Phenotypes based on respiratory drive and effort to identify the risk factors when P0.1 fails to estimate ∆PES in ventilated children.

BACKGROUND: Monitoring respiratory effort and drive during mechanical ventilation is needed to deliver lung and diaphragm protection. Esophageal pressure (∆PES) is the gold standard measure of respiratory effort but is not routinely available. Airway occlusion pressure in the first 100 ms of the breath (P0.1) is a readily available surrogate for both respiratory effort and drive but is only modestly correlated with ∆PES in children. We sought to identify risk factors for P0.1 over or underestimating ∆PES in ventilated children. METHODS: Secondary analysis of physiological data from children and young adults enrolled in a randomized controlled trial testing lung and diaphragm protective ventilation in pediatric acute respiratory distress syndrome (PARDS) (NCT03266016). ∆PES (∆PES-REAL), P0.1 and predicted ∆PES (∆PES-PRED = 5.91*P0.1) were measured daily to identify phenotypes based upon the level of respiratory effort and drive: one passive (no spontaneous breathing), three where ∆PES-REAL and ∆PES-PRED were aligned (low, normal, and high effort and drive), two where ∆PES-REAL and ∆PES-PRED were mismatched (high underestimated effort, and overestimated effort). Logistic regression models were used to identify factors associated with each mismatch phenotype (High underestimated effort, or overestimated effort) as compared to all other spontaneous breathing phenotypes. RESULTS: We analyzed 953 patient days (222 patients). ∆PES-REAL and ∆PES-PRED were aligned in 536 (77%) of the active patient days. High underestimated effort (n = 119 (12%)) was associated with higher airway resistance (adjusted OR 5.62 (95%CI 2.58, 12.26) per log unit increase, p < 0.001), higher tidal volume (adjusted OR 1.53 (95%CI 1.04, 2.24) per cubic unit increase, p = 0.03), higher opioid use (adjusted OR 2.4 (95%CI 1.12, 5.13, p = 0.024), and lower set ventilator rate (adjusted OR 0.96 (95%CI 0.93, 0.99), p = 0.005). Overestimated effort was rare (n = 37 (4%)) and associated with higher alveolar dead space (adjusted OR 1.05 (95%CI 1.01, 1.09), p = 0.007) and lower respiratory resistance (adjusted OR 0.32 (95%CI 0.13, 0.81), p = 0.017). CONCLUSIONS: In patients with PARDS, P0.1 commonly underestimated high respiratory effort particularly with high airway resistance, high tidal volume, and high doses of opioids. Future studies are needed to investigate the impact of measures of respiratory effort, drive, and the presence of a mismatch phenotype on clinical outcome. TRIAL REGISTRATION: NCT03266016; August 23, 2017.

Observation of enhanced transmission for s-polarized light through a subwavelength slit.

Enhanced optical transmission (EOT) through a single aperture is usually achieved by exciting surface plasmon polaritons with periodic grooves. Surface plasmon polaritons are only excited by p-polarized incident light, i.e. with the electric field perpendicular to the direction of the grooves. The present study experimentally investigates EOT for s-polarized light. A subwavelength slit surrounded on each side by periodic grooves has been fabricated in a gold film and covered by a thin dielectric layer. The excitation of s-polarized dielectric waveguide modes inside the dielectric film strongly increases the s-polarized transmission. A 25 fold increase is measured as compared to the case without the dielectric film. Transmission measurements are compared with a coupled mode method and show good qualitative agreement. Adding a waveguide can improve light transmission through subwavelength apertures, as both s and p-polarization can be efficiently transmitted.

Uranus: variability of the microwave spectrum.

Radio astronomical observations of Uranus show that the radio emission spectrum is evolving in time. Ammonia vapor must be depleted in the Uranian atmosphere as Gulkis and his co-workers previously suggested. Since 1965, ammonia either has been decreasing in time or is a decreasing function of latitude, or both, provided that the radio emission is atmospheric in origin. If Uranus has an observable low-emissivity "surface," these trends may be reversed. The microwave observations made in 1965, at the time when the spin axis of Uranus was nearly perpendicular to the sun-Uranus line, are consistent with an atmospheric opacity profile that would be produced by saturated ammonia vapor in a predominantly hydrogen atmosphere. At the present time, when the spin axis of Uranus is nearly aligned with the sun-Uranus line, the measurements require an opacity that would be produced by saturated water vapor. A large thermal gradient between the pole and equator is ruled out.

Outburst of Jupiter's synchrotron radiation after the impact of comet Shoemaker-Levy 9.

Jupiter's nonthermal microwave emission, as measured by a global network of 11 radio telescopes, increased dramatically during the Shoemaker-Levy 9 impacts. The increase was wavelength-dependent, varying from approximately 10 percent at 70 to 90 centimeters to approximately 45 percent at 6 and 36 centimeters. The radio spectrum hardened (flattened toward shorter wavelengths) considerably during the week of impacts and continued to harden afterward. After the week of cometary impacts, the flux density began to subside at all wavelengths and was still declining 3 months later. Very Large Array and Australia Telescope images of the brightness distribution showed the enhancement to be localized in longitude and concentrated near the magnetic equator. The evidence therefore suggests that the increase in flux density was caused by a change in the resident particle population, for example, through an energization or spatial redistribution of the emitting particles.

[Intermittent vomiting in a patient with superior mesenteric artery syndrome]. / Intermitterend braken van een patiënte met het A.-mesenterica-superiorsyndroom.

A 51-year-old woman presented with nausea, vomiting and weight loss. The diagnosis of superior mesenteric artery syndrome was established by CT and upper-gastrointestinal contrast radiography. This revealed a characteristic dilatation of the first and second parts of the duodenum and an abrupt cutoff in the third part due to vascular compression. The obstruction disappeared when the patient was placed in the left lateral recumbent position. The thin habitus of this patient probably played an important role in the development of the syndrome. She was given dietary and positioning advice and within 4 months relief of symptoms was accompanied by a weight gain of 4 kg.

Estrogen replacement therapy after localized breast cancer: clinical outcome of 319 women followed prospectively.

PURPOSE: To determine whether estrogen replacement therapy (ERT) alters the development of new or recurrent breast cancer in women previously treated for localized breast cancer. PATIENTS AND METHODS: Potential participants (n = 319) in a trial of ERT after breast cancer were observed prospectively for at least 2 years whether they enrolled onto the randomized trial or not. Of 319 women, 39 were given estrogen and 280 were not given hormones. Tumor size, number of lymph nodes, estrogen receptors, menopausal status at diagnosis, and disease-free interval at the initiation of the observation period were comparable for the trial participants (n = 62) versus nonparticipants (n = 257) and for women on ERT (n = 39) versus controls (n = 280). Cancer events were ascertained for both groups. RESULTS: Patient and disease characteristics were comparable for the trial participants versus nonparticipants, as well as for the women on ERT versus the controls. One patient in the ERT group developed a new lobular estrogen receptor-positive breast cancer 72 months after the diagnosis of a ductal estrogen receptor-negative breast cancer and 27 months after initiation of ERT. In the control group, there were 20 cancer events: 14 patients developed new or recurrent breast cancer at a median time of 139.5 months after diagnosis and six patients developed other cancers at a median time of 122 months. CONCLUSION: ERT does not seem to increase breast cancer events in this subset of patients previously treated for localized breast cancer. Results of randomized trials are needed before any changes in current standards of care can be proposed.

Leukocyte scanning with 111In is superior to magnetic resonance imaging in diagnosis of clinically unsuspected osteomyelitis in diabetic foot ulcers.

OBJECTIVE: To compare the accuracies of MRI and leukocyte scanning in diagnosing clinically unsuspected osteomyelitis in diabetic foot ulcers. RESEARCH DESIGN AND METHODS: A prospective study of 16 diabetic foot ulcers in 12 patients, including both ambulatory and hospitalized patients, was performed at a university medical center. Pedal images were obtained by leukocyte scanning with [111In]oxyquinoline and MRI. Definitive diagnosis of osteomyelitis then was determined by bone biopsy for culture and histology. RESULTS: Biopsy-proven osteomyelitis was present in 7 (44%) of the 16 foot ulcers. The diagnosis was suspected clinically in 0%. Leukocyte scanning was 100% sensitive, whereas MRI was only 29% sensitive in diagnosing osteomyelitis in diabetic foot ulcers. Specificities were 67 and 78%, respectively. The positive and negative predictive values (70 and 100%, respectively) for the leukocyte scan also were greater than those of MRI (50 and 58%, respectively). CONCLUSIONS: Leukocyte scanning is superior to MRI in detecting clinically unsuspected osteomyelitis in diabetic foot ulcers.

Chemistry and biological behavior of samarium-153 and rhenium-186-labeled hydroxyapatite particles: potential radiopharmaceuticals for radiation synovectomy.

Hydroxyapatite (HA), a natural constituent of bone, was studied as a particulate carrier for beta-emitting radionuclides in radiation synovectomy. Particles were radiolabeled with 153Sm or 186Re and their in vivo safety was investigated following intra-articular injection into knees of normal rabbits and rabbits with antigen-induced arthritis (AIA). Radiolabeling efficiency was greater than 95%; in vitro studies showed minimal (< or = 1%) loss of activity from particles over a 6-day period with 153Sm-labeled HA and about 5% loss of activity over a 5-day period with 186Re-labeled HA. The total cumulative extra-articular leakage of 153Sm over 6 days was 0.28% in normal rabbits and 0.09% in AIA rabbits. Leakage of 186Re from the joint was 3.05% over a 4-day period with 80% of extra-articular activity found in the urine. Histopathological evaluation of treated knees showed that HA particles are distributed throughout the synovium, embedded in the synovial fat pad. The ease and efficiency with which this HA carrier is labeled, coupled with observed extremely low leakage rates from the joint, make radiolabeled HA particles an attractive candidate as a radiation synovectomy agent for evaluation in rheumatoid arthritis patients.

Ontogenesis of proopiomelanocortin gene expression and regulation in the rat pituitary intermediate lobe.

During ontogenesis, proopiomelanocortin (POMC) mRNA appears in the pituitary intermediate lobe (IL) at embryonic day 16 (E16), rather later than in the hypothalamic arcuate nucleus (E13) or the pituitary anterior lobe (E15). POMC mRNA onset in the IL correlates with the appearance of POMC-derived peptides detected by immunocytochemistry (ICC), indicating that there is probably no time lag between POMC mRNA translation. Subsequently, while the IL lobular organization developed progressively, the number of in situ hybridization- (ISH) and ICC-positive cells increased until after birth. During postnatal development, coinciding with innervation of the IL, the POMC mRNA level in the lobe, measured by quantitative ISH, increased about 4-fold to reach the adult value at weaning. The effects of acute or chronic postnatal treatment with a dopamine antagonist (haloperidol) or a dopamine agonist (bromocriptine) show that the physiological dopaminergic inhibitory control of POMC gene expression operates as early as postnatal day 5. The subsequent increase in mRNA levels despite the inhibitory innervation raises the question of the existence of some unknown positive regulation active during postnatal development.

Diabetic ketoacidosis associated with lithium: case report.

Diabetic ketoacidosis developed in a 41-year-old man who had been receiving lithium for 4 months. The patient required daily insulin administration following the discontinuation of lithium.

Granulomatous Pneumocystis carinii pneumonia in three patients with the acquired immune deficiency syndrome.

Pneumocystis carinii pneumonia is a frequent manifestation of the acquired immune deficiency syndrome (AIDS). It usually presents radiologically as diffuse bilateral infiltrates and histologically as a foamy, eosinophilic intra-alveolar exudate containing the organisms' cysts. We recently studied two rare cases of P carinii pneumonia presenting as pulmonary nodules on chest x-ray films in two patients with AIDS. The corresponding histologies were a combination of the usual intra-alveolar pattern, with an alveolar and interstitial granulomatous appearance. Pneumocystis carinii was present in both areas and was the only organism found in the tissues examined. A third case presented with the more common radiographic appearance but also had a granulomatous histology. We conclude that P carinii pneumonia should be considered in the differential diagnosis of pulmonary nodules in immunocompromised patients and that pathologists should be aware of the possibility of a granulomatous reaction to this organism.

Study of the potential reversal of triazolam memory and cognitive deficits by RU 41 656 in healthy subjects.

The potential antagonism of a single oral dose of RU 41 656 (10 mg) on the memory and attention disturbances induced by oral administration of triazolam (0.25 mg) have been investigated in a 3-period, placebo controlled, double blind, cross-over study involving 12 healthy young volunteers. The effects of the compounds were evaluated by objective tests (Buschke selective reminding test, CFF, simple reaction time, tapping, arithmetical calculation) and subjective measurements (visual analogue scale, side effects questionnaire). Measurements were taken before treatment and 2, 4 and 7 h after RU 41 656 intake. Triazolam caused anterograde amnesia as already described with other benzodiazepine with few sedative effects at this dosage. Under the experimental conditions of the trial, RU 41 656 failed to counteract the memory deficits induced by triazolam.

Triiodothyronine supplementation for hypothalamic obesity.

Patients with suprasellar lesions develop profound hypothalamic obesity and listlessness with no effective treatment. We added triiodothyronine (T(3)) supplementation in 3 such patients and present their response. All had previous nutritional counseling without benefit. All were treated for diabetes insipidus (DI) and hypopituitarism; serum free thyroxine (T(4)) level was normal. A 24-year-old woman (pineal tumor and astrocytoma) had weight gain (4.7 kg/yr for 3 years), cold intolerance, fatigue, dry skin, and constipation; after T(3), she lost 14 kg over 27 months and reported overall improvement. Her bone mineral density also improved. A 10.6-year-old boy (optic glioma) was gaining 6 kg/yr for 4 years; after T(3) supplement, he lost 4.3 kg over 11 months. A 12-year-old girl (mixed germ cell tumor) had weight gain (8.3 kg/yr for 3 years) and listlessness; after T(3), she lost 8.1 kg over 16 months and had improved alertness. All patients were asymptomatic despite supraphysiologic T(3) levels. We suggest that T(3) may serve as a simple and effective supplement, which can promote weight loss and improve the well being of these patients with hypothalamic obesity.

Expression of the oxytocin and vasopressin genes in the rat hypothalamus during development: an in situ hybridization study.

Oxytocin (OT)- and vasopressin (VP)-mRNAs were detected in the hypothalamus, during development, by in situ hybridization with synthetic oligonucleotide probes. The presence of VP- and OT-mRNAs was first detected in the supraoptic nucleus at E16 and E17 respectively, and simultaneously at E18 in the paraventricular nucleus. VP- (but not OT-) mRNA then appeared in the suprachiasmatic nucleus at E21, and OT- (but not VP-) mRNA, in the anterior commissural nucleus at time of birth. In the different nuclei, the relative distribution of cells containing OT- or VP-mRNA was comparable, from the earliest stages on, with that observed in the adult. These data suggest that the later appearance of mature OT (E20), versus VP (E16), reported in immunocytochemical studies, may not be due to a delayed transcription. Moreover, since the presence of both OT- and VP-prohormones has been reported at E16, the results support the idea of a rapid translation of both OT- and VP-mRNAs. In no location could OT- and VP-mRNAs be detected before final cell settlement; the possible role of environmental factors in final non-proliferative differentiation is discussed.

Detection of c-fos expression in benign and malignant musculoskeletal lesions.

The proto-oncogene c-fos has been implicated in the development of both benign and malignant lesions of bone. Although c-fos expression in such lesions has been well studied in transgenic mouse models, less is known about its role in human musculoskeletal pathology. To clarify this relationship, we used in situ hybridization to localize c-fos m-RNA transcripts in 26 fibrous lesions (eight cases of extra-abdominal fibromatosis and six cases each of fibrous dysplasia, fibrosarcoma, and malignant fibrous histiocytoma of bone) as well as six chondrosarcomas and eight conventional high grade osteosarcomas. We found detectable levels of c-fos expression in tissues from each type of lesion tested. Moreover, all fibrous lesions consistently demonstrated high levels of expression in a majority of cells in each lesion. Chondrosarcomas and osteosarcomas exhibited more heterogeneity in c-fos expression than fibrous tissues. Three of six chondrosarcomas showed moderate expression of c-fos while only one of six was considered high. Similarly, only three of eight osteosarcomas had high expression of c-fos. These findings indicate that the expression of c-fos may be important in the development of a broad range of fibrous lesions as well as in bone and cartilaginous tumors. Additionally, this is the first report, to our knowledge, of detectable c-fos m-RNA in human chondrosarcoma.

Ontogenesis of the rabbit pituitary intermediate lobe. An ultrastructural and immunocytochemical study.

The development of the intermediate lobe of the rabbit pituitary was investigated by light and electron microscopy and by using immunocytological techniques. The first immunoreactive melanotrophic cells were detected at the fetal day 17 in the dorsal zone of Rathke's pouch epithelium facing the neural lobe; this coincided ultrastructurally with the appearance in this area of a few cells exhibiting secretory vesicles and granular condensations in the Golgi saccules. The differentiation of the gland probably required an infundibular inductive effect. Secretory cells increased in number following a dorsoventral gradient during the next fetal and neonatal stages until postnatal day 20, the stage at which the intermediate lobe exhibited its definitive organization. The gland innervation occurred during the first days after birth. The advent of these oxytocin- and neurophysin-immunoreactive fibres coincided with an obvious stimulation of the synthetic activity of the melanotrophic cells. The possible neurotrophic effect of these cells on their innervating system remains to be established.