Diastolic coronary artery pressure-flow velocity relationships in conscious man.

We characterised the diastolic pressure-flow velocity relationship in the normal left coronary artery of conscious man before and after vasodilatation with angiographic contrast medium. Phasic coronary artery pressure and flow velocity were measured in ten patients during individual diastoles (0.5 to 1.0 s) using a 20 MHz catheter-tipped, pulsed Doppler transducer. All pressure-flow velocity curves were linear over the diastolic pressure range of 110 +/- 15 (SD) mmHg to 71 +/- 7 mmHg (r = 0.97 +/- 0.01). In the basal state, values for slope and extrapolated zero flow pressure intercept averaged 0.35 +/- 0.12 cm X s-1 X mmHg-1 and 51.7 +/- 8.6 mmHg, respectively. Vasodilatation resulted in a 2.5 +/- 0.5 fold increase in mean flow velocity. The diastolic pressure-flow velocity relationship obtained during peak vasodilatation compared to that during basal conditions was characterised by a steeper slope (0.80 +/- 0.48 cm X s-1 X mmHg-1, p less than 0.001) and lower extrapolated zero flow pressure intercept (37.9 +/- 9.8 mmHg, p less than 0.05). Mean right atrial pressure for the group averaged 4.4 +/- 1.7 mmHg, while left ventricular end-diastolic pressure averaged 8.7 +/- 2.8 mmHg. These observations in man are similar to data reported in the canine coronary circulation which are consistent with a vascular waterfall model of diastolic flow regulation. In this model, coronary blood flow may be regulated by changes in diastolic zero flow pressure as well as in coronary resistance.

Confirmation of the Catania brachydactylous type of acrofacial dysostosis: report of a second family.

The acrofacial dysostoses (AFD) are a heterogeneous group of disorders combining varying severities of mandibulofacial dysostosis (MFD) with pre- and/or postaxial limb abnormalities. In 1993, Opitz et al. [Am J Med Genet 47:660-678] described a new AFD with mental retardation in a Sicilian mother and her four sons characterized by intrauterine growth retardation (IUGR), postnatal short stature, microcephaly, widow's peak, MFD without cleft palate, mild pre- and postaxial limb hypoplasia with brachydactyly, mild interdigital webbing, and cryptorchidism and hypospadias in males. We report a mother and daughter with this same phenotype, confirming this new type of AFD and expanding the clinical phenotype to include frequent dental caries. Analysis of cephalometric and metacarpophalangeal profiles in this family showed no distinctive diagnostic abnormalities. This family confirms the Catania brachydactylous type of AFD and supports an autosomal dominant mode of inheritance, although male-to-male transmission has not been demonstrated.

Antenatal diagnosis of lethal skeletal dysplasias.

Lethal skeletal dysplasias (LSD) are a heterogeneous group of rare but important genetic disorders characterized by abnormal growth and development of bone and cartilage. We describe the diagnosis and outcome of 29 cases of lethal skeletal dysplasias evaluated between January 1989 and December 1996 at the University of Maryland Medical Center and the Ultrasound Institute of Baltimore. Two cases presented at delivery with no prenatal care while the remaining 27 cases were identified by antenatal sonography. Final diagnoses included thanatophoric dysplasia (14), osteogenesis imperfecta, type II (6), achondrogenesis (2), short rib syndromes (3), campomelic syndrome (2), atelosteogenesis (1), and no evidence of a skeletal dysplasia (1). Twenty out of 27 pregnancies were terminated with an average at detection of 21.6 weeks. The other 7 pregnancies that went on to deliver had an average age at detection of 29.2 weeks. Fetal abnormalities in the terminated pregnancies were identified at a significantly earlier gestational age (P = 0.0016) than the pregnancies that continued. While the identification of LSD by sonography was excellent (26/27), only 13/27 (48%) were given an accurate specific antenatal diagnosis. In 8/14 (57%) cases with an inaccurate or nonspecific diagnosis there was a significant or crucial change in the genetic counseling. Thus, while antenatal sonography is an excellent method for discovering LSD, clinical examination, radiographs, and autopsy are mandatory for making a specific diagnosis.

Ureaplasma urealyticum respiratory tract colonization is associated with an increase in interleukin 1-beta and tumor necrosis factor alpha relative to interleukin 6 in tracheal aspirates of preterm infants.

OBJECTIVE: To determine whether Ureaplasma urealyticum respiratory tract colonization in very low birth weight infants during the first week of life is associated with changes in tracheal aspirate concentrations of the cytokines interleukin 1-beta (IL-1-beta), tumor necrosis factor alpha (TNF-alpha) and IL-6. METHODS: Infants with birth weights < or =1250 g were prospectively enrolled. Samples were obtained from the endotracheal tube or nasopharynx on Day 1 and again between Days 7 and 10 for U. urealyticum culture. The concentrations of IL-1-beta, TNF-alpha and IL-6 were measured in tracheal aspirate samples by enzyme-linked immunosorbent assay. RESULTS: There were 18 positive cultures for U. urealyticum from 15 of 96 infants (15.6%). IL-1-beta in tracheal aspirates expressed as concentration per volume or as a ratio of IL-1-beta to IL-6 were 7- and 14.9-fold higher, respectively, in Ureaplasma-positive infants than in Ureaplasma-negative infants (P < 0.05). The TNF-alpha/IL-6 ratio was 18.9 and 15.5 times higher in the Ureaplasma-positive aspirates than in the Ure aplasma-negative aspirates on Day 1 and Days 7 to 10 (P < 0.05). Concentrations of IL-1-beta and TNF-alpha were significantly correlated on Day 1 and Days 7 to 10. Although there was no clinical association demonstrated between U. urealyticum colonization and the development of bronchopulmonary dysplasia (BPD) in this study, infants who developed BPD had significantly higher IL-1-beta concentrations and ratios of IL-1-beta to IL-6 in Day 1 aspirates than infants who did not develop BPD. Conclusions. Isolation of U. urealyticum from the respiratory tract is associated with increased IL-1-beta concentrations and IL-1-beta-IL-6 ratios on Day 1 and increased TNF-alpha-IL-6 ratios on Days 1 and 7 to 10 in tracheal aspirates of colonized infants. Infants who developed BPD had higher IL-1-beta concentrations and IL-1-beta-IL-6 ratios, suggesting that these may be early markers of lung inflammation.

Strategic planning in health care: methods and applications.

This article reviews planning methods currently being used by health care organizations to meet current challenges and investigates the relationship of these planning methods to total quality management. It suggests that planning methods that stress the achievement of objectively defined and measurable outcomes directly related to organizational priorities are superior to methods that emphasize as endpoints the implementation of programs (processes) without direct measurement of their effectiveness. Finally, it provides an overview of planning practices within the ScrippsHealth system.

Feasibility of a neutron detector-dosemeter based on single-event upsets in dynamic random-access memories.

The feasibility was investigated of a solid-state neutron detector/dosemeter based on single-event upset (SEU) effects in dynamic random-access memories (DRAMs), commonly used in computer memories. Such a device, which uses a neutron converter material to produce a charged particle capable of causing an upset, would be light-weight, low-power, and could be read simply by polling the memory for bit flips. It would have significant advantages over standard solid-state neutron dosemeters which require off-line processing for track etching and analysis. Previous efforts at developing an SEU neutron detector/dosemeter have suffered from poor response, which can be greatly enhanced by selecting a modern high-density DRAM chip for SEU sensitivity and by using a thin 10B film as a converter. Past attempts to use 10B were not successful because the average alpha particle energy was insufficient to penetrate to the sensitive region of the memory. This can be overcome by removing the surface passivation layer before depositing the 10B film or by implanting 10B directly into the chip. Previous experimental data show a 10(3) increase in neutron sensitivity by chips containing borosilicate glass, which could be used in an SEU detector. The results are presented of simulations showing that the absolute efficiency of an SEU neutron dosemeter can be increased by at least a factor of 1000 over earlier designs.

Recertification: toward the development of standards for assuring continued competence.

NCCPA, in collaboration with NBME, has begun an investigation that may lead to the development of standards for measuring continued competence. In 1981, the 1980 Primary Care Physician's Assistants Certification Examination was administered as a recertification examination to 1,166 PAs who were originally certified in 1975. The scores were standardized by using the standardization constants for the 1980 Certification Examination reference group. There was a difference between the performance of the certification examinees and the performance of the recertification examinees, with recertification examinees doing less well on all sections than the certification examinees. Correlations calculated between recertificants' performance on their original certification examination and their performance on the recertification examination showed a positive relationship between the two examinations. Their performance on a variety of biographical variables was also analyzed, and the only variable that significantly changed their performance was their current employment status. The validity of the test for making judgments about the competence of experienced practitioners was not addressed by the current study and is a crucial question in evaluating the test as a recertification instrument.

Plasma platinum levels: relationship to cisplatin dose and nephrotoxicity.

Renal dysfunction is the dose-limiting toxic effect for many patients receiving cisplatin (CP). Despite hydration and/or forced diuresis, some patients develop nephrotoxicity, and patients at risk cannot be easily identified. We studied 77 patients with several types of carcinoma who received 115 cycles of CP, by 24-hour infusion, at doses of 40-100 mg/m2. Blood samples for platinum (Pt) analysis were obtained during and after CP infusion; plasma Pt levels were dose- and time-dependent. A significant rise in serum creatinine was seen after the first cycle and cumulatively over subsequent CP cycles. The largest subgroup of patients, those who received 80 mg/m2, was analyzed for predictors of nephrotoxicity. Twenty-five percent of patients exhibited nephrotoxicity (greater than 30% rise in serum creatinine or greater than 30% fall in creatinine clearance). These nephrotoxic patients had significantly higher plasma Pt levels during CP infusion than did nonnephrotoxic patients. Age, sex, cycle number, and pretreatment creatinine did not predict nephrotoxicity. Patients predisposed to nephrotoxicity with CP chemotherapy may be identifiable, on the basis of elevated plasma Pt, early in the course of CP infusion.

Anomalies of pulmonary veins: usefulness of spin-echo and gradient-echo MR images.

OBJECTIVE: We compared the value of spin-echo and gradient-echo MR images in the evaluation of anomalies of pulmonary veins. MATERIALS AND METHODS: Fourteen patients with a variety of developmental anomalies of pulmonary veins underwent MR imaging examination. Axial T1-weighted spin-echo and gradient-echo MR images were evaluated retrospectively on separate occasions during which visualization of normal and anomalous pulmonary veins was determined. RESULTS: Of 52 pulmonary veins, 46 (88%) were identified on T1-weighted spin-echo images and 50 (96%) on gradient-echo images. Two patients had atresia of both left pulmonary veins. Of 14 anomalous veins, 11 (79%) were revealed on spin-echo images and 13 (93%) on gradient-echo images. CONCLUSION: Both spin-echo and gradient-echo MR images were accurate in revealing anomalies of pulmonary veins. In our study, gradient-echo images were equal or superior to spin-echo images.

Recognition of common childhood malignancies.

Although cancer has an annual incidence of only about 150 new cases per 1 million U.S. children, it is the second leading cause of childhood deaths. Early detection and prompt therapy have the potential to reduce mortality. Leukemias, lymphomas and central nervous system tumors account for more than one half of new cancer cases in children. Early in the disease, leukemia may cause nonspecific symptoms similar to those of a viral infection. Leukemia should be suspected if persistent vague symptoms are accompanied by evidence of abnormal bleeding, bone pain, lymphadenopathy or hepatosplenomegaly. The presenting symptoms of a brain tumor may include elevated intracranial pressure, nerve abnormalities and seizures. A spinal tumor often presents with signs and symptoms of spinal cord compression. In children, lymphoma may present as one or more painless masses, often in the neck, accompanied by signs and symptoms resulting from local compression, as well as signs and symptoms of systemic disturbances, such as fever and weight loss. A neuroblastoma may arise from sympathetic nervous tissue anywhere in the body, but this tumor most often develops in the abdomen. The presentation depends on the local effects of the solid tumor and any metastases. An abdominal mass in a child may also be due to Wilms' tumor. This neoplasm may present with renal signs and symptoms, such as hypertension, hematuria and abdominal pain. A tumor of the musculoskeletal system is often first detected when trauma appears to cause pain and dysfunction out of proportion to the injury. Primary care physicians should be alert for possible presenting signs and symptoms of childhood malignancy, particularly in patients with Down syndrome or other congenital and familial conditions associated with an increased risk of cancer.

MR imaging of congenital anomalies of the thoracic veins.

Congenital anomalies of the thoracic veins are infrequent but important developmental abnormalities. Thoracic venous anomalies can be classified as systemic or pulmonary. Systemic venous anomalies are often incidental findings, whereas pulmonary venous anomalies are more likely to manifest with cyanosis and to be associated with congenital cardiac abnormalities, especially atrial septal defect. Magnetic resonance (MR) imaging provides excellent delineation of the abnormal vessels and associated cardiac defects. Conventional spin-echo (SE) techniques show blood flow as a signal void and are sufficient for demonstrating the aberrant venous anatomy in most cases. Gradient-echo images show flowing blood as high signal intensity and are useful for clarifying the course of anomalous veins when vessel walls are difficult to visualize on SE images. Phase-contrast images are valuable for ascertaining the direction of blood flow and thus provide a physiologic method of distinguishing the vertical vein of anomalous pulmonary venous return from a left superior vena cava. MR imaging is useful for delineating both the thoracic venous and accompanying intracardiac anomalies and is a valuable, complementary technique to echocardiography, angiography, and computed tomography in the evaluation of patients with these abnormalities.

Cromolyn sodium prophylaxis inhibits pulmonary proinflammatory cytokines in infants at high risk for bronchopulmonary dysplasia.

An imbalance of proinflammatory cytokines such as TNF-alpha, IL-1 beta, and the neutrophil chemotactic factor IL-8 and inhibitors (e.g., soluble TNF receptors and IL-1ra) in the lung during the first week of life may contribute to prolonged pulmonary inflammation and fibrosis in bronchopulmonary dysplasia (BPD). Disodium cromoglycate (DSCG) has anti-inflammatory effects in asthma, a disease with many similarities with BPD. In a prospective, randomized, blinded study, we examined whether early DSCG therapy inhibits proinflammatory cytokines in infants at risk for BPD. Twenty-six infants who were identified as high risk (> or = 75% probability) for oxygen-dependency at 28 d by a 12-h predictive score and survived 48 h were randomized to nebulized DSCG 20 mg (n = 13) or 2 cc NS (control, n = 13) every 6 h from Day 3 to Day 28. Lung lavage was collected on Day 3 (pre-study) and Day 7 and analyzed for cell count and differential and TNF-alpha, sTNFR1, sTNFR2, IL-1 beta, IL-1ra, and IL-8 concentrations. The groups' pre-study lavage cytokine concentrations were similar, but TNF-alpha and IL-8 concentrations were 3.6- and 4.9-fold lower in the DSCG group on Day 7 compared with levels in the control group. Soluble TNF receptors were unaffected by DSCG. There was a trend towards lower IL-1 beta levels in DSCG-treated infants on Day 7, but IL-1ra levels were unaffected by DSCG therapy. Three control subjects, but no DSCG-treated infants, died during the study period (p = 0.07). There were no significant differences between survivors of the two groups for oxygen-dependency at 28 d (100% control subjects; 85% DSCG). These results suggest that nebulized DSCG may exert an anti-inflammatory effect in the lungs of infants < or = 1,000 g at risk for BPD.

Interpretation and physiological significance of diastolic coronary artery pressure-flow relationships in the canine coronary bed.

We analyzed the relationship between diastolic coronary artery pressure and flow in the canine coronary bed, using an electrical analog model of the coronary circulation based on the theory of critical closure. The model contains a voltage-dependent nonlinear resistance and capacitance. The behavior of the resistive element was described using experimental diastolic pressure-flow curves obtained in the absence of compliance effects. Compliance free zero flow pressure intercepts (Pf0) exceeded coronary venous pressure (Pv) by 2- to 5-fold and were related to initial diastolic coronary artery pressure Pa(0) and flow F(0), and Pv by: Pf0 = 14.3 [(Pa(0) - Pv)/F(0)] + Pv + 4.0 (r = 0.93). When coronary artery pressure was suddenly lowered to values less than or equal to the compliance-free Pf0, diastolic flow abruptly decreased and, after a transient reversal, remained at zero for up to 8 seconds. In the model, zero flow pressure represents critical closing pressure and the resistance regulating flow is the difference between coronary artery and venous pressure divided by flow. Theoretically predicted pressure-flow curves were in good agreement with existing experimental data, including the effects of elevating coronary venous pressure on zero flow pressure. Differences between compliance-free pressure-flow curves and those obtained with pressure gradually decreasing were explained by a coronary arterial compliance whose magnitude varies inversely with pressure and is dependent on vasomotor tone. In conclusion, the results of this study demonstrate the existence of a diastolic pressure gradient across the canine coronary bed at zero flow which is dependent on coronary vasomotor tone. A theoretical model of the coronary circulation based on the concept of critical closure describes the observed relationship between diastolic coronary artery pressure and flow during various experimental conditions.

Human herpesvirus-8 (HHV-8) associated with small non-cleaved cell lymphoma in a child with AIDS.

The association of human herpesvirus-8 (HHV-8) with a small non-cleaved cell lymphoma is described in a child with the acquired immunodeficiency syndrome (AIDS) who developed a malignant pleural effusion and radiologic evidence of multiple solid tumors. HHV-8 DNA and Epstein-Barr virus DNA were identified in pleural fluid cells by polymerase chain reaction (PCR) amplification. The serum antibody titer against lytic HHV-8 proteins was 1:640; antibodies to latent HHV-8 proteins were not detected. Cytogenetic analysis of malignant cells revealed three abnormal karyotypes sharing the common finding of a t(8;14) translocation. Rearrangement of c-myc was demonstrated by PCR analysis. Oligoclonal JH immunoglobulin bands were found. Insufficient pleural fluid cells were available to permit localization of HHV-8 to malignant cells by in situ hybridization. This malignancy contrasts with HHV-8-associated lymphomas reported in adult patients with AIDS with respect to cell morphology, c-myc translocation, and oligoclonal immunoglobulin gene rearrangement. HHV-8 is associated with a wider spectrum of malignancies than recognized previously.