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Biomedical subjects

T J Wieman

Publications and source records attributed to T J Wieman.

At least 55 records · Page 3Linked to original sources

Metatarsal head resection for diabetic foot ulcers.

Twenty-five diabetic patients underwent 34 metatarsal head resections for chronic neuropathic ulceration. All ulcers were located on the plantar surface beneath the metatarsophalangeal joints. The ulcers had been present for a mean of 9.0 +/- 7.8 months before operation, yet they healed in a mean of 2.4 +/- 1.6 months postoperatively. None recurred during the mean follow-up time of 13.8 +/- 11.0 months. Moderate peripheral vascular disease, impaired renal function, and retinopathy did not affect the time required for ulcer healing. There were two complications: one wound infection and one hematoma. No extremities were lost, and none of the patients suffered any long-term sequelae. We recommend metatarsal head resection to achieve the healing of chronic diabetic foot ulcers under the metatarsophalangeal joints.

Diabetes Mellitus, Type 1↗

The influence of renal function on diabetic foot ulceration.

We examined the effect of renal function on the formation, severity, and outcome of diabetic foot lesions. Information was collected from a retrospective hospital chart survey and analyzed by univariate and multivariate linear regression analysis. Creatinine clearance, peripheral neuropathy, and peripheral vascular disease were all found to be independently associated with formation of foot lesions, indicating that each of these acts by distinct biologic mechanisms. Renal function had no bearing on the severity of lesions or on their eventual healing. We conclude that foot ulcers are more likely to develop in diabetic patients who also suffer from renal impairment, but they are no less likely to heal than are those in patients with normal renal function. We further conclude that attempts to preserve functional limbs in these patients are justified.

Adult↗

Operative cholangiography.

The value of operative cholangiography in the management of biliary tract disease has been questioned. To better define the role of cholangiography, we reviewed 579 consecutive cholecystectomies done by 1 group of surgeons in a small rural practice over 8 years. Cholangiography demonstrated unsuspected common bile duct disease in 5% of the procedures, while 12% of the patients were spared an unnecessary choledochotomy after a normal cholangiogram was obtained. There was no morbidity, mortality, or prolongation of the hospital stay attributed to the cholangiographic procedure. These findings bolster the argument for routine cholangiography as a safe, effective, and helpful screening examination for patients who are at risk for having common bile duct disease.

Adolescent↗

Stroke volume measurements by electrical bioimpedance and echocardiography in healthy volunteers.

To evaluate the validity of three equations for estimation of thoracic electrical field size in a new bioimpedance algorithm, stroke volume (SV) as calculated by these equations was compared with that calculated by Doppler echocardiography in 48 healthy volunteers, both lean and obese. When the volume of electrically participating tissue was estimated from body height (modified Sramek) or body height corrected for body habitus (Sramek-Bernstein), there was considerable variation between bioimpedance and Doppler stroke volumes. When the volume of electrically participating tissue was estimated from the actual measurement of the height of the thorax and the circumference at the base of the thorax, the variation in SV differences decreased substantially (Sramek equation), although still considerable for clinical use, and there was no relationship between SV thus obtained and body habitus. Analysis of calculated stroke indices derived by our Doppler echocardiographic standard, as compared with values in the literature, revealed a systematic underestimation. We conclude that the original Sramek equation systematically underestimates SV by 15% to 20%, and the modified Sramek and Sramek-Bernstein equations systematically underestimates SV by 15% to 20%, and the modified Sramek and Sramek-Bernstein equations systematically overestimate SV in females by about 15%, but provide SV values in males in the predicted range. Further studies on the current assumption that the electrical field size is a truncated cone may improve precision of the bioimpedance method.

Adult↗

Cholangiocarcinoma in association with multiple biliary microhamartomas.

The rarity of cholangiocarcinoma occurring in von Meyenburg complexes is well appreciated. We describe the case of a 35-year-old man found to have cholangiocarcinoma in association with multiple biliary microhamartomas of the liver. Areas of ductal proliferation and atypia within the bile duct hamartomas suggest malignant transformation to cholangiocarcinoma.

Adenoma, Bile Duct↗

The response of the rat urinary bladder microcirculation to photodynamic therapy.

Light activation of dihematoporphyrin ether (photofrin II) has been used in the treatment of bladder tumors, yet the effects of this treatment on the normal urinary bladder microcirculation have not been determined. This study involved the use of in vivo television microscopy to observe the effects of light activation (530 to 560 nm., 175 mW/cm.) on the urinary bladder microcirculation of female Sprague-Dawley rats. Animals pretreated with dihematoporphyrin ether 30 minutes prior to light activation had high serum and low tissue concentrations of the photosensitizer and activation resulted in a statistically significant reduction of red blood cell column diameter in both arterioles and venules. The reduction was primarily due to mural thrombus formation with the occlusion remaining 60 minutes after activation. Animals pretreated 48 hours before activation had low serum and high tissue concentrations of dihematoporphyrin ether and activation had no microcirculatory effects apart from occasional platelet aggregation. These results suggest that the photodynamic effect on normal (non-neoplastic) tissue treated more than 48 hours after administration of dihematoporphyrin ether is probably due to a direct effect of light and the sensitizer on the smooth muscle of the bladder rather than an effect on the microcirculation.

Animals↗

Complications of whole bladder dihematoporphyrin ether photodynamic therapy.

Photodynamic therapy with dihematoporphyrin ether was used to treat superficial bladder tumors in 7 patients with a followup of at least 1 year. Each patient received treatment to the whole bladder and those with papillary lesions received additional focal treatment. At 3 months 4 of the 5 patients with papillary tumors (stages Ta and T1) and 1 of the 2 with diffuse carcinoma in situ (Tis) were free of disease. However, at 1 year only 3 patients remained free of disease. Of 5 patients with an increase in irritative bladder symptoms 4 had a contracted bladder, hydroureteronephrosis and vesicoureteral reflux. Deep bladder biopsies showed replacement of smooth muscle by fibrous tissue. Six patients had mild to moderate skin phototoxicity. We conclude that although photodynamic therapy is an attractive and exciting method to treat cancer, its use with dihematoporphyrin ether in cases of bladder carcinoma can be associated with significant complications. The correct treatment parameters for safe, effective therapy are not known to date.

Adult↗

The microvascular effects of photodynamic therapy: evidence for a possible role of cyclooxygenase products.

Photodynamic therapy (PDT) of malignant tumours may involve the interruption of tumor and peritumor microcirculation. We have studied the effect of light activation of the photosensitizing drug dihematoporphyrin ether (DHE) on rat subcutaneous arterioles and the modulation of these effects by cyclooxygenase inhibitors indomethacin and acetyl salicylic acid (ASA). Animals received DHE 48 h prior to light activation and additionally either indomethacin, ASA or saline 3 h prior to treatment. Light activation (630 nm, 60 J/cm2) resulted in a significant reduction to 62 +/- 2% SEM of initial blood flow. This effect was inhibited by ASA (98 +/- 8% SEM) and indomethacin (87 +/- 8% SEM). Results from the administration of various doses of both compounds indicate that this inhibition is dose related. The data presented here show that PDT causes a significant reduction in blood flow in normal arterioles and that this effect was inhibited by ASA and indomethacin indicating that prostaglandins or thromboxane A2 may play an important role in the microvascular response to PDT.

Animals↗

The effect of photodynamic therapy on tumor oxygenation.

Oxygen microelectrodes were used to measure tumor partial pressure of oxygen (PO2) before and after photodynamic therapy (PDT) in a rat transplantable subcutaneous chondrosarcoma. Before PDT there was a gradient of PO2 from the superficial layers of the tumor (PO2 = 46 +/- 6 mm Hg) toward the center of the tumor (PO2 = 10 +/- 1 mm Hg). Mean tumor PO2 (21 +/- 2 mm Hg) was significantly reduced to 3 +/- 1 mm Hg 1 hour after PDT, and this reduction in PO2 persisted 4 hours (8 +/- 2 mm Hg) and 24 hours (6 +/- 1 mm Hg) after PDT. The largest percentage decrease in PO2 occurred at a depth of only 50 microns into the tumor. Inasmuch as PDT has been shown to decrease blood flow, our data suggest that PDT actions on blood vessels in the peripheral areas of the tumor are of major importance for eliciting the tumor hypoxia that contributes to tumor necrosis after PDT.

Animals↗

Peripheral somatic sensory neuropathy and skin galvanic response in the feet of patients with diabetes.

The relationship between abnormality in the peripheral sympathetic nervous system (skin galvanic response) and in the peripheral somatic sensory nerve fibers was studied in the lower extremities of 51 patients with diabetes. Deficits in temperature and pain sensations (the small sensory nerve fibers) were related to abnormal sympathetic nervous function (temperature sensation, p less than 0.001; pain sensation, p less than 0.05). The deficits in temperature sensation, in particular, predicted abnormal sympathetic nervous function reliably and vice versa. There was no relationship between deficits in touch and vibration sensations (the large sensory nerve fibers) and abnormal sympathetic nervous function. There was a relationship between skin galvanic response and RR-variation (p less than 0.01). However, abnormality in RR-variation was not related to the deficits in any of the four sensory modalities.

Adult↗

A comparison of the effects of photodynamic therapy on normal and tumor blood vessels in the rat microcirculation.

The effects of light activation of the tumor photosensitizer dihematoporphyrin ether (DHE) were studied in the microcirculation of the rat cremaster muscle. Arterioles and venules in an implanted chondrosarcoma were studied by in vivo television microscopy and were compared to normal vessels of the same size elsewhere in the preparation and in control preparations. Activation with green light (530-560 nm, 200 mW/cm2, 120 J/cm2) 48 h after intraperitoneal injection of DHE (10 mg/kg body wt) resulted in significant narrowing of diameters of red blood cell columns in tumor arterioles and venules. The response in normal and control arterioles and venules was not significantly different from that seen in the tumor vessels except that the control arterioles did not remain significantly constricted during the treatment period. Treatment resulted in stasis of blood flow in 90% of tumor and normal arterioles at the completion of light activation. In venules, stasis of blood flow was observed in 75% of tumor and 70% of normal vessels. Vasoconstriction was the primary response in arterioles, while thrombosis predominated in venules. Morphologic assessment of light-activated vessels in the cremaster preparation by transmission electron microscopy revealed platelet aggregation with damage to endothelial cells and smooth muscle cells. Perivascular effects observed included interstitial edema and damage to skeletal muscle cells. In the tumor-bearing preparation, no direct cytotoxic effect on the tumor cells was shown. The surrounding vessels exhibited similar vascular stasis, but the lining cells appeared minimally affected. Photoactivation of DHE results in significant changes in the microcirculation which lead to stasis of blood flow. In this model, the response was similar for the normal microvasculature and for the microcirculation of an implanted chondrosarcoma. These effects may account, in part, for the mechanism of action of photodynamic therapy.

Animals↗

Postoperative percutaneous choledochoscopy.

Postoperative percutaneous choledochoscopy (PC) is becoming an important aid to surgeons in the diagnosis and treatment of complex biliary tract disease. The authors retrospectively examined the results of 27 PCs performed on 22 patients at the University of Louisville Affiliated Hospitals from 1980 to 1987. Indications for PC included: suspected choledocholithiasis stricture, sclerosing cholangitis, and cholangiocarcinoma. The biliary tree was accessed through a T-tube tract in 18 patients, and through a biliary-enterocutaneous fistula in four patients. The patient population included 11 men and 11 women with a mean age of 62 years. T-tubes varied in size from #16F to #24F. The time allowed for T-tube tract maturation ranged from four weeks to five months. Percutaneous choledochoscopy was performed 16 times in 13 patients for possible choledocholithiasis. Stones were present in 13, and 11 of 13 attempted extractions were successful. Two patients underwent PC for stent placement. Nine procedures were performed on eight patients to obtain biopsies or to evaluate possible strictures. Four studies were normal, two patients had sclerosing cholangitis, one had a stricture of the Sphincter of Oddi, and one patient had benign ductal tissue on biopsy after an iridium implantation for cholangiocarcinoma. Two minor complications occurred in this series. The authors conclude that by using PC the surgeon may safely manage complicated biliary problems and avoid re-operation in selected cases.

Adult↗

The effect of photodynamic therapy on the microcirculation.

Photodynamic therapy (PDT) is a new form of cancer therapy involving tumor localization by photosensitizing drugs such as dihematoporphyrin ether (DHE). Light irradiation of drug-sensitized tissue results in photoactivation of DHE and tumor necrosis. The mechanism of action is incompletely understood but involves the generation of singlet oxygen which produces cytotoxic effects on tissues containing the compound. In addition, microcirculatory aberrations have been described during PDT. We have studied the acute effects of PDT on the microcirculation using in vivo television microscopy of the rat cremaster. This has enabled us to observe the effects of PDT on both paired and unpaired arterioles and venules using two different wavelengths of activating light (blue, 450-490 nm, and green, 530-560 nm). For both wavelengths of activating light, significant reduction in blood flow of all vessels was seen during PDT. This, in combination with the formation and embolization of platelet thrombi, resulted in stasis of blood flow in 80% of arterioles and 90% of venules. Observation for 2 hr after the completion of photoactivation revealed reperfusion in 20% of the arterioles but none of the venules. Blood flow was reduced by a combination of vasoconstriction and platelet thrombus formation. Reducing the total activating energy from 120J/cm2 to 24J/cm2 significantly reduced the response in venules and the incidence of stasis in both arterioles and venules. We conclude that the photoactivation of DHE results in significant vasoconstriction and thrombosis of normal vessels and that if these effects are seen at later times after DHE administration and in tumor neovasculature they may contribute to the mechanism by which PDT results in tumor necrosis.

Animals↗

Endoscopic implantation of iridium wire for treatment of carcinoma of the bile duct.

Primary bile duct carcinoma presents serious challenges in management. These tumors are often not completely resectable. They frequently lead to death by producing obstruction to bile flow and hepatic failure. Initial operations frequently fail because of progression of primary disease. Although bile duct carcinomas respond to radiation, technical constraints limit delivery using an external beam technique. A number of studies have appeared in the literature describing the use of local irradiation delivered by way of catheters placed intraoperatively. In the present study, we have described an alternative method of implantation using a simple endoscopic technique utilizing a choledochojejunocutaneous fistula for access. The advantage of their approach is that the extent of the tumor can be determined visually and biopsy performed, facilitating accurate implant placement. In addition, serial examinations may allow early detection of recurrent disease and fecal retreatment.

Bile Duct Neoplasms↗

Effect of photodynamic therapy on blood flow in normal and tumor vessels.

The aim of this series of experiments was to determine the dynamic blood flow changes that occur in normal and neoplastic tissues during photodynamic therapy. Mice bearing SMT-F tumors and rats with transplanted chondrosarcomas were injected with graded doses of dihematoporphyrin ether. Studies of changes in single-vessel and whole-tumor blood flow were carried out with 630 nm light activation. A helium neon laser Doppler velocimeter was used to stimulate dihematoporphyrin ether, as well as to measure changes in flow velocity in both single-vessel and whole-tumor models. There was a reduction of flow velocity in all vessels and tumors in animals injected with 1 to 40 mg/kg dihematoporphyrin ether intraperitoneally. The extent of flow reduction was related to drug dose administered. Decreases in blood flow began within 10 seconds of light stimulation and were maximal within 5 minutes. Both normal and tumor vessels responded similarly. We conclude that photodynamic therapy leads to significant microcirculatory changes that may be pertinent to the mechanism of tumor necrosis.

Animals↗

Primary gastric lymphoma and pseudolymphoma.

Eighteen patients with primary gastric lymphomas and two with pseudolymphomas treated at the University of Louisville affiliated hospitals were analyzed in order to develop a more precise understanding of these rare diseases. Abdominal pain and weight loss were the most common initial symptoms. Only one patient presented with an abdominal mass. Upper GI series were helpful but failed to show a definite abnormality in two of 18 cases. Endoscopic examinations in all 18 were compatible with malignancy on gross finding, but six out of 15 endoscopic biopsies were not conclusive. All four cases, which proved fatal in less than two years, showed serosal invasion and diffuse histological pattern. On the basis of our analysis, we suggest that in patients with abdominal pain and weight loss of more than two months duration an aggressive course of evaluation should include upper gastrointestinal x ray and repeated endoscopic biopsy. If symptoms persist, laparotomy and biopsy may be warranted even if endoscopic biopsy shows no neoplasm. Curative surgery is the treatment of choice, but radiation therapy should be added in patients with serosal involvement. Very careful histological assessment of pseudolymphomas is necessary, because they may contain malignant lymphoma.

Adult↗