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Biomedical subjects

K Lam

Publications and source records attributed to K Lam.

119 records · Page 7Linked to original sources

Production of mucoid microcolonies by Pseudomonas aeruginosa within infected lungs in cystic fibrosis.

Direct electron microscopic examination of postmortem lung material from cystic fibrosis patients infected with Pseudomonas aeruginosa has shown that these bacterial cells form distinct fiber-enclosed microcolonies in the infected alveoli. Similar examination of bronchoscopy material from infected cystic fibrosis patients showed that the fibres of the enveloping matrix are definitely associated with the bacterial cells. The fibers of the extracellular matrix stain with ruthenium red and are therefore presumed to be polyanionic. When mucoid strains of P. aeruginosa were recovered from cystic fibrosis patients and grown in a suitable liquid medium, they were found to produce large microcolonies whose component cells were embedded in a very extensive matrix of polyanionic fibers that could be stabilized by reaction with antibodies to prevent collapse during the dehydration steps of preparation for electron microscopy. When these mucoid strains of P. aeruginosa were used to produce pulmonary infections of rats by the agar bead method, the infected alveoli contained large fiber-enclosed bacterial microcolonies. We conclude that the cells of P. aeruginosa that infect cystic fibrosis patients form microcolonies that are enveloped in a fibrous anionic matrix and that these microcolonies can be duplicated in in vitro cultures and in animal model systems.

Cystic Fibrosis↗

Speech sounds: evaluation of a device for their visual presentation.

Two experiments were designed to evaluate a prototype device developed to provide a visual presentation of speech sounds as a potential assistive device for hearing-imparied persons. In the 1st experiment, the ability of adults with unimpaired hearing to recognize the visual patterns of 3 vowels spoken by 3 different speakers was assessed, and in the 2nd experiment, visual and auditory distinctiveness of the 3 vowels was compared. Results showed that subjects received different speech information from the Visual Speech Spectrum Analyzer (VISSA) and the normal auditory system; however, differences were judged minor. The device has potential as a speech therapy aid and may prove helpful to hearing imparied persons.

Adult↗

Use of adenosine 5'-triphosphate as an indicator of the microbiota biomass in rumen contents.

A number of techniques were tested for their efficiency in extracting adenosine 5'-triphosphate (ATP) from strained rumen fluid (SRF). Extraction with 0.6 N H(2)SO(4), using a modification of the procedure described by Lee et al. (1971), was the most efficient and was better suited for extracting particulate samples. Neutralized extracts could not be stored frozen before assaying for ATP because large losses were incurred. The inclusion of internal standards was necessary to correct for incomplete recovery of ATP. The ATP concentration in rumen contents from a cow receiving a ration of dried roughage (mainly alfalfa hay) ranged from 31 to 56 mug of ATP per g of contents. Approximately 75% of the ATP was associated with the particulate material. The ATP was primarily of microbial origin, since only traces of ATP were present in the feed and none was found in "cell-free" rumen fluid. Fractionation of the bacterial and protozoal populations in SRF resulted in the isolation of an enriched protozoal fraction with a 10-fold higher ATP concentration than that of the separated rumen bacteria. The ATP pool sizes of nine functionally important rumen bacteria during the exponential phase of growth ranged from 1.1 to 17.6 mug of ATP per mg of dry weight. This information indicates that using ATP as a measure of microbial biomass in rumen contents must be done with caution because of possible variations in the efficiency of extraction of ATP from rumen contents and differences in the concentration of ATP in rumen microbes.

Journal Article↗

Interstitial thermoradiotherapy for recurrent head and neck cancer.

From 1985 to 1987, 22 head and neck sites in 20 patients with recurrent tumors were treated with interstitial thermoradiotherapy (ITRT). The sites treated were 15 neck (68%), four tongue (18%), two parotid (9%), and one buccal mucosa (4%). Squamous cell carcinoma was diagnosed in 21 sites and adenocarcinoma in the other. All patients had prior radiotherapy (RT), including 15 who underwent a combination of RT and surgery. Interstitial RT with iridium 192 (mean dose, 40 Gy) was combined with interstitial microwave hyperthermia (mean thermal dose, 90 units). Complete response (CR) was obtained in 15 (68%) sites and partial response (PR) in seven (32%) sites. There were no local recurrences in the 15 CR patients during a period of observation of up to 30 months. Of the seven PR patients, one had radical neck dissection and is free of tumor after 28 months. Tumor volume was an important factor influencing CR (P less than .001), whereas RT and thermal dose were not (P = .3). Of the 20 patients treated, 19 experienced major subjective benefit. Serious complications occurred in two patients: one had localized soft tissue necrosis, the other had aspiration pneumonia. ITRT was well-tolerated by patients despite prior aggressive therapy. High objective response rate and low toxicity demonstrate the value of this treatment combination in the management of patients with postradiation recurrence of head and neck tumors.

Aged↗

The role of the microcolony mode of growth in the pathogenesis of Pseudomonas aeruginosa infections.

In nature Pseudomonas aeruginosa grows in two modes, the mobile "swarmer" cell and the glycocalyx-enclosed microcolony. The microcolony mode is numerically dominant perhaps because it provides adhesion in a favorable niche and protection from bacteriophages and phagocytic predators. When this organism colonizes the compromised human host, a broad spectrum of different types of infection is produced, ranging from asymptomatic persistent cystitis to the overwhelming bacteremia seen in neutropenic patients. These infections differ radically both in their degree of toxicity and invasiveness and in their susceptibility to control with specific antibodies and/or antibiotics. These differences may reflect the degree to which intact host defense mechanisms force the bacteria to adopt the defensive, microcolony mode of growth. As examples, the nearly intact host defense mechanisms and vigorous immune response of patients with cystic fibrosis force P. aeruginosa in pulmonary infections into a demonstrably cryptic, microcolony mode of growth that allows its persistence in the face of specific antibodies and antibiotics but limits its toxic activity and its dissemination. In contrast, the ruined defense mechanisms of burned skin allow the spread of bacteria in the mobile mode; toxic effects are seen in neighboring tissues, and a mixed mobile-microcolony reservoir population, whose mobile members can subsequently invade the circulatory system, is built up in the burned tissue. Thus, it is important to define the mode of bacterial growth in each type of P. aeruginosa infection and, where the microcolony mode is predominant, to understand the chemistry of the enveloping exopolysaccharide in order to limit its synthesis and/or facilitate its penetration by antibodies and antibiotics.

Animals↗

Prevention and control of bacterial infections associated with medical devices.

Bacteria that grow in association with medical devices always form slime enclosed biofilms, within which they are protected, to a large extent, from the bactericidal activity of chemical biocides and antibiotics. Mature biofilms (> 7 days) are demonstrably resistant to 500-5,000 times the concentrations of these agents than are necessary to kill free floating (planktonic) cells of the same organism. The authors have discovered that this well established inherent resistance of biofilm bacteria to antibacterial agents can be completely obviated if these agents are applied to these adherent populations within an electric field. The killing of biofilm bacteria by antibiotics can be dramatically enhanced by relatively weak electric fields (1.5 V/cm and 15 microA/cm2) that, in themselves, have no deleterious effects on these slime protected populations adherent to plastic or metal surfaces. This bioelectric technology can readily be used to enhance the preimplantation sterilization of medical devices by biocides. The authors suggest that it may also be used to control biofilm formation and consequent infection by electrically enhanced perioperative antibiotic prophylaxis and by electrically enhanced penetration of antibiotics to kill the biofilm bacteria that form the inherently resistant nidus of chronic device related infections.

Anti-Bacterial Agents↗

Ascending infection of the biliary tract after surgical sphincterotomy and biliary stenting.

It has been widely accepted that there is an ascending route of bacterial infection of the biliary tract but there is a lack of direct evidence. This hypothesis was tested in an animal experiment using the cat as an animal model. The implantation of biliary stents and surgical sphincterotomy were performed in these animals, with sham controls. Stents bypassing the sphincter of Oddi with the tip in the duodenal micro-organisms and the biliary tract was heavily contaminated. Blockage of these stents resulted in biliary obstruction. Stents implanted within the common bile duct, proximal to the sphincter were largely unaffected by biofilm formation. After surgical sphincterotomy the biliary tract was also contaminated but, in the absence of obstruction, the animals did not develop any symptoms. It was concluded that ascending infection by duodenal biliary reflux, via the sphincter of Oddi, is an important route of infection in the biliary system.

Animals↗

Bacterial biofilm, brown pigment stone and blockage of biliary stents.

Bacterial pathogens gain access into the biliary system by descending via the portal venous circulation or ascending through the sphincter of Oddi in duodenal-biliary reflux. Bacteria thrive as glycocalyx-enclosed microcolonies, coalescing to form an adherent biofilm. The establishment of biofilm is a key event in the formation of biliary sludge and pigment gallstones, and the blockage of biliary stents. The biofilm mode of growth is very effective because it provides bacteria with a measure of protection from antibacterial agents and phagocytic leucocytes. Calcification of the matrix confers further protection for the micro-organisms living inside the biofilm. To date, attempts to prevent blockage of biliary stent have employed physical methods by using large self-expandable stents and stents without side hole. Incorporation of antibiotics within stents has not been successful presumably because bacteria once living in their biofilm are quite resistant to antimicrobial agents. Even the most toxic bile salts have no effect on the biofilm bacteria. Yet, hydrophobic bile salts reduce bacterial adhesion on biomaterial, suggesting that incorporation of such bile salts might prevent the formation of bacterial biofilm.

Animals↗

Interstitial thermoradiotherapy for recurrent or persistent tumours.

Between 1984 and 1986, 31 sites in 27 patients with biopsy proven tumours were treated with a combination of interstitial microwave hyperthermia (HT) and iridium 192 implants (RT). The 31 sites treated included fifteen (48 per cent) head and neck, six (20 per cent) breast, four (13 per cent) vagina and cervix, and six (20 per cent) others. All patients had prior surgery, RT, or chemotherapy. Of the 31 sites treated, 19 (61 per cent) had complete response (CR) with no recurrence in the volume treated. Additionally, eight patients remained free of tumour from 3 to 24 months. Partial response (PR) was seen in 11 (36 per cent) sites while one (3 per cent) had lesser degree tumour regression. Tumour control rate correlated well with the dose of radiation, p = 0.02, and tumour volume, p = 0.02, but not with thermal dose. Treatment complications of significance occurred in one (3 per cent) site, which developed soft tissue necrosis. This study again has demonstrated the effectiveness of RT-HT combination in treatment of recurrent tumours.

Adult↗