Cardiac decompensation due to massive pericardial effusion. A manifestation of hypothyroidism in children with Down's syndrome.
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Biomedical subjects
Publications and source records attributed to T A Wilson.
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We have determined the level of phosphorylated insulin-like growth factor binding protein-1 (pIGFBP-1) in serum during two catabolic states: diabetes mellitus and trauma. Human sera were incubated with [125I]IGF-I for 2 h followed by non-denaturing PAGE. [125I]IGF-I/IGFBP-1 complexes from serum co-migrated with a pure p4IGFBP-1 standard. Complex formation was specifically inhibited by unlabeled IGF-I. The migration of IGF-I/pIGFBP-1 complexes was retarded by IGFBP-1 antibodies, but not by antibodies against IGFBP-2 or IGFBP-3. Sera from three severely traumatized patients had up to 12-fold more pIGFBP-1 than sera from age-matched controls. The level of pIGFBP-1 was reduced in all three patients upon hospital discharge. Sera from three patients with insulin dependent diabetes mellitus (IDDM) and severe ketoacidosis (DKA) had more pIGFBP-1 than controls. Administration of insulin to DKA patients lowered the level of pIGFBP-1. The present study shows that IGFBP-1 exists as a free, high affinity, phosphorylated form in vivo during two catabolic states.
The complex interaction of leukemia inhibitory factor (LIF) with its specific receptor present on the cell surface, in isolated membranes and in solution, has been examined in detail. Several aspects of this complexity have been highlighted, including the presence of high- and low-affinity murine LIF receptors, biphasic dissociation of human LIF from apparently homogeneous high- or low-affinity human LIF receptors, and unusual species cross-reactivity. The unusual species cross-reactivity observed between murine and human LIF has also been exploited to map an important receptor binding epitope on human LIF.
We report on 2 infants with the DiGeorge anomaly born to diabetic mothers treated with insulin. Both infants had unilateral renal agenesis. One of the mothers has manifestations suggestive of velo-cardio-facial syndrome (VCFS). Cytogenetic studies on both patients and the mother with apparent VCFS were normal. Molecular studies utilizing probes from the DiGeorge critical region did not demonstrate a 22q11 microdeletion in either patient or the mother with apparent VCFS. We conclude that maternal diabetes is a pathogenetic factor in the DiGeorge anomaly, and infants of diabetic mothers who have this anomaly should also be screened for renal agenesis.
Thyroid dysfunction is rare in tuberous sclerosis, although papillary adenomas (hamartomas) of the thyroid gland have been reported in a few autopsy cases. We describe a child with tuberous sclerosis and primary congenital hypothyroidism secondary to a dysgenetic thyroid gland. To our knowledge, this association has not been reported previously. Although the association of these two disorders in one patient may be merely coincidence, we speculate that the dysgenetic thyroid gland in this patient may represent a "hamartia" as a consequence of the tuberous sclerosis gene.
OBJECTIVE: To compare presenting manifestations of meningioma in elderly patients with those in younger patients. DESIGN: Retrospective survey. SETTING: Tertiary care center. PATIENTS: All hospitalized adult patients with the primary diagnosis of meningioma over a 5-year period (n = 116). Nine patients with recurrence of a previously resected meningioma were excluded. Fifty-two percent (56/107) of patients were > or = 65 years of age. MEASUREMENTS: Presenting symptoms were classified as asymptomatic, focal, non-specific, or both focal and non-specific. Presenting neurologic signs on physical examination were classified as focal, non-focal, or normal. Duration of symptoms was classified as < or = 1 week, 1 week to 1 month, 1 to 6 months, and > 6 months. RESULTS: Older patients presented more commonly with confusion (32% vs 4%) and dystaxia (28% vs 10%) than younger patients and presented less commonly with headache (23% vs 49%) and visual changes (21% vs 43%). While 2% of patients were asymptomatic at presentation, the remainder had symptoms categorized as focal (38%), non-specific (26%), or both (34%). There was no significant difference between older and younger age groups in the proportions of patients having focal symptoms. Duration of symptoms for all patients was categorized as < or = 1 week (15%), 1 week to 1 month (16%), 1 to 6 months (23%), and > 6 months (44%). In general, older patients were diagnosed earlier than younger patients. The presence of focal neurologic signs was not significantly different between older and younger patients. CONCLUSIONS: Presenting manifestations of meningioma differ between older and younger adult patients, but focality of symptoms and signs is similar. In this case series, the duration of symptoms prior to diagnosis was shorter in older than in younger patients.
The parasternal intercostals are the primary determinant of the inspiratory cranial displacement of the ribs in the dog. When they contract, however, these muscles also cause a caudal displacement of the sternum, presumably an expiratory motion. The present studies were designed to assess the effects of this sternal displacement on the cranial displacement of the ribs and on lung volume. Twelve supine anesthetized animals were studied. We first measured, in four paralyzed animals, the displacement of the ribs and sternum produced by known external forces applied to the ribs, the sternum, or both simultaneously. From these measurements, the elastic coupling between the ribs and sternum was determined. We then studied, in eight animals, the effect of sternal motion on rib motion and tidal volume during spontaneous breathing. Rib and sternal displacements and tidal volume were measured first with the sternum free to move caudally during inspiration and then with the sternum constrained to prevent caudal motion. Preventing the sternum from moving caudally caused a 24% increase in the inspiratory cranial displacement of the ribs; this increased displacement of the ribs agreed well with the elastic coupling between the sternum and the ribs as determined from the force-displacement observations. Tidal volume, however, remained unchanged. These observations indicate that the caudal displacement of the sternum produced by the parasternal intercostals reduces the cranial displacement of the ribs but probably increases the lateral expansion of the rib cage.
In a previous paper (J. Appl. Physiol. 73: 2283-2288, 1992), respiratory effect was defined as the change in airway pressure produced by active tension in a muscle with the airway closed, mechanical advantage was defined as the respiratory effect per unit mass per unit active stress, and it was shown that mechanical advantage is proportional to muscle shortening during the relaxation maneuver. Here, we report values of mechanical advantage and maximum respiratory effect of the intercostal muscles of the dog. Orientations of the intercostal muscles in the third and sixth interspaces were measured. Mechanical advantages of the muscles in these interspaces were computed by computing their shortening from these data and data in the literature on rib displacement. We found that parasternal internal intercostals and dorsal external intercostals of the upper interspace have large inspiratory mechanical advantages and that dorsal internal intercostals of the lower interspace and triangularis sterni have large expiratory mechanical advantages. Mass distributions in the two interspaces were also measured, and maximum respiratory effects of the muscles were calculated from their mass, mechanical advantage, and the value for maximum stress in skeletal muscle. Estimated maximum respiratory effects of the inspiratory and expiratory muscle groups of the entire rib cage were tested by measuring the maximum inspiratory pressures that were generated by the parasternal and external intercostals acting alone. Measured pressures, -13 cmH2O for the parasternals and -11 cmH2O for the external intercostals, agreed well with the computed values.
OBJECTIVE: To test the hypothesis that puberty is a necessary factor in the pathogenesis of autoimmunity to sperm in men with cystic fibrosis (CF), we studied prepubertal and postpubertal males with CF versus an age-matched group of males with type 1 diabetes as controls. DESIGN: Sera from CF and diabetic males treated at University Hospital, State University of New York, Stony Brook, were tested by indirect immunobead binding for antisperm antibodies and by radioimmunoassay for testosterone (T), luteinizing hormone, and follicle-stimulating hormone. The finding of autoantibodies to spermatozoa was correlated with chronological age, as well as with clinical and hormonal pubertal status. RESULTS: Autoimmunity to sperm, as detected by humoral antisperm antibodies, was documented solely in postpubertal males, as judged by hormonal and clinical criteria. Eighty-three percent of sexually mature CF males and 6.3% (1 of 16) diabetic males exhibited autoantibodies to sperm. These antibodies were only detected when serum T levels were > 8.7 nmol/L (250 ng/dL). CONCLUSIONS: These results suggest that puberty, and presumably, active spermatogenesis is a requirement for the development of autoimmunity to sperm in men with CF.
The anatomic distributions of ventilation (VA) and perfusion (Q) in prone and supine dogs have been described in the literature. These data also provide frequency distributions, i.e., the distribution of lung units as a function of VA or Q. A comprehensive distribution that encompasses these two distributions is described, and the properties of the comprehensive distribution that determine the width of the VA/Q distribution are identified. Using data on the VA and Q distributions taken from various sources in the literature, we estimated the widths of the VA/Q distributions. The widths estimated from the independent data on the VA and Q distributions agree well with the widths obtained from gas exchange data. The analysis provides information about the relative contributions of the VA and Q distributions to the width of the VA/Q distribution. In the prone dog, the VA and Q distributions, as described by the available data, have different length scales, and we argue that these distributions are therefore not highly correlated. As a result, the variance of the VA/Q distributions is approximately the sum of the variances of the VA and Q distributions. Two-thirds of the variance in VA/Q is a result of nonuniform Q, and one-third is a result of nonuniform VA. In the supine dog, the variance of VA is larger than in the prone dog because of a vertical gradient and the variance of Q is larger, in part, because of a vertical gradient. Because the magnitudes of the vertical gradients of VA and Q are about equal, the vertical gradient of VA/Q is small, and these components of the VA and Q inhomogeneities contribute little to the width of the VA/Q distribution. The other components of Q inhomogeneity cause the additional variance of VA/Q in the supine dog.
Both continuum and micromechanical models have been used to describe the mechanics of lung parenchyma. Different authors, using different models, have come to different conclusions about parenchymal stability. We show that the continuum model, augmented by bounds on the elastic moduli obtained from recent micromechanical modeling, yields the same conclusions about stability that have been obtained from purely micromechanical modeling: if the lung were homogeneous, it would be stable; local atelectasis would not occur at positive transpulmonary pressure. However, the same analysis yields the prediction that if the surface-to-volume ratio is not uniform throughout the lung, regions of higher surface density collapse if surface tension is large and insensitive to surface area. A micromechanical model that illustrates regional collapse is described.
The chest wall is modeled as a linear system for which the displacements of points on the chest wall are proportional to the forces that act on the chest wall, namely, airway opening pressure and active tension in the respiratory muscles. A standard theorem of mechanics, the Maxwell reciprocity theorem, is invoked to show that the effect of active muscle tension on lung volume, or airway pressure if the airway is closed, is proportional to the change of muscle length in the relaxation maneuver. This relation was tested experimentally. The shortening of the cranial-caudal distance between a rib pair and the sternum was measured during a relaxation maneuver. These data were used to predict the respiratory effect of forces applied to the ribs and sternum. To test this prediction, a cranial force was applied to the rib pair and a caudal force was applied to the sternum, simulating the forces applied by active tension in the parasternal intercostal muscles. The change in airway pressure, with lung volume held constant, was measured. The measured change in airway pressure agreed well with the prediction. In some dogs, nonlinear deviations from the linear prediction occurred at higher loads. The model and the theorem offer the promise that existing data on the configuration of the chest wall during the relaxation maneuver can be used to compute the mechanical advantage of the respiratory muscles.
Newborn infants minimally symptomatic with non-central nervous system (CNS) infections due to Streptococcus agalactiae (group B streptococcus [GBS]) and other pathogens may not require skilled nursing care during the entire course of parenteral antibiotic therapy. In 1985, treatment guidelines were made available to private practitioners in Oregon for therapy of newborn infants at low risk of complications from their infections. In 1988, patient data were collected and analyzed retrospectively. Outpatient management during convalescence of 51 infants (21 with culture-positive infections due to GBS) was accomplished with once-daily physician follow-up examinations and IM injection of ceftriaxone. Long-term (greater than or equal to two months) follow-up data were available for 67% of GBS-infected infants, with no complication of infection or significant complication of therapy reported. Outpatient parenteral antibiotic management of selected, low-risk infants may offer the clinician an alternative to hospitalization for a portion of the duration of parenteral antibiotic therapy.
Leukaemia inhibitory factor (LIF) is a polyfunctional cytokine that has been identified and characterized in several laboratories by virtue of a number of different biological activities. LIF is encoded by a unique gene located at 11A1 in the mouse and at 22q12 in man. However, loci related to sequences in the 3' untranslated region of the mRNA have been detected and located elsewhere in the genome. The LIF gene from four mammalian species has been cloned and sequenced; the sequences are highly conserved within the coding regions and largely non-conserved within the non-coding regions. However, a number of non-coding segments displaying high interspecies similarity are evident; these are candidate control regions. Intriguingly, an exon corresponding to the 5' end of a variant LIF transcript in the mouse that encodes a potentially matrix-associated form of LIF is not conserved in the human, ovine and porcine genes. The promoter region of the LIF gene contains four well-conserved TATA elements, and two start sites of transcription have been identified. Three regions within the 5' flanking region have been identified as important for the function of the LIF promoter, including a candidate repressor sequence. The LIF gene is transcribed at only very low levels in normal tissues, but its expression can be increased by various stimuli.
Symptomatic thoracic disk herniation is unlikely to be encountered with significant frequency in clinical practice. Subtle manifestations required a high index of suspicion if the work-up is to be efficient. In the appropriate candidate, magnetic resonance imaging is the best screening tool, and it may be the only diagnostic study required. In the symptomatic patient with neurologic dysfunction or persistent pain refractory to nonsurgical therapy, surgical diskectomy is a safe and effective treatment with limited morbidity.
The gravitational work of breathing was determined by measuring the vertical motion of body mass. The subject, seated or lying supine on a force platform, performed breathing maneuvers in which rib cage volume (Vrc) and abdominal volume (Vab) were changed in varying proportions. The increment in the vertical force exerted on the platform and Vrc and Vab were measured over the course of each maneuver. The force signal was integrated twice with respect to time to obtain the change in the product of mass and height of the subject. This was multiplied by the gravitational acceleration to obtain the change in the gravitational potential (Ug). Simultaneous values of Ug, Vrc, and Vab were taken from the data, and the values of the coefficients for which the following equation best fit these values were determined: Ug = a1 Vrc + a2 Vab + (1/2)a11 Vrc2 + a12 Vrc Vab + (1/2)a22 Vab2. The coefficients a1 and a2 can be interpreted as the values of the expiratory gravitational forces on the rib cage and abdomen, respectively. In the seated posture, the force on the rib cage is expiratory and the force on the abdomen is inspiratory; the magnitudes of both are approximately 8 cmH2O. In the supine posture, both are expiratory forces of approximately 9 cmH2O. The coefficients of the quadratic terms in Ug are all positive, and the gravitational work per unit volume of chest wall expansion increases with increasing volume in both postures. The coefficients of the quadratic terms can be interpreted as gravitational contributions to the elastances of the compartments.
Data on the shape of the chest wall at total lung capacity (TLC) and functional residual capacity (FRC) were used as boundary conditions in an analysis of the deformation of the dog lung. The lung was modeled as an elastic body, and the deformation of the lung from TLC to FRC caused by the change in chest wall shape and gravity were calculated. Parenchymal distortions, distributions of regional volume at FRC as a fraction of the volume at TLC, and distributions of surface pressure at FRC are reported. In the prone dog there are minor variations in fractional volume along the cephalocaudal axis. In transverse planes opposing deformations are caused by the change of shape of the transverse section and the gravitational force on the lung, and the resultant fractional volume and pleural pressure distributions are nearly uniform. In the supine dog, there is a small cephalocaudal gradient in fractional volume, with lower fractional volume caudally. In transverse sections the heart and abdomen extend farther dorsally at FRC, squeezing the lung beneath them. The gradients in fractional volume and pleural pressure caused by shape changes are in the same direction as the gradients caused by the direct gravitational force on the lung, and these two factors contribute about equally to the large resultant vertical gradients in fractional volume and pleural pressure. In the prone position the heart and upper abdomen rest on the rib cage. In the supine posture much of their weight is carried by the lung.(ABSTRACT TRUNCATED AT 250 WORDS)
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