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Biomedical subjects

K Law

Publications and source records attributed to K Law.

12 recordsLinked to original sources
PubMed1997

Myringotomy and ventilation tube insertion: a ten-year follow-up.

Eighty children who had myringotomy performed for otitis media with effusion in 1984 were reviewed in 1994. This had involved surgery on 158 ears. Three aspects of ear condition were studied: hearing loss, tympanic membrane perforation, and tympanosclerosis. Hearing losses were present in 13 ears (8.2 per cent), involving 10 children (12.5 per cent), although losses were under 20 dB in seven of these ears (five patients). Of the six ears with losses more than 20 dB (3.8 per cent), in five patients bilateral losses of 30 dB were due to a recurrence of effusions, a large dry posterior perforation was the cause of a 30 dB loss, an infected anterior perforation had caused a 30 dB loss, an ear which had a cholesteatoma, and had a mastoidectomy and ossiculoplasty in 1987, had a 30-40 dB loss, and one ear which had a Type 1 tympanoplasty in 1994 had a 50 dB loss. Therefore in only three ears (1.9 per cent) could hearing loss be associated directly with myringotomy and ventilation tube insertion. Perforations had persisted unilaterally in seven patients, three having had tympanoplasties. Of the remaining perforated tympanic membranes, two were free of symptoms, one had only a slight hearing loss, and one had a more significant loss with recurrent infection. Tympanosclerosis was only found in those ears which had ventilation tubes inserted (and not those which had myringotomy only), occurring in 48 ears (31 per cent, of 39 per cent of those which had a ventilation tube inserted). There was no link between tympanosclerosis and hearing loss. The site of tympanosclerosis was not restricted to the site of myringotomy, and in many cases was present only in other areas of the tympanic membrane. There was a tendency for more extensive tympanosclerosis to occur in those ears which had more ventilation tube insertions. The risk of perforation in particular lends support to a policy of 'watchful waiting'.

Child↗
PubMed1996

Increased release of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha by bronchoalveolar cells lavaged from involved sites in pulmonary tuberculosis.

Mycobacterium tuberculosis and its components have been shown to stimulate mononuclear phagocytes in vitro to release interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6). Animal models of tuberculosis (TB) also demonstrate the presence of cytokines in granulomas. We hypothesized that bronchoalveolar lavage (BAL) cells from patients with pulmonary TB would have increased spontaneous release of IL-1 beta, IL-6, and TNF-alpha and would have a concomitant alveolitis. We performed BAL on 26 patients with active TB and on six normal volunteers. BAL fluid from radiographically involved and uninvolved sites was evaluated separately for cell types and the spontaneous release of cytokines. The alveolar inflammation in involved sites was characterized by an increase in lymphocytes (miliary TB, 38 +/- 10%; involved sites, 22 +/- 4%; uninvolved sites, 13 +/- 2%; normal, 5 +/- 2%) and neutrophils (involved sites, 21 +/- 7%; uninvolved sites, 3 +/- 2%). There was a significant increase in the spontaneous release of IL-1 beta (501 +/- 280 pg/ml), TNF-alpha (782 +/- 165 pg/ml), and IL-6 (473 +/- 157 pg/ml) from involved sites of TB patients that was 5- to 20-fold greater than uninvolved sites, normal controls, or miliary TB. Northern analysis revealed increased gene expression of IL-1 beta, TNF-alpha, and IL-6 from the involved sites from two patients with TB compared with two negative controls. We conclude that BAL cells, especially alveolar macrophages, are activated in the alveolar inflammation of active TB and spontaneously release increased quantities of IL-1 beta, IL-6, and TNF-alpha, and that these cytokines are likely to be involved in directing granuloma formation and control of M. tuberculosis infection.

AIDS-Related Opportunistic Infections↗
PubMed1995

Human host response to Mycobacterium tuberculosis.

Despite the importance of tuberculosis as the leading cause of death due to infectious disease in the world, it has only been recently that an understanding of the human host response in this infection has begun to emerge. The key components of this response are cytokines and components of cellular immunity, predominantly T-lymphocytes and macrophages. Though the relationships among the components of the immune response are complex, it seems likely that in response to mycobacterial infection associated with active disease, cytokines such as TNF-alpha and IL-1 beta are produced; these cytokines serve to recruit more lymphocytes, generally of the T(H) (T helper) phenotype, which then produces substances such as the macrophage activating factor interferon-gamma. Macrophages activated by IFN-gamma ar thus stimulating to enhance intracellular killing of mycobacteria. The role of other cytokines, such as IL-6 and IL-8, both of which are induced by M. tuberculosis or its cell was components, is less clear. Further elucidation of the human host response to tuberculosis should help in the development of new vaccines and treatment strategies.

Cytokines↗
PubMed1995

Enhanced interleukin-8 release and gene expression in macrophages after exposure to Mycobacterium tuberculosis and its components.

Mycobacterium tuberculosis infection is accompanied by acute and chronic inflammatory infiltrates associated with necrotizing granulomas in lung tissue. The cellular infiltrate is characterized by inflammatory cells which include neutrophils, lymphocytes, and macrophages. In animal and in vitro models of mycobacterial infection, cytokines including tumor necrosis factor-alpha (TNF-alpha), interferon gamma (IFN-gamma), and interleukin-1 beta (IL-1 beta) participate in granulomatous inflammation. We hypothesized that interleukin-3, a potent chemoattractant for neutrophils and lymphocytes, could be released by activated alveolar macrophages after exposure to M. tuberculosis or its components and contribute to granulomatous lung inflammation. A quantitative immunoassay revealed that IL-8 protein release was significantly elevated in supernatants of macrophages and in lavage fluid obtained from patients with pulmonary tuberculosis compared to normal controls. In addition, Northern blots demonstrated striking up-regulation of IL-8 mRNA in macrophages from these patients. M. tuberculosis and its cell wall components lipoarabinomannan (LAM), lipomannan (LM), and phosphoinositolmannoside (PIM) stimulated IL-8 protein release and mRNA expression in vitro from alveolar macrophages, but deacylated LAM did not. Neutralizing antibodies to TNF-alpha and/or IL-1-alpha and beta blocked 83% of the stimulation. IL-8 synthesis and release is an early response of macrophages after phagocytosis of M. tuberculosis. Its production serves to attract both acute and chronic inflammatory cells of active infection and thus participates in the process of containment of the pathogen.

Adult↗
PubMed1992

An immunohistochemical investigation of diagnostic biopsy material taken from short and long term survivors with small cell lung cancer.

An immunohistochemical study has been carried out on fibre optic-biopsy specimens from patients with small cell lung cancer (SCLC) who had either died within 3 months, or who had survived more than 2 years. Long term survivors (LTS) were identified from completed clinical trials at major UK centres and were matched for age and sex within the trial with short term survivors (STS). The panel of immunohistochemical markers included those previously reported to be associated with prognosis, and reagents representative of both neuroendocrine and epithelial differentiation. A preliminary screen of 17 antibodies identified 11 as consistently reactive on paraffin-embedded material using streptavadin-biotin immunoperoxidase. Of 186 identified patients, 110 biopsy samples were retrieved. Of these, 70 gave sufficient material for analysis. All sections were scored by three observers without knowledge of the prognosis. The analysis failed to identify any antigen whose expression was correlated with prognosis. We conclude that, in fibre-optic biopsy specimens, immunohistochemical analysis does not add prognostic information in SCLC.

Antibodies, Monoclonal↗
PubMed1990

Quality of life during chemotherapy for small cell lung cancer: assessment and use of a daily diary card in a randomized trial.

Fifty-three patients who were taking part in a randomized trial of chemotherapy in small cell lung cancer (SCLC) were entered into a study of quality of life measurement using a daily diary card. Patients received either four or eight cycles of initial chemotherapy and daily records were scored, using a four point scale of nausea, sickness, appetite, sleep, mood, pain, activity and general well being. Two hundred and fifty-six of a possible 379 cards were returned (68% compliance). The first 31 patients took part in an assessment of the diary card where comparison was made with nurse ratings using the card, the EORTC questionnaire and the Spitzer quality of life index. These comparisons showed appropriate convergent and divergent validity and demonstrated the sensitivity of the diary card to short term changes compared with the other measures. In the randomized trial the diary card demonstrated a worsening of sickness and related variables as treatment continued. This spilled over into mood and general well being although physical variables of pain, sleep and activity were largely unaffected. Prophylactic cranial irradiation was associated with a transient increase in sickness and vomiting. The study shows that the diary card is an instrument sensitive to short term changes in quality of life and thus especially useful for comparing effects during the period of treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Longevity in small cell lung cancer. A report to the Lung Cancer Subcommittee of the United Kingdom Coordinating Committee for Cancer Research.

An analysis of the long-term results of treatment of 3,681 patients with small cell lung cancer (SCLC) is presented. The data were obtained from major centres in the UK who were conducting treatment trials during the period 1978-1986 and for whom complete computer records and follow-up were available. A total of 217 (5.9%) survived 2 years or more. Two year survival for patients presenting with limited disease (LD) was 8.5% and for extensive disease (ED) 2.2%. Death from SCLC continued until 7 years after diagnosis but not thereafter. At this point overall survival was 3% (3.6% LD, 1.1% ED). Survival after 2 years was not affected by initial disease extent, sex, thoracic radiotherapy or prophylactic cranial irradiation. Death from causes other than SCLC continued throughout the period of observation. Vascular disease, respiratory failure and second tumours were the main other causes of death. The better survival in younger patients was mainly attributable to few deaths from these other causes. These results indicate that only a small proportion of patients with SCLC are cured by current treatment. Although shorter term improvement in survival has been obtained with current treatment, the poor overall long-term results support studies exploring new approaches to cure and to palliation.

Carcinoma, Small Cell↗
PubMed1990

Recombinant targeted proteins for biotherapy.

In an effort to improve existing biotherapies, researchers have used recombinant techniques to alter the structure of toxins, monoclonal antibodies, and other receptor and effector molecules. Experimental research has demonstrated that the extent of problems such as nonspecific toxicity and rapid clearance by the immune system are not as great with genetically engineered toxins as opposed to native toxins. Fusion proteins, which combine portions of toxins, antibodies, or various effector molecules, exhibit the preferred biologic properties of their constituents. Unlike their murine counterparts, chimeric antibodies have the ability to invoke cell-mediated immunity and are less immunogenic to humans. Because they display different antigen-binding specificities on the same molecule, hybrid hybridomas are a potential means of juxtaposing effector cells or toxins to tumor cells. These and other positive features of recombinant proteins offer a decided advantage over previous biotherapeutic agents, and these molecules are expected to find application in the treatment of cancer, the acquired immunodeficiency syndrome, and autoimmune diseases.

Animals↗
PubMed1975

Ossiculotympanic transplantation.

Continued investigations into current tympanoplasty problems have been carried out in the Eye and Ear Clinic, Royal Victoria Hospital, Belfast. Retrospective studies have been helpful in identifying some of the main problems responsible for many of our unsatisfactory results, both in the irradication of disease and the restoration of aural function. Prospective studies into the behavior of grafting materials for tympanic reconstruction in the experimental animal have led us to an overwhelming preference for natural materials as opposed to plastics or stainless steel. Both homologous and autologous bone and cartilage appear to offer good prospects in ossicular replacement techniques. The most satisfactory material we have used for repair of tympanic membrane defects continues to be either autologous or homologous temporalis fascia. The long-term success of these materials in functional restoration is utterly dependent on continued aeration of the tubotympanic cleft.

Animals↗