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.     

Impaired memory and executive function associated with decreased medial temporal and prefrontal blood flow in Clinical Dementia Rating 0.5 status: the Osaki‐Tajiri project

Aim: The Clinical Dementia Rating (CDR) is an assessment of dementia severity based on observations of activities of daily living, and a CDR of 0.5 (CDR 0.5) represents questionable dementia. A combination of the Cognitive Abilities Screening Instrument (CASI) and the Trail Making Test (TMT) scores discriminated CDR 0.5 subjects from healthy participants with a high degree of accuracy. We investigated the neurological background of CDR 0.5 subjects by correlating CASI and TMT scores with regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT). Methods: From a community‐based cohort, 22 CDR 0.5 participants were recruited. CASI and TMT scores, rCBF measure using [¹²³I]‐N‐isopropyl‐p‐iodoamphetamine and SPECT were obtained. We evaluated the relationships between the CASI domain scores, between TMT scores and rCBF in a regions‐of‐interest‐based analysis, and voxel‐based analysis using Statistical Parametric Mapping 5 software. Results: We found that lower rCBF in the left medial temporal cortex correlated with a decreased CASI domain recent memory score both in the regions‐of‐interest and statistical parametric mapping analysis. In both the regions‐of‐interest and statistical parametric mapping analysis, the rCBF in the left prefrontal cortex correlated with CASI domain remote memory and mental manipulation and concentration. Conclusions: Our results indicate that some CDR 0.5 subjects have functional impairments in the medial temporal lobe as well as in the prefrontal cortex, as reflected in the cognitive decline measured by CASI and TMT.     

Yamaguchi fox–pigeon imitation test (YFPIT) for dementia in clinical practice

Background: In out‐patient clinics, having simple procedures to check for signs of dementia is invaluable. In the present study, we evaluated the imitation of hand gestures to detect visuomotor deficits in dementia in clinical practice. Methods: In all, 1219 subjects were enrolled in the present study, including 497 with Alzheimer's disease (AD), 98 with dementia with Lewy bodies (DLB), 71 with other types of dementia diseases, 175 with a Clinical Dementia Rating (CDR) of 0.5, and 378 normal controls. All subjects were aged 65 years or older. Subjects were recruited from 10 clinics and two communities. Visuomotor function was evaluated by the Yamaguchi fox–pigeon imitation test (YFPIT), which consists of a simple one‐handed sign for ‘fox’ and a complex two‐handed sign for ‘pigeon’, a rapid, game‐like test with low psychological burden. Results: The success rate (successful/total) for imitating the ‘pigeon’ hand gesture was reduced as the severity of the dementia increased: 85.7% in normal controls, 60.6% in CDR 0.5 (mild cognitive impairment), 39.2% in CDR 1 (mild dementia), 21.2% in CDR 2 (moderate dementia), and 5.7% in CDR 3 (severe dementia). The success rate for imitating the ‘pigeon’ hand gesture was higher in patients with DLB than AD within the CDR 1 group (51.2% vs 35.4%, respectively), but lower for patients with DLB than AD within the CDR 2 group (12.5% vs 24.4%, respectively). The success of imitating the hand gesture for ‘fox’ was similar for patients with AD and DLB. Of those subjects who failed to imitate the hand gesture for ‘pigeon’, 49.5% of those with AD showed the palm–palm pattern (both palms facing outward), suggesting deficits of perspective conversion from the first‐person to the third‐person. Conversely, 52.8% of patients with DLB showed a dorsum–dorsum pattern (both dorsa facing outwards), suggesting deterioration of visual attention and recognition. Conclusion: In conclusion, the YFPIT is a useful test to detect visuomotor deficits in dementia that can differentiate between AD and DLB.