Reversible cardiac dysfunction associated with foscarnet therapy for cytomegalovirus esophagitis in an AIDS patient.
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AIDS-Related Opportunistic Infections↗
Biomedical subjects
D L Brown
Publications and source records attributed to D L Brown.
Reversible disassembly of transcription domains in lymphocyte nuclei during inhibition of RNA synthesis by DRB.
We are investigating the roles of RNA synthesis, chromatin structure and nuclear matrix organization in establishing and maintaining transcription domains, using mitogen stimulated lymphocytes as a model system. In a continuing study, the effects of the RNA polymerase inhibitor DRB and of its removal on nuclear organization have been examined by EM cytochemistry and by immunofluorescence labelling of the nuclear matrix PI1, Sm and nucleolar fibrillarin antigens. Chromatin, interchromatin granules and nucleoli were extensively restructured after DRB, as were matrix antigens. According to cytochemical staining properties, the conformation of DRB-induced condensed chromatin resembled that in partially stimulated lymphocytes. The nucleoplasmic fibrogranular RNP network appeared little altered, but the fibrillar proteinaceous interchromatinic regions, interpreted as representing the nuclear matrix in situ, were more affected. After removal of DRB, nuclei recovered the organization and transcriptional activity of controls within 8 h. These results suggest that the matrix subtending transcription domains remains stable when transcription is arrested, even though the chromatin and individual RNP components of the domains are disorganized. The data further indicate that absence of transcription is not solely accountable for the highly aggregated state of the chromatin in resting lymphocytes.
Animals↗
Management of postoperative pain: influence of anesthetic and analgesic choice.
Improved control of postoperative pain is being increasingly scrutinized yet concomitantly demanded by patients, physicians, and even the federal government. Our ever-increasing subspecialization in medicine has compartmentalized much of perioperative care and has created substantial difficulty for physicians in understanding the overall influence of other physicians' perioperative decisions, including control of pain. Clearly, intraoperative anesthetic management can affect patients' pain and perioperative course remote from the surgical procedure through modulation of analgesic and perioperative stress responses. Additionally, outcome studies show that provision of improved analgesia and minimization of the perioperative stress response enhance clinical outcome in both low- and high-risk patients. This article highlights new information on how anesthetic and analgesic management influences perioperative pain and decreases the incidence of complications in surgical patients.
Analgesics↗
Linkage mapping of dopa-responsive dystonia (DRD) to chromosome 14q.
Dopa-responsive dystonia (DRD) is an autosomal-dominant neurological disorder which appears to result from a genetically determined deficiency of striatal dopamine. Pathological evidence suggests that this may be due to the establishment of a reduced number of dopaminergic nerve terminals in the striatum, or to an excessive reduction (pruning) of these terminals in early development. We have mapped the DRD gene to chromosome 14 by linkage analysis in 3 families with a maximum 2-point lod score of 4.67 at 8.6 centiMorgans from D14S63; maximum multipoint lod scores > 6 were obtained for the intervals D14S47-D14S52 and D14S52-D14S63. The flanking loci D14S47 and D14S63 define a region of about 22 cM as containing the DRD gene.
Chromosome Mapping↗
Effects of dense, high-volume, artificial surfactant aerosol on a heated exhalation filter system.
OBJECTIVE: To evaluate a supplemental heated filter system during mechanical ventilation with continuous nebulization of an artificial surfactant by a new, high-volume nebulizer. DESIGN AND METHODS: A new nebulizer system, containing artificial surfactant, provided half of a 20-L minute ventilation and the remainder of this minute ventilation was provided by a commonly used mechanical ventilator. Ventilation sources were joined in the inspiratory limb of the breathing circuit, which was connected to a test lung system. A supplemental filter system was placed upstream of the ventilator's heated filter in the expiratory limb of the circuit. Circuit pressures at the inlet of the supplemental filter (P1), between the filters (P2), and after the ventilator expiratory filter (P3) were monitored and recorded. Nebulizer canisters containing artificial surfactant were replaced every 4 hrs. The performance of four supplemental filters in continuous use was examined. Another four filters were each used over 4 hrs, steam autoclaved, and reused. SETTINGS: The ventilator was set at a rate of 20 breaths/min, with a tidal volume of 0.5 L, a flow rate of 40 L/min, and positive end-expiratory pressure of 10 cm H2O. The nebulizer provided an equal volume and flow rate so that the delivered tidal volume was 1.0 L with a flow rate of 80 L/min. RESULTS: Ventilator failure and/or excessive airway pressure caused by increased filter resistance occurred at a mean of 7.3 +/- 1.3 (SD) hrs of continuous ventilation. Mean P1-peak increased from 67.5 +/- 8.2 to 94.0 +/- 10.7 cm H2O (p < .001) and P1-baseline increased from 9.3 +/- 1.0 to 53.5 +/- 17.1 cm H2O (p = .014). Filters that were autoclaved after 4 hrs of ventilation and reused lasted a total of 7.0 +/- 1.3 hrs. Mean P1-peak increased from 68.9 +/- 4.9 to 84.8 +/- 19.1 cm H2O and P1-baseline increased from 9.5 +/- 1.7 to 30.8 +/- 14.2 cm H2O (p < .05). CONCLUSIONS: The supplemental filter system was able to protect the ventilatory exhalation sensors for approximately 7 hrs at a minute ventilation of 20 L/min. Steam sterilization did not extend the supplemental filter life.
Aerosols↗
Spontaneous in vitro production of rheumatoid factor during infectious exacerbations of cystic fibrosis: correlation with circulating immune complex levels.
Rheumatoid factor (RF) production has been demonstrated during infections, including infectious exacerbations of cystic fibrosis (CF). The aim of this study was to evaluate the relationship of RF production to infection, and examine the mechanisms involved. Serial peripheral blood mononuclear cell (PBMC) cultures with measurement of spontaneous production of IgM RF, IgA RF, total IgM and IgA, and measurement of serum levels of immune complexes were carried out during exacerbations of CF. The percentage of B cells expressing CD5 was examined in a second cohort of acutely infected CF patients, and related to IgM RF production. IgM RF production was significantly elevated during acute infection compared with convalescence (P < 0.05), stable CF subjects (P < 0.005) and normal controls (P < 0.05). IgM RF production did not correlate with total IgM production in the majority of patients, but was closely related to circulating immune complex levels in 8/10 subjects. IgA RF production did not increase significantly during infection, and did not correlate with total IgA or IgM RF production, or with circulating immune complex levels. CD5+ B cells were not increased in the CF group, and the percentage of CD5+ B cells did not correlate with IgM RF synthesis. These observations suggest that RF production during infection is specifically induced, possibly by immune complex autoimmunization, and is not simply the result of polyclonal B cell activation. Different patterns of IgM RF and IgA RF synthesis suggest different mechanisms of induction.
Acute Disease↗
Circulating T cell subtypes in polymyalgia rheumatica and giant cell arteritis: variation in the percentage of CD8+ cells with prednisolone treatment.
OBJECTIVES: Some reports have described a decreased percentage of circulating CD8+ cells in patients with polymyalgia rheumatica and giant cell arteritis (PMR/GCA) before treatment and persisting for some months during treatment with corticosteroids. Other studies have found no such changes. There are overt methodological variations between these studies and there may also hidden differences, such as the timing of blood samples. The purpose of this study was to investigate T cell subtypes in patients with PMR/GCA while controlling for variables known to affect T cells. METHODS: Circulating T cell subsets were measured in 36 patients with PMR/GCA before and during treatment with prednisolone. Blood samples during treatment were taken before the daily dose of prednisolone. The whole blood lysis method was used followed by flow cytometry. RESULTS: Compared with controls, CD8+ cells were not reduced before treatment in patients with PMR/GCA (0.44 x 10(9)/l; 28% of lymphocytes). CD4+ cells were also normal (0.78 x 10(9)/l; 48% of lymphocytes). During treatment with prednisolone total T cells increased from 1.18 to 1.59 x 10(9)/l and CD4+ cells increased from 0.78 to 1.05 x 10(9)/l. The percentage of CD8+ cells decreased on treatment from 28 to 25%. CONCLUSIONS: This study does not confirm the finding of some groups that the percentage of circulating CD8+ cells is reduced in patients with PMR/GCA before treatment. It does show that the percentage of CD8+ cells decreases during treatment with corticosteroids. This needs to be considered when designing studies of lymphocyte subsets in diseases treated with corticosteroids.
Aged↗
Effects of single dose compared with three days' prednisolone treatment of healthy volunteers: contrasting effects on circulating lymphocyte subsets.
AIMS: To investigate the effects of longer term corticosteroid treatment on circulating lymphocyte subsets. METHODS: Prednisolone (20 mg daily) was given to 12 healthy volunteers in a single morning dose for three days. Circulating lymphocyte subsets were measured by flow cytometry after whole blood lysis. RESULTS: Seven hours after the first dose of prednisolone there was a significant fall in absolute numbers of lymphocytes, T cells, CD4+ and CD8+ cells, and B cells. The percentage of T cells fell significantly, due to a fall in percentage of CD4+ cells. In contrast to the seven hour findings, at 72 hours there was a significant rise in absolute numbers of lymphocytes, T cells, CD4+, CD8+, and B cells. This trend was already apparent by 24 hours. The percentage of CD4+ cells was significantly raised at 72 hours, while that of CD8+ cells had fallen significantly. The percentage of natural killer cells had fallen at 72 hours; that of B cells remained increased at 72 hours. CONCLUSIONS: These findings show that corticosteroid treatment causes significant changes in lymphocyte subsets, and that such changes must be considered when designing studies of lymphocyte subsets during illness.
Adult↗
Defective IgG2 response to Pneumovax in HIV seropositive patients.
OBJECTIVE: To determine whether HIV (Human Immunodeficiency Virus) antibody positive adults are capable of mounting an effective immune response when immunized with polyvalent pneumococcal vaccine. DESIGN: 28 patients (nine homosexual men, one bisexual man, three heterosexual females, 10 injecting drug abusers, five haemophiliacs) and 11 healthy volunteers, were immunised with Pneumovax II and titres of IgG1 and IgG2 specific antibody measured before and 1 month after immunisation. Magnitude of immune response was related to CD4 T-lymphocyte count at time of immunisation to establish whether responses are better in early disease. MAIN OUTCOME MEASURES: Based on our data in healthy volunteers we defined an adequate response to Pneumovax II as a post immunisation IgG2 antibody level at least 50% greater than the pre immunisation level. RESULTS: The magnitude of the response was significantly higher in the normal volunteers (U = 95; p = 0.0328). Adequate IgG2 responses were seen in 11/11 normals but in only 14/28 HIV seropositives (chi 2 = 8.58; p < 0.01). Poor responses were unrelated to the CD4 T-lymphocyte count at immunisation. Absolute IgG2 deficiency accounted for the poor response in only 1 HIV patient. CONCLUSION: 50% of HIV antibody seropositive individuals fail to mount adequate immune responses to polyvalent pneumococcal vaccine. Non responders are unlikely to be protected.
Adult↗
Diagnosis of ectopic pregnancy with endovaginal color Doppler US.
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Female↗
Supraclavicular nerve block: anatomic analysis of a method to prevent pneumothorax.
Supraclavicular nerve blocks are technically easy to perform, but may be associated with pneumothorax. The objective of this study is to define the parasagittal anatomy important to our modified technique of supraclavicular nerve block designed to decrease the incidence of pneumothorax and to determine whether this technique is anatomically sound. Two cadaver specimens were studied. One embalmed specimen was dissected to establish the relationship of the brachial plexus to our modified needle entry site. The neck and upper thorax of an unembalmed cadaver were frozen, and parasagittal serial sections were made to establish the relationship of the brachial plexus to surface features and the chest cavity. Additionally, 12 volunteers underwent magnetic resonance (MR) imaging and anatomic measurements of their supraclavicular anatomy important to our modified block. MR imaging showed that in no instance using our modified technique was the lung contacted by the simulated needle before entering either the subclavian artery or contacting the brachial plexus. Our technique has been used in more than 110 patients without pneumothorax. The combination of our cadaver and magnetic resonance data suggests that our plumb-bob technique of supraclavicular nerve block is anatomically sound and may minimize the development of pneumothorax during supraclavicular block.
Brachial Plexus↗
Sonography of the fetal heart: normal variants and pitfalls.
Sonographic evaluation of the fetal heart is an important part of obstetric sonography. The sonographer and sonologist should be familiar with the sonographic appearance of the normal fetal heart and with common structural abnormalities. Occasionally, normal structures in or adjacent to the fetal heart may simulate an abnormality. Although one should seek consultative sonography in instances of uncertain or questionable findings, unnecessary referral and concern may be avoided in some cases if the sonologist is familiar with normal variants and pitfalls. In this pictorial essay, we present several such pitfalls that we and others have observed in the four-chamber view (Fig. 1) and in views of the ventricular outflow tracts (Figs. 2 and 3).
Female↗
Predicting aneuploidy in fetuses with cardiac anomalies: significance of visceral situs and noncardiac anomalies.
To determine whether the risk of aneuploidy in fetuses with cardiac anomalies is affected by abnormal visceral situs or coexisting noncardiac anomalies (NCA), were reviewed 125 cases in which a structural cardiac anomaly was detected by prenatal sonography. Forty-three of the 125 fetuses (34%) had an abnormal karyotype (31 autosomal trisomies, 12 other). None of the 13 fetuses with abnormal visceral situs had an abnormal karyotype, whereas an abnormal karyotype was present in 43 of 112 with normal visceral situs (P < 0.01, Fisher's exact test). The karyotype was abnormal in 33 of 52 (63%) with coexisting NCA and in only 10 of 73 (14%) without coexisting NCA (P < 0.001, chi-square). Therefore, among fetuses with structural cardiac anomalies, abnormal visceral situs is strongly predictive (100% in our series) of normal karyotype, whereas the presence of coexisting NCA significantly increases the risk of aneuploidy. These findings can help guide recommendations concerning prenatal karyotyping.
Aneuploidy↗
Other uses of surfactant.
Surfactant is found not only in the alveoli but in bronchioles and small airways. Along with its important role in surface-tension reduction in alveoli, surfactant has several other properties. Any condition characterized by mucus abnormality, mucociliary transport deficiency, airway obstruction, or bronchoalveolar collapse could potentially benefit from exogenous surfactant therapy. Anti-inflammatory and bactericidal properties of surfactant could provide additional benefit in a variety of diseases.
Humans↗
Extracts of wheat gluten activate complement via the alternative pathway.
We studied the ability of wheat gluten and its subfractions to activate complement directly. A sensitive sandwich ELISA employing a monoclonal antibody (MoAb) to a C9 neoepitope exposed in the terminal complement complex (TCC), a functional haemolytic assay for C5b6 generation, and Laurell's electrophoretic method of estimating C3 conversion to C3bi were used. On a weight-for-weight basis, enzyme solubilized Frazer's fraction three of gluten (FIII) produced approximately 75% of the complement activation seen with the potent activator zymosan. By contrast, activation with whole insoluble undigested gluten was very weak and similar to that seen with ovalbumin or beta-lactoglobulin. The results were the same using normal human serum or sera from patients with coeliac disease, dermatitis herpetiformis, or hypogammaglobulinaemia as the complement source. Activation by both zymosan and FIII was blocked in 0.01 M EDTA, but not in 0.01 M EGTA with 0.0025 M magnesium chloride. Zymosan and FIII activated complement in a serum from a patient with an intact alternative pathway but classical pathway haemolytic activity (CH50) of zero. Preferential heat inactivation of the alternative pathway inhibited both zymosan- and FIII-induced activation. Our results confirm that FIII is a strong activator of the alternative pathway. We discuss how gluten enteropathy might be initiated by complement.
Adult↗
Dysphagia lusoria: aberrant right subclavian artery with a Kommerell's diverticulum.
A retroesophageal right subclavian artery, the most common congenital aortic arch abnormality, is an unusual cause of dysphagia in adults. The embryologic abnormality of the aortic arch is involution of the fourth vascular arch, along with the right dorsal aorta, leaving the seventh intersegmental artery attached to the descending aorta. This persistent intersegmental artery assumes a retroesophageal position as it proceeds out of the thorax into the arm. Since compression of the esophagus by this right subclavian artery may produce dysphagia, the term "dysphagia lusoria" ("dysphagia by freak of nature"), has been used to describe the symptom complex. The presence of an aneurysm of the artery or Kommerell's diverticulum at its aortic origin is more likely to produce symptoms from esophageal compression. This case presents a middle aged adult with an associated Kommerell's diverticulum and dysphagia. Surgical correction was used to relieve his symptoms and to correct the diverticulum of the proximal right subclavian artery. The embryologic changes that occur are discussed in detail.
Aorta, Thoracic↗
Anti-reticulin antibody in gluten sensitive enteropathy.
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Autoantibodies↗
A novel germline p53 splicing mutation in a pediatric patient with a second malignant neoplasm.
A novel germline p53 splicing mutation was identified in a pediatric patient with two metachronous primary cancers that are constituent tumors of the Li-Fraumeni syndrome. Genomic DNA from the second tumor showed the same mutation and loss of heterozygosity at the p53 locus. The mutant mRNA and protein were present in the tumor tissue. In contrast, in the normal tissues bearing the germline mutation in the heterozygous state, predominantly normal mRNA was expressed and the mutant p53 protein was not detectable. The functional silence and relative lack of mutant p53 mRNA expression in the normal tissues of this patient may be caused by decreased stability or decreased production. If this proves a more general pattern of expression of mutant p53 in individuals with germline mutations, these findings may explain the paucity of tumors in individuals affected with the Li-Fraumeni syndrome.
Adult↗