Cardenolide analogues. 2. 22-Methylenecard-14-enolides.

22-Methylene-3beta-hydroxy-5beta,20(S)-card-14-enolide (11) and 22-methylene-3beta-hydroxy-5beta,20(R)-card-14-enolide (12) were synthesized from digitoxin (1). Attempts to prepare the 14beta-hydroxy-22-methylene analogues were unsuccessful. The 20(R) isomer (12) was found in Na+, K+-ATPase inhibition studies to be twice as active as 14-dehydrogitoxigenin (17). The 20(S) isomer (11) was significantly less active than 17. The hydrolysis of steroid 3beta-tert-butyldimethysilyl ethers was also found to be much more difficult than with nonsteroids.     

Lactones. 22. Synthesis and reduction of alpha-aminomethylene-delta,delta-diphenyl-delta-valerolactones

Treatment with tris-(dimethylamino)-methane resp. formylation and reaction with piperidine transfer 1 to 5a,b, which can not be reduced to the corresponding alpha-aminomethyllactones 4a,b, in contrast to the homologue 6 and other alpha-aminomethylene-gamma- and delta-lactones. Isolation of products and gc/ms-investigations verify the reaction course: The aminomethyl moiety in alpha-position of delta,delta-diarylated delta-lactones is instable and eliminates amine to give 7 (NaCNBH3) or 9 (H2/Pt). Only cleavage of the lactone ring enables the formation of stable aminomethyl compounds (10,11). 5a shows weak parasympatholytic and no H1-antihistaminic activity at the isolated guinea-pig ileum.     

Inhibition of cholesterol side-chain cleavage by 22-azacholesterol.

The side-chain of cholesterol is oxidatively cleaved by a cytochrome P-450-dependent enzyme system present in mammalian adrenal mitochondria. The reaction was postulated to proceed via one or more hydroxylated intermediates. Inhibition of the reaction by the potent inhibitor 22-azacholesterol did not result in a build-up of the postulated intermediates: (20S)-20-hydroxycholesterol, (22R)-22-hydroxycholesterol, (20R,22R)-20,22-dihydroxycholesterol or (20S)-cholesterol hydroperoxide. Spectral studies indicate a modified type II spectrum for the reaction of 22-azacholesterol with adrenal mitochondrial cytochrome P-450. In addition, spectral and electron spin resonance studies indicate a common interaction of cholesterol and 22-azacholesterol with the cytochrome. Although this study does not resolve the question of the intermediacy of the oxygenated derivatives in the cleavage reaction, it indicates that the binding of 22-azacholesterol depends on its steroid structure rather than on its amine character. A discussion of the proximity of the heme to the substrate binding site is also presented.     

Modification of guide wire for 22-gauge safe guide.

Safe guide is a central venous catheterization kit that serves as both pilot needle and introducer. With a single puncture, a guide wire can be introduced by inserting it through the side port of the 22-gauge needle. The advantage is that this needle can be placed within a blood vessel using no more force than is required to insert a pilot needle. However, the 0.018-inch guide wire is vulnerable to kinks and locking. Because the tip has been shaped into a sharp J-shaped angle, it can kink at the puncture site, and locking sometimes occurs when the guide wire is passed through the side port of the needle, or when the dilator is introduced. In order to resolve these issues, we modified the device by making an experimental guide wire with a gentler angle. In addition, we fortified the body of the wire without altering its thickness. We then investigated the effectiveness of our modifications. The subjects of the study were 120 patients, who required central venous catheterization. They were divided into 2 groups. The original J-type guide wire was used in one group (Group A: n = 60) and the modified guide wire in the other group (Group B: n = 60). Catheters were introduced by right internal jugular vein puncture. We observed the following: 1) incidence of back-flow appearing at withdrawal of the needle without back-flow during advancement, 2) incidence of kinking or locking of the guide wire when it was passed through the side port, 3) incidence of kinking of the guide wire at the puncture site when introducing the dilator, and 4) complications. The results were as follows: 1) back-flow appeared upon withdrawal in 3.4% of both groups; 2) kinking and locking occurred when passing the guide wire through the side port of the Safe guide needle in 16.7% of Group A and 1.7% of Group B; 3) kinking of the guide wire occurred when introducing the dilator in 5 % of Group A in contrast to 0% in Group B; 4) the only complication caused by the passing of the guide wire was accidental puncture of the common carotid artery, which occurred in 1.7% of both groups. No problems with the guide wire were noted in either group. The use of our modified guide wire decreased the incidence of kinking and locking of the guide wire when passing it through the side port. In addition, no guide wire kinking at the puncture site occurred when introducing the dilator. Issues associated with the original J-type guide wire were resolved by 1) changing the guide wire tip to a gentler angle, and 2) fortifying the guide wire by altering its composition.     

Multiple myeloma in Ethiopians: analysis of 22 cases.

Twenty-two cases of multiple myeloma were seen in the Department of Internal Medicine, Tikur Anbessa (Black Lion) Hospital, a teaching and referral hospital in Addis Abeba, Ethiopia, from January 1983 to December 1990. The age range was 38 to 76 (mean +/- SD = 51.5 +/- 12.2) years; a third were in the fifth decade. The male:female ratio was 1.75:1. The common clinical findings were bone pain in 20 (91%), bone tenderness in 15 (68%), anaemia in 14 (64%) and spinal cord compression in 8 (36%). The erythrocyte sedimentation rate (ESR) was raised in 21. Serum protein was raised in 17 (77%) and hyperglobulinaemia was seen in 20 (91%). Serum uric acid, blood urea nitrogen (BUN) and calcium were elevated in 10, 8 and 5 patients respectively, Bence-Jones proteinuria and albuminuria were each found in 9 patients. All patients had radiological abnormalities; 9 had a combination of lytic lesions, osteoporosis and pathological fractures (41%). Ten patients presented in clinical stage III. Four patients are being followed after 3-84 (median 40.5) months; eight were lost to follow-up 1-8 (median 2.0) months after diagnosis. Ten patients have died after 1-55 (median 11) months. Multiple myeloma is not uncommon in Ethiopians. Except for a lower age at presentation, the clinical, haematological, biochemical, and radiological findings, and the response to therapy, are similar to those reported elsewhere.     

Disrupted dopaminergic neurotransmission in 22q11 deletion syndrome.

22q11 Deletion syndrome (22q11DS) is associated with chromosome 22q11 microdeletions and high rates of psychiatric disorders. Susceptibility for these disorders could be explained by haploinsufficiency of the catechol-O-methyltransferase gene, which encodes an enzyme involved in dopamine (DA) breakdown. It is unknown how dopaminergic neurotransmission is affected in people with 22q11DS. To date, there have been no controlled studies investigating dopaminergic neurotransmission in people with 22q11DS. We report the results of a challenge study in high-functioning adults with 22q11DS and age- and gender-matched controls using neuro-endocrine and peripheral dopaminergic markers. At baseline, 22q11DS subjects compared to controls had higher urine DA levels and lower plasma levels of the predominant DA metabolite homovanillic acid (HVA). Following DA depletion, 22q11DS subjects showed lower urine and plasma HVA levels and a lower prolactin response than controls. The ratio of DA/HVA, a rough index of DA turnover, was significantly higher in the 22q11DS subjects at baseline and after DA depletion. Our results suggest that adults with 22q11DS have disrupted dopaminergic neurotransmission, which might explain their susceptibility for psychiatric disorders.     

Enamides of phosphoric acid- and thiophosphoric acid esters. 22. Studies on acyl-enamines

Enamides of Phosphoric Acid- and Thiophosphoric Acid-Esters Phosphoric acid- and thiophosphoric acid ester-amides ( 1a–c, 5 ) react with substituted acetaldehydes ( 3a–d ) to the enamides 4a–h and 6a–d . They are transformed by catalytic hydrogenation in N-substituted phosphoric acid ester-amides ( 7a, b ), by reaction with aldehydes ( 3b, d ) in 3-azapentadienes ( 12a, b ).     

支气管肺泡灌洗治疗肺部感染22例

目的：探讨支气管肺泡灌洗治疗肺部感染性疾病的价值。方法：22例治疗组患者在全身抗感染基础上，经纤维支气管镜在病变的叶、段用37℃无菌生理盐水进行灌洗治疗，术后局部应用抗生素。20例对照组患者单纯行全身抗感染治疗。结果：22例治疗组患者经治疗后显效14例，有效8例，总治疗有效率100％。20例对照组患者经治疗后显效8例、有效9例、无效3例，总治疗有效率85％。两组准确度有显著性（P＜0．05）。结论：支气管肺泡灌洗治疗肺部感染性疾病是一种安全可靠有效的治疗方法。     

Ungesättigte Oxime, 22. Mitt. 2-Alkoximino-4-phenylbutene

Unsaturated Oximes, XXII: 2-Alkoximino-4-phenylbutenes 4-Phenyl-3-buten-2-one oxime (1) is reacted with methylating and benzylating agents. The isomeric ethers 3, 4 and 5 are separated by thin-layer chromatography and studied by nmr spectroscopy.