Moderate Necrosis Research Articles

Holmium: YAG laser arthroscopy of the temporomandibular joint

A new pulsed midinfrared laser has become available for use in arthroscopic surgery of the temporomandibular joint (TMJ). This article reviews holmium:YAG (yttrium-aluminum-garnet) laser physics, its tissue effects, and reports initial experience with its use in TMJ arthroscopy. Because the Ho:YAG laser can precisely and rapidly resect cartilaginous tissues with only moderate necrosis, can function in a saline environment, and can be transmitted through conventional optical fibers, it has the potential of becoming a useful and adaptable system for TMJ arthroscopic surgery.

Diagxxnostic Accuracy of 99mTc-Anti-CEA Immuno- scintigraphy in Patients with Liver Metastases from Colorectal Carcinoma

17 patients with 43 liver metastases from colorectal carcinoma were studied by immunoscintigraphy (IS) using a 99mTc-labelled monoclonal anti-CEA antibody (BW 431/26). Sensitivity and diagnostic accuracy were 21% for all liver lesions, but 47% considering the number of patients (at least one positive finding out of multiple metastases) and 77% in patients with a single metastasis. SPECT imaging did not improve sensitivity markedly in this series. There was no correlation with CEA serum levels. Liver metastases of intermediate size with moderate tumour necrosis seem to be favourable to IS. Major reason for the low sensitivity is the poor tumour-to-background ratio caused by high unspecific uptake of 99mTc-labelled antibodies in the RES of the liver. At the moment, IS seems be only a supplementary method to conventional diagnostic procedures.

Extravascular Toxicity of Two Magnetic Resonance Contrast Agents

We compared the relative toxicities of standard concentrations of two magnetic resonance imaging (MRI) contrast agents, ionic gadolinium diethylenetriaminepentacetic acid (DTPA) and low-osmolar gadolinium-1, 4, 7 tris (carboxymethyl)-10-(2'-hydroxypropyl)-1, 4, 7, 10 tetra-azacyclododecane (HP-DO3A) with that of the conventional radiographic contrast medium meglumine diatrizoate, when extravasated into the deep dermal tissues of laboratory rats. Gadolinium-DTPA caused moderate necrosis, hemorrhage, and edema which was not statistically different than meglumine diatrizoate. In contrast, gadolinium HP-DO3A was significantly less toxic than meglumine diatrizoate. Additional experience will be needed in order to determine whether these laboratory results will be clinically relevant in humans.

Toxicities in rats with free versus liposomal encapsulated cisplatin

Wistar rats (five in each group) were given either 1 mg/kg of free cisplatin, 1 or 2 mg/kg of liposomal encapsulated cisplatin, or saline solution intraperitoneally biweekly for 15 injections. Rats in the free drug group showed significantly less weight gain; two rats died during the study. At necropsy, the free cisplatin--treated rats showed gross and microscopic evidence of peritoneal fibrosis that was not detected in any of the remaining groups. The free cisplatin--treated rats showed serum and histologic evidence of renal damage; all five rats had moderate or severe acute tubular necrosis. No renal abnormalities were detected in rats that received 1 mg/kg, and only focal or mild changes were found in rats that received 2 mg/kg of the liposomal preparation. Neurotoxicity, as determined by nerve conduction and inclined plane studies, developed in rats treated with free and liposomal cisplatin. These results are encouraging and warrant further investigation.

Conjugates of ursodeoxycholate protect against cholestasis and hepatocellular necrosis caused by more hydrophobic bile salts: In vivo studies in the rat

The protective effect of ursodeoxycholate conjugates against bile salt hepatotoxicity was studied in chronic bile fistula rats. Taurochenodeoxycholate or taurodeoxycholate, infused intraduodenally at 24 or 16 μmol/100 g rat per hour, respectively, caused cholestasis and severe hepatocellular necrosis within 8 hours. In contrast, tauroursodeoxycholate or taurocholate at 48 μmol/100 g rat per hour were choleretic. Tauroursodeoxycholate was not hepatotoxic, whereas taurocholate produced moderate hepatocellular necrosis. Simultaneous infusion of tauroursodeoxycholate to rats receiving taurochenoxycholate or taurodeoxycholate preserved bile flow and ameliorated hepatic injury in a dose-dependent manner. Tauroursodeoxycholate protected equally by intravenous and intraduodenal routes. Intravenous glycoursodeoxycholate also was protective. The hydrophobicity index of infused bile salts correlated well with their toxicity. Concurrent administration of ursodeoxycholate conjugates did not reduce biliary recovery of intraduodenally infused [24-14C]-taurocholate. Biliary alkaline phosphatase secretion was stimulated by infusion of taurocholate, taurodeoxycholate, or taurochenodeoxycholate; simultaneous infusion of ursodeoxycholate conjugates failed to prevent this increase. We conclude that ursodeoxycholate counteracts hepatotoxicity of more hydrophobic bile salts via a direct effect at the level of the liver.

Iridium 192 implantation of T1 and T2 carcinomas of the mobile tongue

Between 1970 and 1986, 166 patients with T1 or T2 epidermoid carcinomas of the mobile tongue were treated by iridium 192 implantation (70 T1N0, 83 T2N0, 13 T1-2 N1-3). Five-year actuarial survival was 52% for T1NO, 44% for T2aNO, and 8% for or T1-2 N1-3. Cause specific survivals were 90%, 71%, and 46%, respectively. Local control was 87% for both T1 NO and T2NO, and 69% for T1-2 N1-3. Seven of 23 failures were salvaged by surgery, increasing local control to 96% for T1 and 90% for T2. Thirty-six patients developed a minor or moderate necrosis (16% Tl, 28% T2). Half of these involved bone but only five required surgical intervention. Both local control (LC) and necrosis (nee) increased with increasing dose but improvement beyond 65 Gy is minimal (≤60 Gy: LC = 78% nec = 13%; 65 Gy: LC = 90% nee = 29%; ≥70 Gy: LC = 94% nee = 23%). For NO patients, neck management consisted of surveillance (n = 78), elective neck dissection followed with external irradiation for pathologically positive nodes (n = 72), or irradiation (n = 3). Clinically positive nodes (13 patients) were managed by either neck dissection followed by external irradiation if pathologically positive (n = 10) or irradiation alone (n = 3). Regional control was 79% for NO patients, improving to 88% after surgical salvage, and was 9/13 for N1-3 patients. We recommend that T1 and T2 carcinomas of the mobile tongue be treated by iridium 192 implantation to deliver 65 Gy. Mandibular necrosis should be reduced by using an intra-oral lead-lined dental mold.

Inhibition of liver, kidney, and erythrocyte δ-aminolevulinic acid dehydratase (porphobilinogen synthase) by gallium in the rat

Selective inhibition of enzymes in the heme biosynthesis pathway with concomitant urinary excretion of heme precursors serve as potentially important biological markers of chemical exposure and cell injury. Intratracheal administration of gallium arsenide particulate suspensions has been shown to result in inhibition of delta-aminolevulinic acid dehydratase (ALAD) in several tissues and increased excretion of the heme precursor aminolevulinic acid (ALA). This study was undertaken to evaluate in vivo the role of gallium alone in ALAD inhibition and increased urinary excretion of ALA. Male CD rats received a single ip injection of Ga2(SO4)3 at doses of 12.5, 25, 50, 100, and 200 mg Ga/kg. A dose-dependent inhibition of ALAD was observed 24 hr later in liver, kidney, and erythrocytes. After injection of 25 mg Ga/kg, maximal inhibition (42 to 49% of control) of ALAD occurred between 6 and 24 hr in liver and kidney with full recovery of activity at 96 hr. In erythrocytes, maximal inhibition (48% of control) occurred between 24 and 48 hr with recovery of activity at 96 hr. Mild to moderate renal proximal tubular necrosis in the pars recta was observed 24 hr after administration of 100 and 200 mg/kg, but no histopathologic changes were evident at lower doses. No consistent changes in urinary excretion of ALA were observed. Lineweaver-Burk analyses of renal and hepatic ALAD activities in the absence and presence of gallium indicated that the inhibition of ALAD by this element is noncompetitive (same Km, decreased Vmax). Gallium was shown to possess an inhibition constant (Ki) of approximately 3 microns for ALAD, similar to the Ki obtained for lead in other studies. Incubation of ALAD in vitro with gallium and lead, an active thiol group inhibitor, resulted in a greater inhibition of the enzyme. Further in vitro studies demonstrated the attenuation of gallium inhibition of hepatic and renal ALAD by zinc, suggesting that the mechanism of gallium action may involve competition for or displacement of zinc from the sulfhydryl group of the enzyme active site. Since ALAD inhibition occurred at doses at which no histopathologic changes were evident, the determination of ALAD activity in various tissues, including blood, may be of potential value as a biomarker of exposure/toxicity to metals such as gallium. The effect of chemical form and route of exposure of gallium and effects of other Group III metals on inhibition of ALAD and excretion of ALA is discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulsed holmium:yttrium-aluminum-garnet (Ho:YAG) laser ablation of fibrocartilage and articular cartilage

A new, near-infrared, pulsed holmium laser (wavelength, 2.1 microns; pulse duration, 400 microseconds) was used to ablate bovine articular cartilage and meniscal fibrocartilage. Microscopic examination revealed zones of thermal damage extending 550 microns from ablation sites. Ablation rates were measured with a mass loss technique. Above threshold, mass removal rates were proportional to laser radiant exposure. Threshold radiant exposure for ablation was 50 J/cm2 for articular cartilage and 11 J/cm2 for meniscal fibrocartilage. Because the holmium laser can precisely and rapidly resect cartilaginous tissues with only moderate necrosis, function in a saline environment in direct contact with tissue, and be transmitted through conventional optical fibers, it has the potential to become a useful tool for the precise arthroscopic removal of intraarticular tissue.

Evidence for two types of cytotoxic necrotizing factor in human and animal clinical isolates of Escherichia coli

We have characterized the in vitro and in vivo toxic properties of cell sonic extracts from 22 animal and human clinical isolates of Escherichia coli that caused both necrosis in the rabbit skin and multinucleation in tissue cultures, two toxic properties previously reported as being specific for E. coli cytotoxic necrotizing factor (CNF). Two distinct toxic phenotypes were observed. Type 1, which was displayed by originally described CNF strains, was characterized by extensive multinucleation and rounding of cells in HeLa cell culture assays, moderate necrosis in the rabbit skin test, and absence of necrosis in the mouse footpad test. Type 2, which has recently been shown to be associated with E. coli Vir plasmid, was characterized by moderate multinucleation, by polymorphism and elongation of HeLa cells, and by an intense necrotic response in both the rabbit skin test and the mouse footpad test. The distinction between the two cytotoxins accounting for these effects (CNF 1 and CNF 2), together with their partial relatedness, was confirmed by seroneutralization studies of both cytopathic effects and necrosis in the rabbit skin test. In addition, type 2 extracts were more lethal in the mouse intraperitoneal test and induced a moderate, although not totally repetitive, fluid accumulation in the ileal loop test. The original toxic properties of these recently recognized categories of E. coli strains, together with their association with enteritis and septicemia, suggest that these strains may play a significant role in pathology.

Neurological damage in a cardiopulmonary arrest model in the rat

In view of the interest in cerebral protection in the framework of cardiopulmonary arrest (CPA), we assessed the neurological damage in a CPA model in the rat. CPA was induced in anesthetized Wistar rats by discontinuation of the jet ventilation and intracardiac injection of KCl. The animals were resuscitated after a CPA of either 7 min, 10.5 min, or 14 min. Six rats were used as nonischemic controls. All nonischemic rats survived, whereas in the resuscitated rats the 7-day survival rate decreased with increasing CPA duration. In the resuscitated rats, the neurological score was worse than in the control rats, and the score after 10.5-min CPA was worse than after 7-min CPA. Seizures were observed in 68% of resuscitated rats. Histopathological evaluation revealed moderate but selective neuronal necrosis in the hippocampus of all ischemic rats, and no cortical necrosis. However, neither the occurrence of seizures nor the extent of neuronal necrosis was related to the CPA duration. We conclude that in this model survival rate, neurological score, occurrence of seizures, and histopathological assessment can be used to evaluate neurological damage, although the contribution of other organ failure to these effects cannot be excluded.

Changes in hepatic function tests to induced toxicity in the bovine liver.

Graded hepatic damage was induced in mature lactating dairy cows to measure the sensitivity of several hepatic diagnostic tests. In a preliminary study, cows were dosed with .05, .10 and .20 ml/kg body weight of carbon tetrachloride. Extreme changes occurred in hepatic tests by 24 h post-dosing, and all died by 35 h with massive diffuse centrilobular necrosis of hepatic cord cells. Dosing was decreased to induce non-fatal hepatic changes. Cows in Groups 1, 2, 3 and 4 were orally dosed with .002, .004, .006 or .01 ml/kg body weight of carbon tetrachloride, respectively. Serum enzymes of hepatic origin, bilirubin, plus bromosulfophthalein dye clearance were assayed before dosing and up to d 14 post-dosing. Liver biopsies were performed 24 h post-dosing for histological evaluation and cytochrome P-450 content. Hepatic concentrations of cytochrome P-450 were decreased in all the dosed cows. Serum activities of sorbitol dehydrogenase and gamma-glutamyl transferase were elevated in cows of Groups 3 and 4 and glutamic-oxaloacetic transaminase in cows of Group 4 by 24 h. Serum alkaline phosphatase, glutamic-pyruvate transaminase, lactate dehydrogenase, bilirubin, urobilinogen and bromosulfophthalein dye clearance were not significantly different. Mild to moderate diffuse centrolobular necrosis was observed in livers of cow of Groups 3 and 4, but no pathological changes were seen in Groups 1 and 2.

Hepatic artery embolization of experimental hepatic tumors with absolute ethanol.

Hepatic artery embolization with absolute ethanol (HAEE) was done in rats and rabbits with experimentally induced liver tumors, and its effects on liver parenchyma and tumors were analyzed microscopically in comparison with those of controls. HAEE with 0.1 ml in rats brought massive tumor necrosis and minimal damage to liver parenchyma. But HAEE with 0.15 ml in rabbits induced moderate to massive necrosis of liver parenchyma with minimal to moderate tumor necrosis. Damage to the intrahepatic bile ductules was also seen in both animals. Many problems should be resolved before clinical use.

Regeneration of the uterine epithelium in later stages of pseudopregnancy in the rabbit. An ultrastructural study.

Morphological changes of the uterine epithelium in later stages of pseudopregnancy in the rabbit have been studied using different morphological methods. The highly proliferated mucosa with numerous symplasms of a pseudopregnant animal returns to the morphology of a nonpregnant animal by apoptosis, moderate necrosis and lytic transformation of symplasms back to typical endometrial cells without desquamation of cells. The first signs of lytic transformation are observed on Day 8 of pseudopregnancy. Enhanced regeneration with apoptosis and lysis of the symplasmic nuclei is observed between Day 14 and Day 16. Full restoration of the epithelium with reappearance of ciliated cells, typical columnar and partly mucified epithelial cells is not completed earlier than Day 24 p. hCG. This epithelium, however, differs clearly from the epithelium of a virgin rabbit due to several residues of epithelial transformation. Thus, from a morphological point of view, pseudopregnancy in the rabbit lasts up to or even longer than Day 28 p. hCG with persisting ultrastructural remnants of the preceding cycle.

Status epilepticus in well-oxygenated rats causes neuronal necrosis.

Neuronal necrosis in the brain resulting from status epilepticus of 15 to 120 minutes duration in ventilated and well-oxygenated rats was assessed. Seizures were induced by inhalation of the convulsant gas flurothyl, and terminated by withdrawal of flurothyl and a single injection of thiopental. The animals were allowed to recover for one week, and neuronal damage was assessed by cell counts following subserial sectioning of the brain and microscopical examination of the sections. Infarction of the pars reticulata of the substantia nigra occurred in 5 of the 6 animals with seizure duration of 30 minutes, and in all animals with longer seizure durations. There also was a common affectation of the central parts of the globus pallidus. The pars compacta of the substantia nigra was never affected. After 45 to 120 minutes of seizures, moderate neuronal necrosis was observed in the neocortex (layers 3 and 4), and after 60 to 120 minutes was seen in amygdaloid and thalamic nuclei, as well as in CA4 and CA1 hippocampal pyramidal cells. Notably, CA3 neurons were not damaged nor were dentate granule cells affected. After 120 minutes of seizures, damage regularly affected the neocortex and the ventral-posterior nuclei of the thalamus. A conspicuous feature was the localization of neuronal necrosis at sites close to the ventricles.

Effect of transfer factor on tumor-associated immunity and tumor growth of the Dunning R-3327G rat prostate adenocarcinoma.

Of importance in the design and application of improved or new modalities of treatment are their evaluation on relevant animal models. In the case of prostate cancer (PCa) the Dunning R-3327 rat prostate adenocarcinoma (PCa), and its variant sublines, is one such experimental tumor model of its human counterpart. In a preliminary study, the effect of transfer factor (TF), one form of passive immunotherapy, on tumor-associated immunity (TAI) and tumour growth and histology of the G subline (a poorly differentiated, fast-growing, androgen sensitive, and poorly metastatic tumour of the Dunning R-3327 rat PCa) has been evaluated. TF prepared from the leukocytes of tumor-bearing animals and nontumor-bearing animals referred to as sensitized (STF) and unsensitized (UTF), respectively, had no significant effect on TAI or tumor size. The only noticeable effect of TF in this study was the presence of variable and moderate lymphocytic infiltrates, necrosis, and degenerative-type cells in tumors of animal recipients of STF. The failure to observe significant differences in TAI among tumor bearing and nontumor bearing animals raises doubt in part, of the immunogenicity of the G subline tumor and its appropriateness, at least for subsequent immunological studies. Further factors considered in this regard, are questions of tumor load, including the possible need for the use of adjuvant, and the parameters and sensitivity of immune responsiveness selected for evaluation and immunocompetency. Subsequent evaluation of the effect of TF on other more immunogenic variant sublines of the Dunning R-3327 rat tumor may yet provide further and more useful information.

Relationship of Hypoglycemia to Tumor Necrosis Factor Production and Antitumor Activity: Role of Glucose, Insulin, and Macrophages<xref ref-type="fn" rid="FN2">2</xref>

The role of hypoglycemia in tumor necrosis factor (TNF) production was examined. TNF was produced from sera of animals presensitized with reticuloendothelial system stimulants after lipopolysaccharide (LPS) challenge. Blood glucose was strongly reduced during TNF production. Glucose administration to presensitized mice (before LPS challenge) caused inhibition of TNF production. Exogenous insulin injection inhibited TNF production in a dose-related manner. Peritoneal exudate cells (PEC) from Propionibacterium acnes-primed mice revealed increased glucose consumption during in vitro TNF production but showed no relationship between the degree of glucose consumption and the ability to produce TNF. Insulin addition to the culture medium caused inhibition of TNF production from PEC, which indicated that insulin may block TNF production from macrophages. Administration of highly purified TNF (without concomitant LPS) induced extensive tumor necrosis but did not induce hypoglycemia; LPS induced moderate necrosis with accompanying hypoglycemia; insulin induced hypoglycemia but did not induce tumor necrosis. It is concluded that hypoglycemia does not accompany the action of TNF.

Testicular germ cell tumours in Denmark 1976-1980. Pathology of 1058 consecutive cases.

In the first five-year period of the Danish Testicular Carcinoma Study (DATECA) 1058 consecutive testicular germ cell tumours were examined. Of these, 554 were seminomas comprising 515 of typical type, 26 anaplastic and 13 spermatocytic; 497 were non-seminomas comprising 145 pure tumours and 352 mixed tumours of various types. Among the various subtypes of non-seminomas embryonal carcinoma (EC) was recorded in 87 per cent, endodermal sinus tumour (yolk sac tumour; EST) in 22 per cent, teratoma (T) in 55 per cent and choriocarcinoma (CC) in 17 per cent. Only very few tumours were pure EST or pure CC. Five tumours were recorded as 'others or uncertain'. The tumours were graded with regard to various histologic features. Moderate and severe necrosis, bleeding, and a large number of mitoses were significantly more frequent in non-seminomas. The presence of tumour tissue at the resection margin was also more frequent in non-seminomas. Tumours with a largest diameter of less than 2.5 cm had already caused metastases in 16 per cent of the seminomas and 29 per cent of the non-seminomas. Increasing size of the tumours was associated with increasing frequency of metastatic disease but this association was not directly proportional. Distribution of the various histologic types according to the stage of disease varied. Thus, 78 per cent of the seminomas presented in stage I while 54 per cent of the non-seminomas had localized disease. Anaplastic seminomas were distributed similarly to the non-seminomas while all spermatocytic seminomas, with one exception, were recorded as stage I. Of non-seminomatous subtypes pure EC was associated with the highest frequency of stage III, followed by mixed tumours containing CC components. Although the present series is large the heterogeneity of germ cell tumours demands further investigation of larger numbers to confirm some of the findings.

Foliar Applications of BA Increase Branching of ‘Welkeri’ Dieffenbachia

Abstract Lateral budbreak was increased significantly on ‘Welkeri’ dieffenbachia [Dieffenbachia maculata (Lodd.) G. Don] with foliar applications of 6-benzylamino purine (BA) at 500,1000, and 2000 mg/liter. Sodium 2,3:4,6-bis-0-(1-methylethylidene)-a-L-xylo-2-hexulofuranosonic acid (dikegulac) at 1000, 1500, and 2000 mg/liter and (2-chloroethyl)phosphonic acid (ethephon) at 500, 1000, and 2000 mg/liter had no effect on branching. Plant height was unaffected by application of growth regulators although moderate foliar necrosis was caused by the highest rate of BA.

Use of the Pavlik harness in treating congenital dislocation of the hip.

The Pavlik harness has made an important contribution to the treatment of congenital dislocation of the hip before walking age. Our experience of 74 cases confirms the good results already reported by several authors; however, four instances of moderate avascular necrosis of the femoral head occurred. The precise indications for the harness and the rules governing its use must be clearly understood. It may be used from the neonatal period up to 6 to 8 months of age for dislocation or subluxation with limitation of hip abduction. Selection of suitable candidates is made more accurate by taking into account the child's general tone and that of the adductor muscles, as well as the data from X-ray films taken in the harness position.

Nonprogressive course of non-A, non-B chronic hepatitis in multitransfused hemophiliacs

Eleven hemophiliacs with chronic liver disease were studied prospectively for 6 yr, with liver function tests and liver biopsies carried out at intervals of 3 yr. The second series of biopsies, compared with the first series, showed continuation of chronic persistent hepatitis in four patients, change to chronic lobular hepatitis in two, and spontaneous improvement of the disease in the four cases who had had chronic active hepatitis characterized by moderate piecemeal necrosis. One patient with active cirrhosis died of liver failure during the follow-up period. Study of the serum and intrahepatic markers for hepatitis B and delta viruses suggests that chronic liver disease is nonprogressive in hemophiliacs who have no intrahepatic viral marker.