In vivo use of a radioiodinated somatostatin analogue: dynamics, metabolism, and binding to somatostatin receptor-positive tumors in man.

Somatostatin analogues, labeled with gamma-emitting radionuclides, are of potential value in the localization of somatostatin receptor-positive tumors with gamma camera imaging. We investigated the application in man of a radioiodinated analogue of somatostatin, 123I-Tyr-3-octreotide, which has similar biologic characteristics as the native peptide. The radiopharmaceutical is cleared rapidly from the circulation (up to 85% of the dose after 10 min) mainly by the liver. Liver radioactivity is rapidly excreted into the biliary system. Until 3 hr after injection, radioactivity in the circulation is mainly in the form of 123I-Tyr-3-octreotide. Thereafter, plasma samples contain increasing proportions of free iodide. Similarly, during the first hours after injection, radioactivity in the urine exists mainly in the form of the unchanged peptide. Thereafter, a progressive increase in radioiodide excretion is observed, indicating degradation of the radiopharmaceutical in vivo. Fecal excretion of radioactivity amounts to only a few percent of the dose. The calculated median effective dose equivalent is comparable with values for applications of other 123I-radiopharmaceuticals (0.019 mSv/MBq).     

Duodenal ulcer healing by separate reduction of postprandial and nocturnal acid secretions have different pathophysiology.

The endoscopic healing rates and factors related to healing of two cimetidine regimens designed to reduce respectively postprandial and nocturnal acid secretions were studied in a randomised trial of cimetidine 200 mg tds with meals, vs 600 mg at bedtime, vs 200 mg tds with meals plus 400 mg at bedtime in 246 patients with duodenal ulcer. The respective healing rates were 62.3%, 63.1%, 77.5% at four weeks and 86.6%, 83.3%, 91.2% at eight weeks. The healing rates at four weeks of both meal time and bedtime regimens were inferior (p less than 0.05) to that of the standard regimen. Analysis of 45 prospectively obtained factors showed that (i) habitual cigarette smoking adversely affected healing with the meal time regimen but not with the others, indicating that its adverse effect disappeared once nocturnal acid secretion was reduced, (ii) habitual use of analgesics impaired and their abstinence favoured healing by both meal time and bedtime regimens but these effects were lost with the standard regimen, suggesting that if analgesics cannot be withdrawn during ulcer treatment, a reduction of both meal time and night time acid secretions should be ensured, (iii) responders with the meal time and bedtime regimens had respectively significantly higher postprandial serum gastrin and higher basal acid output than the corresponding non-responders suggesting that these responders had different pathophysiology, and (iv) high maximal acid output and large ulcers healed less well by any regimen.     

Efficacy of vancomycin plus rifampin in experimental aortic-valve endocarditis due to methicillin-resistant Staphylococcus aureus: in vitro-in vivo correlations

Studies of in vitro and in vivo bactericidal interactions of vancomycin plus rifampin against Staphylococcus aureus have yielded conflicting results. In this study the efficacy of this drug combination in experimental endocarditis due to a methicillin-resistant strain of S. aureus was investigated. Left-sided endocarditis was induced in 84 rabbits by an infecting strain that had been found to be synergistically killed by vancomycin plus rifampin in vitro when tested by the timed-kill curve technique; in contrast, the checkerboard technique had indicated that the two drugs were antagonistic against this strain. Infected animals received no therapy, vancomycin alone (30 mg/kg per day), rifampin alone (20 mg/kg per day), or both drugs (in the same doses). The combination was significantly more effective than the single-drug regimens in terms of (1) reduction of mean methicillin-resistant S. aureus vegetation titers (P less than .05-.0005), (2) rate and incidence of sterilization of vegetations (P less than .0005), and (3) rate of "radical" cure of endocarditis (P less than .005). Vancomycin alone and vancomycin plus rifampin were equally effective in reducing mortality and sterilizing renal abscesses. The use of vancomycin prevented the in vivo development of resistance to rifampin. No evidence that rifampin exerted an antagonistic effect on the in vivo bactericidal activity of vancomycin was found.     

A logistic regression analysis of multiple noninvasive tests for the prediction of the presence and extent of coronary artery disease in men

The incremental diagnostic yield of clinical data, exercise ECG, stress thallium scintigraphy, and cardiac fluoroscopy to predict coronary and multivessel disease was assessed in 171 symptomatic men by means of multiple logistic regression analyses. When clinical variables alone were analyzed, chest pain type and age were predictive of coronary disease, whereas chest pain type, age, a family history of premature coronary disease before age 55 years, and abnormal ST-T wave changes on the rest ECG were predictive of multivessel disease. The percentage of patients correctly classified by cardiac fluoroscopy (presence or absence of coronary artery calcification), exercise ECG, and thallium scintigraphy was 9%, 25%, and 50%, respectively, greater than for clinical variables, when the presence or absence of coronary disease was the outcome, and 13%, 25%, and 29%, respectively, when multivessel disease was studied; 5% of patients were misclassified. When the 37 clinical and noninvasive test variables were analyzed jointly, the most significant variable predictive of coronary disease was an abnormal thallium scan and for multivessel disease, the amount of exercise performed. The data from this study provide a quantitative model and confirm previous reports that optimal diagnostic efficacy is obtained when noninvasive tests are ordered sequentially. In symptomatic men, cardiac fluoroscopy is a relatively ineffective test when compared to exercise ECG and thallium scintigraphy.     

Hypoglossal nerve palsy in nasopharyngeal carcinoma.

BACKGROUND: The aim of the study was to use magnetic resonance (MR) imaging to determine the cause of hypoglossal nerve palsy and the sites of injury in patients with nasopharyngeal carcinoma before radiation therapy and during postradiation therapy follow-up. METHODS: The clinical records and MR studies of 21 patients with hypoglossal nerve palsy were retrospectively studied. These 21 patients belonged to a cohort of 387 patients with nasopharyngeal carcinoma (153 with newly diagnosed disease and 234 on postradiation follow-up) who underwent MR imaging in a 2.5-year period. RESULTS: Four patients had hypoglossal nerve palsy at initial diagnosis and all of them had extensive skull base invasion from tumor extending postero-inferiorly to the level of the foramen magnum. The nerve was invaded in the carotid sheath (3), hypoglossal nerve canal (3), and premedullary cistern (1). In 17 patients developing hypoglossal nerve palsy after radiotherapy, only two (12%) had evidence of tumor recurrence. Radiation-induced neuropathy was the probable cause in 14 patients and 1 case was judged indeterminate. MR evidence of fibrosis was demonstrable along the course the nerve in four patients (29%), involving the carotid sheath (4), hypoglossal nerve canal (2), and premedullary cistern (1). No patient had MR evidence of radiation change in the brain stem. Seven patients had a history of a boost dose of radiation to the parapharyngeal region on one or both sides, and nerve palsy occurred on the boosted side in six of them. CONCLUSION: Hypoglossal nerve palsy on presentation was caused by locally advanced nasopharyngeal tumor whereas a palsy arising after radiation therapy was more frequently caused by postradiation damage rather than cancer.     

Parathyroid autotransplantation during thyroidectomy: is frozen section necessary?

OBJECTIVE: To evaluate the accuracy of parathyroid gland identification and the need for routine frozen section examination before parathyroid autotransplantation during thyroidectomy. DESIGN: A prospective case series. SETTING: An endocrine surgical unit. PATIENTS: From January 1, 1995, to December 31, 1997, parathyroid autotransplantation was attempted for devascularized or inadvertently removed glands in 152 (33.7%) of 450 patients during thyroidectomy. Before autotransplantation, a biopsy specimen of the transplanted tissue was sent for histological examination without frozen section confirmation. MAIN OUTCOME MEASURES: Positive identification of parathyroid tissue in microscopic examination. RESULTS: Of 179 attempted autotransplantations of parathyroid glands, parathyroid tissue was confirmed in 167 biopsy specimens (93.3%). Incorrect identification of parathyroid gland occurred in 12 instances. The tissue mistaken as parathyroid gland included fat in 6 cases, thyroid tissue in 4 cases, lymph node in 1 case, and thymus in 1 case. Transplantation of at least 1 parathyroid gland (range, 1-3) was confirmed in 144 patients. For patients with confirmed parathyroid autotransplantation at risk of hypoparathyroidism (n = 112), postoperative transient hypocalcemia occurred in 22 (19.6%), while no patient developed any permanent hypocalcemia during a median follow-up of 6 months. CONCLUSIONS: Devascularized or inadvertently removed parathyroid glands can be identified expeditiously without routine frozen section during thyroid surgery. Immediate autotransplantation should be performed and permanent hypoparathyroidism can be avoided with this measure.     

Development and evaluation of a new composite Laserskin graft

BACKGROUND: Tremendous effort has been made to improve the graft take rate of cultured epidermal autograph. The purpose of this study is to develop and evaluate a new composite Laserskin graft (CLSG) as a human skin substitute for wound resurfacing. METHODS: The seeding efficacy of cultured keratinocytes on plain Laserskin was compared with the 3T3 cell-seeded Laserskin and allogenic fibroblast-populated Laserskin. Three different types of CLSG, 2 cm in diameter each, were prepared and tested in rats. Type A CLSG consisted of proliferative allogenic rat fibroblasts on both sides of the Laserskin with autologous keratinocytes also on the upper side. Fibroblasts and keratinocytes were seeded only on the upper side of the Laserskin in type B CLSG. Keratinocytes alone were seeded on plain Laserskin in type C CLSG. Type B CLSG consisting of autologous keratinocytes and autologous dermal fibroblasts was tested on five selected wounds (5x5 cm each) of a patient with full-thickness burn. In another burn patient, type B CLSG consisting of autologous keratinocytes and allogenic dermal fibroblasts was grafted onto three wounds (5x5 cm each). RESULTS: The seeding efficacy of human keratinocytes on plain Laserskin increased from 75% to 95% when proliferative allogenic fibroblasts were grown as a feeder layer on the Laserskin. The seeding efficacy of rat keratinocytes increased from 36% to 88% in the presence of a proliferative allogenic fibroblast feeder layer, whereas human/rat keratinocytes had respective seeding efficacy of 98%/91% on Laserskin preseeded with mitomycin C-treated 3T3 cells. Skin biopsies of grafted type A CLSG on day 14 after grafting showed complete epithelialization without severe inflammation in 16 of 20 (80%) grafted surgical wounds in rats. There were eight (40%) and seven (35%) "takes" of the CLSG in types B and C, respectively. The infection rate in type B CLSG was two (10%). There was one (5%) infection in types A and C. The respective take rates on the two patients grafted with type B CLSG were 60% and 100%. CONCLUSION: The animal experiment and the preliminary clinical data showed that the CSLGs consisting of autologous keratinocytes and of autologous/allogenic fibroblasts are good human skin substitutes in terms of durability, biocompatibility, high seeding efficacy for keratinocytes, high graft take rate, and low infection rate.     

Pancreaticoduodenectomy with En Bloc Portal Vein Resection for Pancreatic Carcinoma with Suspected Portal Vein Involvement

Pancreaticoduodenectomy combined with portal vein resection is increasingly accepted as a viable treatment option for pancreatic carcinoma with suspected involvement of the portal vein.However, its clinical benefit remains controversial. This study evaluated the outcomes of pancreaticoduodenectomy with portal vein resection for pancreatic carcinoma in a group of Chinese patients operated on by a specialized team in a center with a low case volume of pancreatic cancer. The perioperative and long-term outcomes of 12 patients with portal vein resection for suspected involvement of the portal vein and 38 patients who underwent pancreaticoduodenectomy without portal vein resection during the same period were compared. In the former group, eight patients underwent segmental resection, and four patients underwent wedge resection of the portal vein. There were no significant differences in operative blood loss (median 0.8 vs. 0.8 liter, p = 0.313), hospital mortality (0% vs. 2.6%, p = 1.000), or operative morbidity (41.7% vs. 42.1%, p = 0.979) between the two groups. Patients who required portal vein resection had higher frequencies of microscopic lymphatic permeation (58.3% vs. 18.4%, p = 0.023) and vascular invasion (50.0% vs. 15.8%, p = 0.025). Long-term survival was comparable between patients with portal vein resection and those without it (median 19.5 vs. 20.7 months, p = 0.769). These findings suggest that pancreaticoduodenectomy combined with portal vein resection can be performed safely by a specialized team in a center with a low case volume of pancreatic carcinoma and that it may offer survival benefit in patients with suspected portal vein involvement.