17Beta-estradiol delivered by three different matrix patches 50 microg/day: a three way cross-over study in 21 postmenopausal women.

The aim of this study was to investigate the systemic bioavailability and plasma profiles of 17beta-estradiol (E2) after the application of three matrix patches for the transdermal delivery of E2: Menorest, Tradelia, and Estraderm MX claiming to deliver a dosage of 50 microg E2/day. All three patches were each worn randomly by 21 postmenopausal women volunteers over a 4-day period (i.e. 96 h). Each of the three treatment periods were separated by an at least 7 day wash out period according to a randomized, 3-way crossover design. Blood samples were taken from the antecubital vein before and 3, 6, 9, 12, 24, 28, 33, 48, 57, 72, 81, and 96 h after application. E2 plasma values were determined by a specific direct radioimmunoassay method. The following pharmacokinetic parameters were evaluated: AUC0-96h, Cmax, Tmax, Cmin, C(average). The time to reach the maximal E2 value of 32 h was the only pharmacokinetic parameter which was identical for all three patches. Menorest produced the highest E2 bioavailability judged by the AUC0-96h = 3967.8 +/- 1651.8 pg/ml, C(average) = 41.3 +/- 21.3 pg/ml, Cmin = 36.8 +/- 8.6 pg/ml. Tradelia showed statistically not significantly smaller C(average) = 38.9 +/- 17.0 pg/ml, AUC0-96h = 3737.9 +/- 1637.6 pg/ml x per h, and Cmin = 33.8 +/- 26.7 than Menorest. Estraderm MX showed lowest E2 plasma profiles Cmax = 38.9 +/- 25.1 pg/ml, C(average) = 33.2 +/- 17.1 pg/ml, AUC0-96 = 3192.1 +/- 1646.0 pg/ml per x h. Menorest showed the smallest fluctuation over the entire test period, similar to Estraderm MX, while Tradelia showed the highest E2-fluctuation (P < 0.01): Tradelia exhibited the highest Cmax = 48.0 +/- 20.3 pg/ml. When E2 baseline levels, prior to patch application are subtracted individually from the produced E2 plasma level, Estraderm MX is not bioequivalent to Menorest (P < 0.05). A circadian curve pattern of the E2 plasma level was observed for all patches: in the evening higher E2 plasma level were always detected compared with the morning, however, less pronounced with Estraderm MX. Individual comparison of AUC0-96h of each patch exhibited a large interindividual variability of 2000-8000 pg/ml per h for all three patches but relatively small individual variability: women with high E2 bioavailability (high responders) maintained high bioavailability in all applied patches, women identified as low and medium responders remained the same regardless of the applied patch. Menorest produced in 2/3 of all postmenopausal women with the highest E2 bioavailability (AUC0-96h), Tradelia was found in less than 1/3 (28.6%), and Estraderm MX in only one postmenopausal woman. Menorest only produced the highest reduction in postmenopausal symptoms together with Tradelia. Estraderm MX produced a smaller reduction in postmenopausal symptoms compared to Menorest and Tradelia. The observed side-effects were approximately equal in all three patches, with a maximum value after 72 h. It can be concluded that the three patches for the transdermal delivery of E2 claiming to deliver 50 microg E2/day differed from each other in their pharmacokinetic performance, although statistically not significant: Menorest exhibited the highest C(average), AUC and Cmin, and the lowest fluctuation, followed by Tradelia and Estraderm MX.

H2-receptor antagonists and antacids have an aggravating effect on Helicobacter pylori gastritis in duodenal ulcer patients.

BACKGROUND: Antacids, such as aluminium-magnesium hydroxide (AIMg(OH)3), or H2-receptor antagonists, such as ranitidine, are common drugs used for treating peptic ulcer disease and acid-related symptoms. METHODS: In a prospective double-blind controlled study, 174 patients were randomized to a 4-week course of treatment with either AIMg(OH)3 (acid-binding capacity: 280 mval/day) or ranitidine 300 mg for active Helicobacter pylori-associated duodenal ulcers (as determined by histology and the urease test). Before and after treatment, two biopsy specimens each were obtained from the antrum and corpus, and the grade and activity of gastritis, as well as H. pylori density, were determined using a score ranging from 0 = none to 4 = severe. RESULTS: Pre- and post-treatment histology were available for 138 patients (AIMg(OH)3: 67, ranitidine; 71). Treatment with AIMg(OH)3 significantly increased the activity of corpus gastritis (Wilcoxon signed-rank: P = 0.0014), while ranitidine treatment significantly increased both the grade and activity of corpus gastritis (P = 0.0002 and P = 0.0001 respectively). In the antrum, both regimens provoked a significant increase in the frequency of intestinal metaplasia, but this may be a consequence of sampling error. CONCLUSIONS: Ranitidine and AIMg(OH)3 have an aggravating effect on H. pylori gastritis in duodenal ulcer patients. This should be considered a side-effect of the respective drugs and is more pronounced with ranitidine.

Continuous versus cyclical transdermal estrogen replacement therapy in postmenopausal women: influence on climacteric symptoms, body weight and bleeding pattern.

OBJECTIVES: To compare continuous and cyclical transdermal estrogen replacement therapy (ERT) with or without an oral progestogen regarding climacteric symptoms, body weight and bleeding pattern. METHODS: A total of 2459 postmenopausal women were treated for three cycles of 28 days in an open, randomized, parallel group multicenter study. Patients received an estrogen matrix patch (50 micrograms 17/beta-estradiol/day) twice weekly, either continuously (eight patches/cycle) or cyclically (six patches/cycle, i.e. 3 weeks on, 1 week off). A total of 1232 patients were treated continuously and 1227 cyclically. In the study group 1150 patients had an intact uterus (543 in the continuous and 607 in the cyclical treatment arm) and received, in addition to the estrogen patch, an oral progestogen in a transformation dose for 12 days of each cycle. Hysterectomized patients totaling 1309 (689 in the continuous versus 620 in the cyclical group) did not receive progestogen. Of the 2459 patients, 771 (31.4%) participated in a follow-up study with two further treatment cycles, which was offered to the patients at the end of the main study. The main outcome measures were climacteric symptoms, measured at the end of cycles 1-3 by a Visual Analogue Scale at baseline, and body weight measured at baseline at the end of cycles 3 and 5. In addition, the bleeding time per cycle (days) was evaluated in all patients with an intact uterus. RESULTS: Continuous and cyclical transdermal ERT reduced, over three treatment cycles, the average climacteric symptom score by 1.77 and 1.70, respectively. The percentage remission and improvement rates for the ten climacteric symptoms ranged between 69.3 and 88.0% and did not differ between the two groups. In patients with a higher symptom score at baseline, the continuous treatment was slightly more effective. However, this effect was statistically not significant. After three treatment cycles body weight increased in both treatment groups by between 500 and 700 g. Further treatment during the follow-up study induced an additional average weight gain of 200-400 g. These results were not influenced by the addition of an oral progestogen. In patients with an intact uterus, the average bleeding time at the end of the first cycle (5.4 days in the continuous versus 5.3 days in the cyclical group) increased slightly during cycle 2 and returned to baseline values at the end of cycle 3. CONCLUSIONS: Continuous and cyclical transdermal ERT were equally effective in reducing climacteric symptoms. The short term use of five cycles transdermal ERT induced a slight increase in body weight which was independent of the treatment regimen. These results were not influenced by the type and mode of administration of a progestogen. Both ERT regimens were very well tolerated and are suitable alternatives for estrogen replacement therapy of postmenopausal women.

[Antacids for postoperative prevention of stress ulcer in infants: a dose finding study]. / Antazida zur postoperativen Stressuljusprophylaxe bei Süglingen: Studie zur Dosisfindung.

UNLABELLED: In the prophylaxis of stress ulcers with antacids in young infants there are no recommendations of dosages that consider the physiologic maturation of gastric acid secretion. During the first six month of life the amount of gastric acid secretion in relation to body weight and body surface area increases exponentially. Therefore adult dosages of antacids cannot be transferred to infants. METHODS: In a cross over study 12 infants aged between 4 and 174 days, who had been undergoing a cardiosurgical intervention with the heart lung machine, were treated during 48 hours with 2 different antacid regimens over a period of 24 hours each, monitoring the gastric pH continuously. The used antacid consisted of an aluminium-magnesium complex (Al(OH)3, 90 mg/ml and Mg(OH)2, 60 mg/ml): Regimen A: 6 x 0.5 ml per kg body weight. Regimen B: 0.25 ml per kg body weight at a gastric pH less than 3, with the pH read every 30 minutes. RESULTS: Compared to 28 applications under regimen B, 72 single doses were given under regimen A, 58 of them at a gastric pH of higher than 3. Thus, the mean administered dose was significant lower under regimen B (2.2 ml) than under regimen A (12.0 ml). Consequently, the mean level of gastric pH was higher under regimen A (median: 5.96 +/- 1.31 versus 4.94 +/- 1.16). pH-values lower than 3 were more often measured under regimen B, whereas the phases at this pH-level were longer under regimen A. CONCLUSION: The usual body weight related dosage of antacids seems to be to high for early infancy. In the face of the discrepancy of the administered antacid quantity comparing regimen A with regimen B, it seems to be reasonable for the studied age group to reduce the single antacid dose to 0.25 ml/kg body weight while adhering to a high application frequency of 6 times a day.

[Kinetics of a new patch for transdermal administration of 17 beta-estradiol]. / Kinetik eines neuen Pflasters zur transdermalen Applikation von 17 beta-Estradiol.

A novel patch containing 17 beta-Estradiol exhibits improved kinetic profiles compared to the currently available leading transdermal product. The blood concentrations produced by the newly developed matrix patch are stable over 3 to 4 days, thus avoiding the occurrence of 17 beta-Estradiol peaks in the blood. In an additional clinical study an almost linear relationship could be identified between the patch size (Test patch: 7.25, 14.5 and 29.0 cm2) and the obtained 17-estradiol bioavailability (judged on AUC, cmax, c(ave), Cmin). These results are corroborated by the additional in vitro experiments. An almost constant drug delivery rate of 48 micrograms +/- 15 micrograms/day of 17 beta-Estradiol per 13.85 cm2 patch over 4 days can be detected through excised human skin. No statistically significantly different transdermal flux rates of 17 beta-Estradiol were detected in 3 different batches of the transdermal drug delivery system in vitro. Statistical evaluations were performed with the 3-Way-Anova test on the 0.05 significance level. This newly developed product presents a kinetically optimized transdermal 17 beta-estradiol patch for hormone substitution therapy.

Nitric oxide in gastroprotection by aluminium-containing antacids.

Pretreatment with aluminium-containing antacids at their original pH or after acidification is known to protect the gastric mucosa against the damaging action of strong irritants and this protection is accompanied by an increase in gastric blood flow (GBF) but the mechanisms underlying these effects have not been elucidated. We investigated the role of endogenous nitric oxide (NO) and prostaglandins (PS) in the prevention of ethanol-induced gastric damage and the alteration of GBF by Maalox and its active component Al(OH)3. Maalox and Al(OH)3 at their original and acidic pH induced dose-dependent gastroprotection accompanied by attenuation of the reduction in GBF caused by 100% ethanol; similar protective and hyperemic effects were recorded after treatment with nocloprost, a locally active PGE2 analog, and nitroglycerin, a donor of NO. Pretreatment with indomethacin that suppressed mucosal PGE2 by about 90%, failed to affect the protective influence of Maalox or Al(OH)3 at their original or acidic pH. On the contrary, pretreatment with NG-nitro-L-arginine (L-NNA), a potent selective inhibitor of NO synthase, reversed the gastroprotective and hyperemic effects of Maalox or Al(OH)3 at original and acidic pH and this reversal was significantly antagonized by L-arginine but not D-arginine. The gastroprotective and hyperemic effects of nocloprost were not influenced by the pretreatment with L-NNA. We conclude that aluminium-containing antacids activate the NO system, which may contribute to the gastroprotective activity of these drugs through an increase in mucosal microcirculation.

Low-dose antacid therapy in the treatment of duodenal ulcer--a multicentre double-blind trial vs. misoprostol.

We conducted a 4-week double-blind randomized controlled multicentre trial to compare low-dose-antacid (AA) therapy (225 meq total neutralizing capacity per day) with therapy using the prostaglandin E1-analogue, misoprostol (MS) (400 micrograms bid), on ulcer healing and relief of symptoms in 100 outpatients with endoscopically proven duodenal ulcer (DU, 49 patients on AA, 51 patients on MS). Of the 100 patients enrolled in the study 96 could be evaluated; 49 received AA, 47 MS. Endoscopies were performed before treatment, 2 and 4 weeks after initiation of treatment. Healing rates of AA- and MS-treatment were 36.7% vs. 25.5% (2 weeks) and 79.6% vs. 74.4% (4 weeks) and did not differ as much as relief of pain during the daytime. Rates of relief of nighttime pain were significantly higher on AA-treatment after 2 weeks of treatment (81.1% vs. 48.6%; p less than 0.05), but not during the later course of treatment. Thus, it can be concluded that low-dose AA-treatment using an aluminum/magnesium hydroxide preparation in tablet form represents an effective and safe therapy for duodenal ulcer.

Intragastric pH in the gastroprotective and ulcer-healing activity of aluminum-containing antacids.

Antacids containing aluminum have been shown to stimulate the protective processes in the gastric mucosa and to enhance the healing of chronic gastroduodenal ulcerations, but the mechanisms of these effects are still unexplained. This study was designed to compare the protective effects of unmodified and acidified (pH 2.0) Maalox 70 and Al(OH)3 on the formation of acute gastric mucosal lesions induced by absolute ethanol, taurocholate, acidified aspirin and stress, and to determine the role of gastric acid in healing of chronic gastroduodenal ulcerations by these antacids in rats. Acidified Maalox 70 and Al(OH)3 were significantly more potent than unmodified agents against all four tested types of acute mucosal lesions, and this action was probably due to their 'mild irritant' effect as evidenced by extensive exfoliation of the surface epithelial cells observed microscopically after the exposure of the mucosa to these agents. Mucosal generation of prostaglandins does not appear to be involved in the gastroprotection by acidified Maalox because the pretreatment with indomethacin did not affect this protection. In contrast to the protective effect, the ulcer-healing capacity of Maalox or Al(OH)3 does not appear to be dependent upon the presence of gastric acid because the reduction or elimination of endogenous acid by the pretreatment with ranitidine or omeprazole did not affect the healing of gastroduodenal ulcerations. We conclude that aluminum-containing antacids induce the mucosal protection that is enhanced in the presence of luminal acid but exhibit an ulcer-healing property that appears to be unrelated to gastric acid secretion or mucosal generation of prostaglandins.

Duodenal ulcer therapy with low-dose antacids: a multicenter trial.

One hundred outpatients with endoscopically verified duodenal ulcer were treated in a double-blind, randomized, multicenter trial with either low-dose antacid (AA, Supralox, 1 tablet three times a day 1 h a.c. and 2 tablets at bedtime, with acid binding capacity of 225 mEq) or misoprostol (MS, Cytotec, 400 micrograms p.o. b.i.d.). Patients were treated up to 4 weeks and underwent endoscopic and clinical evaluation at 2 and 4 weeks. Clinical symptoms were recorded at the beginning and at 2 and 4 weeks. Ninety-eight patients completed the study. After 4 weeks of treatment, the healing rate in the AA group was 79.6% compared with 74.4% in the MS group. The difference in healing rates between these two groups was statistically not significant. The effect on clinical symptoms assessed as percentage improvement during the therapy was similar under both medications. However, the relief of night pain was significantly higher during the first 2 weeks of AA therapy. The side effects of both treatments were minimal, with a higher rate of side effects (especially diarrhea) in the MS group. Thus, a low-dose antacid tablet regimen is safe and effective therapy for duodenal ulcer patients.

Healing of chronic gastroduodenal ulcerations by antacids. Role of prostaglandins and epidermal growth factor.

Antacids show gastroprotective action against various irritants in experimental animals and enhance the healing of chronic gastroduodenal ulcers in humans but the mechanisms of these effects are unknown. The present study was designed to determine whether prostaglandin (PG) and epidermal growth factor (EGF), which also have protective and antiulcer properties, contribute to the action of antacids on rat's stomach. It was found that Maalox 70 and its active component, Al(OH)3, enhance significantly the healing of chronic gastric and duodenal ulcers observed during 7 and 14 days after their induction. Pretreatment with indomethacin caused a significant prolongation of ulcer healing, and this was accompanied by a significant reduction in PG and EGF formation, suggesting that both factors may be involved in ulcer healing. Maalox and Al(OH)3 failed to prevent the suppression of PG by indomethacin but were equally effective in ulcer healing in rats without and with indomethacin administration, suggesting that endogenous PG may not play any important role in the healing process by these drugs. Removal of salivary glands, the major source of EGF, also prolonged ulcer healing but, again, Maalox was as effective in ulcer healing as in rats with intact salivary glands. Our findings that Maalox at pH above 3.0 binds significant amounts of EGF, enhances the binding of EGF to the ulcer area, and stimulates mucosal growth, suggest that EGF may be involved in ulcer healing; however, because antacids are also effective after sialoadenectomy, EGF does not seem to be the major factor in ulcer healing by these drugs.

Role of intragastric pH in cytoprotection by antacids in rats.

Antacids containing Al(OH)3 have been shown to stimulate the protective and reparative processes in the gastric mucosa exposed to various ulcerogens but the mechanisms of these effects are unknown. This study was designed to determine the role of intragastric pH and mucosal formation of prostaglandins (PG) in antacid-induced protection of gastric mucosa against ethanol or aspirin damage. Maalox 70 and its active component, Al(OH)3, were used alone at the original pH (7.5 and 6.0, respectively) and lower pH or were combined with ranitidine or histamine before intragastric administration of 100% ethanol or acidified aspirin to induce acute mucosal lesions. Maalox and Al(OH)3 were relatively more effective to protect against the damage due to ethanol, and to some extent also due to aspirin, when given at a pH (pH 2) lower than at their original pH. Pretreatment with ranitidine, which itself did not change ethanol-induced damage, greatly reduced the protection afforded by Maalox or Al(OH)3, whereas pretreatment with histamine enhanced this protection. Maalox and Al(OH)3 at their original or low pH did not alter significantly the capability of gastric mucosa to generate PG but resulted in a significant increase in luminal release of PG. Pretreatment with indomethacin to reduce mucosal generation of PG failed to affect the protective effects of Maalox or Al(OH)3 at their original or lower pH. We conclude that Maalox 70 and Al(OH)3 protect the gastric mucosa against ethanol damage but that this protection requires the presence of acid and may not depend entirely upon the mucosal production of PG.

Gastroprotection by an aluminium- and magnesium hydroxide-containing antacid in rats. Role of endogenous prostanoids.

This study was designed to determine the gastroprotective actions of an antacid (Maalox 70) and its components, Al(OH)3 and Mg(OH)2, against acute gastric lesions induced by absolute ethanol, acidified aspirin (ASA), and water immersion and restraint stress in rats. Given orally, the antacid prevented dose-dependently the formation of gastric lesions by all three ulcerogens, and these effects were similar to those obtained with a methylated prostaglandin E2 (PGE2) analog. Active Al(OH)3 gel was equipotent with Maalox, whereas Mg(OH)2 was significantly less effective in gastroprotection than Maalox 70. Chemically inactive Al(OH)3 wet gel showed only small and insignificant protective properties. Since the gastroprotective activities of Maalox 70 against ethanol lesions cannot be reversed by pretreatment with indomethacin, and since neither Maalox 70 nor its active components affected the mucosal generation of PGE2 and leukotriene C4, we postulate that mucosal prostanoids are not the primary mediators in the mechanism of their protective action on the gastric mucosa.

Hemorrheologic effects of iotrolan after intra-arterial injection in rabbits: comparison with other types of contrast media.

Aqueous solutions of the x-ray contrast media (CM) iotrolan and meglumine diatrizoate with and without gelatin added were injected into the rabbit aorta just above the bifuraction in a dose of 0.3 g I/kg and the duration of opacification of the vessel was measured. The difference between the periods recorded for iotrolan and the viscous diatrizoate solution (4 to 6 seconds) and those for the pure diatrizoate solution (3 to 4 seconds) was statistically significant (p less than or equal to 0.05). The differences are directly correlated to the viscosity of the CM solutions. At first the intra-aortal injection of iotrolan causes a somewhat more marked decline in femoral artery blood flow than diatrizoate. The increase in blood flow, which begins 10 seconds after injection is, however, significantly (p less than or equal to 0.05) less after iotrolan than after diatrizoate. This is attributable to the differences in the osmolalities of the two CM. Due to the fact that it is isotonic to blood and because of its viscosity, iotrolan has certain advantages over conventional agents for arteriography that are relevant to clinical practice.

Experimental evaluation of radiographic contrast media in perivascular pain receptors in the perfused isolated rabbit ear.

The algesic effects of intravascularly injected solutions of sorbitol and ionic and nonionic contrast media (CM) with high and low osmolality were tested in the perfused isolated rabbit ear connected to the body by the great auricular nerve. The threshold for the pain reflex effect was found to be at an osmolality of between 600 and 700 mosm/kg H2O, that is, at about twice the osmolality of blood. This result is consistent with results obtained to date in investigations in the non-anesthetized rat and in diagnostic examinations with CM in humans. The effects of both sorbitol and the ionic CM at a given osmolality were dose dependent only after low doses and not after a high dose. There were no pain reactions after injection of ionic and nonionic CM with a low osmolality. Release of prostacyclin was observed in preliminary tests after injection of ionic substances with high osmolality, but not after injection of CM with low osmolality.

Experimental urography in dogs: diagnostic quality and pharmacokinetic behavior of iotrolan in comparison to nonionic and ionic, monomeric contrast media.

A dose of 0.3 g I/kg iotrolan yields much better opacification of the renal parenchyma in dogs (n = 6, intraindividual comparison) than sodium diatrizoate or iopromide, and imaging of the urinary tract is practically equally as good. The plasma iodine levels of all three agents 2 minutes after the bolus injections are 3 mg/ml and the half-lives in the blood are 8 to 10 minutes. The injection of iotrolan causes the hematocrit value to drop by maximum 3.8% 10 minutes after the injection, and corresponding figure after iopromide is 10.8% and that for sodium diatrizoate at 4 minutes is 18.9%. In a further study in dogs (n = 4, intraindividual comparison; dose 0.6 g I/kg) it was found that in the period 10 to 240 minutes after a bolus injection of iotrolan or iopamidol the iodine concentration in the urine was 1.5 to 2 times higher after iotrolan than after iopamidol. Iopamidol causes much higher urinary flow than iotrolan, especially in the first 20 minutes after injection. The properties of iotrolan described here appear to indicate that this novel nonionic, dimeric contrast medium has certain advantages over the monomeric, ionic and nonionic agents for urographic indications.

Craniofacial osteosarcomas: plain film, CT, and MR findings in 46 cases.

Forty-six osteosarcomas of the cranial and facial bones were reviewed radiographically by using the conventional parameters for long bone tumors. There were 32 de novo osteosarcomas (11 maxillary, 13 mandibular, and eight cranial) and 14 postradiation osteosarcomas. All the maxillary tumors originated from the alveolar ridge, and the majority of mandibular lesions began in the body of the mandible. The postradiation osteosarcomas occurred in portions of bones at the borders of the radiation field; the latent period ranged from 4 years, 2 months to 50 years (mean, 14 years). The majority of de novo or postradiation craniofacial osteosarcomas were osteolytic with a long transition zone and no periosteal reaction; the exception was in the mandible, where nearly half the cases were osteoblastic and periosteal reaction was occasionally present. Tumor matrix mineralization occurred in more than 75% of the cases, and osteoid matrix calcification was most frequent, even though most tumors were chondroblastic. Soft-tissue extension of tumor was present in all cases and contained calcifications in more than half. Conventional radiographs are of limited value in evaluating head and neck osteosarcomas because of the superimposed bony structures. CT provides excellent detection of tumor calcification, cortical involvement, and, in most instances, soft-tissue and intramedullary extension. MR is even more effective in demonstrating the intramedullary and extraosseous tumor components on both T1- and T2-weighted images. However, CT and plain films are superior to MR in detecting the matrix calcifications and bone destruction or reaction.

Lymphomas of the head and neck: CT findings at initial presentation.

CT findings were reviewed in 68 patients with untreated head and neck lymphoma. More than half of the patients with either Hodgkin's disease or non-Hodgkin's lymphoma were detected in the earlier stages (stage I or II). Four types of abnormalities were identified with CT: nodal involvement alone (type 1), extranodal involvement alone (type 2), a combination of extranodal and nodal disease (type 3), and multifocal extranodal disease with or without nodal involvement (type 4). In the 18 patients with Hodgkin's disease, a subgroup of mixed cellularity was most common; type 1 was the prevailing CT presentation, and no type 2 or 4 lesions were observed. In the 50 patients with non-Hodgkin's lymphoma, diffuse large-cell lymphoma was the most common histologic subtype, and the most common CT presentation was type 2, followed by type 3. Lymphomatous nodes may be extensive and confluent, but often they are smaller than 2 cm and rarely are necrotized. The most frequent extranodal sites of head and neck lymphomas are Waldeyer's ring, paranasal sinuses, and nasal cavity. Extranodal lymphoma cannot be differentiated reliably from the more commonly occurring carcinoma, although it is less often associated with invasion and destruction of adjacent bony structures. Multiple sites of extranodal involvement, with or without neck lymphadenopathy, may suggest a diagnosis of non-Hodgkin's lymphoma.

Treatment-related white matter changes in cancer patients.

Forty cancer patients with bilateral diffuse cerebral white matter hypodensities on computerized tomography (CT) scan were reviewed. Brain irradiation and/or chemotherapy were considered responsible for the CT abnormalities in all patients but one, whose changes were presumably due to demyelination related to the aging process. Among these 39 patients, 7 had clinical symptoms of leukoencephalopathy. Two patients had acute transient leukoencephalopathy, and one of them experienced permanent neurologic changes after continuing treatment. Six additional patients had delayed leukoencephalopathy. The interval between whole-brain irradiation (WBXRT) alone and the CT detection of white matter hypodensities was almost always longer than 1 year. This interval was shortened to less than 1 year in a significant number of patients when WBXRT was followed by various chemotherapeutic protocols. More importantly, there was an increased incidence of clinical leukoencephalopathy. A higher incidence of clinical leukoencephalopathy in patients receiving intracarotid chemotherapy in the treatment of brain tumors and in patients receiving combination chemotherapy for central nervous system relapse of adult leukemia suggests a need for further investigation.

[Intravascular rheologic changes following the administration of a contrast medium--animal experiment studies]. / Intravasale rheologische Veränderungen nach Kontrastmittelapplikation--Tierexperimentelle Untersuchungen.

An angiographic animal study showed that hyperosmolar, ionic contrast media with a low viscosity produce the greatest increase in blood flow and the shortest diagnostically useful contrasting time of the vessels. The longest vessel contrast time and the smallest secondary increase in blood flow is seen for a nonionic, nearly isotonic contrast medium with a somewhat higher viscosity.