Simulation-based optimisation to quantify heterogeneity of specific ventilation and perfusion in the lung by the Inspired Sinewave Test.

The degree of specific ventilatory heterogeneity (spatial unevenness of ventilation) of the lung is a useful marker of early structural lung changes which has the potential to detect early-onset disease. The Inspired Sinewave Test (IST) is an established noninvasive 'gas-distribution' type of respiratory test capable of measuring the cardiopulmonary parameters. We developed a simulation-based optimisation for the IST, with a simulation of a realistic heterogeneous lung, namely a lognormal distribution of spatial ventilation and perfusion. We tested this method in datasets from 13 anaesthetised pigs (pre and post-lung injury) and 104 human subjects (32 healthy and 72 COPD subjects). The 72 COPD subjects were classified into four COPD phenotypes based on 'GOLD' classification. This method allowed IST to identify and quantify heterogeneity of both ventilation and perfusion, permitting diagnostic distinction between health and disease states. In healthy volunteers, we show a linear relationship between the ventilatory heterogeneity versus age ([Formula: see text]). In a mechanically ventilated pig, IST ventilatory heterogeneity in noninjured and injured lungs was significantly different (p < 0.0001). Additionally, measured indices could accurately identify patients with COPD (area under the receiver operating characteristic curve is 0.76, p < 0.0001). The IST also could distinguish different phenotypes of COPD with 73% agreement with spirometry.

Tidal changes in PaO2 and their relationship to cyclical lung recruitment/derecruitment in a porcine lung injury model.

BACKGROUND: Tidal recruitment/derecruitment (R/D) of collapsed regions in lung injury has been presumed to cause respiratory oscillations in the partial pressure of arterial oxygen (PaO2). These phenomena have not yet been studied simultaneously. We examined the relationship between R/D and PaO2 oscillations by contemporaneous measurement of lung-density changes and PaO2. METHODS: Five anaesthetised pigs were studied after surfactant depletion via a saline-lavage model of R/D. The animals were ventilated with a mean fraction of inspired O2 (FiO2) of 0.7 and a tidal volume of 10 ml kg-1. Protocolised changes in pressure- and volume-controlled modes, inspiratory:expiratory ratio (I:E), and three types of breath-hold manoeuvres were undertaken. Lung collapse and PaO2 were recorded using dynamic computed tomography (dCT) and a rapid PaO2 sensor. RESULTS: During tidal ventilation, the expiratory lung collapse increased when I:E <1 [mean (standard deviation) lung collapse=15.7 (8.7)%; P<0.05], but the amplitude of respiratory PaO2 oscillations [2.2 (0.8) kPa] did not change during the respiratory cycle. The expected relationship between respiratory PaO2 oscillation amplitude and R/D was therefore not clear. Lung collapse increased during breath-hold manoeuvres at end-expiration and end-inspiration (14% vs 0.9-2.1%; P<0.0001). The mean change in PaO2 from beginning to end of breath-hold manoeuvres was significantly different with each type of breath-hold manoeuvre (P<0.0001). CONCLUSIONS: This study in a porcine model of collapse-prone lungs did not demonstrate the expected association between PaO2 oscillation amplitude and the degree of recruitment/derecruitment. The results suggest that changes in pulmonary ventilation are not the sole determinant of changes in PaO2 during mechanical ventilation in lung injury.

Ancient genetic variation in one of the world's rarest seabirds.

The Chatham Island Taiko (Tchaik, Pterodroma magentae) is one of the world's rarest seabirds. In the past there were millions of breeding pairs of Taiko and it was the most abundant burrowing petrel on Chatham Island. The present population consists of just 120-150 birds, including only 8-15 breeding pairs. Surprisingly high genetic variation was revealed by DNA sequencing of almost every known adult Taiko (N=90). Given the massive population decline, genetic variation may have been even larger in the past. Therefore, we investigated past genetic diversity by sequencing regions of the mitochondrial cytochrome b gene in 44 ancient Taiko bones. We identified a total of 12 haplotypes in Taiko. Eight haplotypes were revealed in the ancient DNA: four were unique to the bones and four corresponded to those found in the modern Taiko population. Surprisingly, despite the critically endangered status of the Taiko, no significant reduction in mitochondrial DNA haplotype diversity was observed between ancient samples (N=44) and modern adult Taiko (N=90). The modern population may have however lost four haplotypes present in the ancient populations.

Oral midazolam with an antacid may increase the speed of onset of sedation in children prior to general anaesthesia.

BACKGROUND: The aim of the study was to see whether sodium citrate solution would speed the gastric absorption of oral midazolam. METHODS: Forty presurgical ASA I and II patients (aged 2-6 years) were randomly assigned to one of two groups. Group I received midazolam 0.5 mg x kg(-1) mixed with sodium citrate while group II (control) received midazolam 0.5 mg x kg(-1) mixed with Hawaiian fruit punch. RESULTS: There was no statistical difference between the ages, weights, preoperative sedation and anxiety scores in the two groups. After premedication, the onset of sedation (mean +/- SD) measured by the first change in sedation score was found to be significantly faster (P < 0.05) in group I (17.8 +/- 7.11) compared with group II (21.9 +/- 5.34). There was no statistical difference in anxiety at any time intervals, separation or induction scoring for both groups. Gastric volumes and the pH of gastric aspirates between the two groups were not statistically significant. CONCLUSIONS: The time to onset of sedation can potentially be shortened, by using a preparation of intravenous midazolam and antacid, given orally.

Neurotrophin receptor (p75) in the trigeminal thalamus of the rat: development, response to injury, transient vibrissa-related patterning, and retrograde transport.

We report on the transient, patterned expression of p75 in the ventrobasal (VB) thalamus, the major thalamic relay for somatosensation. We immunostained the brains of developing rats ranging in age from embryonic day (E) 14.5 to postnatal day (PD) 15 with an antibody against p75. To compare p75 expression with the developing synaptic organization within VB, we also immunolocalized the synaptic-vesicle-associated protein, synaptophysin (SYN), on alternate sections. p75-immunoreactivity (IR) was dense and uniform in the ventroposterior medial nucleus (VPM) in the late embryonic and early postnatal periods (E 16.5 to PD 3). In contrast, from PD 4-10, p75-IR in the VPM was patterned, reminiscent of cytochrome-oxidase-stained barreloids, a characteristic feature of the VB in rodents. By PD 14, p75-IR in the VPM was no longer detectable. The ventroposterior lateral nucleus (VPL), in contrast, exhibited no p75-IR. No p75-IR was detected in the ventroposterior lateral nucleus (VPL) at any developmental stage in which VPM could be distinguished from VPL. Light, but clearly patterned SYN-IR, first detectable on PD 2-3, increased in intensity in both VPL and VPM through PD 15. Sectioning the infraorbital nerve on PD 0 resulted in blurred patterns of p75- and SYN-IR within VPM in PD 7-9 rat pups. Removing large portions of the somatosensory cortex on PD 0 resulted in subsequent greatly reduced p75- and SYN-IR within VB. To specify the source of the p75-IR terminals, we stereotaxically injected into the VPM of PD 4-5 rats a monoclonal antibody to p75. One to 2 days later, IR of retrogradely transported p75 antibodies could be traced within axons and cell bodies of neurons associated with the trigeminothalamic pathway through the caudal diencephalon and mesencephalon; labelling was confined to the contralateral trigeminal principal sensory nucleus. The observed, transiently patterned p75-IR in VPM the early postpartum period suggests a role for p75 in synaptogenesis and pattern formation.

Solid-phase extraction of 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid from urine drug-testing specimens with the cerex polycrom-THC column.

Confirmation of drugs of abuse by gas chromatography-mass spectrometry (GC-MS) is the most time-consuming process used by drug-testing laboratories. Cost effectiveness and competitive turnaround times for testing results demand fast, efficient, and reliable extraction methods. We applied the Cerex Polycrom-THC solid-phase extraction (SPE) column to the extraction of 11-nor-delta9-tetrahydrocannabinol carboxylic acid (9-THCA) from urine. This column uses an anion exchange divinyl-benzene copolymer, which requires no pH adjustment after hydrolysis of the THC-glucuronide with base, as is necessary with many other SPE columns. With urine, no preconditioning of the SPE column was necessary. After extraction, trimethylsilation derivatization was performed with N-methyl-N-(trimethylsilyl) trifluoroacetamide. This further improved efficiency because no heated incubation was required. A method correlation to an existing liquid-liquid extraction was performed. Analysis was on a Finnigan Voyager GC-MS with a 2.5-min run time per injection. Using 9-THCA-d9 deuterated internal standard, the assay was linear from 2 to 2000 ng/mL. Total precision at the 15-ng/mL cutoff concentration was 4.4%. The Cerex column was also evaluated for interference using two common drug-test adulterants, Klear and Urine Luck. Considerably less interference was observed when compared to an existing liquid-liquid method.

Comparison of four derivatizing reagents for 6-acetylmorphine GC-MS analysis.

The propionyl, trimethylsilyl, trifluroacetyl, and heptafluoroacyl derivatives of 6-acetylmorphine (6-AM) were evaluated with respect to optimal method performance, derivative stability, and methods characterization for use in gas chromatographic-mass spectrometric (GC-MS) analysis with electron ionization mode and selected ion monitoring. The most common potential interferences and compatibility with other derivatives when used on the same GC-MS were determined for the derivatizing reagents. The propionyl, trimethylsilyl, and trifluroacetyl derivatives produced adequate stability, accuracy, and precision for the method. The 6-AM derivatization with commercially available propionic anhydride generated a relatively small amount of 6-AM-propionyl derivative from the free morphine present in a specimen. The trimethylsilyl derivative obtained by the reaction with MSTFA did not require incubation, was the easiest to prepare, and had the highest potential for use on an automated sample-preparation device. An important advantage of derivatization with MSTFA is elimination of the possibility of heroin decomposition to 6-AM that is due to incubation at elevated temperature.

Distribution of the low-affinity neurotrophin receptor (p75) in the developing trigeminal brainstem complex in the rat.

The low-affinity neurotrophin receptor (p75) binds all members of the neurotrophin family. In the rat, during the first week postpartum, dense p75-immunoreactivity (IR) is present throughout all components of the trigeminal brainstem complex (TBC), largely associated with primary sensory afferents. Within subnucleus caudalis (SpC) of the TBC, intense p75-IR is present in all laminae at birth. During the second and third postnatal weeks, p75-IR in SpC gradually fades within the deeper laminae, becoming generally restricted in the adult to laminae I and II. Similar declines in p75-IR intensity occur in the subnucleus oralis (SpO); in the SpO in the adult, p75-IR is confined to the dorsalmost portion of SpO. In subnucleus interpolaris, an emerging, vibrissa-related pattern of p75-IR is detectable on PD0 (first 24 hr postpartum), which becomes fully differentiated during PD4-PD7. However, this pattern gradually disappears during the third postnatal week. Ventrally in the nucleus principalis (PrV), a pattern of p75-IR that mirrors the topographical arrangement of the vibrissae is detectable by PD0-PD1, is fully differentiated by the end of the first postnatal week, and persists into adulthood. Perinatal unilateral sectioning of the infraorbital nerve on PD0-PD1, but not as late as PD4, disrupts p75-IR patterning in the adult PrV. Although p75 appears to be associated with primary afferent pattern formation, to determine whether it is essential, we examined mutant mice unable to form functional p75. In the TBC of these knockout mice, examined as adults, patterns of cytochrome oxidase staining (which parallel those of p75-IR) appeared to be normal. In summary, during early development, p75 is widely expressed in the TBC during periods of active synaptogenesis and pattern formation, whereas in the adult, its expression is restricted to association with populations of primary sensory afferents. However, the absence of functional p75 in genetically altered mice does not appear to prevent primary afferent pattern formation.

Extracranial repair of pediatric traumatic cerebrospinal fluid rhinorrhea.

OBJECTIVE: To examine the methods of extracranial repair of traumatic defects in the cribriform plate and ethmoid roof resulting in persistent cerebrospinal fluid (CSF) rhinorrhea in pediatric patients. DESIGN: Retrospective case series. SETTING: A single-institution, tertiary care, pediatric hospital. PATIENTS: Four children, ranging in age from 3 1/2 to 9 years, who sustained fractures in the cribriform plate or ethmoid roof. INTERVENTION: Transnasal endoscopic repair in 4 patients, with 2 patients also undergoing external ethmoidectomy because of the large bony defect and the need for further exposure for repair. MAIN OUTCOME MEASURES: Time free from CSF leaks or recurrence, meningitis, and other postoperative complications. RESULTS: All patients except 1 have been free of recurrent CSF leaks, meningitis, and other postoperative complications. The 3 patients who solely underwent the extracranial approach did not experience the complications of the traditional intracranial approach. CONCLUSIONS: In a select group of pediatric patients, the extracranial approach for the repair of CSF leaks is appropriate. Successful use of an extracranial approach in 3 of 4 patients supports this method.

Twelve hours of gastric ventilation: a recipe for disaster (a suggested remedy).

A forty-three-day-old infant was intubated by the Neonatal Intensive Care Unit (NICU) staff. A nasogastric tube was in place for the duration. The patient's vital signs remained stable during 12 h of positive pressure ventilation. A Broviac catheter placement was scheduled in the NICU. The position of the tracheal tube (TT) was not verified prior to induction of anaesthesia. After the induction, the patient's condition deteriorated. The TT was found to be positioned within the oesophagus. A near catastrophe was successfully averted by discovering the malpositioned TT and replacing it with a properly positioned TT. We believe that had we clamped the existing nasogastric tube preoperatively, a noticeable abdominal distention would have occurred alerting us to a malpositioned TT. We suggest that clamping a preexisting nasogastric tube may have merit to alert one to a malpositioned TT.

Nitrite adulteration of workplace urine drug-testing specimens. I. Sources and associated concentrations of nitrite in urine and distinction between natural sources and adulteration.

The active ingredient in the commercial workplace urine drug-testing adulterant, Klear, was previously determined to be nitrite ion. Nitrite adulteration compromises the confirmation of some drugs, notably the marijuana metabolite. A previously reported bisulfite step overcomes some nitrite adulteration, but it cannot do so in every case, which leaves the laboratory to report the specimen as not suitable for testing. Unlike many other adulterants, nitrite is found in normal urine at low concentrations. In order to defend a report of nitrite adulteration, it is necessary to provide evidence that the amount of nitrite in a workplace urine specimen could not arise by normal means. The objectives of this study were to identify all sources of nitrite in urine and the range of concentrations associated with these sources and to determine if nitrite adulteration can be supported based upon a quantitative result. The scientific literature was reviewed for internal and external sources of nitrite and their concentration ranges and are reported. The following specimens were obtained and nitrite concentrations measured by a spectrophotometric method: clinical specimens nitrite positive by test strip (< 15 micrograms/mL); specimens culture positive for nitrate-reducing microorganisms (< 36 micrograms/mL); specimens from patients on medications that may metabolize to nitrite (< 6 micrograms/mL); and drug-test specimens, both negative (< 130 micrograms/mL) and others that appeared to be adulterated with nitrite (range 1910-12,200 micrograms/mL, mean 5910). The literature and the nitrite measurements of this study indicate a substantial difference between concentrations from natural sources compared with adulteration. A quantitative measurement of nitrite by a well-structured assay can provide scientifically valid and forensically defensible proof of adulteration with a nitrite-containing substance.

The structure of posttraumatic stress symptoms.

Posttraumatic stress disorder, as defined by the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev. and 4th ed.; American Psychiatric Association, 1987, 1994, respectively), is characterized by 17 symptoms, descriptively clustered into 3 groups: (a) intrusions, (b) hyperarousal, and (c) avoidance and numbing. The present study sought to identify the basic dimensions (factors) that underlie these symptoms. Two samples were assessed: 103 victims of motor vehicle accidents and 419 United Nations peacekeepers deployed in Bosnia. A principal axis factor analysis was conducted for each sample. In each sample, 2 correlated factors were obtained, which were very similar across samples. Factor 1 was labeled Intrusions and Avoidance, and Factor 2 represented Hyperarousal and Numbing. These factors loaded on a single higher order factor. The higher order factor accounted for 13% to 38% of variance in symptom severity, and the lower order factors accounted for an additional 8% to 9% of variance. If the authors assume that each factor corresponds to a distinct mechanism (R. B. Cattell, 1978), then the results suggest that posttraumatic stress reactions arise from a general mechanism, with contributions from 2 specific mechanisms.

Analysis of organic volatile impurities as a forensic tool for the examination of bulk pharmaceuticals.

This discussion offers an overview of some formally accepted methodology in the USA for the determination of organic volatile impurities in pharmaceuticals. Particular advantages of equilibrium headspace sampling with capillary gas chromatography for this task are outlined and some important considerations are expressed. Specific adaptations which we have made for forensic applications are described along with mention of select applications within the context of the detection of the counterfeiting of bulk pharmaceuticals. Finally, a brief description is provided of statistical techniques which can be used to effectively manipulate multivariate data sets for purposes of distinguishing between the manufacturers of a product based upon impurity profiles.

Esthesioneuroblastoma in the pediatric age-group: the role of chemotherapy and autologous bone marrow transplantation.

Esthesioneuroblastoma, a malignant neoplasm arising from olfactory epithelium, is unusual in the pediatric age-group. Management has traditionally involved surgery and radiotherapy, alone or in combination, with chemotherapy reserved for recurrent or high grade disease. We report a single institution experience utilizing chemotherapy and radiotherapy as the initial treatment and successful control of the primary tumor in two patients. In one patient, neck dissection and high dose chemotherapy combined with autologous bone marrow transplantation were used as successful salvage therapy of neck metastasis. Both patients are alive and disease free with a mean follow-up of 56 months. These results support the role of chemotherapy in the treatment of esthesioneuroblastoma and suggest that chemotherapy be used as part of the initial combined modality treatment plan.

Comparison of surgical bypass and percutaneous balloon dilatation with primary stent placement in the treatment of central venous obstruction in the dialysis patient: one-year follow-up.

Central venous stenosis and occlusion are complications that are being observed with increasing frequency as a result of the use of long-term central venous catheters. These complications are especially problematic in patients with end-stage renal disease and functioning ipsilateral arteriovenous (AV) grafts or fistulas (AV grafts). We have previously demonstrated that the 1-year patency rate for simple balloon angioplasty in these patients is less than 10%. To compare the results of surgical treatment vs. percutaneous dilatation with stent placement, we undertook this retrospective study. All patients underwent multiple central venous catheter placements and had functioning ipsilateral AV grafts. Twenty-six patients were divided into two groups. The surgical treatment group included 13 patients: 10 with subclavian vein thrombosis and three with innominate vein thrombosis. All patients in the surgical group had arm swelling and edema. Surgical bypass procedures were performed in these patients using either polytetrafluoroethylene or saphenous vein. The stent group also included 13 patients; all of them had a diagnosis of subclavian or innominate vein obstruction and were treated with percutaneous transluminal angioplasty and placement of either a self-expanding rigid stent (n = 6) or a balloon-expandable flexible stent (n = 7). Two patients required multiple stent placements. No significant complications occurred in either group. The 1-year mortality rate in both groups was 31%. The percentages of patients who were symptom free at 6 and 12 months were also similar in the two groups. We conclude that surgical bypass and percutaneous transluminal angioplasty with stent placement are both efficacious in the treatment of central venous obstruction.

The effects of supraceliac aortic clamping on the anticoagulant effects of heparin.

BACKGROUND: Coagulopathy is frequently encountered during supraceliac aortic clamping. Patients are routinely heparinized during these operations. This experiment was undertaken to evaluate the effect of supraceliac aortic cross-clamping (XC) on heparin pharmacodynamics. MATERIAL AND METHODS: Fourteen mongrel dogs were randomly divided into three groups: Group 1 (X; n = 6), 90 minutes aortic XC; Group 2 (SH; n = 4), sham operation and heparin, 100 mg/kg intravenously; and Group 3 (XH; n = 4), heparin, 100 mg/kg intravenously 3 minutes before XC. Prothrombin time (PT) and partial prothrombin time (PTT) were measured serially. Heparin concentrations were estimated via automated titration with protamine sulfate. RESULTS: After XC, PTT is increased during reperfusion. Heparin administration (XH) before aortic XC increases PTT above those with X or SH. Anticoagulation was potentiated and prolonged by XC. There was no difference in heparin concentration or PT. CONCLUSION: Supraceliac aortic clamping significantly affects heparin pharmacodynamics and may contribute to coagulopathy.

False aneurysm of the thyrocervical trunk.

False aneurysm of the thyrocervical trunk as a complication of central venous catheterization is rare. We report a case of this complication in a 63-year-old white man and review the history, diagnosis, pathophysiology, and treatment of these aneurysms.

Cervical thymic cyst: case reports and review of the literature.

Due to its rarity, cervical thymic cyst is seldom included in the differential diagnosis of a neck mass. Approximately 80 cases have been reported thus far, and most of these cases have occurred asymptomatically in children and adults. Only 5 cases have involved patients younger than 1 year of age. The authors report four new patients with thymic cyst in the neck. Two of the patients were newborns in whom the cyst caused airway obstruction and dysphagia. All four patients underwent successful resection of the lesions, with complete resolution of symptoms. The embryology, histopathology, and differential diagnosis of cervical thymic cysts are also reviewed. The authors recommend that despite its infrequent occurrence cervical thymic cyst should be considered in the evaluation of neck masses in children.