Micro-determination of cyclic AMP levels in human epidermis, dermis and hair follicles

In order to study the biological and possible pathological roles of cyclic adenosine 3',5'-monophosphate (cyclic AMP) in the skin, it is mandatory to measure cyclic AMP in 50-100 mug of microdissected epidermis, dermis or appendages. In the present study, we offer a method of extracting cyclic AMP from less than 100 mug of tissue, removing contaminating nucleotides and scaling down Gilman's method to fit the analysis of small amounts of tissue. Cyclic AMP levels in the dermis, epidermis, and hair follicles (bulbs) were approximately 1, 2 and 3-5 pmols/mug dry weight tissue respectively. This procedure is applicable to the measurement of cyclic AMP levels in limited foci of healthy or diseased skin.     

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.     

Decreased serum carnitine is independently correlated with increased tissue accumulation levels of advanced glycation end products in haemodialysis patients

Aim: There is accumulating evidence that advanced glycation end products (AGE) play a role in cardiovascular disease (CVD) in patients with haemodialysis (HD). Carnitine deficiency is frequently observed in HD patients, which may also contribute to CVD. In this study, we examined whether carnitine deficiency was independently associated with increased tissue accumulation levels of AGE in HD patients. Methods: One hundred and twenty‐nine HD patients underwent determinations of blood chemistries including serum level of carnitine. Tissue AGE levels were evaluated by measuring skin autofluorescence with an AGE‐reader. Results: Serum carnitine levels were significantly lower, while skin AGE levels were significantly higher in HD patients compared with healthy controls (P < 0.001). In univariate analysis, β₂‐microglobulin (β₂‐MG) and carnitine (inversely) were correlated with skin AGE levels. Multiple stepwise regression analysis revealed that carnitine levels were one of the independent determinants of skin AGE levels (P = 0.024). When β₂‐MG‐adjusted skin AGE levels were stratified by serum carnitine levels, a statistical significance and dose‐response relationship were observed (P = 0.043). Furthermore, skin AGE levels were one of the independent determinants of serum carnitine levels as well (P = 0.012). Conclusion: The present study demonstrated that decreased carnitine levels were independently associated with increased skin AGE levels in HD patients. Since carnitine is reported to inhibit the formation of AGE in vitro, our study suggests that supplementation of carnitine may be a therapeutic target for preventing the accumulation of tissue AGE and subsequently reducing the risk of CVD in HD patients.     

Prediction of transfusions in extremely low-birthweight infants in the erythropoietin era

BACKGROUND: The purpose of the present paper was to detect the clinical factors most predictive of red blood cell (RBC) transfusion in extremely low-birthweight (ELBW) infants in the recombinant human erythropoietin era. METHODS: Between 1995 and 2000, 66 ELBW infants were admitted to a level III neonatal intensive care unit. Fifty-four of 66 infants were eligible for enrollment in the present study. Infants were treated with erythropoietin 200 IU/kg per dose s.c. twice a week with 4-6 mg/kg per day iron supplement. RESULTS: The mean gestational age and birthweight were 26.5 +/- 2.1 weeks and 776 +/- 134 g, respectively. Ten of 54 ELBW infants (18.5%) died during the first 21 days. Eight of 10 dead infants (80.0%) and 27 of 44 surviving infants (61.4%) received one or more RBC transfusions. The overall requirement for RBC transfusions in the surviving infants was 3.0 +/- 3.2 per infant/hospital course (range: 0-9) . There were significant differences in gestational weeks, birthweight, initial hemoglobin value, 5 min Apgar score, phlebotomy loss, phlebotomy loss/birthweight, duration of mechanical ventilation, duration of oxygen supplement, and incidence of both intraventricular hemorrhage and chronic lung disease between the transfused and non-transfused group. The predictive variables, initial hemoglobin level (odds ratio [OR] 2.61; 1 g/dL), birthweight (OR 3.00; 100 g), and gestational week (OR 1.89; 1 week), were found to be most predictive for transfusion on logistic regression analysis. CONCLUSION: ELBW infants are still the population at greatest risk for repeated blood transfusions after introduction of erythropoietin treatment. If labor develops, it is often impossible to extend the pregnancy period, therefore efforts should be made to increase hemoglobin level at birth.     

Idiopathic Left Ventricular Tachycardia with Block Between Purkinje Potential and Ventricular Myocardium

We performed radiofrequency current catheter ablation in a patient with idiopathic LV. While mapping the inferoapical LV septum during tachycardia, spontaneous termination of tachycardia was observed with block between Purkinje (P) potential and ventricular electrogram (P-V block). The cycle length of the tachycardia was associated with prolongation of P-P interval and P-V interval. P potential recording at this site was earliest and at very low amplitude during tachycardia. The radiofrequency current at this site was successful. These findings indicated that Purkinje fiber was a critical part of the tachycardia circuit. Ablation was successful at a site where both an earliest and low amplitude P potential was recorded during tachycardia, and where P-V block that was induced by catheter manipulation was observed during tachycardia.     

A Case of Widely Split Double P Waves with Marked Intra-Atrial Conduction Delay

Widely Split Double P Wave. We report a 78-year-old man as the first documented case of double P waves separated by 400 msec on 12-lead ECG. These P waves had different polarities on lead V₁. The first P wave represented activation of the lateral wall of the right atrium, and the latter P wave represented activation of the nudial right atrium and the left atrium. Widely spaced double potentials were recorded craniocaudally along the line, presumably corresponding to the crista terminalis during sinus rhythm. For this to occur, conduction disturbance has to be present both in the upper and lower right atrium. Conduction disturbance in the upper right atrium would interrupt excitation from the sinus node to the medial wall, and conduction disturbance in the lower right atrium would interrupt excitation spreading from the lower lateral right atrium to the isthmus area where fragmented potentials were recorded. These multiple discrete lesions appear to constitute a unique electrical atriopathy in this patient.     

Developmental brain-stem pathology in sudden infant death syndrome

The brain-stems of control and sudden infant death syndrome (SIDS) infants were examined developmentally with Golgi and immunohistochemical methods. The development of dendritic spines changed dramatically from the prenatal to postnatal period in the ventrolateral medulla as well as in the reticular formation and vagal nuclei in controls, but persisted in SIDS infants. These observations suggest a delay in maturation of the meduallary respiratory neurons and transneuronal connection between the central chemoreceptor and neural respiratory center in SIDS. In addition, substance P (SP)-positive nerve fibers were increased in the pons of SIDS infants. An increased activity in the afferent SP neurons in SIDS may be due to chronic hypoxia as in brain-stem gliosis, and may be involved in cardiorespiratory regulation.