Rapidly growing tumor-like brain lesion.

Listeria monocytogenes accounts for 8-11% of the cases of bacterial meningitis which is associated with high mortality in patients with serious underlying diseases or those receiving immunosuppressive treatment. Brain abscess due to L. monocytogenes is a very rare occurrence. The case reported here concerns a 54-year-old female patient with a rapidly growing tumor-like brain lesion. L. monocytogenes type 4b could be cultured from blood and brain biopsy. Despite antimicrobial therapy with ampicillin and gentamicin, the patient died 11 days after admission to the hospital. The growing numbers of elderly and immunocompromised patients will increasingly confront physicians with patients with listeriosis. Delayed therapy in patients treated with corticosteroids may result in a fatal outcome.

Sex differences in HAART-associated dyslipidaemia.

OBJECTIVES: Because female sex protects against dyslipidaemia and atherosclerosis in normal subjects, we aimed to reveal potential sex differences in metabolic side-effects of a newly initiated highly active antiretroviral therapy (HAART) regimen, and to relate these changes to endothelial cell activation as measured by levels of circulating E-selectin (cE-selectin). DESIGN: Prospective longitudinal cohort study. SETTING: Tertiary care centre at a University Hospital. METHODS: HIV-seropositive male (n = 27) and female patients (n = 13) with a plasma viral load of > or = 10 000 copies/ml and 35 healthy controls were enrolled in the study. All participants were weight stable, free of acute opportunistic infections, and had not taken any protease inhibitors before. Serum levels of lipids, insulin, leptin, and cE-selectin were measured before initiation of HAART, and at 3 and 6 months thereafter. RESULTS: HAART increased serum levels of triglycerides, leptin, and low-density lipoprotein (LDL) cholesterol; these effects were more distinct in women. Fasting insulin levels and the LDL : high density lipoprotein (HDL) ratio increased only in female HIV-infected patients (P < 0.02 versus men). In contrast, endothelial activation, as measured by cE-selectin, decreased more in men (P < 0.02) than in women. As a consequence, women had higher triglycerides and leptin levels after therapy than did men, and the LDL : HDL ratio and cE-selectin levels, which were initially higher in men, were no longer different between the sexes. CONCLUSIONS: Metabolic adverse effects during HAART are more pronounced in women than in men. Hence, female HIV-infected patients seem to loose part of their natural protection from atherosclerosis during antiretroviral therapy.

Beneficial effects of protease inhibitors on body composition and energy expenditure: a comparison between HIV-infected and AIDS patients.

OBJECTIVES: (i) To investigate whether protease inhibitor (PI) (nelfinavir)-containing highly active antiretroviral therapy (HAART) affects body composition differently in HIV-infected and AIDS patients without wasting syndrome. (ii) To delineate the changes in resting energy expenditure (REE) under PI therapy, and to determine whether sustained reductions in HIV RNA would decrease REE. DESIGN: Prospective longitudinal cohort study with individually matched healthy controls. SETTING: Tertiary care centre at a University Hospital. METHODS: HIV-seropositive (n = 20) and AIDS patients (n = 17) with a plasma viral load of at least 10000 copies/ml and 37 healthy volunteers were enrolled. All participants were weight stable, free of acute opportunistic infections, and naive to PI therapy. Patients underwent testing of bioelectrical impedance analysis (BIA), indirect calorimetry and food intake, shortly before the initiation of HAART and 24 weeks thereafter. RESULTS: Both patient groups gained weight, body mass index (BMI), and fat-free mass (FFM) (P < 0.05 versus baseline), whereas only AIDS patients gained fat mass. Increases were more pronounced in the AIDS group. REE was elevated compared with corresponding controls at baseline, and decreased similarly in HIV and in AIDS patients during PI therapy (P < 0.05). The reduction in the viral burden preceded the decrease in REE by several weeks. CONCLUSION: Body composition and metabolic parameters improved during PI therapy in HIV-infected and AIDS patients without wasting. Although an early reduction in viral load as a result of HAART does not seem to influence REE directly, sustained viral load suppression may promote a decrease in energy expenditure.

Survival of cryopreservation and thawing with all blastomeres intact identifies multicell embryos with superior frozen embryo transfer outcome.

OBJECTIVE: To assess the impact of survival of cryopreservation and thawing with all blastomeres intact on the outcome of multicell frozen ET. DESIGN: Retrospective study. SETTING: Academic assisted reproductive technology program. PATIENT(S): One hundred sixteen exclusively multicell frozen ETs in 78 patients. INTERVENTION(S): Frozen ET. MAIN OUTCOME MEASURE(S): Relation of embryonic blastomere survival to the outcome of frozen ET (i.e., pregnancy). RESULT(S): When at least one embryo survived with all blastomeres intact, the total pregnancy rate (biochemical, clinical, or delivered) was 37.7%, the clinical pregnancy rate was 24.6%, and the delivered pregnancy rate was 18.8%. When no embryo survived with all blastomeres intact, the corresponding rates were 10.6%, 8.5%, and 6.4%. The differences in the total pregnancy rate and the clinical pregnancy rate were statistically significant. The delivered pregnancy rates approached statistical significance. CONCLUSION(S): Multicell embryonic survival of cryopreservation and thawing with all blastomeres intact identifies embryos with superior developmental potential.

Immunoapheresis in paraneoplastic pemphigus.

BACKGROUND: Paraneoplastic pemphigus was first described in 1990 in 5 patients with extensive mucocutaneous erosions, a distinct set of autoantibodies, and underlying neoplasia. Since then, patients described have been middle-aged, have suffered from prognostically unfavorable malignant neoplasms, and have responded poorly to immunosuppressive agents. OBSERVATION: A 16-year-old boy was examined with extensive oral erosions, halitosis that interfered with his quality of life, and rapid weight loss. The suspected clinical diagnosis of paraneoplastic pemphigus was confirmed by histopathological, immunofluorescence, and biochemical (eg, immunoblotting and immunoprecipitation) findings as well as by the demonstration of an inflammatory myofibroblastic tumor of the left retroclavicular region. Despite administration of corticosteroids, followed by excision of the neoplasm, clinical symptoms improved only slightly, and autoantibody titers decreased only marginally. We therefore initiated an immunoapheresis regimen with the use of sheep anti-human-IgG bead-formed agarose gel (Sepharose; Pharmacia Biotech Comp, Vienna, Austria), which led to the disappearance of circulating autoantibodies and the patient's recovery. CONCLUSION: Immunoapheresis may represent a novel therapeutic option for patients with paraneoplastic pemphigus who show little improvement after curative treatment of their neoplasms.

Synergistic growth inhibitory and differentiating effects of trimidox and tiazofurin in human promyelocytic leukemia HL-60 cells.

Increased ribonucleotide reductase (RR) activity has been linked with malignant transformation and tumor cell growth. Therefore, this enzyme is considered to be an excellent target for cancer chemotherapy. We have examined the effects of a newly patented RR inhibitor, trimidox (3,4,5-trihydroxybenzohydroxamidoxime). Trimidox inhibited the growth of human promyelocytic leukemia HL-60 cells with an IC50 of 35 mumol/L. Incubation of HL-60 cells with 50 mumol/L trimidox for 24 hours decreased deoxyguanosine triphosphate (dGTP) and deoxycytidine triphosphate (dCTP) pools to 24% and 39% of control values, respectively. Incubation of HL-60 cells with 20 to 80 mumol/L trimidox even up to a period of 4 days did not alter the distribution of cells in different phases of cell cycle. Sequential incubation of HL-60 cells with trimidox (25 mumol/L) for 24 hours and then with 10 mumol/L tiazofurin (an inhibitor of inosine monophosphate dehydrogenase) for 4 days produced synergistic growth inhibitory activity, and the cell number decreased to 16% of untreated controls. When differentiation-linked cell surface marker expressions were determined in cells treated with trimidox and tiazofurin, a significantly increased fluorescence intensity was observed for the CD 11b (2.9-fold). CD 33 (1.9-fold), and HLA-D cell surface antigens. Expression of the transferrin receptor (CD71) increased 7.3-fold in cells treated with both agents, compared with untreated controls. Our results suggest that trimidox in combination with tiazofurin might be useful in the treatment of leukemia.

NPPB inhibits the basolateral membrane K+ conductance in the isolated bullfrog cornea.

The effects of the Cl- channel blocker, 4-nitro-2-(3-phenylpropylamino)benzoate (NPPB) on active transepithelial Cl- transport were measured in the isolated bullfrog cornea. With a Cl(-)-free Ringers, stromal-side 10(-5) M NPPB elicited a maximum depolarization of the membrane voltage from -72 +/- 6 to -48 +/- 9 mV (n = 6, P less than 0.05) and reduced the magnitude of the depolarization induced by a 10-fold increase in K+ concentration. Subsequent exposure to 10(-4) M ouabain decreased the membrane voltage from -41 +/- 6 mV to -25 +/- 2 mV (n = 6, P less than 0.05). After stimulation with 10(-5) M amphotericin B of a short-circuit current, Isc, largely accounted for by tear to stroma K+ diffusion, this Isc was effectively inhibited by 10(-5) M NPPB on the stromal-side. This decrease reflected a fall in basolateral membrane K+ conductance. In NaCl Ringers, inhibition of the essentially Cl(-)-originated Isc either on the tear- or stromal-sides required instead 10(-4) M NPPB. NPPB depolarized the membrane voltage from -55 +/- 7 to -38 +/- 6 mV (n = 14, P less than 0.05). The direction of the change in the fractional apical membrane resistance (fRo) depended upon its initial value; in those corneas with a lower value it increased whereas if they had a higher fRo, 10(-4) M NPPB consistently caused fRo to fall. However, following exposure to 5 x 10(-3) M Ba2+ and a fall in fRo, NPPB consistently caused fRo to increase significantly from 30 +/- 8 to 53 +/- 4% (n = 5). Therefore, inhibition of active Cl- transport by 10(-4) M NPPB may be associated with declines in: (1) a basolateral membrane K+ conductance that is distinct from a Ba2(+)-sensitive pathway; (2) an apical membrane Cl- conductance. Neither of these effects may be the result of a direct effect of NPPB on a conductance pathway because: (1) the drug was equipotent from either bathing solution; (2) following a one hour washout the Isc had not fully recovered to its control value.

Secretagogues increase apical membrane conductance of isolated bullfrog corneal epithelium pretreated with loop diuretics.

Bullfrog (Rana catesbeiana) corneas were mounted in an Ussing type chamber and impaled with an intracellular microelectrode and the short circuit current was inhibited by pretreatment with the loop diuretics furosemide (0.3 to 1 mM) or bumetanide (10 to 100 microM). Subsequent addition of the secretagogues prostaglandin E2, forskolin, or 3-isobutyl-1-methylxanthine (IBMX) caused the fractional voltage drop of the apical barrier to decrease from 0.72 +/- 0.05 to 0.48 +/- 0.04 and the chloride-dependent conductance to increase by 0.15 +/- 0.03 mS/cm2, but caused only a small, transient increase in short circuit current. The loop diuretics by themselves always greatly reduced the short circuit current but did not consistently reduce conductance or fractional voltage drop of the apical membrane. Because the secretagogues were able to increase the apical membrane conductance of diuretic-inhibited corneas without large effects on the short circuit current, the loop diuretics must have a major effect at a site other than the apical membrane Cl- conductance, presumably at the basolateral membrane. An additional effect of the loop diuretics at the apical membrane is also possible.

[The effect of chemotherapy on survival time in advanced breast carcinoma]. / Wirkung der Chemotherapie auf die Uberlebenszeit bei fortgeschrittenem Mammakarzinom.

Survival time of 119 consecutive patients with metastasizing carcinoma of the breast who had been treated with various chemotherapeutic schedules after radical operation was determined retrospectively. 57 women received chemotherapy and hormones, as well as radiotherapy, while 62 had radiotherapy plus hormone treatment. The mean prolongation of life in the former group over that of the latter was 12 months (P less than 0.01). Although chemotherapy delayed death, the dynamics of the cancer were not fundamentally affected. The chemotherapy-induced prolongation (2.5 months--five years) was independent of any extra risk, primary location of the metastases or age.

Effects of oxytocin on cation content and electrophysiology of frog skin epithelium.

We measured effects of oxytocin on current-voltage (I-V) relations of frog (Rana catesbeiana) skins impaled with an intracellular microelectrode. In both Cl- and Cl(-)-free (SO4(2-) solutions, oxytocin caused an approximate doubling short-circuit current (Isc) and a depolarization of the cell membrane. Increase in apical membrane slope conductance, chord conductance, and permeability after oxytocin correlated with the increase in amiloride-sensitive Isc. Oxytocin also increased basolateral membrane conductance (gb). In Cl-, the shift in the voltage intercept of the apical membrane I-V relation (Ea) implied increased intracellular Na+ activity (a(Na)c) after oxytocin. In isolated frog skin epithelia, a similar increase in intracellular [Na+] after oxytocin was demonstrated by flame photometry. In SO4(2-), changes caused by oxytocin in both Ea and in flame photometrically determined cell [Na+] were minimal. The voltage intercept of the basolateral membrane I-V relations (Eb) was shifted by oxytocin in both Cl- and SO4(2-) solutions. Assuming that the basolateral membrane is selectively permeable to K+, changes in K+ obtained from Eb were in disagreement with those obtained by flame photometry. These results suggest that 1) the increase in a(Na)c caused by oxytocin is not essential to produce either the increase in gb or Isc and 2) ions other than K+ make an important contribution to basolateral membrane conductance.

Insulin action on electrophysiological properties of apical and basolateral membranes of frog skin.

We measured the effects of insulin on the current-voltage (I-V) relations of frog skins impaled with an intracellular microelectrode. The current across the cell membranes was assumed to be equal to the amiloride-inhibitable current. Insulin increased short-circuit current (Isc) approximately 40% from the control value. The increase in Isc was associated with a depolarization of the cell membrane. In addition there was an increase in the value of the parameters that describe the ease of movement of Na+ across the apical membrane, namely, slope conductance (ga), chord conductance (Ga), and permeability (PNa). The values of these parameters show remarkable linear correlations with membrane current both before and after stimulation. Intracellular Na+ activity (acNa) was determined from the I-V relations of the apical membrane. Insulin did not significantly modify acNa. Insulin also increased the value of the basolateral membrane conductance, however, the relationship between this parameter and current was complex. These experiments show that the stimulatory effect of insulin on Isc is associated with an increase in the conductance of both the apical and basolateral membranes.

Role of prostaglandin release in the response of tight epithelia to Ca2+ ionophores.

We have studied the effects of the Ca2+ ionophores A23187 and ionomycin on ion transport across amphibian skin and urinary bladder. Both A23187 and ionomycin stimulated transepithelial Na+ transport across the skin. Ionomycin also markedly increased the conductance of an amiloride-insensitive pathway. Both ionophores markedly stimulated the release of prostaglandin E2 (PGE2) into the solution bathing the serosal surface of the skin. Addition of indomethacin to the serosal bathing solution of the skin blocked both the stimulation of short-circuit current (Isc) and the release of prostaglandin caused by the ionophores. Acetylsalicylic acid also blocked the ionomycin-induced stimulation of Isc. These results suggest that the stimulation of Na+ transport caused by Ca2+ ionophores is mediated by the release of a product of the cyclooxygenase pathway, very likely PGE2. Ca2+ ionophores also stimulated the release of PGE2 in urinary bladders; however, they generally depressed Isc. Since the effect on Isc caused by the addition of exogenous PGE2 was different in urinary bladders than in skins, we suggest that at least part of the difference in the action of ionophores is due to the difference in the sensitivity of these epithelia to PGE2. Our results suggest that the heterogeneity of effects that Ca2+ ionophores cause in the physiological parameters of tight epithelia are not always the direct result of increased cytoplasmic Ca2+ but that they may be mediated by other tissue responses triggered by the addition of the ionophores.

Radionuclide assessment of a normal left ventricular response to exercise in patients without evidence of heart disease.

The aim of this study was to define normal left ventricular performance at rest and during supine bicycle exercise with equilibrium radionuclide ventriculography in a normal population other than young healthy volunteers. Thirty-one patients (mean age 45 years +/- 9 SD) with chest pain of varying origin and no evidence of heart disease proven by means of noninvasive and invasive techniques were studied. Left ventricular ejection fraction (LVEF) at rest averaged 0.64 +/- 0.07 SD and increased with peak exercise to 0.73 +/- 0.08 SD (P less than 0.005). Change in LVEF from rest to maximum exercise ranged within 0-0.19. Six patients (19%) failed to augment LVEF with exercise to more than 0.05; none of the patients dropped LVEF during exercise. Multivariate analysis revealed no significant predictors of LVEF response to exercise. However, there was a tendency that resting LVEF and enddiastolic volume index with exercise might influence LVEF response to exercise. Peak left ventricular ejection rate (LVER) at rest averaged 3.3 s-1 +/- 0.6 SD and increased to 5.1 s-1 +/- 1.1 SD (P less than 0.005) with exercise. Peak left ventricular early filling rate (LVFR) was 2.8 s-1 +/- 0.6 SD at rest and was measured 5.5 s-1 +/- 1.3 SD at maximum exercise (P less than 0.005). Left ventricular enddiastolic volume (EDV) did not change significantly from rest to maximum exercise, whereas left ventricular endsystolic volume (ESV) decreased to 79% +/- 19 SD (P less than 0.01) of the value at rest.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of receptor blockers (methysergide, propranolol, phentolamine, yohimbine and prazosin) on desimipramine-induced pituitary hormone stimulation in humans--I. Growth hormone.

In this report the effects of various receptor blockers on desimipramine (DMI)-induced growth hormone (GH) secretion in healthy male subjects are presented. Each trial consisted of two administrations: one of DMI i.v. alone and one of DMI i.v. in combination with the respective receptor blocker: methysergide (serotonin (5-HT) receptor blocker), propranolol (beta receptor blocker), phentolamine (alpha-1/alpha-2 receptor blocker), yohimbine (alpha-2 greater than alpha-1 receptor blocker), and prazosin (alpha-1 receptor blocker). DMI-induced GH stimulation was not significantly different after DMI i.v. alone (n = 12) than after three days' pretreatment with 12 mg methysergide p.o. in another group of subjects (n = 12). Following combined administration of DMI and propranolol (15 mg i.v.), GH secretion was significantly increased by 25 mg DMI (p less than 0.05) and 50 mg DMI (incomplete block design, n = 18). GH secretion was significantly lower (p less than 0.01) after DMI in combination with 60 mg phentolamine i.v. compared to that after administration of DMI alone in the same group (n = 12). Following 10 mg yohimbine i.v. in combination with DMI (n = 6), the DMI-induced GH increase was also significantly less (p less than 0.05) than that after DMI alone. The DMI-induced GH increase following DMI plus 1 mg prazosin p.o. (n = 12) was comparable to that after DMI alone. The results indicate that the GH-stimulating effect of DMI is primarily related to the ability of DMI to inhibit noradrenaline (NA) reuptake. Should serotonergic receptors be involved in the DMI-induced GH secretion at all, they transmit a positive stimulus. The alpha-1 receptors are most likely not (or not essentially) involved, whereas alpha-2 receptors affect the DMI-induced secretion positively, and beta receptors have an inhibitory effect.

Effects of receptor blockers (methysergide, propranolol, phentolamine, yohimbine and prazosin) on desimipramine-induced pituitary hormone stimulation in humans--III. Hypothalamo-pituitary-adrenocortical axis.

In this report the effects of various receptor blockers on the desimipramine (DMI)-induced cortisol (ACTH) secretion in healthy male subjects are presented. Each trial consisted of two administrations: one of DMI i.v. alone and one of DMI i.v. in combination with the respective receptor blocker, i.e. methysergide (serotonin (5-HT) receptor blocker), propranolol (beta receptor blocker), phentolamine (alpha-1/alpha-2 receptor blocker), yohimbine (alpha-2 greater than alpha-1 receptor blocker), and prazosin (alpha-1 receptor blocker). In addition, the effect of prazosin on DMI-induced ACTH stimulation was examined. DMI-induced cortisol stimulation was not significantly different after DMI alone (n = 12) from that after three days pretreatment with methysergide (12 mg p.o.) in another group of subjects (n = 12). Neither the combination of DMI plus propranolol (15 mg i.v. n = 18, incomplete block design) nor that of DMI plus phentolamine (60 mg i.v. n = 12) had a significant influence on DMI-induced cortisol secretion. Following combined administration with yohimbine (10 mg i.v.), cortisol secretion was higher compared to that after DMI alone in the same group (n = 6). DMI-induced cortisol secretion was significantly lower (p less than 0.01) following combined administration with prazosin (1 mg p.o. n = 12), as was DMI-induced ACTH secretion (p less than 0.05) in these subjects. The findings of these trials, especially those of the prazosin trial, indicate that DMI-induced stimulation of cortisol and ACTH secretion is attributable to the noradrenaline (NA) reuptake inhibiting effect of DMI, and that the stimulus is transmitted with the aid of noradrenergic alpha-1 receptors. Alpha-2 receptors possibly exert a negative influence on this effect.

Effects of receptor blockers (methysergide, propranolol, phentolamine, yohimbine and prazosin) on desimipramine-induced pituitary hormone stimulation in humans--II. Prolactin.

In this report the effects of various receptor blockers on desimipramine (DMI)-induced prolactin (PRL) secretion in healthy male subjects are presented. Each trial consisted of two administrations: one of DMI i.v. alone and one of DMI i.v. in combination with the respective receptor blocker: methysergide (serotonin (5-HT) receptor blocker), propranolol (beta receptor blocker), phentolamine (alpha-1/alpha-2 receptor blocker), yohimbine (alpha-2 greater than alpha-1 receptor blocker), and prazosin (alpha-1 receptor blocker). Following administration of methysergide (12 mg p.o., n = 12), a significantly lower (p less than 0.01) DMI-induced PRL secretion compared to DMI alone in another group of subjects (n = 12) was observed. Combined administration with propranolol (15 mg i.v.) significantly enhanced the DMI-induced PRL secretion compared to DMI 50 mg i.v. alone (n = 18, incomplete block design) (p less than 0.01). Neither combined administration with phentolamine (60 mg i.v., n = 12), yohimbine (10 mg i.v., n = 6), nor prazosin (1 mg p.o., n = 12) significantly influenced the DMI-induced PRL secretion compared to DMI alone in the same subjects. The results of the present study, especially the inhibitory effect on DMI-induced PRL secretion of methysergide, indicate that the primarily noradrenaline (NA) and lesser serotonin (5-HT) reuptake inhibiting antidepressant DMI stimulates PRL secretion via 5-HT neurons. Furthermore, the significantly enhanced PRL release following combined administration of DMI and propranolol suggests that a noradrenergic inhibitory effect also may be involved in the transmission of the PRL stimulus.

Current-voltage relations of the apical and basolateral membranes of the frog skin.

We determined the current-voltage (I-V) relations of the apical and basolateral barriers of frog skins by impaling the cells with an intracellular microelectrode and assuming that the current across the cellular pathway was equal to the amiloride-inhibitable current. We found that: (a) The responses in transepithelial current and intracellular potential to square pulses of transepithelial potential (VT) varied markedly with time. (b) As a consequence of these transient responses, the basolateral I-V relation was markedly dependent on the time of sampling after the beginning of each pulse. The apical I-V plot was much less sensitive to the time of sampling within the pulse. (c) The I-V data for the apical barrier approximated the I-V relations calculated from the Goldman constant field equation over a relatively wide range of membrane potentials (+/- 100 mV). (d) A sudden reduction in apical bath [Na+] resulted in an increase in apical permeability and a shift in the apical barrier zero-current potential (Ea) toward less positive values. The shift in Ea was equivalent to a change of 45 mV for a 10-fold change in apical [Na+]. (e) The transient responses of the skin to square VT pulses were described by the sum of two exponentials with time constants of 114 and 1,563 ms, which are compatible with the time constants that would be produced by an RC circuit with capacitances of 65 and 1,718 microF. The larger capacitance is too large to identify it comfortably with a true dielectric membrane capacitance.

Basolateral membrane responses to transport modifiers in the frog skin epithelium.

Application of transepithelial square voltage pulses to the frog skin leads to responses in the transepithelial current and intracellular potential which include transient components. Determinations at 600 ms allow for meaningful estimates of basolateral membrane responses to transport modifiers. Oxytocin produced a large and sustained increase in the amiloride-inhibitable short circuit current (Im) which was accompanied by a large increase of both apical and basolateral membrane conductance (ga and gb, respectively). While Im and ga increased nearly simultaneously, gb started to increase several minutes after the increase in the two other parameters. Insulin also increased Im, ga and gb. As with oxytocin, the increases in Im and ga often preceded the changes in gb. Ouabain reduced Im and ga. The effects on gb were more complex, since sometimes the inhibition of Im was first accompanied by an increase followed by a decrease while in other instances only minor changes in conductance could be observed. The currently available information regarding the control of cytoplasmic [Ca2+] and the effects of Ca2+ on cell membrane properties are used to construct a model in which changes in cytoplasmic [Ca2+] account for the observed behavior of the basolateral membrane.

Dose-dependent growth hormone, prolactin and cortisol stimulation after i.v. administration of desimipramine in human subjects.

In previous studies it was shown that the tricyclic antidepressant desimipramine (DMI) had different stimulatory effects on growth hormone (GH), prolactin (PRL), ACTH and cortisol secretion in healthy subjects, depending on the mode of administration. The present study examined the effects following i.v. administration of placebo and DMI (5, 15, 25, 50 and 75 mg) on GH, PRL and cortisol secretion in male subjects (n = 6). This primarily noradrenergic and secondarily serotonergic reuptake-inhibiting substance was found to stimulate the secretion of GH, PRL and cortisol in a dose-dependent manner. Compared to placebo, significant increases occurred in GH (p less than 0.05) and in PRL (p less than 0.05) from a dose of DMI 25 mg on, and in cortisol (p less than 0.05) from 15 mg on. The results indicate that, in addition to the dose, the method of administration influenced the effects of DMI on the three hormones.