Female labour force integration and the alleviation of urban poverty: a case study of Kingston, Jamaica.
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Americas↗
Biomedical subjects
J Holland
Publications and source records attributed to J Holland.
Savant characteristics in a child with developmental delay and deletion in the short arm of chromosome 20.
The development outcome of a four-year-old boy with a deletion of the short arm of chromosome 20 is described. Despite a number of early medical problems, including infantile hypoglycemic convulsions secondary to growth hormone deficiency and delayed motor and language development, he has been reading (self-taught) since 2.5 years and currently has computer proficiency, and exceptional memory for maps and spatial locations, an extremely rich and active fantasy life, good diction, and an extensive spoken vocabulary. Neuropsychological evaluation revealed low-average intelligence with normal language, memory and attention functions, and impaired visuomotor and graphomotor ability and motor skills. He showed extremely advanced decoding and reading comprehension skills while mathematics, spelling and general knowledge abilities were average.
Achievement↗
Affinity, conservation, and surface exposure of hemopexin-binding proteins in Haemophilus influenzae.
Haemophilus influenzae can acquire heme from hemopexin for use as a source of both essential porphyrin and iron. In classical ligand-binding studies, we observed time-dependent, saturable, and displaceable binding of human 125I-labelled hemopexin to intact cells of H. influenzae type b (Hib) strain 760705 grown in an iron-restricted medium. From these experiments, which demonstrate that hemopexin associates with a single class of binding site, the affinities (Kds) and receptor numbers were calculated for heme-hemopexin (Kd, 205 nM; 3,200 receptors per cell) and apohemopexin (Kd, 392 nM; 4,400 receptors per cell). Thus, Hib expresses a specific hemopexin receptor which shows some preference for the heme-protein complex. Affinity chromatography on hemopexin-Sepharose 4B of detergent-solubilized membranes from Hib strain 760705 results in the copurification of three proteins with molecular masses of 57, 38, and 29 kDa. Trypsinization of whole cells of Hib 760705 abolishes hemopexin binding and correlates with the disappearance of the 57-kDa hemopexin-binding protein and appearance of a 52-kDa species which does not bind either hemopexin in ligand blot assays or a monoclonal antibody (MAbT11-30) raised against the 57-kDa protein. From immunoblotting assays and NH2-terminal amino acid sequence analysis, the 38-kDa protein isolated following hemopexin affinity chromatography was identified as the porin protein P2. These data, taken together with the receptor-binding studies which support a single class of hemopexin-binding site, suggest that P2 and the 29-kDa protein function as accessory proteins to the 57-kDa hemopexin-binding protein to facilitate the uptake of heme from receptor-bound hemopexin. To determine whether hemopexin binding and the 57-kDa protein are conserved in Haemophilus strains, whole-cell dot blots and immunoblots of the outer membrane proteins prepared from strains belonging to each of 21 different Hib outer membrane protein subtypes, six nontypeable strains, and five Haemophilus parainfluenzae strains were probed with either hemopexin or MAbT11-30. Only the H. parainfluenzae strains which lack the 57-kDa protein do not bind hemopexin. Since H. influenzae has also been shown to produce a soluble 100-kDa hemopexin-binding protein, cell-free culture supernatants were also examined for the presence of this protein. Apart from Hib 760705 and H. parainfluenzae, the 100-kDa hemopexin-binding protein was detected in all the other Haemophilus strains. The abilities of Hib 760705 to both bind and acquire heme from hemopexin without expressing a 100-kDa soluble hemopexin-binding protein show that in strain 760705, this 100-kDa protein is not essential for the utilization of heme from hemopexin.
Amino Acid Sequence↗
Combination chemotherapy for metastatic or recurrent carcinoma of the breast--a randomized phase III trial comparing CAF versus VATH versus VATH alternating with CMFVP: Cancer and Leukemia Group B Study 8281.
PURPOSE: We sought to compare three doxorubicin-based therapies for metastatic breast cancer for response frequency, time to treatment failure (TTF), and survival. MATERIALS AND METHODS: Women with metastatic breast cancer who had measurable disease, required laboratory tests, had received no prior chemotherapy for metastases, had a Cancer and Leukemia Group B (CALGB) performance status < or = 2, and provided informed consent were eligible. Treatment included the following: arm I--cyclophosphamide, doxorubicin, and fluorouracil (CAF); arm II--vinblastine, doxorubicin, thiotepa, and halotestin (VATH); and arm III--VATH alternating with cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP) on cycles 3, 5, 7, 9, etc. Doses were modified for toxicities. Standard CALGB response and toxicity criteria were used. RESULTS: Between August 1982 and February 1987, 497 women were entered and 491 were treated on study. Pretreatment characteristics were well balanced and the median follow-up duration was 79 months. There were no significant differences in response (complete [CR] plus partial [PR]) at 50% on arm I, 57% on arm II, and 51% on arm III. The median TTFs were 8, 8, and 9 months, respectively, in favor of arm III when compared with arm I (P = .028). The median survival times for treatment arms I, II, and III were 15, 17, and 17 months, respectively. After multivariate regression analyses, only estrogen receptors (ER), performance status, and number of metastatic sites influenced TTF and survival. Leukopenia was the most common grade 3 or 4 toxicity, occurring in 90%, 80%, and 92% of patients per arm, respectively. Lethal toxicities were seen in four, five, and six women, respectively. Overall, there were more grade > or = 3 toxicities on arm II than I, and most occurred on arm III (P = .02). CONCLUSION: The VATH regimen appears similarly effective to the CAF regimen as initial therapy. Alternating CMFVP with VATH did not improve response rate or survival. After accounting for other variables, treatment arm was not related to outcome. New therapeutic regimens are still needed.
Adult↗
Telematics and protocols of care in critical care environments.
The paper discusses the potential roles for protocols of care within critical care environments from the perspective of providing real-time support for their application. The discussion is based around a conceptual model of care in critical care environments. This model has been developed in the wider context of developing information technology systems to support clinical care in critical care environments. The conceptual model of care is a three layer model which demonstrates both the hierarchical and temporal aspects of the care delivered to patients. It is proposed that if the value of protocols of care is to be realised in critical care environments then they must be seamlessly integrated into the routine data management associated with the care of patients. In order to demonstrate this and to evaluate the utility of this concept in the clinical environment, the systems from the AIM TANIT (Telematics in Anaesthesia and Intensive Therapy) project have been used as prototype platforms. The application of the concepts developed are described in two critical care environments: the anaesthesia department and the intensive care unit. Problems in using protocols of care in intensive care units suggest that integrating these with a problem solving methodology to create an integrated care plan may be a more appropriate approach to patient management.
Anesthesia Department, Hospital↗
Skin care for patients receiving radiation.
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Humans↗
Behavioural interventions for HIV/AIDS prevention.
OBJECTIVES: The aim of this study was to identify and critically review behavioural interventions in the HIV prevention and sexual health fields. METHODS: Electronic and hand searches were conducted to retrieve relevant published and unpublished reports of outcome evaluations. A methodological review was carried out to identify those with sufficient methodological strengths to generate reliable conclusions as to effectiveness. Soundly designed studies were defined as those which met the four core criteria of employing control groups, providing pre- and post-intervention data and reporting on all targeted outcomes. RESULTS: A total of 68 separate reports of outcome evaluations were located. Only 18 were judged to be methodologically adequate. Major problems found were lack of a control group or non-equivalent/unbalanced control groups, small sample sizes, failures to report pre-intervention measures, short follow-up, and high attrition rates. Academic reviewers were more likely than the authors of papers to judge reports of evaluations as providing insufficient information to assess effectiveness. CONCLUSION: Evaluation design in this field needs to be improved. Recommendations include more use of randomized controlled trials and the raising of publication standards by journals.
Acquired Immunodeficiency Syndrome↗
The red queen reigns in the kingdom of RNA viruses.
Two clonal populations of vesicular stomatitis virus of approximately equal relative fitness were mixed together and allowed to compete during many transfers in vitro as large virus populations. Eventually, one or the other population suddenly excluded its competitor population, yet both the winners and losers exhibited absolute gains in fitness. Our results agree with the predictions of two major theories of classical population biology; the Competitive Exclusion Principle and the Red Queen's Hypothesis, where (in Lewis Carroll's words) "it takes all the running you can do to keep in the same place."
Animals↗
Isolation of cosmid and cDNA clones in the region surrounding the BTK gene at Xq21.3-q22.
A regional physical and transcription map involving yeast artificial chromosomes (YACs), cosmids, and cDNAs has been constructed for Xq21.3-q22 around the gene BTK (formerly atk or BPK) defective in X-linked agammaglobulinemia (XLA). With a positional cloning strategy employing direct cDNA selection, novel cDNAs were found to cluster in the region of approximately 100 kb flanking the XLA and alpha-galactosidase A loci. While these widely expressed transcripts are in the area known to contain CpG islands, a less evolutionarily conserved gene, located more than 130 kb distal of DXS178, maps to cosmid clones that could not be digested with rare-cutting restriction enzymes. The presence of transcribed sequences flanking the BTK allowed us to investigate their involvement in complex XLA phenotypes. Southern blot analysis using cDNA clones isolated from this region permitted us to exclude a contiguous deletion syndrome as an underlying defect in three patients with XLA and associated growth hormone deficiency. A single XLA patient with torsion dystonia and cosegregating X-linked deafness has been found with a deletion in the 3' part of BTK extending centromerically into the flanking expressed sequence DXS1274E. This suggests a possible involvement of the DXS1274E in this phenotype. The GenBank accession numbers for novel cDNA sequences are as follows: DXS1269E (L20773), DXS1271E (UO1923), DXS1273E (UO1925), and DXS1274E (UO1922).
Agammaglobulinaemia Tyrosine Kinase↗
TANIT AIM project (A2036): Telematics for ANaesthesia and Intensive Therapy.
On-going work relating to the development of advanced telematics systems for Critical Care environments is described. This work is in part sponsored by the Commission of European Communities under the AIM TANIT project. Two example departments have been selected for piloting in the project: Intensive Care and Anaesthesia. The objective of this paper is to outline the complex issues that need to be addressed when developing such systems.
Anesthesia Department, Hospital↗
Identification and characterization of an iron-regulated hemopexin receptor in Haemophilus influenzae type b.
Heme can serve Haemophilus influenzae as a source of both essential porphyrin and iron. In extracellular mammalian body fluids neither free heme nor free iron is available, since they are tightly bound to hemopexin and transferrin, respectively. Since H. influenzae grows in the presence of iron-transferrin and heme-hemopexin and is known to express a saturable receptor for transferrin, we investigated the process by which this pathogen acquired heme from hemopexin for use as an iron source. The ability of human and rabbit hemopexin to donate heme as a source of iron to H. influenzae type b strains was demonstrated by plate bioassays. With a dot enzyme assay with biotinylated hemopexin as ligand, H. influenzae bound heme-hemopexin and apo-hemopexin following growth in iron-restricted, but not in iron-sufficient, medium. Competitive binding studies with heme-hemopexin and apo-hemopexin demonstrated saturability of binding. Neither heme, protoporphyrin IX, hemoglobin, nor transferrin blocked the binding of hemopexin to whole cells, demonstrating the specificity of binding. Treatment of whole H. influenzae cells with trypsin abolished binding. Taken together, these observations suggest that H. influenzae type b expresses an outer membrane protein(s) which acts as a receptor for hemopexin and which is regulated by the availability of iron in the growth medium. In iron-restricted media, H. influenzae 706705 and DL42 did not express the 100-kDa hemopexin-binding protein previously reported (M.S. Hanson, S.E. Pelzel, J. Latimer, U. Muller-Eberhard, and E.J. Hansen, Proc. Natl. Acad. Sci. USA 89:1973-1977, 1992). The putative iron-regulated hemopexin receptor was solubilized from cell envelopes of H. influenzae 706705, DL42, and Eagan with the detergent CHAPS (3-[(3-cholamidopropyl)-dimethyl-ammonio]-1-propanesulfonate) and isolated by affinity chromatography on heme-hemopexin-Sepharose 4B. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the proteins bound to the affinity resin revealed three proteins of 29, 38, and 57 kDa, of which the 57- and 29-kDa proteins bound hemopexin after Western blotting (immunoblotting). A monoclonal antibody to the 57-kDa hemopexin-binding protein of 706705 recognized a 57-kDa protein on Western blots of the cell envelope proteins of 706705, DL42, and Eagan; no reaction was observed with the 100-kDa hemopexin-binding protein of DL42. These data suggest that some H. influenzae strains possess at least two hemopexin receptors, the expression of which is determined by the prevailing growth environment.
Aerobiosis↗
Prospective endoscopic study of stress erosions and ulcers in critically ill adult patients treated with either sucralfate or placebo.
OBJECTIVE: To compare the frequency of stress erosions and ulcers in critically ill adult patients treated with either sucralfate or placebo. DESIGN: Prospective, randomized study. SETTING: Intensive care unit in a university hospital. PATIENTS: Twenty-six adult patients. All patients were mechanically ventilated and were at risk of developing stress ulceration. INTERVENTIONS: Patients were randomized to receive either sucralfate (2 g every 8 hrs) (group 1) via the nasogastric tube (flushed with 10 mL of sterile water) or 20 mL of sterile water every 8 hrs (group 2) via the nasogastric tube. MEASUREMENTS AND MAIN RESULTS: At the time of intensive care unit admission, the frequency of stress (acute) erosions (as assessed with the endoscope) was 21.7%. No ulcers were detected. By day 3, the frequency had increased to 37.5% in group 1 and 88.9% in group 2. Mucosal deterioration was more likely in the patients treated with placebo (water) (p < .05). In total, seven patients developed acute ulceration in group 2 compared with only one patient in group 1 (p < .05). The frequency of gastric colonization with aerobic Gram-negative bacilli was 25.6% in group 1 and 28.6% in group 2. Only one retrograde nosocomial pneumonia developed (group 1). CONCLUSION: Based on our findings, we strongly recommend the adoption of sucralfate as opposed to no prophylaxis in the prevention of acute upper gastrointestinal ulceration.
Adult↗
Antigenic relationships of transferrin-binding proteins from Neisseria meningitidis, N. gonorrhoeae and Haemophilus influenzae: cross-reactivity of antibodies to NH2-terminal peptides.
The NH2-terminal amino sequence through the first 20 amino acids was obtained for transferrin-binding protein (TBP)1 from three strains of Neisseria meningitidis. These were identical except for a glutamine to a glycine substitution at residue 6 in one case. The sequences of the NH2-terminal 20 amino acids of TBP2 from the same three strains were also determined; one TBP2 had a M(r) of 68,000 and the other two of 78,000. Sequences were identical up to residue 13 in all three proteins. Peptides based on the NH2-terminal sequences of TBP1 and 2 were synthesized, linked to Keyhole Limpet haemocyanin and used to raise antibodies in rabbits. Anti-peptide antibodies cross-reacted on immunoblotting with the respective TBPs from all meningococcal strains tested, as well as with those from N. gonorrhoeae, suggesting that the NH2-terminals of these proteins are well conserved in the Neisseria. Neither anti-peptide serum reacted with the analogous TBP1 and 2 from Haemophilus influenzae, although common epitopes have previously been shown to exist.
Amino Acid Sequence↗
The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases.
X-linked agammaglobulinaemia (XLA) is a human immunodeficiency caused by failure of pre-B cells in the bone marrow to develop into circulating mature B cells. A novel gene has been isolated which maps to the XLA locus, is expressed in B cells, and shows mutations in families with the disorder. The gene is a member of the src family of proto-oncogenes which encode protein-tyrosine kinases. This is, to our knowledge, the first evidence that mutations in a src-related gene are involved in human genetic disease.
Agammaglobulinemia↗
The role of the urethrogram during simulation for localized prostate cancer.
Urethrograms on 89 consecutive patients with localized prostate cancer were evaluated retrospectively, and the inferior border of the treatment field based on this study was compared with the inferior border that would have been defined by using the lower border of the ischial tuberosities. An analysis of the relationship between the margin used and the dose at the inferior border of the prostate supported our policy of requiring a 2 cm margin for optimal coverage of the prostate. Inclusion of at least 1 cm of proximal penile urethra was essential to ensure this 2 cm margin. Based on this assumption, twenty-five percent of patients would have had an inadequate margin if the lower border of the ischial tuberosities had been used instead of the urethrogram to define the inferior border of the treatment field. Assuming that a margin of more than 3 cm inferiorly is excessive, 11% of patients would have had excessive urethral irradiation if the bottom of the ischial tuberosities had been used to define the inferior border. Combining these two extremes, more than one in three patients would have had an inappropriate inferior margin if the bottom of the ischial tuberosities had been used to define the inferior border of the treatment field. There was no apparent increase in morbidity as a result of the urethrograms or an increase in treatment related toxicity in association with using the treatment fields defined by urethrography. Computed tomography was complimentary in defining the apex of the prostate. These data support the routine use of the urethrograms during simulation for localized prostate cancer. The use of the lower border of the ischial tuberosities to define the inferior border of the treatment field is associated with an unacceptable risk of either underdosing the apical portion of the prostate or overdosing the urethra.
Aged↗
Vertical integration of cosmid and YAC resources for interval mapping on the X-chromosome.
The vertical integration of cosmid and yeast artificial chromosome (YAC) resources is of particular importance in the development of high-resolution maps of selected regions of the human genome. A resource of approximately 95,000 cosmids constructed using DNA from primary fibroblasts of karyotype 49,XXXXX was validated by detailed characterization of a 200-kb cosmid contig spanning exons 8-20 of the dystrophin gene. This resource was used to construct contigs in 0.65 Mb of Xq26 by hybridization of gel-purified YAC DNA to high-density gridded arrays of the cosmid library; positive cosmids were overlapped by finger-printing. Contigs were oriented and ordered relative to existing YACs in the region using cross-hybridization. The overlaps between a representative set of cosmids define 54 intervals of 5-20 kb and were used to construct a high-resolution cosmid interval map of the region, locating markers, dinucleotide repeats, and candidate CpG islands. This approach can be applied rapidly to large regions of the genome and without recourse to subcloning of individual YACs.
Aneuploidy↗
Cross-cultural differences in the care of patients with cancer. A review.
In order to assure optimal care of patients with chronic medical illnesses it is necessary to take into account the cultural factors that may influence health-related behaviors. By using cancer as a model, this paper discusses the major cultural issues that should be considered in order to increase cultural sensitivity in the medical setting: family function, sex roles, language, disclosure of disease-related information, pain, attitudes towards illness and health practices, immigration, region, autonomy versus dependency, and death and bereavement. Case histories illustrating the relevance of such socio-cultural factors in the cancer setting are reported.
Adult↗
Psychiatric consultation for women undergoing rehabilitation for upper-extremity lymphedema following breast cancer treatment.
Breast cancer presently affects one in nine women in the United States. Women receiving radiation and surgical resection of axial lymph nodes are at risk for development of lymphedema of the ipsilateral upper extremity. Mental health consultation and intervention can be an important part of rehabilitative efforts aimed at improving both lymphedema itself and the overall psychosocial adjustment of the patient. Such consultation begins with a careful consideration of possible psychiatric diagnosis but must necessarily depart from standard psychiatric considerations to include an assessment of psychosexual and social factors. Additionally, the consultant must gauge the degree of success the patient has had in adjustment to lifestyle changes brought on by lymphedema. This paper discusses the psychological problems posed by lymphedema and offers case examples. These cases illustrate the nature of psychiatric and psychological factors encountered in this population and the interventions that can help improve both compliance with rehabilitative efforts and psychological adjustment.
Adult↗