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Biomedical subjects

J Newton

Publications and source records attributed to J Newton.

At least 19 recordsLinked to original sources

Communication between general practitioners and consultants: what should their letters contain?

OBJECTIVE: To canvass the views of all general practitioners and consultants working in Newcastle upon Tyne on the content of referral letters and replies, the feasibility of standardising certain aspects of referral letters, and the use of communications data for audit purposes. DESIGN: A postal questionnaire was sent to all general practitioners and consultants in Newcastle upon Tyne in May 1991. Questions were asked about the clinical and administrative content of letters, the utility of standard categories to state the reason for referral, the idea of using letters for feedback purposes, and communications as a potential topic for professionally led audit. SETTING: Area served by Newcastle upon Tyne Family Health Services Authority and District Health Authority. RESULTS: Replies were received from 274 (77%) doctors (115 general practitioners and 159 consultants). A majority (225; 82%) were in favour of items defined as "always important" forming a minimum requirement for referral letters and for consultants' replies. Using standardised categories to state the reason for referral was not endorsed: 102 (89%) general practitioners and 132 (83%) consultants preferred referrers to use their own words. Using referral communications to provide feedback was less popular with consultants (54; 34%) than general practitioners (72; 63%). Finally, a majority of doctors (179; 65%) were in favour of using written communications as a topic for professionally led audit. CONCLUSIONS: A high degree of consensus exists among clinicians about the content of referral communications. Although doctors may still reject the concept of standardised communications, they have unambiguously endorsed a standard for communication that they can aspire to, and they are prepared to use it as a yardstick for their actual performance.

Communication

A review of the effects of long-acting progestogen-only contraceptives on ovarian activity.

Progestogen-only contraception acts mainly by blocking cervical mucus and preventing sperm penetration through it does have a variable pattern of contraceptive effects on the endometrium and ovary. In contrast with the complete suppression of ovarian function with combined pill or injectable use, a variable degree of endocrine activity is demonstrated in women choosing a long-acting progestogen-only contraceptive. This degree of suppression of ovarian activity explains the decrease in systemic side-effects, the rapid resumption of ovulation and recovery of fertility following the discontinuation of the method. New delivery systems of progestogens, the vaginal ring and implant, offer better and more consistent contraceptive effects.

Cervix Mucus

Risk factors for melanoma: site variation in minimal erythema dose.

Skin types 1 and 2, increased numbers of moles, and excessive intermittent sun exposure are known risk factors for cutaneous melanoma, but the inter-relationship between UV radiation exposure, moles and melanoma remains unclear. There is a noteworthy site variation in melanoma, it being more common on the lower leg in women and on the back in men. In order to determine whether this site variation could provide further clues to the pathogenesis of melanoma, we examined site variation in photosensitivity and its relationship to other known melanoma risk factors (number of moles, skin type and skin colour) in 25 healthy volunteers. A marked site variation in photosensitivity was found. The pale skin of the volar aspect of the forearm was markedly less photosensitive than the darker skin of the back. Females were more photoresistant than males on the lower legs even though this is the more common site for melanoma in women. There was some correlation between the number of moles and photosensitivity at the two sites.

Adult

Pharmacology of the pyrroloimidazole, SK&F 105809--I. Inhibition of inflammatory cytokine production and of 5-lipoxygenase- and cyclooxygenase-mediated metabolism of arachidonic acid.

SK&F 105809 [2-(4- methylsulfinylphenyl)-3-(4-pyridyl)-6,7-dihydro-[5H]-pyrrolo[1,2- a] imidazole] was determined to be a prodrug for the sulfide metabolite SK&F 105561 [2-(4- methylthiophenyl)-3-(4-pyridyl)-6,7-dihydro-[5H]-pyrrolo[1,2-a] imidazole] which inhibited interleukin-1 (IL-1) production in vitro and both 5-lipoxygenase (5-LO) and prostaglandin H (PGH) synthase activities in vitro and ex vivo. SK&F 105561 inhibited partially purified 5-LO with a half-maximal concentration (IC50) of 3 microM. This inhibition was reversible, independent of preincubation time, and dependent on the concentration of the substrate arachidonic acid. SK&F 105561 also inhibited purified PGH synthase with the potency dependent on the level of peroxidase activity. The IC50 was 100 microM in the absence of peroxidase activity, whereas an IC50 of 3 microM was observed in the presence of peroxidase activity. Using human monocytes, SK&F 105561 inhibited A23187-stimulated prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) production with IC50 values of 0.1 and 2 microM, respectively. In addition, IL-1 production by lipopolysaccharide-stimulated human monocytes was also inhibited (IC50 2 microM). Oral administration of SK&F 105809 to rats resulted in a dose-related generation of SK&F 105561 and in the inhibition of thromboxane B2 and LTB4 production ex vivo with a half-maximal dose (ED50) of 15 and 60 mg/kg, respectively. SK&F 105561 showed weak inhibitory activity on 12-lipoxygenase with an IC50 of greater than 200 microM. Neither SK&F 105561 nor SK&F 105809 inhibited the stimulated-turnover of arachidonic acid-containing phospholipids in human monocytes or the activity of cell-free phospholipases A2 and C. Moreover, neither SK&F 105561 nor SK&F 105809 antagonized the binding of LTB4 or leukotriene D4 to membrane receptors. From these results, SK&F 105561, the active principle of SK&F 105809, acts as an inhibitor of both inflammatory cytokine and eicosanoid production.

Animals

Pharmacology of the pyrroloimidazole, SK&F 105809--II. Antiinflammatory activity and inhibition of mediator production in vivo.

SK&F 105809 [2-(4-methylsulfinylphenyl)-3-(4-pyridyl)- 6,7-dihydro-[5H]-pyrrolo[1,2,a] imidazole] demonstrated unique antiinflammatory activities in murine models that are resistant to selective cyclooxygenase (CO) inhibitors. Both edema and inflammatory cell infiltration induced by the topical application of arachidonic acid to the mouse ear were decreased by SK&F 105809 (ED50 values of 44 mg/kg, p.o.). Polymorphonuclear leukocyte (PMN) infiltration following the intraperitoneal injection of either monosodium urate crystal or carrageenan was inhibited with ED50 values of 64 and 72 mg/kg, p.o., respectively. These inflammatory responses were unaffected by the selective cyclooxygenase inhibitor naproxen. SK&F 105809 also inhibited leukotriene B4 (LTB4) and prostaglandin E2 production in vivo in arachidonic acid-induced inflammatory exudates (ED50 values of 41 and 15 mg/kg, p.o., respectively). The inhibition of LTB4 production preceded the inhibition of PMN infiltration. The impact of inhibition of both 5-lipoxygenase (5-LO) and CO was seen with platelet-activating factor-induced vascular permeability which was inhibited markedly by SK&F 105809. However, the 5-LO inhibitor, phenidone, only strongly inhibited when coadministered with the selective CO inhibitor, indomethacin. In spite of a short half-life (14-18 min) for both SK&F 105809 and the active metabolite SK&F 105561 [2-(4- methylthiophenyl)-3-(4-pyridyl)-6,7-dihydro-[5H]-pyrrolo[1,2-a] imidazole], the pharmacological activity lasted at least 1.5 hr. The biochemical evidence of inhibition of interleukin-1 (IL-1) production and 5-LO and CO activity, in vitro, by the metabolite (SK&F 105561) seen in the companion paper (Marshall PJ, Griswold DE, Breton J. Webb EF, Hillegass LM, Sarau HM, Newton J Jr, Lee JC, Bender PE and Hanna N, Pharmacology of the pyrroloimidazole, SK&F 105809--I. Inhibition of inflammatory cytokine production and of 5-lipoxygenase- and cyclooxygenase-mediated metabolism of arachidonic acid. Biochem Pharmacol 42: 813-824, 1991) and inhibition of the fluid and cellular phases of the inflammatory response, in vivo, by SK&F 105809 suggest that this compound possesses a unique profile of activity.

Animals

Developmental and age-related changes in reflexes of the human jaw-closing system.

Reflex responses of the jaw-closing system to innocuous mechanical stimulation of the tongue and palate were examined in a group of 25 girls aged 7-8 years and in a group of 25 women aged 70-80 years. Responses were measured both as changes in background biting force and from bilateral recordings of masseter EMGs. For comparative purposes, results from an earlier study of 35 young adult women (aged 18-25 years) were available. Compared to younger groups of subjects, reflex responses of the elderly were reduced in numbers and amplitude, were characterized by fewer initial excitatory component responses, and had longer latency to onset. Analyses of responses of the children indicated that age 7-8 years is a transitional period. Some children show adult-like responses, while others display responses that appear to represent earlier forms or transitional responses. These results suggest that oral-motor reflexes are not fixed response patterns upon which more complex motor skills, such as speech, are built. Rather, oral reflex development appears to occur in concert with the acquisition of complex motor skills. Systematic changes in reflex responses also occur in the period from young adulthood to seventh decade of life. This result indicates a continuous evolution of oral sensorimotor systems throughout the human life span.

Adult

Two flaps to resurface the basal flexion-crease of the finger area.

Two flaps are described which have been designed to resurface the skin around the basal flexion crease of the fingers. Their most common use is on the ulnar side of the hand but any finger can be resurfaced. Both flaps are 1 cm in width so the donor sites can be repaired directly without the use of skin grafts. Mobilisation of the fingers is therefore permissible within 24 hours and thus postoperative stiffness avoided. The one-stage cross-finger flap is of particular value in resurfacing and preventing the recurrence of Dupuytren's in the M.P. joint area. The palmar transposition flap based on the inter-digital cleft is useful for the release of volar contractures and resurfacing localised full thickness burns. They are quick to raise and very reliable, providing their nutrient vessel is retained. The donor site distortion is minimal. We have had no flap loss and no limitation of flexion.

Dupuytren Contracture

Factors influencing general practitioners' referral decisions.

This paper presents some findings from a small scale qualitative study of referral decision making conducted in south-east Northumberland in 1988-89. The study was prompted by an interest in variability in referral rates and the view that existing studies had not attempted to understand referral from the perspective of those involved in making the decisions. Our findings suggest that such understandings are crucial in the analysis of referral decisions and in any policy making initiatives designed to influence the pattern of referring.

Clinical Competence

Strategies for enhancing the consonant to vowel intensity ratio with in the ear hearing aids.

Numerous investigators have suggested that increasing the consonant to vowel intensity ratio (CVR) may improve speech intelligibility. This investigation was designed to determine the extent to which analog circuits, small enough to fit into in the ear hearing aids, can increase the CVR, and whether CVR enhancement is of benefit to hearing-impaired listeners. Real ear CVRs, calculated from real ear recordings of nonsense syllables, were obtained from eight hearing-impaired listeners. Recordings from each listener were obtained through each of four hearing aid circuits: (1) an adaptive high-pass filter; (2) a faster acting adaptive high-pass filter; (3) the fast-acting adaptive high-pass filter with expansion; and (4) an infinite amplitude clipper. The amount of CVR enhancement was compared to performance of the subjects with a NST speech recognition task. Subjects also ranked the four circuits for amount of consonant emphasis provided. Results indicated that the four hearing aid circuits increased the real ear CVR by 4 to 6 dB, relative to unaided. Aided CVR varied, however, across circuits and between fricative and stop consonants. Performance on the NST recognition task was generally consistent with the amount of CVR increase provided. Rank ordering for consonant emphasis was consistent with aided CVR for stop consonants, but not for fricatives.

Equipment Design

Distribution of Oriental and German cockroaches, Blatta orientalis and Blattella germanica (Dictyoptera), in the United Kingdom.

Results are presented of a survey carried out by Rentokil Ltd on the distribution of the Oriental cockroach Blatta orientalis L. and the German cockroach Blattella germanica L. in the United Kingdom. The known ranges of both species are increased considerably by the findings of the survey, with several new vice-county records for Scotland (including the Western Isles), England and Wales. The frequency at which Blatta orientalis was observed in outdoor habitats may indicate that this species sometimes spreads to new areas without human assistance.

Animals

Human serum megakaryocyte colony-stimulating activity appears to be distinct from interleukin-3, granulocyte-macrophage colony-stimulating factor, and lymphocyte-conditioned medium.

Sera from patients with bone marrow megakaryocyte aplasia are a rich source of megakaryocyte colony-stimulating activity (Meg-CSA). Other biologic materials exhibiting Meg-CSA include phytohemagglutinin-stimulated human lymphocyte-conditioned medium (PHA-LCM), recombinant interleukin-3 (IL-3), and recombinant granulocyte macrophage colony-stimulating factor (GM-CSF). Neutralizing antisera to both recombinant IL-3 and GM-CSF were used to evaluate the relationship among these sources of Meg-CSA. Varying dilutions of IL-3 and GM-CSF antisera were tested in plasma clot cultures of normal human peripheral blood megakaryocyte progenitors optimally stimulated by either IL-3 (1 U/mL), GM-CSF (1 U/mL), PHA-LCM (2.5% to 5% vol/vol), or aplastic human serum (10% vol/vol). IL-3 antiserum at dilutions up to 1/2,000 totally abrogated megakaryocyte colony growth stimulated by IL-3. A 1/500 dilution of GM-CSF antiserum completely eliminated GM-CSF-induced megakaryocyte colony development. A combination of anti-IL-3 and anti-GM-CSF, each at a 1/500 dilution, inhibited all megakaryocyte colony growth stimulated by optimal concentrations of IL-3 and GM-CSF together. There was no neutralizing crossreactivity between the IL-3 and GM-CSF antisera. At maximally neutralizing concentrations, IL-3 antiserum inhibited 66% of the megakaryocyte colony growth stimulated by PHA-LCM. Residual megakaryocyte colony growth was eliminated by the addition of a 1/500 dilution of anti-GM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Aplastic

Patients' attitudes following chorionic villus sampling.

The attitudes of 190 patients who had undergone chorionic villus sampling (CVS) were assessed by means of a questionnaire. One hundred and fifty-two patients replied of whom 68 (45 per cent) were referred because of increased maternal age and in the other 84 cases the indications included previous chromosomal abnormalities, fetal sexing, DNA analysis, and biochemical analysis. One hundred and twenty-two patients had a transcervical procedure, 24 had a transabdominal, and six patients required both procedures. One hundred and forty-one patients (93 per cent) reported CVS to be a satisfactory procedure, and the same percentage thought earlier diagnosis was beneficial. Thirty-nine patients (81 per cent) reported a better experience with CVS than with a previous amniocentesis. A majority of patients (93 per cent) wished a CVS in a future pregnancy and 137 patients (97 per cent) would accept a risk of miscarriage from the procedure of twice that quoted for amniocentesis (1 per cent).

Attitude

Pharmacological profile of SK&F 105809, a dual inhibitor of arachidonic acid metabolism.

The effects of SK&F 105809, 6,7,-dihydro-2-[4(methylsulfinyl) phenyl]-3-(4-pyridyl) -5[H]-pyrrolo[1,2-a] imidazole, on eicosanoid metabolism, inflammatory responses, algesia and ulcer formation are described. SK&F 105809 was determined to be a prodrug for the sulfide metabolite SK&F 105561 which is an inhibitor of 5-lipoxygenase (5-LO) and prostaglandin H (PGH) synthase activities seen with both the isolated enzyme (IC50S 3 microM) and human monocyte production of the eicosanoids leukotriene B4 (LTB4, IC50 1.0 microM) and prostaglandin E2 (PGE2, IC50 0.1 microM). In-vivo conversion of SK&F 105809 to the active principle SK&F 105561 was observed in both mice and rats. SK&F 105809 inhibited LTB4 and PGE2 production in vivo in inflammatory exudates as well as the production of LTB4 and thromboxane B2 (TxB2) ex vivo in rat blood. SK&F 105809 inhibited oedema and inflammatory-cell infiltration in arachidonic acid-induced inflammation in the mouse ear and rat paw as well as in carrageenan- and monosodium urate crystal-induced peritonitis. SK&F 105809 was also effective in inhibiting mouse collagen-induced arthritis and associated acute-phase reactant protein. At the same time, these acute and chronic models of inflammation were found to be resistant to the action of selective cyclooxygenase inhibitors such as naproxen. In addition, SK&F 105809 possessed analgesic activity in phenylquinone-induced abdominal constriction assay and inhibited indomethacin-induced ulcers.

Administration, Oral

A flow cytometric study of Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH), or histiocytosis X, is now generally considered to be a non-malignant condition. A flow cytometric (FCM) study of a single case has, however, been published which claimed to provide evidence to contradict this. The presence of DNA-ploidy as detected using this technique is a feature of malignant and pre-malignant disease. In this reported single case, DNA-ploidy was present but the clinical features of this patient were atypical for LCH. We have performed a FCM study of the DNA of nine biopsies of LCH lesions from six patients with well-established disease. In addition, in one of these, fresh tissue studies including the use of an anti-CD I monoclonal antibody to specifically label the LCH cells were performed. In all cases the DNA content of the cells was entirely normal. We therefore found no evidence that LCH is a neoplastic disorder.

Adult