Contributi scientifici in memoria di Antonio Fusco.

Come si leggerà nell'Introduzione della sezione propriamente scientifica del Volume, il presente testo nasce dalla volontà e, soprattutto, dall'esigenza culturale di omaggiare il fu Prof. Antonio Fusco. Un debito scientifico ed umano che trova il suo locus naturale in questa prima parte del testo stesso, cui farà poi seguito la parte propriamente scientifica. In siffatta parentesi dovuta per le ragioni appena menzionate, il lettore, l'amico o l'allievo dell'opera del Prof. Fusco potranno trovare un suo sintetico Curriculum Vitae, correlato da una specifica ed accurata prosa, svolta dal già Magnifico Rettore Carlo Cipolli; il quale, oltre che evidenziare, ricordando, i meriti del collega oramai scomparso, aggiunge alsuo scritto un elemento che sarebbe imprescindibile a non trasformare lo stesso in una mera sequenza di parole: l'amicizia e l'affetto per un amico che, oramai, non c'è più. A fine lettura, evidente risuonerà il fatto che la vita di ognuno, se mossa dalla passione per ciò per cui si è predisposti cognitivamente e psicologicamente, può essere ricca di riconoscimenti, riconoscenze e soddisfazioni che, lungi dal divenire un cuscino di allori su cui adagiarsi, per una mente creativa come quella del Prof. Fusco hanno funto solo da motivazioni ad agire instancabilmente guardando sempre al futuro. Il lavoro di una vita che, materialmente, è sancito da un supporto poco più di cm 25x15: una targa. Una materialità evidente che, con grande commozione e riconoscenza, è stata affissa il 25 ottobre 2019 sull'aula fronte l'Aula Magna del Campus "La Folcara", a testimonianza che quello spirito creativo in continua evoluzione non si ferma; non si arresta neppure con la fine biologica di chi lo ha "posseduto". Rimangono le opere ed il pensiero del Prof. Fusco e restano gli affetti. A tal proposito, il lettore troverà una breve e sentita sezione su Testimonianze; coloro i quali hanno avuto modo, nell'arco della vita accademica ed umana, personale, di Fusco di conoscerlo. Ecco, allora, che i ricordi saranno i veri protagonisti di questa parentesi. Dopo di ciò, prima dei contributi prettamente scientifici dei lavori, tenutisi in occasione del Convegno Internazionale Psicologia, Arte, Letteratura. Antiche e Nuove Tendenze, seguiranno i saluti delle autorità che in quei due giorni si sono succedute a rappresentare non solo l'istituzione affiliata, ma anche la relazione di stima e di affetto che le legava al compianto Professore. Si passerà, infine, al volume tradizionalmente inteso.

Differential effects of earthquakes on patients with bipolar disorder versus schizophrenia: Findings from Crete, Greece, 2008-2010.

Electromagnetic radiation influences in many ways humans and animals, while earthquakes are known to be related with electromagnetic phenomena. We recently showed that large earthquakes reduced admissions of psychiatric patients, whereas small earthquakes were associated with increased number of admissions. Our aim was to examine the effect of seismic-related electromagnetic activity on two chronic and severe psychiatric disorders varying in terms of etiology and treatment, i.e. bipolar disorder and schizophrenia. Retrospective data concerning monthly admission rates of patients diagnosed with schizophrenia or bipolar disorder in the Psychiatric Unit of the University Hospital of Heraklion, Crete, Greece between 2008 and 2010 were analyzed in relation to the number of earthquakes with small (≥2) or larger magnitude in the Crete region in Greece. Results showed a marked reduction of acute admissions during a storm of large earthquakes, which was greater in patients with bipolar disorder (91.2%) than schizophrenia patients (52.4%). In addition there was a significant increase of admissions during a period of frequent small earthquakes, primarily among patients with bipolar disorder. The results suggest that electrostatic fields that accompany large earthquakes may have a protective effect on psychiatric disorders, particularly on bipolar disorder. These findings are consistent with the ameliorating effect of electromagnetic fields used in Electroconvulsive therapy (ECT) and Transcranial Magnetic Stimulation (TMS) in patients with bipolar disorder. Future studies focusing on the underlying mechanisms may lead to more specific treatments of psychiatric disorders.

The healthy donor effect impacts self-reported physical and mental health - results from the Danish Blood Donor Study (DBDS).

AIMS: This study aimed at quantifying the healthy donor effect by comparing self-perceived mental and physical health between blood donors and non-donors. BACKGROUND: In theory, the selection process known as the healthy donor effect should result in better self-perceived, health-related quality of life in donors than in non-donors. METHODS: The Short Form-12 data from the Danish Twin Registry (DTR) was compared with the data from the Danish Blood Donor Study (DBDS). Data on age, sex and smoking status were included in the analyses. The multivariable linear regression analysis was stratified by sex and age group intervals. Outcome variables were the mental component score (MCS) and the physical component score (PCS). RESULTS: A total of 28 982 and 36 913 participants from the DTR and the DBDS, respectively, were included in this study. Younger donors had higher MCS than non-donors, whereas MCS was only marginally high in older donors compared with non-donors. In contrast, PCS was almost similar for both young donors and non-donors. With the increase in age, non-donors had lower PCS than donors. CONCLUSIONS: Two selection patterns were revealed. Among young individuals, better self-perceived mental health was associated with a blood donor. With the increase in age, better self-perceived physical health was associated with blood donation.

Iron deficiency among blood donors: experience from the Danish Blood Donor Study and from the Copenhagen ferritin monitoring scheme.

Blood components collected from blood donors are an invaluable part of modern-day medicine. A healthy blood donor population is therefore of paramount importance. The results from the Danish Blood Donor Study (DBDS) indicate that gender, number of previous donations, time since last donation and menopausal status are the strongest predictors of iron deficiency. Only little information on the health effects of iron deficiency in blood donors exits. Possibly, after a standard full blood donation, a temporarily reduced physical performance for women is observed. However, iron deficiency among blood donors is not reflected in a reduced self-perceived mental and physical health. In general, the high proportion of iron-deficient donors can be alleviated either by extending the inter-donation intervals or by guided iron supplementation. The experience from Copenhagen, the Capital Region of Denmark, is that routine ferritin measurements and iron supplementation are feasible and effective ways of reducing the proportion of donors with low haemoglobin levels.

Low-grade inflammation is associated with lower haemoglobin levels in healthy individuals: results from the Danish blood donor study.

BACKGROUND AND OBJECTIVES: Chronic inflammation can lead to anaemia of chronic disease due to the sequestration of iron caused by inflammatory cytokines and the protein hepcidin. However, the effect of low-grade inflammation (LGI) on haemoglobin among healthy individuals is not known. This study examines the effect of LGI on haemoglobin among Danish blood donors. MATERIALS AND METHODS: We performed multivariable linear regression to assess the effect of LGI (i.e. high-sensitivity C-reactive protein above 3 mg/l but below 10 mg/l) on haemoglobin in 17 322 Danish blood donors. We also performed multivariable logistic regression to evaluate the effect of LGI on the risk of having low haemoglobin (below the 10th percentile among men and women, respectively). We adjusted for donation activity, age, sex, low ferritin, oral contraceptives and menopause. All analyses were stratified by current smoking status. RESULTS: LGI was associated with lower haemoglobin (0·08 mm lower [0·12 g/dl], 95% confidence interval (CI): -0·11-0·05) and increased risk of low haemoglobin (OR = 1·22, 95% CI: 1·05-1·43) in non-smokers. Conversely, LGI was associated with higher haemoglobin in smokers (0·12 mm [0·19 g/dl], 95% CI: 0·06-0·18). CONCLUSION: In this first study of LGI and haemoglobin in healthy individuals, there was a negative association between LGI and haemoglobin in non-smokers. The association was positive in smokers, probably because smoking leads to both increased inflammation and increased haemoglobin through CO exposure.

γ -H2AX: A Novel Prognostic Marker in a Prognosis Prediction Model of Patients with Early Operable Non-Small Cell Lung Cancer.

Cancer is a leading cause of death worldwide and the prognostic evaluation of cancer patients is of great importance in medical care. The use of artificial neural networks in prediction problems is well established in human medical literature. The aim of the current study was to assess the prognostic value of a series of clinical and molecular variables with the addition of γ -H2AX-a new DNA damage response marker-for the prediction of prognosis in patients with early operable non-small cell lung cancer by comparing the γ -H2AX-based artificial network prediction model with the corresponding LR one. Two prognostic models of 96 patients with 27 input variables were constructed by using the parameter-increasing method in order to compare the predictive accuracy of neural network and logistic regression models. The quality of the models was evaluated by an independent validation data set of 11 patients. Neural networks outperformed logistic regression in predicting the patient's outcome according to the experimental results. To assess the importance of the two factors p53 and γ -H2AX, models without these two variables were also constructed. JR and accuracy of these models were lower than those of the models using all input variables, suggesting that these biological markers are very important for optimal performance of the models. This study indicates that neural networks may represent a potentially more useful decision support tool than conventional statistical methods for predicting the outcome of patients with non-small cell lung cancer and that some molecular markers, such as γ -H2AX, enhance their predictive ability.

The presence of asthma, the use of inhaled steroids, and parental education level affect school performance in children.

OBJECTIVE: Childhood asthma is a frequent cause of absenteeism that affects school performance. We aimed to investigate the impact of asthma on absenteeism and school performance level of elementary and high school students. METHODS: Data about sociodemographics, absenteeism, and academic achievement were obtained from 1539 students attending 98 schools in Greece. School performance was assessed for the last two years of school attendance using parents' and teachers' reports and grade point average promotion. RESULTS: The mean of the days of absence of students with asthma was higher compared to the healthy students (6.2 ± 11.7 versus 0.3 ± 3.1, resp., P < 0.001). Students with reduced healthcare use presented less absenteeism than those with increased healthcare use for asthma (4.3 ± 8.6 versus 12.4 ± 17.0 days, resp., P < 0.001). Asthma and healthcare use for asthma accounted for an overall estimated variability in absence days of 13.8% and 9%, respectively. Absenteeism was associated with poor school performance for the last two years of school (P = 0.002) and with lower grade point promotion in elementary school students (P = 0.001) but not in high school students (P = 0.316). Higher level of parental education was associated with better school performance (P < 0.001). Asthma was associated with a decreased possibility for excellent performance (OR = 0.64, P = 0.049, 95%CI = 0.41-1.00) in elementary students. Students with asthma using inhalers were four times more likely to perform excellently in elementary school (OR = 4.3, P = 0.028, 95%CI = 1.17-15.95) than their asthmatic peers with alternative asthma treatments. Conclusions. Asthma and increased healthcare use enhance school absenteeism. Inhaled steroid use and the higher parental education level were the most important predicting factors for good school performance in elementary school asthmatic children.

An intelligent system approach for asthma prediction in symptomatic preschool children.

OBJECTIVES: In this study a new method for asthma outcome prediction, which is based on Principal Component Analysis and Least Square Support Vector Machine Classifier, is presented. Most of the asthma cases appear during the first years of life. Thus, the early identification of young children being at high risk of developing persistent symptoms of the disease throughout childhood is an important public health priority. METHODS: The proposed intelligent system consists of three stages. At the first stage, Principal Component Analysis is used for feature extraction and dimension reduction. At the second stage, the pattern classification is achieved by using Least Square Support Vector Machine Classifier. Finally, at the third stage the performance evaluation of the system is estimated by using classification accuracy and 10-fold cross-validation. RESULTS: The proposed prediction system can be used in asthma outcome prediction with 95.54 % success as shown in the experimental results. CONCLUSIONS: This study indicates that the proposed system is a potentially useful decision support tool for predicting asthma outcome and that some risk factors enhance its predictive ability.

A periodogram-based test for weak stationarity and consistency between sections in time series.

In one approach to spectral estimation, a sample record is broken into a number of disjoint sections, or data is collected over a number of discrete trials. Spectral parameters are formed by averaging periodograms across these discrete sections or trials. A key assumption in this approach is that of weak stationarity. This paper describes a simple test that checks if periodogram ordinates are consistent across sections as a means of assessing weak stationarity. The test is called the Periodogram Coefficient of Variation (PCOV) test, and is a frequency domain test based on a technique of spectral analysis. Application of the test is illustrated to both simulated and experimental data (EMG, physiological tremor, EEG). An additional role for the test as a useful tool in exploratory analysis of time series is highlighted.

A semi-parametric approach for comparing the estimated spectra of two stationary point processes.

In this paper, we provide a semi-parametric test for the hypothesis that the spectra of two stationary point processes (SPPs) are the same. The estimates of the second-order spectral density functions of the SPPs are obtained by using two different approaches: (a) by smoothing the modified periodogram statistics using a moving average weighting scheme, (b) by employing the Welch's method on the modified periodogram statistics. The test is based on the likelihood ratio function under two alternative hypotheses. The first alternative hypothesis suggests that the ratio of the spectra is a constant (there is a shift to the power) while the second one adopts a quadratic model for the logarithmic ratio of the spectra. A comparison with a log-linear model indicates coincidence in the results. This is explained by using an illustrative example from the field of neurophysiology. It is shown that the information transferred to the spinal cord by the sensory axons, closely related with the complex physiological system called muscle spindle, under the influence of two different stimuli can be separated in two parts. The first part corresponds to the range of frequencies 0-19 Hz while the second to the range of frequencies 19-100 Hz. However, the dependence on the frequency in both parts is of a quadratic form.

Therapeutic potential of CDK inhibitor NU2058 in androgen-independent prostate cancer.

Antiandrogens are initially effective in controlling prostate cancer (CaP), the second most common cancer in men, but resistance, associated with the loss of androgen-regulated cell cycle control, is a major problem. At present there is no effective treatment for androgen-independent prostate cancer (AIPC). Cellular proliferation is driven by cyclin-dependent kinases (CDKs) with kinase inhibitors (for example, p27) applying the breaks. We present the first investigation of the therapeutic potential of CDK inhibitors, using the guanine-based CDK inhibitor NU2058 (CDK2 IC(50)=17 microM, CDK1 IC(50)=26 microM), in comparison with the antiandrogen bicalutamide (Casodex) in AIPC cells. A panel of AIPC cells was found to be resistant to Casodex-induced growth inhibition, but with the exception of PC3 (GI(50)=38 microM) and CWR22Rv1 (GI(50)=46 microM) showed similar sensitivity to NU2058 (GI(50)=10-17 microM) compared to androgen-sensitive LNCaP cells (GI(50)=15 microM). In LNCaP cells and their Casodex-resistant derivative, LNCaP-cdxR, growth inhibition by NU2058 was accompanied by a concentration-dependent increase in p27 levels, reduced CDK2 activity and pRb phosphorylation, a decrease in early gene expression and G1 cell cycle phase arrest in both cell lines. In response to Casodex, there were similar observations in LNCaP cells (GI(50)=6+/-3 microM Casodex) but not in LNCaP-cdxR cells (GI(50)=24+/-5 microM Casodex).

Shockwave therapy as first-line treatment for Peyronie's disease: a prospective study.

BACKGROUND AND PURPOSE: To assess in a prospective study whether shockwave therapy (SWT) is effective as a first-line treatment for Peyronie's disease. PATIENTS AND METHODS: Forty patients with previously untreated Peyronie's disease underwent SWT with the Epos overhead-module device (Dornier). The pain severity (visual analog pain scale [VAS] 0-5), the degree of penile angulation after vasoactive drug injection, plaque size by ultrasound measurement, and erectile dysfunction (IIEF score) were assessed prior to and after treatment. Of the 40 patients, 7 underwent two sessions and the rest three sessions. The time interval between treatments was 2 weeks. At a power level of 2 to 5 (mean 4), a maximum of 3000 shockwaves per plaque per treatment were applied. The mean follow-up was 12 months. RESULTS: All patients completed the protocol. The tolerance and safety were excellent. Of the 25 patients with pain on erection, 12 (48%) noticed relief after the first session, while 9 more were pain free at the end of the treatment (VAS reduction 2.8; P<0.0001, and 2; P<0.001, respectively). For 25 patients (62.5%), an improvement in penile angulation>20 degrees was observed, with a mean reduction of 35 degrees (range 20 degrees-60 degrees ) (P<0.001). No significant change in plaque size was noted. Among 28 patients with erectile dysfunction, 18 (64.2%) had a marked increase in erection quality (IIEF score change: +4 for 10 patients, +6 for 4 patients, +8 for 2 patients, +9 for 2 patients). CONCLUSION: Our results support SWT as an effective and safe first-line treatment for Peyronie's disease.

Pelvi-ureteric junction obstruction by crossing renal vessels: clinical and imaging features.

OBJECTIVE: To present the characteristic clinical and imaging findings of pelvi-ureteric junction (PUJ) obstruction caused by crossing renal vessels (CRV), as it presents particular features within the spectrum of congenital hydronephrosis. PATIENTS AND METHODS: Between April 1982 and December 2000, 384 children underwent surgery for PUJ obstruction. In 71 (18.5%; mean age 8.5 years, range 2 months to 14 years; 49 aged> 5 years), the obstruction was caused by CRV. The data collected from the medical records of these patients were analysed for their clinical presentation and imaging findings, i.e. ultrasonography (US), intravenous urography (IVU) and diuretic renography. RESULTS: The main presenting symptom was recurrent renal colic (pain, nausea, vomiting) in 59%, followed by urinary infection (UTI) in 20%, gross haematuria in 11% and an incidental diagnosis in 10%. By contrast, in the 313 children with intrinsic PUJ obstruction, renal colic was present in only 10.5%. Moreover, from 1991 to 2000, when the use of prenatal US became widespread, hydronephrosis was detected prenatally in 42 of 212 children (20%) with intrinsic PUJ obstruction, but in only two of 31 (6%) with obstruction by CRV. However, in 10 children with CRV operated on during this period, prenatal US had shown mild hydronephrosis (< 15 mm), which during the follow-up decreased until the children became symptomatic after 5-9 years (eight renal colic, two UTI). US during acute symptoms showed significant hydronephrosis (> 25 mm), and colour Doppler US of two patients directly showed the CRV. In all 71 children with CRV obstruction diuretic IVU and renography during the acute symptoms had an obstructive pattern, and in 24 renal colic was reproduced during the examination. The differential kidney function was < 40% in 11 children who presented with UTI; two required nephrectomy and in the remaining 69 an Anderson-Hynes pyeloplasty, after which none had an episode of renal colic or UTI during a mean (range) follow-up of 10.2 (2-20) years. CONCLUSIONS: PUJ obstruction by CRV should be suspected in older children presenting with recurrent renal colic and hydronephrosis. Good kidney function is expected in most of these children, despite their age, because the vascular obstruction is intermittent. Mild prenatal hydronephrosis that could decrease postnatally does not exclude the possibility of vascular obstruction, which may later become symptomatic. Imaging (US, diuretic IVU and renography) during an episode of pain is essential and colour Doppler US could help to establish the diagnosis in these cases. Knowing that a child has a CRV is important for choosing an open surgical approach rather than endoscopic pyelotomy, to avoid potential complications

Rhenium-186-HEDP palliative treatment in disseminated bone metastases due to prostate cancer.

Prostate carcinoma is the most commonly associated with osseous metastases malignancy in males. The lesions, being usually of a mixed sclerotic/lytic variety and less often of the pure sclerotic type, need to be treated by a bone seeking radioactive element with an as low as possible radiobiological burden on the surrounding (peritumoral) tissues. Rhenium-186-HEDP was used to treat these osseous metastatic lesions due to its bone seeking kinetics attractive radiochemical properties. Of a total of 16 prostate cancer patients. 3 experiment loss of pain, 8 experienced obvious and 2 some improvement. No change was observed in 3 patients. Ten patients manifested a flare syndrome increasing pain approximately 2 to 6 days, after Re-186-HEDP i.v. application. Six patients showed a definite and 9 a slight decrease in platelet levels and absolute number of polymorphonuclear white blood cells, up to fourth week following treatment. One patient underwent a whole blood transfusion and in 2 peripheral neuropathy was observed lasting about 9 to 12 days. Re-186-HEDP appears to be a promising new metal ion complex for the palliation of painful bone metastases in prostate cancer. Compared to Sr-89 therapy, it shows a longer analgetic efficacy and has the advantage of emitting gamma rays, a fact which facilitates dosimetric calculations.

Estimation of certain parameters of a stationary hybrid process involving a time series and a point process.

A method is presented for estimating the cross-spectral density of a hybrid process involving a time series and a point process. The method is based on the generalized cross-periodogram statistic, which is smoothed by splitting the whole record of the data into a number of disjoint subrecords. Estimates of the coherence function and the cross-covariance function can also be obtained by using the estimate of the cross-spectral density. The distribution of the cross-covariance function between a time series and a point process is shown to be asymptotically normal. The theoretical results are used in the study of a complex physiological system. It is shown that the presence of a gamma motor neuron (gamma stimulation) modifies the effect of the length changes on the complex system at low frequencies (the length changes, and the response of the system become uncorrelated in the range 3-30 Hz) while the effect remains unchanged at higher frequencies. As a comparison it is shown that the presence of the length changes weakens the effect of the gamma stimulation on the complex system.

The relationship between insurance class and severity of presentation of inflammatory bowel disease in children.

OBJECTIVE: To determine whether there is an association between insurance class and the severity of presentation of inflammatory bowel disease in children. METHODS: Twenty underinsured (either no insurance or Medicaid) children were computer-matched with 20 children with private insurance with regard to diagnosis and age but without regard to severity of disease from a pool of 63 patients (20 underinsured patients and 43 insured patients). We compared four patient-reported parameters and eight laboratory values. RESULTS: There were 22 patients with Crohn's disease (11 underinsured and 11 insured) and 18 patients with ulcerative colitis (nine underinsured and nine insured), with a mean age at diagnosis of 13.7 +/- 4.2 yr in the underinsured and 13.4 +/- 3.8 yr in the privately insured patients. Patients in the underinsured category had more than 2.5 times the weight loss of the privately insured patients (20.0 +/- 13.9 vs. 7.8 +/- 8.6, p < 0.005) and longer delay in months (10.3 +/- 10.9 vs. 2.7 +/- 2.6, p < 0.005) before the diagnosis was made. Laboratory data in the underinsured children indicated that they were more ill at time of presentation than the insured patients. The underinsured patients had significantly lower hemoglobins (10.5 +/- 2.4 vs. 12.5 +/- 2.1, p < 0.01), a higher erythrocyte sedimentation rate (59 +/- 35 vs. 21 +/- 24, p < 0.005), and higher platelet counts (536 +/- 205 x 10(3) vs. 418 +/- 140 x 10(3), p < 0.05) compared to the insured group. Alkaline phosphatase levels, normally elevated in children during osseous growth, were significantly depressed in the underinsured group when compared with the insured group (117 +/- 42 vs. 155 +/- 71, p = 0.05). CONCLUSION: Underinsured children have clinical and laboratory parameters that indicate that their disease is more severe at presentation than privately insured patients. We postulate that this is partly related to the fact that underinsured patients have inferior access to quality healthcare when compared to privately insured patients.

Breast-feeding and maternal smoking in the etiology of Crohn's disease and ulcerative colitis in childhood.

Medical records concerning pediatric or adolescent patients first diagnosed with Crohn's disease or ulcerative colitis in two New York hospitals during a 5-year period (1986 to 1990) were abstracted, and information concerning sex, age, race, birthplace, sibship size, birth order, maternal age at birth, month of birth, duration of breast-feeding, and maternal smoking was recorded. Medical records of patients presenting at the respective pediatric gastroenterology departments immediately before or after the patients with inflammatory bowel disease were seen were also abstracted in order to generate a control series. Data concerning 68 patients with Crohn's disease, 39 patients with ulcerative colitis, and 202 control patients were analyzed through multiple logistic regression. Breast-feeding was negatively associated with Crohn's disease (P approximately 0.04) and ulcerative colitis (P approximately 0.07), with relative risk point estimates around 0.5 and with evidence of duration-dependent trends in both instances. There was no evidence of association of either disease with maternal age at birth, birth order, maternal smoking, or season of birth.

Spectra-based estimates of certain time-domain parameters of a bivariate stationary-point process.

We consider estimates of certain time-domain parameters of a bivariate stationary-point process based on modified periodogram statistics. These estimates are shown to be asymptotically normal under regularity conditions. In the computations of the estimates, the advantage of using the FFT algorithm is demonstrated. Three examples, obtained by analyzing two data sets from the field of neurophysiology, are illustrated.

Arachidonic acid metabolism by rat liver cells (the C-9 cell line).

Rat liver cells (the C-9 cell line) are capable of producing, from endogenously liberated arachidonic acid, prostaglandins I2, E2 and F2 alpha. Greater than 95% of these cyclooxygenase products is prostaglandin I2. Arachidonic acid metabolism is stimulated by treatment of the C-9 cells with epidermal growth factor, vasopressin, angiotensin II or thrombin. Stimulation by combined treatments with vasopressin, angiotensin II or thrombin is additive; but each stimulation, when incubated in the presence of epidermal growth factor, is synergistic. These stimulations are dependent on Ca++. They are inhibited by indomethacin and dexamethasone. The cells exhibit homologous, but not heterologous, desensitization to vasopressin and thrombin. The synergistic stimulation by epidermal growth factor and vasopressin is inhibited by prior treatment of the cells with epidermal growth factor.