bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of capnography for recognition of esophageal intubation in the neonatal intensive care unit
Authors: Roberts William A. , Maniscalco William M. , Cohen A. Ross , Litman Ronald S. , Chhibber Ashwani
Published: March 2007

Failure to recognize esophageal intubation can result in severe hypoxia and permanent neurologic injury. Capnography is a standard monitoring modality in the operating room but has not been utilized fully in other environments. We used capnography at the time of endotracheal intubation in the neonatal intensive care unit (NICU) to determine whether capnography could more quickly and accurately identify endotracheal tube position than other clinical indicators of endotracheal tube position. One hundred intubation episodes were studied in 55 neonates. Capnograms were obtained 15 and 120 sec following tube placement. Intubating personnel were blinded to the capnographic data and determined endotracheal tube location (trachea vs. esophagus) by clinical criteria only. The sensitivity and specificity of capnography and clinical examination for identification of tube position were analyzed, and the time required for establishing by clinical confirmation whether the tube was in the trachea or not was compared to that required for capnography. Forty of 100 intubation attempts resulted in esophageal intubation. Capnography correctly identified these errant tube placements in 39 of 40 instances and did so in 1.6 sec (SD ± 2.4). Capnography failed to identify successful endotracheal intubation on only one occasion. Clinical indicators of tube position required 97.1 sec (SD ± 92.6) to identify an esophageal intubation and failed to identify successful endotracheal intubation in 5 of 60 cases. We conclude that capnography is a valuable adjunct to clinical examination to demonstrate whether an endotracheal tube is placed correctly in the trachea of neonates in the NICU. © 1995 Wiley‐Liss, Inc.
Does continuous positive airway pressure (CPAP) during weaning from intermittent mandatory ventilation in very low birth weight infants have risks or benefits? A controlled trial
Authors: Tapia José L. , Bancalari Aldo , González Alvaro , Mercado Maria E.
Published: March 2007

Objective: The purpose of this study was to evaluate three ventilator weaning strategies and to evaluate whether the use of continuous positive airway pressure (CPAP) via a nasopharyngeal or endotracheal tube would increase the likelihood of extubation failure in very low birth weight (VLBW) infants. Study design: We studied prospectively 87 preterm infants (mean ± SD; birth weight: 1078 ± 188 g; gestational age: 28.8 ± 2.2 weeks) who were in the process of being weaned from intermittent mandatory ventilation (IMV). Infants were assigned by systematic sampling to one of the following three treatment groups: (1) direct extubation from IMV (D.EXT) (n = 30); (2) preextubation endotracheal CPAP (ET‐CPAP) for 12–24 hr (n = 28); or (3) postextubation nasopharyngeal CPAP (NP‐CPAP) for 12–24 hr (n = 29). Failure was defined as the need for resumption of mechanical ventilation within 72 hr of extubation due to frequent or severe apnea and/or respiratory failure (pH < 7.25, PaCO2 > 60 mm Hg, and/or requirement for oxygen FiO2 > 60%). Results: There were no significant differences in failure rates among the three procedures. Failures were 2/30 (7%) in D.EXT; 4/28 (14%) in ET‐CPAP; and 7/29 (24%) in the NP‐CPAP. There were also no differences in FiO2, PaO2, and respiratory rates before and after discontinuation of IMV among the three groups. PaCO2 values were slightly higher in the NP‐CPAP group 12–24 hr after weaning from IMV. Conclusion: We were unable to demonstrate a clear difference in extubation outcome by use of CPAP administered via an endotracheal or nasopharyngeal tube when compared to direct extubation from low‐rate IMV in VLBW infants. © 1995 Wiley‐Liss, Inc.
Tracheal stenting improves airway mechanics in infants with tracheobronchomalacia
Authors: Zinman R.
Published: March 2007

The compliance and expiratory resistance of the tracheobronchial tree is increased in infants with tracheobronchomalacia because of a weakness in cartilaginous support of the airway. Life threatening episodes may occur in these patients due to airway collapse. The goals of this study were to compare the effects on respiratory system mechanics of stenting the airway with either continuous positive airway pressue (CPAP) or a long tracheostomy tube. Five infants were studied: two had bronchopulmonary dysplasia (BPD), 2 had associated congenital anomalies, and one had tracheomalacia and polydactyly; none had a tracheoesophageal fistula. All patients required tracheostomy and were treated with CPAP. Lung mechanics were evaluated by measuring transpulmonary pressure, obtained by subtracting airway opening pressure from pleural pressure measured with an esophageal balloon, and flow measured with a pneumotachometer placed in series with the tracheostomy. Dynamic compliance (Cdyn) and total respiratory system resistance (Rt) were calculated by two‐factor, least‐mean‐squares analysis, solving for the equation of motion of the lung with the PeDS® system (MAS, Hatfield). In all subjects Cdyn increased and R, decreased with increasing CPAP. In 4 subjects the airway was stented with a specially designed, long tracheostomy tube which reached to just above the carina; the special tube improved dynamic mechanics sufficiently to permit the discontinuation of CPAP. Speech was improved by fenestrating the tube and the use of a one‐way inspiratory valve, placed over the tracheostomy. Inspiration occurred via the tracheostomy and expiration was directed to the larynx. © 1995 Wiley‐Liss, Inc.
Dose‐response to inhaled nitric oxide in acute hypoxemic respiratory failure of newborn infants: A preliminary report
Authors: Bührer C. , Merker G. , Falke K. , Versmold H. , Obladen M.
Published: March 2007

In acute hypoxemic respiratory failure of term and near‐term neonates, extra‐ and intrapulmonary right‐to‐left shunting contribute to refractory hypoxemia. Inhaled nitric oxide (NO) decreases pulmonary arterial pressure and improves ventilation–hperfusion mismatch in a variety of animal models and selected human patients. We report on 10 consecutive term and near–term newborns with severe acute hypoxemic respiratory failure due to diaphragmatic hernia, meconium aspiration syndrome, group B streptococcus sepsis, pneumonia or acute respiratory distress syndrome, who received increasing doses of inhaled NO (up to 80 ppm) to improve the arterial partial pressure of oxygen (PaO2). The response to NO and the optimum NO concentration which improved PaO2 varied considerably between patients. Improvement of PaO2 was absent or poor (less than 10 mm Hg) in the 4 newborns with meconium aspiration syndrome and in 1 patient with congenital diaphragmatic hernia, while in the other 5 patients inhaled NO increased the mean (± SE) PaO2 from 41 ± 6 to 57 ± 9 mm Hg (P < 0.05). Optimum NO concentrations determined by dose‐response measurements performed during the first 8 hr of NO inhalation were 8–16 ppm except for 2 newborns with congenital diaphragmatic hernia who required 32 ppm to effectively increase PaO2. Four of the 5 patients in whom the PaO2 rose by more than 10 mm Hg received inhaled NO for extended periods of time (5 to 23 days) with no signs of tachyphylaxis. The optimum NO concentration dropped to less than 3 ppm after prolonged mechanical ventilation or when intravenous prostacyclin was given concomitantly. The response to inhaled NO and the optimum NO concentration to improve arterial oxygenation were virtually identical with conventional and high frequency oscillatory ventilation (HFO). We conclude that the optimal concentration of NO to improve PaO2 of neonates with acute hypoxemic respiratory failure varies considerably between patients, shows temporal variations, and requires individual and repeated adjustments of the concentration of inhaled NO. © 1995 Wiley‐Liss, Inc.
The single breath test in neonates: Does pressurization of the pneumotachograph make a difference?
Authors: Coates Allan L. , Fletcher Margaret E. , Dundas Isobel , Stocks Janet
Published: March 2007

The single breath test for the measurement of respiratory system resistance and compliance in newborns consists of an end inspiratory occlusion which is subsequently released, allowing expiration to proceed through a pneumotachograph (PNT). The measured flow is then integrated to give volume. The simplicity of the test is one of the major reasons for its popularity. However, some investigators have cautioned against the use of an occlusion distal to the PNT because pressurization of the PNT may introduce artifacts in the flow measurement. Despite this caution, many commercial systems use a pressurized PNT. This study investigated the errors that would result from pressurization of the PNT by providing a step function of flow to two infant PNTs, a Fleisch #0 and a Hans Rudolph 4500, in the unpressurized and pressurized state. In each case there was an initial rapid rise of the flow signal, followed by some overshoot and oscillations that rapidly died out. The overshoot and oscillations for the Hans Rudolph PNT were greater when pressurized whereas pressurization had little effect on the Fleisch PNT. Unpressurized, the two were similar. In either case, the artifact introduced by pressurization of the PNT died out so quickly that it would have little effect on any measurement in an infant. © 1995 Wiley‐Liss, Inc.
A cotton rat model of effectors of immunity to respiratory syncytial virus other than serum antibody
Authors: Piazza Franco M. , Schmidt H. Joel , Johnson Susan A. , Dotson Don L. , Darnell Miriam E. R. , Ottolini Martin G. , Porter David D. , Prince Gregory A.
Published: March 2007

A model for studying effectors of immunity to respiratory syncytial virus (RSV) was developed. Pairs of inbred cotton rats (Sigmodon hispidus) were joined surgically using the technique of parabiosis. One week later, one animal of each pair was primed intranasally with small volume of RSV suspension. Fourteen days after priming, both animals of each pair were bled for determination of serum neutralizing antibody titers, and challenged intranasally with standard dose of RSV suspension. Single, unprimed cotton rats were challenged concomitantly and served as controls. Four days after challenge, all animals were sacrificed for virus titration of nasal tissues and lungs. Parabiosed cotton rats were surgically separated at varying intervals between priming and challenge (days 7, 9, 12, or 14 after priming) or were kept joined until sacrificed (day 18). Significant transfer of nasal and pulmonary immunity from primed to unprimed parabionts began 9 days after priming, gradually increasing through 18 days. Resistance to RSV challenge in spite of low levels of serum neutralizing antibody suggests that non‐antibody immunologic mediators were responsible for the transferred immunity. Evidence is presented for three broad categories of RSV immunologic effectors: systemic, local with transient systemic phase, and local without systemic phase. These categories are now amenable to further study using the described model. © 1995 Wiley‐Liss, Inc.
Characteristics of near‐fatal asthma in childhood
Authors: Martin A. J. , Campbell D. A. , Gluyas P. A. , Coates J. R. , Ruffin R. E. , Roder D. M. , Latimer K. M. , Luke C. G. , Frith P. A. , Yellowlees P. M. , McLennan G.
Published: March 2007

As part of the South Australian asthma mortality survey, we examined 30 cases of near‐fatal asthma attacks in children under 15 years of age who were seen over a 3‐year period from May 1988 to June 1991. Subjects presented with asthma and either respiratory arrest, PaCO2, above 50 mm Hg, and/or an altered state of consciousness or inability to speak on presentation at a metropolitan Adelaide teaching hospital. A standardized interview and questionnaire was completed with subjects/parents and medical practitioners. Data were reviewed by the assessment panel which made collective judgments based on predetermined criteria. Seventeen patients (57%) were male, 20% were less than 7 years of age, and the majority (53%) were aged between 12 and 15 years. The majority (83%) had severe asthma and only one case (3.3%) had mild asthma. Half of the subjects were waking every night due to asthma and 79% had significant exercise limitation. A quarter of the subjects had a previous ICU admission and 70% had a hospital admission in the last 12 months. Primary care was carried out by a general practitioner in 57% of cases, and 70% of subjects had a crisis plan. Only 46% of those older than 7 years of age had ever used a peak‐flow meter. Eighty percent of subjects or their families had high denial scores, and in 73% of cases psychosocial factors were considered to be significant. Eighty percent of cases experienced acute progressive respiratory distress, and 63% of cases delayed seeking medical care. The episode was judged as preventable in 83% of cases. This study suggests that most pediatric cases of near‐fatal asthma have severe asthma, significant denial, psychosocial pathology, and delay in seeking care, all of which contribute to the near‐fatal nature of these episodes. Pediatr Pulmonol, 1995; 20:1–;8 © 1995 Wiley‐Liss, Inc.
The effects of hyperoxia, mechanical ventilation, and dexamethasone on pulmonary antioxidant enzyme activity in the newborn piglet
Authors: Davis Jonathan M. , Robbins Carolyn G. , Anderson Tarek , Sahgal Namita , Genen Linda , Tierney Joan , Horowitz Stuart
Published: March 2007

It has been previously shown that prophylactic, intravenous dexamethasone (DEX) and intratracheal recombinant human Cu/Zn superoxide dismutase (SOD) ameliorate lung injury in newborn piglets treated with 48 hr of hyperoxia and mechanical ventilation. DEX has many pharmacologic effects, including the possible induction of antioxidant enzyme systems. To investigate whether the effects of DEX are mediated by an increase in endogenous antioxidant enzyme activity, 5 groups of term newborn piglets were studied: Group 1 piglets were ventilated with room air for 48 hr; Group 2 animals were ventilated with 100% O2, for 48 hr; Group 3 animals were ventilated with room air for 48 hr and received DEX (0.7 mg/kg) every 12 h; Group 4 were ventilated with 100% O2, for 48 hr and also received DEX; Group 5 animals were not ventilated and were sacrificed at time 0. At the conclusion of the studies, bronchoalveolar lavage (BAL) was performed and the lungs were removed and homogenized. Lung tissue and BAL were analyzed for SOD, catalase, GPX activities, and total protein concentration. No significant differences in any of these assays were seen in either lung tissue or BAL in the 5 groups. These observations indicate that 48 hr of hyperoxia, mechanical ventilation, or dexamethasone treatment does not induce activity of SOD, catalase, or glutathione peroxidase (GPX) in the lungs of newborn piglets. Thus postnatal DEX appears to minimize neonatal lung injury by mechanisms that are independent of these enzymes. Pediatr Pulmonol. 1995; 20:107–111. © 1995 Wiley‐Liss, Inc.
Bronchoalveolar lavage studies in children without parenchymal lung disease: Cellular constituents and protein levels
Authors: Midulla Fabio , Villani Alberto , Merolla Rocco , Bjermer Lief , Sandstrom Thomas , Ronchetti Roberto
Published: March 2007

We evaluated bronchoalveolar lavage fluid (BAL) for cellular constituents, concentration of total protein (TP), albumin (AL), fibronectin (FN), and hyaluronic acid (HA) in 16 children aged 2‐32 months without pulmonary inflammatory or parenchymal disease to establish reference values. We compared our data to those reported in older children and in normal adult volunteers. BAL results were obtained simultaneously from the right middle lobe and the lingula. Results indicated that children younger than 3 years of age had a higher number of cells/mL than older children and adults (59.9 × 104 vs. 17.6 × 104 and 12 × 104). Differential cell count revealed that the percentages of alveolar macrophages (AM), lymphocytes (LYM), and eosinophils (EOS) were similar to those obtained in older children and in adults, whereas the percentage of neutrophils (NEU) was higher in younger children (NEU 5.5 vs 1.6 and 1.2%, respectively) than in older children and adults. The latter difference was even greater in infants under 12 months of age (NEU 7.6%). The concentrations of TP, AL, FN, and HA in children's BAL samples were compared to values reported for adults. There were no differences between infants and children 13–32 months of age or normal adults. BAL fluid obtained simultaneously from the middle lobe and lingula were not significantly different. In conclusion, this is the first report on BAL values (cellular and noncellular constituents) in children younger than 3 years. The results may be used as reference values for further studies in children with parenchymal lung disease in this age group. Pediatr Pulmonol. 1995; 20:112–118. © 1995 Wiley‐Liss, Inc.
Glutathione metabolism in newborns: Evidence for glutathione deficiency in plasma, bronchoalveolar lavage fluid, and lymphocytes in prematures
Authors: Jain Ajey , Mehta Taral , Auld Peter A. M. , Rodrigues Jose , Ward Robert F. , Schwartz Morton K. , Mårtensson Johannes
Published: March 2007

Respiratory distress in premature newborns is associated with deficiency of surfactant in the bronchoalveolar lining fluid; this may be influenced by a local deficiency of antioxidants. Severe L‐buthionine‐S, R‐sulfoximine‐induced depletion of glutathione (GSH, a major antioxidant) in rodents is associated with lung type 2 cell lamellar body damage and decreased concentrations in lung and bronchoalveolar lavage fluid (BALF) of phosphatidyl choline (a major component of surfactant). At birth, prematurely born newborns (30–34 weeks) had lower peripheral venous plasma GSH concentrations than term (>36 weeks) babies; these levels decreased further with increasing prematurity (>27 weeks, with respiratory distress). On day 2, the peripheral venous plasma GSH concentrations reached a nadir, and the lowest levels were found in the most premature newborns. Lymphocyte GSH concentrations were lowest on day 2 and day 7, and in prematures (< 27 weeks, with respiratory distress) remained below adult lymphocyte GSH levels for at least 4 weeks. At birth, prematures (<27 weeks, with respiratory distress) had a central plasma arterio‐venous (A‐V) GSH gradient across the lung (an estimate of lung uptake of GSH) of 0.72±0.15 (mean ± SD) μ‐mol/L; on day 2, the A‐V gradient did not change significantly (0.49 ± 0.09 μmol/L). At birth, these prematures had markedly decreased BALF GSH concentrations (compared with adult levels), and they were not significantly changed during the first 4 weeks of life. These results suggest that GSH deficiency is present in prematures and that it increases with the degree of prematurity. At birth, GSH deficiency will compromise the lungs' defense against oxidative stress injury. Oxidative stress is likely to increase if hyperoxic treatment is given for respiratory distress in these infants. Pediatr Pulmonol. 1995; 20:160–166. © 1995 Wiley‐Liss, Inc.
Prediction of maximum voluntary ventilation (MVV) in African‐American adolescent girls
Authors: Fulton Janet E. , Pivarnik James M. , Taylor Wendell C. , Snider Sharon A. , Tate Amanda L. , Frankowski Ralph F.
Published: March 2007

The purposes of the present study were to: (1) develop original equations to predict maximum voluntary ventilation (MVV) in African‐American adolescent girls; and (2) determine the validity of existing MVV prediction equations for use in African‐American subjects by comparing predicted MVV values in the literature with actual MVV values obtained in this study. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and 12 second MVV were measured with a clinical respirometer (Spirometrics model 2451) in 93 African‐American adolescent girls (13.5 ± 1.0 years). Age (r = 0.29). height (r = 0.38), FEV1 (r = 0.52), and FVC (r = 0.48) were significantly (P < 0.01) correlated with MVV. Multiple regression analysis was used to develop equations to predict MVV with age, height, and FEV1 as predictor variables. Using Mallow's Cp criterion, age‐FEV1 and FEV1, equations appeared to be the most accurate predictors of MVV. When MVV was regressed on FEV1, in a no‐intercept model, the result was the commonly cited equation MVV = 35.0 × FEV1. Thus, the previously established relationship between FEV1 and MVV can be extended to African‐American adolescent girls. Comparison of predicted MVV values calculated from other published equations with our subjects' actual values indicated that equations using age and/or height as predictors did not accurately predict MVV in our subjects. Pediatr Pulmonol. 1995; 20:225–233. © 1995 Wiley‐Liss, Inc.
Postnatal rat lung retinoic acid receptor (RAR) mRNA expression and effects of dexamethasone on RAR β mRNA
Authors: Grummer Mary A. , Zachman Richard D.
Published: March 2007

Retinoids exert multiple effects upon lung differentiation and growth. Although the mechanisms involved are presently poorly understood, increasing evidence points to a central role of nuclear retinoic acid receptors (RAR). The purpose of this study was to determine RAR mRNA expression profile during postnatal alveolarization, compared with the expression in prenatal and adult rat lung, and to describe the effects of dexamethasone (DEX) and oxygen on postnatal lung RAR gene expression. Total RNA was isolated from lungs of Sprague‐Dawley rats on prenatal day 19, on postnatal days 1,3,7,10, and 14 of life, and from adults. One subgroup of littermate pups was treated with DEX daily for 3 or 7 days. In a second experiment, rats were exposed to room air or to 95% oxygen for 72 hours, and received either DEX or saline. Northern hybridization showed that the levels of all RAR subtypes in fetal lung were 45% or less of levels at postnatal day 1. The 3.7 kb RAR a transcript levels were lower than day 1 on days 10 and 14 (relative to day 1, day 10 = 0.54 ± 0.05; day 14 = 0.54 ± 0.08), but there was no change in a 2.7 kb RAR α transcript over this time period. By contrast, RAR βmRNA levels were significantly higher at days 3,10, and 14 compared with day 1 (day 3 = 1.79 ± 0.19; day 10 = 1.41 ± 0.14; day 14 = 1.53 ± 0.05). Similarly, RAR γ mRNA expresison levels were higher on day 10 (1.45 ± 0.09), but by day 14 there was no difference from day 1. Adult lung 3.7 kb RAR α, 2.7 kb RAR α, and RAR γ were lower than day 1, but RAR β was significantly greater (3.7 α = 0.52 ± 0.05; 2.7 α = 0.49 ± 0.26; γ = 0.74 2 ± 0.06; β = 1.63 ± 0.22). Treatment with DEX prevented the rise in RAR ß mRNA occurring on day 3 and significantly lowered (0.65 ± 0.06) the amount of RAR β mRNA in day 7 lung. Exposure of rat pups to oxygen caused an increase in RAR β mRNA (1.21 ± 0.03). DEX treatment again decreased RAR β mRNA in both control (0.55 ± 0.06) and oxygen‐exposed pups (0.67 ± 0.12). In addition, 2.7 kb RAR α mRNA was decreased with the combination of DEX and oxygen exposure (0.63 ± 0.06). The differential gene expression profiles and the response to DEX and oxygen of the various members of the RAR family suggest that each subtype may have a specific role during the period of alveolarization in rat lung. Pediatr Pulmonol. 1995; 20:234–240. © 1995 Wiley‐Liss, Inc.
Pulmonary vascular disorders masquerading as interstitial lung disease
Authors: Sondheimer Henry M. , Lung M. Colleen Lum , Brugman Susan M. , Iklé David N. , Fan Leland L. , White Carl W.
Published: March 2007

During the acquisition of a series of 92 children with interstitial lung disease (ILD) over a 14 year period, a significant minority (8/92 or 9%) were initially diagnosed as having ILD, but were subsequently found to have a variety of arterial, venous, and/or capillary disorders that explained their initial pulmonary findings. This subgroup of patients has had a very high morbidity and mortality, with only three of eight patients currently surviving. The presentation, evaluation, and natural history of these eight children were reviewed. We developed a strategy of cardiac and pulmonary evaluation for children presenting with clinical and radiographic features of ILD that helped us to identify rapidly those with pulmonary vascular disorders. Pediatr Pulmonol. 1995; 20:284–288. © 1995 Wiley‐Liss, Inc.
Diagnosis of Mycoplasma pneumoniae pneumonia in pediatric patients by polymerase chain reaction (PCR)
Authors: Buck George E. , Eid Nemr S.
Published: March 2007

Polymerase chain reaction (PCR) testing was performed on respiratory tract specimens obtained by throat swab in 21 children admitted to the hospital with suspected Mycoplasrna pneurnoniae pneumonia. Of 13 patients with a clinical condition compatible with mycoplasma infection and an immunological response to M. pneurnoniae, 11 were positive by PCR. Eight patients were negative by serology and/or had a clinical condition not compatible with mycoplasma infection, and all were negative by PCR. The antibody response to M. pneurnoniae was delayed for a week or more in 3 (23%) of the 13 patients with documented mycoplasma infection. These results suggest that PCR performed on a respiratory tract specimen obtained by a throat swab may be useful in the initial evaluation of children with suspected M. pneurnoniae pneumonia, especially in patients in whom the serological response is delayed. Pediatr Pulmonol. 1995; 20:297–300. © 1995 Wiley‐Liss, Inc.
Frequency and number of neuroendocrine tumor cells in prostate cancer: No difference between radical prostatectomy specimens from patients with and without neoadjuvant hormonal therapy
Authors: Shimizu Shinichiro , Kumagai Jiro , Eishi Yoshinobu , Uehara Toshitaka , Kawakami Satoru , Takizawa Touichiro , Koike Morio
Published: March 2007

BACKGROUND

Neuroendocrine tumor cells in prostate cancer are thought to increase after hormonal therapy due to neuroendocrine differentiation of tumor cells. This assumption is based on the histological analyses of limited portions of the cancerous lesions examined.

METHODS

Radical prostatectomy specimens were obtained from 122 consecutive patients with prostate adenocarcinoma, 70 of whom underwent prostatectomy alone (Group A) and 52 with neoadjuvant hormonal therapy (Group B). Sections from all the 5‐mm‐thick slices from formalin‐fixed specimens were immunostained for chromogranin‐A, and the total number of choromogranin‐A‐positive neuroendocrine tumor cells were counted.

RESULTS

No difference was found between Groups A and B in the frequency of cancer with neuroendocrine cells. The total number of neuroendocrine cells in cancer varied widely with no difference of median values in the two groups.

CONCLUSIONS

These results do not support the assumption that hormonal therapy induces neuroendocrine differentiation, but suggest androgen‐independent neuroendocrine cells existed before therapy. Prostate 67: 645–652, 2007. © 2007 Wiley‐Liss, Inc.
Non‐invasive bioluminescent detection of prostate cancer growth and metastasis in a bigenic transgenic mouse model
Authors: Hsieh Chia‐Ling , Xie Zhihui , Yu Jie , Martin W. David , Datta Milton W. , Wu Guang‐Jer , Chung Leland W.K.
Published: March 2007

BACKGROUND

We previously established a bioluminescent transgenic mouse model, sPSA‐Luc, with luciferase gene expression restricted to the prostate under the control of the supra prostate‐specific antigen (sPSA) promoter. We now assess the feasibility of generating bigenic mice, TRAMP‐Luc, with the sPSA‐Luc as the founder strain crossbred with TRAMP (transgenic adenocarcinoma mouse prostate) mice, to evaluate non‐invasively the metastatic potential of prostate tumors.

METHODS

TRAMP‐Luc mice were obtained as [C57BL/6 TRAMP × FVB sPSA‐Luc] F1 offspring. Tumor development in 10 TRAMP‐Luc males was followed by bioluminescence imaging from 8 to 24 weeks of age. Immunohistochemical (IHC) staining for T antigen (Tg), androgen receptor (AR), luciferase and/or pathological analysis verified the tumor distribution in the imaged tissues including prostate gland, lymph node and bone.

RESULTS

Group I animals that presented with no grossly visible tumors showed prostate‐confined bioluminescence with slightly increased signal intensity with age. Group II animals that developed large tumors displayed a widely distributed and biphasic bioluminescence pattern. The peak was reached between 10 and 14 weeks of age, then markedly decreased or even disappeared beyond week 16, except for one mouse that showed an increased bioluminescence signal at the jaw bone and hind limbs at week 22. These tumors were shown by IHC to contain Tg but lost AR and luciferase beyond week 16 in poorly differentiated prostate tumors.

CONCLUSION

A direct correlation between bioluminescence emission and AR expression was found in TRAMP‐Luc tumor progression model. This model allows non‐invasive imaging of prostate cancer metastases to bone and soft tissues. Prostate 67: 685–691, 2007. © 2007 Wiley‐Liss, Inc.
DNA copy number alterations in prostate cancers: A combined analysis of published CGH studies
Authors: Sun Jishan , Liu Wennuan , Adams Tamara S. , Sun Jielin , Li Xingnan , Turner Aubrey R. , Chang Baoli , Kim Jin Woo , Zheng Siqun Lilly , Isaacs William B. , Xu Jianfeng
Published: March 2007

BACKGROUND

Identifying genomic regions that are commonly deleted or gained in neoplastic cells is an important approach to identify tumor suppressor genes and oncogenes. Studies in the last two decades have identified a number of common DNA copy number alterations in prostate cancer. However, because of various sample sizes, diverse tumor types and sources, as well as a variety of detection methods with various sensitivities and resolutions, it is difficult to summarize and fully interpret the overall results.

METHODS

We performed a combined analysis of all published comparative genomic hybridization (CGH) studies of prostate cancer and estimated the frequency of alterations across the genome for all tumors, as well as in advanced and localized tumors separately. A total of 41 studies examining 872 cancers were included in this study.

RESULTS

The frequency of deletions and gains were estimated in all tumors, as well as in advanced and localized tumors. Eight deleted and five gained regions were found in more than 10% of the prostate tumors. An additional six regions were commonly deleted and seven were commonly gained in advanced tumors. While 8p was the most common location of deletion, occurring in about a third of all tumors and about half of advanced tumors, 8q was the most commonly gained region, affecting about a quarter of all tumors and about half of all advanced tumors.

CONCLUSIONS

The large number of tumors examined in this combined analysis provides better estimates of the frequency of specific alterations in the prostate cancer cell genome, and offers important clues for prioritizing efforts to identify tumor suppressor genes and oncogenes in these altered regions. Prostate 67: 692–700, 2007. © 2007 Wiley‐Liss, Inc.
IRL‐1620, a tumor selective vasodilator, augments the uptake and efficacy of chemotherapeutic agents in prostate tumor rats
Authors: Rajeshkumar N.V. , Matwyshyn George , Gulati Anil
Published: March 2007

BACKGROUND

IRL‐1620, a potent endothelin B receptor agonist, enhanced the efficacy of paclitaxel in a breast tumor model, but its effect in prostate cancer is not known. The present study was conducted to evaluate the effect of IRL‐1620 on tumor perfusion, uptake of [14C]‐doxorubicin in the tumor and efficacy of doxorubicin (DOX), and 5‐flurouracil (5‐FU) in a rat prostate tumor model.

METHODS

JHU‐4 (Mat‐Lu) cells inoculated prostate tumor model in Copenhagen rats was used for the study.

RESULTS

Administration of IRL‐1620 (3 nmol/kg, i.v) significantly increased (102.8%) prostate tumor perfusion and tumor uptake of [14C]‐doxorubicin (115%) compared to vehicle treated rats. Results of the efficacy study demonstrate that IRL‐1620 administration 15 min prior to DOX (5 mg/kg) or 5‐FU (50 mg/kg) on every third day for a total of four doses significantly reduced tumor volume compared to vehicle treated rats.

CONCLUSIONS

IRL‐1620 significantly enhanced the uptake and efficacy of anticancer agents in prostate cancer. Prostate 67: 701–713, 2007. © 2007 Wiley‐Liss, Inc.
Sonic and desert hedgehog signaling in human fetal prostate development
Authors: Zhu Guodong , Zhau Haiyen E. , He Hui , Zhang Linlin , Shehata Bahig , Wang Xinyang , Cerwinka Wolfgang H. , Elmore James , He Dalin
Published: March 2007

Background

Hedgehog signaling is thought to play an important role in rodent prostate organogenesis and morphogenesis. However, the role of this signaling pathway in human fetal prostate development has not been investigated.

Methods

Twenty‐five human fetal prostates at various developmental stages (10–39 weeks) were included. Fifteen specimens were processed for H&E and immunohistochemical staining of the Hedgehog signaling components: Sonic Hedgehog (SHH), Desert Hedgehog (DHH), Patched‐1(PTC1), Patched‐2 (PTC2), Smoothened (SMO), GLI1, and proliferating cell nuclear antigen (PCNA). SHH, DHH, and GLI1 expression was also analyzed in ten snap‐frozen specimens by Western blot.

Results

SHH, DHH, SMO, PTC1, GLI1, and PCNA expression, assessed by a semi‐quantitative immunohistochemical method, was found mainly in the developing prostatic epithelial ducts, beginning at 10 weeks and peaking at 16 and 28 weeks with a dip occurring at 20 weeks, with the exception of PTC2.

Conclusion

Both SHH and DHH signaling components were detected during human fetal prostate development. Despite the high expression of PTC2 in the epithelium as well as the stroma in the early time of development, the expression of SHH, DHH, SMO, PTC1, and a SHH/DHH target transcription factor, GLI‐1, were all largely restricted to epithelium in the developing prostate, suggesting that SHH/DHH signaling is primarily through an autocrine mechanism in human fetal prostate organogenesis. Prostate 67: 674–684, 2007. © 2007 Wiley‐Liss, Inc.
Phloem mobility of xenobiotics. V. Structural requirements for phloem‐systemic pesticides
Authors: Kleier Daniel A.
Published: March 2007

Remote and relatively inaccessible parts of plants such as roots and meristematic tissue can readily be reached by foliar‐applied xenobiotics if the latter are capable of entering into and moving in the phloem Development of a passivetransport model provides a description of the time course of this movement and its dependence upon the physical properties of the chemical and the condition of the plant vascular system. The model so developed is used to formulate principles for rendering otherwise non‐systemic xenobiotics phloem‐mobile. These principles can be categorized according to the nature of the chemical modifications that facilitate phloem translocation. These modifications include (a) sugar conjugation, (b) acid functionalization, and (c) formation of quaternary salts from basic parents. The potential of these modifications to facilitate the phloem translocation of wide range of pesticides is discussed.
Correlation analysis for longitudinal data: applications to HIV and psychosocial research
Authors: Tu X. M. , Feng C. , Kowalski J. , Tang W. , Wang H. , Wan C. , Ma Y.
Published: March 2007

Correlation analysis is widely used in biomedical and psychosocial research for assessing rater reliability, precision of diagnosis and accuracy of proxy outcomes. The popularity of longitudinal study designs has propelled the proliferation in recent years of new methods for longitudinal and other multi‐level clustered data designs, such as the mixed‐effect models and generalized estimating equations. Despite these advances, research and methodological development on addressing missing data for correlation analysis is woefully lacking. In this paper, we consider non‐parametric inference for the product–moment correlation within a longitudinal data setting and address missing data under both the missing completely at random and missing at random assumptions. We illustrate the approach with real study data in mental health and HIV prevention research. Copyright © 2007 John Wiley & Sons, Ltd.
Immunoisolating Pancreatic Islets by Encapsulation with Selective Withdrawal
Authors: Wyman Jason L. , Kizilel Seda , Skarbek Ryan , Zhao Xiangyang , Connors Matthew , Dillmore William S. , Murphy William L. , Mrksich Milan , Nagel Sidney R. , Garfinkel Marc R.
Published: March 2007

This manuscript reports the application of the selective‐withdrawal coating technique to the microencapsulation of insulin‐producing pancreatic islets within thin poly(ethylene glycol) coatings. These polymer coatings permit the islets to respond to changes in glucose concentration by producing insulin with a dose‐response profile that is substantially similar to that of unencapsulated islets. Furthermore, the hydrogel capsules exclude the large molecules of the immune system. These results suggest that the microencapsulation technique—which combines droplet formation from a flow of two immiscible fluids with polymerization chemistries—has the characteristics required for the transplantation of islets for the treatment of Type I diabetes.
Temperature‐, pH‐, and Magnetic‐Field‐Sensitive Hybrid Microgels
Authors: Bhattacharya Sanchita , Eckert Franziska , Boyko Volodymyr , Pich Andrij
Published: March 2007

We demonstrate a simple route for the preparation of novel hybrid particles with multiple sensitivities. Aqueous polymeric microgels are modified by magnetite nanoparticles in the preparation of temperature‐ and pH‐sensitive hybrids with a high magnetic response. Up to 15 wt % of magnetite nanoparticles are loaded into microgels. The influence of the amount of magnetite in the microgel structure on the morphology and colloidal properties is discussed. The presence of the magnetite nanoparticles in the microgel decreases its degree of swelling and shifts the volume phase‐transition temperature to higher values. Nanostructured composite films with controlled morphologies can be prepared by water evaporation and deposition of the hybrid microgels on a solid substrate.
Amino Starches as pH‐Sensitive Coatings: Synthesis and Application
Authors: Bohrisch Jörg , Zimmermann Arvid
Published: March 2007

The aim of this work was to carry out a systematic investigation of the preparation conditions of starch materials with pH‐dependent solubility. Furthermore, appropriate conditions for application of those materials as surface coatings should be established. Thus, samples of starch derivatives with tertiary amino substituents were synthesised and characterised by 1H‐NMR spectroscopy and pH‐turbidimetry. Variation of both kind and molar mass of the used starch substrate and the nature and degree of substitution of the amino component led to two materials containing diisopropylamino groups with the desired properties in a single‐ or two‐component coating. Using a commercial fluidised‐bed coating procedure spherules of a waxy surfactant were coated with different modified starches. The stabilities of the shells were examined under dishwasher‐like conditions and monitored by tensiometry.
Geographical variation in frond size, rootstock density, and sexual reproduction inMatteuccia struthiopterispopulations in Norway
Authors: Odland Arvid
Published: March 2007

The main aim of this study was to quantify differences in the structure of denseMatteuccia struthiopteris(L) Todaro among geographically separated populations in Norway, and to relate these differences to variation in environmental variables. A stratified random sampling procedure was applied to select 4 m2quadrats restricted to populations dominated (>75% cover) by the fern. This dimorphic fern can produce three types of leaves (fronds): fertile (sporophyll) and sterile (trophophyll), and in addition also intermediate fronds. In all, 178 populations from different parts of the country were analysed, and in total 9,346 rootstocks were measured. Fifteen percent of the rootstocks were fertile, each producing from one to eight sporophylls, and 2.0% had developed intermediate fronds. Rootstocks with five or more sporophylls were mainly found in Southern Norway. Within the plots, there were major variations in density (10–112), number of small (new) ramets (0–58), total number of sporophylls (0–94) and estimated total fern wet‐weight (0.33–22.8 kg). All new additions to the populations were connected to a mother plant (ramets), and none were of sexual origin (genets). The main environmental variables associated with the variation in population structure were mean July temperature (highly correlated with altitude and latitude), mean precipitation and density of the canopy cover. The density of small ramets and number of intermediate fronds increased from south to north. The latitudinal variation in sporophyll development and maximum trophophyll height was best explained by a unimodal model. There were statistically significant differences in the population structure between the eight studied geographic areas in Norway.
Recent advances in newborn screening
Authors: Wilcken B.
Published: March 2007

The introduction of tandem mass spectrometry has unquestionably been the most striking recent advance in newborn screening. A single test is applied for the simultaneous diagnosis of a number of disorders, making it possible to screen for some disorders that might otherwise have seemed too rare. Current screening is for disorders of metabolism of amino acids, organic acids and fatty acids. Assay performance for detection of disorders appears very good, but rarity of disorders, varied definitions and systems for follow‐up and lack of databases for inborn errors of metabolism diagnosed clinically means that there is as yet insufficient information about most disorders. The technology can be applied to a much wider range of compounds, and the field looks set to expand. A key feature of newborn screening programmes must be the assessment of outcomes, and a major reason for the lack of uniformity in the approach adopted in different countries is the paucity of information on this. The available evidence points to overall advantages flowing from early diagnosis by screening, with reduction in mortality and morbidity. More studies are clearly needed and some are under way. The next new group of disorders already proposed for newborn screening is the lysosomal storage disorders. Attitudes may be changing about what it is desirable to include in a newborn screening programme, and this will indeed pose new ethical dilemmas.
PKCζII is a target for degradation through the tumour suppressor protein pVHL
Authors: Iturrioz Xavier , Parker Peter J.
Published: March 2007

PKCζII is a rapidly degraded variant of PKCζ that suppresses epithelial cell polarisation. It is shown here that PKCζII is a target for the E3 ligase and tumour suppressor Von Hippel‐Lindau protein (pVHL). Deletion studies demonstrate that the C‐terminal region is required for the pVHL and proteasome dependent turnover of PKCζII, however it is the N‐terminal PB1 domain of PKCζII that is required for pVHL complex formation. Reciprocal deletion studies define the pVHL effector domain as the dominant PKCζII binding site. The results indicate that pVHL recruits PKCζII via its PB1 domain and causes ubiquitination and degradation via the distal C‐terminus of PKCζII.
The role of Asp‐295 in the catalytic mechanism of Leuconostoc mesenteroides sucrose phosphorylase probed with site‐directed mutagenesis
Authors: Mueller Mario , Nidetzky Bernd
Published: March 2007

Replacements of Asp‐295 by Asn (D295N) and Glu (D295E) decreased the catalytic center activity of Leuconostoc mesenteroides sucrose phosphorylase to about 0.01% of the wild‐type level (k
cat
= 200 s−1). Glucosylation and deglucosylation steps of D295N were affected uniformly, ∼104.3‐fold, and independently of leaving group ability and nucleophilic reactivity of the substrate, respectively. pH dependences of the catalytic steps were similar for D295N and wild‐type. The 105‐fold preference of the wild‐type for glucosyl transfer compared with mannosyl transfer from phosphate to fructose was lost in D295N and D295E. Selective disruption of catalysis to glucosyl but not mannosyl transfer in the two mutants suggests that the side chain of Asp‐295, through a strong hydrogen bond with the equatorial sugar 2‐hydroxyl, stabilizes the transition states flanking the β‐glucosyl enzyme intermediate by ⩾23 kJ/mol.
Predominantly buried residues in the response regulator Spo0F influence specific sensor kinase recognition
Authors: McLaughlin Patrick D. , Bobay Benjamin G. , Regel Erin J. , Thompson Richele J. , Hoch James A. , Cavanagh John
Published: March 2007

Several alanine mutations in the response regulator Spo0F induce hypersporulation in Bacillus subtilis. L66A, I90A and H101A mutants are purported to be involved in contacts stabilizing the orientation of the α4‐helix and hence the β4–α4 kinase recognition loop. Y13A is thought to affect the orientation of the α1‐helix and consequently phosphatase action. Using comparative NMR chemical shift analyses for these mutants, we have confirmed these suppositions and isolated residues in Spo0F critical in sensor kinases discrimination. In addition, we discuss how buried residues and intra‐protein communication networks contribute to precise molecular recognition by ensuring that the correct surface is presented.
Plastid division coordination across a double‐membraned structure
Authors: Maple Jodi , Møller Simon Geir
Published: March 2007

Chloroplasts still retain components of the bacterial cell division machinery and research over the past decade has led to an understanding of how these stromal division proteins assemble and function as a complex chloroplast division machinery. However, during evolution plant chloroplasts have acquired a number of cytosolic division proteins, indicating that unlike the cyanobacterial ancestors of plastids, chloroplast division in higher plants require a second division machinery located on the chloroplast outer envelope membrane. Here we review the current understanding of the stromal and cytosolic plastid division machineries and speculate how two protein machineries coordinate their activities across a double‐membraned structure.
Putting the clamps on membrane fusion: How complexin sets the stage for calcium‐mediated exocytosis
Authors: Melia Thomas J.
Published: March 2007

Three recent papers have addressed a long‐standing question in exocytosis: how does a sudden calcium influx trigger a coordinated synchronous release in regulated exocytosis [Giraudo, C.G., Eng, W.S., Melia, T.J. and Rothman, J.E. (2006) A clamping mechanism involved in SNARE‐dependent exocytosis. Science 313, 676–680; Schaub, J.R., Lu, X., Doneske, B., Shin, Y.K. and McNew, J.A. (2006) Hemifusion arrest by complexin is relieved by Ca2+–synaptotagmin I. Nat. Struct. Mol. Biol. 13, 748–750; Tang, J., Maximov, A., Shin, O.H., Dai, H., Rizo, J. and Sudhof, T.C. (2006) A complexin/synaptotagmin 1 switch controls fast synaptic vesicle exocytosis. Cell 126, 1175–1187]? Using diverse approaches that include cell‐free reconstitution of the membrane fusion machinery and in vivo manipulation of fusogenic proteins, these groups have established that the complexin proteins are fusion clamps. By arresting vesicle secretion just prior to fusion, complexin primes select vesicles for a fast, synchronous response to calcium.
POVERTY AND CITIZENSHIP: AN OVERVIEW OF THE SOCIAL-POLICY ENVIRONMENT IN REPUBLICAN TURKEY
Authors: Bugra Ayse
Published: March 2007

Social policy constitutes an area that clearly reflects the nature of state–society relations and the content of citizenship in a given country. The present article develops this idea by situating the analysis of the Turkish modernization experience in a historical overview of perspectives on poverty and social policy in the republican period.