Molecular dissection of the beta subunit of F1-ATPase into peptide fragments.

Partial digestion of the native beta subunit of F1-ATPase from the thermophilic Bacillus strain PS3 by three different proteases produced a limited number of peptide fragments. In most cases, the peptides remained associated, and the gross structure of the beta subunit was not destroyed. Furthermore, most peptides were able to reassociate into the form of the beta subunit after denaturating urea treatment. Therefore, the cleaved sites are most likely located in water-exposed loop regions in the tertiary structure of the protein. Almost all peptides were analyzed, and 17 cleaved sites were determined. From the analysis of the distribution of cleaved sites and deletions or insertions in the multiple amino acid sequence alignment of proteins homologous to the beta subunit, locations of five loops and four candidate loops in the beta subunit are suggested. There are two large loops in the central region of the beta subunit sequence, and dicyclohexylcarbodiimide-reactive Glu190 is located in one of them. Tyr341, involved in putative catalytic ATP binding, is also found in one of the loops. Then, taking cleaved sites as a reference, two kinds of expression plasmids, each of which carried genes of two complementary peptide fragments, 1-193 and 198-473 or 1-284 and 285-473, were constructed and expressed in Escherichia coli. For each plasmid, two peptides were coexpressed, associated into a stable beta subunit form in E. coli cells, and purified without dissociation. When these beta subunits were denatured by urea and applied to polyacrylamide gel without denaturant, a protein band with the same mobility as that of the beta subunit appeared, indicating that reassociation of peptide fragments into the form of the beta subunit occurred upon removal of urea. These beta subunits retained the ability to reconstitute the alpha 3 beta 3 gamma complexes even though the efficiency of reconstitution and the recovered ATPase activities were decreased. These complexes were stable at high or low temperature, and ATPase activities were sensitive to inhibition by N3-.


Evidence for monomeric and dimeric forms of CD45 associated with a 30-kDa phosphorylated protein.

Glycoprotein CD45, a transmembrane protein tyrosine phosphatase of leukocytes, is topographically similar to the epidermal growth factor receptor, a transmembrane tyrosine kinase. Since the latter is thought to be allosterically regulated through conversion between monomeric and dimeric forms, we sought to determine whether CD45 undergoes similar oligomerization. Our analysis, employing a thiol-cleavable and homobifunctional chemical cross-linker, dithiobis succinimidyl propionate, revealed that CD45 indeed formed homodimers. In addition, a protein of molecular mass 30,000 daltons (30 kDa) was found to be associated with both the CD45 monomer and dimer. The 30-kDa protein was phosphorylated and was not labeled by cell surface radioiodination. Distinct differences in protein tyrosine phosphatase activity were detected among the various populations of CD45 separated by sucrose gradient ultracentrifugation. However, the differences observed could not be explained simply by dimerization and instead suggest the presence of other factor(s) involved in the regulation of CD45 enzyme activity.


Localization and characterization of a 7.3-kDa region of caldesmon which reversibly inhibits actomyosin ATPase activity.

Cleavage of caldesmon with chymotrypsin yields a series of fragments which bind both calmodulin and actin and inhibit the binding of myosin subfragments to actin and the subsequent stimulation of ATPase activity. Several of these fragments have been purified by cation exchange chromatography and their amino-terminal sequences determined. The smallest fragment has a molecular mass of about 7.3 kDa and extends from Leu597 to Phe665. This polypeptide inhibits the actin-activated ATPase of myosin S-1; this inhibition is augmented by smooth muscle tropomyosin and relieved by Ca(2+)-calmodulin. The binding of the 7.3-kDa fragment to actin is competitive with the binding of S-1 to actin. Thus, this polypeptide has several of the important features characteristic of intact caldesmon. However, although an intact caldesmon molecule covers between six and nine actin monomers, the 7.3-kDa fragment binds to actin in a 1:1 complex. Comparison of this fragment with others suggests that a small region of caldesmon is responsible for at least part of the interaction with both calmodulin and actin.


An unusual splicing mutation in the HEXB gene is associated with dramatically different phenotypes in patients from different racial backgrounds.

Sandhoff disease is caused by mutations affecting the beta subunit of lysosomal beta-hexosaminidase (EC 3.2.1.52) and displays a wide spectrum of clinical phenotypes. We report a 57-year-old patient with a very mild phenotype, although residual hexosaminidase A activity in his cultured fibroblasts was less than 3% of normal activity, a level observed in juvenile onset patients. Northern and Western blot analyses confirmed a similar low level of beta subunit-mRNA and mature beta-protein, respectively. Two mutations of the HEXB gene were identified in this patient, a partial 5' gene deletion (a null allele), and a C----T transition 8 nucleotides downstream from the intron 10/exon 11 junction affecting the splicing of the beta subunit-mRNA. In their homozygous forms, the 5' deletion has been previously shown to result in a severe infantile phenotype, and the C----T transition in a juvenile phenotype. The genotype and the low level of residual hexosaminidase A activity would be expected to produce a juvenile Sandhoff phenotype in this patient, as well as in four of his six clinically normal siblings. The biochemical basis of his mild phenotype is uncertain, but may result from genetic variations in the RNA splicing machinery.


Restricted heterogeneity of T cell receptor transcripts in rheumatoid synovium.

RA is characterized by massive proliferation of synovial tissue, accompanying infiltration of the tissue with CD4+ T lymphocytes, and a genetic linkage to the MHC antigen HLA-DR4. Since T cells are restricted by class II MHC molecules such as DR4, this suggests a direct role for these CD4+ cells in pathogenesis. To investigate T cell receptor (TCR) usage in RA, we used oligonucleotide primers specific for each of the major alpha and beta TCR subfamilies to amplify cDNA derived from whole synovium or synovial tissue T cell lines in a family-specific manner. Detection of amplified DNA was facilitated by utilizing oligonucleotide probes derived from the constant regions of the TCRs. The TCR repertoire present in the synovial T cell lines was quite heterogeneous, with an average of 15 alpha chains and 15.8 beta chains detected. When synovial tissue was analyzed, the predominant TCR subfamilies detected tended to be more restricted, with an average of 4.6 alpha chains and 8.6 beta chains detected. This compared with an average of six alpha chains and 12 beta chains in nonrheumatoid synovial samples. The average percentage of synovia positive per TCR beta family was significantly lower for RA versus non-RA specimens (46.1 vs 65.6%, P = 0.034). These findings indicate that while a polyclonal population of T cells is present in RA synovium, the predominant patterns of TCR transcript expression may be somewhat more restricted, suggesting that TCR-based therapy of RA is possible.


A novel lymphoproliferative/autoimmune syndrome resembling murine lpr/gld disease.

In mice, the two distinct autosomal recessive genes lpr and gld can induce a syndrome characterized by autoantibody formation and the progressive accumulation of an unusual CD4-CD8- T cell population in peripheral lymphoid tissue. This phenotype does not precisely mirror any human disease. In this report we describe two patients with a progressive lymphoproliferative disorder associated with autoimmunity. The peripheral blood and lymph nodes of these patients contained large numbers of an unusual CD4-CD8- T cell population. These CD4-CD8- T cells express surface markers characteristic of mature peripheral blood T cells (CD3, CD2, CD5), express the alpha/beta form of the T cell receptor, and do not express surface markers characteristic of immature thymocytes (CD1) or NK cells (CD16, CD56). Functionally, these cells exhibited deficient proliferation and lymphokine production upon stimulation with mitogenic antibodies to CD3 or CD2. Both proliferation and lymphokine production could be augmented by co-stimulation with an antibody directed at the CD28 determinant. The clinical and immunological features of this syndrome resemble the lymphoproliferative/autoimmune disease seen in lpr and gld mice.


Surface expression of Fc gamma receptor III (CD16) on chemoattractant-stimulated neutrophils is determined by both surface shedding and translocation from intracellular storage compartments.

Stimulation of neutrophils (PMN) with chemoattractants markedly increases surface expression of several membrane proteins, including the complement receptors, CR1 and CR3, by translocation from intracellular storage compartments to the cell surface. When we stimulated freshly-isolated PMN with FMLP, we observed little net change in surface Fc gamma receptor (R) III expression. However, if elastase was first used to cleave most (85-90%) of the Fc gamma R III from the PMN surface, subsequent treatment with FMLP induced a rapid renewal of surface Fc gamma R III, achieving levels of approximately 70% of that originally present on the cell surface after 15 min, suggesting translocation of intracellular receptors. This was confirmed by demonstrating concomitant depletion of greater than 80% of the intracellular Fc gamma R III. Studies of density gradient fractions of N2-cavitated PMN indicated at least two distinct intracellular membrane fractions that contain Fc gamma R III. Shedding of Fc gamma R III induced by FMLP was about half-maximal by 15 min and nearly complete by 60 min. Stoichiometric assessment of FMLP-induced changes in PMN surface and intracellular Fc gamma R III showed a marked depletion in intracellular Fc gamma R III, little net change in surface Fc gamma R III, and a large overall loss of total cell Fc gamma R III that could be attributed to shedding. We conclude that stimulation by chemoattractants causes a rapid translocation of intracellular Fc gamma R III to the PMN surface that is roughly balanced by the concomitant FMLP-induced shedding of this receptor.


Osteogenesis and growth of the nasal ventral conchae of the piglet.

The present study investigated the osteogenesis and growth of the nasal ventral conchae of piglets aged from 1 to 28 days. Serial transverse sections of paraffin wax-embedded noses were stained and examined by light microscopy. Bone formation occurred in a rostrocaudal direction in the ventral scroll, dorsal scroll, connecting zone, transverse lamina and articular lamina, successively, and occurred by two ossification processes: endochondral ossification and intramembranous bone apposition. Endochondral ossification was responsible for the longitudinally, rostrally directed growth. Rapid transverse bone growth and modelling were centrifugally directed and occurred by intramembranous bone apposition at the eccentric side of the scrolls and resorption at the concentric scroll side. Elongation of the distal scroll extremities took place by intramembranous bone apposition.


Human neutrophil annexin I promotes granule aggregation and modulates Ca(2+)-dependent membrane fusion.

The mechanism and cofactor requirements of exocytotic membrane fusion in neutrophils are unknown. Cytosolic proteins have been implicated in membrane fusion events. We assessed neutrophil cytosol for the presence of fusogenic proteins using a liposome fusion assay (lipid mixing). A fusogenic 36-kD protein containing amino acid sequence homology with human annexin I was purified from the cytosol of human neutrophils. This protein also shared functional characteristics with annexin I: it associated with and promoted lipid mixing of liposomes in a Ca(2+)-dependent manner at micromolar Ca2+ concentrations. The 36-kD protein required diacylglycerol to promote true fusion (contents mixing) at the same Ca2+ concentrations used for lipid mixing. The 36-kD protein exhibited a biphasic dose-response curve, by both promoting and inhibiting Ca(2+)-dependent lipid-mixing between liposomes and a plasma membrane fraction. The 36-kD protein also promoted Ca(2+)-dependent increases in aggregation of a specific granule fraction, as measured by a turbidity increase. Antiannexin I antibodies depleted the 36-kD protein from the cytosol by greater than 70% and diminished its ability to promote lipid mixing. Antiannexin I antibodies also decreased by greater than 75% the ability of neutrophil cytosol to promote Ca(2+)-dependent aggregation of the specific granules. These data suggest that annexin I may be involved in aggregation and fusion events in neutrophils.


Interleukin-1 receptor antagonist in normal and psoriatic epidermis.

The objective of these studies was to characterize the IL-1 inhibitory activity present in normal and psoriatic epidermis from clinically stable lesions. Fractionation of normal epidermal cytosol on a molecular sizing column failed to reveal the presence of IL-1 inhibitory bioactivity. However, specific ELISAs indicated that both the IL-1 receptor antagonist (IL-1ra) and IL-1 alpha were present in overlapping peaks. Further fractionation of the normal epidermal cytosol by anion exchange chromatography separated these two molecules, revealing the IL-1 inhibitory bioactivity of the IL-1ra molecule. Similar studies on psoriatic epidermal cytosol indicated the presence of IL-1 inhibitory bioactivity and IL-1ra protein. The IL-1 inhibitory bioactivity of both normal and psoriatic cytosol was neutralized by a mAb specific for IL-1ra. The ratio of IL-1ra to IL-1 alpha proteins was significantly increased in involved psoriatic skin compared with normal skin. By Western blot analysis this IL-1ra was approximately 20 kD, slightly larger than monocyte-derived IL-1ra and equivalent to an intracellular variant of IL-1ra expressed by keratinocytes. Polymerase chain reaction indicated the presence of mRNA for both forms of IL-1ra in normal epidermis, with both forms increased in psoriatic-involved skin. Immunofluorescence studies revealed the IL-1ra protein to be concentrated in the stratum granulosum of normal skin and in the basal-midbasal layers of psoriatic epidermis. These results suggest that the balance between intracellular IL-1ra and IL-1 alpha may be an important influence on keratinocyte growth and/or differentiation, as well as on the inflammatory potential of IL-1 in injured skin.


Oral spironolactone therapy in male patients with rosacea.

Spironolactone at 50 mg/day was orally administered for four weeks to 13 male patients with rosacea in order to observe its clinical effectiveness. Serum estradiol (E2), 17OH-progesterone (17OH-P4), testosterone (T), androstenedione (delta 4 A), dihydrotestosterone (DHT), dehydro-epiandrosterone sulfate (DHEA-S) were measured prior to and after treatment. Although there were no significant changes in T, delta 4A, DHT, or DHEA-S, the serum levels of 17OH-P4 increased significantly. E2 tended to increase, although the change was not significant. Two of the 13 patients discontinued spironolactone treatment because of general malaise, but seven of the remaining eleven patients exhibited an improvement in their rosacea. These findings demonstrate that a low dose of spironolactone is effective in the treatment of rosacea in some male patients and suggest that it is possible that changes in the metabolism of sex steroid hormones such as cytochrome p-450 isozymes have some bearing on the etiology of rosacea.


Experiences of informal carers providing nursing support for disabled dependants.

This paper provides an account of the experience of a group of informal carers who provided nursing support for their physically disabled dependants. The project was designed to establish the extent to which carers are equipped to fulfil their role in terms of equipment, facilities, skills, levels of personal health and the extent of support available to them from agencies outside the home. The carers were found to be providing the majority of nursing support required by their dependants. This mainly involved carrying out tasks of personal care although, for some, more technical procedures were involved. The findings indicate there is scope for professional nurses to make a greater contribution to the support of informal carers, particularly by regular review of the nature and level of assistance which carers provide and by giving training in the skills which carers require.


Field-testing the new DECtalk PC system for medical applications.

Synthesized human speech has now reached a new level of performance. With the introduction of DEC's new DECtalk PC, the small system developer will have a very powerful tool for creative design. It has been our privilege to be involved in the beta-testing of this new device and to add a medical dictionary which covers a wide range of medical terminology. With the inherent board level understanding of speech synthesis and the medical dictionary, it is now possible to provide full digital speech output for all medical files and terms. The application of these tools will cover a wide range of options for the future and allow a new dimension in dealing with the complex user interface experienced in medical practice.


Huntington's disease in Thailand: a case report.

The first documented case of Huntington's Disease (HD) in Thailand is reported. The patient presented with classical clinical picture, clinical course and family history. Although hereditary chorea is most frequently associated with HD, other hereditary basal ganglion diseases, Syndenham's chorea, and other causes of abnormal movements were considered and excluded by clinical profiles and investigations. Various recent aspects of HD are briefly mentioned.


Low back pain in eight areas of Britain.

The aim was to assess the geographical variation in low back pain and associated disability in Britain. This was a cross sectional survey with information collected by postal questionnaire. General practices in seven British towns and one rural district. 1172 men and 1495 women aged 20-59 years were selected from the age-sex registers of 136 general practitioners in the study areas. The overall lifetime and one year period prevalences of low back pain were 58.3% and 36.1%. Rates in men and women were similar. Symptoms were more common in men with manual occupations than in those with non-manual jobs, but in women there was no clear trend in relation to social class. Geographical differences in prevalence were small, but the threshold for consulting general practitioners about symptoms varied markedly from place to place. After allowance for age, sex, social class, and severity of symptoms, subjects in the northern towns of Arbroath and Peterlee who had suffered from low back pain in the past year were three to four times as likely to have consulted their doctor about the problem as those living in the southern towns of St Austell and Dorking. Consultation rates in the Midlands were intermediate. Geographical variation in rates of general practice consultation for low back pain in Britain is due largely to differences in patient behaviour once symptoms have developed. The distribution of important causes of low back back pain across the country is probably fairly uniform.


Risk of low back pain in people admitted to hospital for traffic accidents and falls.

The aim was to assess the risk of back symptoms in people admitted to hospital because of traffic accidents and falls. The study was a cross sectional survey with information collected by postal questionnaire. Main outcome measures were associations between hospital admission for a traffic accident or fall and reported first onset of back symptoms at the same age and at later ages. General practices in seven towns and one rural district. 1172 men and 1495 women aged 20-59 years were selected from the age-sex registers of 136 general practitioners in the study areas. Low back pain was reported by 1556 subjects and hospital admission for a traffic accident or fall by 362. The incidence of low back pain was unusually high during the year of age at which subjects were first admitted to hospital for trauma (RR = 5.5, 95% CI 3.8-7.8). The risk of first developing symptoms in subsequent years was lower, but still significantly increased (RR = 1.3, 95% CI 1.1-1.6). Low back pain which started at the age of an accident tended to last longer than that occurring in other circumstances, and was more often ascribed to injury (56% of cases). However, this proportion was smaller than the calculated attributable proportion for traffic accidents and falls (82%). The data suggest that a person under age 60 years who is admitted to hospital for a traffic accident or fall has a 7% chance of developing low back pain as result of the injury. However, the link between the injury and subsequent symptoms is often not obvious to the patient.


Oral contraceptive use and cardiovascular disease: is the relationship real or due to study bias?

Epidemiologic studies link oral contraceptive use with several cardiovascular events, but the literature is difficult to summarize, and potential biases remain poorly addressed. This study uses meta-analysis to summarize study results and to analyze the influence of study characteristics, including susceptibility to bias, on study outcome. Forty-seven case-control and cohort studies of oral contraceptives and four cardiovascular events were coded for relative risk (RR) and study characteristics, including adherence to 14 bias-control standards. Key RRs were pooled to summarize findings for each disease type. Univariate determinants of the magnitude of the relative risks were identified, and partial correlation analysis was performed for each disease type. Relative risks were significantly greater than 1.0 for venous thromboembolism (RR = 2.8, CI = 2.4 to 3.2), stroke (RR = 1.8, CI = 1.6 to 2.0), and myocardial infarction (RR = 1.6, CI = 1.4 to 1.8), but not for death due to any cardiovascular cause (RR = 1.0, CI = 0.8 to 1.3). Study characteristics were diverse, and potential biases were frequently uncontrolled. For three of ten study characteristics identified as independently influencing relative risk, methodologically stronger studies of venous thromboembolism tended to have higher RRs. The RRs for stroke and myocardial infarction were lower in studies that were methodologically stronger with regard to variables identified as important. In studies of cardiovascular death, bias-control standards identified as important were generally well addressed by the studies. Oral contraceptive use does not appear to increase overall cardiovascular mortality. The associations noted with stroke and myocardial infarction may be due to methodologic flaws in the studies, while the association with venous thromboembolism is more likely to be valid.


Interactions between phospholipase C-coupled and N-methyl-D-aspartate receptors in cultured cerebellar granule cells: protein kinase C mediated inhibition of N-methyl-D-aspartate responses.

The N-methyl-D-aspartate (NMDA) receptor of rat cerebellar granule cells in primary culture is inhibited by phospholipase C-coupled receptor activation. In the absence of ionotropic agonist, cells modulate their cytoplasmic free Ca2+, [Ca2+]c, in response to stimulation of M3 muscarinic receptors, metabotropic glutamate receptors, and endothelin receptors by the respective agonists carbachol, trans-1-amino-1,3-cyclopentanedicarboxylic acid, and endothelin-1. The response is consistent with the ability of phospholipase C-coupled receptors to release a pool of intracellular Ca2+ and induce a subsequent Ca2+ entry into the cell; both of these responses can be abolished by discharge of internal Ca2+ stores with low concentrations of ionomycin or thapsigargin. In the case of cells stimulated with NMDA, the [Ca2+]c response to the phospholipase C-coupled agonists is complex and agonist dependent; however, in the presence of ionomycin each agonist produces a partial inhibition of the NMDA component of the [Ca2+]c signal. This inhibition can be mimicked by the protein kinase C activator 4 beta-phorbol 12,13-dibutyrate. It is concluded that NMDA receptors on cerebellar granule cells are inhibited by phospholipase C-coupled muscarinic M3, glutamatergic, and endothelin receptors via activation of protein kinase C.


Postsynaptic, but not presynaptic, activity controls the early time course of long-term potentiation in the dentate gyrus.

The early time course (less than 1 hr) of long-term potentiation (LTP) in the dentate gyrus of the guinea pig hippocampal slice was examined using extracellular recordings from the outer two-thirds of the dendritic layer. LTP was induced by a single brief (2-40 impulses) high-frequency (20-400 Hz) train, or by pairing a single test stimulus with a brief heterosynaptic high-frequency train. The induction of LTP was facilitated by blockade of fast GABAergic postsynaptic inhibition. It was found that, irrespective of induction conditions and the amount of LTP induced, the onset of LTP was characterized by a latency of a few seconds following the induction event, and a rapid 30 sec growth phase. After a 1-2 min period of little or no further growth, LTP decayed but in a highly variable manner, from cases in which more than 60% of the peak value remained 1 hr after the induction to cases in which LTP decayed completely within 10 min. Factors increasing presynaptic activity (frequency or number of afferent stimulations) during the induction event did not affect the relative amount of LTP decay. Repetitive presynaptic activity was found not to be a necessary condition for eliciting long-lasting LTP (greater than 1 hr), as shown by experiments in which a single presynaptic impulse was paired with a brief heterosynaptic train. Factors increasing postsynaptic activity during the induction event, such as increased stimulus intensity, temporal pairing of two weak trains, or reduced postsynaptic inhibition, all reduced the relative amount of LTP decay. Moreover, partial pharmacological blockade of NMDA receptor channels increased the relative amount of decay. In conclusion, the amount of postsynaptic activity and associated NMDA receptor activation during the induction event appeared to be the main factor governing the early stability of LTP in the dentate gyrus.


Techno-stress. A psychophysiological study of employees with VDU-associated skin complaints.

Little is known about the causes of health complaints associated with work with video display units (VDUs). The symptoms are to a large degree similar to those of "multiple chemical sensitivity." We observed 47 white-collar employees with and without VDU-associated skin complaints during a regular workday and a day of leisure. VDU workers with skin symptoms had higher levels of the stress-sensitive hormones thyroxin and prolactin compared with employees without symptoms. They also had lower levels of the anabolic hormone testosterone during work. VDU workers with skin complaints also reported more occupational mental strain. A model is proposed in which physiological signals act as unconditioned stimuli and the VDU environment as the conditioned stimuli.


State of the art: regional anesthesia using anesthetic admixtures.

Aging, high-risk, and ambulatory patients comprise a growing population of surgical candidates. The advantages of regional anesthesia for these patients has promoted technological and pharmacological advances. As new anesthetic agents are developed, methods to improve existing local anesthetics continue. This article reviews the current practice of local anesthetic admixtures. The physiological action of the local anesthetics and their additives is explained relative to their chemical properties. The advantages and risks when adding bicarbonate and epinephrine are described. Nursing implications for the care of the patient receiving regional anesthesia using admixtures are reviewed. An actual case report is presented to demonstrate the clinical application of local anesthetic admixtures.


From theory to practice: Orem's self-care nursing model and ambulatory care.

Delivery of patient care based on theoretical principles can promote successful practice. Orem's Self-Care Nursing Theory offers direction for the practitioner in the ambulatory surgery setting. In this model, the nurse assists clients by acting for, teaching, guiding, supporting, and providing a developmental environment. Levels of care range from performing total care to educating the patient and family. Promoting self-care as soon as feasible is the goal of the ambulatory care plan. Consequently, self-care deficits created during surgery and anesthesia must be overcome so that the patient is dismissed from the ambulatory setting with the ability to meet self-care needs.


Telephone follow-up of ambulatory surgery patients following discharge is a nursing responsibility.

The ambulatory surgery nurse manages care for a diverse population of patients who may or may not be ideal candidates for early discharge after surgery. Integral to the nursing care is the postdischarge follow-up contact, which allows the nurse to assess the patient's level of recuperation and evaluate the care provided. A number of reasons, besides completion of the nursing process, indicate that this contact is a nursing obligation. These include compliance with national standards of care, improvement of quality of care, and reduction of the facility's liability exposure. These calls also show a sense of caring about patients and help to market the ambulatory surgery program in the community. The nurse develops a true sense of professionalism and often benefits by increased job satisfaction.


Practical points in the management of a postoperative acoustic neuroma patient.

Presented in this article is a brief overview of cranial anatomy and pathophysiology. Highlights of preoperative signs and symptoms and three surgical procedures performed on acoustic neuroma patients are discussed. Postoperative complications and nursing interventions are emphasized.


Concept analysis methodology: applications to altered level of consciousness.

Concept analysis is the first step in instrument development. Steps in the concept analysis process are discussed and applied to the analysis of altered level of consciousness (ALC) as a potential nursing diagnosis for submission to the North American Nursing Diagnosis Association. Criteria regarding ALC have been defined for the assessment of neurologically impaired patients and not for the neurologically intact postanesthesia patient. It is assumed that postanesthesia patients experience chemically induced ALC, and consensus regarding what constitutes this concept needs to be validated by PACU nurses. The first step in instrument development is a clear definition of the concept of interest. The criteria for ALC determined by the PACU nurses could then be used to construct a pencil-and-paper instrument that would allow the concept to be tested on postanesthesia patients as they emerge from anesthesia. This concept analysis-to-instrument development process discussion can be applied to any concept of interest to the PACU nurse.


Traumatic neuropathic spinal arthropathy.

Traumatic spinal neuropathy is a condition which results as a loss of the feedback response from the insensate spine. Clinically a severe kyphotic deformity and gross instability is apparent. Radiographically, severe joint destruction with a "ball and socket" pseudarthrosis is seen. An infectious process must be excluded and surgical stabiliation has an excellent prognosis.


Typing of human red cell and serum mixtures in three electrophoretic systems.

The isoenzymes erythrocyte acid phosphatase and phosphoglucomutase were typed in mixed red cell samples which had been derived from two individuals; the protein group specific component was typed in mixed serum samples. Typing was performed by isoelectric focusing on ultrathin polyacrylamide gels. Depending upon the mixture, from 2 to 20% (but typically 5-10%) by volume of a second blood or serum needed to be present in a mixture before it could be detected. In the majority of cases when there was significant mixing, samples were readily identified as a mixture when the results consisted of unusual band patterns or unusual band intensities. There would be a few instances when blood or serum could not be identified as a mixture when masking effects occurred or when the mixture produced a combined, apparently normal, pattern.


Thymopentin in Sézary syndrome.

Response to the treatment of Sézary syndrome (a cutaneous T-cell lymphoma) is poor. Since patients with this syndrome are elderly, aggressive chemotherapy is poorly tolerated and deep immunodepression may result in fatal opportunistic infections. Immunomodulating therapy seems important in the management of Sézary syndrome. In a pilot study, we assessed the efficacy of thymopentin (TP-5), a synthetic pentapeptide, correlating clinical responses to the histologic and immunologic effects of the drug. Twenty Sézary syndrome patients received 50 mg TP-5 intravenously three times a week for a mean time of 16.3 months. Skin and lymph node histology and immunohistochemistry, circulating lymphoid cell subpopulations, and soluble interleukin-2 receptors were evaluated before treatment and during follow-up. Eight complete remissions and seven partial remissions were obtained (75%). No change was observed in three patients, and disease progression was observed in two patients. The median duration of response was 22 months (complete remission, 25.5 months; partial remission, 14 months). Four-year survival probability was 53.9%. The responses were obtained when circulating Sézary cells were less than 2600/mm3. A significant reduction of CD4+ cells paralleled a CD8+ cell increase. An increase in NK cells (CD16+ and CD56+) was accompanied by significantly longer survival. Serum soluble interleukin-2 receptor values were a useful monitor of the clinical course and treatment. Loss of epidermotropism, reduction of Langherhans' cells, and HLA-DR+ keratinocytes were found. TP-5 is a potentially useful agent in the treatment of a subgroup of patients with Sézary syndrome; its activity seems to be mediated by an effect on a normal NK cell-like subpopulation. The biological and clinical role of this therapy in combination with conventional treatments will be the subject of future investigations.


Correlation of inflammatory infiltrate with the enlargement of experimental aortic aneurysms.

Inflammatory cells often are seen in the walls of human aortic aneurysms, but their significance is uncertain. To investigate their actions an in vivo model of arterial aneurysms was developed in the rat. Fifteen units of hog pancreatic elastase were infused for 2 hours into the isolated abdominal aorta in 26 rats. The vessels were measured in vivo and were excised for conventional histologic and immunohistologic study at selected intervals. In untreated control rats the diameter of the aorta was 1.04 +/- 0.02 mm. Immediately after infusion with elastase the aorta dilated 26% to 1.31 +/- 0.02 mm (p = NS), with no histologically demonstrable remaining elastic lamellae. Two and one half days after infusion the aorta dilated nearly 300% to 3.09 +/- 0.08 mm (p less than 0.05). These vessels exhibited large numbers of activated macrophages and T cells in the media. Three and 4 days after infusion the vessels dilated 388% to 4.04 +/- 0.09 mm and 367% to 3.82 +/- 0.31 mm, respectively. These vessels also exhibited numerous inflammatory cells in the media. Six days after infusion the vessels enlarged 421% to 4.38 +/- 0.03 mm (p less than 0.05), and the infiltrate persisted staining immunohistologically for macrophages, polymorphic neutrophils, and T lymphocytes. Twelve days after infusion the aneurysms remained enlarged but stable at 4.23 +/- 0.14 mm (p = NS). At this time the number of inflammatory cells regressed to control levels. The temporal correlation between inflammatory infiltrate and aneurysmal enlargement suggests that inflammatory cells may participate in the destruction of the aneurysmal vessel wall thereby promoting progressive enlargement.(ABSTRACT TRUNCATED AT 250 WORDS)


Dapsone syndrome in Vanuatu: a high incidence during multidrug treatment (MDT) of leprosy.

Side-effects of leprosy treatment with dapsone are said to be uncommon, with drug allergy occurring in only one of every several hundred patients treated with dapsone. The dapsone or sulphone syndrome (DDS) has been recognized since the earliest days of sulphone therapy but until recently its incidence had been decreasing. In Vanuatu, during the years 1988-1991, nine leprosy patients have developed the dapsone syndrome, four of whom have died. During the last 4 years only 37 patients were started on treatment, which is an incidence of the dapsone syndrome of 24% with a fatality rate of 11%. All the patients were being given multi-drug treatment (MDT) of daily dapsone (100 mg) and clofazimine (50 mg) and monthly rifampicin (600 mg) and clofazimine (300 mg). There has been speculation that the increased incidence of what was previously described as a rare reaction is due to the use of MDT, and the reasons for this are discussed. We feel the increase in the number of reactions in Vanuatu since starting MDT is probably due to the high starting dose of 100 mg of dapsone, possibly enhanced by the combination with clofazimine and rifampicin and a genetic susceptibility of the Melanesian population.


Functional and metabolic responses to ischemia in the isolated perfused hypothyroid rat heart.

It has been demonstrated that the V3 cardiac myosin isozyme has a higher efficiency and consumes less oxygen in doing mechanical work than the V1 myosin isozyme. The purpose of the present study is to investigate the functional and metabolic responses to ischemia following reperfusion of the hypothyroid heart, in which ventricular myosin isozyme is shifted from V1 predominance to V3 predominance. The heart was perfused by the working heart method for 15 min, and then global ischemia was induced for 10, 20 and 30 min with pacing at a rate of 320/min until cardiac cessation. The ischemic heart was reperfused for 30 min. The extent of recovery of pressure-rate product after reperfusion, following 20 min of ischemia in the hypothyroid heart, was higher than that in the control heart (p less than 0.01). The level of adenosine triphosphate (ATP) declined more slowly in the hypothyroid heart than in the control heart. The level of ATP and energy charge potential in the hypothyroid heart reperfused after 20 min of ischemia were higher than those in the reperfused control heart (p less than 0.01, p less than 0.05, respectively), though they did not differ from each other in preischemia. There were no significant differences in the levels of tissue lactate between the 2 hearts during ischemia and reperfusion. The recovery rate of the coronary flow of the 2 hearts did not differ from each other significantly. These data suggest that there is probability of the V3 predominant heart recovering from ischemic damage to the metabolism and cardiac function better than the V1 predominant heart because the transformation of myocardium, due to an increase in V3 into a slower but more efficiently working muscle results in conservation of tissue ATP during ischemia.


Molecular mechanism of hypertrophied failing heart--abnormalities of the diastolic properties and contractility.

The clinical syndrome of heart failure occurs as a consequence of the limitation of compensatory mechanisms, such as cardiac hypertrophy. To clarify transcriptional changes in specific genes in failing hearts, we examined the expression of cardiac Ca(2+)+Mg(2+)-dependent ATPase in the sarcoplasmic reticulum and transforming growth factor beta genes in the ventricles of rat hypertrophied heart, and the expression of guanine nucleotide-binding protein and "fetal" contractile protein genes in the ventricles of cardiomyopathic Syrian hamsters of Bio14.6. Northern blot analysis of total cellular RNA revealed that the mRNA levels of Ca(2+)+Mg(2+)-dependent ATPase were decreased by pressure overload and became 32% of sham in 1 month, and were correlated with corresponding protein levels. Transforming growth factor beta mRNA, a potent activator of collagen synthesis, was increased by pressure overload. The expression levels of the Gs alpha mRNA, which stimulated the adenylate cyclase, in Bio14.6 ventricles were lower than the levels in ventricles of the F1B hamster strain, and decreased as the stage of cardiomyopathy progressed. Moreover, re-expression of fetal mRNA was observed in the ventricle of cardiomyopathic Syrian hamsters of the Bio14.6 strain. These results indicate that reprogramming of cardiac gene expression both of myofibrillar and nonmyofibrillar components might occur in the failing heart.


Augmentation of interleukin-2 production after cardiac operations in patients treated with erythropoietin.

It has been reported recently that cardiac operations can be followed by a transient impairment of cell-mediated immunity. In this study we examined indices of cell-mediated immunity in patients undergoing cardiac operations. Twenty-five of the patients received erythropoietin (200 U/kg) daily for 2 weeks before and after operation, and 30 matched control patients did not receive erythropoietin. On postoperative day 1, the numbers of total T cells and helper/inducer T cells were significantly higher in erythropoietin-treated patients than in control patients. The ability of patients' cells to make interleukin-2 in vitro increased after erythropoietin injection in the preoperative period. By postoperative day 1, erythropoietin-treated patients exhibited a fall in interleukin-2 production that was significantly less than that in control patients; levels increased by day 2 to a mean value twice that of the preoperative baseline and more than four times the corresponding mean level in the control groups, and levels returned to the baseline range by postoperative day 14. Levels of interleukin-2 production in erythropoietin-treated patients were significantly higher than those in control patients at each interval tested through postoperative day 7. These findings indicate that erythropoietin treatment not only augmented levels of circulating erythrocytes but also improved indices of cell-mediated immunity. Although the mechanism responsible for this effect remains to be determined, the finding suggests that erythropoietin might help to ameliorate or prevent the impairment of immune function that can occur after cardiac operations.


Warm retrograde cardioplegia. Protection of the right ventricle in mitral valve operations.

Hypothermia is believed to be the most important aspect of successful myocardial protection with retrograde coronary sinus cardioplegia. Because nutritive capillary flow to the right ventricle and septum is thought to be diminished with retrograde perfusion, these areas of the myocardium are considered at higher risk for intraoperative deterioration without the added protection of hypothermia. Recently we introduced warm aerobic arrest as an alternative to conventional methods of myocardial protection. We present our clinical results in 37 patients with mitral valve disease (+/- aortic valve, aortic root, or coronary artery disease) who underwent various cardiac procedures for which warm blood cardioplegic solution was delivered continuously via the coronary sinus after antegrade arrest. Thirty-five of the patients were in New York Heart Association class III or IV, and 19 patients had grade 3 or grade 4 left ventricular function. Sixteen patients had pulmonary hypertension, three with suprasystemic pressures, and marked right ventricular hypertrophy. Two patients had associated left ventricular hypertrophy. Nearly all patients returned to normal sinus rhythm shortly after removal of the aortic crossclamp, and they were easily discontinued from cardiopulmonary bypass even with crossclamp times of 3 hours. The 30-day hospital mortality rate was 2.7%. The perioperative myocardial infarction rate was 5.4%, and the prevalence of low-output syndrome was 10.8%. The results suggest that retrograde coronary sinus perfusion of blood cardioplegic solution at 37 degrees C is an effective method of myocardial protection even in patients with pulmonary hypertension at high risk for right ventricular failure. Its efficacy in this circumstance does not reside in its ability to deliver hypothermia.


Innervation of the paralyzed laryngeal muscles by phrenic motoneurons. A quantitative study by light and electron microscopy.

In the cat, inspiratory opening of the paralyzed glottis recovered after unilateral or bilateral reinnervation of the posterior cricoarytenoid (PCA) muscles by phrenic axons. The morphometric analysis of the regenerated recurrent laryngeal nerves (RLNs), showed that proliferation was abundant; 4 months after the nerve anastomosis, more than 500 myelinated axonal branches repopulated the RLNs. The mean diameter of motor axons (3.5 to 5.0 microns) was lower than in normal phrenic and RLN (8 to 10 microns), and the mean internode length was about half that of the normal RLN. Histochemical examination of the PCA muscle revealed that muscle fiber composition (44% type I and 56% type II muscle fiber) was fairly similar to that of normal PCA. The contraction time of the reinnervated muscles was as long as 60 msec at the time of movement recovery, but it shortened to 25 to 30 msec when the reinnervation time increased. These anatomical and functional results support the choice of the phrenic nerve for laryngeal reinnervation.


Use of the holmium:YAG laser in urology.

The tissue effects of a holmium:YAG (Ho:YAG) laser operating at a wavelength of 2.1 mu with a maximum power of 15 watts (W) and 10 different energy-pulse settings was systematically evaluated on kidney, bladder, prostate, ureteral, and vasal tissue in the dog. In addition, various urologic surgical procedures (partial nephrectomy, transurethral laser incision of the prostate, and laser-assisted vasovasostomy) were performed in the dog, and a laparoscopic pelvic lymph node dissection was carried out in a pig. Although the Ho:YAG laser has a strong affinity for water, precise tissue ablation was achieved in both the contact and non-contact mode when used endoscopically in a fluid medium to ablate prostatic and vesical tissue. Using the usual parameters for tissue destruction (blanching without charring), the depth of thermal injury in the bladder and ureter was kept superficial. In performing partial nephrectomies, a 2-fold reduction in the zone of coagulative necrosis was demonstrated compared to the use of the continuous wave Neodymium:YAG laser (Nd:YAG). When used through the laparoscope, the Ho:YAG laser provided precise cutting and, combined with electrocautery, allowed the dissection to proceed quickly and smoothly. Hemostatic control was adequate in all surgical procedures. Although the results of these investigations are preliminary, our initial experience with the Ho:YAG laser has been favorable and warrants further investigations.


In vitro laser recanalization of chronically occluded prosthetic grafts.

Polytetrafluoroethylene (PTFE) and Dacron grafts were implanted in canine femoral and carotid arteries using PTFE and Prolene suture, respectively. Arteries containing occluded grafts were explanted and laser recanalization was attempted in vitro. Laser recanalization was successful in 78% of PTFE grafts compared to 30% of Dacron grafts. Recanalization was complete (residual stenosis less than 5%) in opened PTFE grafts, whereas residual stenosis averaged 60% in recanalized Dacron grafts. PTFE graft/PTFE suture anastomotic tensile strength was unchanged after recanalization, while Dacron graft/Prolene suture anastomotic tensile strength decreased significantly. In addition, anastomotic bursting pressure was significantly higher for lased PTFE grafts with PTFE sutures (300 mg Hg) compared to lased Dacron grafts with Prolene sutures (70 mm Hg). Chronically occluded PTFE grafts with PTFE suture can be safely and effectively opened by laser recanalization. In contrast, attempted laser recanalization of Dacron grafts sutured with Prolene suture is seldom successful, significantly weakens the graft artery anastomosis, and should be avoided.


Escherichia coli integration host factor stabilizes bacteriophage Mu repressor interactions with operator DNA in vitro.

Using gel retardation and DNase I protection techniques, we have demonstrated that the Escherichia coli integration host factor (IHF) stabilizes the interaction between Mu repressor and its cognate operator-binding sites in vitro. These results are discussed in terms of a model in which IHF may commit the phage to the lytic or lysogenic pathway depending on the occupancy of the operator sites by the repressor.


Stabilization of bacteriophage Mu repressor-operator complexes by the Escherichia coli integration host factor protein.

All of the previously described effects of integration host factor (IHF) on bacteriophage Mu development have supported the view that IHF favours transposition-replication over the alternative state of lysogenic phage growth. In this report we show that, consistent with a model in which Mu repressor binding to its operators requires a particular topology of the operator DNA, IHF stimulates repressor binding to the O1 and O2 operators and enhances Mu repression. IHF would thus be one of the keys, besides supercoiling and the H-NS protein, that lock the operator region into the appropriate topological conformation for high-affinity binding not only of the phage transposase but also of the phage repressor.


Characterization of a non-tissue-specific, 3',5'-cyclic adenosine monophosphate-responsive element in the proximal region of the rat prolactin gene.

The nature of a DNA element located in the -100 to -85 region of the rat PRL gene has been characterized. Previous studies demonstrated that this region may contribute to basal and hormonally regulated expression of the PRL gene. As this region contains a sequence with similarity to a consensus cAMP-responsive element (CRE), a possible role for the cAMP response element binding protein (CREB) has been explored. A point mutation which made the PRL CRE-like sequence less like a consensus CRE had little effect on basal or cAMP-stimulated expression of a PRL-luciferase reporter gene. DNase footprint studies demonstrated that the proximal region of the PRL gene does not contain a high affinity CREB binding site. Mobility shift experiments demonstrated that the major GH3 nuclear protein which interacts with the -100 to -85 region of the PRL gene in vitro is not CREB. Transfection of a dominant inhibitor of CREB action had little or no effect on expression of an indicator gene containing the PRL proximal region. Thus, the PRL proximal region does not contain a high affinity CREB binding site, and it is unlikely that CREB plays a major role in expression of the PRL gene. The functional capabilities of the -100 to -85 region of the PRL gene were then tested in a transfection assay. Synthetic multimers of this region were found to be sufficient to permit a transcriptional response to cAMP or TRH in GH3 cells and cAMP in Rat-1 cells.(ABSTRACT TRUNCATED AT 250 WORDS)


The human mast cell receptor binding site maps to the third constant domain of immunoglobulin E.

The characterization of the site on the IgE molecule which accommodates the high affinity receptor for IgE (Fc epsilon RI) should allow the design of IgE analogues which can be utilized to block allergic responses. Using chimeric human IgE molecules in which different constant region domains were exchanged with their murine homologues, we demonstrate here that the C epsilon 3 in its native configuration is essential for the binding to the alpha subunit of the human Fc epsilon RI. Deletion of the human C epsilon 2 from such chimeric molecules did not impair their ability to interact with the Fc epsilon RI, indicating that C epsilon 2 is not directly involved in the human Fc epsilon RI binding site and that C epsilon 3 alone is necessary and sufficient to account for most of the human Fc epsilon RI-binding capacity.


The human T cell receptor gamma genes are transcribed from TATA-less promoters containing a conserved heptamer sequence.

We have used the anchored polymerase chain reaction (A-PCR) to clone and compare the 5' upstream regions of the human T cell receptor gamma (TRG) genes. Whereas little homology was found among subgroups I, II, III and IV, sequence alignment of TRG subgroup I members revealed a high degree of homology in the 5' sequences. A conserved heptamer sequence (CTGCAGG), which was found upstream from the translation initiation site of all TRG genes in our analysis. Determination of the transcription initiation site located the conserved heptamer 65 base pairs upstream from the cap sites of V5. No TATA box or other cis-acting promoter sequences could be identified in any of the human TRG upstream sequences.


Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators.

Left ventricular dilatation and dysfunction after myocardial infarction are major predictors of death. In experimental and clinical studies, longterm therapy with the angiotensin-converting--enzyme inhibitor captopril attenuated ventricular dilatation and remodeling. We investigated whether captopril could reduce morbidity and mortality in patients with left ventricular dysfunction after a myocardial infarction. Within 3 to 16 days after myocardial infarction, 2231 patients with ejection fractions of 40 percent or less but without overt heart failure or symptoms of myocardial ischemia were randomly assigned to receive doubleblind treatment with either placebo (1116 patients) or captopril (1115 patients) and were followed for an average of 42 months. Mortality from all causes was significantly reduced in the captopril group (228 deaths, or 20 percent) as compared with the placebo group (275 deaths, or 25 percent); the reduction in risk was 19 percent (95 percent confidence interval, 3 to 32 percent; P = 0.019). In addition, the incidence of both fatal and nonfatal major cardiovascular events was consistently reduced in the captopril group. The reduction in risk was 21 percent (95 percent confidence interval, 5 to 35 percent; P = 0.014) for death from cardiovascular causes, 37 percent (95 percent confidence interval, 20 to 50 percent; P less than 0.001) for the development of severe heart failure, 22 percent (95 percent confidence interval, 4 to 37 percent; P = 0.019) for congestive heart failure requiring hospitalization, and 25 percent (95 percent confidence interval, 5 to 40 percent; P = 0.015) for recurrent myocardial infarction. In patients with asymptomatic left ventricular dysfunction after myocardial infarction, long-term administration of captopril was associated with an improvement in survival and reduced morbidity and mortality due to major cardiovascular events. These benefits were observed in patients who received thrombolytic therapy, aspirin, or beta-blockers, as well as those who did not, suggesting that treatment with captopril leads to additional improvement in outcome among selected survivors of myocardial infarction.


Identification by mutagenesis of a Mg(2+)-block site of the NMDA receptor channel.

The N-methyl-D-aspartate (NMDA) receptor channel is highly permeable to Ca2+ but is blocked by Mg2+ in a voltage-dependent manner. These characteristics are essential for the NMDA receptor channel to mediate the induction of long-term potentiation of synaptic efficacy, a form of activity-dependent synaptic plasticity thought to underlie memory, learning and development. Recent studies have revealed the molecular and functional diversity of the NMDA receptor channel subunits, which are classified into the epsilon and zeta families according to the amino-acid sequence homology. Here we report that replacement by glutamine of asparagine 598 in putative transmembrane segment M2 of the zeta 1 subunit, strongly reduces the sensitivity of the heteromeric epsilon 2/zeta 1 NMDA receptor channel to Mg2+ block. The corresponding mutation of the epsilon 2 subunit has a similar effect. Furthermore, the heteromeric epsilon 2/zeta 1 NMDA receptor channel with the mutation on both subunits shows greatly reduced sensitivity to MK-801, a channel blocker of the NMDA receptor channel, but is still susceptible to inhibition by Zn2+. These findings suggest that the conserved asparagine residue in segment M2 constitutes a Mg(2+)-block site of the NMDA receptor channel, and that the MK-801 site overlaps the Mg2+ site.


The identification of spinal pathology in chronic low back pain using single photon emission computed tomography.

Bone scintigraphy with single photon emission computed tomography (SPECT) offers improved lesion detection and localization when compared to conventional planar imaging. The SPECT findings were investigated in 80 consecutive patients (aged 18-70 years, median 44) referred to a rheumatology outpatient clinic with low back pain persisting for more than 3 months. Lesions of the lumbar spine were demonstrated in 60% of patients using SPECT but in only 35% with planar imaging. Fifty-one per cent of all lesions were only detected by SPECT, and lesions visualized on SPECT could be precisely localized to the vertebral body, or different parts of the posterior elements. Fifty per cent of lesions involved the facetal joints of which almost 60% were identified on SPECT alone. X-rays of the lumbar spine, with posterior oblique views, failed to demonstrate abnormalities corresponding to almost all SPECT posterior element lesions although it identified abnormalities corresponding to over 60% of anterior SPECT lesions. Computed tomography (CT) was performed in 30 patients with a SPECT lesion and sites of facetal joint activity corresponded to facetal osteoarthritis in 82%. It is concluded that bone scintigraphy with SPECT in patients with chronic low back pain demonstrates many lesions not seen with either X-ray or conventional planar imaging. In addition anatomical localization is greatly enhanced with bone SPECT. The technique offers improved diagnosis in a group of patients often difficult to evaluate, and in particular a means of detecting apophyseal joint pathology which may be responsive to treatment.


123I-methylene blue: an unsatisfactory parathyroid imaging agent.

This study was designed to examine the possible use of 123I-labelled methylene blue as a parathyroid imaging agent. Five patients were studied, all of whom had parathyroid adenomas which were successfully localized preoperatively with 201Tl and 99Tcm-sestamibi, and which were subsequently proven at surgery. The 123I-labelled methylene blue localized only one of these adenomas, was negative in two and had equivocal uptake in the remaining two patients. It is therefore concluded that compared to other radionuclide methods for localizing parathyroid adenomas this agent is unsatisfactory.


Laparoscopic oophorectomy: comparative study of ligatures, bipolar coagulation, and automatic stapling devices.

We assessed laparoscopic oophorectomy using three techniques. From January 1989 to October 1991, 65 patients underwent laparoscopic oophorectomy using three techniques: bipolar coagulation, pretied ligature placement, and automatic stapling devices. The patients were aged 18-57 years and had the indications of pain, ovarian endometriosis, adhesions, unilateral blocked tubes, breast cancer, and recurrent benign ovarian cysts. The primary method of adnexal removal involved the automatic stapling device in 17, bipolar coagulation in 30, and pretied ligatures in 18. Total anesthesia time ranged from 45-123 minutes, with means of 77 minutes for pretied ligatures, 84 minutes for bipolar coagulation, and 84 minutes for automatic stapling devices. Sixty-two patients were discharged within 23 hours, two stayed two nights, and one stayed three nights. Rectus muscle bleeding and hematoma formation were the only complications in this series. All three methods of laparoscopic oophorectomy are effective, with similar operative times and uniformly good results for the patients.


Expectant management of ectopic pregnancy.

To evaluate expectant management in selected cases of ectopic pregnancy. Transvaginal sonography and estimation of serum hCG concentrations were used in the evaluation and follow-up of ectopic pregnancy. Entry criteria for expectant management were: decreasing level of serum hCG, diameter of the ectopic pregnancy less than 4 cm, and no signs of rupture or acute bleeding by vaginal sonography. Expectant management was studied in 83 patients, representing 26% of all ectopic pregnancies during a 2-year period. In 57 patients (69%), spontaneous resolution occurred, corresponding to 18% of all ectopic pregnancies. Laparoscopy was performed in 26 because of clinical symptoms or a rise in hCG level after expectant management for 1-18 days. One patient had a tubal rupture requiring tubal resection by laparoscopy. No serious complications occurred. With increasing experience, the rate of expectant management and spontaneous resolution increased during study period. Expectant management with repeated vaginal sonography and estimations of serum hCG concentrations is a useful form of treatment for ectopic pregnancy in selected cases.


Ultrasonographic measurements of fetal ear.

To establish nomograms of fetal ear measurements. Newborns with trisomies have smaller ears than the normal population. This observation led us to believe that ear measurements might be useful in the antenatal prediction of fetuses with abnormal karyotypes. Fetal ear length and width were obtained ultrasonographically in 124 normal singleton pregnancies between 18-42 weeks' gestation. Regression analyses were used to create the nomograms. Linear relationships were found between ear length and width and gestational age (r = 0.956 and 0.898, respectively). In addition, there were significant correlations between ear measurements and biparietal diameter, head circumference, abdominal circumference, and femur length. The ear width-length ratio and the biparietal diameter-ear length ratio were independent of gestational age. These normative data may be helpful in the antenatal prediction of chromosomal abnormalities.


The laser-assisted scalpel: initial clinical evaluation of its use in gynecologic endoscopy.

The laser-assisted scalpel is a new disposable laparoscopic instrument that improves the precision and control of fiberoptic laser energy delivery and provides a means of tactile probing and blunt tissue dissection. The instrument simplifies laparoscopic technique by providing the surgeon with the ability to place tissue under tension when firing the laser, thus minimizing the need to exchange instruments. We describe the use and our impressions of the laser-assisted scalpel for six common human laparoscopic gynecologic procedures performed in 68 patients.


Limb-body wall complex associated with cocaine abuse: further evidence of cocaine's teratogenicity.

Limb-body wall complex is a complicated fetal malformation with the essential features of body wall disruption and limb abnormalities. Data from studies in the rat model suggest that vascular disruption is an etiology for limb-body wall complex. Because of its vasospastic properties, cocaine can act as a teratogen by impairing uteroplacental fetal blood flow during critical periods of development. We describe the prenatal detection of two fetuses with limb-body wall complex, whose mothers smoked large amounts of cocaine during the first trimester of pregnancy. Ultrasonographic evaluation of the fetus should be offered routinely in pregnancies complicated by maternal cocaine abuse.


Body stalk anomaly: congenital absence of the umbilical cord.

On ultrasound examination, a 20-year-old pregnant woman was found to have a fetus with a large ventral abdominal wall defect diagnosed as a fetal omphalocele. The neonate was delivered by cesarean; the abdominal viscera including liver, stomach, spleen, pancreas, intestine, and uterus were contained in an extraembryonic sac directly attached to the placenta without an umbilical cord. Body stalk anomaly (also known as absence of the umbilical cord syndrome) is a fatal condition resulting from maldevelopment of embryonic body folding and is associated with multiple congenital defects. Prenatal ultrasonographic recognition of the absence of an umbilical cord and direct apposition of the membranous sac to the amniochorionic membrane would permit early termination of pregnancy or avoidance of operative intervention.


Laparoscopic oophoropexy for preservation of ovarian function before pelvic node irradiation.

Pelvic irradiation for the treatment of Hodgkin disease in premenopausal women invariably results in ovarian failure unless the ovaries are shielded. Oophoropexy by laparotomy has been used previously to move the ovaries away from the pelvic nodal areas. We have designed, and used in one patient, a new laparoscopic technique that can be performed as an outpatient procedure and that allows radiation therapy to begin immediately. Oophoropexy was performed laparoscopically with placement of sutures through the utero-ovarian ligaments and posterior uterus. Surgical clips were placed to help identify the position of the ovaries postoperatively.


Laparoscopic repair of ureter resected during operative laparoscopy.

Ureteral injury is a recognized complication of gynecologic surgery. During operative laparoscopy performed to treat extensive endometriosis of the pelvic sidewall, a 1.5-cm portion of the right ureter was resected and was repaired successfully. Repair of a resected ureter may be effectively accomplished endoscopically by experienced operative laparoscopists.


Uterine dehiscence following laparoscopic myomectomy.

Laparoscopic myomectomy is a new procedure that is growing in popularity. The natural history of pregnancy following laparoscopic myomectomy is unknown. A 24-year-old white woman, gravida 0, with infertility and endometriosis, conceived after a laparoscopic procedure that included myomectomy. At 34 weeks' gestation, the patient experienced uterine dehiscence at the site of myomectomy. An emergency cesarean delivery was performed and the uterus was oversewn. Both mother and infant had satisfactory hospital courses. Meticulous closure of the myometrial bed following myomectomy is difficult via the laparoscope, and this could interfere with the integrity of the scar. If further studies confirm this experience, then laparoscopic myomectomy may need to be limited to patients who do not desire further childbearing.


[In vitro activity of vancomycin and teicoplanin against gram-positive cocci].

The activities of vancomycin and teicoplanin against 148 strains of Gram-positive cocci were tested using agar diffusion and liquid microdilution MIC determination. Tested strains included 84 staphylococci, 32 S. aureus, 52 coagulase-negative staphylococci (CNS), 52 enterococci, and 12 streptococci. Most strains (136) were susceptible to both agents, with inhibition diameters of 17 mm or more. MRSA strains exhibited lower geometric MIC means with teicoplanin (0.90 micrograms/ml) than with vancomycin (1.79 micrograms/ml); this difference was found for methicillin-susceptible S. aureus strains (1.07 and 1.38 micrograms/ml for teicoplanin and vancomycin, respectively). In contrast, methicillin-susceptible and methicillin-resistant strains of CNS exhibited similar MICs (1.60 micrograms/ml approximately). Enterococci were more susceptible to teicoplanin (MIC 0.25 micrograms/ml) than to vancomycin (MIC 1.35 micrograms/ml). Both vancomycin and teicoplanin were thus found to be consistently effective against Gram-positive cocci; however, teicoplanin proved more effective than vancomycin against enterococci and methicillin-resistant S. aureus strains and may therefore be a valuable therapeutic alternative for these multiresistant organisms.


Characteristics of association of oleoyl derivatives of 5-fluorodeoxyuridine and methotrexate with low-density lipoproteins (LDL).

In order to prepare cytotoxic drug-low density lipoprotein (LDL) particles, we have synthesized lipophilic prodrugs of two broad-spectrum antineoplastic agents, methotrexate (MTX) and 5-fluorodeoxyuridine (FUdR), by coupling them to oleic acid. 3H-Labeled prodrugs were incorporated in 125I-LDL carriers, allowing the study of both drug and carrier simultaneously. Utilizing the dry film procedure, monooleoyl FUdR showed the highest incorporation efficiency with over 40% of the initial drug associated with LDL. The prepared prodrug-LDL solution was found to be a single complex of 30 molecules of prodrug per LDL particle when examined by agarose gel electrophoresis and density gradient ultracentrifugation. No unbound FUdROl1 could be recovered, indicating that all dissolved prodrug associates with LDL. After incubation of FUdROl1 with human serum, 22% of the compound associates with lipoproteins and 78% was recovered in the albumin-containing fraction. When human serum was pretreated with oleic acid in order to saturate albumin's fatty acids binding sites, a strong decrease (from 78 to 22%) in association to the albumin-containing fraction was observed, accompanied by a threefold increase (from 22 to 67%) in lipoprotein association. It is concluded that existing hydrophilic antineoplastic agents can be successfully modified in order to achieve association with LDL. This may ultimately lead to an increased delivery of cytotoxic drugs to tumor cells.


Neocarzinostatin acts as a sensitive probe of DNA microheterogeneity: switching of chemistry from C-1' to C-4' by a G.T mismatch 5' to the site of DNA damage.

The diradical form of thiol-activated neocarzinostatin chromophore resides in the minor groove of DNA, where it has access to hydrogen atoms at the C-5', C-1', and C-4' positions of deoxyribose on each strand. In a dodecamer oligodeoxyribonucleotide containing the sequence AGC.GCT, a bistranded lesion staggered two nucleotides in the 3' direction, is generated that consists primarily of an abasic site (2'-deoxyribonolactone) at the C due to 1' chemistry and a direct strand break at the T due to 5' chemistry. Sequencing-gel analysis reveals that 72% of the damage at the C results from 1' chemistry with minor lesions consisting of a strand break due to 5' chemistry (15%) and 4' chemistry (less than 2%) and an abasic site (4'-hydroxylation product) (12%) due to 4' chemistry. Replacement of the G.C base pair 5' to the C by a G.T wobble mismatch results in a remarkable switching of the chemistry of damage at the C from C-1' to C-4'. The 1' chemistry is almost eliminated and replaced by 4' chemistry, so that the latter accounts for 64% of the damage, mainly in the form of the 4'-hydroxylation product (abasic site) and a smaller amount of the DNA fragment with a phosphoglycolate at the 3' end (strand break). Substitution of the radiation sensitizer misonidazole for dioxygen markedly enhances partitioning of the 4' chemistry in favor of the glycolate-containing product. On the complementary strand the G.T mismatch results in an increase in 4' chemistry at the T residue, but 5' chemistry remains the main mechanism. When a G.A mismatch is inserted 5' to the C, there is a marked decrease in all damage at this site without detectable switching of chemistry. These results show that the diradical form of thiol-activated neocarzinostatin chromophore acts as sensitive probe of DNA microheterogeneity.


Neurosteroids: pregnenolone in human sciatic nerves.

The characterization and quantification of pregnenolone in human sciatic nerves were undertaken, following previous demonstration of the synthesis of this steroid in rat brain oligodendrocytes, to explore the hypothesis that Schwann cells may demonstrate the same biosynthetic activity. Pregnenolone was definitively identified by mass spectrometry and quantified by specific radioimmunoassay. Its concentration (mean +/- SD, 63.9 +/- 45.9 ng/g of wet tissue, n = 12) was greater than or equal to 100 times the plasma level and concentration found in tendons and muscle. No correlation was found with sex or age. Free dehydroepiandrosterone as well as sulfate and fatty acid esters of pregnenolone and dehydroepiandrosterone were also measured. Results are discussed in terms of the concept that these "neurosteroids" may be synthesized in the peripheral nervous system.


Carotid-aortic and renal baroreceptors mediate the atrial natriuretic peptide release induced by blood volume expansion.

Our previous studies have shown that stimulation of the anteroventral third ventricle (AV3V) region of the brain increases atrial natriuretic peptide (ANP) release, whereas lesions of the AV3V region or median eminence of the tuber cinereum block the release of ANP caused by blood volume expansion. These results suggest that participation of the central nervous system is critical to this response. The role of baroreceptors in the response was evaluated in the current research by studying the response of plasma ANP to blood volume expansion induced by intravenous injection of hypertonic saline solution (0.3 M NaCl, 2 ml/100 g of body weight, over 1 min) in conscious, freely moving male rats. Plasma samples were assayed for ANP by radioimmunoassay. In sham-operated rats, blood volume expansion induced a rapid increase in plasma ANP: the concentration peaked at 5 min and remained elevated at 15 min after saline injection. One week after deafferentation of the carotid-aortic baroreceptors, basal plasma ANP concentrations were highly significantly decreased on comparison with values of sham-operated rats; plasma ANP levels 5 min after blood volume expansion in the deafferented rats were greatly reduced. Unilateral right vagotomy reduced resting levels of plasma ANP but not the response to blood volume expansion; resting concentrations of plasma ANP and responses to expansion were normal in bilaterally vagotomized rats. In rats that had undergone renal deafferentation, resting levels of ANP were normal but the response to blood volume expansion was significantly suppressed. The evidence indicates that afferent impulses via the right vagus nerve may be important under basal conditions, but they are not required for the ANP release induced by blood volume expansion. In contrast, baroreceptor impulses from the carotid-aortic sinus regions and the kidney are important pathways involved in the neuroendocrine control of ANP release. The evidence from these experiments and our previous stimulation and lesion studies indicates that the ANP release in response to volume expansion is mediated by afferent baroreceptor input to the AV3V region, which mediates the increased ANP release via activation of the hypothalamic ANP neuronal system.


Human T-cell lymphotropic virus type I (HTLV-I) transcriptional activator, Tax, enhances CREB binding to HTLV-I 21-base-pair repeats by protein-protein interaction.

HTLV-I Tax protein activates transcription from three 21-base-pair (bp) repeat sequences in the viral enhancer. The HTLV-I 21-bp repeat contains a TGACGT motif that is homologous to the cAMP-responsive element (CRE) and crucial for tax transactivation. Tax exhibits marginal affinity for DNA but rather interacts with cellular CRE-binding proteins to enhance their affinity for the HTLV-I 21-bp repeats. Using the HTLV-I 21-bp repeat and Jurkat T-lymphocyte nuclear extract in a gel electrophoretic mobility-shift assay, we previously detected three protein-DNA complexes that are specific for the CRE in the 21-bp repeat (complexes I, II, and IV). Complexes I and II but not IV interacted with Tax. We now show that complexes I, II, and IV are composed of CREB (CRE binding protein) homodimer, CREB/ATF-1 (activating transcription factor 1) heterodimer, and ATF-1 homodimer, respectively. Tax stabilizes complexes I and II via a direct interaction with the CREB moiety. In the absence of DNA, CREB and Tax continue to form a complex that can be immunoprecipitated by a Tax-specific antibody. These results suggest that one mechanism by which Tax activates transcription may be mediated through the direct interaction with CREB homodimer and/or CREB/ATF-1 heterodimer to stabilize their assembly on the Tax-responsive CRE motifs in the HTLV-I enhancer.


Partial loss of function mutations in DnaK, the Escherichia coli homologue of the 70-kDa heat shock proteins, affect highly conserved amino acids implicated in ATP binding and hydrolysis.

A set of 37 mutations in DnaK, the Escherichia coli homologue of the 70-kDa heat shock proteins, was isolated using a selection for high constitutive expression of heat shock proteins. Of these, 11 mutants were able to carry out some but not all functions of DnaK. These partial function mutants were divided into two classes. Class I mutants are recessive and permit replication of bacteriophage lambda and growth of cells up to 40 degrees C. Class II mutants are dominant, do not permit growth of lambda, and are temperature-sensitive for growth above 34 degrees C. Mutations in both classes alter amino acids that are highly conserved in the 70-kDa heat shock protein family. The dominant negative mutations provide strong genetic evidence that at least one form of DnaK is multimeric. Moreover, every dominant negative mutation occurs at an amino acid that has been hypothesized to be intimately involved in the process of ATP binding and hydrolysis. Our findings provide strong support for the hypothesis that such mutations are excellent tools for identifying amino acids that play critical roles in protein function.


Defensive attribution hypothesis and serious occupational accidents.

Based on the defensive attribution hypothesis, we assume that the victims of serious occupational accidents tend to attribute their accidents to external factors, while their coworkers and foremen tend to attribute the accidents to the victims' own action. The data to test this hypothesis consisted of 99 serious occupational accidents in southern Finland. In connection with the accident, or after the investigation at the accident site, 73 victims, 65 coworkers, and 71 foremen were interviewed. The results support our assumption, as the victims tended to use external attributions, whereas the foremen and coworkers attributed the accidents to internal factors. The defensive attribution hypothesis seems to explain the differences in how each party interpreted the basis for each accident.


The caregiver reaction assessment (CRA) for caregivers to persons with chronic physical and mental impairments.

The development and testing of a multidimensional instrument to assess the reactions of family members caring for elderly persons with physical impairments, Alzheimer's disease, and cancer is reported. Forty items were administered to a sample of 377 caregivers of persons with physical impairments and Alzheimer's disease. Five dimensions of caregivers' reactions were identified through exploratory factor analysis. Using confirmatory factor analysis on an independent sample (N = 377), these dimensions were tested for factorial invariance across spouse and nonspouse caregivers and between caregivers of persons with cancer and those caring for persons with Alzheimer's disease. The subscales also had a high level of factorial invariance across a three-wave panel study (N = 185). The subscales appeared consistent with first order tests of construct validity.


[Ergonomic and postural aspects in a central supply unit].

Unsuitable environmental factors can lead to back injuries. In order to develop a critical thinking about the workplace effects on human health, this paper discuss ergonomic and postural aspects in a Central Supply Unit.


[Etiologic aspects of low back pain in rheumatic patients in Kinshasa (Zaire). Apropos of 169 cases].

A study over a period of 27 consecutive months showed that among patients seen in a Kinshasa hospital outpatient clinic for rheumatologic diseases, 46.5% sought medical advice for lower back pain. Lumbar arthrosis (74.5%), spondylodiscitis (9.5%) and unilateral sacroiliitis (9%) were the main causes of this complaint. A single patient had osteoporosis and no cases of ankylosing spondylarthritis were seen. Lumbar arthrosis was prevalent among females. Mean age of patients with disk disease was fairly low (43 years). Infectious spondylodiscitis and unilateral sacroiliitis, presumably reactive or infectious in origin, were also more common in women. HIV-infection was found in 44% of patients with spondylodiscitis and in 53% of patients with sacroiliitis. Age of HIV-infected individuals ranged from 21 to 40 years. Bacteriologic studies proved indispensable for determining the cause of these conditions in which leukocyte courts failed to rise. In young individuals in Kinshasa with spondylodiscitis or unilateral sacroiliitis, routine HIV testing is warranted.


[Swiss Register for unrelated bone marrow donors: preliminary results].

Bone marrow transplantation from the unrelated volunteer donor is today a realistic possibility for patients lacking an HLA-identical family donor. In 1988, the Swiss Unrelated Bone Marrow Donor Registry was founded to coordinate such bone marrow transplants and create the Swiss volunteer donor registry. Thus for a search has been initiated for 71 patients and 16 transplants have been performed. Donor and recipient were HLA-A-, -B- identical by serology and HLA-Dr-identical by DNA-oligotyping. 10 of the 16 patients are alive without signs of basic disease 2 weeks to 2 years and 4 months after the transplant. These results illustrate that unrelated donor transplantation, using careful selection criteria, is a realistic new therapeutic modality.


[Effects of Iodine-131 in sheep depending on the content of stable iodine in the diet].

The biological effect of 131I was studied in sheep kept on a diet deficient in stable iodine. An increased capture and accretion of iodine in the thyroid gland and in the whole body were observed. The disturbances in the structure and function of the thyroid gland, liver and haemopoietic organs were more pronounced in the animals kept on the iodine deficient diet.


Human cyclin B1 gene (CCNB1) assigned to chromosome 5 (q13-qter).

Cyclins play an important role in cell cycle regulation. At least five classes of cyclins have been identified--A, B, C, D, and E. B cyclins are generally of two types in most organisms--B1 and B2. We have mapped the gene for human cyclin B1 (CCNB1) to human chromosome 5 (region q13-qter) by Southern blot analysis of human x Chinese hamster somatic cell hybrid panels. Many more cyclin B-related sequences have been identified in the mouse (Cycb-1 to Cycb-10) and have been mapped to chromosomes 4, 5, 7, 8, 13, 14, 15, and 17. Based on our mapping of human CCNB1 and known evolutionary conservation of chromosomal regions, we propose that the homologous cyclin B1 locus, Cycb-4, on mouse chromosome 13 is a functional gene.


Factors that influence the outcome of aortoiliac and femoropopliteal percutaneous transluminal angioplasty.

In the past, patients with peripheral arterial occlusive disease were managed by conservative treatment or by vascular reconstructive surgery. Now, percutaneous transluminal angioplasty and other endovascular methods provide an important alternative for managing selected patients with peripheral arterial occlusive disease. Overall, the 5-year success rate after iliac angioplasty is 53.4%, but the success rate is higher if percutaneous transluminal angioplasty is performed on the common iliac artery or on a stenosed artery. In contrast, percutaneous transluminal angioplasty of the femoral and popliteal arteries has a relatively poor long-term success rate except for the treatment of patients with stenoses with good run-off. When the run-off is poor or an arterial occlusion is present, the role of femoropopliteal angioplasty is limited, and the procedure should be considered only for high-risk patients who do not have autogenous tissue for reconstructive surgery.


Patient and anatomical selectivity in postoperative radiotherapy for early breast cancer: a British perspective.

As radiotherapy following surgery for early breast cancer carries morbidity, financial cost, and potential mortality we have sought to select characteristics that will allow these risks to be minimised. The causes of increased mortality shown in the overview of mature trials of radiotherapy have been studied in a single large randomised trial. This has identified patients with large, poorly differentiated tumours to be most likely to benefit from the reduction in incidence of local recurrence achieved by radiotherapy while remaining at the lowest risk from suffering the increased mortality associated with the treatment. Much of the morbidity of radiotherapy is due to routine irradiation of lymphatic pathways. Three hundred and seven patients treated by breast-conserving surgery and breast radiotherapy have been evaluated. None received irradiation to their axilla or internal mammary lymphatics. Relapse in locoregional lymphatics (axilla or supraclavicular fossa) occurred in 15 patients. Only 4 had persisting symptoms from this relapse following further treatment.


Ultrasound recanalization of diseased arteries. From experimental studies to clinical application.

At present, percutaneous peripheral ultrasound angioplasty should be considered in those patients with symptoms of claudication or resting limb ischemia. With the development of an over-the-wire system, we treat patients with suprageniculate or infrageniculate lesions. It is expected that the over-the-wire probe will allow application of ultrasound angioplasty not only to lesions below the knee but to contralateral vascular occlusions as well. An intraoperative device for plaque ablation and arterial recanalization is in development for use in less accessible sites such as the coronary arteries. Experimental studies have shown that catheter-delivered therapeutic ultrasound recanalizes complete occlusions, reduces stenoses, dissolves thrombus, vasodilates, and enhances arterial distensibility. The potential clinical applications of therapeutic ultrasound include recanalizing total arterial occlusions, dissolving thrombi, facilitating balloon angioplasty by increasing arterial compliance, and as a stand-alone angioplasty device.


Biology of restenosis and therapeutic approach.

Numerous attempts have been made to prevent restenosis after successful transluminal dilation of an atherosclerotic vessel using a variety of pharmacologic and mechanical approaches. This article reviews the pathobiology of the restenosis process, offers a hypothesis as to its cause, reviews attempts to modify the process, and outlines therapeutic approaches to future treatment.


Effects of methacholine induced bronchoconstriction and procaterol induced bronchodilation on cough receptor sensitivity to inhaled capsaicin and tartaric acid.

The direct effect of bronchoconstriction on cough receptor sensitivity is unknown, and the antitussive effect of beta 2 adrenergic agonists in man has been controversial. This study was designed to throw light on these questions. The threshold of the cough response to inhaled capsaicin, a stimulant acting on C fibre endings, and tartaric acid, a chemostimulant, was measured before and 10 minutes after inhalation of methacholine, which caused a nearly 20% fall in forced expiratory volume in one second (FEV1), in 14 normal subjects (study 1), and also before and 30 minutes after inhalation of procaterol (30 micrograms), placebo, and saline in eight normal subjects (study 2). Progressively increasing concentrations of capsaicin and tartaric acid solutions were inhaled for 15 seconds by mouth tidal breathing at one minute intervals and cough threshold was defined as the lowest concentration of capsaicin and tartaric acid that elicited five or more coughs. In study 1 the geometric mean values of the cough threshold of response to capsaicin and tartaric acid before methacholine callenge, 2.98 (GSE 1.30) micrograms/ml and 46.6 (1.22) mg/ml, were not significantly different from those of the response to methacholine inhalation, 3.45 (1.33) micrograms/ml and 32.9 (1.37) mg/ml. In study 2 the geometric mean value of the cough threshold of response to capsaicin before inhalation of procaterol (4.61 (GSE 1.84) micrograms/ml) was not different from that after inhalation of procaterol (4.61 (GSE 1.84) micrograms/ml), which had significant bronchodilator effects. The cough threshold was not altered by placebo or saline. These findings suggest that muscarinic receptor stimulation, bronchoconstriction, beta 2 receptor stimulation, or bronchodilation might have no direct effect on the sensitivity of the cough receptors in normal subjects.


[Myocardial fibrosis of cattle in Hesse].

Between 1986 and 1989 there were 9 cases of idiopathic congestive heart failure at this clinic. Normally heifers in the last 1/3 of pregnancy and young cows aged between 2.5 and 3.5 years were affected, but the disease also occurred in one younger (1.5 years), one older (6 years) and in one male animal. In contrast to other reports, myocardial fibrosis in the State of Hesse was only seen in the Rotbunte breed. The animals suffered from a severe heart failure with venous congestion and congestive edema of the brisket, the submandibular area and the ventral abdomen. In most cases there is no precise difference in history, clinical findings and laboratory findings between myocardial fibrosis, traumatic pericarditis and endocarditis valvularis. Only pathological and histological examinations of the heart confirm a suspected myocardial fibrosis: The heart is enlarged and dilatated and seems to be non-elastic. Microscopically a scattered interstitial fibrosis and signs of myocardial degeneration are visible.


Primed allogeneic reactions to leukocytes and epithelial cells in the bicolor damselfish.

The studies presented here describe allogeneic reactions in the bicolor damselfish, Pomacentrus partitus, a tropical marine teleost. Damselfish were immunized twice at 2-week intervals either by placement of reciprocal allografts or with primary cultures of epithelial cells. Two weeks after the second immunization, recipient splenocytes were tested for alloreactivity toward donor and third-party pronephros cells. For those animals immunized with cultured cells, reactivity toward donor and third-party epithelial cells was also examined. Unprimed animals responded to allogeneic pronephros between days 8 and 10 (28 degrees C). Fish immunized with epithelial cells showed accelerated mixed leukocyte reactions, with optimal responses occurring between days 4 and 6. Moreover, responses to the immunogen preceded responses to donor pronephros tissue by 2 days, occurring on day 2 or day 4. In addition, primed responses were of significantly greater magnitude than primary reactions. Reactivity toward third-party pronephros tissue paralleled responses of naive animals, indicating the specificity of response. No reactivity toward epithelial cells was observed in the absence of immunization, suggesting that accessory cell functions of damselfish pronephros and epithelial cells differ.


The less common occupational dermatoses.

Contact dermatitis and nonmelanoma skin cancer are the most common occupational skin disorders in North America, but there are many other occupational dermatoses that illustrate the wide range of pathological and adaptive responses of the skin to workplace exposure. Discussed are acne, chemically induced leukoderma, nail diseases, contact-related burns, high-pressure injection injuries, contact urticaria, heat reactions and photosensitivity, and infections.


Selective loss of functional antidonor cytolytic T cell precursors following donor-specific blood transfusions in long-term renal allograft recipients.

Pretransplant administration of donor-specific blood transfusions prolongs the survival of HLA-disparate renal allografts to a level comparable to that of HLA-identical transplants. To test the hypothesis that DST recipients develop immunologic tolerance of their donors, we examined antidonor T cell immunity in a group of DST recipients with long-term well-functioning allografts. Limiting dilution analysis studies indicated that 5/14 long-term DST recipients exhibit a complete absence of detectable antidonor cytolytic T lymphocyte precursors (CTLp). In contrast, 4/4 long-term non-DST recipients who received conventional or cyclosporine immunosuppression exhibited significant levels of antidonor CTLp. Nonresponsive DST recipients retained the capacity to mount antidonor responses in mixed lymphocyte reactions and IL-2 production assays, and exhibited normal levels of CTLp directed to third-party antigens. Addition of exogenous IL-2 to cell-mediated lympholysis cultures did not restore antidonor CTL responses. In summary, our data suggest that the DST conditioning regimen induces a complete yet selective loss of functional antidonor CTLp in some long-term renal transplant recipients.


Positive correlation of T cell sensitization with frequencies of alloreactive T helper cells in chronic renal failure patients.

Chronic renal failure patients are often "sensitized" to foreign alloantigens following renal transplantation or blood transfusion. B cell sensitization is assessed by measuring the reactivity of cytotoxic antibodies in the patient's serum against a panel of allogeneic cells (panel-reactive antibodies, [PRA]). However, this technique provides no information about T cell allosensitization. T cell allosensitization may be important since T cells play a central role in allograft rejection and since "primed" alloreactive cells--i.e., T cells that have previously encountered their specific alloantigen, are relatively resistant to immunosuppression. In order to detect T cell sensitization we used a limiting dilution analysis assay, which measured both total and primed frequencies of alloreactive T helper (Th) cells. Total alloreactive Th cell frequencies were generally high. Primed alloreactive Th cell frequencies could be detected in all patients studied, although there was considerable variation in frequencies between different patients. Frequencies of primed Th cells did not correlate with levels of PRA. However, in all three of the patients who had received DR-mismatched kidneys, and who had subsequently rejected these grafts rapidly, high primed frequencies were detected against the mismatched DR antigens. This was not the case for two patients who had lost their grafts two or more years after transplantation.


Differences between the anticoccidial potencies of monensin in maize-based or wheat-based chicken diets.

Experiments were carried out to investigate why the anticoccidial ionophore monensin is more potent against the coccidium Eimeria tenella in chickens fed on a maize-based diet (as in the USA) than in chickens fed on a wheat-based diet (as in the UK). The explanation seems to be that the pathogenicity of E. tenella is lower in maize-fed chickens than in wheat-fed chickens, whether monensin is present in the diet or not. Possible reasons for this are suggested. The better survival of maize-fed birds may be partly due to protective effects of the higher concentrations of vitamins A and E derived from their diet. Furthermore, the higher concentrations of niacin and riboflavin in wheat than in maize may enhance coccidial pathogenicity. These opposing factors might combine to cause equivalent infection levels to produce more severe coccidiosis in chickens fed on a wheat-based diet than on a maize-based diet.


Identification of the major metabolites of [3H]-(+)-8-chloro-5-(2,3- dihydrobenzofuran-7-yl)-7-methoxymethyloxy-3-methyl-2,3,4,5-tetrahydro- 1H-3- benzazepine in rats.

1. The in vivo urinary metabolites of 3H(+)-8-chloro-5(2,3- dihydrobenzofuran-7-yl)-7-methoxymethyloxy-3-methyl-2,3,4,5-tetrah ydro-1H-3- benzazepine isolated from Wistar rats have been characterized by mass spectrometry and n.m.r. spectroscopy. 2. Metabolites are formed by N-demethylation, hydroxylation of the dihydrobenzofuran moiety, and elimination of the methoxymethyl group followed by glucuronidation. All combinations of these metabolic pathways were found in the metabolites in urine. 3. In the faeces metabolites formed by hydroxylation of the dihydrobenzofuran moiety and elimination of the methoxymethyl moiety dominate, while N-demethylated metabolites are present only in small amounts. 4. The major plasma metabolite was formed by elimination of the methoxymethyl group followed by glucuronidation. Only minute amounts of other metabolites were present.


[An epidemiological analysis of postoperative suppurative pathology in surgical hospitals].

Approaches to the epidemiological analysis of postoperative wound complications in surgical hospitals are summarized. The indices for the evaluation of the epidemic situation in surgical departments (the ratio of severe and mild forms of complications, severe and posthospital complications) are proposed. To determine the site of infection, the method of graphic analysis, involving the fixation of dates of the operation and the appearance of the complication and taking into account regularities in the development of the outbreak, the depth and severity of the lesion, is proposed. Epidemiological surveillance at medical institutions permits the prognostication of the epidemiological situation. The realization of epidemiological surveillance at the level of individual medical institutions is the prerequisite of effective functioning of the program of epidemiological surveillance at a given territory.


[The comprehensive differentiated protection against influenza and acute respiratory diseases of medical workers in industrial enterprises].

Acute diseases of the respiratory organs rank first among temporary invalidity causes (30.5%). For the first time workers of a health center of an industrial enterprise were protected from influenza and ARVI during an epidemic outbreak of influenza A by specific and nonspecific protection means with due consideration for the subject's health status and will. Comprehensive differentiated protection from influenza and ARVI proved highly effective, its index reaching 2.5 and the invalidity periods being shorter by 2.4-4 days.