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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 433 records · Page 24Linked to original sources

Right fetal cardiac axis: clinical significance and associated findings.

OBJECTIVE: To ascertain the clinical significance of right fetal cardiac axis. METHODS: Fetal cardiac axis was assessed prospectively in ultrasound examinations of 16,562 fetuses over a 6-year period. RESULTS: Twenty-two fetuses had a right cardiac axis. When classified by ventricular and atrial configuration, six fetuses had mirror-image hearts with situs inversus, 12 had rotation of the heart axis alone, and four had inversion of the ventricles. Fourteen of the 22 had underlying structural cardiac defects, most of which were atrioventricular septal defects, double outlet right ventricles, or common atria. The chromosomes and/or phenotypes of all 22 were normal. All four fetuses with polysplenia and asplenia died. Major extracardiac defects were few (two) but lethal. CONCLUSION: Right cardiac axis in the fetus is associated with a high incidence of structural cardiac defects. In the absence of severe extracardiac defects, polysplenia, or asplenia, neonatal outcome was good.

Dextrocardia↗

Alterations in the hypothalamic pituitary adrenal axis during pregnancy and the placental clock that determines the length of parturition.

Although corticotrophin releasing hormone (CRH) was initially identified as a hypothalamic peptide it is also synthesised in the placenta and secreted into both the maternal and fetal circulation. The presence of large molecular weight forms in the placenta suggest that secretion may be constitutive rather that regulated. Placental CRH is bioactive but causes only modest increases in ACTH and cortisol in the pregnant woman because of agonist induced desensitisation of pituitary CRH receptors. CRH concentrations increase exponentially in maternal plasma as gestation advances. Elevated concentrations, compared with gestational age matched controls, occur in patients in preterm labour. The exponential curve describing the CRH increase is shifted to the left in women who will subsequently deliver preterm and to the right in women who will deliver post dates indicating that CRH is linked to a placental clock which determines the length of gestation. Maternal plasma CRH concentrations may be useful in identifying women at high risk of preterm delivery and CRH antagonists may prevent preterm labour. As significant CRH production by the placenta is restricted to primates future research must take into account the species specificity of the mechanisms regulating parturition.

Biological Clocks↗

Cytophagic histiocytic panniculitis--a syndrome associated with benign and malignant panniculitis: case comparison and review of the literature.

Many cases of hemophagocytic syndromes with cytophagic histiocytic panniculitis (CHP) are being classified and considered as a natural disease progression of subcutaneous panniculitic T-cell lymphoma (SPTL). Review of the literature on both CHP and SPTL discloses distinct patterns suggesting these disorders may not be equivalent, even though a terminal hemophagocytic syndrome may be associated with each. Some SPTL appear to have association with Epstein-Barr virus (EBV), show malignant histopathology in the skin, and may disseminate terminally, with a majority of cases showing a rapidly fatal progression. On the other hand, classic cases of CHP without proven lymphoma may not be associated with EBV, appear to be histologically benign, and have an indolent course unless terminal hemophagocytic syndrome develops. We compared and contrasted a case of CHP and a case of SPTL and reviewed the literature. Our observations suggest that the often fatal hemophagocytic syndrome may be associated with both benign and malignant subcutaneous panniculitis.

Adult↗

The psychiatric clinical nurse specialist/nurse practitioner: an example of a combined role.

The purpose of this article is to provide an historical overview of the clinical nurse specialist and nurse practitioner roles in psychiatric nursing. This article is written as a follow-up to that of Dyer, Hammill, Regan-Kubinski, Yurick, & Kobert, (1997), Archives of Psychiatric Nursing, 11, 2-11, in which a new paradigm for delivering comprehensive mental and general health services is conceptualized, i.e., the psychiatric-primary care nurse practitioner role. In this article an alternative model is presented: the psychiatric clinical nurse specialist/nurse practitioner role. Similarities and differences in the two roles are discussed.

Curriculum↗

17 alpha-hydroxylase/17,20-lyase dysregulation is not caused by mutations in the coding regions of CYP17.

STUDY OBJECTIVE: To determine whether mutations occur in the 17 alpha-hydroxylase/17,20-lyase (CYP17) gene in patients with mild hyperandrogenism. DESIGN: Clinical and molecular genetic study. SETTING: Pediatric endocrine outpatient clinic in an academic research environment. PARTICIPANTS: Girls (n = 11) referred for evaluation of premature pubic hair and adolescent girls (n = 16) referred for evaluation of hirsutism and/or oligomenorrhea. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Mutation detection analysis of the coding regions and intron/exon boundary regions of the CYP17 gene. RESULTS: Two polymorphic nucleotides were identified in the CYP17 gene. No mutations were detected in the 27 subjects. CONCLUSIONS: Mutation detection studies presented herein exclude CYP17 as a candidate gene for premature pubic hair and adolescent hyperandrogenism.

Adolescent↗

Extracapsular cataract extraction to phacoemulsification: why and how?

PURPOSE: To determine what factors influence a decision to move from extracapsular cataract extraction to phacoemulsification as the cataract removal technique of first choice, and to investigate how the transition is managed. METHOD: Questionnaire surveys were carried out in 1996 and 1997 of consultant ophthalmologists in the former Oxford Region. RESULT: 'Evidence of clinical benefit' was the strongest factor influencing a decision to change technique, but 'fear of becoming a dinosaur' and 'peer pressure' were also important factors. Beliefs about advantages of phacoemulsification were little changed with increasing experience, but personal contraindications to phacoemulsification diminished with time. Hard nuclei, mature cataracts and poor zonular support remained relatively strong contraindications to phacoemulsification by the second survey. Only 46% of 14 respondents had performed phacoemulsification under supervision before 'going solo', but 64% felt well or adequately prepared for their first solo phacoemulsification. Influence of non-clinical factors such as equipment availability on the choice of technique did not diminish significantly between surveys. Increasing experience of phacoemulsification appeared to reinforce beliefs about its advantages. CONCLUSIONS: Respondents appear to have adopted phacoemulsification with careful preparation, and enthusiasm for the technique has been reinforced by increasing experience. Courses and wet-labs provide limited preparatory experience, but peer supervision is difficult to arrange for consultants. Respondents generally felt that learning phacoemulsification had been stressful, but not as difficult as feared. Implications for the introduction of new surgical techniques into ophthalmological practice in the future are discussed.

Cataract Extraction↗

Analysis of the value of empiric vancomycin administration in febrile neutropenia occurring after autologous peripheral blood stem cell transplants.

We conducted a retrospective review of 125 patients undergoing high-dose therapy and stem cell rescue in order to evaluate the incidence of documented infection and the utility of the administration of vancomycin empirically. All patients received prophylactic oral quinolone therapy. Because neutropenia in this setting is relatively brief, 21 patients never manifested fever, and no patient died of infection. Of the remaining 104 patients, positive blood cultures were obtained in only 10, nine with a gram stain positive and one with a gram stain negative organism. Sixty-two patients without any evidence of gram positive infection received vancomycin according to the existing algorithm for care of neutropenic fevers. In this population of patients, empiric administration of vancomycin for neutropenic fevers without culture documentation appears to be unnecessary, could be discontinued safely and at substantial cost savings, and might slow the appearance of vancomycin-resistant organisms.

Adult↗

A case-control study of true-positive versus false-negative cervical smears in women with cervical intraepithelial neoplasia (CIN) III.

Cervical smears (n = 150) from five departments showing high-grade dyskaryosis were examined by three cytologists. All the smears came from patients with biopsy-proven CIN III. One hundred had been correctly reported (true positives) but 50 had originally been reported as negative and had been found to be positive only on review (false negatives). There were significant differences between the two sets in the characteristics of the dyskaryotic cell population. The false-negative smears tended to have fewer than 200 dyskaryotic cells. The nuclei of the dyskaryotic cells tended to have fine rather than coarse nuclear chromatin. A smear with fewer than 50 dyskaryotic cells is 26 times more likely to be reported as negative than one with more than 200 dyskaryotic cells. The results suggest that there is a type of severely dyskaryotic smear that is inherently likely to be missed on routine screening.

Case-Control Studies↗

Melanocortin 1 receptor variants in an Irish population.

The identification of an association between variants in the human melanocortin 1 receptor (MC1R) gene and red hair and fair skin, as well as the relation between variants of this gene and coat color in animals, suggests that the MC1R is an integral control point in the normal pigmentation phenotype. In order to further define the contribution of MC1R variants to pigmentation in a normal population, we have looked for alterations in this gene in series of individuals from a general Irish population, in whom there is a preponderance of individuals with fair skin type. Seventy-five per cent contained a variant in the MC1R gene, with 30% containing two variants. The Arg151Cys, Arg160Trp, and Asp294His variants were significantly associated with red hair (p = 0.0015, p < 0.001, and p < 0.005, respectively). Importantly, no individuals harboring two of these three variants did not have red hair, although some red-haired individuals only showed one alteration. The same three variants were also over-represented in individuals with light skin type as assessed using a modified Fitzpatrick scale. Despite these associations many subjects with dark hair/darker skin type harbored MC1R variants, but there was no evidence of any particular association of variants with the darker phenotype. The Asp294His variant was similarly associated with red hair in a Dutch population, but was infrequent in red-headed subjects from Sweden. The Asp294His variant was also significantly associated with nonmelanoma skin cancer in a U.K. population. The results show that the Arg151Cys, Arg160Trp, and Asp294His variants are of key significance in determining the pigmentary phenotype and response to ultraviolet radiation, and suggest that in many cases the red-haired component and in some cases fair skin type are inherited as a Mendelian recessive.

Adult↗

Impact of migraine on the family.

The extensive literature on pain and the family contains little on migraine and the family. A national sample of migraine sufferers, interviewed by telephone, was questioned on how they perceived migraine affected their family life. Sixty percent believed that their families were significantly affected. Most stated that their families were understanding. but a considerable number reported that family members took a negative attitude. This was particularly so with younger children deprived of parental care during migraine attacks. Spousal relationships also suffered. Frequency and quality of sexual relationships were affected; and in a small number of cases divorce was the outcome. The significance of these findings in migraine management is discussed.

Adolescent↗

Osteoporosis during pregnancy and its management.

Osteoporosis leading to fracture can occur during pregnancy. Bone density may be low before pregnancy due to recognised causes such as coeliac disease, osteogenesis imperfecta and previous anorexia nervosa (secondary osteoporosis). In some patients there is no identifiable cause. This condition is referred to as "pregnancy associated or pregnancy related osteoporosis"; it is not known whether pregnancy causes the osteoporosis or merely coincides with it. Typically the loss of bone leads to vertebral fracture with loss of height or pain in the hips also sometimes with fracture. Symptoms most often begin in the third trimester of the first pregnancy and improve after delivery; they do not usually recur in subsequent pregnancies. The cause is unknown and there is no specific treatment; follow up bone density measurements show that the osteoporosis slowly improves post partum. Recent research in non osteoporotic women shows that breast feeding maintains a low bone density; it is therefore contraindicated in pregnancy associated osteoporosis.

Adult↗

A novel method for selection of chymotrypsin inhibitors from a phage peptide library.

A novel screening strategy has been developed for the identification of alpha-chymotrypsin inhibitors from a phage peptide library. In this strategy, the standard affinity selection protocol was modified by adding a proteolytic cleavage period to avoid recovery of alpha-chymotrypsin substrates. After four cycles of selection and further activity assay, a group of related peptides were identified by DNA sequencing. These peptides share a consensus sequence motif as (S/T)RVPR(R/H). Then, a corresponding short peptide (Ac-ASRVPRRG-NH2) was synthesized chemically and proved to be an inhibitor of alpha-chymotrypsin. The present work provides a useful way for searching proteinase inhibitors without detailed knowledge of the molecular structure.

Bacteriophages↗

Trophoblast IFN-tau differentially induces lymphopenia and neutropenia in lambs.

Type I interferons (IFN), including IFN-alpha and IFN-beta, cause severe lymphopenia, resulting from altered lymphocyte recirculation and redistribution. IFN-tau, a product of trophectoderm of ruminant conceptuses and new member of the type I IFN family has not been examined for its effect on leukocyte recirculation. Additionally, differential effects of type I IFNs on the redistribution and recirculation of subsets of T cells have not been reported. The present study determined the effects of IFN-tau on the redistribution and recirculation of ovine leukocytes and T cell subsets. Total peripheral blood leukocytes, lymphocytes, and segmented neutrophils were reduced (p < 0.05) following treatment of lambs with IFN-tau. Furthermore, administration of IFN-tau caused an acute, differential reduction in peripheral blood CD4+ T cells (p < 0.05), CD5+ cells (p < 0.05), and gammadelta TCR+ (p < 0.01) T cells but had no effect on CD8+ T cells (p > 0.05). IFN-tau reduced the percentage of gammadelta T cells by 8-fold and that of CD4+ T cells and CD5+ cells by <2-fold in peripheral blood when compared with control lambs. The reduction in leukocytes, lymphocytes, and neutrophils was observed as early as 6-12 h after administration of IFN-tau, but levels returned to control values within 48 h. These results indicate that IFN-tau, like other members of the type I IFN family, can have immediate effects on leukocyte recirculation and redistribution. The present study is the first to demonstrate that IFN-tau differentially regulates T cell recirculation with the greatest effect on gammadelta TcR+ T cells.

Analysis of Variance↗

A randomized trial of two doses of cyclophosphamide with etoposide and G-CSF for mobilization of peripheral blood stem cells in 318 patients with stage II-III breast cancer.

The purpose of this study was to develop a less toxic outpatient chemotherapy regimen for mobilizing peripheral blood stem cells (PBSC). Three hundred eighteen patients with newly diagnosed stage II-III breast cancer who had received conventional dose adjuvant chemotherapy were randomized to receive intermediate-dose cyclophosphamide (2 g/m2), etoposide (600 mg/m2), and granulocyte colony-stimulating factor (G-CSF) 6 micrograms/kg/day (ID-Cy, n = 162) or high-dose cyclophosphamide (4 g/m2) and the same doses of etoposide and G-CSF (HD-Cy, n = 156) followed by collection of PBSC. Three hundred seventeen of 318 patients had apheresis performed, and 315 received high-dose chemotherapy (HDC) followed by PBSC support. The median numbers of CD34+ cells collected in a median of two apheresis following ID-Cy and HD-Cy were 19.9 and 22.2 x 10(6)/kg, respectively (p = 0.04). The fractions of patients achieving CD34+ cell doses > or = 2.5 or > or = 5.0 x 10(6)/kg were not different between the two regimens. More patients receiving HD-Cy had grade 3-4 nausea (p = 0.001), vomiting (p = 0.03), and mucositis (p = 0.04). The fractions of patients having a neutrophil nadir < 0.5 x 10(9)/L following ID-Cy and HD-Cy were 0.83 and 0.95, respectively (p = < 0.001). The fractions of patients having a platelet nadir < 25 x 10(9)/L following ID-Cy and HD-Cy were 0.13 and 0.51, respectively (p = < 0.001). More patients in the HD-Cy group received platelet (p < 0.001) and red blood cell (p < 0.001) transfusions and were admitted to the hospital more frequently (p = 0.03) than patients receiving ID-Cy. Three hundred fifteen patients received HDC followed by infusion of PBSC. There were no significant differences in the incidence of transplant-related death or early survival between patients receiving ID-Cy or HD-Cy followed by HDC. It was concluded that a regimen of Cy 2 g/m2 with etoposide and G-CSF was effective for mobilization of PBSC with low morbidity and resource utilization in patients with limited prior chemotherapy exposure.

Adult↗

Undetectable serum prostate-specific antigen associated with metastatic prostate cancer: a case report and review of the literature.

A 63-year-old man, who had undergone prostatectomy for prostate cancer that was positive for prostate-specific antigen (PSA) was examined and found to have metastatic disease, proven radiologically and pathologically, but with an undetectable PSA and highly elevated prostatic acid phosphatase (PAP). Prostatic acid phosphatase levels fell in response to chemotherapy but his clinical status continued to deteriorate. A review of the literature is presented and several possible explanations for PSA remaining undetectable in these situations are discussed. The authors conclude that although PSA can be used to monitor the majority of patients postprostatectomy, physicians may still need to rely on clinical suspicion, serum PAP, and bone scan for the detection of recurrent disease.

Acid Phosphatase↗

A randomised comparison of strategies for reducing infective complications of induced abortion.

OBJECTIVES: To determine lower genital tract carriage rates of C. trachomatis, N. gonorrhoeae and bacterial vaginosis among women seeking termination of pregnancy. To compare two clinical management strategies for minimising the risks of infective morbidity after induced abortion. DESIGN: Prevalence of infections was assessed by screening women undergoing abortion. Clinical management strategies were compared by a randomised trial. SETTING: The gynaecology departments of four hospitals in Scotland. PARTICIPANTS: 1672 women undergoing induced abortion. INTERVENTIONS: Women randomised to prophylaxis received metronidazole 1 g rectally before abortion plus doxycycline 100 mg twice daily for seven days. Women randomised to screen-and-treat received appropriate antibiotics only if screening proved positive for one or more infection. MAIN OUTCOME MEASURES: Prevalences of infections; morbidity in the eight weeks following abortion as assessed by reported symptoms, general practitioner consultation and prescription rates and hospital re-attendances; costs to the NHS of alternative managements. RESULTS: Prevalence rates: C. trachomatis 5.6%; N gonorrhoeae 0.19%; bacterial vaginosis 17.5%. Overall, women allocated to receive prophylaxis had lower rates of measures of short term infective morbidity than those allocated to screen-and-treat. These differences only reached statistical significance for women who were reported negative on screening. The direct costs to the NHS of prophylaxis and screen-and-treat were calculated to be 8.17 and 18.34 per woman, respectively. CONCLUSIONS: Prevalences of lower genital tract infections which have been implicated in increased rates of infective morbidity after abortion are similar to those reported elsewhere. Universal antibiotic prophylaxis is at least as effective as a policy of screen-and-treat in minimising the risk of short term infective morbidity and is far more cost efficient.

Abortion, Induced↗

FDG-PET and MRI in temporal lobe epilepsy: relationship to febrile seizures, hippocampal sclerosis and outcome.

OBJECTIVE: To correlate the volumetric head magnetic resonance imaging (MRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET) scan findings with the history, intracarotid amobarbital procedure, pathology, and outcome in patients with medically refractory temporal lobe epilepsy. MATERIAL AND METHODS: Thirty-eight patients with temporal lobe epilepsy treated surgically following a comprehensive presurgical evaluation. Follow-up ranged from 12 to 44 months. RESULTS: Volumetric MRI showed ipsilateral hippocampal atrophy in 29 (76%), and PET scan showed ipsilateral temporal hypometabolism (PET-TH) in 31 (81.5%) of patients. Eighty-three percent of those patients with hippocampal sclerosis on MRI (MRI-HS) had ipsilateral PET-TH. Sixty-six percent of patients with MRI-HS had a history of prolonged febrile convulsions or a childhood febrile illness accompanied by convulsions, and 77% of patients with MRI-HS had pathologically proven hippocampal sclerosis (HS). Ninety percent became seizure free or had rare seizures. CONCLUSION: FDG-PET scans and head MRIs were complementary; 95% of patients had either MRI-HS or temporal hypometabolism. MRI-HS correlated with a history of febrile seizures and pathologically demonstrated hippocampal sclerosis. Ninety-three percent of patients had focal functional deficits on the epileptogenic side. Concordance between PET temporal hypometabolism and MRI-HS correlated with better outcome.

Adolescent↗