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Biomedical subjects

J Macfarlane

Publications and source records attributed to J Macfarlane.

At least 19 recordsLinked to original sources

Dissociation of hypertension and fixed interval responding in two separate strains of genetically hypertensive rat.

The behaviour of spontaneously hypertensive rats (SHR) may model attention-deficit hyperactivity disorder. For example, SHR are hyperactive in an open field and show high terminal rates of responding on certain fixed-interval schedules. Open field behaviour has been dissociated from the accompanying spontaneous hypertension but fixed interval responding has not. We compared the fixed interval responding of two unrelated strains of genetically hypertensive rat, the SHR (n = 6) and the New Zealand genetically hypertensive rat (GH, n = 5), with their normotensive control strains, the Wistar Kyoto (WKY, n = 6) and Wistar (n = 5), respectively. Both hypertensive rat strains showed increased terminal lever-pressing rates on a multiple fixed-interval schedule (FI-EXT) compared to controls. In order to investigate the association of hypertension and the behavioural characteristics in question, an F-2 hybrid strain was obtained by cross-breeding GH and Wistar rats. When these F-2 hybrids (n = 33) were tested on the FI-EXT schedule, terminal lever-pressing rate was not correlated with blood pressure. The independent segregation of these phenotypical characteristics in the hybrids suggests independent genetic control. By contrast, other behavioural characteristics, including high lever-pressing rates during the extinction component and a tendency to emit responses in bursts, did cosegregate with terminal lever-pressing rates. Taken together, these findings suggest that the genetic loci for high blood pressure and responding on the FI-EXT schedule in these two unrelated rat strains are close but distinct.

Animals↗

Pulmonary actinomycosis.

Pulmonary actinomycosis is a rare but important and challenging diagnosis to make. Even when the clinical suspicion is high, the disease is commonly confused with other chronic suppurative lung diseases and with malignancy. An early, accurate diagnosis will prevent the considerable psychological and physical morbidity, including unwarranted surgery, associated with delayed diagnosis. The clinical, radiological and therapeutic characteristics of the infection are reviewed here. Respiratory physicians should be aware of this important differential when investigating patients for persistent pulmonary shadowing. This will expedite the diagnosis of an otherwise highly treatable condition with an excellent prognosis if picked up early.

Actinomycosis↗

Another knotted epidural catheter.

A lumbar epidural catheter inserted in a 24-year-old woman for labour analgesia, and subsequently used for post-caesarean epidural analgesia, proved difficult to remove. After multiple attempts, the entrapped catheter was dislodged intact, revealing a knot near its distal tip. Knotting of an epidural catheter leading to entrapment is a rare complication of epidural catheterization.

Adult↗

Fate of linear alkylbenzenes released to the coastal environment near Boston Harbor.

Linear alkylbenzenes (LABs) were used to assess the fates of hydrophobic organic compounds (HOCs) released to a large urban harbor and the adjoining offshore waters. We found that particulate concentrations of the individual C12 LAB isomers in 1996 summertime surface waters decreased from 1 pM in Boston Harbor to 20-200 fM in coastal Massachusetts and Cape Cod Bays. Levels fell to only a few fM in offshore Gulf of Maine locations. These observations were consistent with municipal wastewater in Boston Harbor as the predominant input followed by dispersal via known circulation patterns in this region. Phase-dependent removal rate coefficients for flushing, vertical scavenging, volatilization, photodegradation, and biodegradation of individual LAB isomers were constrained from literature, field observations, and laboratory experiments and combined with estimates of wastewater release rates into a predictive 3-box model. Vertical scavenging, biodegradation, and flushing were predicted to be the most important fate processes for C12 LABs in the Boston Harbor-MA Bay-Cape Cod Bay flow system with about 1% of the harbor releases "surviving" passage. For HOCs such as the relatively bio-recalcitrant LAB, 6-phenyldodecane, it appears that we are at present able to predict the coastal fate of harbor-introduced HOCs in this system within a factor of 2. Contrary to expectations from biodegradation experiments, the ratio of internal-to-external (I/E) LAB isomers decreased offshore in both water and sediment samples, suggesting we are "missing" an important process affecting LAB fates.

Alkylation↗

Prospective study of the incidence, aetiology and outcome of adult lower respiratory tract illness in the community.

BACKGROUND: Acute lower respiratory tract illness in previously well adults is usually labelled as acute bronchitis and treated with antibiotics without establishing the aetiology. Viral infection is thought to be the cause in most cases. We have investigated the incidence, aetiology, and outcome of this condition. METHODS: Previously well adults from a stable suburban population consulting over one year with a lower respiratory tract illness were studied. For the first six months detailed investigations identified predetermined direct and indirect markers of infection. Evidence of infection was assessed in relation to presenting clinical features, indirect markers of infection, antibiotic use, and outcome. RESULTS: Consultations were very common, particularly in younger women (70/1000 per year in previously well women aged 16-39 years), mainly in the winter months; 638 patients consulted, of whom 316 were investigated. Pathogens were identified in 173 (55%) cases: bacteria in 82 (Streptococcus pneumoniae 54, Haemophilus influenzae 31, Moraxella catarrhalis 7), atypical organisms in 75 (Chlamydia pneumoniae 55, Mycoplasma pneumoniae 23), and viruses in 61 (influenza 23). Seventy nine (24%) had indirect evidence of infection. Bacterial and atypical infection correlated with changes in the chest radiograph and high levels of C reactive protein but not with (a) the GP's clinical assessment of whether infection was present, (b) clinical features other than focal chest signs, and (c) outcome, whether or not appropriate antibiotics were prescribed. CONCLUSIONS: Over 50% of patients have direct and/or indirect evidence of infection, most commonly bacterial and atypical pathogens, but the outcome is unrelated to the identified pathogens. Many patients improve without antibiotics and investigations do not help in the management of these patients. GPs can reassure patients of the causes and usual outcome of this self-limiting condition.

Acute Disease↗

A mammalian oocyte-specific linker histone gene H1oo: homology with the genes for the oocyte-specific cleavage stage histone (cs-H1) of sea urchin and the B4/H1M histone of the frog.

Oocytes and early embryos of multiple (non-mammalian) species lack the somatic form of the linker histone H1. To the best of our knowledge, a mammalian oocyte-specific linker (H1) histone(s) has not, as yet, been reported. We have uncovered the cDNA in question in the course of a differential screening (suppression subtractive hybridization (SSH)) project. Elucidation of the full-length sequence of this novel 1.2 kb cDNA led to the identification of a 912 bp open reading frame. The latter encoded a novel 34 kDa linker histone protein comprised of 304 amino acids, tentatively named H1oo. Amino acid BLAST analysis revealed that H1oo displayed the highest sequence homology to the oocyte-specific B4 histone of the frog, the respective central globular (putative DNA binding) domains displaying 54% identity. Substantial homology to the cs-H1 protein of the sea urchin oocyte was also apparent. While most oocytic mRNAs corresponding to somatic linker histones are not polyadenylated (and remain untranslated), the mRNAs of (non-mammalian) oocyte-specific linker histones and of mammalian H1oo, are polyadenylated, a process driven by the consensus signal sequence, AAUAAA, detected in the 3'-untranslated region of the H1oo cDNA. Our data suggest that the mouse oocyte-specific linker histone H1oo (1) constitutes a novel mammalian homolog of the oocyte-specific linker histone B4 of the frog and of the cs-H1 linker histone of the sea urchin; (2) is expressed as early as the GV (PI) stage oocyte, persisting into the MII stage oocyte, the oocytic polar bodies, and the two-cell embryo, extinction becoming apparent at the four- to eight-cell embryonic stage; and (3) may play a key role in the control of gene expression during oogenesis and early embryogenesis, presumably through the perturbation of chromatin structure.

Amino Acid Sequence↗

Local antibiotic guidelines for adult community-acquired pneumonia (CAP): a survey of UK hospital practice in 1999.

We investigated the guidelines in British hospitals for the management of adults admitted with community-acquired pneumonia (CAP). A questionnaire was sent to one consultant respiratory physician in each of the 263 hospitals in the British Thoracic Society (BTS) Directory of Training Posts and Services. Two hundred and thirteen (81%) responses were received: 178 (84%) had written CAP guidelines, of which 123 (69%) printed copies were received. For non-severe CAP a single antibiotic (74% of guidelines-most frequently amoxycillin or ampicillin) was the usual recommendation with the combination of a beta-lactam and a macrolide the second most frequent (24%). The latter combination was recommended for severe CAP in 81% of guidelines. Clostridium difficile-associated diarrhoea had influenced guideline recommendations, or was commented on as a concern, in 18% of responses. Written guidelines for antibiotic therapy in adults with CAP exist in most British hospitals and follow broadly the 1993 BTS guidelines, although combination therapy is used not infrequently for non-severe CAP.

Adult↗

Lower respiratory tract infection and pneumonia in the community.

Community-acquired pneumonia (CAP) is common. There is no entirely satisfactory way of defining pneumonia using clinical criteria alone. New focal chest signs on examination in the presence of a systemic illness that is suggestive of a lower respiratory tract infection seems to be the best clinical finding that indicates pneumonia. Progress has been made in identifying simple clinical features that relate to prognosis and allow the general practitioner to decide whether care in the community is appropriate or hospital referral is required. Psychosocial factors for the patient will also remain important. Most patients who have CAP that is mild enough to be managed in the community will require few, if any, investigations. A chest radiograph is appropriate in all patients to exclude an underlying lung tumor. Measurement of surrogate markers of acute infection, such as C-reactive protein, may prove useful to the general practitioner if near testing were to become feasible. The antibiotic management for CAP for patients well enough to be managed at home can be simple and logical, providing general practitioners have some knowledge regarding likely pathogens and etiologic and epidemiological clues. Any antibiotic chosen must suppress Streptococcus pneumoniae, which remains the most common cause of CAP.

Adult↗

Prospective case-control study of role of infection in patients who reconsult after initial antibiotic treatment for lower respiratory tract infection in primary care.

OBJECTIVE: To assess direct and indirect evidence of active infection which may benefit from further antibiotics in adults who reconsult within 4 weeks of initial antibiotic management of acute lower respiratory tract infection in primary care. DESIGN: Observational study with a nested case-control group. SETTING: Two suburban general practices in Arnold, Nottingham, over 7 winter months. SUBJECTS: 367 adults aged 16 years and over fulfilling a definition of lower respiratory tract infection and treated with antibiotics. 74 (20%) patients who reconsulted within 4 weeks for the same symptoms and 82 "control" patients who did not were investigated in detail at fallow up. MAIN OUTCOME MEASURES: Direct and indirect evidence of active infection at the time of the reconsultation or the follow up visit with the research nurse for the controls. Investigations performed included sputum culture, pneumococcal antigen detection, serial serology for viral and atypical pathogens and C reactive protein, throat swabs for detecting viral and atypical pathogens by culture and polymerase chain reaction, and chest radiographs. RESULTS: Demographic and clinical features of the groups were similar. Two thirds of the 74 patients who reconsulted received another antibiotic because the general practitioner suspected continuing infection. Any evidence of infection warranting antibiotic treatment was uncommon at reconsultation. The findings for the two groups were similar for the occurrence of identified pathogens; chest x ray changes of infection (present in 13%); and C reactive protein concentrations, which had nearly all fallen towards normal. Only three patients in the reconsultation group had concentrations > or = 40 mg/l. Pathogens identified at follow up in the 156 patients in both groups included ampicillin sensitive bacteria in six. Atypical infections diagnosed in 27 (Chlamydia pneumoniae in 22) and viral infections in 54 had probably been present at the initial presentation. CONCLUSION: Our study suggests that active infection, which may benefit from further antibiotics, is uncommon in patients who reconsult after a lower respiratory tract infection, and a repeat antibiotic prescription should be the exception rather than the rule. Other factors, such as patients' perception of their illness, may be more important than disease and infection in their decision to reconsult.

Adolescent↗

Influence of patients' expectations on antibiotic management of acute lower respiratory tract illness in general practice: questionnaire study.

OBJECTIVE: To assess patients' views and expectations when they consult their general practitioner with acute lower respiratory symptoms and the influence these have on management. DESIGN: General practitioners studied consecutive, previously well adults and recorded clinical data, the certainty regarding their prescribing decision, and the influence of non-clinical factors on that decision. Patients completed a questionnaire at home after the consultation. SETTING: 76 doctors from suburban, inner city, and rural practices. SUBJECTS: 1014 eligible patients entered; 787 (78%) returned the questionnaire. MAIN OUTCOME MEASURES: The views of the patient, the views of and antibiotic prescription by the doctor. RESULTS: Most patients thought that their symptoms were caused by an infection (662) and that antibiotics would help (656) and had both wanted (564) and expected (561) such a prescription. 146 requested an antibiotic, 587 received one. Of the 643 patients who thought they had an infection, 582 wanted an antibiotic and thought it would help. Severity of symptoms did not relate to wanting antibiotics. For those prescribed antibiotics, their doctor thought they were definitely indicated in only 116 cases and not indicated in 126. Patient pressure most commonly influenced the decision to prescribe even when the doctor thought antibiotics were not indicated. Doctors considered antibiotics definitely indicated in only 1% of the group in whom patient pressure influenced the prescribing decision. Patients who did not receive an antibiotic that they wanted were much more likely to express dissatisfaction. Dissatisfied patients reconsulted for the same symptoms twice as often as satisfied patients. CONCLUSION: Patients presenting with acute lower respiratory symptoms often believe that infection is the problem and antibiotics the answer. Patients' expectations have a significant influence on prescribing, even when their doctor judges that antibiotics are not indicated.

Adult↗

Contemporary use of antibiotics in 1089 adults presenting with acute lower respiratory tract illness in general practice in the U.K.: implications for developing management guidelines.

Respiratory symptoms are the most common cause of general practitioner (GP) consultation, and hospital-based specialists are often called on to provide management guidelines, particularly in the area of antibiotic prescribing. The present authors have assessed factors associated with antibiotic use by 115 GPs when managing 1089 adults with an acute lower respiratory tract illness, including cough. They prescribed antibiotics to three-quarters of patients, but felt antibiotics to be definitely indicated in less than one-third of these cases and not needed in one-fifth. Univariate analysis revealed that antibiotics were prescribed more frequently by older GPs for older patients in the presence of underlying disease, discoloured sputum, shortness of breath, wheeze, fever, signs on chest examination, and 'other factors'. Multivariate logistic regression confirmed an independent effect for all these findings except for the presence of underlying disease, shortness of breath and wheeze. 'Other factors' included patient 'pressure' and social factors, and GP work pressure or prior experience with the patient. These factors were an important influence on prescribing, especially if the GP felt an antibiotic was not indicated. Amoxycillin was the first choice (58% of total) except where the patient had recently received antibiotics for the same illness. Broader spectrum antibiotics were used more commonly in patients with chronic lung disease, discoloured sputum, chest signs on examination and where the GP felt antibiotics were indicated. However, these antibiotics were also prescribed to 14% of previously well patients. General practitioners used a wide variety of terms to describe the illness with little consistency or structure. The decision concerning the use and choice of antibiotics and the confidence with which the GP makes that decision is a complex interaction between patient, doctor and disease, being affected not only by clinical features but also by the social and psychological elements of the presenting problem. Such issues need to be appreciated by hospital specialists when called on to advise on developing relevant guidelines for primary care.

Acute Disease↗

Radiographic features of staphylococcal pneumonia in adults and children.

BACKGROUND: Clinical and laboratory features do not accurately correlate with the cause of community acquired pneumonia. A study was performed to examine whether the radiographic features of staphylococcal pneumonia are sufficiently distinct to aid early diagnosis. METHODS: The chest radiographs of 34 patients (including eight children) with proven staphylococcal pneumonia were reviewed by two experienced observers using methods described previously. Features on presentation and follow up were noted. RESULTS: The most striking features were the presence of multilobar consolidation on presentation, cavitation, pneumatocoeles and spontaneous pneumothorax, together with a tendency to radiographic deterioration after admission in both adults and children. Some of these features are much less common with other causes of community acquired pneumonia. However, most of the cases did not have these classic features. CONCLUSIONS: The presence of certain radiographic features, including multilobar shadowing, cavitation, pneumatocoeles, and spontaneous pneumothorax, are seen with staphylococcal pneumonia in adults and children, but their absence does not exclude the diagnosis.

Adult↗