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Biomedical subjects

D M Harris

Publications and source records attributed to D M Harris.

At least 55 records · Page 3Linked to original sources

Autologous fibrin tissue adhesive biodegration and systemic effects.

A series of experiments was conducted to investigate the rate of Autologous Fibrin Tissue Adhesive (AFTA) degradation by the fibrinolysis inhibitor, epsilon amino caproic acid (EACA). The duration of AFTA clots in vitro, subcutaneous, and in the middle ear was prolonged for a time interval that was proportional to the concentration of EACA in Component II of the adhesive. No toxic reactions were observed in the middle or inner ear. Systemic pathology (thrombosis or emboli) could not be related to the presence of EACA applied in the middle ear or directly into the blood stream at concentrations (mg/kg body weight) up to 1,500 times that expected to occur during surgery on humans.

Aminocaproic Acid↗

Porphyrin fluorescence and photosensitization in head and neck cancer.

Indistinct margin demarcation and autofluorescence are problems in fluorescence delineation of porphyrin-containing head and neck squamous cell cancer (HNSCC). We studied the time course and in vivo localization of porphyrin fluorescence in a squamous cell cancer hamster model and in human HNSCC. After intravenous injection, a gradient in fluorescence intensity developed rapidly until tumors fluoresced above a lower-intensity mucosal background. Hamster tumor and ulcerated HNSCC without porphyrin injection demonstrated autofluorescence grossly indistinguishable from fluorescence in porphyrin-injected tumors. However, fluorescence microscopy revealed autofluorescence to be a surface phenomenon and showed injected porphyrin localized in tumor stroma. We conclude that autofluorescence must be considered when interpreting porphyrin fluorescence. In addition, empirically designed photodynamic therapy can be effective in selected HNSCC. Data from animal experiments provide useful guidelines for the delivery of this therapy.

Aged↗

Fluorescent microscopy of hematoporphyrin derivative in the nude mouse tumor model.

Mechanisms for localization of hematoporphyrin derivative (HPD) within malignant tissue and for tumor necrosis after photodynamic therapy have not yet been established with certainty. We describe a modified freeze-drying technique to study these mechanisms. Normal tissues and squamous cell carcinoma xenografts were examined in nude mice after administration of HPD. Skin reveals marked fluorescence in connective tissue cells. No fluorescence is visible in surface epithelial cells or keratin. Liver shows diffuse fluorescence only in cells lining sinusoids. In tumor, malignant cells do not fluoresce and connective tissue cells fluoresce brilliantly. This technique provides a clear view of HPD fluorescence, frozen instantaneously in location and time. Fluorescence from connective tissue cells in skin and tumor suggests that localization and photodynamic action may be targeted in part at cells that critically support malignant epithelial cell growth as well as at malignant epithelial cells directly.

Animals↗

Photodynamic therapy for head and neck cancer xenografts in athymic mice.

This study examines efficacy and optimal treatment variables of photodynamic therapy (PDT) for human head and neck squamous cancer (HNSC) xenografts in athymic mice. Two and four days after injection of hematoporphyrin derivative (HPD), tumors were illuminated with red light from an argon-dye laser. Sixty-three tumors were treated. With HPD dose and light intensity constant at 7.5 mg/kg and 100 mW/cm2, respectively, the extent of tumor necrosis was strongly dependent on duration of light exposure. There was no substantial difference in results for 30- and 60-minute treatment durations between animals injected with HPD 2 and 4 days before treatment. After 30 minutes treatment time, responses were seen in 8 of 10 mice (2 days post-HPD) and 11 of 12 mice (4 days post-HPD). After 60 minutes treatment time, toxicity was high. We conclude that, in this model, PDT is effective in selective killing of HNSC. For future comparison studies in this model, if the indicated HPD dose and light intensity are used we recommend a 2-day delay after HPD injection and a light exposure duration of 30 minutes.

Animals↗

Light dosimetry in animal models: application to photodynamic therapy in otolaryngology.

Photodynamic therapy (PDT) for treatment of head and neck cancer uses a photoactive compound that is illuminated with 630 nm (red) light. The effectiveness of PDT depends on the penetration of light into tissue that is both tissue and wavelength dependent. The characterization of the optical properties of an animal oral mucosa and skin has been done to determine the amount of light below these tissues available to be used for photodynamic therapy. The tissue absorbance of visible light from 400 nm to 700 nm has been determined in vitro for hamster check pouch mucosa and for athymic mouse skin. The pattern of absorbance is similar for both tissues and demonstrates greater transmission at the longer wavelengths. The diffuse transmittance of light in vivo for these animal models was measured with an interstitial fiberoptic probe. At 630 nm the diffuse transmittance for nude mouse skin averages 10% of the incident light energy, and that for the hamster mucosa almost 50% of the incident light energy.

Animals↗

Extended experimental and preliminary surgical findings with autologous fibrin tissue adhesive made from patients own blood.

A surgical tissue adhesive can be made from the patient's own blood. We have been refining the procedures for manufacturing autologous fibrin tissue adhesive to facilitate its use in the operating room and to increase its bonding strength. Fibrin tissue adhesive efficacy depends on fibrinogen concentration. We found that fibrinogen precipitation using the ammonium sulfate method produced the highest concentration. Bonding power was compared with that of the commercial glue 10 minutes and 30 minutes after glueing two pieces of 1 X 1 cm2 human dura together. Bonding strength of the autologous product was close to that of the commercial product. Comparisons of fibrinolysis inhibition time of autologous fibrin tissue adhesive and commercial glue in experiments on rats over a period of one hour to six days after subcutaneous injection are described.

Aminocaproates↗

Microcomputer surveillance as an aid to rational antibiotic therapy for urinary tract infection (UTI) in general practice.

We report our experience with an inexpensive microcomputer system for the storage and retrieval of susceptibility data on urinary isolates for general practitioners and doctors working in the University of Sheffield Student Health Service. Together with the results from a simple questionnaire into their prescribing habits, we believe that help can be given, enabling practitioners to achieve rational prescribing of antibiotics in their treatment of urinary tract infection.

Anti-Bacterial Agents↗

From angiography to angioscopy: informal discussion.

Devices for visualizing blood vessels have evolved from a rigid, illuminated tube (1913), to a tube with an added convex lens (1922), to one with a transparent inflatable balloon for displacing blood from the line of vision (1943), to a flexible angioscope (1960s). Recent fiberoptic developments make it possible to visualize the orifices of the coronary arteries and simultaneous laser angioplasty. The characteristic fluorescence of hematoporphyrin derivative under ultraviolet light has been visualized angioscopically in experimental atherosclerotic plaque, where it accumulates and acts as a marker. However, several requirements need to be met in order for angioscopy to fulfill its therapeutic possibilities in angioplasty, thrombolytic therapy, intraoperative inspection of vascular anastomoses, and its diagnostic potential in distinguishing plaques from clots and pulmonary embolisms from other obstructions. These requirements are: (1) variously-sized angioscopes to accommodate iliac, femoral, renal, and coronary arteries; (2) percutaneous introducers in the various sizes to prevent back-bleeding; (3) a more flexible, easily manipulated fiberoptic; (4) a sufficiently inflatable balloon tip; (5) cross hairs and reference points in the optical system; and (6) optimal focal lengths for the areas to be visualized.

Journal Article↗

Microscopic fluorescence in photodynamic therapy.

The use of hematoporphyrin derivative (HPD) as a photosensitizer has been studied in malignant tumor detection via fluorescence and in tumor destruction via a toxic photochemical reaction. Squamous cell carcinoma has been induced in hamster buccal mucosa utilizing the known carcinogen dimethyl-benzanthracene. HPD was injected intraperitoneally, then at 24 and 48 hours following injection, unstained frozen section specimens were studied with fluorescent microscopy and photographed. The same specimens were then stained with hematoxylin and eosin and the microscopy correlated. HPD fluorescence was documented in the fibrous stroma of the tumor and in the keratin layer. Essentially no fluorescence was noted in the malignant squamous cells themselves. No consistent differences between the two postinjection times were noted. These qualitative observations support the postulated mechanism of HPD accumulation in tumors.

Animals↗

Evaluation of Malthus 128H microbiological growth analyser for detecting significant bacteriuria.

In a pilot study a prototype Malthus 128H microbiological growth analyser was used to study the growth of six commonly encountered urinary pathogens in a range of five different laboratory media. No single medium had been able to show acceptable conductance changes for all bacteria within five hours. Subsequently, the Malthus system, with fastidious anaerobe broth as the culture medium, was used to screen 500 consecutive clinical specimens of urine for significant bacteriuria. After two and a half hours the Malthus system detected 32 out of the 40 true positives and eight of the 44 contaminated urines. Increasing the detection time to five hours permitted the recognition of 39 true positives and 37 contaminated urines.

Bacteriological Techniques↗

Fibrin tissue adhesive and glass ceramic strut for ossicular chain replacement. Electrophysiologic and histologic findings.

The tolerance of the inner ear to fibrin tissue adhesive was tested. In experimental surgery on thirty-four chinchilla ears, Fibrin Sealant was applied to the inner ear contents by closing the oval window with a connective tissue graft dipped in the adhesive and gluing a Macor glass ceramic strut between this graft and tympanic membrane. No inner ear changes or tissue damage were found. The loss in auditory sensitivity monitored by auditory brain stem response thresholds was commensurate with the amount of loss to be expected with ossicular chain replacement. The findings suggest that this tissue glue can be safely applied to the labyrinth.

Animals↗

Autologous fibrin tissue adhesive.

Various methods of making fibrin tissue adhesive from a patient's own blood were evaluated. The method using ammonium sulfate for fibrinogen preparation produced the greatest bonding strength. The average bonding strength of the commercially manufactured adhesive and of the autologous fibrin tissue adhesive were compared at 10 minutes and 30 minutes after glueing together 1 X 1 cm samples of fresh human dura. Results indicate the commercial glue holding 57 gms/cm2 at 10 minutes and 123 gms/cm2 at 30 minutes, while autologous glue prepared with the "ammonium sulfate method" has a bonding strength of 41 gms/cm2 at 10 minutes and 217 gms/cm2 at 30 minutes.

Ammonium Sulfate↗

Donor transportation.

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Health Services Accessibility↗

Ontogenetic changes in frequency mapping of a mammalian ear.

Cochlear microphonic iso-response functions reported here suggest an explanation of frequency-dependent changes in hearing sensitivity during early development. The work is a direct demonstration of developmental changes in the spatial frequency map of the mammalian hearing organ. Intracochlear recordings from the midbasal turn in a series of age-graded gerbils reveal a progressive increase in best frequency, spanning approximately two octaves, from the time of onset of function until adultlike responses are seen. It is, therefore, suggested that ontogenetic changes in the cellular structure of the organ of Corti contribute to an age-dependent shift in micromechanical response.

Aging↗

Experimental use of fibrin tissue adhesive in middle ear surgery.

The biocompatibility of a new tissue adhesive was tested. Its major advantages are adhesions, hemostasis, and the promotion of wound healing. In experimental surgery on 43 middle ears of chinchillas, documented by histological evidence obtained 45 days after operation, the validity of the following two hypotheses was established. That fibrin tissue adhesive placed upon the footplate of the stapes is biologically compatible, biodegradable and does not cause toxic, inflammatory or foreign body reactions, or other tissue damage to middle ear structures. That a small piece of bone glued on the long process of the incus with fibrin tissue adhesive shows permanent tissue union. In addition, in cases where the inner ear was accidentally opened by surgically subluxating the stapes and adhesive was free to enter the vestibule, evidence was obtained that there was no damage to inner ear structures. This finding deserves further investigation.

Animals↗