Improvement of oxygen metabolic reserve after extracranial-intracranial bypass surgery in patients with severe haemodynamic insufficiency

Summary The effectiveness of extracranial-intracranial arterial bypass (EC-IC bypass) surgery on impaired haemodynamic status was studied in 12 patients with reduced regional cerebral perfusion pressure (rCPP) and elevated regional oxygen extraction fraction (rOEF) in the area distal to the symptomatic arterial lesion. Postoperative positron emission tomography (PET) study demonstrated a statistically significant decrease of rOEF in the operated hemispheres with disappearance of the pre-operative interhemispheric rOEF difference. Regional cerebral blood flow (rCBF) and regional cerebral oxygen metabolism (rCMRO2) were also increased in the operated hemispheres with disappearance of the pre-operative interhemispheric differences. Regional CBF/regional cerebral blood volume (rCBV) ratios of the symptomatic hemispheres were increased after surgery, but were still lower than in the contralateral hemispheres. We conclude that EC-IC bypass surgery improves impaired cerebral oxygen metabolic reserve.     

Platelet glutathione peroxidase activity in long-term total parenteral nutrition with and without selenium supplementation.

Selenium (Se) is not routinely included in total parenteral nutrition (TPN) solution; thus, patients receiving long-term TPN may be at risk of Se deficiency, which may cause fatal cardiomyopathy. Platelet glutathione peroxidase (GSH-Px) activity, as well as Se levels and GSH-Px activity in plasma and erythrocytes during prolonged TPN, was measured in six patients with chronic gastrointestinal disease. During the time course of TPN, Se administration was discontinued for 12 weeks, and then resupplemented for another 12 weeks. Before the study period, all Se indices had been maintained within the normal range. After discontinuation of Se supplementation, a significant decrease in platelet GSH-Px activity was observed after 1 week (from 64 +/- 7 [mean +/- SD] to 39 +/- 5 U/g of protein). After resupplementation, it increased after 1 week (from 44 +/- 9 to 65 +/- 10 U/g of protein). Plasma Se indices significantly changed within 3 weeks after withdrawal and reintroduction of Se (Se: from 136 +/- 28 to 75 +/- 14 and from 61 +/- 22 to 125 +/- 33 micrograms/L; GSH-Px: from 236 +/- 50 to 140 +/- 36 and from 128 +/- 32 to 220 +/- 64 U/L). Erythrocyte Se indices showed no significant changes during the study period. The results demonstrate that platelet GSH-Px activity is the most sensitive index of Se status in TPN patients.     

Evaluation of image-diagnosing methods of enlarged parathyroid glands in chronic renal failure

Three noninvasive image-diagnosing methods, computed tomography (CT), scintigraphy with²⁰¹T1C1 and^99mTcO_h4 ^–, and ultrasonography (US), were preoperatively performed on 50 patients with chronic renal failure and secondary hyperparathyroidism who underwent total parathyroidectomy and parathyroid autograft. The detection rates of the 3 methods on the 191 excised parathyroid glands were compared according to weight and location. CT detected 57.1% of all glands and 78.6% of 103 glands weighing over 500 mg. Scintigraphy detected 51.8% and 75.7%, and US detected 42.4% and 53.4%, respectively. The detection rate of upper glands was best with CT at 58.9% and 89.1%; that of lower glands was best with scintigraphy at 65.3% and 80.4%. Although the combination of the 3 methods diagnosed 69.6% and 89.5%, CT and scintigraphy, the best 2 combinations, visualized 67.5% and 88.3%.

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Resumen Tres métodos diagnósticos no invasivos, la tomografía computadorizada (TC), la centelleografía con²⁰¹T1C1 y^99mTcO₄ y la ultrasonografía (US) fueron realizados preoperatoriamente en 50 pacientes con falla renal crónica e hiperparatiroidismo secundario sometidos a paratiroidectomía y autotransplante paratiroideo. Las tasas de detección de los 3 métodos fueron comparados sobre las 191 glándulas paratiroideas resecadas en relación a los pesos y a los sitios de ubicación. La TC detectó el 57.1% del total de glándulas y el 78.6% de aquellas glándulas (103) con pesos superiores a 500 mg. La centelleografía detectó 51.8% y 75.7%, y la US 42.4% y 53.4% respectivamente. La tasa de detección para las glándulas superiores fue optima con TC, con 58.9% y 89.1%; la de las glándulas inferiores fue óptima con centelleografía, con 65.3% y 80.4%. Aunque la combinación de los 3 metodos diagnosticó el 69.6% y 89.5%, la TC y la centelleografía, la mejor de las combinaciones, visualizó el 67.5% y el 88.3% respectivamente.

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Résumé Trois méthodes d'imagerie non invasives, la tomodensitométrie, la scintigraphie (avec T1C1²¹⁰ et TcO₄ ^99m), et l'ultrasonographie ont été pratiquées avant l'intervention chez 50 malades qui présentaient une insuffisance rénale chronique compliquée d'hyperparathyroïdisme secondaire et qui furent traités par parathyroïdectomie totale et autogreffe parathyroïdienne. Les taux de détection de ces 3 méthodes concernant 191 glandes parathyroïdes réséquées ont été évalués en fonction du poids et du siège des lésions. La tomodensitométrie a permis de découvrir 57.1% de toutes les glandes et 78.6% des glandes dont le poids dépassait 500 mg; la scintigraphie 51.8% et 75.7%; l'ultrasonographie 42.4% et 53.4%. Le taux de détection des glandes supérieures fut plus élevé avec la tomodensitométrie: 58.9% et 89.1%; celui des glandes inférieures le fut avec la scintigraphie: 65.3% et 80.4%. Si la combinaison des 3 méthodes permet le diagnostic dans 69.6% et 89.5% des cas la tomodensitométrie associée seulement à la scintigraphie donne des résultats très voisins, les taux respectifs étant de 67.5% et de 88.3%.

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Presented at the International Association of Endocrine Surgeons in Paris, September 1985.     

Effects of a new histamine H2-receptor antagonist, Z-300, on gastric secretion and gastro-duodenal lesions in rats: comparison with roxatidine.

We examined the effects of a new compound, N-[3-[3-(piperidinomethyl)phenoxy]-propyl]-2-(2-hydroxyethyl-1- thio)acetamido.2-(4-hydroxy benzoyl)benzoate (Z-300), on the histamine H2-receptor, gastric secretion in rats and dogs, and acute gastro-duodenal lesions or chronic gastric ulcers in rats. Roxatidine acetate hydrochloride (roxatidine), a known histamine H2-receptor antagonist, was used as a reference compound. The pA2 values for Z-300 and roxatidine for the isolated guinea pig atrium were 6.8 and 7.0, respectively. These agents at less than 10(-5) M did not affect the contraction of guinea pig ileum in response to carbachol. Z-300, administered either orally or parenterally, significantly inhibited the basal and histamine-stimulated gastric acid secretion in rats. Gastric acid secretion stimulated by histamine, pentagastrin or carbachol in Heidenhain pouch dogs was also significantly inhibited by the compound. The effect persisted for greater than 7 hr in the case of histamine-stimulation. Oral Z-300 significantly protected the gastric mucosa from water-immersion stress-, indomethacin-, aspirin- and HCl.ethanol-induced lesions and protected the duodenal mucosa against mepirizole- and cysteamine-induced ulcers. These effects on gastric secretion and lesion formation were, as a whole, stronger than those observed with roxatidine. Z-300, but not roxatidine, significantly accelerated the spontaneous healing of acetic acid ulcers induced in rats and prevented the delay in ulcer healing caused by indomethacin. The mechanism of action of Z-300 on acute lesions and chronic ulcers appears to be mostly related to its potent antisecretory and mucosal-protective activities.     

Clinical Pharmacokinetics of Anti‐angiogenic Photodynamic Therapy with Benzoporphyrin Derivative Monoacid Ring‐A in Dogs Having Naturally Occurring Neoplasms

The aim of this study was to examine the pharmacokinetics of clinically applied benzoporphyrin derivative monoacid ring‐A (BPD‐MA; Verteporfin^®), a second‐generation photosensitizer, during a trial of photodynamic therapy (PDT) in nine dogs having naturally occurring neoplasms. After injecting BPD‐MA at 0.5 mg/kg intravenously, its mean half‐life (t_1/2) was found to be 8.14 ± 5.34 h, mean clearance (Cl) 35.13 ± 9.62 ml/(h kg), the mean value of the volume of distribution (V_c) 0.08 ± 0.01 l/kg and the mean steady state volume of distribution (V_ss) 0.38 ± 0.31 l/kg respectively. With the exception of a transitional increase in serum alkaline phosphatase activity, no other clinical abnormalities were observed. The t_1/2 in dogs with naturally occurring tumours was longer than that in humans, but similar to that in rats. The values of Cl and V_ss in dogs having naturally occurring neoplasms were lower than those in humans. It is suggested that the pharmacokinetics of BPD‐MA in tumour‐bearing dogs would be helpful in determining the protocol of a short drug‐light interval PDT with BPD‐MA that mainly targets the tumour vasculature.     

Functional and phenotypic analysis of tumor-infiltrating lymphocytes isolated from human primary and metastatic liver tumors and cultured in recombinant interleukin-2

Tumor-infiltrating lymphocytes (TIL) were isolated from 40 of 51 consecutive human liver tumor samples (primary hepatocellular carcinoma, 16 of 18; metastatic, 23 of 29; benign, one of four). Functional and phenotypic characteristics of fresh and recombinant interleukin-2 (rIL-2)-expanded TIL were evaluated. The expansion of TIL from hepatic tumors in the presence of 1000 units/ml of rIL-2 was possible in 60% of cases. In comparison to TIL from metastatic liver tumors, TIL obtained from primary liver tumors expanded faster and better in rIL-2 cultures. Expanded TIL from primary tumors had significantly higher cytotoxicity against K562 targets, but not Raji targets, than those from metastatic tumors. Cytotoxicity against fresh autologous tumor targets was detected in seven of eight cultures tested. TIL from primary tumors retained antitumor reactivity significantly longer in culture. The optimal in vitro cytotoxicity was achieved between days 20 and 60 of culture in the presence of rIL-2. Antitumor activity was associated with the increase in these TIL cultures of a cell population expressing the Leu19 antigen with or without the CD3 antigen. The frequency of the CD3+Leu19+ population showed a bimodal distribution during culture: the first peak of CD3+Leu19+ cells occurred between days 30 and 60 and was associated with the increased antitumor activity; the second peak occurred after day 60 and was not associated with activity. These findings demonstrate that TIL from most human hepatic tumors can be successfully isolated, cultured in rIL-2, and enriched in Leu19+ effectors. In addition, these TIL upon IL-2 activation in vitro are capable of lysing fresh autologous and/or allogeneic tumor targets.