechanisms. Real-time results and in situ localization analyses demonstrated co-regulated transcriptional patterns in root epidermal cells for genes putatively involved in nitric oxide synthesis/scavenging. Our findings, in addition to strengthening already known mechanisms, revealed the existence of a new complex signaling framework in which brassinosteroids (BRI1), the module MKK2-MAPK6 and the fine regulation of nitric oxide homeostasis via the co-expression of synthetic (nitrate reductase) and scavenging (hemoglobin) components may play key functions in maize responses to nitrate.

Double-blind, placebo-controlled trial to assess the efficacy and tolerability of mepartricin in the treatment of BPH.

BACKGROUND: Mepartricin, a semisynthetic polyene derivative with a favorable effect on urethro-prostatic function, was clinically evaluated, adopting the diagnostic and research criteria recommended by the First International Consultation on BPH. METHODS: A multicenter, randomized, double-blind, parallel-group study compared mepartricin 40 mg/daily to placebo in the treatment of 196 patients with newly diagnosed BPH and mild-to-moderate symptomatology. International Prostate Symptom Score (I-PSS), quality of life (QoL) index and maximum urinary flow-rate (Qmax) were determined every 4 weeks for 6 months; postvoiding volume, prostate volume, and prostate-specific antigen (PSA) were assessed after 3 and 6 months of therapy. RESULTS: Mepartricin was shown to determine a statistically significant improvement over placebo in I-PSS and QoL index from month 2 onwards, and a significant linear increase in Qmax over the study period. At month 6, the improvement in the mepartricin and placebo groups in I-PSS, QoL index, and Qmax was 6.3 (standard error (SE) 0.51) and 4.2 (SE 0.60) points (P = 0.003), 0.99 (SE 0.14) and 0.62 (SE 0.12) points (P = 0.036), and 2.7 (SE 0.46) and 1.2 (SE 0.46) ml/sec (P = 0.051), respectively. No significant differences were noted in postvoiding residual volume, prostate volume, or PSA. Mepartricin tolerability was good, showing no adverse events on sexual function. CONCLUSIONS: Mepartricin proved to be an effective treatment of benign prostatic hyperplasia, determining an improvement in symptoms, quality of life, and peak urinary flow.

Comparative anti-gonococcal activity of S-565, a new rifamycin.

The in vitro activity of S-565, a semi-synthetic rifamycin chemically related to rifampicin but with a longer half-life, has been compared with that of rifampicin, ciprofloxacin, spectinomycin, azithromycin and amoxycillin against Neisseria gonorrhoeae. Modal MICs against 20 strains were 0.13 mg/l for rifampicin and 0.5 mg/l for S-565. There was cross-resistance between the two rifamycins, and each selected for resistance at similar rates. In a time-kill study, S-565 was more rapidly bactericidal than rifampicin at x 1 and x 2 MIC.

In-vitro activity of 3-azinomethyl-rifamycin (SPA-S-565) against Chlamydia trachomatis.

The in-vitro activity of a 3-azinomethyl-rifamycin (SPA-S-565) against Chlamydia trachomatis was compared to that of rifampicin and of erythromycin. The compound showed excellent activity for standard strains as well as isolates from patients with sexually transmitted diseases, being more active than the other drugs tested. SPA-S-565 also showed a low frequency of emergence of resistance. Passage of standard strains at sub-inhibitory concentrations caused an increase in MIC values of rifampicin while those for SPA-S-565 remained unchanged.

Evaluation of neuron-specific enolase, tissue polypeptide antigen, and carcinoembryonic antigen as markers for staging and monitoring response to therapy of lung cancer.

Serum neuron-specific enolase (NSE), tissue polypeptide antigen (TPA), and carcinoembryonic antigen (CEA) were measured in 60 patients with small-cell lung carcinoma (SCLC) and in 94 patients with advanced non-small-cell lung carcinoma (NSCLC) at diagnosis, during induction chemotherapy, and at restaging. At diagnosis, the positivity rates of NSE, TPA, and CEA were 88, 52, and 43% in SCLC, and 20, 62, and 53% in NSCLC, respectively. Serum NSE and TPA levels were significantly higher in extensive than in limited SCLC. TPA and CEA levels were significantly correlated with the extent of NSCLC. NSE and TPA were significantly concordant with the clinical response to initial combination chemotherapy, the former in SCLC, the latter in both SCLC and NSCLC. By discriminant analysis, the presentation levels of the markers were not predictive of response to induction chemotherapy, whereas changes in NSE and TPA levels after the first cycle of chemotherapy were.

Past, present and future trends in tuberculosis epidemiology in a region of northern Italy. An analysis carried out through the application of a simulation model (Eskimo).

The epidemiological model Eskimo has been utilized to simulate some epidemiological parameters relative to tuberculosis in a restricted geographical area of northern Italy. After having identified a series of features relative to the regimens applied in the area in the period 1982-86 and which were found to be compatible with the observed data, this hypothesis has been utilized to project data on tuberculosis for the period 1986-1996. The results have indicated that the incidence in the area should stabilize around values of 20 new cases per year (per 100,000 population). A decrease in the incidence can be expected to occur only if the regimens so far employed are brought to a greater part of the patients' population (increasing coverage). The effects of importing the disease from developing countries through immigration and of the AIDS epidemic are likely to negatively affect the trend of tuberculosis incidence in the future.

Eskimo: an epidemiological simulation kinetic model for tuberculosis.

A simple, easy to use, kinetic model allowing the simulation of the main epidemiological parameters of tuberculosis and of the financial costs associated with the implementation of different anti-tuberculous policies, has been developed and described. The model, which has been denominated "ESKIMO" (Epidemiological Simulation Kinetic Model) can be utilized on a personal computer and requires, for its use, the knowledge of a series of easily available census data relative to a given country or geographical area, an essential epidemiological profile of the disease in the same area and data which characterize one or more antituberculous treatments in therapeutic and financial terms. The rationale of the model, which is a multicompartemental system, derive from an analysis of the relationships (transfer rates) between sub-populations of individuals in relation to tuberculosis either when the dynamic state of the system is governed by "natural forces" (no treatment) or when an external action is applied to it with an aim to alter its internal pathways in a favourable sense (vaccination, long-term hospitalization, chemotherapy). The model is based on the assumption that the main objective of any antituberculous program is the reduction in size of the subpopulation of patients who can infect other individuals and therefore perpetuate the disease. Validation and projection tests carried out through Eskimo seem to indicate that concentrating the analysis on the effect of various treatments on this group of patients simplifies the calculations while the relative precision of the estimates of other parameters is very satisfactory. The results of several simulations substantiate and quantify the opinions expressed by several experts in the past that the policy of applying cheap regimens of low efficacy to a relatively small fraction of the patients' population, as frequently done in developing countries, not only does not alter the trend of the disease but produces essentially negative results (increase in the number of new cases and in the frequency of resistant M. tuberculosis). Treatment with highly effective regimens of the same number of patients as those treated now (constant coverage) and therefore without the extra costs resulting from the improvement of the available sanitary infrastructures, produces much better results in clinical terms and overall saving of financial resources.

Comparative bioavailability of isoniazid, rifampin, and pyrazinamide administered in free combination and in a fixed triple formulation designed for daily use in antituberculosis chemotherapy. I. Single-dose study.

A comparative bioavailability study of the antituberculosis drugs isoniazid, rifampin, and pyrazinamide was carried out in a group of 10 healthy volunteers after administration of the three compounds, once in individual association and once in a combined, fixed preparation. The investigation was designed as an open, crossover study where each subject received five tablets of a preparation containing 50 mg isoniazid, 120 mg rifampin, and 300 mg pyrazinamide (corresponding to a total dose of 250 mg isoniazid, 600 mg rifampin, and 1,500 mg pyrazinamide). The same doses were administered in the session where the drugs were combined using the individual formulations. For each subject and experimental session, 15 blood samples were collected over a period of 24 h, and the plasma concentrations of the three drugs were assessed. The results indicated the absence of negative pharmacokinetic interactions between the drugs when administered in both free and this new, fixed combination.

Comparative bioavailability of isoniazid, rifampin, and pyrazinamide administered in free combination and in a fixed triple formulation designed for daily use in antituberculosis chemotherapy. II. Two-month, daily administration study.

The time course of the plasma concentrations of isoniazid, rifampin, and pyrazinamide was assessed in a group of 13 patients with lung tuberculosis treated over a period of 2 months on a continuous daily basis with a fixed triple combination of the same drugs. The blood kinetics of the three antituberculosis drugs were determined on Days 1, 15, 30, and 60 of treatment. The triple combination employed in this study contained 50 mg isoniazid, 120 mg rifampin, and 300 mg pyrazinamide per tablet, the number of tablets ranging from four to seven per day according to the body weight of the patients. Almost superimposable plasma concentration curves for isoniazid were observed during the 4 days of the study. For rifampin, a fall in the plasma concentrations at the time intervals after the peak was observed comparing the data on Day 1 with those on Days 15, 30, and 60, which did not differ from each other. This finding is thought to be due to the well-known phenomenon of self-induction, which leads to an increased rate of disposal of the antibiotic from the blood compartment within the first and second weeks of continuous treatment. For pyrazinamide, an equilibrium in the opposite sense as that of rifampin seemed to take place within the 2 months of the study. Because of the relatively high plasma levels observed 24 h after each administration, an increase in plasma concentrations with respect to those observed on Day 1 was found on Days 15, 30, and 60, the levels on these days no differing from each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Penetration of roxithromycin in bronchial secretions.

Roxithromycin sputum and serum concentrations after administration of therapeutic doses (150 mg in a single dose) were evaluated in six patients. Blood samples and pooled sputum samples were collected at corresponding time intervals up to 24 h after drug administration. Roxithromycin sputum levels were found to be almost always above serum concentrations, the highest sputum levels being 5.85 +/- 2.5 micrograms/ml in the interval ranging from 2 to 4 h after drug administration. Due to its antibacterial spectrum and favourable pharmacokinetic properties, roxithromycin, like other macrolide antibiotics, seems to be particularly indicated in the treatment of respiratory tract infections.