Biomedical subjects
Publications and source records attributed to S Hughes.
The third of our back to basics series reviews the efficacy of continence aids such as pads and barrier creams, and their role in maintaining skin integrity. Many studies had flaws and new research is needed to avoid subjective choice of products.
To discover laboratory ascertainment and reporting practice for cases of cryptosporidiosis in two health authority regions, we surveyed laboratories serving Wales and the North West of England for faecal screening policies and methods for detection of Cryptosporidium. Forty-eight of the 49 laboratories responded, of which 39 (81%) screen all stool specimens from symptomatic individuals for Cryptosporidium and 9 (19%) screen selected specimens. Although laboratory screening is more complete than has been reported in other regions, we identified discrepancies where patient age was used as a selection criterion, and we make suggestions to amend this. Forty-two (88%) responding laboratories report confirmed cases to the regional Communicable Disease Surveillance Centre (CDSC) and 45 (94%) report to the local authority environmental health department. We also surveyed local authorities in both regions for policy and practice concerning the investigation of reported cases of cryptosporidiosis in the same regions. All 59 local authorities responded, of which 57 (97%) investigate cases by completion of an exposure questionnaire as well as providing advice on the prevention of spread of infection. Variation in case ascertainment may influence perception of incidence, clusters and outbreaks of cases of cryptosporidiosis.
We have identified three novel chicken CC chemokine genes among cDNA clones derived from lipopolysaccharide-stimulated cells of the chicken macrophage cell line HD11. Two of these chemokines show DNA sequence homology to the mammalian genes SCYA20 (MIP-3alpha) and SCYA5 (RANTES), while the third shows similar levels of homology to several mammalian CC chemokines. Sequencing of genomic DNA showed that all three chicken chemokines possess the three-exon structure and conserved intron positions typical of mammalian CC chemokines. Genetic mapping of the three chicken chemokines locates them in three chromosomal regions which correspond to regions containing homologous chemokines in humans. Phylogenetic analysis of the currently known chicken and human chemokines suggests that individual chicken and human chemokines derive from common ancestral genes in patterns that reflect their genomic positions, indicating that the diversity of chemokine genes pre-dated avian-mammalian divergence. Since the function of the chemokines is principally to act as intermediates between stimulated cells and specific subsets of responding immune cells, this suggests that the complex organization of the immune system and diversity of responding cells were largely in place at that time.
The presence of astrocyte precursor cells (APCs) and time course and topography of astrocyte differentiation during development were investigated by triple-label immunohistochemistry with intact fetal and adult human retinas. Throughout retinal development and adulthood, expression of Pax2 was restricted to cells of the astrocytic lineage. Three distinct stages of astrocytic differentiation were identified during development: i) Pax2+/vimentin+/GFAP- APCs; ii) Pax2+/vimentin+/GFAP+ immature perinatal astrocytes; and iii) Pax2+/vimentin-/GFAP+ mature perinatal astrocytes. In adult, cells with the antigenic phenotype of mature perinatal astrocytes were restricted to a region surrounding the optic nerve head (ONH), whereas cells at a fourth stage of differentiation, adult astrocytes (Pax2-/vimentin-/GFAP+), were apparent throughout the vascularized retina. APC appearance was centered around the ONH and preceded the appearance of perinatal astrocytes. A cluster of Pax2+ somas was also present in a small region surrounding the ONH at the ventricular surface of the developing retina, which suggests the existence of two distinct sites of astrocytic differentiation. The coincidence in the location of APCs and perinatal astrocytes at the ventricular zone with that of optic nerve colobomas, together with the association of Pax2 gene mutations with this condition, suggests that coloboma formation may result from impaired astrocyte differentiation during development.
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Serum antibodies to the Yo antigen are usually associated with paraneoplastic cerebellar degeneration arising in female patients with gynecological or breast malignancy and are rarely associated with other tumors. We report a male patient who presented with paraneoplastic cerebellar degeneration and anti-Yo antibodies following removal of an esophageal adenocarcinoma. This is only the third report of anti-Yo antibodies occurring in a male patient. The Yo antigen was expressed by the esophageal tumor but not in a frontal lobe cerebral metastasis identified at postmortem. Interestingly, CD8+ T-cell infiltration was also found in the tumor, but not in the metastasis, consistent with down-regulation of Yo expression by the tumor cells leading to evasion from immune-mediated tumor surveillance.
The presence and extent of prostatitis on the patients' preimplant biopsy slides was correlated with their postimplant course to determine if any relationship exists between histological prostatitis and postimplant morbidity. Biopsy slides from 56 patients treated with I-125 (144 Gy, TG-43), Pd-103 (125 Gy, NIST-1999), or Pd-103 plus supplemental external beam radiation (20-44 Gy) were studied. As part of ongoing prospective protocols, treatment-related morbidity is monitored by mailed questionnaires at 1, 3, 6, 12, and 24 months postimplant, using standard American Urologic Association (I-PSS) and Radiation Therapy Oncology Group criteria. Patient's preimplant biopsies, stained with standard hematoxylin and eosin, were retrieved for review by one uropathologist (LT). Separate evaluations of the degree and extent of inflammation in biopsy cores free of cancer and in cancerous biopsy cores were undertaken. Infiltrates were classified as periglandular if they were within 50 microns of a glandular structure. They were otherwise classified as stromal. Distribution of the inflammation was reported as focal, multifocal, or diffuse. The intensity of inflammation was separately graded as mild if there were fewer than 10 inflammatory cells per high-power field, moderate if there were 10-200 cells per high-power microscopic field, or severe if there were more than 200 cells per field. In all cases the great majority of inflammatory cells were mononuclear, predominantly lymphocytes. Periglandular inflammation was most common, with 18% of patients having focal periglandular and 20% having multifocal periglandular inflammation on their preimplant biopsies. Cancer-related infiltrates were the second most common, with 23% of patients having focal, 13% multifocal, and 13% diffuse cancer-related inflammation on their preimplant biopsies. Eight of the 55 patients developed postimplant urinary retention, requiring catheterization for 2 to 8 days. The overall incidence of postimplant urinary retention was low and there was no obvious relationship between the presence of inflammation on preimplant biopsy and the likelihood of postimplant urinary retention. AUA score changes at 1 and 6 months postimplant were highly variable and unrelated to the presence or severity of periglandular or cancer-related inflammation. Considering the apparent lack of relationship between histological findings and clinical outcomes in the patients reported here, the authors conclude that histologic evidence of prostatitis is not a contraindication to brachytherapy.
We compared nonsynonymous substitution rates (Ka) of nuclear coding genes between four major groups of living sauropsids (reptiles): birds, squamates, crocodiles, and turtles. Since only 9 orthologous genes are known in all the four taxonomic groups, we searched for orthologous genes known in chicken and at least one of any representative of poikilotherm sauropsids. Thus, we analyzed three additional data sets: 28 genes identified in chicken and various squamates, 24 genes identified in chicken and crocodilians, and 20 genes identified in chicken and turtles. To compare nonsynonymous substitution rates between all lineages of sauropsids, we used the relative-rate test with human genes as the outgroup. We show that 22/28 nuclear coding genes of squamates, especially snakes (15/16), have an higher evolutionary rate than those in chicken (in mean, 30-40% faster). However, no such difference is detected between crocodiles, turtles and chicken. Higher substitution rate in squamates nuclear coding genes than in chicken, and probably than in other sauropsids, could explain some of the difficulties in resolving the molecular phylogeny of reptiles.
Patients' concerns about reporting pain and using analgesics have been cited as major contributors to the problem of inadequate pain management. The purpose of this paper is to describe a program of research in which we have focused on these patient concerns, or as we refer to them, "patient-related barriers to pain management." We present a summary of descriptive studies on this topic, describe educational interventions that have been tested, and suggest future avenues of research and practice.
Laboratory tests were carried out on larvae and adults of the cattle tick Boophilus microplus to determine the toxicity of macrocyclic lactone acaricides (MLs). Technical and commercial MLs were used in larval packet test (LPT), larval immersion test (LIT) and adult immersion test (AIT). In LIT and AIT the toxicity of MLs was much higher than for LPT. In the AIT, diluting the injectable formulation of MLs in water was as effective as dilution in ethanol+Triton X-100. LC50, LC99.9 and 95% confidence limits were determined so that a discriminating dose (DD) could be set for larval and adult tests in order to diagnose potential resistance to MLs in field samples of the tick. These DDs are for Australian strains of B. microplus and may not be suitable for other strains until further work is carried out. The value of these diagnostic tests can only be verified if or when resistance to MLs emerges in ticks.
Tomatoes are an excellent source of the carotenoid lycopene, a compound that is thought to be protective against prostate cancer. They also contain small amounts of flavonoids in their peel ( approximately 5-10 mg/kg fresh weight), mainly naringenin chalcone and the flavonol rutin, a quercetin glycoside. Flavonols are very potent antioxidants, and an increasing body of epidemiological data suggests that high flavonoid intake is correlated with a decreased risk for cardiovascular disease. We have upregulated flavonol biosynthesis in the tomato in order to generate fruit with increased antioxidant capacity and a wider range of potential health benefit properties. This involved transformation of tomato with the Petunia chi-a gene encoding chalcone isomerase. Resulting transgenic tomato lines produced an increase of up to 78 fold in fruit peel flavonols, mainly due to an accumulation of rutin. No gross phenotypical differences were observed between high-flavonol transgenic and control lines. The phenotype segregated with the transgene and demonstrated a stable inheritance pattern over four subsequent generations tested thus far. Whole-fruit flavonol levels in the best of these lines are similar to those found in onions, a crop with naturally high levels of flavonol compounds. Processing of high-flavonol tomatoes demonstrated that 65% of flavonols present in the fresh fruit were retained in the processed paste, supporting their potential as raw materials for tomato-based functional food products.
The safety and efficacy of adjusted continuous infusion (CI) of recombinant factor IX (FIX; BeneFix) was assessed in vitro and in a clinical study. BeneFix was reconstituted at 100 IU mL-1 with or without unfractionated heparin (4 U mL-1) and stored at either 4 degrees C or room temperature. Reconstituted BeneFix retained at least 90% activity over 14 days if stored at 4 degrees C but stability was reduced at room temperature. BeneFix reconstituted in a sterile pharmacy was free of bacterial contamination. Six patients with haemophilia B received seven CIs of BeneFix to cover routine surgery and severe bleeding episodes. The CIs lasted between 3 and 10 days. In all cases, haemostasis was excellent and the desired therapeutic FIX level was easily maintained. No thrombotic episodes or inhibitor development occurred but two patients developed thrombophlebitis at the infusion site when heparin was not added to the infusion. BeneFix is not currently licensed for CI and we suggest that studies to enable licensing should be established as soon as possible.
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An 18-year-old primigravida was admitted to hospital complaining of abdominal pain and vomiting. An ultrasound examination suggested the diagnosis of advanced abdominal pregnancy and this was confirmed using magnetic resonance imaging. Two days later she underwent operative delivery of a live fetus. The placenta was left in situ as it was attached to a large number of pelvic structures. Such surgery can result in maternal death due to massive haemorrhage as there is no mechanism to stem blood loss from the placental bed. Death can also occur in the post-partum period from septic complications if the placenta is left in situ. The management of such patients requires personnel and equipment to deal with massive and rapid haemorrhage; aortic cross clamping may be required to control bleeding. In this case, surgery and recovery were uneventful.
We assessed the safety of insulin lispro in gestational, type 1 and type 2 diabetes mellitus, analysing 635 pregnancies over a period of 7 years. We also evaluated patient satisfaction, sending an internationally-accepted anonymous diabetes treatment satisfaction questionnaire to 22 patients (three type 1, 19 gestational diabetes) who received regular and lispro insulin in successive pregnancies. The success rate of pregnancies in women with gestational diabetes managed with diet alone (n=325) was 99.3%. All 213 pregnancies in women with gestational diabetes requiring insulin were successful. There was no difference in maternal or fetal outcomes whether patients used regular insulin (n=138) or insulin lispro (n=75), but pre-delivery HbA1c was lower with insulin lispro (p<0.05). Pregnancy loss in patients with pre-gestational diabetes (89 pregnancies in type 1 and eight in type 2 diabetes) was 18.6% for insulin and 3.7% for insulin lispro (p=0.10). The incidences of congenital anomalies with regular insulin were 7.9% and 15.8% in gestational and pre-gestational diabetes, respectively; the figures for insulin lispro were 6.6% (p=0.79) and 3.8% ( p=0.16), respectively. Nineteen of the 22 surveyed patients completed the questionnaire. Satisfaction was higher with insulin lispro (26.3+/-2.3 vs. 18+/-8.9, p=0.0005). We found no increase in adverse outcome using lispro insulin in diabetic pregnancies, in either gestational or pre-gestational diabetes. Patient satisfaction favoured insulin lispro. Several patients with type 1 diabetes who used regular insulin during pregnancy, chose lispro after delivery, but all who used lispro in pregnancy preferred to continue.
OBJECTIVE: To examine the degree to which physicians and nurses use their first postnatal contact with mothers and babies to learn about their psychosocial strengths and problems. METHOD: Forty-two consecutively born infants and their mothers were observed during their initial postnatal visit with a public health nurse and their physician in Montreal. Both visits were audiotaped. Tapes were analyzed for the number of physical and psychosocial topics discussed during the visits. Observers also rated the professionals' communication skills. During a later home visit, mothers were given the Edinburgh Postnatal Depression Scale, the Symptom Checklist-90-Revised, and the Working Model of the Child Interview (WMCI). RESULTS: Nurses spent more time with families, discussed more psychosocial issues, and were rated to be more sensitive interviewers than physicians. They were also concerned about the psychological well-being and psychological difficulties of more mothers than were the physicians. In contrast, physicians were more sensitive to pregnancy complications in younger mothers. Mothers' satisfaction correlated with the number of psychosocial issues discussed by both professional groups. WMCI data suggest that recent non-Western immigrants are overrepresented among insecurely attached mothers. CONCLUSIONS: Nurses and physicians obtain different data from the same patients and should increase their collaboration.
The presence of additional hox clusters in the zebrafish has led to the hypothesis that there was a whole genome duplication at the origin of modern fish. To investigate the generality of this assumption, we analyzed all available actinopterygian fish gene families, and sequenced nuclear receptors from diverse teleost fish. The origin and timing of duplications was systematically determined by phylogenetic analysis. More genes are indeed found in zebrafish than in mouse. This abundance is shared by all major groups of euteleost fish, but not by eels. Phylogenetic analysis shows that it may result from frequent independent duplications, rather than from an ancestral genome duplication. We predict two zebrafish paralogs for most mouse or human genes, thus expressing a note of caution in functional comparison of fish and mammalian genomes. Redundancy appears to be the rule in fish developmental genetics. Finally, our results imply that the outcome of genome projects cannot be extrapolated easily between fish species.
The object of this study was to measure knowledge in a rural Hispanic community about the adverse health effects of smoking and to compare knowledge between current smokers and nonsmokers. A survey was administered to waiting room patients (n =137) over 16 years old at three predominantly Hispanic rural community health centers in the central San Joaquin Valley of California. Proportions of respondents who believed that smoking caused a specific consequence were calculated and compared between smokers and nonsmokers by chi-square tests. Likelihood of attributing negative health consequences to smoking was determined and compared between smokers and nonsmokers. A majority of all participants (smokers and nonsmokers) knew that smoking causes lung cancer (93 percent) and emphysema (91 percent). Many fewer participants knew that smoking contributes to problems such as osteoporosis (39 percent) or sexual dysfunction (33 percent). Current smokers were less likely than nonsmokers (P=0.01) to say that smoking causes any adverse health outcome, including those not known to be related to smoking. Although this is a culturally, ethnically and geographically unique group, knowledge of smoking risks among smoking and nonsmoking rural Hispanics is similar to that found in the general population. When compared with nonsmokers, current smokers underestimate the risk that smoking poses to health.