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Biomedical subjects

B Peters

Publications and source records attributed to B Peters.

At least 73 records · Page 4Linked to original sources

Abdominal wall hernias in patients with abdominal aortic aneurysmal versus aortoiliac occlusive disease.

BACKGROUND: This study was undertaken to determine the incidence of ventral incisional hernias (VIHs) and inguinal hernias (IHs) in patients with abdominal aortic aneurysmal (AAA) versus those with aortoiliac occlusive disease (AIOD). PATIENTS AND METHODS: The medical records of 193 patients (128 with AAA and 65 with AIOD) who had undergone elective aortic reconstruction were reviewed to determine the number and location of abdominal wall hernias (AWHs). RESULTS: Forty-one AWHs (28 IHs and 13 VIHs) were detected in patients with AAA compared to 13 (11 IHs and 2 VIHs) in patients with AIOD. There was a significantly greater incidence of VIHs in patients with AAA versus patients with AIOD (10% versus 3%, P < 0.05) and recurrent AWHs (28% versus 19%, P < 0.01), but not of IHs (22% versus 17%). CONCLUSION: Patients with AAA have a higher incidence of VIHs and recurrent AWHs--without a corresponding increase in patient-related risk factors--than patients without aneurysm, suggesting that as yet unidentified etiologic factors may contribute to the development of AWHs in these patients.

Aorta, Abdominal↗

A survey in action. The "next wave assessment" takes shape.

With the initiation of the Health Care 2000 vision project in 1988, the MHA established itself as one of the first state hospital associations to strategically assess important health care trends and craft a framework for the future of health care delivery and financing for its membership. The 1990s have brought much change and unprecedented challenge to the health care field. As MHA continues to transform to meet the needs of its members, the time has come to reassess our health care environment and critically examine our assumptions about the future.

Delivery of Health Care↗

Effects of chronic low level lead exposure on the expression of GFAP and vimentin mRNA in the rat brain hippocampus analysed by in situ hybridization.

In this study we used in situ hybridization to examine the effects of chronic low level lead toxicity during different periods of brain development. Low level lead is known to affect astroglia. GFAP and Vimentin were chosen as glialtypic markers for neurotoxicity. The effects of lead were investigated on male Wistar rats. Animals were divided into four groups: a control group, a permanent group exposed during gestation, lactation and post-weaning (E0-P100), a perinatal group exposed during gestation and postnatally until weaning (E0-P16), and a post-weaning exposed group (P16-P100). All experimental animals were fed a diet containing 750 ppm lead acetate. With respect to Vimentin mRNA no major differences could be detected among the treatment groups. Significant differences in GFAP mRNA levels were detected in the post-weaning group relative to controls. In this group we observed a strong increase of GFAP mRNA in the polymorphic zone of the dentate gyrus and in the CA1 region of the hippocampus. Permanent and perinatal groups showed no overt changes compared to controls. Our findings suggest that an irritation of the mature astrocyte results in a change from the quiescent to the reactive state. The majority of astrocytes that have been exposed during their development and differentiation fail to react even if the exposure is continued to adulthood. This suggests an irreversible insult by low level lead exposure during this period of time.

Animals↗

Protein-DNA interactions in the epsilon-globin gene silencer.

The developmental control of expression of the human epsilon-globin gene appears to be mediated, at least in part, by a transcriptional silencer in the DNA 5' to the cap site of this gene. We have used site-directed mutagenesis and DNA-protein binding assays to define the active motifs of this epsilon-globin silencer. DNase I foot-printing of the silencer region with K562 cell nuclear extracts defined a sequence, which we designate as the epsilon-globin silencer motif or epsilon GSM (epsilon -278 to -258 base pairs (bp)) containing a region (epsilon -270 to -258) with 90% homology to the yeast mating type silencer, ABF-1 (autonomous replicating sequence binding factor one) and which also overlaps at (epsilon -269 to -262) with the human YY1 consensus sequence, an element which mediates transcription repression and activation of viral, mouse, and human genes. The DNase I footprint extended 5' in the silencer region to include an inverted repeat of a six-nucleotide motif (epsilon -267 to -278 bp) which shares 5 of 6 bases with the GATA-1 consensus sequence. In gel mobility shift assays, two specific proteins (A and B) in nuclear extracts from erythroleukemia K562 cells bound to the DNase I-footprinted region. Protein B, associated with epsilon-globin silencer activity in vitro, required an intact epsilon GSM sequence for binding. Mutation of 5 bases within the epsilon GSM in an epsilon-globin promoter-containing fragment extending upstream to 1400 bp in transient transfection assays increased activity by 3.0-fold compared with the native sequence, suggesting that the silencer activity was mediated by the epsilon GSM sequence. We found that protein A could be displaced by a competitor containing the GATA-1 consensus sequence, suggesting that protein A is a GATA-like protein. The region from -267 to -271 within the epsilon GSM and GATA-1 homology region was important for binding of both proteins A and B. These data suggest that protein binding to the epsilon GSM and GATA motifs mediate the negative effect of the silencer on transcription, possibly via direct competition for binding to this DNA region. Recombinant yeast ABF-1 and human YY1 bound to the epsilon GSM. Mutating three bases (epsilon -259, -262, -264) in the epsilon GSM decreased the binding affinity of protein B and recombinant human YY1 but increased the binding affinity of recombinant yeast ABF-1. Furthermore, competitor containing the YY1 consensus sequence competed for protein B binding, whereas competitor containing a perfect yeast ABF-1 consensus sequence did not.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Sequence↗

Pneumothorax in patients with AIDS.

Eighty-seven inpatients were treated for 93 episodes of Pneumocystis carinii at St Mary's Hospital between January 1989 and December 1990. During this period, 298 patients with the acquired immunodeficiency syndrome (AIDS) were treated at this hospital. Sixteen episodes of pneumothorax occurred and 12 of these, occurring in ten patients, were unrelated to procedure. In six of 12 (50%), the pneumothoraces occurred concurrently with Pneumocystis carinii pneumonia (PCP) and in ten (83%) cases there was a past history of PCP. Bilateral pneumothorax occurred in five cases (42%). In seven (58%) of the cases, patients had been using aerosolized pentamidine as prophylaxis for PCP. This retrospective study confirms the association of pneumothorax with current PCP and also shows an association with previous infection. The use of aerosolized pentamidine was not associated with pneumothorax development. It is important to suspect pneumothorax in a patient with PCP who deteriorates acutely. The high incidence of bilateral pneumothorax means that pleurodesis should be considered early.

AIDS-Related Opportunistic Infections↗

The epsilon-globin gene silencer. Characterization by in vitro transcription.

K562 human erythroleukemia cells constitutively express epsilon- and gamma- but not beta-globin genes. We have previously shown that the differential expression of globin genes observed in intact K562 cells could be simulated in vitro as K562 nuclear extract (NE) actively transcribes the epsilon-globin (with 2 kilobases of 5'-flanking sequence) and gamma-globin gene DNA templates but not beta-globin gene templates. We have now used the K562 in vitro transcription system to examine a silencer transcriptional control element which has been reported to be localized between -177 and -392 base pairs (bp) 5' of the canonical cap site for the epsilon-globin gene. We find that K562 NE has markedly reduced synthesis of RNA in vitro from epsilon-globin gene DNA deletion templates which contain the silencer sequence, or part thereof, but not the adjacent 5'-positive regulatory region (-453 to -535 bp). Furthermore, those transcripts generated in vitro from DNA templates extending to -453 bp or less of the epsilon-globin gene were not correctly initiated at the canonical cap site. Separating the K562 NE by ion exchange chromatography, we isolated a fraction (F175) transcriptionally active for all tested globin genes including the epsilon-globin gene containing the silencer sequence and a fraction (F50) which contains the trans-acting factors associated with the silencer activity. F50 showed a strong dose-dependent inhibitory effect on correctly initiated epsilon-globin gene transcription directed by either unfractionated K562 NE or F175. This suppression by F50 was not observed on transcriptional activity of the permissive adenovirus 2 major late promoter. In electrophoretic mobility shift assays using the epsilon-globin gene silencer region as probe, F50 and F175 exhibited different DNA binding protein patterns; a specific protein band in F50 appears to be associated with the silencer activity. These studies suggest that this protein may be specifically responsible for the activity of the silencer element of the epsilon-globin gene. The expression and silencing of the epsilon-globin gene during development may be modulated by the interactions of this protein with the cis-acting DNA silencer.

Amanitins↗

A phase II study of sulofenur, a novel sulfonylurea, in recurrent epithelial ovarian cancer.

A total of 16 patients with recurrent epithelial ovarian cancer were treated with sulofenur (LY 186641), a novel oral sulfonylurea. All subjects had received previous chemotherapy. Anaemia occurred in all 16 patients, 14 of whom required a blood transfusion, and 2/16 patients received methylene blue for breathlessness due to methaemaglobinaemia. Treatment was discontinued in 2/16 cases due to rising liver enzyme values, which reverted to normal on cessation of the drug. There was no nausea or alopecia. Only two minor responses were seen. Plasma drug levels were insufficient to result in antitumour activity as extrapolated from animal data. Further studies that attempt to increase the bioavailability and improve the therapeutic index are warranted.

Adolescent↗

A phase II study of sulofenur (LY186641) in gastric cancer.

Sulofenur is a novel diarylsulfonylurea with proven anti-tumor activity in murine tumor models. In this phase II study in patients with advanced gastric or gastroesophageal adenocarcinoma, 17 patients were treated with sulofenur orally at 700 mg/m2 for 14 days every 3 weeks. No tumor responses were seen. The main toxicities were anemia, methemoglobinemia and abnormalities in liver function tests. These toxicities precluded dose escalation. However, plasma levels of sulofenur, and its hydroxy and keto metabolites were probably insufficient to exert anti-tumor effect in comparison with data from murine studies. Further structure-activity studies are warranted.

Adenocarcinoma↗

Kaposi's sarcoma in HIV infection treated with vincristine and bleomycin.

OBJECTIVE: To evaluate the efficacy and toxicity of vincristine and bleomycin when used in combination to treat patients with progressive Kaposi's sarcoma. DESIGN: A retrospective case notes review. SETTING: The departments of Immunology and Genito-Urinary Medicine, St Mary's Hospital, London, UK. PATIENTS: All patients presenting with progressive Kaposi's sarcoma and requiring chemotherapy between January 1987 and January 1990, who had received no previous systemic chemotherapy. INTERVENTIONS: Treatment with vincristine (2 mg) and bleomycin (30 mg, 18 h infusion), or vinblastine (2.5-5.0 mg) if peripheral neuropathy developed. Treatment with zidovudine and prophylaxis of opportunistic infections where indicated. OUTCOME MEASURES: Response, toxicity and survival. RESULTS: Overall, patients had a poor prognosis: 33 out of 46 (72%) had had a previous opportunistic infection, had a mean CD4 count of 144 x 10(6) (20 out of 46 tested) and a mean Karnofsky index of 75.4. They received a median of five cycles of therapy: a partial response was achieved in twenty-six patients (57%), disease progression was halted in a further 16 (35%), while disease progression continued in four (9%) despite therapy; there were no complete responders. Mean duration of response was 2 months (s.d., 1.26 months), survival was 8 months (s.d., 6.7 months) from start of therapy and 17 months (s.d., 8.9. months) from first AIDS diagnosis. On multivariate analysis the best predictor of mortality was the presence of previous opportunistic infection (P = 0.00653). Side-effects were minimal in comparison with other studies. The most common side-effect, in 13 cases (28%), was peripheral neuropathy, which may in part represent the prevalence of HIV neuropathy or remain as background. Haematological toxicity was uncommon. CONCLUSIONS: Treatment for HIV-related Kaposi's sarcoma in advanced HIV disease is becoming more necessary as disease profiles change. Conventional chemotherapy regimens for malignancy are not well tolerated in these patients and may not be indicated. This regimen is effective and has low toxicity in AIDS patients. Non-responders should be considered for more intensive regimens.

Acquired Immunodeficiency Syndrome↗

Different degree of ileal colonization by segmented, filamentous bacteria in two strains of mice.

Segmented, filamentous bacteria (SFBs) are autochthonous, apathogenic inhabitants of the ileum of various animal species. Outbred Swiss (Cpb:SE) mice have significantly higher degrees of SFB colonization than do inbred BALB/c mice. The present studies were carried out to identify determinants of this strain difference. In a cross-fostering experiment it was shown that SFB colonization of the pups is determined by the strain of the pups themselves rather than by the strain of the nursing dam. Thus, maternal effects may not be involved in SFB colonization. In a cross-infecting experiment using germ-free and SFB-positive animals of the two mouse strains, it was found that ileal SFB colonization is determined by host characteristics rather than by origin of the SFBs. Thus, SFBs that are specific for a given mouse strain may not exist in the two strains of mice. It is concluded that the mouse strain difference in SFB colonization is determined by host characteristics, which probably have a genetic basis.

Animals↗

[Mycobacterium kansasii seroma of the skin in HIV infection].

We report on an HIV-infected patient with AIDS in whom a smoothly demarcated area of resistance in the size of a fist was found on the inside of the thigh. Investigation by sonography for clinical differential diagnosis confirmed that a haematoma, a seroma or an abscess might be present. Upon puncture of the cavity, serous exudate was obtained. The microbiological investigation resulted in the growth of Mycobacterium kansasii. The detection of this agent in throat and sputum samples from the patient and the occurrence of an osteomyelitis lesion at the same time indicate that the seroma was a partial manifestation of a disseminated Mycobacterium kansasii infection. No indications of a transcutaneous route of infection was found. Upon antimicrobial chemotherapy after the determination of resistance the seroma disappeared.

Abscess↗

A protective thermoplast splint for the forearm and hand in nonhuman primates.

A custom-made thermoplastic splint was developed for the protection of the upper extremity after experimental surgery. It was used in 39 cases for a duration of 12-79 days. Complications were minimal and transient. The cast was easy to make, in one piece and inexpensive. Frequent removal for wound inspection was simple. This splint provides a good immobilization and protection of the arm and hand in the nonhuman primate.

Animals↗

Micronucleated erythrocytes as an index of cytogenetic damage in humans: demographic and dietary factors associated with micronucleated erythrocytes in splenectomized subjects.

Erythrocytes containing micronuclei serve as an indicator of genotoxic exposure in splenectomized individuals. Micronucleated erythrocytes, derived from cytogenetically damaged RBC precursors, are not selectively removed from peripheral blood in individuals who lack splenic function. The relationship between micronucleated cell frequencies and demographic, environmental, and dietary factors was examined in 44 subjects with previous splenectomy due to trauma. Their micronucleated cell counts fit a log-normal distribution, with geometric means of 3.3 micronucleus-containing cells/1000 reticulocytes and 2.7/1000 normochromatic erythrocytes. A multiple regression analysis showed that drinking five cups of coffee or tea/day (relative to none) was associated with an approximately 2-fold higher frequency of micronucleated cells. Weaker statistical associations were also noted with micronucleus frequency and the consumption of calcium supplements (associated with a higher frequency) and vitamins A, C, or E (lower frequency). An apparent trend of higher micronucleus counts with age was attenuated when other factors were considered in the regression. Cigarette smoking and decaffeinated coffee consumption were among the factors not associated with elevated micronucleated cell frequencies. Because the occurrence of micronuclei in reticulocytes reflects cytotoxic exposures within the past 3-8 days, it may be possible to test directly the relationship of these factors to micronucleus formation through intervention studies.

Chromosome Aberrations↗

Pulmonary cavitation with Nocardia and Aspergillus in a renal transplant patient.

We present an autopsy case of concomitant pulmonary aspergillosis and nocardiosis undiagnosed during life in a long-term surviving renal transplant recipient. The patient had fever and a newly developed cavitary lesion on a chest x-ray. The working diagnosis was pulmonary tuberculosis with possible colonization by Aspergillus species. Cultures of bronchial washings became positive for Aspergillus fumigatus 1 day after death. The study of tissue from the lung cavity at autopsy revealed Aspergillus fumigatus (confirmed by postmortem culture) and the filaments of Nocardia species. Increased numbers of surviving immunosuppressed patients will require aggressive, comprehensive diagnostic techniques for the detection of polymicrobial infections.

Aspergillosis↗