Concepts of drugs: differences in conceptual structure across groups with different levels of drug experience

Seventy-seven college students varying in degree of drug use experience rated the perceived similarities of all possible combinations of 16 drug classes (cigarettes, other tobacco, alcohol, marijuana, barbiturates, minor and major tranquilizers, amphetamines, amphetamine derivatives, cocaine, heroin, opiates, hallucinogens, inhalants, PCP, anti-depressants). Multi-dimensional scaling (INDSCAL) and network models (PFNET) indicated that abstainers had only one pharmacological category involving sedatives/depressants, and that they attached more importance to whether drugs were licit vs. illicit than to whether they were depressants vs. stimulants. Conceptions became more coherent, differentiated and based on pharmacological properties for more experienced drug users. In line with previous work, groups with greater experience with drugs had more sophisticated conceptions not only about the drugs they had used, but also about drugs they had not used. These findings suggest that early on in drug behavior sophisticated and interrelated concepts are developing that should be taken into account when designing interventions and information campaigns.     

A Case of Small Cell Carcinoma of the Lung Producing ADH, ACTH, MSH and Calcitonin: Successful Treatment of Severe Hyponatremia with Furosemide and Hypertonic Saline

A 48-year-old man with a small cell carcinoma of the lung presentedhyponatremia and was diagnosed as having the syndrome of inappropriateADH secretion. A plasma ADH bioassay confirmed this syndrome.During the clinical course, the patient developed a hyponatremiccrisis with a serum sodium of 108mEq/l. His hyponatremia wasrapidly corrected by infusing furosemide in conjunction withhypertonic saline. The postmortem studies demonstrated ADH bioactivityin the tumor tissues, as well as immunoreactive ACTH, ß-MSHand calcitonin. Tumor hypersecretion of ACTH appeared to bethe cause of the patient's hyperresponsiveness to exogenousACTH and of the bilateral adrenocortical hyperplasia observedat the time of autopsy. Therefore, this was a case of a multiple hormone-producing smallcell carcinoma of the lung, in which the severe clinical manifestationsof SIADH were successfully treated with furosemide and hypertonicsaline.     

Tamoxifen in Advanced Breast Cancer; Response Rate, Effect on Pituitary Hormone Reserve and Binding Affinity to Estrogen Receptor

Patients with advanced breast cancer were treated with antiestrogen,tamoxifen, 20 mg orally, twice a day. Of the evaluable 23 patients,one achieved complete response with a duration of 16 months,and five achieved partial response lasting from two to eightmonths, indicating that the response rate was 26%. In the fiveperi-and postmenopausal patients, basal and LH-RH stimulatedplasma LH levels decreased but stayed within the postmenopausalrange in three patients during the tamoxifen therapy. Basaland LH-RH stimulated FSH levels decreased also but stayed withinthe postmenopausal range in all five patients. In a premenopausalpatient, basal and stimulated plasma LH and FSH levels did notchange significantly during the tamoxifen therapy. The plasmaTSH responses did not change significantly. In three of thesix patients, basal and TRH-stimulated prolactin levels decreasedslightly during the tamoxifen therapy. These relatively inconsistentand small changes in the pituitary hormone secretion observedduring the tamoxifen therapy suggest that the anti-tumor effectof tamoxifen was not due to alteration of the pituitary hormonesecretion. The binding of tamoxifen for the estrogen receptorwas examined in the estrogen receptor assay system. The doseresponse curve for tamoxifen was parallel to that for estradiol,indicating that tamoxifen competes with estradiol for the estrogenreceptor. The affinity constants of tamoxifen for the estrogenreceptor in eight cytosols of human breast cancer tissues were(139 ±79) X 10^–10M (mean±SD), indicatingthat the binding affinity of tamoxifen was about 0.7% that ofestradiol. The affinity constants for nuclear receptors weresimilar to those for cytosol receptors. These data suggest thattamoxifen is a useful drug for treatment of advanced breastcancer, and that the anti-tumor effect could be related to itsbinding to estrogen receptors in tumor tissues, and not causedby altering the secretion of pituitary hormones.     

Hepatocyte apoptosis and hepatic expression of transforming growth factor-β1 mRNA during involution of hyperplastic rat liver induced by hepatocyte growth factor

Hepatocyte apoptosis occurs during involution of hyperplastic liver induced by administration of xenobiotic compounds in rats. With this hyperplasia and involution, hepatic transforming growth factor (TGF)-β₁ is reported to be expressed to stimulate hepatocyte apoptosis. In regenerating liver after partial resection showing no hyperplasia, such expression of TGF-β₁ is also seen. However, no hepatocyte apoptosis develops despite the high levels of TGF-β₁. When rats received an intravenous injection of human hepatocyte growth factor at 12 h intervals for 14 days, the hepatic DNA content was increased 12 h after the last injection to 140% of control. This DNA content was significantly decreased at 108 and 180 h after discontinuation of treatment. At 60 h after the last injection, the number of apoptotic bodies positive for nick end-labelling of DNA in hepatocytes was significantly greater in treated rats than in control rats. Hepatocyte apoptosis was also identified electron micrographically. Hepatic TGF-β₁ mRNA levels in treated rats were significantly lower than in control rats at 12 h and then gradually increased towards control levels. We conclude that hyperplastic liver induced in normal rats by hepatocyte growth factor regresses with hepatocyte apoptosis and suppressed hepatic TGF-β₁ mRNA levels.     

Effects of Hypophysectomy on Patients With Advanced Breast Cancer in Relation to Pituitary Hormone Reserve Before and After the Operation

In four patients with advanced breast cancer, the TSH, prolactin,LH and FSH reserve was measured, before and after hypophysectomy,by stimulation with TRH and LH-RH. Two out of the four patientswere objectively improved following the operation. It was foundthat the clinical effects of hypophysectomy did not correlatewith changes in secretion of any of these pituitary hormones.In addition, the complete absence of pituitary hormones afteroperation did not necessarily mean that treatment had been effective. ^*This study was supported by Grants for Cancer Research andfor Specific Diseases from the Ministry of Health and Welfareand by a Grant-in-Aid for Cancer Research from the Ministryof Education, Science and Culture, Japan     

Intracellular Transcobalamins in Various Cultured Cell Lines Established from Hematological Malignancies

Intracellular transcobalamins (TCs) in 17 cultured cells establishedfrom hematological malignancies were measured to solve the cellularorigin of TCs. The cultured cell lines used in this study areas follows: myeloid cell lines K-562, HL-60, NALM-1; T-celllines P12/lchikawa, MOLT-4B, CCRF-CEM, RPMI-8402, MT-1; B-celllines P3HR-1, Daudi, BALL-1; nonT, nonB cell lines NALM-16,KOPN-1, Reh, P30/Ohkubo, NALL-1; and, as control cells, P13/Koyamaderived from normal B-cells, normal human lymphocytes and granulocytes.The homogenized cytoplasmic fraction was incubated with ⁵⁷CoB₁₂ and subjected to DE₅₂ cellulose column chromatography andpolyacryla mide gel electrophoresis (PAGE) to separate TC₁₁from R-binders. In myeloid cell lines established from blasticcrises of chronic myeloid leukemia, K-562 had the highest TC₁₁/R-bindersratio, while NALM-1 had the lowest, suggesting that the myeloidand lymphoid crises of chronic myeloid leukemia may have differentTC₁₁/R-binders ratio. T and B cell lines showed no differencein intracellular TC levels. NonT, nonB cell lines had the lowestlevel of intracellular TC. ^*Present address: Department of Internal Medicine, JikeikaiUniversity Auto Hospital, Tokyo.     

A case of primary hyperparathyroidism that had been treated under a diagnosis of depression for 10 years

Abstract A 66 year old man who had been treated under a diagnosis of depression for 10 years was referred to the Kyoto Prefectural University of Medicine, Kyoto because of general fatigue and appetite loss. The patient was diagnosed as having primary hyperparathyroidism (PHPT) based on the increased parathyroid hormone (PTH) and serum calcium levels. Computed tomography revealed solitary adenoma of parathyroid gland. The resection of this solitary adenoma improved the PTH and serum calcium concentrations to normal ranges, which resulted in an improvement in his depressive state. This case suggests that ionic calcium levels contribute to the mental symptoms associated with PHPT. As PHPT is curable, the possibility of PHPT should be taken into account when patients have depressive symptoms.     

Epidemic enterocolitis possibly as a result of Norwalk virus infection presenting as ischemic colitis

Ischemic colitis usually presents as an isolated event, and clustering seldom occurs. Although a majority of instances of colonic ischemia have no clearly identifiable cause, many kinds of predisposing factors for the occurrence of ischemic colitis are pointed out. These include high age, generalized atherosclerosis, impaired cardiac function, hypovolemia, hypotension, colonoscopy, obstructing colonic cancer, coagulopathies and use of vasoconstrictors or contraceptives. However, infectious viral enterocolitis has not been regarded as a predisposing factor for colonic ischemia. We present here two cases of epidemic enterocolitis presenting as ischemic colitis that occurred almost simultaneously in two compromized long‐term patients in Noda Hospital, Chiba Prefecture. At the time, viral enterocolitis due to Norwalk virus infection was epidemic in Japan, including in the region of the hospital. It is likely that epidemic enterocolitis induced strong gut peristalsis and caused colonic spasm that mediated colonic ischemia. Indeed, both patients were elderly and had prominent signs of atherosclerosis, and one patient suffered from diabetes mellitus. Notably, the physician who performed the rectosigmoidoscopy in the two patients presented with enterocolitis 1 day after the procedure. This indicates that occupational transmission of epidemic enterocolitis can occur in medical staff during endoscopy procedures.