Optimization by simulated annealing of three-dimensional, conformal treatment planning for radiation fields defined by a multileaf collimator: II. Inclusion of two-dimensional modulation of the x-ray intensity.

Interest is rapidly growing in using multiple x-radiation fields defined by a multileaf collimator to achieve conformal radiotherapy. Three-dimensional treatment planning in such situations is in its infancy and most 3D planning systems provide no tools for optimizing therapy. A previous paper addressed how to calculate optimum beamweights when both the target volume and all or some parts of organs at risk were in the fields-of-view. This work allowed a maximum of two weights per field. The present paper extends this technique to allow each radiation port to be spatially modulated across the geometrically shaped field. An optimization method based on simulated annealing is presented. It is shown that including spatial modulation leads to a wider separation between the dose-volume histograms of the target volume and organs at risk. The improvement is quantified in terms of the tumour control probability at constant normal tissue complication probability. Possible limitations of the a posteriori applied biological model are discussed in detail.


Physical characterization of the replication origin of the cryptic plasmid pCB101 isolated from Clostridium butyricum NCIB 7423.

The complete nucleotide sequence of a 3484-bp Sau3A fragment, previously shown to carry the replication origin of the Clostridium butyricum NCIB 7423 plasmid pCB101 (6.05 kb), has been determined. Of the four open reading frames (ORF A-D) identified within this fragment, two (B and C) were shown to be encoding by in vitro transcription/translation assays. Evidence was obtained that both polypeptides are required for autonomous replication of the plasmid in Bacillus subtilis. ORF C is immediately preceded by a small ORF (C') that encodes a relatively small polypeptide (50 amino acids) that demonstrates significant homology with RepA of plasmid pLS1. Whereas the ORF C polypeptide (27,100 Da) exhibits no homology to any known protein, that encoded by ORF B (RepB, 43,039 Da) exhibits significant homology with the Rep proteins of the pC194/pUB110 subfamily of single-strand (ss) DNA plasmids, which are widely distributed in gram-positive bacteria. Conserved amino acids include the presumed active site of topoisomerase activity and four cysteine residues in the N-terminus of all Rep proteins compared. The repB gene is preceded by a sequence motif exhibiting substantial homology to the "plus" origins of this family of ss DNA plasmids and was shown to act as a "hot spot" for deletion formation in certain plasmid chimaeras. The compelling suggestion that pCB101 replicates via a rolling circle mechanism was substantiated by the demonstration of ss DNA replication intermediates in B. subtilis cells carrying a pCB101-derived plasmid.


Construction and characterization of shuttle plasmids for lactic acid bacteria and Escherichia coli.

The chimeric plasmid pBN183 was first constructed in Escherichia coli by ligating the BamHI-digested E. coli plasmid pBR322 and a Bg/II-linearized streptococcal plasmid, pNZ18. The pBN183 transformed E. coli to ApR at a frequency of (8.2 +/- 1.2) x 10(5) colony forming units (CFU)/microgram DNA. Electrotransformation of Streptococcus thermophilus with pBN183 yielded CmR, ApS clones at a frequency of (2.6 +/- 0.3) x 10(1) CFU/microgram DNA. Plasmid screening with pBN183-transformed S. thermophilus clones revealed that ca. 70% of these transformants contained deleted plasmids. Plasmid pBN183A, a pBN183 deletion mutant lacking one copy of a tandemly arranged, highly homologous DNA sequence, was isolated for further study. It transformed E. coli to ApR and S. thermophilus to CmR with frequencies of (4.8 +/- 0.1) x 10(5) and (8.1 +/- 0.2) x 10(2) CFU/microgram DNA, respectively. Screening of S. thermophilus transformants did not show the presence of deleted plasmids. Based on the structure of pBN183A, a new shuttle plasmid, pDBN183, was constructed from pBN183 by removal of the small (1.2 kb) Sa/I fragment. Transformation frequencies of pDBN183 were (5.0 +/- 1.3) x 10(5) and (4.6 +/- 0.2) x 10(2) CFU/microgram DNA with E. coli and S. thermophilus, respectively. In contrast to the parent pBN183, only 17% of the pDBN183-transformed S. thermophilus contained deleted plasmids. Plasmid copy numbers of the three vectors in E. coli were estimated at 17-18 per chromosome. The three plasmids conferred ApR and CmR to E. coli, but only CmR to S. thermophilus. The insertion of a Streptomyces cholesterol oxidase gene (choA) into pDBN183 did not affect the plasmid's stability in Lactobacillus casei, but resulted in deletion of the recombinant DNA in S. thermophilus.


Dictyostelium giganteum plasmid Dgp1 is a member of the Ddp2 plasmid family.

Dgp1, a circular 4.4-kb plasmid found in the nuclei of Dictyostelium giganteum strain DG61, is a member of the same plasmid family as plasmids Ddp2 and pDG1. Dgp1 has sequence similarity to a conserved region of the Ddp2 and pDG1 open reading frames. As with Ddp2 and pDG1, a single large RNA is transcribed from Dgp1. This 3.3-kb transcript is present at about 350 copies per vegetative cell. The transcript abundance decreased about 10-fold in early aggregation and continued at this lower level until late culmination when it returned to the level seen in vegetative cells. Dgp1 has a repeat of several hundred base pairs in a location, relative to the transcribed region, similar to the inverted repeats found in Ddp2 and pDG1. Dgp1 cannot be maintained as a plasmid in Dictyostelium discoideum AX4 cells, suggesting that Dgp1 carries species-specific maintenance elements.


Selection of Dictyostelium discoideum transformants and analysis of vector maintenance using live bacteria resistant to G418.

A protocol that allows the rapid isolation and growth of large numbers of independent G418-resistant Dictyostelium discoideum transformant colonies on the surface of agar media with live bacteria was developed. Transformants grown under these conditions form normal fruiting bodies. Discovery that aggregation of nontransformants was inhibited at a nonselective level of G418 (25 to 35 micrograms/ml) led to the development of a vector maintenance assay. Using this assay we examined the stability of recombinant plasmids derived from the D. discoideum native plasmids Ddp1 and Ddp2. We conclude that the origin of replication of plasmid Ddp1 does not alone confer stable maintenance and thus, Ddp1 must bear additional sequences required for its own maintenance. Analysis of the maintenance of vectors derived from Ddp2 showed that autonomously replicating shuttle vectors that contained bacterial plasmid DNA and from which one element of the Ddp2 inverted repeat was removed were much less stable than vectors that contained a complete inverted repeat or that did not carry a bacterial plasmid. Sequences between the 3' end of the rep gene and the inverted repeat appear to play a role in plasmid maintenance. An intact rep gene and one copy of the inverted repeat element were required for extrachromosomal replication. Maintenance of extrachromosomal vectors was found to be strain dependent. Four traits distinguishing integrating vectors from those capable of autonomous replication were identified.


Transfer of a plasmid determining bacteriocin Bc-48 production and immunity, and response to sexual pheromones in Enterococcus faecalis S-48.

Production of bacteriocin Bc-48 by Enterococcus faecalis S-48 is encoded by the conjugative plasmid pMB1, which is approximately 90 kb and also responds to sex pheromones of E. faecalis OG1X. Mutants harboring deleted forms of this plasmid (pMB1-del, 75 kb) have lost both the phenotype Bc-48 (production and immunity) and the clumping response. The conjugal transfer of pMB1 to E. faecalis OG1X results in the acquisition by this strain of both bacteriocin production and immunity and also the clumping response. In the transconjugants isolated, the bacteriocinogenic trait is associated with a smaller plasmid (52 kb), which we call pMB1-1. The relationship among plasmids pMB1, pMB1-del, and pMB1-1 has been demonstrated by DNA hybridization. Plasmid pMB1-1 has been transferred with high frequency to E. faecalis mutants cured of Bc-48 production (carrying pMB1-del), conferring to them the Bc-48 trait and clumping response. In the transconjugants from a second mating, pMB1-1 and pMB1-del coexist without appreciable segregation.


Plasmid pTB913 derivatives are segregationally stable in Bacillus subtilis at elevated temperatures.

We studied the effects of temperature on the segregational stability of derivatives of the rolling-circle-type plasmid pTB913 in Bacillus subtilis. This 4.5-kb plasmid is a deletion derivative of pTB19, which was originally isolated from a thermophilic Bacillus. pTB913 derivatives carrying large inserts or lacking the minus origin for complementary strand synthesis were segregationally unstable at 37 degrees C. In contrast, at 47 degrees C all pTB913 derivatives tested were stably maintained in B. subtilis. The increased stability at 47 degrees C was attributed, at least partly, to increased copy numbers at this temperature. Although considerable amounts of single-stranded and high-molecular-weight plasmid DNA were formed at 47 degrees C, these products did not reduce plasmid stability at this temperature. The increased stability and increased copy number of pTB913 at elevated temperatures extend the use of this plasmid as a cloning vector in B. subtilis and other bacilli.


Nucleotide sequence of Mycoplasma mycoides subspecies Mycoides plasmid pKMK1.

To facilitate the development of mycoplasmal cloning vectors, we have determined the nucleotide sequence of pKMK1, a cryptic plasmid isolated from Mycoplasma mycoides subsp. mycoides. It is 1875 bp in length and contains two open reading frames (ORFs) that share homology with ORFs from members of a large family of gram-positive bacterial plasmids which replicate via a single-stranded DNA intermediate. Putative origins of replication and candidate cloning sites have been identified.


The environment and population growth: decade for action.

The signs of environmental stress grow as the world's population increases: worn-out farmlands, eroded hillsides, polluted water, parched grasslands, smoke-laden air, depleted ozone, and treeless ranges. Each year about 17 million hectares of tropical forest vanish--an area the size of Tunisia or Uruguay. Fish catches are leveling off. Cities are clogged with refuse. Water and air, instead of sustaining life, cause disease.


Self-rated inhibited anger, somatization and depression.

In order to examine the relationship of self-rated inhibited anger to somatization, the authors administered several self-rating scales, including the SCL-90 and a Likert scale pertaining to inhibited anger, to psychiatric patients and family practice patients of both sexes. In a linear stepwise regression, depression predicted inhibited anger in all four groups. Previous studies have reported an association of inhibited anger and somatization; the present study suggests that depression is the link between the two in the majority of patients. The relationship of inhibited anger to depression may have implications for psychotherapy.


Critical life changes. A review of research.

This review of ideas presented in life event research presents a psychological and a sociological research tradition. Physiological recordings of endocrine factors have been utilized in studies of life events both in the study of natural course (bereavement and accidents, for instance) and in the laboratory during talk about critical life events. Recently, several programmes have been started for improving people's life event tolerance. However, 'eventlessness' has also been observed to be a possible disease-provoking factor.


Psychological reactions to medical procedures.

Many medical procedures evoke anxiety and discomfort. Despite substantial research effort showing the efficacy of psychological interventions, there is abundant evidence that patients remain inadequately prepared. This review of well-tried approaches demonstrates that varied interventions are required to reduce stress and discomfort and outlines ways in which staff should apply the research findings.


Hyperprolactinaemia as a result of immaturity or regression: the concept of maternal subroutine. A new model of psychoendocrine interactions.

Pathological hyperprolactinaemia (PH) is significantly associated with: (1) paternal deprivation during childhood, (2) depression, (3) non-specific symptoms including obesity and weight gain. The clinical onset of the symptoms often follows pregnancy or a loss. Prolactin is an insulin antagonist which does not promote weight gain. Hyperprolactinaemia and increased metabolic efficiency are parts of a system of interdependent behavioural and metabolic mechanisms necessary for the care of the young. We call this system, which is available as a whole package, maternal subroutine (MS). An important number of cases of PH are due to activation of the MS that is not induced by pregnancy. The same occurs in surrogate maternity and in some animal models. Most women with PH developed a malignant symbiotic relationship with their mothers in the setting of absence, alcoholism or devaluation of the father. These women may regress to early developmental stages to the point that they identify themselves both with their lactating mother and with the nursing infant as has been found in psychoanalysed patients and in the paradigmatic condition of pseudopregnancy. Such regression can be associated with activation of the MS. Prolactinomas represent the extreme of the spectrum of PH and may result from somatic mutations occurring in hyperstimulated lactotrophs.


The training of the psychiatrist in relation to the new trends in psychiatry.

One of the most important things to realize about modern Psychiatry is that many factors are involved in the pathogenesis and especially in the evolution of mental diseases. The results of epidemiological research and the development of different schools with separate specializations have shown the importance of extrasubjective factors such as family environment, social context, life events and life stressors, and therefore the need to find therapeutic strategies which are able to influence the different areas. From this wide spectrum arises the necessity for a functional integration of the different therapeutic areas in the operative context, also because of the nonhomogeneity and the frequent random choice of reference models by the operators and the mental health services. In this study we propose a training model which allows the achievement of this integration ability at an operative level, and which at the same time defines its limits.


Alexithymia and obesity. Study of the impaired symbolic function by the Rorschach test.

Many authors consider alexithymia a predisposing factor to psychosomatic and somatopsychic pathologies. In this study we investigated the presence of alexithymic characteristics in a group of 106 massive obese patients who requested a surgical intervention. 6 Rorschach alexithymia variables in the protocols of patients and a non-patient reference group (n = 600) were studied. Findings supported the presence of a striking alexithymic element among severely obese patients in comparison with their lean counterparts.


Relationship between conjugate lateral eye movements and alexithymia.

The relationship between conjugate lateral eye movements (CLEMs) and alexithymia was investigated in a group of 60 (23 male and 37 female) right-handed university students. Subjects completed the Toronto Alexithymia Scale (TAS), the Schalling-Sifneos Personality Scale, and the Basic Personality Inventory, which measures 12 basic dimensions of personality and psychopathology, CLEMs were recorded while subjects were asked 20 general knowledge questions that have no tendency to elicit eye movements predominantly in one direction. A series of gender by CLEM preference (left vs. right mover) ANOVAs were conducted with the various measures. There was a significant relationship between right CLEM preference and higher scores on the TAS, but no relationships between CLEMs and any of the other measures. These results suggest that alexithymia is associated with left cerebral lateralization, and support the hypothesis that alexithymic characteristics reflect a variation in brain organization.


Selected topics in pediatric ultrasonography--1992.

In children, ultrasonography has been valuable in demonstrating a wide range of congenital lesions that were previously seen indirectly or only after more invasive procedures. It has replaced many studies that necessitated oral or vascular contrast and ionizing radiation. Real-time ultrasonography has found a role in the evaluation of the diaphragm, gastroesophageal reflux, bowel peristalsis, and hip stability.


Recent advances in sonography of the testis and scrotum.

Ultrasonography remains an accurate, rapid, and safe tool in the imaging of disorders of the testes and scrotum. The strengths of gray scale sonography lie in its ability to distinguish intratesticular from extratesticular processes. Improvements in resolution permit greater confidence in the characterization of lesions as representing simple fluid, complex fluid, or solid lesions. The addition of flow information by color Doppler ultrasonography and duplex Doppler ultrasonography represents the most exciting recent advancement, permitting even more diagnostic information in the evaluation of these patients.


Ultrasonographic evaluation of renal transplantation.

Ultrasonography of the renal transplant is still a key screening examination for transplant dysfunction. The addition of Doppler technology has permitted screening for hemodynamic alterations. Ambitious researchers predicted that these hemodynamic profiles would permit the differentiation of rejection from other complicating factors; however, recent research and clinical experience has shown this to be ineffective. Imaging identification of a dilated collecting system identifies the patient population that should undergo a Whitaker procedure. Identification of large or increasing fluid collections helps focus attention to possible hemorrhage or urine leak. Similarly, the ultrasonographic identification of a lymphocele as the cause of leg edema or hydronephrosis rapidly focuses surgical treatment. Doppler evaluation of hemodynamics must be performed on all renal transplant recipients. Although the role of the resistive index in predicting rejection has been minimized lately, numerous vascular complications, if untreated, would result in loss of the kidney. Doppler sonography identifies those patients who would benefit most from renal arteriography. The evaluation of renal morphology on the basis of ultrasonography alone has little role in predicting the cause of transplant dysfunction. We continue to evaluate renal size and to correlate it with the clinical presentation as well as resistive index to defer patients from biopsy if a more obvious cause of dysfunction is identified.


Endoscopic ultrasonography of the upper gastrointestinal tract.

Endoscopic ultrasonography combines the advantages of conventional endoscopy with the capabilities of ultrasonography. This permits the examiner to see through the wall of the gastrointestinal tract. The close proximity permits the use of relatively high frequencies, with the resulting increase in tissue contrast and resolution. There are limitations to its use, however, with the main one being a field of view limited to a 7-cm radius. Discussed in this article is its use for the gastrointestinal wall, the esophagus, the stomach, the duodenum, and the pancreas.


Intraoperative ultrasonography.

Four major benefits of intraoperative ultrasonography (IOU) were determined after its use in more than 2400 operations. They are the acquisition of new information not otherwise available, complement of or replacement for operative radiography, guidance of surgical procedure, and confirmation of completion of operation. IOU also has the advantages of safety, speed, higher accuracy, acquisition of more information, and wider application over operative radiography. Intraoperative color Doppler imaging, which has been introduced recently, seems to provide additional beneficial information during cardiovascular and general surgery. We believe that IOU should have a wider application and that surgeons and radiologists should develop cooperative working relations similar to those that exist for operative radiography.


Ophthalmic ultrasonography.

Definition and differentiation of ocular structures and abnormalities necessitates the use of high-frequency, high-resolution, and high-definition ultrasound. Frequencies of 10 to 100 MHz are being employed. Color Doppler imaging, tissue characterization, parameter image staining, and three-dimensional volume rendering are new and useful adjuncts to ocular diagnosis.


Arterial vascular ultrasonography.

A new generation of high frequency, high resolution ultrasound scanners has provided unprecedented information about the state of the arterial wall in a variety of superficial vessels and can document the disturbed flow within them. The information now available is of great clinical value to many clinicians, including vascular surgeons and subspecialty internists who care for individuals at risk for accelerated atherosclerosis and other vascular diseases.


Venous ultrasonography.

Compression ultrasonography supplemented by pulsed and color Doppler imaging is the diagnostic modality of choice for evaluating lower extremity deep vein thrombosis in symptomatic and asymptomatic high-risk patients. Furthermore, this technique frequently can characterize the clot as occlusive or nonocclusive or acute or chronic and can define the extent of disease. In patients without thrombosis, this modality can suggest an alternative diagnosis in 12% of patients.


Current status of intravascular ultrasonography.

Intravascular ultrasonography provides unique diagnostic information about vessel wall structure and underlying disease. It has been shown to be superior in both the detection of atherosclerotic plaque and in the quantification of extended disease. Future applications will include three-dimensional ultrasound and integration into interventional devices. It has been of particular clinical value in the performance of percutaneous atherectomy and intravascular stent deployment.


Musculoskeletal ultrasonography.

The scope of musculoskeletal ultrasonography has broadened considerably since its inception. Ultrasonography has established itself as a reliable cost-effective modality for the diagnosis and follow-up of a wide variety of lesions. Its real-time dynamic capability adds a perspective that other modalities lack. Growth within this field will continue, driven by improved technology, cost consciousness, and the creativity of those who employ this powerful diagnostic tool.


Ultrasonography of the shoulder.

Shoulder sonography has been shown to be an effective noninvasive means of detecting rotator cuff tears and biceps tendon abnormalities. The examination requires careful attention to technique and a thorough knowledge of normal gross and sonographic anatomy. Rotator cuff tears generally cause a diffuse or focal decrease in the space between the humeral head and the deltoid muscle. Therefore, tears are easiest to detect by noting abnormally close apposition of the deltoid and humeral head.


Ultrasonography of the neck.

The anatomic and pathologic involvement of the structures in the neck can be accurately studied with small parts ultrasonography. The thyroid and parathyroid glands and nodal chains are treated in this article; masses of the neck spaces are not considered because of their relative rarity.


Transvaginal ultrasonography.

Transvaginal ultrasonography has provided new anatomic and pathophysiologic information about the female pelvis. Because of probe proximity to the organ of interest and higher insonating frequency, resolution is dramatically improved. Problems previously encountered during transabdominal scanning, such as obesity, bowel gas, and a retroverted uterus, no longer preclude accurate diagnosis. Patient acceptance is nearly universal. Physiologic information concerning the endometrium and ovarian follicles has improved infertility diagnosis and treatment. Hormonal and vascular Doppler changes can be correlated with cyclic endometrial patterns and follicle size. Oocyte retrieval, management of pre-existing inflammatory disease, and treatment of complications of pregnancy are easier and safer with a transvaginal approach. Uterine malformations, leiomyomas, and cancers are more easily detected in premenopausal and postmenopausal women. The documentation of early intrauterine or ectopic pregnancy has decreased maternal morbidity and mortality. Tube-sparing procedures with preservation of reproductive potential are now more commonly employed due to earlier recognition of unruptured tubal pregnancy. Interventional TVS has led to improved recognition and treatment of pelvic cysts and abscesses and multiple pregnancy. Chorionic villous sampling can be performed more easily without the need for anesthesia, with adequate tissue obtained.


Smaller parts scanning of the fetus.

Current instrumentation provides capabilities for minute fetal anatomic exploration and for integrative physiologic inference. This extends the complexity of the study and the diagnostic obligation of the examiner. The direction of study and clarification of findings devolve increasingly upon pathology and pathophysiology rather on than prior imaging experience. We believe that smaller parts scanning has a role in every fetal examination. An increasing number of reports in the literature attest to the improvement in anatomic imaging for first trimester detection of anomalies. Focused, microregion anatomic perusal is applicable throughout pregnancy, provides information for physiologic inference, and can be used for prediction of pathology, detection of abnormalities, and, in most examinations, in a wellness role of confirming normality. A conceptual paradox is associated with smaller parts scanning. As the examiner concentrate on progressively more minute regions and structures, it becomes increasingly important to analyze findings in a holistic, or perhaps holographic, context. This is evident in fetal studies in which any local facet of development affects the entire process of gestation. The specific signs we use for sampling the developmental process vary in utility and reliability depending on technical capabilities, operator expertise, and regional population effects. Fetal studies are inseparable from parental emotional, physical, and genetic factors, which must be recognized and addressed as the study proceeds.


Breast ultrasonography.

Ultrasound of the breast has a role both as the primary and as an ancillary modality in the work-up of breast abnormalities. Its main role is to differentiate cystic from solid abnormalities and to thereby guide further work-up and intervention. Only the diagnosis of a simple cyst will obviate the need for further evaluation or therapy. Doppler ultrasonography of breast lesions may give further information in the future, although this is currently not employed in clinical practice. Various types of ultrasound examinations may yield useful information in the patient with breast cancer or in women with breast prostheses.


[The reference and counter-reference system in a community health service].

This study has been carried out at the Community Health Service of the Conceição Hospital/Porto Alegre/RS, with the aim of describing its reference and contra reference system. After two weeks observing this system, patients were interviewed at home. The results showed the demand of the service relating to the various levels of assistance. Some problems that prevent the reference system from its best functioning in this service were also pointed out.


Transcatheter treatment of pulmonary outflow tract obstruction: a review.

The role of transcatheter methods in the management of pulmonary outflow tract obstruction are discussed in this review. Balloon pulmonary valvuloplasty for relief of isolated pulmonary valve stenosis has been successfully used by many investigators and is the procedure of choice for the management of these lesions. Supravalvar pulmonic stenosis, if discrete, can be relieved by balloon dilatation. Cyanotic children with interatrial right-to-left shunts secondary to severe valvar pulmonary stenosis respond in a manner similar to that observed with isolated pulmonary valve stenosis. In these patients, balloon valvuloplasty is the treatment of choice and may be corrective in most patients. In patients with interventricular right-to-left shunting secondary to pulmonary outflow tract obstruction and in patients with narrowed BT shunts, balloon dilatation may be an effective palliative procedure in a substantial proportion of patients obviating the need for an initial or second palliative shunt. Balloon dilatation is recommended if the patient's size or cardiac anatomy make them unsuitable for safe total surgical correction. In patients with pulmonary atresia, either initial opening of the atretic pulmonary valve by laser or by surgery with subsequent balloon dilatation are potentially beneficial in reducing the total number of surgical procedures that these children are likely to require. However, further clinical trials are needed before their general use.


[Developing critical thinking on the questions of nursing teaching and practice].

The aim of this article is to offer an overview about the applicability of critical thinking to nursing education and nursing practice. Following, Brookfiels's (1987) model is applied to nursing situations.


[Is nursing a science or a profession?].

Traditionally, human knowledge has been considered in the context of disciplines which can be divided in two groups: Academics and professionals. The aim of academic disciplines is the knowledge and their theories are descriptive in nature. For this reason they are named science. In contrast, professional disciplines are move comprehensive, directed toward practical aims and there is a need to and to work. Nursing as a professional discipline has been influenced by four school of thought named; service, administration, academic and practice. Currently the nursing practice is developed based on three different theoretic and philosophic branches.


[The thinking about women, health and work in the hospital].

This article deals with the relation women, health and work at hospital. Working relationships are thought in a gender perspective represented in a sexual division of work. Through a discussion about this subject, we intend to rise questions and reflect upon the reality of health care female workers.


[Reflections on the introduction of informatics into the nursing profession].

The paper is an analysis about the impact of introducing informative technology and its consequences in the society, in general professions and mainly, in nursing practice. The authors emphasize the need of major discussions about the insertion of this new technology in nursing profession.


[Invasive procedures and complications in patients with craniocerebral trauma hospitalized in an intensive therapy unit].

The present study realized with 50 patients from an Intensive Care Unit, due to head injury and considering that the majority of them presented a score equal or below six (6) in the Glasgow Coma Scale, has shown that the utilization of invasive procedures is high. Regarding complications, there was predominance of fever, upper airway secretions, hematomas at the arterial puncture localization and diarrhea. Proportionally, the patients under a clinical treatment presented a lower number of invasive procedures and problems and the reverse occurred with those under surgery. The analysis of the association of the invasive procedures and problems compared to the level of consciousness has been affected.


[An analysis of the socioeconomic and reproductive conditions of women from a peripheral community of Porto Alegre, Rio Grande do Sul].

This work is based on the analysis of a research where the socioeconomic conditions of women, with ages ranging from 15 to 44 years old, living in a community situated in the outskirts of Porto Alegre, were investigated. A relation was established between those conditions and the reproductive behavior of the subjects.


Immunoblotting as a valuable tool to differentiate human visceral leishmaniasis from lymphoproliferative disorders and other clinically similar diseases.

Diseases presenting with splenomegaly, fever and pancytopenia require intensive differential diagnostic considerations. These diseases include lymphoproliferative and autoimmune diseases, but also chronic infections like mansonian schistosomiasis or visceral leishmaniasis (kala-azar). Diagnosis for the latter is usually performed by testing for the presence of antileishmanial antibodies using the immunofluorescence test (IFT) or the enzyme-linked immunosorbent assay (ELISA) technique. Here, we report on patients who displayed positive antileishmanial antibody titres in the IFT and/or ELISA, but did not develop kala-azar and were eventually diagnosed as having one of the non-kala-azar diseases listed above. These false-positive sera proved to be seronegative when tested on a Leishmania immunoblot. Our studies lead us to recommend the immunoblot technique as a confirmatory test in cases with doubtful IFT or ELISA antibody titres.


Milky spots in the mouse omentum may play an important role in the origin of peritoneal macrophages.

In the milky spots, precursors of cells belonging to the mononuclear phagocyte system (MPS), such as monoblasts, can be found on the basis of ultrastructural endogenous peroxidase cytochemistry. Therefore, in the present study, we investigated the milky spots using a panel of monoclonal antibodies, especially antibodies (ER-MP) that recognize macrophage precursor antigens. Early macrophage precursor antigens ER-MP12 and ER-MP58 were detected only on cells localized inside the milky spots. On the other hand, an antigen which disappears late in the course of macrophage differentiation, ER-MP20, was detected in high amounts on cells both inside and around the milky spots. This clearly indicates that macrophage precursors are centrally localized inside the milky spots, while more differentiated cells are found in peripheral areas. Moreover, long-term culture of milky spot tissue resulted in the forming of a monolayer of stromal cells which supported macrophage proliferation in vitro. In conclusion, both in situ and in vitro studies demonstrated that mouse milky spots have a microenvironment in which precursor cells of the MPS can home and proliferate, illustrating that milky spots play a role as a source of local macrophage generation, e.g. that of the free peritoneal macrophages.


Correlation between a hepatic copper accumulation and an altered expression of glutathione S-transferase Ya/Yc subunits in LEC mutant rat.

Long-Evans Cinnamon (LEC) rat, an animal model of Wilson's disease, that develops a necrotizing hepatic injury with an abnormally high hepatic copper accumulation exhibits an altered expression of glutathione S-transferase (GST) subunits, that is, a low percentage of the Ya and a high percentage of the Yc subunit expression in males. The altered expression of GST subunits and the abnormal copper accumulation in liver were found to be completely correlated in male LEC mutant rat liver, suggesting that the copper toxicity caused by the anomaly of copper metabolism in LEC rat liver leads to the altered expression of GST subunits.


Effect of p-xylene metabolites, p-methylbenzyl alcohol and 2,5-dimethylphenol, on rat hepatic and pulmonary microsomal metabolism.

Pulmonary metabolites of p-xylene, p-methylbenzyl alcohol (PMBA) and 2,5-dimethylphenol (DMP), were employed to investigate the divergent effects of p-xylene on pulmonary and hepatic metabolism. Rats were given PMBA, DMP, or 10% cremophore (control) ip daily for 3 days, and effects on hepatic and pulmonary microsomal metabolism were determined 12 hours later. Both PMBA and DMP mimic the decrease in pulmonary benzyloxyresorufin-O-debenzylase activity previously reported for p-xylene, but neither could account for the potent induction of cytochrome P450 in the liver. Only PMBA had a consistent effect on P450IIB apoprotein levels, decreasing them in both the liver and lung. These data suggest that PMBA may have a significant role in the inhibition of pulmonary P450 caused by p-xylene.


The effects of isoproterenol on the isolated perfused rat heart.

In isolated hearts infused with up to 100 ug/ml isoproterenol (ISO), there was only a transient effect on the frequency of contraction, and no effect on buffer flow through the heart. Infusion of hearts with 40-60 or 70-100 ug/ml ISO produced an increase in the release of lactate dehydrogenase, but not creatine kinase. Microscopic examination of hearts revealed myocyte separation and cytoplasmic vacuolation, of similar severity, in both control and ISO infused hearts; there was no necrosis. The data from this experiment are consistent with the view that ISO has little or no direct toxic effect on the heart. Since ISO is cardiotoxic In vivo, it is reasonable to suppose that this toxicity is linked primarily to the pharmacological effects of the drug. However, our study does not exclude the possibility that under the stressed conditions prevailing in vivo following a challenge with ISO, the susceptibility of myocytes to a direct toxic effect of ISO may increase.


Factors affecting acetohexamide reductase activities in microsomes and cytosol from the kidney of male rats: age and castration.

Acetohexamide reductase activity in microsomes from the kidney of male rats increased markedly at puberty to approach the maximum level at 8 weeks of age; it was not detected until 4 weeks of age. Furthermore, castration suppressed effectively the activity in kidney microsomes at 8 weeks of age. These findings clearly indicate that the activity in kidney microsomes can be regulated by androgens. On the other hand, in cytosol from the kidney of male rats, a higher acetohexamide reductase activity was observed at all weeks of age tested. Castration had no significant effect on the activity in kidney cytosol.


Identification of a constitutive form of cytochrome P-450 with high activity towards macrolide antibiotics in Syrian golden hamster liver.

The presence of cytochromes P450 belonging to the P450IIIA family was investigated in the liver of untreated Syrian golden hamsters and compared to those of untreated, phenobarbital- and dexamethasone-treated rats. The microsomal preparations from untreated Syrian golden hamster livers exhibited higher activities of N-demethylation towards the macrolide antibiotics, erythromycin and troleandomycin, than those from untreated and phenobarbital-treated rats. Western blots analysis revealed larger amounts of proteins immunorelated to the rat cytochrome P450IIIA1 isozyme in Syrian golden hamster liver than in untreated and phenobarbital-treated rats. The N-demethylation of erythromycin and troleandomycin were strongly inhibited after preincubation of the microsomes from Syrian golden hamsters with anti-P450IIIA1. We conclude that a cytochrome P450 belonging to the P450IIIA family is expressed constitutively in the liver from Syrian golden hamsters, whereas it is not in rat liver.


Clinical significance of benzoate-metabolizing capacity in patients with chronic liver disease: pharmacokinetic analysis.

Benzoate-metabolizing capacity was studied in control subjects and in liver disease patients after intra-venous loading of 15 mg benzoate per kg of body weight. In the 7 control subjects, the mean level (+/- SEM) of Cmax for serum benzoate was 104.1 +/- 6.8 micrograms/ml, AUC was 2.57 +/- 0.32 mg.min/ml, MRT was 21.5 +/- 1.5 min and T1/2 was 15.5 +/- 1.3 min. For serum hippurate, on the other hand, Tmax was 27.9 +/- 6.0 min, Cmax was 33.4 +/- 2.1 micrograms/ml, AUC was 1.96 +/- 0.13 mg.min/ml, MRT was 39.6 +/- 2.9 min and T1/2 was 30.7 +/- 2.4 min. In 12 patients with chronic hepatitis, Cmax, AUC, MRT and T1/2 for benzoate and Tmax, MRT and T1/2 for hippurate remained at control levels, but Cmax and AUC for hippurate were slightly decreased compared to controls. However, in 18 patients with liver cirrhosis, Cmax and AUC for benzoate were in the control range but MRT and T1/2 were significantly delayed (p less than 0.01 for both). Moreover, the MRT value was increased in proportion to the severity of liver disease (p less than 0.01). AUC for hippurate was not changed to any extent, and Tmax, MRT and T1/2 were slightly delayed, while Cmax was significantly reduced. AUC, MRT and T1/2 for benzoate and Tmax, MRT and T1/2 for hippurate showed significant correlation with serum albumin levels, prothrombin time and indocyanine green clearance rate. These results suggest that benzoate-metabolizing capacity, especially as indicated by the MRT value for serum benzoate, appears to be a better index than the indocyanine green clearance rate for determining hepatic functional reserve in chronic liver disease.


A novel two-site enzyme immunoassay for the sensitive detection of beta-endorphin in specific human brain stem regions.

On the line of experiences previously made in the development of a two-site immunoradiometric assay (TS-IRMA), we generated, in the present study, a novel, sequential, noncompetitive two-site immunoenzymometric assay (TS-IEMA) for the determination of the non-acetylated form of human beta-endorphin (beta h-EP). At variance with other assays reported in the literature, but in analogy to the TS-IRMA, the TS-IEMA does not require previous separation of beta h-EP. The TS-IEMA detects beta h-EP in central nervous tissues at a very low detection limit, and to a high degree of reproducibility, precision, sensitivity, and accuracy. The newly developed assay was then used to determine beta h-EP levels in the tissues of distinct brainstem regions. Tissues were collected, by the Palkovits's punching technique, from a series of victims of "Sudden Infant Death Syndrome" and of miscellaneous infections. The TS-IEMA, combined with the punching technique, has revealed, in the measure of its application in the present study, an unprecedented high degree of resolution of the neurochemical architecture of beta h-EP in the human infantile brainstem.


Newly evidenced pyrimidinoceptors and the P2x purinoceptors are present on the vascular smooth muscle and respectively mediate the UTP- and ATP-induced contractions of the dog maxillary internal vein.

P2 purinergic receptors and pyrimidinoceptors were studied by comparing the contractile responses to UTP with those to ATP, in the dog internal maxillary vein (IMV) after endothelium removal. The contraction curves were very different: rapid subsidence with ATP and sustained contraction with UTP. alpha beta methylene ATP induced desensitization to ATP, whereas it did not antagonize the UTP-induced contractions. Reactive blue 2 (RB2) was incapable of antagonizing contractions to ATP and UTP in this vessel. We showed that Nicardipine, a calcium antagonist, was more potent on the UTP-induced than on the ATP-induced contractions. The fact that RB2 did not potentialize the UTP-induced contractions, unlike what has been observed in the dog saphenous vein, suggests that a new category of pyrimidinoceptors have been evidenced on the IMV. Our results also indicate that ATP induces contraction via P2x rather than P2y purinoceptors. The receptors described here are localized on the vascular smooth muscle.


Collagenolytic cathepsin B and L activity in experimental fibrotic liver and human liver.

To clarify the role of individual collagenolytic cathepsin in hepatic collagen degradation, cathepsin B and L activities were determined in normal and CCl4-induced fibrotic liver, together with non-collagenolytic cathepsin H. Cathepsin B and L activities increased 1.9- and 2.0- fold, respectively, in the fibrotic liver as compared with the normal liver, and were significantly correlated with hepatic hydroxyproline levels. By contrast, cathepsin H activity was not altered in fibrotic rats. Similar results were also obtained from autopsied human livers. These results suggest that cathepsin B and L are similarly induced by hepatic collagen levels and are implicated in degrading collagens, especially soluble collagen.


Cross-reactive potential of monoclonal antibodies raised against proteolysed tobacco etch virus.

Monoclonal antibodies (mAb) capable of reacting with different potyviruses were obtained by immunizing mice with proteolysed tobacco etch virus. The mAb were not equally effective in all ELISA formats and some were specific for different conformational states of the viral coat protein. The mAb also detected antigenic differences between purified virus particles and viral antigen in infected plant sap. In an ELISA format using antigen-coated plates, 5 different potyviruses (out of 7 viruses tested) could be detected in plant sap by one mAb. Different combinations of mAb and polyclonal antiserum could also be used for detecting several potyviruses by ELISA.


Association between HIV1 infection and sexually transmitted disease among men in Central Africa.

In Africa, heterosexual contact is the major route of transmission of the human immunodeficiency virus (HIV). Previous studies have strongly suggested that other sexually transmitted diseases (STD) may facilitate HIV transmission. However, the association of HIV infection with other STD may simply be a marker of sexual promiscuity. Thus, we compared the association of different STD, HIV status, and sexual behaviour of 160 STD patients and 95 STD-free control individuals. Results showed that STD patients differed from controls in most of the sociological and behavioural parameters, as well as in HIV serological status. Within the STD group, people with genital ulcer disease (GUD) (n = 62) were more likely to be HIV-seropositive (21%) than people with urethritis (n = 98, 11.2%). Meanwhile, there was almost no difference in the sociological and behavioural parameters between the GUD and the urethritis group. Thus, our results reinforce the specific role of mucosal breakage (i.e. genital ulcers) in the transmission of HIV.


Electron microscopic identification of Zinga virus as a strain of Rift Valley fever virus.

Electron microscopic examination of a negatively stained suspension of Zinga virus showed particles 90-100 nm in diameter, enveloped with spikes 12-20 nm in length and 5 nm in diameter. Further identification of the virus by immune electron microscopy showed the reactivity of human Rift Valley fever virus-positive serum with Zinga virus. Results of this study are in agreement with earlier reports that Zinga virus is a strain of Rift Valley fever virus.


[Intra-bullous ventilation of giant bulla: does slow ventilation space on multi-breath nitrogen washout test mean that giant bulla is present?].

Intra-bullous ventilation and uneven ventilation in patients with giant bulla were studied by the multi-breath nitrogen washout and 133Xe washout tests. Fourteen patients underwent the nitrogen washout test before and after bullectomy; 2 of them also underwent the 133Xe washout test before surgery. After bullectomy, pulmonary nitrogen clearance delay and alveolar dilution rate (ADR) of slow ventilation space improved significantly (p less than 0.01) from 202.5% to 51.5%, and from 0.98 to 0.95, respectively. The dilution rate of 133Xe in the bullous region, based on the 133Xe clearance curve, showed the same values as the nitrogen washout test. Therefore, we considered that bullous ventilation could be estimated by the ADR of the nitrogen washout test and that uneven ventilation resulted from the ADR difference between the giant bulla and the nonbullous lung. When the nonbullous lung region was emphysematous, however, it was impossible to estimate the intra-bullous ventilation from the nitrogen washout test.


[Validation of Doppler arterial flow in humans].

A method of measuring volumetric flow in human arteries with pulsed Doppler technique was developed. Doppler flowmetry was assessed in 11 adult patients whose admission-diagnoses included aneurysm of the aorta or dissections. During surgery, regional blood flows of the left common carotid artery, terminal aorta, common iliac artery, external iliac artery or common femoral artery were measured by Doppler method and electromagnetic flowmeter. Eighty four arterial flow determinations were obtained from the 11 patients studied. On comparison of simultaneous electromagnetic and Doppler measurements of blood flow, an excellent correlation (r = 0.93) was found between the two methods. The slope of the regression line was 0.587. Regional blood flow was measured with Doppler flowmetry in another 9 patients. The values of the left common carotid, celiac, superior mesenteric and terminal aortic flows were 251 +/- 62, 608 +/- 399, 687 +/- 381, 783 +/- 324 ml.min-1, respectively. This method provides an easy, reliable way of measuring regional blood flow.


[A case report of primary pulmonary hypertension: congestive heart failure induced by pregnancy and delivery].

A thirty-year-old woman had complaints of general fatigue and gain in body weight, which had developed since the third trimester of pregnancy. On admission, she had lip cyanosis, general edema, and tachycardia. A chest rentogenogram showed cardiomegaly and dilatation of the pulmonary arteries. On cardiac catheterization, pulmonary artery pressure and pulmonary vascular resistance were elevated moderately. A pulmonary perfusion scintigram revealed a defect in the left lower lung field with no evidence of thrombus in a pulmonary artery angiogram. In this case, an underlying disease which caused pulmonary hypertension might have been the underfined cause. For this reason, primary pulmonary hypertension was the diagnosis. In the present case there is a danger that congestive heart failure may be induced by pregnancy and delivery and, furthermore, there is a possibility that during the clinical course of the illness pulmonary infarction might occur.


[Repeated blackout in a patient with accelerated idioventricular rhythm].

There has been no report that Accelerated Idioventricular rhythm (AIVR) causes a syncope attack. The patient described in this report is very rare because AIVR chronic without any heart diseases has been observed for 13 years, and because it is considered that AIVR is closely associated with his repeated blackouts. A 62-year-old male was admitted to our hospital because of repeated syncopal attacks. He reported that he occasionally felt lightheaded after strenuous lifting and pushing or pulling against resistance. We found that AIVR could produce a remarkable arterial pressure drop partly because of ventricular asynergy and loss of timed atrial contribution. Furthermore, we observed syncopal attacks during Valsalva maneuver and found abnormalities of baroreceptor reflex (Lack of reflex tachycardia and weakened evershoot phenomenon). It is concluded that AIVR is not a benign arrhythmia in this patient because it has been a possible cause of syncope attack due to systemic arterial pressure drop and baroreceptor abnormalities.


[A case of acute myocardial infarction following intracoronary thrombi caused by coronary artery spasm].

A 65-year-old man underwent coronary angiography (CAG) after 10 hours from the onset of myocardial infarction. We observed large Thrombi at the filling defect in the proximal site and mid-portion of the right coronary artery. CAG showed that they had disappeared completely without residual stenosis on the 4th day. In addition to this segmental spasms developed spontaneously at the proximal site of a thrombus accompanied by ST elevation, but these spasms recovered after intracoronary infusion of isosorbide dinitrate on the 26th day CAG. Thus, our case indicates that acute myocardial infarction may be caused by secondary coronary artery thrombosis and accompanying coronary artery spasm.


[Report of a case with aortic regurgitation in progressive systemic sclerosis].

Aortic valve lesions in progressive systemic sclerosis (PSS) are very uncommon. To our knowledge, aortic regurgitation (AR) associated with PSS has not been reported previously. We would like to report the case of a 58-year-old woman who had PSS with AR due to Raynaud's symptom, fever, positive ANA, accelerated ESR, and diastolic blowing murmur along the left sternal border. After treatment with adreno-cortico steroid and an immunosuppressive agent, the patient improved serologically and symptomatically. However, she was later admitted to our hospital again due to heart failure with progressive AR. She died of refractory heart failure with severe AR and tricuspid regurgitation (TR). The former was caused by aortic cusp lesions and the latter by pulmonary hypertension. An autopsy confirmed the diagnosis of PSS, which was found to have involved the heart, lungs and pancreas. Vasculitis with infiltration and fibrotic changes were noted in these organs. Moreover, there were fibrotic thickenings and shortenings in the aortic cusps with cell infiltration. There were no indications of rheumatic disease. These results suggest that the cause of our patient's aortic valve disease may have been PSS vasculitis.


[A case of subarachnoid hemorrhage with sick sinus and advanced AV block].

A 35-year-old man was hospitalized after a sudden onset of transient syncopal attack without accompanying complaints of headache or nausea. He was slightly disorientated but neurologically normal. He had a blood pressure of 150/90mmHg and a pulse rate of 40/min. An ECG showed marked sinus brady-cardia with ventricular escaped rhythm followed by advanced atrioventricular (AV) block. Some components of conducted ventricular beats showed aberration. There was no significant ST or T wave abnormality in normally captured QRS components except for prominent T in leads II, III and aVF. At first, we thought that he might require temporary pacing because of Adams-Stokes attack. However, after administration of atropine sulfate, the ECG returned to normal sinus rhythm with heart rate of 88/min. Then he began to complain of headache followed by a convulsive seizure. A CT scan and angiogram revealed a ruptured aneurysm at the top of the basilar artery, which was successfully clipped. A wide spectrum of ECG changes can be demonstrated in practically all patients with subarachnoid hemorrhage (SAH). Prolonged QT interval, ST-T changes, U wave, sinus tachycardia, or ventricular premature complex are the common abnormalities probably caused by increased circulating catecholamine. As bradyarrhythmia in patients with SAH is an uncommon finding, its mechanism has not yet been defined. Transient sinus bradycardia with advanced AV block in this patient might have been caused not by elevated intracranial pressure (Cushing phenomenon) but by drastic discharge of the parasympathetic nerve. This case serves to illustrate the vigilance required in determining whether abnormalities of cardiac rhythm are instrumental in causing neurological symptoms and signs or a disorder of cerebral function.


[A case of angina pectoris with cardiac arrest at treadmill stress test].

We reported a case of angina pectoris with cardiac arrest immediately after treadmill exercise test, and the effect of PTCA in the same case. A 69-year-old Japanese male had chest oppression on exertion. Initial treadmill test showed 2 mm ST-segment depression in leads V4-6. Two minutes after exercise, he had atrio-ventricular (A-V) block and cardiac arrest with episodes of fainting. He was resuscitated by chest thump. Coronary angiography showed 90% stenosis in the right coronary artery (RCA). PTCA for RCA was able to dilate the stenotic lesion. The second treadmill test after PTCA did not induce bradycardia nor A-V block. It was suggested that the RCA lesion may play a critical role.


[Two cases of vocal cord dysfunction and bronchial asthma indicated contrary course of bronchial responsiveness based on astography].

We encountered two cases of patients who showed vocal cord dysfunction and bronchial asthma. By using an ++astograph , we found that bronchial responsiveness of these ailments differed. In the case of vocal cord dysfunction, bronchial responsiveness to methacholine indicated a false high level by adduction of the vocal cord. Therefore other evaluations including pulmonary function and bronchoscopy were required to distinguish it from bronchial asthma. On the other hand, in the case of bronchial asthma, bronchial responsiveness to methacholine was mild, but life threatening asthmatic attack occurred after inhalation of methacholine. Psychological factors were not neglected in considering both of these cases. Therefore we must consider these results and psychological factors when evaluating bronchial responsiveness.


Structure and function of the external gill filaments of embryonic skates (Raja erinacea).

We have investigated structure and function of the external gill filaments, which occur transiently in the embryonic little skate, Raja erinacea. Approximately 25-30 days after spawning (body mass 0.03-0.05 g) external gill filaments appear as an outgrowth from the caudal side of the gill arches. These filaments are thread-like, each containing one afferent and one efferent blood vessel, and by day 70-75 (body mass 0.4-0.5 g) they reach their maximum size at a length of about 1 cm and a blood vessel diameter of 70-80 microns. Subsequent resorption of the filaments is characterized by a decrease in both length and diameter of the blood vessel. By day 90-95 (body mass 0.9-1.0 g) the external gill filaments are completely resorbed and replaced by internal gills. Blood velocity, measured in these external filaments, increased with development from 0.1 mm.sec-1 to about 0.7 min.sec-1, and decreased again during resorption. Blood flow, calculated therefrom with blood vessel diameter, showed a similar maximum curve. A model analysis supports the hypothesis that in a full grown filament respiratory gas exchange is mainly perfusion-limited and can contribute significantly to the total oxygen uptake of the embryo. Analysis of the results indicates, however, that the gill filaments are not adequate as a gas exchange organ for later developmental stages.


Capillary-to-fiber geometry and mitochondrial density in hummingbird flight muscle.

We investigated structural characteristics for high O2 flux in hummingbird flight muscle, i.e. the most O2 demanding skeletal muscle per unit tissue mass among vertebrates. Pectoralis and supracoracoideus muscles of 3-4 g hummingbirds (Selaphorus rufus) were perfusion fixed in situ, processed for electron microscopy and analyzed by morphometry. Small fiber size (group mean +/- SE, 201 +/- 14 microns 2 at 2.1 microns sarcomere length), large capillary length per fiber volume (8947 +/- 869 mm-2) and high mitochondrial volume density per volume of muscle fiber (34.5 +/- 0.9%) were characteristic features of the muscles. Considering capillary supply and mitochondrial volume on an individual fiber basis showed that the size of the capillary-to-fiber interface (i.e. capillary surface per fiber surface) was also high in the muscles. Comparison with mammalian hindlimb pointed to a major role of the size of the capillary-to-fiber interface in providing a great potential for O2 flux rate from capillary to muscle fiber mitochondria in hummingbird flight muscle.


Influence of lung volume history and increased surface forces on collateral resistance.

In order to investigate the major route for collateral ventilation, the influences of lung volume history and increased surface forces on collateral resistance (Rcoll) were studied in excised canine lower lobes. Measurements were made during inflation and deflation in two states, i.e. before (control) and after stiffening by large tidal ventilation raising peak recoil pressure (Ptp) by 8-10 cmH2O. Air flowed into a wedged segment via a double lumen catheter (Vcoll) keeping segmental pressure (PS) constant at 2 cmH2O as monitored through the other lumen, giving Rcoll = Ps/Vcoll. Rcoll vs lung volume (VL) showed little hysteresis, in sharp contrast to Rcoll vs Ptp (Rcoll higher during inflation). Thus, in each state, Gcoll (= 1/Rcoll) depended primarily on VL, but the stiffed state appeared to have permanently enlarged channels or recruited new ones. The relations between Gcoll and VL or Ptp somewhat resemble reported bronchial diameter behaviour. The ventilation process itself, rather than higher surface forces per se, appeared to distend collateral channels in the stiff lung. The results are consistent with the major component of Gcoll being located at the bronchiole level.


Mechanical independence of wingbeat and breathing in starlings.

The pectoral muscles in birds comprise up to a third of the body weight and provide the principal drive to the wing. Their attachment to the sternum suggests that they could compress the thorax and assist ventilation during flight. Most, but not all, birds have an integer ratio relationship between wingbeat and breathing frequency, but no measurements of the respiratory flow associated with the act of wingbeat are available. We recorded respiratory flow and wing timing in three starlings that flew at 22 knots (11 m.s-1) for up to 5 min in a wind tunnel. Triggering on wingbeat, we ensemble averaged flow records for many wingbeats in each flight. Because wingbeats occurred throughout the respiratory cycle, breathing flow tended to average to zero, and a small flow event related to wingbeat emerged. The volume change associated with wingbeat ranged from 3 to 11% of tidal volume, and this is probably an overestimate. We conclude that wingbeat and breathing in starlings are essentially mechanically independent, despite the direct attachment of the locomotor muscles to the thorax.


Breath-to-breath variability in hypoglossal motor unit firing.

Instability in the magnitude and timing of motor output to pharyngeal dilator muscles occurs during breathing. This contributes to alterations in upper airway resistance, and is one of several factors that play a role in the pathophysiology of obstructive apneas. To define the motor unit mechanisms accounting for such variability, geniohyoid motor unit activity was recorded simultaneously with diaphragm EMG in anesthetized cats spontaneously breathing 7% CO2 in O2. Variability was quantified with the coefficient of variation [CV = (SD/mean) x 100%]. In this preparation, we confirmed greater breath-to-breath variability of geniohyoid compared to diaphragm peak moving average EMGs. During recordings of geniohyoid motor unit activity, average CV of other respiratory parameters were as follows: peak diaphragm EMG 5.8%, inspiratory time 3.5%, expiratory time 3.8%. The average CV for geniohyoid motor unit activity patterns were substantially higher: spikes per breath 15.6%, mean firing frequency 13.3%, peak firing frequency 19.0%, minimal firing frequency 26.3%, onset time 40.9%, offset time 10.0% and duration of firing 12.8%. Values differed considerably among motor units, even when activity was recorded simultaneously. These findings suggest that variability is present in both intensity and timing of geniohyoid motor unit firing during breathing, and that different geniohyoid motor units appear to have varying degrees of stability during breathing.


Ventilatory response to sustained eucapnic hypoxia in the adult conscious dog.

The ventilatory response to 20 min sustained isocapnic hypoxia (SaO2, 80 +/- 2%) was examined in 5 trained unanesthetized adult dogs breathing through an endotracheal tube. End tidal PCO2 was maintained at the resting levels. The dogs' conscious status was monitored by recording EEG and EOG on a chart recorder. The room temperature was kept between 19 and 21 degrees C. All tests were repeated in each dog on 2 occasions: (1) unloaded tracheal breathing or (2) resistive loaded breathing. During unloaded tracheal breathing, the average ventilation in response to sustained hypoxia rose from a control of 5.1 +/- 0.3 L/min (mean +/- within-dog SE) to 19.2 +/- 1.1 L/min at the initial stage of hypoxia. Ventilation remained at 20.7 +/- 1.3 L/min at 10 min, and then 19.7 +/- 1.4 L/min at the completion of the 20 min hypoxic exposure. There was no ventilatory adaptation observed (P greater than 0.05). After release from hypoxia, the ventilation fell abruptly to 7.6 +/- 0.8 L/min, which was higher than the resting baseline level (P less than 0.05), and then gradually returned to the resting baseline within 10 min. Experiments exposing the dogs to 40 min sustained hypoxia also failed to elicit significant adaptation. During resistive loading, the pattern of average ventilation in response to sustained hypoxia was similar to that observed in unloaded breathing tests. But the ventilatory recovery was longer than unloaded breathing, returning to the resting baseline within 20 min. Again, there was no ventilatory adaptation observed.(ABSTRACT TRUNCATED AT 250 WORDS)


Respiratory response to positive and negative inspiratory pressure in humans.

To investigate the effect of positive or negative inspiratory pressure on respiration, eight subjects breathed, either without or with added external dead space (VD, 600 ml), through either added inspiratory laminar flow resistances (RES; peak inspiratory airway pressure, Pinsp, down to -9 cmH2O) or with inspiratory pressure support (IPS; Pinsp up to +10 cmH2O). IPS, triggered by the subject's inspiratory effort, provided positive airway pressure throughout inspiration, but allowed for attainment of the subject's own respiratory pattern. The following main results were obtained with IPS or RES relative to the control (no IPS, no RES): (1) with VD, IPS led to small, but significant, increases in tidal volume (VT), respiratory frequency (fR) and ventilation (VE), with no changes in inspiratory time (TI) or duty cycle (TI/TT). Mean inspiratory flow (VT/TI) increased, and mouth occlusion pressure 0.1 sec after onset of inspiration (P0.1) decreased significantly with IPS. The changes during RES were essentially in the opposite direction; (2) without VD, similar, but smaller effects were observed, and only the changes in VT/TI and P0.1 during IPS were significant; (3) highly significant decreases were observed during IPS in end-tidal PCO2 (PETCO2); on the average from 39.6 to 29.2 Torr without VD, and from 45.7 to 39.3 Torr with VD breathing. A small, but significant decrease in PETCO2 occurred also during RES with VD. We conclude that while resistive loading is nearly completely compensated with but small changes in PETCO2, inspiratory pressure support leads to marked hyperventilation, which is not effectively counteracted by central timing commands.


Airway anesthesia during positive and negative inspiratory pressure breathing in man.

We have measured the effects of airway anesthesia (aerosolized 5% lidocaine) on the respiratory pattern during positive or negative inspiratory pressure in 8 resting subjects. The subjects breathed through a 600 ml dead space (peak inspiratory airway pressure, Paw = -2 cmH2O) without or with negative (approx. -5 or -10 cmH2O) or positive (approx. +5 or +10 cmH2O) inspiratory pressure, provided by a laminar flow resistance or a positive pressure source, respectively. Control measurements were performed before and after measurements with airway anesthesia. Measurements included tidal volume, respiratory frequency, ventilation, inspiratory and expiratory duration, occlusion pressure (P0.1) and end-tidal PCO2. None of the parameters measured was significantly altered by airway anesthesia, which was effective in suppressing the cough reflex. We conclude that information from lung afferents that are suppressed with the elimination of the cough reflex is not important for the breathing pattern during resting ventilation with elevated tidal volume (dead space load) and with positive or negative inspiratory pressure.


Ventilatory and P0.1 response to hypercapnia in quadriplegia.

Unlike individuals with comparable degrees of respiratory muscle weakness from other causes, quadriplegic patients have a blunted ventilatory and P0.1 response to hypercapnia. This suggests that the diminished response in quadriplegia is due, in part, to an alteration in respiratory drive. We measured the hypercapnic response in 9 subjects with chronic quadriplegia (Q) and 8 normal controls (N). Ventilatory muscle strength, maximum voluntary ventilation (MVV), and lung volumes were measured in all subjects. The ventilatory response (HCVR) in Q was significantly less than in N (0.73 +/- 0.37 vs 2.95 +/- 0.4 L.min-1.mmHg-1; P less than 0.001), even when normalized for indices of respiratory muscle performance (e.g., vital capacity, MVV). There was no significant change in the HCVR in Q after the administration of naloxone. We also serially studied 2 subjects with acute quadriplegia, and found that despite progressive improvement in respiratory muscle performance, there was no accompanying increase in the response to hypercapnia. These data suggest that muscle weakness alone cannot explain the blunted hypercapnic response in quadriplegia, and are consistent with the hypothesis that these subjects have a reduced ventilatory drive.


Collinearity diagnosis for a relative risk regression analysis: an application to assessment of diet-cancer relationship in epidemiological studies.

In epidemiologic studies, two forms of collinear relationships between the intake of major nutrients, high correlations, and the relative homogeneity of the diet, can yield unstable and not easily interpreted regression estimates for the effect of diet on disease risk. This paper presents tools for assessing the magnitude and source of the corresponding collinear relationships among the estimated coefficients for relative risk regression models. I show how to extend three tools (condition indices, variance decomposition proportions, and standard inflation factors) for diagnosing collinearity in standard regression models to likelihood and partial likelihood estimation for logistic and proportional hazards models. This extension is based on the analogue role of the information matrix in such analyses and the cross-product matrix in the standard linear model. I apply the methodology to relative risk models that relate crude intakes (on the log scale) and nutrient densities to breast cancer cases in the NHANES-I follow-up study. The three diagnostic tools provide complementary evidence of the existence of a strong collinearity in all models that is due largely to homogeneity of the population with respect to our risk scale for the crude intakes. The analysis suggests that the non-significant relative risks for the crude intakes in these models may be due to their involvement in collinear relationships, while the nonsignificant relative risks for the nutrient densities are far less affected by multicollinearity.


Smoothing reference centile curves: the LMS method and penalized likelihood.

Refence centile curves show the distribution of a measurement as it changes according to some covariate, often age. The LMS method summarizes the changing distribution by three curves representing the median, coefficient of variation and skewness, the latter expressed as a Box-Cox power. Using penalized likelihood the three curves can be fitted as cubic splines by non-linear regression, and the extent of smoothing required can be expressed in terms of smoothing parameters or equivalent degrees of freedom. The method is illustrated with data on triceps skinfold in Gambian girls and women, and body weight in U.S.A. girls.


Comparing in-patient classification systems: a problem of non-nested regression models.

Since 1983, hospitals in the United States have been receiving prospective payment for their in-hospital patient admissions covered under Medicare. Under such schemes each patient is placed in a group by a classification system, known as the Diagnosis Related Groups (DRG), and the hospital is reimbursed by the Health Care Financing Administration according to some predetermined group average, adjusted for hospital level characteristics, such as size, location and teaching activity. Recent interest has focused on refining the DRG system or considering totally different systems of classification. Studies designed to compare the ability of different systems to account for between-patient variability in resource consumption in the same dataset lead to the problem of model selection between large non-nested regressions, where resource consumption, measured by length of hospital stay or costs, is regressed on dummy-indicator variables representing different patient groups. We use a simple measure of fit to develop a symmetric test of the null hypothesis that the two systems account equally well for variability in resource consumption. With this method, unlike methods such as Akaike's AIC criterion, we can quantify the probability of a false positive, and thereby limit the probability of choosing one system over another when it is no better at accounting for variability in resource consumption.


A retrospective assessment of the 75/75 rule in bioequivalence.

The 75/75 rule was originally proposed by the U.S. Food and Drug Administration (FDA) as an alternative means of testing the bioequivalence of two formulations of a pharmaceutical agent. The rule specified that the ratio of test-to-reference formulation of a bioavailability measure arising in a bioequivalence study must be between 75 and 125 per cent of unity in at least 75 per cent of subjects to declare two formulations bioequivalent. The rule has garnered criticism in the literature and the FDA no longer uses the rule formally in assessing bioequivalence. The basis, however, for all criticism of the rule has been simulation arguments. In this paper, we derive the sampling model implied by the rule and place the rule in the framework of a statistical hypothesis test. We show how the significance level of the test depends upon variability of the formulations, and thus why the rule performs in the way that has received criticism.


Optimal checking procedures for monitoring laboratory analyses.

Many clinical, environmental, and epidemiologic studies rely heavily upon biochemical data, and the quality of these data is of paramount importance to the validity of study conclusions. Traditionally, far more attention has been given to the analysis of study data than has been given to monitoring the quality of the data. In this paper we draw an analogy between monitoring a laboratory system and an industrial production process and discuss the limitations of industrial quality control plans when applied in a laboratory setting. We derive methods for computing optimal checking schedules for laboratory analyses. These schedules formalize traditional laboratory practices of periodic checking and provide guidelines for the frequency and placement of checks within a finite batch of analyses. When laboratory system failure can be reasonably approximated by an exponential or geometric distribution, optimal checking schedules are relatively easy to compute. For more complex failure distributions, we present a dynamic programming approach. We describe an application to the measurement of selenium status in plasma samples using an electrothermal atomic absorption spectrophotometry procedure.


Withdrawal censoring and the sequential logrank procedure.

The effects of withdrawal censoring on the power of the group sequential logrank procedure are examined in the context of survival studies. Special attention is given to an assumption that the withdrawal censoring mechanism is only conditionally independent of survival time. Simulation studies of two-sample, fixed duration trials, under random right censoring, staggered entry and exponential life times, reveal a general decrease in statistical power that is most pronounced when the withdrawals are unbalanced, the majority occurring in the group with the higher hazard rate. Generally, this decrease in power is not of practical concern under typical withdrawal rates except when conditional independence is present in which case large fluctuations in power and type I error rates can occur.


Creation of a semiannual report for a multicentre co-operative clinical trials group.

The Southwest Oncology Group (SWOG) is a multicentre co-operative group that performs prospective clinical trials in cancer. The SWOG Statistical Center is responsible for preparing a report of studies for the semiannual meetings. The report includes a summary of study design and eligibility criteria, current accrual, baseline patient characteristics, toxicity, and, for studies closed to accrual and with sufficiently mature outcome data, tumour response or patient survival. A software program, Statisticians' Report Worksheet (SRW), has been developed by the programming staff at the SWOG Statistical Center. This program enables each disease specific chapter to be created independently, but ensures that tables and graphs for all chapters are of uniform style. We describe here the coordination of the report, and the use of the SRW program. This reporting system can serve as a model for other groups.


Bayesian methods for phase I clinical trials.

Phase I clinical trials are conducted to determine the dose-response curve of a new drug with respect to toxic side effects and, in particular, to estimate the maximum tolerated dose (MTD). In this paper we take a Bayesian approach to the problem of making inferences about the MTD. Working with broad classes of priors, we obtain the posterior distribution of the MTD and study its properties. We also address the question of providing updated assessments of the risk of toxicity for new patients entering the study at a specific dose level. These assessments would be useful in deciding issues of study management and ethics. Our analysis pays particular attention to the sensitivity of the inferences and risk assessments to the choice of prior and the choice of model for the dose-response relationship.


Sample size determination for group sequential clinical trials with immediate response.

The use function approach to group sequential methods has been explored previously. Any group sequential design requires specifying the frequency and times of repeated analyses, but only the use function approach allows deviations from those specified in the design, without affecting the type I error in the analysis. This paper illustrates how the use function provides a simple and flexible design procedure and how the initially projected maximum sample size can be calculated for randomized clinical trials in which responses are known relatively soon after patient entry and for which there is an early stopping rule built into the study protocol. Also the consequence of using the proposed design procedure is investigated in terms of the operating characteristics of the subsequent group sequential analyses.


Sleep and cardiorespiratory characteristics of infant victims of sudden death: a prospective case-control study.

We studied the polygraphic sleep recordings of 30 infants who eventually died of sudden infant death syndrome (SIDS) and those of 60 matched control infants. All records were extracted from 20,750 sleep studies collected prospectively in 10 sleep laboratories. Of the 30 future SIDS victims, 5 were siblings of SIDS victims and 9 were studied after an apparent life-threatening event. For each SIDS victim, two normal control infants were matched for sex, gestational age, postnatal age and weight at birth. The future SIDS infants were reported to have more frequent episodes of regurgitations after feeding (p = 0.01) and profuse sweating during sleep (p = 0.01) than the control subjects. Only two polysomnographic variables characterized the future SIDS infants. Compared to control subjects, the SIDS infants moved less during sleep (p = 0.04) and had significantly more frequent obstructed breathing events. Obstructive and mixed apneas were seen in 23 of 30 future SIDS victims, but in only 9 of 60 control subjects (p = 0.01). The obstructed and mixed apneas lasted longer in the SIDS than in the control infants (p = 0.01) but did not exceed 15 seconds. The obstructed breaths occurred mainly in rapid eye movement sleep (78% of the events) and were accompanied by drops in heart rates to 68 beats per minute and in SaO2 levels to 75%. The present report adds further indirect evidence for a possible sleep-related impairment of respiratory control in some infants who eventually died of SIDS.


Wrist actigraphy in insomnia.

To assess the use of actigraphy in evaluating insomnia, 36 patients with a serious complaint of insomnia slept 3 nights each in the laboratory, where the usual polysomnograms (PSGs) were obtained as well as actigraphic assessments of their sleep. Patients also wore actigraphs for 7 days at home, were extensively interviewed and filled out psychometric tests. Based on all this information, the patients were then diagnosed according to the International Classification of Sleep Disorders. Averaged over the 3 nights for each insomniac, the mean discrepancy between actigram and PSG was 49 minutes per night. In three-fourths of the cases, actigram and PSG agreed to within 1 hour on the total amount of sleep per night. Discrepancies, however, were not random: In patients with psychophysiologic insomnia and in insomnia associated with psychiatric disease, the actigram typically overestimated sleep when compared with the PSG. In patients with sleep-state misperception, the actigram was either quite accurate or it underestimated sleep when compared with the PSG. Comparing laboratory with home sleep, one-third of all insomniacs slept better in the laboratory and two-thirds slept better at home. In addition, night-by-night variability was higher at home than in the laboratory. Based on our study, we now recommend actigraphy as an additional tool in the clinical evaluation of insomnia, but we believe that in complex cases it should be combined with 1 PSG night in the sleep disorders center.


Patients' acceptance of psychological and pharmacological therapies for insomnia.

This study evaluated the acceptance of psychological and pharmacological therapies among chronic insomniacs and noncomplaining good sleepers. After reading a brief written description of two treatment methods commonly used for persistent insomnia (i.e. cognitive-behavior therapy and pharmacotherapy), the subjects rated in a counter-balanced order several dimensions of these two treatment modalities. The results showed that the psychological intervention was rated as more acceptable and more suitable than the pharmacological one among both insomniacs and their noncomplaining significant others. Behavior therapy was also expected to be more effective on a long-term basis and to produce fewer side effects as well as more benefits on daytime functioning. The clinical implications and relevance of treatment acceptance in the management of insomnia are discussed.


Time-of-night patterns in PLMS activity.

Time-of-night patterns for periodic leg movement in sleep (PLMS) activity were assessed in 72 patients diagnosed as having PLMS (46 with only PLMS, 10 with narcolepsy and PLMS and 16 with sleep apnea and PLMS). Two distinct patterns of PLMS activity were identified. For one pattern, PLMS activity was high initially upon falling asleep and then decreased across the remainder of the night with the majority of the activity occurring during the first half of the night. For the second pattern, PLMS activity was relatively evenly distributed across the night with slightly greater activity in the middle of the night. These patterns were highly reliable across two nights of recording for group 1 and less so for group 2 even though there was significant variability between nights in the number of PLMS. Patients in group 2 were younger (except for those with sleep apnea) and were sleepier during the day. Implications of these findings for pharmacologic management are discussed.


Periodic limb movement disorder is associated with normal motor conduction latencies when studied by central magnetic stimulation--successful use of a new technique.

This study prospectively tested the hypothesis that patients with periodic limb movement disorder (PLMD) have longer motor conduction latencies than normals. Six healthy adults, 13 patients with PLMD, and 8 patients with long-term multiple sclerosis (MS) had recordings of motor conduction latencies during wake and sleep. MS subjects were included only to show that we could detect prolongation of central conduction; nonMS subjects were used to test the hypothesis. Subjects had no other medical or sleep problems. A novel magnetic stimulator, the Cadwell MES-10, was discharged over the vertex and the C7 cervical spine. It triggered compound muscle action potentials that were recorded in the abductor digiti minimi in the hand. The conduction latencies were the total conduction time (TCT), measured vertex to hand, and the peripheral conduction time (PCT), measured C7 to hand. The difference was the central conduction time (CCT). Only TCT could be obtained during sleep. Supporting the use of TCT as an indirect measure of central conduction was that, in all waking subjects, TCT correlated with CCT (r = 0.91, p = 0.001) but not with PCT. Reliabilities during wake and sleep were 0.95 or higher for TCT and PCT measurements. Waking CCT was greater in MS subjects (13.77 milliseconds) than those without MS (9.21 milliseconds), p = 0.001. Sleeping TCT was much less impressive in distinguishing MS subjects [27.08 milliseconds in nonrapid eye movement (NREM) sleep; 28.64 milliseconds in rapid eye movement (REM) sleep] from nonMS subjects (24.45 milliseconds in NREM; 24.84 milliseconds for REM), p = 0.07 for NREM and p = 0.04 for REM.(ABSTRACT TRUNCATED AT 250 WORDS)


Do patients with the sleep apnea/hypopnea syndrome drink more alcohol?

As alcohol ingestion may worsen the sleep apnea/hypopnea syndrome, we have investigated the alcohol consumption of patients with the sleep apnea/hypopnea syndrome in comparison to control subjects to determine whether patients with the sleep apnea/hypopnea syndrome drink excessively. A lifetime alcohol history was taken from each. There was no significant difference between the 50 patients with the sleep apnea/hypopnea syndrome and 95 age-matched controls in either the lifetime (patients 27, SEM 5 x 10(3); controls 26, SEM 4 x 10(3) units) or current (12, SEM 2; 12, SEM 2 units per week) alcohol consumption. There was no evidence that alcohol consumption was related to the development of arterial carbon dioxide retention or peripheral edema in such individuals.


Daily social rhythms in the elderly and their relation to objectively recorded sleep.

This study tested the hypothesis that the impaired sleep of healthy 71-91 year olds might be due to circadian dysfunction stemming from irregularity of life-style. Twenty-five old women, 20 old men and 21 young controls (19-28 years old) were studied in relation to 1) objective sleep as measured in the laboratory, 2) subjective sleep quality as measured by the Pittsburgh sleep quality index (PSQI) and 3) the social rhythm metric (SRM), an instrument to quantify the daily rhythms of life. Contrary to prediction, the SRM scales revealed that the older group had just as many activities completed and just as much other-person involvement as the young. Moreover, they showed a significantly greater regularity in daily life-style than the young, despite showing reliably impaired subjective and objective sleep. This suggests either that these seniors have always been regular in their life-style and that this has been protective of their health and vigor, or that their regularity has been developed as an adaptive response to age-related changes in the circadian system.


Sleep propensity free-runs with the temperature, melatonin and cortisol rhythms in a totally blind person.

In previous studies, we found that many totally blind people have free-running melatonin rhythms, but that free-running melatonin rhythms were not necessarily associated with periodic insomnia and daytime sleepiness. Thus, it was not clear if the circadian sleep propensity rhythm was free-running with the other circadian rhythms. In the present study, we report that the sleep propensity rhythm (as defined by an ultrashort sleep-wake schedule) free-ran with the melatonin, temperature and cortisol rhythms in a 44-year-old totally blind man even though he maintained a conventional sleep schedule and did not complain of clinically significant insomnia or excessive daytime sleepiness.


Dynamics of EEG slow-wave activity and core body temperature in human sleep after exposure to bright light.

In seven subjects sleep was recorded after a single 3-hour (2100-0000 hours) exposure to either bright light (BL, approx. 2,500 lux) or dim light (DL, approx. 6 lux) in a crossover design. The latency to sleep onset was increased after BL. Whereas rectal temperature before onset and during the first 4 hours of sleep was higher after BL than after DL, the time course of electroencephalographic (EEG) slow-wave activity (SWA, EEG power density in the range of 0.75-4.5 Hz) in nonrapid eye movement sleep (NREMS) differed only slightly between the conditions. After BL, SWA tended to be lower than after DL in the first NREMS-REMS cycle and was higher in the fourth cycle at the time when the rectal temperature did not differ. The differences in SWA may have been due to a minor sleep-disturbing aftereffect of BL, which was followed by a rebound. The data are not in support of a close relationship between SWA and core body temperature.


Sleep in human narcolepsy revisited with special reference to prior wakefulness duration.

Sleep of 11 narcoleptic subjects was recorded on baseline and after 16 and 24 hours of prior wakefulness (16 and 24 hours sleep deprivation). Eleven sex- and age-matched control subjects were recorded for comparisons. All recordings in narcoleptic subjects were characterized by frequent sleep onset rapid eye movement (REM) episodes, increased amounts of wake time after sleep onset and low sleep efficiencies. Mean total sleep time (TST) was significantly decreased in narcoleptic subjects after sleep deprivation (SD). Recovery sleep after 24 hours SD showed reduced nonREM (NREM) sleep stage 2 percentage, whereas percentages of stage 4 and slow-wave sleep (SWS = stages 3 + 4) were significantly increased. The values of REM sleep percentage of TST were remarkably constant throughout and did not differ significantly as a function of experimental conditions, indicating a normal REM sleep pressure in narcolepsy. Sleep stage analysis per sleep cycles revealed significant differences between the two groups. Percentages of stage 4 and SWS were increased during the first cycle of recovery sleep in narcoleptic subjects. Stage 2 was decreased during the third cycle, and SWS decreased rapidly from cycle 1 to cycle 2 and slightly increased thereafter. These results indicate that sleep need is increased in narcolepsy, whereas its decrease over the first NREM-REM cycle is accelerated. We hypothesize that this could reflect an alteration of the homeostatic process of sleep regulation in narcolepsy.


Beta (20-28 Hz) and delta (0.3-3 Hz) EEGs oscillate reciprocally across NREM and REM sleep.

Across-night oscillations of beta (20-28 Hz) and delta (0.3-3 Hz) electroencephalograms (EEGs) were examined with spectral analysis in 10 normal young adult subjects (Ss). In each S, power densities of beta were found to oscillate reciprocally with delta power density across both nonrapid eye movement (NREM) and rapid eye movement (REM) sleep. Linear correlation coefficients between log power density of delta vs. beta were significant (p less than 0.0001) for each S. An incidental observation was that beta power within REM was reliably lower in epochs with more eye movement activity. The reciprocal relationship between beta and delta holds implications for sleep physiology and supplements our earlier finding that sigma (12-15 Hz) oscillates reciprocally with delta within NREM sleep. These descriptions of the continuously varying EEG across sleep provide information not available when EEG measures are tabulated by discrete NREM periods and REM periods.


T-sleep: an improved method for scoring breathing-disordered sleep.

We developed a new method to score sleep fragmented by respiratory events that we call the T-sleep (transitional sleep scoring) method. Five control polysomnograms from subjects without sleep-related breathing abnormalities were scored by the Rechtschaffen and Kales (R&K) method, and 10 polysomnograms from patients with severe obstructive sleep apnea were scored by both the R&K and the T-sleep method. Comparative analyses were performed on sleep variables of the control and apnea polysomnograms, and interscorer correlations were assessed for sleep and apnea variables. The interscorer correlations were high for both R&K control scoring and for apnea recordings scored by the T-sleep method. The number of sleep stage events documented for the 10 apnea recordings was significantly less for the T-sleep method than the R&K method (36, SD 17.0 vs. 332, SD 144.0; p = 0.0002). The T-sleep method was shown to be an effective, accurate and quick method for scoring sleep in patients with sleep-related breathing disorders.


Short technical note: quantification of periodic breathing: preliminary studies.

Although the apnea/hypopnea index is the most widely used measure of breathing pattern abnormality during sleep, this index gives no information about the strength of the oscillation in the breathing pattern, its periodicity or its regularity. Such information may be required in research studies involving breathing patterns and how they are affected by interventions. We are exploring spectral analytic methods to determine two normalized indices, the periodicity index and the modified modulation index, to examine periodic breathing for all-night sleep studies. These methods are automatic and require no user interaction. Data were obtained from 11 heart failure patients who slept for a total of 21 nights in the sleep laboratory. Because individual patients had a marked regularity of their Cheyne-Stokes respiration during sleep, one would expect an extremely high correlation between the traditional measures of breathing pattern abnormality and these spectral analytic techniques. Indeed we found that there was an extremely high correlation between the periodicity index and the modulation index and the traditional measures of apnea/hypopnea index and the proportion of the night with periodic breathing (p less than 0.02 in all cases). When the breathing pattern was irregular but still with many apneas there was a discrepancy between the apnea index and the indices of periodicity. These techniques are still preliminary and future studies will determine their limitations in other patient populations and where the pattern is unstable.


Removal of ocular artifacts from the REM sleep EEG.

The present report concerns the first study in which electrooculographic (EOG) contamination of electroencephalographic (EEG) recordings in rapid eye movement (REM) sleep is systematically investigated. Contamination of REM sleep EEG recordings in six subjects was evaluated in the frequency domain. REM-active and REM-quiet series were obtained for each subject. Transfer coefficients and power spectra of EOG and EEG indicated that (a) increases in transfer coefficients beyond 4.5 Hz are brought about by residual EEG in the EOG, and (b) EOG-EEG contamination in the delta band is most pronounced in frontal, intermediate in central and negligible in occipital leads. It was found that correction of the REM-active series resulted in significant (c) reductions in power, (d) increases in interhemispheric coherences and (e) reductions in degree of lateral asymmetry. These effects were largest for frontal leads, but still marked for central ones. The results are discussed in the light of previous findings concerning models of hemispheric functioning during REM sleep.


Reliability and factor analysis of the Epworth Sleepiness Scale.

The Epworth Sleepiness Scale (ESS) is a self-administered eight-item questionnaire that has been proposed as a simple method for measuring daytime sleepiness in adults. This investigation was concerned with the reliability and internal consistency of the ESS. When 87 healthy medical students were tested and retested 5 months later, their paired ESS scores did not change significantly and were highly correlated (r = 0.82). By contrast, ESS scores that were initially high in 54 patients suffering from obstructive sleep apnea syndrome returned to more normal levels, as expected, after 3-9 months' treatment with nasal continuous positive airway pressure. The questionnaire had a high level of internal consistency as measured by Cronbach's alpha (0.88). Factor analysis of item scores showed that the ESS had only one factor for 104 medical students and for 150 patients with various sleep disorders. The ESS is a simple and reliable method for measuring persistent daytime sleepiness in adults.


The influence of buffalo and bovine serum on transformation of Trypanosoma congolense from metacyclic forms to bloodstream forms in vitro.

The transformation of Trypanosoma congolense metacyclics into bloodstream forms was studied in vitro using light and electron microscopy. The trypanosomes were maintained in culture at 28 degrees C using a medium supplemented with foetal bovine serum. The metacyclics were harvested and separated from the procyclic and epimastigote forms by using anion exchange chromatography. Isolated metacyclics were incubated with different concentrations of buffalo or bovine serum at 35 degrees C for periods ranging from 3 hours to 72 hours. It was noted that the metacyclics transformed at about the same time regardless of the animal serum used. However, most of the buffalo serum tended to kill trypanosomes whereas bovine serum tended to support trypanosome growth. The killing of the trypanosomes may be due to natural toxins present in buffalo serum.