Mescaline and lysergic acid diethylamide (LSD) as discriminative stimuli

The observation that a particular drug state may acquire the properties of a discriminative stimulus is explicable on the basis of drug-induced interoceptive cues. The present investigation sought to determine (a) whether the hallucinogens mescaline and LSD could serve as discriminative stimuli when either drug is paired with saline and (b) whether discriminative responding would occur when the paired stimuli are produced by equivalent doses of LSD and mescaline. In a standard two-lever operant test chamber, rats received a reinforcer (sweetened milk) for correct responses according to a variable interval schedule. All sessions were preceded by one of two treatments; following treatment A, only responses on lever A were reinforced and, in a similar fashion, lever B was correct following treatment B. No responses were reinforced during the first five minutes of a daily thirty-minute session. It was found that mescaline and LSD can serve as discriminative stimuli when either drug is paired with saline and that the degree of discrimination varies with drug dose. When equivalent doses of the two drugs were given to the same animal, no discriminated responding was observed. The latter finding suggests that mescaline and LSD produce qualitatively similar interoceptive cues in the rat.Supported in part by Graduate Training Grant 2-T01-GM 00107 from the Division of Medical Sciences, National Institutes of Health and in part by Grant MH 15406 from the National Institute of Mental Health.     

Maternal activating mutation of the calcium-sensing receptor: implications for calcium metabolism in the neonate

Two infants were studied born of a mother with autosomal dominant hypocalcemia who is heterozygous for an activating mutation in the calcium-sensing receptor gene. Both infants had serum calcium levels in the low-normal range and parathyroid hormone levels in the high-normal range and were healthy. The mother's hypocalcemia had been treated with calcium carbonate and calcitriol and she has nephrocalcinosis and mild renal insufficiency. By genetic testing, both infants were shown to have normal calcium-sensing receptor gene alleles, i.e., they had not inherited the activating mutation from their mother. This provided reassurance to the family and ensured that treatment to correct apparent hypocalcemia would not be necessary. The fact that the infants had high normal parathyroid hormone levels with normal calcium may be due to the fact that with a normal calcium-sensing receptor their parathyroid glands responded in utero to the maternal hypocalcemia with an increase in parathyroid hormone.     

Haplotype structure and genotype-phenotype correlations of the sulfonylurea receptor and the islet ATP-sensitive potassium channel gene region

The genes for the sulfonylurea receptor (SUR1; encoded by ABCC8) and its associated islet ATP-sensitive potassium channel (Kir6.2; encoded by KCNJ11) are adjacent to one another on human chromosome 11. Multiple studies have reported association of the E23K variant of Kir6.2 with risk of type 2 diabetes. Whether and how E23K itself-or other variant(s) in either of these two closely linked genes-influences type 2 diabetes remains to be fully determined. To better understand genotype-phenotype correlation at this important candidate gene locus, we 1) characterized haplotype structures across the gene region by typing 77 working, high-frequency markers spanning 207 kb and both genes; 2) performed association studies of E23K and nearby markers in >3,400 patients (type 2 diabetes and control) not previously reported in the literature; and 3) analyzed the resulting data for measures of insulin secretion. These data independently replicate the association of E23K with type 2 diabetes with an odds ratio (OR) in the new data of 1.17 (P = 0.003) as compared with an OR of 1.14 provided by meta-analysis of previously published, nonoverlapping data (P = 0.0002). We find that the E23K variant in Kir6.2 demonstrates very strong allelic association with a coding variant (A1369S) in the neighboring SUR1 gene (r(2) > 0.9) across a range of population samples, making it difficult to distinguish which gene and polymorphism in this region are most likely responsible for the reported association. We show that E23K is also associated with decreased insulin secretion in glucose-tolerant control subjects, supporting a mechanism whereby beta-cell dysfunction contributes to the common form of type 2 diabetes. Like peroxisome proliferator-activated receptor gamma, the SUR1/Kir6.2 gene region both contributes to the inherited risk of type 2 diabetes and encodes proteins that are targets for hypoglycemic medications, providing an intriguing link between the underlying mechanism of disease and validated targets for pharmacological treatment.     

29例筛窦癌的放射治疗

筛窦癌发病率低,就诊时病期晚,５年无瘤生存率为３０％～５０％。由于解剖部位的限制以及局部浸润,放射和手术均有一定难度。作者回顾性分析皇家Ｍａｒｇｒｅｔ医院１９７６～１９９４年收治的２９例浸润性筛窦癌根治性放射治疗的疗效和影响预后因素。男性２４例,女性４例,中位年龄６２岁,中位随访时间４年。常有鼻出血、鼻塞、疼痛及视力改变等。起病到确诊的平均时间为９个月。２７例吸烟,１０例从事伐木或镍的开采与提炼。　　治疗前均经临床及影像学检查。仅３例局限于筛窦,余侵犯鼻腔、蝶窦、眼眶、上颌窦、额窦及脑内等。Ｔ１…     

Epidermal cyst of the breast: Detection in a screening programme

Two cases of epidermal cyst of the breast, a rare benign condition, were detected during a 3-year period in a mammographic screening programme, from 57 954 screening examinations. It is not uncommon for epidermal cysts to be initially misdiagnosed. The mammographic, ultrasound and histological features are presented. It is recommended that these lesions be resected because they possibly have malignant potential.     

Lactobezoar and cows' milk protein intolerance

A baby girl of an atopic family who developed eczema, asthma, and cows' milk protein intolerance was found to have a gastric lactobezoar at age 9 1/2 months. She responded well to the removal of the bezoar and to the appropriate dietary treatment.     

Familial translocation with partial trisomy of 13 and 22: evidence that specific regions of chromosomes 13 and 22 are responsible for the phenotype of each trisomy.

A newborn infant with clinical and pathological findings typical trisomy 13 and 22 syndromes had an extra chromosome which was a derivative chromosome from maternal balanced translocation affecting Nos. 13 and 22; 47,XY,+der(22),t(13:22)(q22:q12)Mat. The presence of extra specific euchromatic regions of No. 13(13q22 and/or 13q34) and No. 22 (22q11) seem to be responsible for the trisomy 13 and 22 syndromes.