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Biomedical subjects

D N Lockwood

Publications and source records attributed to D N Lockwood.

At least 37 records · Page 2Linked to original sources
PubMed1995

Tumour necrosis factor-alpha (TNF-alpha) synthesis is associated with the skin and peripheral nerve pathology of leprosy reversal reactions.

Leprosy may be complicated by episodes of increased cell-mediated immunity towards Mycobacterium leprae (reversal reactions) which result in severe local immunopathology in skin lesions and peripheral nerves. Using in situ hybridization and MoAb techniques we have demonstrated TNF-alpha mRNA and TNF-alpha protein in macrophages infiltrating leprosy skin and peripheral nerve. Levels of TNF-alpha mRNA are significantly increased in reactional skin and nerve, particularly in borderline tuberculoid patients. TNF-alpha mRNA and TNF-alpha protein levels are higher in reactional nerves then reactional skin. In both reactional skin and nerve TNF-alpha mRNA is more abundant than TNF-alpha protein; this may reflect the rapid turnover of TNF-alpha protein in an immunologically dynamic situation, such as is seen in reversal reaction. Our findings emphasize the importance of documenting both mRNA and protein production when assessing the role of cytokines in pathology. The leprosy reversal reaction may be regarded as a useful model of tissue immunopathology in which TNF-alpha is generated as part of the host response to infection, but also produces local tissue damage.

Humans↗
PubMed1994

Nerve and skin damage in leprosy is associated with increased intralesional heat shock protein.

Leprosy is frequently complicated by the development of reversal reactions in which peripheral nerve and skin lesions become inflamed and irreversible nerve damage may ensue. Increased expression of proteins belonging to the 70-kD heat shock family (hsp 70) occurs in cells of the central nervous system exposed to hyperthermia, physical damage or drug-induced trauma. In the present study we have used immunocytochemical staining to monitor hsp70 levels in peripheral nerves infected by Mycobacterium leprae. Hsp70 was detected in skin and nerve lesions from all leprosy patients, but was particularly prominent in lesions from patients undergoing reversal reactions. Hsp70 immunocytochemistry can thus be used as a marker of neural injury in the peripheral as well as in the central nervous system. The cellular dynamics of nerve damage in leprosy are currently poorly understood, and we postulate that the immunopathology of leprosy may be partly due to an autoimmune response to heat shock proteins.

Biopsy↗
PubMed1993

Infections from animals to man.

A conference on 'Infections from Animals to Man' was held at the Royal College of Physicians on 8 July 1992. The aim of the conference was to discuss the epidemiology and control of the zoonoses and the risks posed by zoonoses.

Animals↗
PubMed1993

Clinical features and outcome of reversal (type 1) reactions in Hyderabad, India.

A retrospective survey of the notes on all patients attending Dhoolpet Leprosy Research Center, India, during 1985 was done to establish the frequency, timing, and clinical features of reversal (type 1) reactions; 494 case notes were examined and clinical evidence of a reversal reaction was found in 44 cases (10.9%). Reactions were most common in borderline patients, with 11.4% and 14.8% of borderline tuberculoid (BT) and borderline lepromatous (BL) patients developing reactions, respectively. Presentation in reaction was frequent with 47.5% of reactional patients having signs of a reversal reaction at the time of their first visit to the Dhoolpet clinic; 50% of skin reactions developing in patients on antileprosy treatment occur within the first month of treatment. Neurological reactions occur later and over a longer time course. Late reactions may occur up to 6 1/2 years after the start of treatment. Further reactional episodes occurred in 31.8% of the patients, and may be repeated. Steroid treatment produced improvement of both skin lesions and neuritis, but improvement in clinical signs and symptoms occurred in only 50% of the neuritic episodes.

Adolescent↗
PubMed1992

Skin problems in returning travelers.

A new skin lesion in a returning traveler often poses a difficult diagnostic problem for the clinician whose knowledge of geographic medicine is limited. To reach a diagnosis the physician has to consider the location and style of travel, exposure to pathogens, length of stay, epidemiology, incubation period, and clinical presentation of dermatologic diseases in the countries visited. As with any dermatologic problem, the appearance of the presenting lesion should help to establish the differential diagnosis. This article is a guide to the diagnosis and investigation of skin lesions in returning travelers; it is not intended as a comprehensive review of tropical dermatology.

Diagnosis, Differential↗
PubMed1991

DLCO/Q and diffusion limitation at rest and on exercise in patients with interstitial fibrosis.

Pulmonary diffusing capacity for carbon monoxide (DLCO) and pulmonary capillary blood flow (Qp) were measured on exercise in patients with a low DLCO with the aim of predicting, from the overall DL/Qp ratio, diffusion limitation for oxygen and relating it to the fall in arterial oxygen saturation actually observed. Five patients with cryptogenic fibrosing alveolitis (DLCO ranging from 20-54% predicted normal) exercised for 5 min at a work load equal to 60% of their maximum (45 to 90 watts). At 5 min (and previously at rest) they rebreathed rapidly for 15 sec from a 1.0 L bag containing helium (He), sulphur hexafluoride (SF6) and freon-22, 30% oxygen in argon and less than 1 ppm 11C-labelled carbon monoxide. Pulmonary capillary blood flow (Qp) and diffusing capacity (DLCO) were measured from flow-weighted breath-by-breath concentrations of freon-22 and 11CO, after correction for gas mixing delays (using He and SF6). Oxygen saturation (SaO2) (ear oximetry), MO2 and MCO2 and cardiac frequency were measured. PAO2 (ideal) was derived and mixed venous O2 saturation and content were calculated (Fick); PaO2 and PVO2 were derived from standard dissociation curves. For comparison, DLCO and Qp were measured in a similar fashion in five normal subjects exercising at 60 watts. Mean DLCO in patients with fibrosis was 9.62 (SD 2.88) ml.min-1, mm Hg-1 on exercise and mean Qp was 10.48 (SD 1.79) L.min-1 giving mean DLCO/Q ratios of 0.92 (SD 0.28). At 60 watts mean DLCO/Qp in normal subjects was 2.54 (SD 0.3), 2.76-times greater than in patients. SaO2% fell in patients by 3-15% on exercise. Predictions of alveolar-end capillary PO2 gradients from these overall DL/Q gradients showed that diffusion limitation accounted for 99% of the alveolar-arterial PO2 gradient on exercise in fibrosing alveolitis. Hughes (1991 Respir. Physiol. 83:167-178) [corrected] suggests that this simple approach overestimates the contribution of diffusion limitation by about 30%.

Adult↗
PubMed1990

Revaccination with BCG: its effects on skin tests in Kuwaiti senior school children.

Following a policy of BCG vaccination adopted in Kuwait more than 20 yrs ago, children receive their first vaccination just before starting school. Those who have a response of less than 10 mm induration to 2 tu of RT23 PPD, when they are 13 yrs old, are revaccinated. The effects of this revaccination on skin test positivity in a group of 18 yr old senior school children have been investigated. In a random study group 23% were found to have received BCG a second time. Revaccination resulted in a significant increase in positivity to tuberculin, and to the other 6 reagents tested, that was much more than would have been expected due to the passage of time alone in low responders. Scars of the second BCG vaccination were larger than those after the first vaccination, and showed a sex difference, with scars being significantly larger in boys than in girls. Boys also tended to show the largest responses to skin tests, with the notable exception of tuberculin to which girls showed the largest response. In most cases responses to skin tests were larger after revaccination than after a single vaccination. Based on this study, it is impossible to be sure that revaccination improved protective immunity, but the increase in tuberculin responsiveness, and recognition of environmental mycobacterial species may be indirect evidence supporting this conclusion.

Adolescent↗
PubMed1989

Parasite infections in AIDS.

'Illnesses no one's got' was the epidemiological clue that led to the identification of AIDS as a new disease in 1981 when a rare infectious organism Pneumocystis carinii was seen in previously healthy homosexuals. Since then a wide range of parasite infections has been recognized in AIDS patients. However, these patients are not susceptible to just any passing parasite. The human immunodeficiency virus (HIV) produces a specific immune defect and only parasites that can exploit that defect will be able to flourish. In this review Diana Lockwood and Jonathan Weber explore the spectrum of parasite diseases recognized in AIDS and also consider those parasites that occur infrequently in AIDS. Analysis of parasitic infections that AIDS patients do not suffer from will yield valuable information about immune recognition and handling of these parasites.

Journal Article↗
PubMed1989

A pilot study of three potential vaccines for leprosy in Bombay.

Three vaccines, BCG Glaxo alone (vaccine A), BCG Glaxo plus 10(7) killed Mycobacterium vaccae (vaccine B), and BCG Glaxo plus 10(7) killed M. leprae (vaccine C), were given to groups of selected children. The effects of these vaccines on subsequent quadruple skin testing 1-3 years after vaccination were compared. All three vaccines equally and significantly (p less than 0.00001) increased positivity to tuberculin, but only vaccine B was found to significantly enhance development of skin-test positivity to leprosin A (p less than 0.002). The data support the evidence previously obtained in rural Iran that the combination of BCG with killed M. vaccae is likely to be a better vaccine for leprosy than is BCG alone.

Adolescent↗
PubMed1988

Recognition of a category of responders to group II, slow-grower associated antigens amongst Kuwaiti senior school children, using a statistical model.

A mathematical model previously developed to test the validity of categorisation of skin test responders has been applied to data obtained from 3 age groups of Kuwaiti school children. Two specially designed sets of 4 new tuberculins were tested on senior school children to determine whether extra categories of responders might exist amongst them. Strong statistical evidence has been obtained that a proportion of the children respond to group ii, slow-grower associated antigen, creating a fourth responder category, but no evidence was found for responses to group iii, fast-grower associated antigen. The significance of group ii antigens in immune protection from tuberculosis has never been considered specifically. It is of special interest to note that responders to these antigens have been readily found in Kuwait, a country where BCG is thought to be effective, whereas no such category could be found in India or Sri Lanka, where the efficacy of the vaccine is less certain.

Adolescent↗
PubMed1988

A severe coagulopathy following volume replacement with hydroxyethyl starch in a Jehovah's Witness.

Blood volume was maintained by an infusion of hydroxyethyl starch 2000 ml (Hespan: HES) during and for the first 28 hours after a major orthopaedic operation in a 13-year-old girl who was a Jehovah's Witness. This was responsible for a generalised clinical haemorrhagic state, an acquired coagulopathy associated with a shortened thrombin, prolonged prothrombin and activated partial thromboplastin times, and an acquired von Willebrand syndrome. The coagulation, after cessation of the infusion of HES, did not become normal until approximately 72 hours later.

Adolescent↗
PubMed1987

Three types of response to mycobacterial antigens.

Responses to pathogenic and environmental mycobacteria were assessed in 2680 children in India and Sri Lanka using quadruple skin-testing with new tuberculins. Statistical analysis of the results, by fitting a log-linear mixture model, confirmed the presence of three different categories of response: category 2 non-responders (about 55%) did not react to any component of the mycobacteria; category 3 responders (about 40%) were sensitive to the species-specific group iv antigens; and category 1 responders (about 5%) were sensitive to the group i antigens which are common to all mycobacteria. The proportions of the three response categories vary with age and with BCG status. BCG vaccination and increasing age act independently to decrease the proportion of category 2 non-responders and increase the proportion of category 3 individuals. BCG vaccination and increasing age interact to increase the proportion of category 1 responders.

Adolescent↗
PubMed1986

Surgical dressers: the theatre experience of junior clinical students.

The teaching of junior surgical dressers in theatre and on the wards was audited in a survey organized by students over a 3-year period. The average dresser in Birmingham, England spent 5 1/2 hours per week in theatre and was scrubbed for more than half of that time. Most students found their time in theatre both instructive and enjoyable. No major differences in teaching practices were found between teaching and peripheral hospitals.

Attitude of Health Personnel↗
PubMed1986

Clinical experience of clerks and dressers: a three-year study of Birmingham medical students.

A survey of the clinical experience of junior medical clerks and surgical dressers on their first clinical attachment in the Birmingham University Teaching Hospitals was organized by students over a three-year period. A typical clinical student had performed basic clinical procedures such as putting up a drip, doing an ECG, bladder catheterization and seen a wide range of other procedures. Most students felt involved in the work of the firm, had clerked routine admissions, and regularly attended the firm's emergency admission night. Consultants on most firms were felt to be concerned about student progress. Students attached to district general hospitals gained a wider range of clinical experience than those at established teaching hospitals. Student-run audit is a useful way of monitoring the clinical experience gained by medical students.

Attitude of Health Personnel↗
PubMed1985

Student audit of clinical teaching: a three year study.

An audit of teaching to junior clinical students in the University of Birmingham organised by students identified several surgical and medical firms on which they received little clinical teaching. Consultants spent an average of four and a half hours a week teaching junior students on the wards, arrived about 10 minutes late for that teaching, but missed less than 10% of teaching sessions. Junior students missed less than 10% of consultant teaching sessions and found them useful, though not always stimulating. Audit organised by students is an acceptable method of monitoring the informal teaching received by clinical students.

Education, Medical, Undergraduate↗