Four patterns of porphyrin accumulation were observed by high-pressure liquid chromatography when chemicals were added to chick embryo liver cells. These patterns provide a guide to the site of action of the chemicals. Protoporphyrin accumulated in response to 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC), a result consistent with its ability to inhibit ferrochelatase. Uroporphyrin and heptacarboxylic acid porphyrin accumulated in response to 3,3′,4,4′-tetrachlorobiphenyl, 2,2′,4,4′,6,6′-hexachlorobiphenyl, and 3,5-diethoxycarhonyl-2,4,6-trimethylpyridine, a result suggesting inhibition of uroporphyrinogen decarboxylase. Coproporphyrin was the major porphyrin to accumulate in response to allylisopropylacetamide, aromatic amides, and steroids, a result suggesting inhibition of coproporphyrinogen oxidase. A mixture of uroporphyrin, heptacarboxylic acid porphyrin and coproporphyrin accumulated in response to aromatic di- and mono-esters, aliphatic diesters, and aliphatic amides. The pattern observed after addition of excess δ-aminolevulinic acid (ALA) the endogenous substrate of the pathway to the cells was proto- > copro- > uro-porphyrin. This pattern resembled that produced by DDC but by none of the other chemicals. It was concluded that porphyrin accumulation can not be attributed solely to the induction of ALA-synthetase. It appears that porphyrin-inducing chemicals exert an additional effect on one or other of the enzymes of the heme biosynthetic pathway.
A 1.9 micrometers laser is used to weld small diameter vessels. The absorption characteristic of tissues at this wavelength renders this laser suitable for welding of vessels with diameters in the 1 to 3 mm range. The appropriate laser power range for welding is 120 to 200 mW with a fluence on target of approximately 100 J/cm2. For vessel wall thicknesses matching the optical absorption depth, measured burst pressure was approximately 400 mmHg. In this case the acute weld strength is greater than 3 X 106 dynes/cm2. Anastomotic compliance of the welded zone was a factor of two lower than native vessel tissue both immediately following welding and after 10 weeks of healing. The advantages offered by this laser wavelength are convenient energy delivery via fiber optics, no irrigation needed for tissue cooling, and applicability to small vessel anastomoses.
The effects of griseofulvin and 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC) on ferrochelatase activity were compared in the 17-day-old chick embryo. While DDC reduced enzyme activity markedly, griseofulvin did not exert an inhibitory effect. These results are consistent with the fact that DDC, but not griseofulvin, causes hepatic porphyrin accumulation in this species. The effects of griseofulvin and DDC on ferrochelatase activity were compared in chick embryo liver cell culture. DDC reduced ferrochelatase activity markedly while griseofulvin caused no significant inhibition. Both DDC and griseofulvin cause marked porphyrin accumulation in this system. The porphyrins were separated and quantitated using high-performance liquid chromatography. Protoporphyrin was the major porphyrin which accumulated in response to DDC, a result consistent with the inhibition of ferrochelatase. In contrast, protoporphyrin was a minor porphyrin accumulating in response to griseofulvin, a result consistent with the failure of griseofulvin to inhibit ferrochelatase; in this case, coproporphyrin was the major porphyrin to accumulate. These findings in the chick embryo contrast with those reported in rodents, where both DDC and griseofulvin exert an inhibitory effect on ferrochelatase. Clearly, species differences exist in the effects of griseofulvin on the enzymes of the heme biosynthetic pathway.
To review the variation in time spent on the waiting list for elective vascular surgery provided by a single team of specialists.A prospective cohort study.An acute care hospital in Ontario.One thousand and eighty-four consecutive patients with vascular problems accepted for elective surgery between 1994 and 1998.Abdominal aortic aneurysm (AAA) repair; carotid endarterectomy (CAD); surgery for peripheral vascular disease (PVD); and arteriovenous fistula (AVF) for long-term access in patients with renal failure.Time-to-treatment curves, admission rates.The weekly admission rate was 9.8% on average. The proportion of patients who underwent operation was 50% at 7 weeks, 75% at 14 weeks and 90% at 26 weeks. The weekly admission rate varied according to clinical priority, from 42% in priority class 1 to 6% in class 5. In any priority class, the admission rate was not constant over time. Although the proportion of patients operated on within the maximum recommended time in classes 1, 2, 3 and 4 was 52%, 50%, 35% and 20% respectively, the last 10% of patients waited 5 to 16 weeks, 10 to 16 weeks, 16 to 37 weeks, and 25 to 39 weeks respectively. There were statistically significant differences in waiting time by surgical procedure among the least urgent cases, with median times of 7, 10 and 19 weeks for AVF, PVD and CAD procedures, respectively.When queuing procedures are uniform, the waiting times for access to elective vascular surgery provided by the same team of specialists differ considerably for patients with equal surgical needs and urgency. It remains to be examined whether delays in scheduling operations and cancellations affect the waiting time after adjustment for urgency and comorbidity.
Under normal circumstances the heme biosynthetic pathway is carefully controlled and porphyrins are formed in only trace amounts. When control mechanisms are disturbed by xenobiotics, porphyrins may be formed and serve as a signal of the interaction between a xenobiotic and the heme biosynthetic pathway. For example, porphyrinuria was an early manifestation of a hexachlorobenzene-induced porphyria outbreak in Turkey. In humans exposed to polybrominated biphenyls and to 2,3,7,8-tetrachlorodibenzo-p-dioxin the urinary porphyrin pattern was significantly different from normal in a large number of exposed individuals. The question is raised whether measurement of urinary porphyrin profiles by improved methods will enable an estimate to be made of the extent of exposure to haloaromatic hydrocarbons in the human population. A wide variety of xenobiotics interact with the prosthetic heme of cytochrome P-450 forming novel N-alkylporphyrins. Identification of these N-alkylporphyrins in body fluids might provide a means of assessing exposure to a variety of xenobiotics in human populations.
