Non-contact respiration monitoring for in-vivo murine micro computed tomography: characterization and imaging applications.

A cone beam micro-CT has previously been utilized along with a pressure-tracking respiration sensor to acquire prospectively gated images of both wild-type mice and various adult murine disease models. While the pressure applied to the abdomen of the subject by this sensor is small and is generally without physiological effect, certain disease models of interest, as well as very young animals, are prone to atelectasis with added pressure, or they generate too weak a respiration signal with this method to achieve optimal prospective gating. In this work we present a new fibre-optic displacement sensor which monitors respiratory motion of a subject without requiring physical contact. The sensor outputs an analogue signal which can be used for prospective respiration gating in micro-CT imaging. The device was characterized and compared against a pneumatic air chamber pressure sensor for the imaging of adult wild-type mice. The resulting images were found to be of similar quality with respect to physiological motion blur; the quality of the respiration signal trace obtained using the non-contact sensor was comparable to that of the pressure sensor and was superior for gating purposes due to its better signal-to-noise ratio. The non-contact sensor was then used to acquire in-vivo micro-CT images of a murine model for congenital diaphragmatic hernia and of 11-day-old mouse pups. In both cases, quality CT images were successfully acquired using this new respiration sensor. Despite the presence of beam hardening artefacts arising from the presence of a fibre-optic cable in the imaging field, we believe this new technique for respiration monitoring and gating presents an opportunity for in-vivo imaging of disease models which were previously considered too delicate for established animal handling methods.

Behaviour profiles after tuberculous meningitis.

The purpose of the study was to investigate child behaviour in children who recovered from tuberculous meningitis (TBM) and to compare behaviour profiles of stage II and stage III patients. The mean age of the cohort of 74 children at the time of evaluation was 10 years and 7 months. At follow-up all patients underwent a thorough neurological examination and a psychometric test battery, which included intellectual assessment and evaluation of behaviour by means of the CBCL/6-18. Results indicated elevated mean scores (T > 60) on CBCL/6-18 scales which measure problems with anxiety, depression, attention, social relationships, disruptive and rule-breaking behaviour. Mean CBCL scores of stage III patients were significantly higher than the mean scores of stage II patients on scales which measure social problems, disruptive and rule-breaking behaviour. In addition, problems with conduct, attention, attention-deficit/hyperactivity problems, affective problems as well as the total problem scores were more pronounced in the patients with stage III TBM. We conclude that general behavioural disinhibitions as well as internalized emotional disorder probably are long-term complications in more than 10% of the survivors of TBM.

Tuberculosis meningitis and attention deficit hyperactivity disorder in children.

The purpose of this study was to investigate the prevalence of attention deficit hyperactivity disorder (ADHD) in children who recovered from tuberculous meningitis (TBM) as part of an ongoing TBM research project. During this study, each TBM group subject underwent a thorough clinical-neurological examination, and a test battery which included the child behaviour check list (CBCL) Teacher's Report Form and Conners Rating Scale. The parents and teachers of each of the 21 TBM group and 21 control group subjects completed the above-mentioned questionnaires. All 21 TBM group subjects displayed symptoms of ADHD. The TBM group was significantly more hyperactive and unable to sustain attention than the control group. Furthermore, TBM group subjects were perceived as being significantly more unpopular, obsessive, compulsive and aggressive than the control group subjects. With regard to the frequency of externalizing behaviour, the TBM group subjects displayed significantly more externalizing behaviours as well as symptoms of attention deficit and hyperactivity. No significant differences between parents' and teachers' ratings were found. We conclude that ADHD is a common long-term complication of TBM.

Long-term follow up of childhood tuberculous meningitis.

The purpose of the present study was to determine the long-term outcome of 76 children (40 females and 36 males) diagnosed and treated with modern antituberculosis drugs. The median age of the children on admission was 29.5 months and on follow-up 9 years. Antituberculosis therapy consisted of daily isoniazid (20 mg/kg), rifampicin (20 mg/kg), ethionamide (20 mg/kg), and pyrazinamide (40 mg/kg) for 6 months. Twenty-three children received daily prednisone (2-4 mg/kg) for the first month of treatment. Raised intracranial pressure was actively monitored and treated. Patients with non-communicating hydrocephalus received ventriculo-peritoneal shunts shortly after admission while communicating hydrocephalus was treated with oral acetazolamide (100 mg/kg/day) and furosemide (1 mg/kg/day) in 3-4 divided doses. Communicating hydrocephalus that did not respond to this regimen within the first month of treatment also underwent ventriculo-peritoneal shunting. Only 20% of children were functionally completely normal at follow-up. Main areas of functional deficit were cognitive impairment (80%), poor scholastic progress (43%), and emotional disturbance (40%). Twenty-five per cent of children had evidence of motor impairment, but all could walk and only 5 of 76 children (6% of total) were unable to run. One child was blind but no child had sensori-neural deafness. It was concluded that these disabilities in children from mainly deprived socioeconomic backgrounds have serious implications for their future social, academic, and career prospects. A high index of suspicion of TBM in high tuberculosis incidence communities will help prevent the morbidity documented in this study.

Adenovirus-mediated p53 gene transfer in sequence with cisplatin to tumors of patients with non-small-cell lung cancer.

PURPOSE: To determine the safety and tolerability of adenovirus-mediated p53 (Adp53) gene transfer in sequence with cisplatin when given by intratumor injection in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced NSCLC and abnormal p53 function were enrolled onto cohorts receiving escalating dose levels of Adp53 (1 x 10(6) to 1 x 10(11) plaque-forming units [PFU]). Patients were administered intravenous cisplatin 80 mg/m(2) on day 1 and study vector on day 4 for a total of up to six courses (28 days per course). Apoptosis was determined by the terminal deoxynucleotidyl- transferase-dUTP nick-end labeling assay. Evidence of vector-specific sequences were determined using reverse-transcriptase polymerase chain reaction. Vector dissemination and biodistribution was monitored using a series of assays (cytopathic effects assay, Ad5 hexon enzyme-linked immunosorbent assay, vector-specific polymerase chain reaction assay, and antibody response assay). RESULTS: Twenty-four patients (median age, 64 years) received a total of 83 intratumor injections with Adp53. The maximum dose administered was 1 x 10(11) PFU per dose. Transient fever related to Adp53 injection developed in eight of 24 patients. Seventeen patients achieved a best clinical response of stable disease, two patients achieved a partial response, four patients had progressive disease, and one patient was not assessable. A mean apoptotic index between baseline and follow-up measurements increased from 0.010 to 0.044 (P =.011). Intratumor transgene mRNA was identified in 43% of assessable patients. CONCLUSION: Intratumoral injection with Adp53 in combination with cisplatin is well tolerated, and there is evidence of clinical activity.

Adenovirus-mediated p53 gene transfer in advanced non-small-cell lung cancer.

BACKGROUND: Preclinical studies in animal models have demonstrated tumor regression following intratumoral administration of an adenovirus vector containing wild-type p53 complementary DNA (Ad-p53). Therefore, in a phase I clinical trial, we administered Ad-p53 to 28 patients with non-small-cell lung cancer (NSCLC) whose cancers had progressed on conventional treatments. METHODS: Patients received up to six, monthly intratumoral injections of Ad-p53 by use of computed tomography-guided percutaneous fine-needle injection (23 patients) or bronchoscopy (five patients). The doses ranged from 10(6) plaque-forming units (PFU) to 10(11) PFU. RESULTS: Polymerase chain reaction (PCR) analysis showed the presence of adenovirus vector DNA in 18 (86%) of 21 patients with evaluable posttreatment biopsy specimens; vector-specific p53 messenger RNA was detected by means of reverse transcription-PCR analysis in 12 (46%) of 26 patients. Apoptosis (programmed cell death) was demonstrated by increased terminal deoxynucleotide transferase-mediated biotin uridine triphosphate nick-end labeling (TUNEL) staining in posttreatment biopsy specimens from 11 patients. Vector-related toxicity was minimal (National Cancer Institute's Common Toxicity Criteria: grade 3 = one patient; grade 4 = no patients) in 84 courses of treatment, despite repeated injections (up to six) in 23 patients. Therapeutic activity in 25 evaluable patients included partial responses in two patients (8%) and disease stabilization (range, 2-14 months) in 16 patients (64%); the remaining seven patients (28%) exhibited disease progression. CONCLUSIONS: Repeated intratumoral injections of Ad-p53 appear to be well tolerated, result in transgene expression of wild-type p53, and seem to mediate antitumor activity in a subset of patients with advanced NSCLC.

Patterns of shortening and thickening of the human diaphragm.

To study how the human diaphragm changes configuration during inspiration, we simultaneously measured diaphragm thickening using ultrasound and inspired volumes using a pneumotachograph. Diaphragm length was assessed by chest radiography. We found that thickening and shortening were greatest during a breath taken primarily with the abdomen. However, the degree of thickening was greater than expected for fiber shortening, assuming parallel muscle fibers and no shear. So, to clarify this unexpected finding, we considered geometric models of the diaphragm. How a muscle thickens as its fibers shorten is critically dependent on geometry. Thus, if a flat rectangular sheet of muscle shortens along one dimension, surface area-to-length ratio along this dimension should remain constant, and thickness would be inversely proportional to length during shortening. The simplest model of the diaphragm, however, is a cylindrical sheet of muscle in the zone of apposition capped by a dome; the ratio of surface area to radial fiber length in the dome is substantially less than the ratio of area to length of the cylindrical zone of apposition; hence, as the zone of apposition shortens while the dome radius remains constant, the ratio of total surface area to combined length (i.e., dome + zone of apposition) must decrease and thickening of the muscle correspondingly must increase more than expected for a simple rectangular strip. A similar relationship can be derived between thickening and length in a muscle sheet with a wedge-shaped insertion into a thin flat tendon. Comparison of calculations with these types of models to data from human subjects indicates that the unexpected thickening in the zone of apposition is explained by the peculiar geometry of the diaphragm. The greater thickening of the diaphragm in the zone of apposition suggests that more of the muscle mass and more sarcomeres are retained in the zone of apposition as the dome descends. Physiologically, this greater thickening may have importance by reducing wall stress in the zone of apposition and reducing the work or energy requirements per sarcomere.

Southwestern Internal Medicine Conference: preoperative pulmonary evaluation.

The purpose of preoperative pulmonary assessment is to predict which patients are at greater risk of pulmonary complications, under which circumstances such complications may occur, and whether surgery should be denied based on that risk. In this article, the author addresses the following major issues in preoperative pulmonary assessment: 1) the risk of pulmonary complications in relation to the type of surgical procedure; 2) the value of preoperative pulmonary function testing, including when such testing should be performed and how the results should be used; and 3) guidelines for assessment of those patients about to undergo resectional surgery of the lung.

Diaphragm thickness heterogeneity at functional residual capacity and total lung capacity.

One of the determinants of muscular force is the number of myofibrils in parallel, which is approximated by thickness. To better understand the heterogeneity of diaphragm thickness, we quantified the interregional and radial patterns of thickness of nine canine diaphragms rapidly perfusion fixed in situ with glutaraldehyde at functional residual capacity (FRC) (n = 6) and total lung capacity (TLC) (n = 3). Thickness was determined gravimetrically from punch biopsies radiating from the central tendon to rib cage insertion in ventral, middle, and dorsal costal and crural regions. For comparison, the contralateral unfixed hemidiaphragm was sampled in the same fashion. The findings of this investigation include the following. 1) The costal diaphragm exhibits the same pattern of interregional heterogeneity at FRC, TLC, and in the freshly excised state. 2) The costal diaphragm is significantly thinner at FRC in situ (0.17 +/- 0.01 cm) than is the freshly excised contralateral diaphragm (0.21 +/- 0.01 cm; P < 0.05), whereas there is no significant difference between thickness at TLC and the freshly excised state. 3) There is significant, previously underscribed, radial tapering from the rib cage attachment (0.24 +/- 0.02) to the central tendon insertion (0.15 +/- 0.01 cm; P < 0.05) that is exaggerated at TLC. 4) With passive inflation from FRC to TLC, the greatest increase in thickness occurs close to the rib cage attachment for the ventral and medial costal regions but close to the central tendon in the dorsal and crural regions. We conclude that the diaphragm at FRC and TLC exhibits radial thickness heterogeneity that cannot be predicted from dimensions of the freshly excised diaphragm.(ABSTRACT TRUNCATED AT 250 WORDS)

Massive perirenal and intra-abdominal bleeding after shock-wave lithotripsy: case report.

Complications of extracorporeal shock-wave lithotripsy are rare, with an incidence of symptomatic perinephric hematoma ranging from 0.2% to 0.66%. A 59-year-old man had massive symptomatic retroperitoneal and intra-abdominal bleeding 24 hours after lithotripsy. The hemorrhage was managed successfully by conservative measures, which consisted of packed red blood cells and fresh frozen plasma. The literature on the bleeding complications of lithotripsy is reviewed and the risk factors are identified.

Localizing the spatial and temporal electromagnetic fields on the axis of a lossy cylinder.

Given a specified form, both in time and space, for the electromagnetic fields on the axis of a lossy cylinder, we determine, analytically, the required azimuthally symmetric source distribution on the surface of the cylinder that generates such internal fields. We then show that this source is equivalent to an array with finite number of cylindrical slots in a metal encasing that are impulsed by specified voltages at a finite sequence of discrete times. A confirming forward calculation exhibits excellent agreement between the specified field form and that generated by the array of cylindrical slots. Potential applications are to hyperthermic cancer therapy, bioelectromagnetics and nondestructive testing.

Tuberculous hydrocephalus: comparison of different treatments with regard to ICP, ventricular size and clinical outcome.

The effect of different treatment regimes on intracranial pressure (ICP), degree of hydrocephalus and clinical outcome was evaluated in 81 children with tuberculous meningitis. 24 children underwent CSF shunting, while 57 with communicating hydrocephalus were randomly assigned to three treatment groups: antituberculous drugs only; or additional intrathecal hyaluronidase or oral acetazolamide and furosemide in addition to antituberculous treatment. The addition of acetazolamide and furosemide was significantly more effective in achieving normal ICP than antituberculous drugs alone. No difference was found in mortality or number of disabled survivors between groups. Of those surviving, nearly two-thirds with stage II tuberculous meningitis were mildly disabled and nearly one-half with stage III were severely disabled at follow-up, emphasising the need for early diagnosis of tuberculous meningitis in the young child.

Diaphragmatic thickness-lung volume relationship in vivo.

To characterize the relationship of changes in diaphragmatic thickness during contraction to changes in lung volume, we developed a technique to measure diaphragm thickness based on M-mode ultrasonography. First, diaphragmatic thickness was measured in situ at necropsy with ultrasound and verified by measuring the same resected segment of diaphragm by ruler (correlation coefficient = 0.93, slope = 0.97). The technique of imaging the diaphragm in living subjects was developed by using a 15-MHz transducer coupled to an M-mode echocardiograph. Ten normal male volunteers were studied while sitting. The ultrasound transducer was held between the ribs in the ninth lateral interspace, and tidal volume was measured by spirometry. The thickening fraction (TF) was calculated as TF = (thickness at peak inspiration - thickness at end expiration)/thickness at end expiration for each of a series of different sized breaths. The function, TF vs. lung volume, for a range of volumes was linear for each subject and had intrasubject reproducibility with intersubject variability. We conclude that diaphragmatic TF is related to function as determined by lung volume, and this may prove to be a useful technique for in vivo studies of diaphragmatic function.

Anginal chest pain in sarcoidosis.

Of 43 consecutive black patients (42 male) with sarcoidosis, 12 (28%) complained of chest pain that met the clinical criteria for typical (four patients) or atypical (eight patients) angina pectoris. These patients underwent cardiopulmonary assessment, which included exercise and redistribution thallium-201 scans and, if indicated, coronary angiography. Nine control patients with sarcoidosis matched for age and duration of disease, but without chest pain, were also studied by thallium-201 scintigraphy. Six of the 12 patients with chest pain had thallium scans indicative of myocardial ischaemia, but all had normal coronary angiograms; no patient from the control group had evidence of ischaemia on the thallium scan. Four additional patients with chest pain and one from the control group had other (non-specific) abnormalities on the thallium scan, so that scans were abnormal in 10 of the 12 patients with sarcoidosis who had chest pain. Most patients with anginal chest pain reported partial or complete relief of symptoms with nitrates. Anginal chest pain appears to be common in black male patients with sarcoidosis, is associated with abnormal myocardial perfusion scans, and may result from myocardial sarcoidosis.

Cardiopulmonary stress testing. A review of noninvasive approaches.

With readily available techniques, cardiopulmonary exercise testing permits noninvasive measurement of such parameters as heart rate, cardiac output, oxygen saturation, ventilation, and gas exchange to bring out abnormalities which are either underestimated or not detectable at rest. These parameters may be used to characterize a patient's primary limitation of exercise tolerance as either cardiac or pulmonary in origin. They can also provide precise data to assess response to treatment. Pulmonary gas exchange is evaluated primarily by measurement of oxygen consumption, carbon dioxide production, and ventilation over time. The relationship of these parameters to one another changes throughout the course of incremental exercise testing. By appreciating these basic relationships, the more complex abnormalities found in disease states can be understood.