Miniaturized intraocular carbon dioxide laser photosurgical system for multi-incision vitrectomy.
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Biomedical subjects
Publications and source records attributed to M R Smith.
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Intraocular carbon dioxide laser has been used for photocautery and photo-incision as an adjunct to vitrectomy. This utilizes a new fluid-tissue interface application for the 10.6 micrometer wavelength infrared radiation. The use of an intraocular probe with an infrared transmitting window through a pars plana incision allows the placement of infrared energy in a fluid medium. The results of animal experimentation and of preliminary clinical trials in human patients are reported. The carbon dioxide laser appears to be a safe and reliable means of intraocular photocautery and photoincision.
Although the concentration of misonidazole measured in human tumours may appear to be only 50--70% of the corresponding blood level, the concentration within the intra- and extracellular fluid of the tumour may be nearer 100% of the blood level. Causes for these apparent low levels of drug which have been investigated are: 1. Presence of fat in the tissue. 2. Presence of non-cellular material in the tissue. 3. Degradation of the drug by anaerobic metabolism after biopsy. An in vitro experiment to test the partitior fractionation study of the distribution of misonidazole showed that it is distributed mainly in the fluid compartment of the cell and that overall drug levels in tissue are related to the fluid content of the tissue. Serial measurements of misonidazole on tissue after removal from the body have shown that breakdown of the drug occurs when the tissue becomes anoxic. These results suggest that the concentration of misonidazole present within tumour cells is higher than the overall level measured for the tissue and that the enhancement ratio to be expected may therefore be higher also.
The indications and contraindications for the use of carbon dioxide laser photocautery at the time of vitrectomy have been reviewed. Indications include posterior retinal tears either in flat or elevated sensory retina; elevated fibrovascular fronds on the optic nerve or elsewhere; flat neovascularization elsewhere, bleeding rubeotic iris vessels. It is also used as a means of panretinal endophotocoagulation. Contraindications include flat disc neovascularization and areas within one disc diameter of the macula and nerve. The advantages and disadvantages of the 10.6 micrometer infrared wavelength of carbon dioxide laser photocautery are discussed.
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Methanosarcina strain 227 grew rapidly and produced methane on a mineral medium containing acetate as the sole added organic substrate. Cell yields but not doubling times were affected by the presence or absence of yeast extract. Greater cell yields occurred in yeast extract medium than in mineral medium. Radioactive labeling studies showed that acetate was decarboxylated in mineral medium, as was shown previously in complex medium. The specific radioactivity of methane produced per specific acitvity of acetate added was not significantly different in yeast extract medium compared with mineral medium. Unequivocal evidence indicates that the cleavage of acetate to methane and carbon dioxide provided the energy for growth in the presence or absence of other organic compounds; these latter compounds do not serve as energy sources, electron donors, or significant sources of methane during this aceticlastic reaction.
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Carbon dioxide laser photocautery was used successfully intraocularly in human patients to seal fibrovascular fronds and retinal tears at the time of vitrectomy. Closure of rubeotic vessels in the iris was demonstrated histologically. The 10.6-microgram infrared radiation was delivered to the intraocular treatment site by means of 1.5-mm-diameter photocautery probe containing a 1.0-mm-diameter lumen closed at the end with an infrared transmitting window. Treatment was localized to the tissue adjacent to the window. Typical energy dosage was 0.4 W for 2 to 4 s duration. These early clinical trials were carried out under the guidelines established by the Food and Drug Administration; informed consent clearly outlined the experimental nature of these studies.
Intraocular carbon dioxide laser photocautery is used to produce localized closure of vascular channels and chorioretinal adhesion in the albino rabbit. The retinal lesion is sharply demarcated because of the high tissue absorption of CO2 laser radiation. Varying degrees of chorioretinal adhesion can be achieved. The CO2 laser photocautery technique may provide a suitable method of closing vessels and sealing retinal tears at the time of vitrectomy. Accurate placement of the cautery tip on the target area can be accomplished under stereoscopic magnified viewing with the operating microscope and contact lens. Electrical shock hazard is completely eliminated with the CO2 laser energy modality.
The distribution and clearance of misonidazole (MIS = Ro-07-0582) were studied in C57 mouse tissues and in transplants of Lewis lung tumour. The half life of the drug in blood after a dose of 1 mg/g i.p. was 3 h. Some tissues, such as liver, were found to have consistently low MIS levels, and this was found to be due to degradation of the drug after removal of the tissues from the host. The in vivo cytotoxicity of MIS to Lewis lung tumour cells was studied using an in-vitro colony assay. After half of the tumours had been irradiated with 10 Gy to kill most of the oxic cells, the mice received i.p. injections of MIS. To simulate the longer drug exposure of human tumour cells (due to the longer half life in man) a repeated injection regime was used in some mice. There was no significant cell kill after a single dose, but with a prolonged exposure to the drug in the multiply injected animals, cell survival was reduced to 50% of control in both the irradiated and unirradiated tumours. Since the hypoxic fraction of the unirradiated tumour is probably not more than 30%, it would appear that MIS is not selectively cytotoxic to hypoxic cells. However, MIS had a much greater cytotoxic effect upon hypoxic Lewis lung tumour cells in vitro, with very little or no effect on cells grown in air. This would support the theory that the presence of hypoxic cells is essential for the expression of MIS cytotoxicity.
Levels of misonidazole in human tumours, normal tissues and blood have been measured in patients given a 1g oral dose of drug before surgery or biopsy. The results show that 50--70% of the blood level was found in a wide range of tumours and that similar levels were found in adjacent normal tissues. Good penetration of drug was achieved within tumours, and up to 90--100% of the blood level was found in the necrotic cyst fluid at the centre of some tumours. CSF studies showed free diffusion into the CNS, which was confirmed by finding 50--70% of the blood level within brain tumours. A delay of passage of drugs into the CSF was noted, which was not found for drug diffusion into bile and saliva.
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A new form of carbon dioxide laser has been developed that allows placement of infrared energy within a fluid medium. Transvitreal photocautery, vitrectomy, and laser scalpel incisions have been accomplished utilizing this delivery modality of infrared energy. Clinical trials are presently underway.
An acetate-fermenting strain of Methanosarcina was isolated from an acetate enrichment culture inoculated with anaerobic sludge from a waste treatment digestor. In pure culture, this organism fermented acetate in the absence of added hydrogen at rates comparable in magnitude to those found in digestor systems. This rate was significantly higher than previously obtained for pure cultures of this genus. Mineral components of yeast extract were highly stimulatory for cultures growing on methanol. Comparable stimulation was not observed for cultures growing on acetate. Labeling studies indicated that acetate was converted to methane and CO2 as predicted by previous studies on mixed cultures. Total oxidation or reduction of acetate was not the mechanism of conversion of acetate to methane by the pure culture. The ability of this strain to form colonies or to produce methane from acetate was apparently influenced by the choice of substrate and conditions used for growing the inoculum.
Methanosarcina strain 227 exhibited exponential growth on sodium acetate in the absence of added H(2). Under these conditions, rates of methanogenesis were limited by concentrations of acetate below 0.05 M. One mole of methane was formed per mole of acetate consumed. Additional evidence from radioactive labeling studies indicated that sufficient energy for growth was obtained by the decarboxylation of acetate. Diauxic growth and sequential methanogenesis from methanol followed by acetate occurred in the presence of mixtures of methanol and acetate. Detailed studies showed that methanol-grown cells did not metabolize acetate in the presence of methanol, although acetate-grown cells did metabolize methanol and acetate simultaneously before shifting to methanol. Acetate catabolism appeared to be regulated in response to the presence of better metabolizable substrates such as methanol or H(2)-CO(2) by a mechanism resembling catabolite repression. Inhibition of methanogenesis from acetate by 2-bromoethanesulfonate, an analog of coenzyme M, was reversed by addition of coenzyme M. Labeling studies also showed that methanol may lie on the acetate pathway. These results suggested that methanogenesis from acetate, methanol, and H(2)-CO(2) may have some steps in common, as originally proposed by Barker. Studies with various inhibitors, together with molar growth yield data, suggest a role for electron transport mechanisms in energy metabolism during methanogenesis from methanol, acetate, and H(2)-CO(2).
Treatment with a combination of trimethoprim and sulfamethoxazole proved lifesaving in a patient with pulmonary melioidosis after therapeutic failure occurred with other antibiotics to which the organisms were sensitive in vitro. Antagonistic interaction of drugs occurred when the combination of trimethoprim and sulfamethoxazole was given along with other antibiotics. The combination of trimethoprim and sulfamethoxazole should be considered a major addition to the pharmacologic armamentarium for the treatment of pulmonary melioidosis.
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