Biomedical subjects
J Watkins
Publications and source records attributed to J Watkins.
Acidogenecy of herbal baby drinks.
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Prevalence of coagulation abnormalities associated with intrauterine fetal death.
PURPOSE: The purpose of this study was to determine factors associated with abnormal coagulation in the setting of intrauterine fetal death (IUFD). METHODS: We reviewed the charts of 238 patients diagnosed with IUFD over ten years. Data included demographics, co-existing obstetric disease and coagulation studies. A coagulation score was assigned based on the platelet count, prothrombin time, activated partial thromboplastin time and plasma fibrinogen concentration. Approximately 90% of the study population had coagulation scores < 4. A score of > or = 4 was considered abnormal. RESULTS: Complete coagulation analysis was available in 183/238 patients (77%) within 24 hr of delivery. One hundred and sixty-four of these (89.6%) had a coagulation score, < 4 and 19 had a score > or = 4 (10.4%). No relationship between the coagulation score and age, parity, gestational age at delivery, and number of days the dead fetus remained in utero was found. A coagulation score > = or 4 was associated with the presence of a pregnancy-related disease (P < 0.05), notably abruption (P < 0.001) and uterine perforation (P < 0.05). Four patients without co-existing disease (3.2%), had a coagulation score > or = 4. CONCLUSION: In most pregnancies complicated by fetal demise, the fetus and placenta are delivered within one week of fetal demise. The previously reported severe coagulation disturbances are largely eliminated by early delivery. Our study shows that coagulation abnormalities occur in some patients with uncomplicated IUFDs (3.2%) and that this number rises in the presence of abruption or uterine perforation.
The role of the therapeutic alliance in psychotherapy and pharmacotherapy outcome: findings in the National Institute of Mental Health Treatment of Depression Collaborative Research Program.
The relationship between therapeutic alliance and treatment outcome was examined for depressed outpatients who received interpersonal psychotherapy, cognitive-behavior therapy, imipramine with clinical management, or placebo with clinical management. Clinical raters scored videotapes of early, middle, and late therapy sessions for 225 cases (619 sessions). Outcome was assessed from patients' and clinical evaluators' perspectives and from depressive symptomatology. Therapeutic alliance was found to have a significant effect on clinical outcome for both psychotherapies and for active and placebo pharmacotherapy. Ratings of patient contribution to the alliance were significantly related to treatment outcome; ratings of therapist contribution to the alliance and outcome were not significantly linked. These results indicate that the therapeutic alliance is a common factor with significant influence on outcome.
Th1/Th2 cell dichotomy in acquired immunity to Bordetella pertussis: variables in the in vivo priming and in vitro cytokine detection techniques affect the classification of T-cell subsets as Th1, Th2 or Th0.
In studies of the mechanism of immunity to Bordetella pertussis in a murine respiratory infection model, we have previously demonstrated that natural infection of immunization with a whole cell vaccine induces a potent protective immune response, which is mediated by T-helper type-1 (Th1) cells. In contrast an acellular vaccine generates Th2 cells and is associated with delayed bacterial clearance following respiratory challenge. In the present study we have investigated the apparent Th1/Th2 cell dichotomy in acquired immunity and have examined the factors that affect their induction or detection. The cytokine profiles of B. pertussis-specific T cells in immune animals were determined using antigen-stimulated ex vivo spleen cells or CD4+ T-cell lines and clones established in the presence of interleukin-2 (IL-2) or IL-4. Antigen-specific T cells derived from mice immunized with the acellular vaccine were almost exclusively of the Th2 cell type. In contrast, T-cell lines and clones established following respiratory infection or immunization with the whole cell vaccine were predominantly of the Th1 type. However, a proportion of T cells from convalescent mice, especially when cultured in the presence of IL-4, secreted IL-4 and IL-5 with or without detectable IL-2 and interferon-gamma (IFN-gamma), suggesting that Th0 or Th2 cells were also primed during natural infection in vivo. Furthermore, when mice were assessed 6 months after infection, spleen cells produced significant levels of IL-4 and IL-5, which were not evident at 6 weeks. The route of immunization and the genetic background of the mice were also found to influence the preferential priming of Th1 cells, and this was directly related to the level of protection against respiratory or intracerebral (i.c.) challenge. Our findings underline the critical role of CD4+ Th1 cells in immunity to B. pertussis, but also demonstrate that a number of factors in the in vivo priming and in vitro restimulation can skew the apparent dominance of one Th cell type over another.
Pulsed wave Doppler measurement of cardiac output from the right ventricular outflow tract.
Doppler ultrasound can be used to measure cardiac output (CO). Intraoperative Doppler cardiac output (DCO) by transesophageal echocardiography (TEE) has been studied using blood flow velocity from the left ventricular outflow tract (LVOT), the mitral valve (MV), and the main pulmonary artery (MPA). The purpose of this study was to compare DCO, measured from a relatively new TEE view of the right ventricular outflow tract (RVOT), with thermodilution cardiac output (TDCO). We also compared changes in DCO from the RVOT to changes in TDCO. A 5.0/3.7 MHz multiplane TEE probe was placed in 45 adult cardiac surgical patients undergoing general anesthesia. Patients were excluded if there was greater than mild tricuspid valve insufficiency. From the transgastric view, at approximately 110-140 degrees, the RVOT was imaged. DCO was calculated from 1) the time-velocity integral (TVI) using pulse wave (PW) Doppler, 2) the area of the RVOT (measured in early systole using the diameter (pi(D/2)2) of the RVOT at the level of the PW Doppler sample volume), and 3) the heart rate. Simultaneous TDCO was performed by a separate examiner. The RVOT was imaged satisfactorily in 84% of patients (38/45). The mean bias between DCO and TDCO was -0.01 L/min (2 SD +/- 0.45 L/min; n = 38). There was good correlation between DCO and TDCO (R2 = 0.97). Changes in TDCO and changes in DCO were compared in 15 patients. The mean bias between changes in DCO and changes in TDCO was 0.04 L/min (2 SD +/- 0.66 L/min). Analysis of the changes in DCO and TDCO showed good correlation (R2 = 0.96). We conclude that there is a good correlation between DCO measured from the RVOT and TDCO. This technique permits cardiac output measurement without the necessity of placing a pulmonary artery catheter, and it also provides a method of evaluating RVOT blood flow.
Sports injuries in children and adolescents treated at a sports injury clinic.
This study presents the results of a three-year (1989-1991) retrospective survey of sports injuries to children and adolescents (5-17 years of age) treated at a sports injuries clinic (Crystal Palace, London). Of the total of 394 injuries, 178 (45.2%) were to females and 216 (54.8%) were to males. In both females and males the frequency of injuries showed a unimodal relationship with increasing age; the peak frequency in females occurred at age 13-14 years and in males at age 15-16 years. Fifty per cent of the injuries (197) were acute, 49.5% (195) were chronic and 0.5% (2) were inconclusive in diagnosis. Most of the acute injuries were muscle/tendon/ligament sprains, strains or contusions (62%) whereas most of the chronic injuries affected articular cartilage, epiphyseal and apophyseal growth plates (53%). Injuries to knees and ankles accounted for 51% of all injuries. The sports responsible for most injuries were characterised by i) explosive and/or high speed movements and/or ii) physical contact with apparatus, equipment or other players.
Medical students in general practice: how do patients feel?
BACKGROUND: The General Medical Council has recommended that medical students should gain more experience in general practice. AIM: The study set out to determine patients' reactions to the presence of medical students in general practice consultations. METHOD: Patients attending a random sample of general practice surgeries completed a questionnaire following consultation with and without a medical student present in six general practices in the Oxford area. RESULTS: The questionnaires were completed by 278 patients. Only eight (3%) of all respondents had negative responses to the presence of a medical student. Of those completing questionnaires following a teaching consultation, 107 (56%) felt positively about the presence of students, compared with 36 (41%) who had attended a nonteaching surgery. Only three patients (1%) felt the quality of the consultation to be impaired by the presence of a student, while 48 patients (17%) felt there to be some improvement. The majority felt that the sex of the student was unimportant, but significantly more female than male patients (17% versus 5%) felt that it made a difference. CONCLUSION: Only a small proportion of patients object to the presence of a medical student in general practice consultations. A significant minority said that the presence of a student improves the consultation.
Decreased platelet function in aortic valve stenosis: high shear platelet activation then inactivation.
OBJECTIVE: To elucidate the mechanism of the bleeding tendency observed in patients with aortic valve stenosis. DESIGN: A prospective study of high and low shear platelet function tests in vitro in normal controls compared with that in patients with severe aortic valve stenosis with a mean (SD) systolic gradient by Doppler of 75 (18) mm Hg before and at least 4 months after aortic valve replacement. SETTING: District general hospital. RESULTS: The patients showed reduced retention in the high shear platelet function tests. (a) Platelet retention in the filter test was 53.6 (12.6)% in patients with aortic valve stenosis and 84.8 (9.6)% in the controls (P < 0.001). (b) Retention in the glass bead column test was 49.8 (19.2) in the patients and 87.4 (8.7) in the controls (P < 0.001). (c) The standard bleeding time was longer in the patients (P < 0.06). Results of the high shear tests (a, b, and c) after aortic valve replacement were within the normal range. The platelet count was low but within the normal range before surgery and increased postoperatively (P < 0.01). There were no differences in the results of standard clotting tests, plasma and intraplatelet von Willebrand's factor, or in 15 platelet aggregation tests using five agonists between patients with aortic valve stenosis and controls. CONCLUSIONS: The high shear haemodynamics of aortic valve stenosis modify platelet function in vivo predisposing to a bleeding tendency. This abnormality of platelet function is detectable only in vitro using high shear tests. The abnormal function is reversed by aortic valve replacement. High shear forces in vitro activate and then inactivate platelets. By the same mechanisms aortic valve stenosis seems to lead to high shear damage in vivo, resulting in a clinically important bleeding tendency in some patients.
Reactions to gelatin plasma expanders.
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Antagonism of presynaptically mediated depressant responses and cyclic AMP-coupled metabotropic glutamate receptors.
The depression of monosynaptic excitation of neonatal rat motoneurones by (1S,3S)- and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate (ACPD) and by L-2-amino-4-phosphonobutyrate (L-AP4), which is probably presynaptically mediated, is antagonized by (+/-)- and (+)-alpha-methyl-4-carboxyphenylglycine (MCPG). The same phenylglycine derivatives also antagonize the depression of forskolin-stimulated cyclic AMP synthesis effected by the two ACPD stereoisomers and by L-AP4. These results support previous suggestions that presynaptic depression is mediated by metabotropic glutamate receptors negatively coupled to adenylyl cyclase activity. MCPG is the first antagonist to be reported for these receptors.
Combination of DTP and Haemophilus influenzae type b conjugate vaccines can affect laboratory evaluation of potency and immunogenicity.
A commonly used Diphtheria-Tetanus-Pertussis (whole-cell) vaccine was combined with each of three different Haemophilus influenzae type b (Hib) capsular polysaccharide vaccines. Each Hib vaccine incorporated one of three different protein conjugates: tetanus toxoid, diphtheria CRM197 toxoid or group B Neisseria meningitidis outer membrane vesicles. The effects of these combinations on the subsequent laboratory control testing were examined. The addition of the Hib vaccines had no significant effect on the reactogenicity or the potency of the whole-cell pertussis component. The potency of, and antibody responses to, the diphtheria component were also unaffected in all three combinations. However, combination with the Hib vaccine comprising polysaccharide conjugated to tetanus toxoid had dramatic effects on tetanus potency and immunogenicity when assayed in mice. This combination resulted in a five-fold potentiation of the tetanus potency and a similarly large increase in the antibody responses to tetanus toxin and toxoid. The level of the antibody response to the Hib polysaccharide in this vaccine was also elevated, more than 20-fold, as a result of the combination. Such phenomena were not evident with combinations involving the other two Hib vaccines. These results have implications for the control testing of combined vaccines containing a whole-cell pertussis component and Hib polysaccharide-tetanus protein conjugate vaccine.
Phenylglycine derivatives as antagonists of metabotropic glutamate receptors.
Metabotropic glutamate receptors represent a family of G protein-coupled receptors that can be activated by L-glutamate, the principal excitatory neurotransmitter in the brain. Until recently, progress in identifying the physiological and pathological roles of metabotropic glutamate receptors has been hampered by the lack of selective antagonists. In this article, Jeff Watkins and Graham Collingridge describe the pharmacology of, and initial physiological studies using, certain phenylglycine derivatives and related substances--the first definitive antagonists of metabotropic glutamate receptors.
Interaction of Haemophilus influenzae type b conjugate vaccines with diphtheria-tetanus-pertussis vaccine in control tests.
The effects of combining three Haemophilus influenzae type b (Hib) capsular polysaccharide vaccines, conjugated to different proteins, with DTP vaccine on the subsequent control testing were examined. The addition of the Hib vaccines had little effect on the reactogenicity or the potency of the whole-cell pertussis component. The potency of, and antibody responses to, the diphtheria component were also unaffected in all three combinations. However, combination with the Hib vaccine comprising polysaccharide conjugated to tetanus toxoid resulted in a fivefold potentiation of the tetanus potency and large increases in the antibody responses to tetanus toxin and toxoid and Hib polysaccharide. These results have implications for the control testing of combined vaccines containing a whole-cell pertussis component and Hib polysaccharide-tetanus protein conjugate vaccine.
Adverse reaction to neuromuscular blockers: frequency, investigation, and epidemiology.
A survey is presented of neuromuscular drug involvement in 390 clinically severe anaphylactoid reactions (grades II-IV reported to a Sheffield laboratory from 1988 to the end of 1992 from hospitals throughout the UK. Despite advances in patient monitoring and newer drugs, the reporting frequency and individual drug involvement were remarkably similar to those of a previous report from the laboratory in 1988. The highly immunogenic drug suxamethonium still predominated (48% of reports), but there was now much reduced use of the similarly immunogenic drug, alcuronium. The incidence of reactions to vecuronium and atracurium remained similar (12% and 18% reports, respectively) and acceptable to the anaesthetist. However, in choosing drugs for individual patients, the anaesthetist may wish to note that vecuronium reactors mainly showed bronchospasm, and atracurium reactors hypotension. By a systematic laboratory investigation, based on measurement of plasma tryptase and urinary methylhistamine, reaction mechanisms were assessed in 53 reactions. Despite their overall clinical similarity, analysis revealed that only one reaction in three was likely to be due to IgE-mediated anaphylaxis (Type 1). Not only was suxamethonium the most frequently reported drug, but in this study 11 reactions were identified as Type 1 response: no allergic reactions were identified for either vecuronium or atracurium, although single cases were identified for alcuronium, gallamine, and tubocurarine, with two unidentified. The remaining reactions were judged to be non-immune, although most involved mast cell degranulation. These reactions were no less hazardous than Type 1 reactions (one death), and two deaths were recorded. The importance of laboratory investigation as a feature of postreaction care is emphasized.
Yeast open reading frame YCR14C encodes a DNA beta-polymerase-like enzyme.
We have shown by activity gel that overexpression in E. coli of a yeast chromosome 3 open reading frame (ORF) designated YCR14C and bearing homology to mammalian DNA polymerases beta results in a new DNA polymerase in the host cells. The molecular mass of this enzyme corresponded to the YCR14C-predicted 67 kDa protein, and NH2-terminal amino acid sequencing confirmed that the expressed protein was encoded by the yeast ORF. This new yeast DNA polymerase was purified to homogeneity from E.coli. In a fashion similar to that of mammalian beta-polymerases, the purified yeast enzyme exhibited distributive DNA synthesis on DNA substrate with a single-stranded template and processive gap-filling synthesis on a short-gapped DNA substrate. Activity of this yeast beta-polymerase-like enzyme was sensitive to the beta-polymerase inhibitor ddNTP and resistant to both 1 mM NEM and neutralizing antibody to E. coli DNA polymerase I. These results, therefore, indicate that YCR14C encodes a DNA beta-polymerase-like enzyme in yeast, and we name it DNA polymerase IV. Yeast strains harboring a deletion mutation of the pol IV gene are viable, they exhibit no increase in sensitivity to ultraviolet light, ionizing radiation or alkylating agents, and sporulation and spore viability are not affected in the mutant.
Drugs responsible for anaphylactoid reactions in anaesthesia in the United Kingdom.
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Improved diagnosis of anaphylactoid reactions by measurement of serum tryptase and urinary methylhistamine.
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