Biomedical subjects

M Kessler

Publications and source records attributed to M Kessler.

At least 127 records · Page 7Linked to original sources

PubMed1997

[Osteosarcoma in cats: epidemiological, clinical and radiological findings in 78 animals (1990-1995)].

In this study 78 cats with osteosarcoma were identified from biopsy logs and evaluated retrospectively regarding breed, sex, and age distribution, tumor location, clinical symptoms, radiographic findings, biologic behavior of the neoplasm, and outcome following therapy. There was no significant breed or sex prediffection among the cats. The average age was 10.1 years, with a range of less than one to over 17 years. 36 (46%) of the osteosarcomas were localized in the bones of the limbs, 42 (54%) were found in flat or irregular bones. The hind limbs (25 cases) were affected significantly more often than the front limbs (10 cases). The most prevalent sites were the distal femur, proximal tibia, the humerus and the digits. Four of the tumors occurred after osteosynthesis of a previous fracture. In most of the cats limb tumors were associated with chronic lameness. The skull was the most common site for tumors of the flat and irregular bones (35 cases), which involved the oral cavity in 27 cases. The most common symptoms were dental problems, deformations of the skull, and nasal discharge. The remaining tumors of the flat and irregular bones were located in the pelvis (3), vertebrae (2), scapula (1), and rib (1). Radiographic findings were very variable and ranged from lytic to purely osteoproliferative forms. With tumors of the flat and irregular bones, tumor recurrence was a common cause for euthanasia. Animals with tumors of the limbs had a good prognosis following amputation.

Age Factors↗

PubMed1997

[Small animal contribution to pediatric oncology].

Retrospective analysis of biopsy material submitted to an Institute of Veterinary Pathology by private veterinary practitioners from 1993-1995 revealed tumors in 157 dogs and 71 cats under one year of age. Both histiocytomas and papillomas were excluded from the study. In the dog 55% (n = 87) and in the cat 73% (n = 52) of all tumors were diagnosed as malignant. In the dog tumors in order of frequency were: mammary neoplasia (n = 24, of those n = 10 malignant), soft tissue sarcomas (n = 24), hematopoietic tumors (n = 23), benign mesenchymal tumors (n = 16), mast cell tumors (n = 15), odontogenic tumors (n = 9), melanomas (n = 9, of those n = 5 malignant), osteosarcoma (n = 6), others (n = 31). In the feline, sarcomas were most common and of those hematopoietic tumors (lymphoma n = 23; 32%; mast cell tumors n = 12; 17%) were the two largest groups. The remaining sarcomas were 13 soft tissue sarcomas (18%) of which fibrosarcomas (n = 8) were most prevalent. Carcinomas where diagnosed in only 2 cases whereas among benign neoplasms (n = 19; 27%), epithelial tumors were the largest group (n = 14). In the order of frequency the following benign neoplasias were identified: fibroadenoma of mammary gland (n = 5), odontogenic tumors (n = 5), benign soft tissue tumors (n = 4), others (n = 6).

Age Factors↗

PubMed1997

Vaccine evaluation studies of replication-defective SIVsmB7.

Non-infectious virus-like particles of SIVsmB7 that expresses env and gag gene products but are defective in pol and vpx/vpr were assessed for their ability to induce protective immunity against infection with pathogenic SIVsmE660 in rhesus macaques. Animals were immunized in three groups: group A was primed with cell-associated SIVsmB7 and boosted with cell-free SIVsmB7; group B was primed with cell-free SIVsmB7 and boosted with cell-free SIVsmB7 conjugated to iron oxide microbeads; group C was primed with cell-free SIVsmB7 mixed with Titer Max adjuvant and boosted with cell-free SIVsmB7 mixed with SAF-M adjuvant followed by secondary boosting with cell-free SIVsmB7 conjugated to microbeads. Animals were challenged intravenously with 20 animal infectious doses of SIVsmE660 grown in rhesus peripheral blood mononuclear cells 3 weeks after final boosting. All animals became infected as evidenced by quantitative virus cultivation. Sera from immunized animals contained low-titer antibodies by ELISA and low or undetectable neutralizing antibodies on the day of challenge but strong anamnestic antibody responses were observed following challenge. Interestingly, 2 of 3 animals in group A showed evidence of transient viremia and more stable CD4 counts following challenge as compared to the other immunized animals and to non-immunized controls. Thus, immunization with cell-associated SIVsmB7 did not provide sterilizing immunity against challenge with a highly pathogenic SIV strain but might have caused virus clearance later in infection.

Animals↗

PubMed1997

[Hemangiosarcoma of the spleen: clinical aspects in 52 dogs].

This study describes clinical aspects, treatment, and survival times of 52 dogs with hemangiosarcoma of the spleen, presented at the Department of Veterinary Surgery, University of Munich, Germany. Depending on the dissemination of the disease the dogs were assigned to three clinical stages: 10 dogs were in stage I (tumor confined to the spleen without metastasis), 18 in stage II (tumor confined to the spleen or ruptured, with or without lymph node involvement but without distant metastasis) and 24 in stage III (with distant metastasis). Dogs in stage I displayed mild and nonspecific symptoms. In stage II and II, half of the patients were presented in shock or collapse after an acute rupture of the tumor. Sonographic examination was found superior in diagnosing splenic neoplasia when compared to radiography. Pronounced laboratory abnormalities were present mainly in patients in stages II or III with anemia, leucocytosis, thrombocytopenia and prolonged bleeding times predominating. Survival times following splenectomy were very variable. The median survival time was 100 days. Because of the high standard deviaton there was no statistically significant difference in survival times between animals of different stages.

Animals↗

PubMed1997

Potential interest of anti-ischemic agents for limiting cyclosporin A nephrotoxicity.

Chronic administration of cyclosporin A induces nephrotoxicity in humans. This is related to a cyclosporin A-induced constriction of afferent glomerular arterioles and mesangial cells, which leads to a decrease in filtration pressure and creatinine clearance. Afterwards, cellular lesions are observed involving mainly tubular atrophy and interstitial fibrosis, both of which are nonspecific. The initial mechanism of its toxicity is not clearly explained. The current pharmacological approach is symptomatic in order to counteract or minimize the consequences of a prime cause, which still remains to be defined. However, cyclosporin A has a deletereous effect on mitochondrial functions and mainly on ATP synthesis, which occurs when Ca2+ accumulates in matrix mitochondria. The effects of trimetazidine, an antischemic drug used in the treatment of angina pectoris, have been assessed. This drug is effective in experimental models of hypoxia induced by cyclosporin A: it restores ATP synthesis previously decreased by Ca2+ and cyclosporin A, and releases a part of Ca2+ excess accumulated by mitochondria at concentrations reached in humans at usual dosage regimens. At higher concentrations, it reverses the mitochondrial permeability transition previously generated (opened) by Ca2+ and a pro-oxidant such as terbutylperoxide (t-BH). It was also observed that trimetazidine does not modify the immunosuppressive effects of cyclosporin A in various models. These data suggest that nephrotoxicity of cyclosporin A is not irrevocably linked to its immunosuppressive effect but that it may be possible to counteract at least partly its nephrotoxic effects without altering its effectiveness in preventing graft rejection.

Adenosine Triphosphate↗

PubMed1996

Effects of heparin on the properties of solubilized and reconstituted rat brain AMPA receptors.

Heparin was found to bind to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors and to alter their functional properties. AMPA receptors solubilized in 0.4% Triton X-100 bound to a heparin-agarose column and were eluted by 0.4 M NaCl. Soluble heparin inhibited 10 nM [3H]AMPA binding to detergent-solubilized receptors by 75% (IC50 = 10 micrograms/ml), but had little effect on binding to membrane-associated receptors. The inhibition of [3H]AMPA binding to detergent-solubilized receptors was not observed when binding was measured in the presence of 0.4 M NaCl, and no effect of heparin was observed on binding of the AMPA receptor antagonist [3H]6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Scatchard analyses of [3H]AMPA binding to solubilized receptors revealed that the inhibition induced by heparin was caused by a decrease in the apparent affinity of a portion of the total binding sites. Studies on AMPA receptors reconstituted in artificial lipid bilayers indicated that 10 micrograms/ml heparin enhanced cooperativity between channels and prolonged the lifetime of the open channel, but did not affect the amplitude of single channel currents. Thus, heparin may be added to the list of compounds known to modulate AMPA receptor function. These data also raise the possibility that heparin-containing proteoglycans, which are known to be concentrated at synaptic junctions, might be able to bind AMPA receptors and influence their functional characteristics.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1996

Facilitation of glutamate receptors reverses an age-associated memory impairment in rats.

The accuracy of memory for recent events is reported to decay between young adulthood and middle age in humans (Crook et al., 1990; Crook and West, 1990; Thomas et al., 1977) due to impairments in acquisition and/or retention (Craik, 1977; Huppert and Kopelman, 1989). Effects of this kind are also found in comparisons of middle-aged (12-18 months) vs. young adult (3 months) rats in tests requiring retention of recently sampled spatial cues (Kadar et al., 1990a; Kadar et al., 1990b; Goudsmit et al., 1990; Weiss and Thompson, 1991). The causes of such changes in memory processing are unknown but might be expected to involve age-related losses in forebrain glutamate receptors (Bahr et al., 1992; Magnusson and Cotman, 1993; Wenk et al., 1991); these receptors mediate fast excitatory transmission in many brain regions and play an essential role in the production of long-term potentiation (LTP), a form of synaptic plasticity that has been implicated in memory encoding (Landfield and Lynch, 1977; Moore et al., 1993). In the present communication we report results indicating that a drug that enhances AMPA-type glutamate receptors acts centrally to selectively increase hippocampal spatial cell firing and improves both acquisition performance and memory retention in middle-aged rats to levels equivalent to those found in young adult animals.

Age Factors↗

PubMed1996

Signal transduction by basic fibroblast growth factor in rat osteoblastic Py1a cells.

Basic fibroblast growth factor (bFGF) is a potent mitogen for bone. In this study, we utilized the clonal rat osteoblastic cell line, Py1a, to examine signal transduction by bFGF and to determine the role of mitogen activated protein kinases (MAPK) and induction of c-fos mRNA in the mitogenic response to bFGF. Stimulation of [3H]thymidine incorporation (TDR) into DNA by bFGF was determined in the presence of phorbol myristate acetate of (PMA) to down-regulate the protein kinase C (PKC) pathway, genistein, an inhibitor of tyrosine kinase and H-7, a PKC inhibitor, bFGF 10(-8) M and PMA 10(-7) M increased TDR by 242 and 245%, respectively. Treatment with bFGF or PMA for 5 or 30 minutes increased tyrosine phosphorylation of multiple proteins, and immunoblotting with MAPK-specific antibody revealed that two of these bands were the 42 and 44 kD isoforms of MAPK. PMA and bFGF induced c-fos mRNA expression at 30 minutes. Genistein at 10 micrograms/ml blocked the mitogenic effect of bFGF and partially inhibited the mitogenic effect of PMA. Genistein at 100 micrograms/ml also blocked both bFGF- and PMA-induced increases in c-fos mRNA. A 24 h pretreatment with PMA at 10(-7) M inhibited the mitogenic response, tyrosine phosphorylation of MAPK, and induction of c-fos mRNA subsequent to the addition of PMA, but not bFGF. H-7 at 50 microM blocked bFGF-induced mitogenesis and c-fos induction, but did not inhibit bFGF-induced tyrosine phosphorylation of MAPK. In this study, we show that the signaling pathway of bFGF and PMA are similar in that they both induce tyrosine phosphorylation of MAP kinases and activate c-fos. However, the signaling pathways ultimately diverge in that once the PKC pathway is down-regulated by PMA pretreatment or blocked by the PKC inhibitor H-7, tyrosine phosphorylation of MAP kinase, c-fos induction, and the mitogenic effect of PMA is blocked. In contrast, down-regulation of the PKC pathway inhibits c-fos and the mitogenic response to bFGF, but not bFGF's effects on tyrosine phosphorylation of MAP kinase.

Analysis of Variance↗

PubMed1996

Effects of partial volume and phase shift between fat and water in gradient-echo magnetic resonance-mammography.

The signal modulations caused by partial volume effect and phase shift between fat and water signal in gradient-echo magnetic resonance mammography (GRE MR-mammography) have been calculated. Based on this, the theoretical sensitivity and specificity of GRE MR-mammography has been investigated considering different evaluation methods for the gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA)-based signal enhancement. The results show that both in- and out-of-phase sequences suffer from partial volume effects in voxels that contain both fat and water. This can decrease sensitivity to Gd-DTPA uptake in small, fat-embedded lesions or in pathology that contains fat interspersed histologically. Additionally, out-of-phase sequences can suffer from phase cancellation effects that can further decrease their sensitivity to Gd-DTPA uptake. In the worst case signal can actually decrease during Gd-DTPA influx. Determination of enhancement relative to the baseline value can decrease the specificity of GRE MR-mammography in the out-of-phase condition and decrease the sensitivity in the in-phase condition. These effects are less pronounced when enhancement is calculated relative to fat. These effects need to be understood since Gd-DTPA uptake is the prime indicator of malignancy in MR-mammography.

Breast↗

PubMed1996

Ultraviolet radiation, thiol reagents, and solubilization enhance AMPA receptor binding affinity via a common mechanism.

The binding properties of membrane-bound or solubilized AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid)-type glutamate receptors from rat brain were tested following exposure to ultraviolet (UV) radiation or incubation with the thiol reagent p-chloromercuriphenyl-sulfonic acid (PCMBS). Brief exposure to UV radiation (254 nm) increased [3H]AMPA binding to brain membranes, while binding to soluble fractions decreased. The increase in brain membrane binding was caused by an apparent interconversion of low-affinity [3H]AMPA binding sites into a higher-affinity state. Incubation with PCMBS caused a significant increase in [3H]AMPA binding to brain membranes but had no significant effect on [3H]AMPA binding to solubilized receptors. There was an interaction between the PCMBS and UV effects in the brain membranes such that prior exposure to one of the treatments reduced the relative magnitude of the other's effects. The present results suggest that ultraviolet radiation, PCMBS and solubilization all increase AMPA receptor binding affinity via a common mechanism.

4-Chloromercuribenzenesulfonate↗

PubMed1996

Distinct distributions of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunits and a related 53,000 M(R) antigen (GR53) in brain tissue.

Polyclonal antibodies against specific carboxy-terminal sequences of known alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunits (GluR-4) were used to screen regional homogenates and subcellular fractions from rat brain. Affinity purified anti-GluR1 (against amino acids 877-899), anti-GluR2/3 (850-862), and anti-GluR4a and anti-GluR4b (868-881) labeled distinct subunits with the expected molecular weight of approximately 105,000. These antigens were shown to have distinct distributions in the brain. While GluR2/3 epitopes had a distribution profile similar to that of the presynaptic marker synaptophysin, GluR1 was notable for its abundance in the hippocampus and its relatively low density in neocortical areas, and GluR4 was highly enriched in cerebellar tissue. An additional antigen (glutamate receptor-related, GR53) of lower molecular weight (50,000-59,000) was recognized in rat, human, frog, chick and goldfish brain samples by anti-GluR4a as well as by anti-GluR1 at, an antibody that specifically recognizes the extracellular aminoterminal domain of GluR1 (amino acids 163-188). Both antibodies also labeled antigens of approximately 105,000 mol. wt in brain tissue from all species tested. The approximately 53,000 mol. wt antigen was concentrated 10-20-fold in synaptic membranes vs homogenates across rat brain regions. Both the 105,000 and the 53,000 mol. wt proteins were also concentrated in postsynaptic densities, and neither of the two antigens were evident in seven non-brain tissue samples. These data indicate that AMPA receptors have regionally different subunit combinations and that some AMPA receptor composites include proteins other than the conventional 105,000 mol. wt GluR subunits.

Amino Acid Sequence↗

PubMed1996

Effects of a centrally active benzoylpyrrolidine drug on AMPA receptor kinetics.

A newly developed benzoylpyrrolidine drug (BDP-20) that increases the size of fast, excitatory synaptic responses was examined for its effects on the kinetic properties of alpha-amino-3-hydroxy-5-methyl-4-isoxalepropionic acid (AMPA)-type glutamate receptors. When long pulses of glutamate were applied to excised hippocampal patches of the rat, the compound BDP-20 caused an approximately 15-fold reduction in the rate at which responses desensitized and a similar size increase in steady-state currents. In experiments using 1-ms glutamate pulses, BDP-20 prolonged response deactivation by a factor of about four and greatly reduced the depression in the second response when two consecutive glutamate pulses were given. Two types of equilibrium binding assays indicated that BDP-20 causes a measurable increase in the affinity of AMPA receptors; the EC50 values for this effect were similar to those obtained in excised patch studies. The actions of BDP-20 on physiology and ligand binding could be adequately reproduced in a receptor model by slowing the rate of desensitization and increasing the affinity of the sensitized states. The biochemical and physiological effects of this benzoylpyrrolidine compound were qualitatively different from those obtained with cyclothiazide, although both types of drug increased AMPA receptor-mediated synaptic responses. Moreover, interactions between the drugs were at most only partially competitive; AMPA receptors may thus have multiple modulatory sites with distinct drug preferences and different effects on receptor kinetics.

Animals↗

PubMed1996

Recurrence of immunoglobulin A nephropathy after renal transplantation in the cyclosporine era.

Immunoglobulin A nephropathy (IgAN) frequently recurs in patients after renal transplantation (RT) on a conventional regimen of immunosuppressive therapy, but little is known about the influence of cyclosporine (Cs) on such a recurrence. We studied 84 patients retrospectively who underwent RT for renal failure attributable to IgAN (n = 71) or Henoch-Schönlein purpura nephropathy (HSPN) (n = 13) in two transplantation units, between January 1985 and June 1991 and were treated with Cs. Four patients died 3 months to 8 years after RT. Graft survival was 88% at 1 year, 75.2% at 5 years, and 63% at 8 years. Fifty patients underwent at least one graft biopsy, but studies with immunofluorescence were performed on only 28 (23 IgAN and 5 HSPN). After a mean follow-up of 68.1 +/- 37.2 months, mesangial IgA deposits recurred in 13 of the 28 patients (12 IgAN and 1 HSP) (prevalence, 46.4%). Among the 13 patients with recurrence of IgA deposits, all but 4 had urinary abnormalities. Light microscopy showed mesangial deposits and focal and segmental glomerular changes in 9 cases. Four patients lost their graft function 69 to 119 months after RT, and 2 had severe graft dysfunction. The rates of graft failure and mean serum creatinine at 1, 5, and 8 years were similar in the 13 patients with recurrence and the 15 patients without proven recurrence. In conclusion, Cs did not reduce the incidence or severity of IgAN recurrence. The latter was the cause of graft loss or dysfunction in 46.1 % of the patients with recurrent IgA deposits. Recurrent glomerulonephritis did not influence the 8-year graft survival in patients with IgAN or HSPN, but it may be an important cause of graft loss as evidenced by more extended follow-up.

Adult↗

PubMed1996

[Comparison between current and high resolution ultrasound for diagnosis of breast lesions].

AIM: To assess the value of high-resolution ultrasound in the diagnosis of breast lesions. METHOD: Fifty women with a clinically suspicious breast mass were examined with mammography, conventional and high-resolution sonography. Ultrasound was performed with a linear-array 7.5-mHz transducer and an annular-array 13.0 MHz transducer. RESULTS: Histology showed carcinoma in 28 patients, fibrocystic changes in 20 and fibroadenoma in 2. High-resolution ultrasound characterized 18 lesions more accurately than conventional ultrasound, including 13 carcinomas, 3 fibrocystic changes and 2 fibroadenomas. The size of 8 carcinomas was measured more accurately with high-resolution ultrasound than with conventional ultrasound. CONCLUSION: High-resolution ultrasound is more valuable in the differentiation and size determination of breast lesions than conventional ultrasound.

Adolescent↗

PubMed1996

[Dynamic MR mammography: is the course of signal intensification suitable for the differentiation of different forms of mastopathy?].

PURPOSE: The capacity of dynamic contrast-enhanced MR mammography to distinguish between different forms and grades of mastopathy according to Prechtel's classification was evaluated in a retrospective study. PATIENTS AND METHODS: MR mammograms of 51 patients with histologically proven mastopathy were retrospectively evaluated in areas subsequently biopsied. RESULTS: Mean values of regressive and hyperplastic types of mastopathy differed significantly no significant differences were found between proliferating and non-proliferating mastopathies or Prechtel grades I-III mastopathy when MRI data obtained with a FLASH 3 D sequence (TR = 8.4 ms, TE = 3 ms, flip angle = 30 degrees at 1.0 T) were compared one minute, three, 5 and 8 minutes after i.v. bolus administration of contrast media (Gd-DTPA, 0.1 mmol/kg body weight). CONCLUSION: Our data indicate that dynamic contrast-enhanced MR mammography does not allow the differentiation of proliferating and non-proliferating mastopathy according to the Prechtel classification. Dynamic MR mammography assessment of breast cancer risk does not seem to be feasible.

Breast↗

PubMed1996

[Technics for the preoperative marking of nonpalpable breast lesions in MRT].

We describe a method of localizing suspicious breast lesions only visible by MRI that does not require additional hardware and can be carried out on any MRI-scanner suited for MR-mammography. We have performed a total of 48 localizations with different techniques: 28 charcoal/Gd-DTPA, 18 with wires and two skin markings. All localizations have been successful; wire localizations provided the best results, since the position of the wire could be corrected under MR-guidance. Until suitable localization- and biopsy coils become available the methods employed by us provide a satisfactory alternative which allows radiologists who perform diagnostic MR-mammography with techniques to carry out precise pre-operative localisations of breast lesions.

Breast↗

PubMed1996

Hepatitis C after renal transplantation: histopathological correlations.

This study evaluates the correlations between liver histology, cytolysis, cryoglobulinaemia, co-infection with hepatitis B virus, and immunosuppressive treatment in renal transplant patients with HCV infection. Forty-five of 378 kidney recipients (January 1973-September 1993) had anti-HCV antibodies (prevalence = 11.9%) detected by second generation ELISA (Abbott Pasteur). Viral RNA was detected in those patients by RT-PCR in serum and liver. HCV-positive patients underwent liver biopsy to assess their liver tissue lesions according to Knodell's score. Patients were also screened for Hbs, Hbc and Hbe antigens (ELISA, Abbott) and cryoglobulins (immunobinding, SEBIA). Of the 45 HCV+ patients, 38 (84.4%) had persistent viral replication in the serum and 29 of the 30 patients having undergone liver biopsy had PCR-positive liver tissue. The liver biopsies revealed no active hepatitis lesion in 14 patients (46.6%, Group CAH-), 16 (53.3%) had chronic active hepatitis (Group CAH+) and 3 (10%) had signs of cirrhosis. Comparing groups CH+ and CH- showed that viral replication was detected in all 16 patients with chronic active hepatitis, versus 10/14 patients in the CAH- group (P < 0.05). Patients were more frequently treated with azathioprine in the CH+ group (12/16 vs 8/14; P < 0.05). The duration of renal transplantation was significantly longer in patients with a Knodell score > 5 (58 +/- 56 months vs 35 +/- 29 months, P < 0.001). Incidence of co-infection with HBV was similar in both groups. The mean values of alanine aminotransferase correlated with the Knodell score (r = 0.4, P = 0.03). Mixed cryoglobulinaemia was more common in the replicant forms of HVC infection (12/38 vs 1/7, P < 0.0001). This study shows that liver histological lesions are correlated with HCV viral replication, are more frequent in patients treated with azathioprine and are more severe as the duration of transplant is longer.

Alanine Transaminase↗

PubMed1996

Psychological effects of a drug that facilitates brain AMPA receptors.

The effects of 1-(quinoxalin-6-ylcarbonyl)piperidine (CX516), a centrally active compound that facilitates AMPA receptor-mediated synaptic responses, were tested in human subjects. Separate tests of delayed recall were given prior to and nearly 3 h after administration of placebo (n = 12) or drug (n = 36). Control subjects exhibited poorer performance in the second session than in the first while subjects given 600-1200 mg of the drug did not. There were no pre- vs post-treatment differences in immediate recall in either group. The drug did not reliably affect self-assessment scores for any of several psychological variables but did disrupt the normally present correlations for within-subject changes in the variables. These results suggest that AMPA receptor modulators may (1) improve memory under some circumstances and (2) produce psychological effects that are subtle or not related to specific mood states.

Adult↗