Folate and folate-dependent enzymes associated with rat CNS development.

Folic acid and its derivatives are important mediators in growth-related cellular processes. The concentration of folate and two folate-dependent enzymes, 10-formyltetrahydrofolate synthetase (10-FTHFS) and 10-formyltetrahydrofolate dehydrogenase (10-FTHFDH), was determined in brain regions over the early period of rat development. Folate concentrations determined at birth were high in all brain regions studied. During the first 2 weeks, folate concentrations declined steadily, followed by a period of significant increase. High and invariant activity of 10-FTHFS was found throughout the period of study. Low amounts of 10-FTHFDH were seen for the first 2 weeks, but increased significantly from postnatal days 14 to 28. These changes correlated with changes determined in the concentration of folate, supporting the idea that this protein is involved with folate uptake and/or storage. Furthermore, immunohistochemical expression of 10-FTHFDH in different rat brain regions revealed glial cells as a preferential cellular location for this folate-binding protein.

Immunohistochemical localization of UDP-glucuronosyltransferases in rat brain during early development.

Extrahepatic glucuronidation, such as that in the central nervous system (CNS), may play a very important role in xenobiotic disposition and may serve to protect the CNS from potentially toxic xenobiotics. UDP-glucuronosyltransferase (UGT) 1A6 is an important catalyst for phenol and polycyclic aromatic hydrocarbon glucuronidation. Studies were designed to determine the immunohistochemical localization of UGT1A6 and the steroid-reactive UGTs 2B2 and 2B3 in brain regions throughout the rat development. Neuronal cells, such as pyramidal cells, in sections from cerebral cortex and hippocampus displayed intensive UGT1A6-specific staining. UGT1A6-specific staining was also found in neuronal cells throughout the cerebral cortex, as well as in the cerebellar white matter. Glial cells revealed no apparent staining. In addition, staining for UGT1A6 was seen in choroid plexus at a later developmental stage. Although UGT1A6 staining was evident, brain sections analyzed for UGT2B2 and UGT2B3 immunoreactivity showed no significant staining. These results provide the first definitive evidence for the presence and cellular localization of UGT1A6, in neurons of developing rat brain, whereas UGT2B2 and UGT2B3 were not detected.

A comparative evaluation of femorofemoral crossover bypass and iliofemoral bypass for unilateral iliac artery occlusive disease.

The purpose of this study was to compare the results of extra-anatomic femorofemoral crossover bypass grafting to the anatomic iliofemoral bypass grafting procedure in the treatment of patients with unilateral iliac artery occlusive disease with respect to patency and limb salvage. The records of all patients with unilateral iliac artery disease who underwent revascularization between January 1988 and December 1995 at the University of Iowa Hospitals and Clinics (UIHC) were retrospectively reviewed; 108 patients were identified and divided into two groups. Group I (n=68; male/female=44/24) was composed of all patients who underwent a femorofemoral crossover extra-anatomic bypass. All patients who underwent an iliofemoral anatomic bypass constituted group II (n=40; male/female=24/16). The mean age for group I was 60 years (range 28-87) and for group II, 54 years (range 14-86). The medical risk factors between both groups were comparable. Except for the higher incidence of gangrene in group II the indications for surgery were comparable between both groups. A polytetrafluoroethylene graft was used in 88% of group I patients and in 90% of group II patients (NS). In the remaining patients, an autogenous vein conduit was used. Two patients from group I (2.9%) died in the perioperative period (NS). Graft patency was assessed by clinical evaluation, Doppler-derived ankle/brachial indices, and color duplex imaging. The cumulative primary and secondary patency rates, limb salvage, and patient survival were calculated by use of life table analysis (SE<0.1). The need for simultaneous outflow and inflow procedures at the time of surgery was comparable between both groups. The proportion of patients who underwent further revascularization during follow-up was also comparable. The 5-year primary and secondary graft patency rates were 81.7% and 90.3%, in group I and 61.3% and 80.5% in group II. Although the difference between both groups was not significant there was a tendency toward higher rates with femorofemoral bypass. The 5-year survival rates of 80.3% for group I and 73.3% for group II were comparable. These data suggest that there is no significant difference in the long-term results between the femorofemoral crossover bypass grafts and iliofemoral grafts. Both procedures result in acceptable patency and limb salvage rates. The femorofemoral bypass is, however, more attractive, for it can be performed under local anesthesia if needed and does not involve the creation of the retroperitoneal incision necessary with the iliofemoral bypass.

Is color duplex surveillance of infrainguinal polytetrafluoroethylene grafts worthwhile?

BACKGROUND: Unlike vein bypasses, the role of duplex surveillance of infrainguinal prosthetic bypass grafts is controversial. The purpose of this study was to evaluate the adequacy of color duplex surveillance in identifying failing infrainguinal polytetrafluoroethylene (PTFE) bypass grafts and to assess its value in predicting continued bypass patency. METHOD: The surveillance data of primarily patent PTFE bypass grafts were compared with those of revised/occluded PTFE grafts. Ninety-five patients underwent 102 infrainguinal PTFE bypass grafts from January 1991 to December 1996 and were enrolled in a duplex surveillance program at 1 month postoperatively, every 3 months in the first year, every 6 months in the second year, and yearly thereafter. RESULTS: Seventy grafts remained primarily patent, 5 were revised and 27 occluded. There was no significant difference in the mean age, gender, indication for surgery, type of original procedure, or duration of follow-up between both groups. Four hundred and seven duplex surveillance data were available for analysis. Focal increase in peak systolic velocity (PSV) 3 x the adjacent segment or low flow manifested by PSV <45 cm/sec were considered abnormal. In the primarily patent group, 5 bypasses had abnormal duplex surveillance and were found to have no abnormality on angiogram and remained patent during the study period. In the revised/occluded group, duplex surveillance was abnormal in 8 bypasses. Twenty-four bypasses occluded without any predicting abnormalities on their last duplex examination, which was performed within 3 months from the occlusion in the majority of the patients. In the 27 occluded bypasses, no intervention was necessary following the occlusion in 7 grafts because of mild or no symptoms. Two patients were treated with a primary amputation and 2 had new bypasses. In 16 occluded grafts, salvage of the PTFE bypass was attempted. Ten of these grafts were patent at the end of the follow-up. The sensitivity of duplex surveillance was 25% with a positive predictive value of 61.5%. CONCLUSION: Duplex surveillance of infrainguinal PTFE bypass grafts has a low yield and is inadequate at predicting continued bypass patency.

Folate and 10-formyltetrahydrofolate dehydrogenase in human and rat retina: relation to methanol toxicity.

Ocular toxicity, a well-recognized outcome of methanol poisoning in humans, correlates with formate accumulation in blood following the ingestion of methanol. Rodents, however, are a species known to be resistant to the toxicity of formate. The present study was designed to determine whether components of folate-dependent formate oxidation, e.g., folate and 10-CHO-H4-folate dehydrogenase (10-FDH), exist in retina and whether differences in these components might explain species-determined susceptibility to methanol intoxication. Total folate levels were determined in human and rat retinal tissues and were found to be much lower than the levels in liver. However, folate levels in human retina were only 14% of those determined in rat retina. Western blot analysis was used to quantify the amount of cytosolic and mitochondrial 10-FDH in retinal tissues. Results of these studies showed that comparable amounts of this enzyme were present in both cellular compartments in each species. However, the amount of 10-FDH in human retina was approximately three times the amount found in rat retina. In order to determine the cell type(s) within the retina that contained 10-FDH, immunohistochemical staining for 10-FDH was carried out. Confocal microscopic image analysis of human and rat retinae showed colocalization of 10-FDH primarily with Muller cell protein markers [glial fibrillary acidic protein (GFAP), vimentin, and carbonic anhydrase]. Therefore, 10-FDH was found to be preferentially localized in this cell type. Since Müller cells appear to represent the target for formate-induced ocular toxicity, our data suggest that formate oxidation reactions might serve two roles, first a protective role and then a role in methanol-induced toxicity in Müller cells.

Revascularization of the ischemic diabetic foot using popliteal artery inflow.

Between March 1988 and June 1994, 35 popliteal to distal artery vein bypasses were done in 32 diabetic patients. There were 16 males and 16 females with an average age of 60 years. Eighteen patients (56%) had insulin dependent diabetes mellitus. Medical risk factors included coronary artery disease (CAD) in 15 (47%), hypertension in 15 (47%), chronic renal failure (CRF) in 9 (28%), and cigarette smoking in 10 (31%). Indications for revascularization were: non-healing ulcerations in 18 (51%), gangrene in 15 (43%), and rest pain in 2 (6%). The distal anastomosis was to the posterior tibial artery in 9, anterior tibial artery in 8, dorsalis pedis artery in 10 and peroneal artery in 8 cases. All the bypasses were done with autogenous saphenous veins (in-situ 11, reversed 17, and free non-reversed 7). The limbs were graded into three groups based on the preoperative angiographic evaluation of their pedal arch: patent arch (Grade "0"), partial occlusion of the arch (grade "1.5") and little or no arch visualized (Grade "3"). Eight limbs had Grade "0", 16 had Grade "1.5" and 11 had Grade "3" pedal circulation. Bypass follow up was done by clinical exam and color duplex surveillance (CDS) for a mean duration of 24 months. CDS identified 4 failing bypasses which were surgically revised and have subsequently remained patent. There were 3 bypass occlusions which resulted in a major amputation in 2 patients. Three additional major amputations were performed for persisting infection despite a patent bypass. By life table analysis the cumulative primary & secondary patency and limb salvage rates for this group of diabetic patients were 75% at 2 years, 89% at 3 years and 82% at 3 years respectively (S.E. < 10%). The 3 bypass occlusions, which occurred at 1 week, 5 weeks, and 20 months, were in patients with both CRF and Grade "3" foot circulation (significantly different outcome compared to the rest of the group, by chi 2 test, p < 0.05). Good results can be achieved in the majority of diabetic patients undergoing short popliteal-distal bypasses. However, the combination of chronic renal failure and very limited foot circulation (Grade "3") has a significant adverse outcome.

Lateral approach to the popliteal and crural vessels for limb salvage.

Twenty-one patients underwent 23 bypasses for limb salvage via a lateral approach with subcutaneous graft tunneling. The reasons for utilizing a lateral approach were medial infection (10 bypasses), scarring from previous surgery (six), limited vein length available (three), prior local radiotherapy (two) and 'high risk' groin (two). The target artery was the anterior tibial in 16 cases, the peroneal in three, the above-knee popliteal in three and the dorsalis pedis in one. The median (range) follow-up was 22(<1-52) months. There were three early (within 30 days) and four late bypass occlusions, three of which occurred in previously revised bypasses and one in a non-compliant patient. The primary patency at 1 year was 61% and the secondary patency 86%. Only one amputation was required in the whole series. The lateral approach represents a simple solution to threatened limbs in otherwise difficult or complicated situations and may be the ideal approach for free vein grafts to the anterior tibial and distal peroneal arteries.

The aortic polytetrafluoroethylene graft: further experience.

OBJECTIVES: We analysed our results with the use of aortic polytetrafluoroethylene PTFE grafts over the last 7.5 years. A historical comparison was also made between the results with non-stretch PTFE (NS-PTFE) (1987-91) and stretch PTFE (S-PTFE) grafts (1991-94). MATERIALS: 244 infrarenal aortic replacements or bypasses with PTFE grafts were performed at the University of Iowa Hospitals and Clinics from January 1987 to June 1994. Infrarenal aortic replacement was indicated for aortic aneurysmal disease in 192 patients (elective 151, symptomatic 20, ruptured 21) and bypass for aorto-iliac occlusive disease in 52 patients (disabling claudication 28, limb salvage 24). Patients ranged in age from 37 to 93 years (mean 68 years). There were 161 males and 83 females. Medical risk factors included hypertension (55%), coronary artery disease (31%), COPD (23%), diabetes mellitus (12%) chronic renal failure (9%), and smoking (61%). Aortic replacement or bypass was done with a NS-PTFE graft in 108 patients (44%) and a S-PTFE graft in 136 patients (56%). Postoperative ultrasound (US) scans and/or CT-studies were available in 40 patients with NS-PTFE and 26 patients with S-PTFE grafts. MAIN RESULTS: The 30 day operative mortality was: elective AAA patients (1.3%), symptomatic AAA patients (10%), ruptured AAA patients (48%), limb salvage patients (4.1%) and disabling claudication patients (0%). Graft related complications included five graft limb thromboses (4 NS-PTFE, 1 S-PTFE). Two thromboses occurred perioperatively and the three others at 24, 28 and 30 months postoperatively. Two other graft related complications included a mixed pseudomonas and streptococcus groin infection with a culture negative perigraft fluid collection occurring 3 weeks following surgery (NS-PTFE), and distal aortic anastomotic suture line bleed on the first postoperative day following replacement of a ruptured AAA with a S-PTFE graft. Based on US and/or CT imaging studies, the mean internal diameters of the bodies of 40 NS-PTFE and 26 S-PTFE grafts were 11% and 10% greater than the manufacturer's specified sizes at a mean follow-up duration of 36 and 10 months respectively. CONCLUSIONS: These data reveal that a PTFE graft performs satisfactorily in the aortic position with minimal adverse clinical sequence over a 7.5 year period. Continued long term follow up data will determine the ultimate suitability of aortic PTFE grafts.

The management of the infected aortic prosthesis: a current decade of experience.

PURPOSE: Newer approaches to the patient with an infected aortic graft are available. We reviewed a recent 10-year experience with a more traditional approach to evaluate its outcome in the 1990s. METHODS: From January 1983 to January 1993, 27 patients with an aortic graft infection were treated at our institution. There were 18 paraprosthetic infections, eight graft enteric erosions, and one aortoduodenal fistula. The involved bypasses included 20 aortofemoral (74%), five aortoiliac (18%), and two aortic tube grafts (8%). Nineteen aortic replacements were done originally for aneurysmal disease (70%). We reviewed the outcome of each patient treated as it related to the method of management. The therapy for graft infection consisted of aortic graft removal and axillofemoral bypass in 20 patients (74%), treatment by an in situ method in four patients (15%), excision of an aortofemoral limb and extraanatomic bypass in two patients (7%), and extraanatomic bypass alone in one patient (4%). In the group treated by graft removal and extraanatomic bypass, four patients (20%) had staged operations (extraanatomic bypass followed by interval aortic graft removal), nine (45%) had single operations with extraanatomic bypass preceding graft removal, and seven (35%) had single operations with graft removal preceding extraanatomic bypass. RESULTS: The 30-day operative mortality rate was 3.7%. There were no instances of aortic stump blowout. The 3-year primary patency rate for axillofemoral bypass limbs was 80.2%, and the secondary patency rate was 87.4%. No limbs were lost as a result of ischemic complications. There was one late amputation for an unrelated problem. CONCLUSIONS: The results of alternate approaches to the management of patients with infected aortic grafts were equivalent both in terms of perioperative mortality and morbidity rates in this group of patients. Complete excision of the aortic graft with axillofemoral bypass provided a satisfactory long-term outcome and remains the standard with which other approaches must be compared.

Technical aspects and results of the open in situ saphenous vein bypass technique.

We reviewed 284 consecutive in situ saphenous vein bypass procedures performed for limb salvage over a 66 month period. All procedures were performed using an open technique with a modified Mills retrograde valvulotome using an incision exposing the whole vein. Ninety-eight percent were to the infrageniculate level (18% below knee popliteal and 80% crural). All patients had preoperative B-mode saphenous vein mapping. Intraoperative arteriographic and continuous wave Doppler evaluations were done on each bypass. Routine color duplex imaging was performed on all bypassess postoperatively. Primary and secondary patency rates for all in situ bypassess at 48 months were 68% and 86%. The perioperative mortality was 2.5%. All deaths were secondary to cardiovascular causes. We believe that the open technique with a retrograde valvulotome provide satisfactory long-term patency, high operability and an excellent vein utilization rate.

[Axillo-femoral bypass--an emergency operation]. / Aksilo-femoralni bypass--operacija nuzde.

Our patient with peritonitis, chronical ileus and ileostoma has had the atherosclerotic occlusive changes in aorto-iliac area on both sides. Hypotensive crises must have made hemodynamic conditions worse, permitting thrombosis in the collateral circulation to cause acute ischemia of the right leg. Because of the bad general condition and infection on the anterior abdomen wall, the axillo-femoral bypass has been the only way for the arterial reconstruction and salvation of the leg.