Residual Force Enhancement Following Eccentric Contractions: A New Mechanism Involving Titin.

Eccentric muscle properties are not well characterized by the current paradigm of the molecular mechanism of contraction: the cross-bridge theory. Findings of force contributions by passive structural elements a decade ago paved the way for a new theory. Here, we present experimental evidence and theoretical support for the idea that the structural protein titin contributes to active force production, thereby explaining many of the unresolved properties of eccentric muscle contraction.

Aphid specialization on different summer hosts is associated with strong genetic differentiation and unequal symbiont communities despite a common mating habitat.

Specialization on different host plants can promote evolutionary diversification of herbivorous insects. Work on pea aphids (Acyrthosiphon pisum) has contributed significantly to the understanding of this process, demonstrating that populations associated with different host plants exhibit performance trade-offs across hosts, show adaptive host choice and genetic differentiation and possess different communities of bacterial endosymbionts. Populations specialized on different secondary host plants during the parthenogenetic summer generations are also described for the black bean aphid (Aphis fabae complex) and are usually treated as different (morphologically cryptic) subspecies. In contrast to pea aphids, however, host choice and mate choice are decoupled in black bean aphids, because populations from different summer hosts return to the same primary host plant to mate and lay overwintering eggs. This could counteract evolutionary divergence, and it is currently unknown to what extent black bean aphids using different summer hosts are indeed differentiated. We addressed this question by microsatellite genotyping and endosymbiont screening of black bean aphids collected in summer from the goosefoot Chenopodium album (subspecies A. f. fabae) and from thistles of the genus Cirsium (subspecies A. f. cirsiiacanthoides) across numerous sites in Switzerland and France. Our results show clearly that aphids from Cirsium and Chenopodium exhibit strong and geographically consistent genetic differentiation and that they differ in their frequencies of infection with particular endosymbionts. The dependence on a joint winter host has thus not prevented the evolutionary divergence into summer host-adapted populations that appear to have evolved mechanisms of reproductive isolation within a common mating habitat.

Seafarer deaths at sea: a German mortality study.

BACKGROUND: Seafarers face numerous hazards during their work at sea. AIMS: To demonstrate the frequency and causes of mortality in German seafarers. METHODS: The deaths of all German seafarers from 1998 to 2008 were counted and evaluated using the German central civil register in Berlin. RESULTS: The study cohort comprised a total of 159588 seafarer-years. During the 11 year period, 68 male seafarers died on board. The average age was 48.5 years (SD 12.7 years) and comprised 35 deck officers, 16 engine officers and 17 general crew members (i.e. non-officers from the deck and engine room crew and galley staff). Cause of death was documented in 45 cases (66%): 26 were due to unnatural causes (occupational accidents, suicides) and 19 due to natural causes (particularly, ischaemic heart disease). The crude annual mortality rate for German seamen was 65 per 100000 seafarer-years. For cardiac causes, this rate was significantly higher among deck and engine officers (24 and 38) than among crew ranks (7 per 100000 seafarer-years) (P < 0.05). Deck and engine offi-cers also showed a higher mortality rate for accidents (28 and 22) than crew ranks (15) (P < 0.05). The age-stratified fatal accident rate of German seafarers aboard was 10 times higher than the mortality of the German general population on shore. CONCLUSIONS: Seafaring constitutes an occupation with a high risk for serious accidents. Due to the unexpectedly high mortality rate among officers associated with work-related accidents, this occupational group should receive more effective education on safety behaviour on board.

The prevalence of BRCA1 and BRCA2 mutations among young Mexican women with triple-negative breast cancer.

Various guidelines recommend that women with triple-negative breast cancer should be tested for BRCA1 mutations, but the prevalence of mutations may vary with ethnic group and with geographic region, and the optimal cutoff age for testing has not been established. We estimated the frequencies of BRCA1 and BRCA2 (BRCA) mutations among 190 women with triple-negative breast cancer, unselected for family history, diagnosed at age 50 or less at a single hospital in Mexico City. Patients were screened for 115 recurrent BRCA mutations, which have been reported previously in women of Hispanic origin, including a common large rearrangement Mexican founder mutation (BRCA1 ex9-12del). A BRCA mutation was detected in 44 of 190 patients with triple-negative breast cancer (23 %). Forty-three mutations were found in BRCA1 and one mutation was found in BRCA2. Seven different mutations accounted for 39 patients (89 % of the total mutations). The Mexican founder mutation (BRCA1 ex9-12del) was found 18 times and accounted for 41 % of all mutations detected. There is a high prevalence of BRCA1 mutations among young triple-negative breast cancer patients in Mexico. Women with triple-negative breast cancer in Mexico should be screened for mutations in BRCA1.

Prevalence of BRCA1 and BRCA2 mutations in unselected breast cancer patients from Peru.

The prevalence of BRCA1 and BRCA2 mutations among breast cancer patients in Peru has not yet been explored. We enrolled 266 women with breast cancer from a National cancer hospital in Lima, Peru, unselected for age or family history. DNA was screened with a panel of 114 recurrent Hispanic BRCA mutations (HISPANEL). Among the 266 cases, 13 deleterious mutations were identified (11 in BRCA1 and 2 in BRCA2), representing 5% of the total. The average age of breast cancer in the mutation-positive cases was 44 years. BRCA1 185delAG represented 7 of 11 mutations in BRCA1. Other mutations detected in BRCA1 included: two 2080delA, one 943ins10, and one 3878delTA. The BRCA2 3036del4 mutation was seen in two patients. Given the relatively low cost of the HISPANEL test, one should consider offering this test to all Peruvian women with breast or ovarian cancer.

[Endoscopic therapy for tumours of the papilla of vater]. / Endoskopische Interventionsmöglichkeiten bei Tumoren der Papille.

BACKGROUND: Ampullary tumours are rare and can be separated in benign and malignant lesions. There are non-invasive diagnostic methods in order to detect ampullary tumours like abdominal ultrasound, computed tomography and MRCP (magnetic resonance cholangiopancreaticography) as well as invasive methods, e. g., gastroscopy, duodenoscopy, endosonography, intraductal ultrasound, ERCP and cholangioscopy. Endoscopy is the method of choice for this indication, whereas a combination of the different diagnostic methods is common. MATERIAL AND METHODS: A selective literature research with descriptive survey has been carried out. RESULTS: The standard method to treat benign tumours of the papilla is endoscopic papillectomy. For malignant tumours surgery is preferred. But in some certain circumstances it is also possible to treat carcinomas of the papilla endoscopically. DISCUSSION: This overview should assist surgeons and endoscopists to choose the right diagnostic approach and to treat adenomas as well as carcinomas of the Papilla of Vater appropriately. CONCLUSION: The treatment of papilla tumours depends primarily on the dignity, the morphology of the findings and the extension of the tumour (extraductal vs. intraductal).

Effect of controlled-release levodopa on the microstructure of sleep in Parkinson's disease.

BACKGROUND: Dopamine is an important neurotransmitter in the regulation of the sleep-wake cycle, and parkinsonian patients suffer from prominent sleep abnormalities. Hence, the question arises whether the disrupted sleep pattern in Parkinson's disease (PD) is responsive to dopaminergic treatment. METHODS: Thirty-two patients (18 women, 45-82 years old; mean 61 ± 8 years) with dopamine-responsive, akinetic-rigid PD, not taking neuroleptic medication or suffering from dementia were randomized into two groups. Both groups had to withhold their usual dopaminergic medication after noon. At bedtime, one group received 200 mg controlled-release (CR) levodopa/carbidopa, whilst the other group spent the night in the 'off'-state. Polysomnographic recordings were obtained in all patients and 16 age-matched, healthy controls. RESULTS: Compared to healthy controls, patients with PD suffered from significantly decreased total sleep time, REM sleep and slow wave sleep (SWS), whilst the time spent awake was increased. The administration of levodopa/carbidopa CR had no impact on any of these variables. CONCLUSION: Levodopa/carbidopa CR has previously been found effective for treating night-time akinesia, but according to this study, it has no impact on the altered sleep structure in PD.

[Deep brain stimulation for Parkinson's disease]. / Tiefe Hirnstimulation bei der Parkinson-Krankheit.

Deep brain stimulation (DBS) is an effective neurosurgical therapy for treatment of motor symptoms in Parkinson's disease (PD). DBS of the subthalamic nucleus (STN-DBS) leads to a significant reduction of hypokinetic and hyperkinetic symptoms and improvement in quality of life. STN-DBS is, however, associated with severe adverse effects including psychiatric symptoms, such as depression, apathy and increased suicidal tendencies. Pallidal DBS might be just as efficacious with fewer adverse effects. Future studies will prospectively compare the clinical effects of STN and pallidal DBS. Alternative targets for treatment of PD have to be considered including the pedunculopontine nucleus, thalamic CM/Pf complex and zona incerta.

Deep brain stimulation of the internal globus pallidus in dystonia: target localisation under general anaesthesia.

UNLABELLED: Deep brain stimulation (DBS) of the internal globus pallidus (Gpi) is an effective therapy for various types of dystonia. The authors describe their technical approach for securing appropriate placement of the stimulating electrodes within the Gpi under general anaesthesia, including MRI based individualised anatomical targeting combined with electrophysiological mapping of the Gpi using micro-recording (MER) as well as macrostimulation and report the subsequent clinical outcome and complications using this method. METHOD: We studied 42 patients (male-female ratio 25:17; mean age 43.6 years, range 9 to 74 years) consecutively operated at the Department of Neurosurgery, University Hospital Schleswig-Holstein, Campus Kiel, between 2001 - 2006. One patient underwent unilateral implantation after a right-sided pallidotomy 30 years before and strictly unilateral symptoms; all other implantations were bilateral. Two patients had repeat surgery after temporary removal of uni- or bilateral implants secondary to infection. Overall, 86 DBS electrodes were implanted. In 97% of the implantations, at least three microelectrodes were inserted simultaneously for MER and test stimulation. Initial anatomical targeting was based on stereotactic atlas coordinates and individual adaptation by direct visualisation of the Gpi on the stereotactic T2 or inversion-recovery MR images. The permanent electrode was placed according to the results of MER and test stimulations for adverse effects. FINDINGS: The average improvement from baseline in clinical ratings using either the Burke-Fahn-Marsden-Dystonia (BFMDRS) or Toronto-Western-Spasmodic-Torticollis (TWSTR) rating scale at the last post-operative follow-up (mean 16.4 ; range 3-48 months) was 64.72% (range 20.39 to 98.52%). The post-operative MRI showed asymptomatic infarctions of the corpus caudatus in three patients and asymptomatic small haemorrhages in the lateral basal ganglia in two patients. One patient died due to a recurrent haemorrhage which occurred three months after the operation. The electrodes were implanted as follows: central trajectory in 64%, medial trajectory in 20%, anterior in 9% and lateral dorsal trajectories in 3.5% each. The reduction in BFMDRS or TWSTR motor score did not differ between the group implanted in the anatomically defined (central) trajectory bilateral (-64.15%, SD 23.8) and the physiologically adopted target (uni- or bilateral) (-63.39%, SD 23.1) indicating that in both groups equally effective positions were chosen within Gpi for chronic stimulation (t-test, p > 0.4). CONCLUSIONS: The described technique using stereotactic MRI for planning of the trajectory and direct visualisation of the target, intra-operative MER for delineating the boundaries of the target and macrostimulation for probing the distance to the internal capsule by identifying the threshold for stimulation induced tetanic contractions is effective in DBS electrode implantation in patients with dystonia operated under general anaesthesia. The central trajectory was chosen in only 64%, despite individual adaptation of the target due to direct visualisation of the Gpi in inversion recovery MRI in 43% of the patients, demonstrating the necessity of combining anatomical with neurophysiological information.

Deep brain stimulation in the subthalamic area is more effective than nucleus ventralis intermedius stimulation for bilateral intention tremor.

BACKGROUND: The ventro-lateral thalamus is the stereotactic target of choice for severe intention tremor. Nevertheless, the optimal target area has remained controversial, and targeting of the subthalamic area has been suggested to be superior. PATIENTS AND METHODS: Eleven patients with disabling intention tremor of different etiology (essential tremor (n = 8), multiple sclerosis (n = 2) and one with, spinocerebellar ataxia) were implanted bilaterally with DBS electrodes targeted to the ventro-lateral thalamus using micro-recording and micro-stimulation. Among five tracks explored in parallel optimal tracks were chosen for permanent electrode implantation. Postoperative tremor suppression elicited by individual electrode contacts was quantified using a lateralised tremor rating scale at least 3 months (in most patients >1 year) after implantation. The position of electrode contacts was determined retrospectively from stereotactic X-ray exams and by correlation of pre- and postoperative MRI. RESULTS: In all patients, DBS suppressed intention tremor markedly. On average, tremor on the left and right side of the body was improved by 68% (+/-19; standard deviation) and 73% (+/-21), respectively. In most patients, distal electrode contacts located in the subthalamic area proved to be more effective than proximal contacts in the ventro-lateral thalamus. In stereotactic coordinates, the optimal site was located 12.7 mm (+/-1.4; mean +/- standard deviation) lateral, 7.0 (+/-1.6) mm posterior, and 1.5 (+/-2.0) mm ventral to the mid-commissural point. In general, the best contacts could be selected for permanent stimulation. Nevertheless, in some instances, more proximal contacts had to be chosen because of adverse effects (paraesthesiae, dysarthria, gait ataxia) which were more pronounced with bilateral stimulation resulting in slightly less tremor suppression on the left and right side of body (63 +/- 18 and 68 +/- 19%, respectively). CONCLUSION: Direct comparison of different stimulation sites in individual patients revealed that DBS in the subthalamic area is more effective in suppressing pharmacoresistant intention tremor than the ventro-lateral thalamus proper. Anatomical structures possibly involved in tremor suppression include cerebello-thalamic projections, the prelemniscal radiation, and the zona incerta.

Inhibition of rat liver RNA polymerases by action of the methylating agents dimethylnitrosamine in vivo and methyl methanesulfonate in vitro.

Dimethylnitrosamine maximally inhibits rat liver nuclear RNA synthesis by 50% at a dose of 40 mg/kg of body weight. The inhibition develops during the first 4 hr and persists through the 12th hr. All parenchymal cells of the lever lobule seem to be affected. The decreased RNA synthesis can be accounted for entirely by an inhibition of the RNA polymerase activities quantitatively solubilized and partially purified. A similar inhibition of the polymerase activities was demonstrated in the intact nuclei by inactivating the endogenous template with actinomycin D and assaying the polymerases with an added exogenous template, poly(deoxy-adenylate-deoxythymidylate). Chromatin was prepared by two methods differing in the extent to which they remove the endogenous polymerase activity. Each preparation was transcribed with either added Escherichia coli or partially purified rat liver nucleoplasmic RNA polymerase. With either polymerase or chromatin preparation, no inhibition of the template activity of liver nuclear chromatin isolated from the DMN-treated animals was detected. A similar mechanism of inhibition of RNA synthesis was produced by the action of the methylating agent methyl methanesulfonate on whole nuclei in vitro. The dose-dependent inhibition of RNA synthesis could be accounted for by an inhibition of the RNA polymerase activities quantitatively solubilized and partially purified from the affected nuclei. Chromatin prepared from the methyl methanesulfonate-treated nuclei had a normal template capacity with either E. coli or rat liver nucleoplasmic RNA polymerase. No preferential methylation of the RNA polymerases by [14C]methyl methanesulfonate could be demonstrated. It is concluded that the action of the two methylating agents on RNA metabolism is similar and that the inhibition of liver nuclear RNA synthesis results from inactivation of the RNA polymerases. At the same time, dimethylnitrosamine and methyl methanesulfonate leave the chromatin template intact, at least quantitatively, for the synthesis of RNA. The implications of such an effect on RNA synthesis are discussed.

N-hydroxy-2-acetylaminofluorene inhibition of rat live RNA polymerases.

Administration of N-hydroxy-2-acetylaminofluorene (N-OH-AAF) to rats inhibits liver nuclear RNA synthesis. This effect is reflected in an in vitro inhibition of RNA synthesis by isolated whole nuclei. The decreased RNA synthesis can be accounted for entirely by an inhibition of the RNA polymerase activities quantitatively solubilized and partially purified from these nuclei. Both nucleolar and nucleoplasmic polymerases are affected. A similar inhibition of the polymerases was demonstrated in intact nuclei by inactivating the endogenous template with actinomycin D and assaying the polymerases with an added exogenous template, poly(deoxyadenylate-deoxythymidylate). Chromatin was prepared from similar nuclear preparations by two methods, differing in the extent to which they remove endogenous polymerase activity. Each chromatin preparation was transcribed with added Escherichia coli or partially purified rat liver nucleoplasmic RNA polymerase respectively. With either polymerase and either chromatin preparation, no inhibition of the template activity of chromatin isolated from N-OH-AAF-treated animals could be detected. It is concluded that N-OH-AAF is a potent inhibitor of rat liver nuclear RNA synthesis and that the mechanism of this inhibition is inactivation of the RNA polymerases. At the same time, N-OH-AAF leaves the chromatin template, at least quantitatively, intact for the synthesis of RNA. The implications of such an effect of N-OH-AAF on RNA synthesis are discussed.

Trabectedin Followed by Irinotecan Can Stabilize Disease in Advanced Translocation-Positive Sarcomas with Acceptable Toxicity.

Background. Preclinical data indicate that trabectedin followed by irinotecan has strong synergistic effects on Ewing sarcoma. This is presumably due to hypersensitization of the tumor cells to the camptothecin as an effect of trabectedin in addition to synergistic suppression of EWS-FLI1 downstream targets. A strong effect was also reported in a human rhabdomyosarcoma xenograft. Procedure. Twelve patients with end-stage refractory translocation-positive sarcomas were treated with trabectedin followed by irinotecan within a compassionate use program. Eight patients had Ewing sarcoma and four patients had other translocation-positive sarcomas. Results. Three-month survival rate was 0.75 after the start of this therapy. One patient achieved a partial response according to RECIST criteria, five had stable disease, and the remaining six progressed through therapy. The majority of patients experienced significant hematological toxicity (grades 3 and 4). Reversible liver toxicity and diarrhea also occurred. Conclusions. Our experience with the combination of trabectedin followed with irinotecan in patients with advanced sarcomas showed promising results in controlling refractory solid tumors. While the hematological toxicity was significant, it was reversible. Quality of life during therapy was maintained. These observations encourage a larger clinical trial.

Serum lipoprotein and apolipoprotein profiles of the genetically obese ob/ob mouse.

The lipid transport system of 3-month-old male C57BL/6J obese (ob/ob) mice was investigated. Serum lipoproteins were separated by density gradient ultracentrifugation and characterized by their chemical and electrophoretic properties as well as their relative apolipoprotein contents, defined according to molecular weight and charge. Obese, ob/ob mice exhibited a marked hyperlipoproteinemia resulting from large increases in low-density lipoproteins (LDL, d 1.021-1.058 g/ml) and high-density lipoproteins (HDL, d 1.058-1.137 g/ml), particularly, the HDL2 subclass (d 1.058-1.109 g/ml). This increase in lipoproteins was entirely responsible for their hypercholesterolemia and hyperphospholipidemia. By contrast, these obese mice had a net decrease in very-low-density lipoproteins (VLDL, d less than 1.016 g/ml) and intermediate-density lipoproteins (IDL, d 1.016-1.021 g/ml), which accounted for their moderate hypotriglyceridemia. The chemical composition of heterogeneous light LDL (d 1.021-1.040 g/ml and dense LDL (d 1.040-1.058 g/ml) overlapped by HDL-like particles was highly modified. These modifications consisted of increases in the percentages of cholesteryl ester and phospholipid and decreases in that of triacylglycerol. There were also marked changes in the relative values of the apolipoproteins of VLDL, but principally, IDL and LDL. IDL and light LDL were poorer in apolipoproteins BH (Mr 340,000-320,000) and eventually in apolipoprotein BL (Mr 220,000-200,000) and enriched in apolipoproteins E (Mr 37,000-35,000) and C-A-II (Mr approximately equal to 12,000). A similar and very significant change occurred in VLDL for both the apolipoproteins BL and C-A-II. Dense LDL, mainly poorer in apolipoprotein BH and enriched in apolipoprotein A-I (Mr 28,000-27,000), closely resembled HDL2 in all the groups, and were enriched in apolipoproteins C-A-II in only the obese mice. We suggest that ob/ob mice are probably protected against atheromata because of the low VLDL and IDL levels, and the increase in HDL2.

Effect of propofol anesthesia on pallidal neuronal discharges in generalized dystonia.

We present the results of continuous microelectrode recordings from individual pallidal neurons in patients with idiopathic torsion dystonia under different levels of propofol anesthesia. Neither the estimated plasma concentration of propofol nor the level of consciousness had a consistent effect on abnormally low neuronal firing rates. Our data support the pathophysiological model of a decreased basal ganglia output in dystonia and argue against a possible pharmacological artifact.

Deep brain stimulation for idiopathic or secondary movement disorders.

Deep brain stimulation has gained increasing interest in the treatment of movement disorders. Presenting our clinical series of 179 patients operated upon since 1999, the indications, risks and benefits for the patients are discussed in order to further improve the techniques and their applications.

Provider-patient communication and metabolic control.

OBJECTIVE: To determine whether nurses' and NIDDM patients' communication styles during consultations are related to subsequent metabolic control and to examine factors influencing patterns of communication in these consultations. RESEARCH DESIGN AND METHODS: A total of 47 NIDDM patients participated in the study and completed the following procedures: 1) assessment of baseline HbA1, 2) attended 3.5 days of diabetes education, 3) returned in 1 mo for a follow-up consultation with a nurse, and (4) returned in 9-12 wk for a follow-up HbA1 assessment. The communication variables coded from the consultations were the frequency with which nurses produced controlling, informative, and patient-centered utterances and the frequency with which patients sought information, engaged in decision making, and expressed negative affect. RESULTS: The results were as follows: 1) patients experienced poorer metabolic control after interacting with nurses who were more controlling and directive in their communication with patients (r = 0.39, P < 0.01); 2) the nurses' use of patient-centered responses was directly related to the degree to which patients expressed feelings (r = 0.34, P < 0.01) and exhibited decision-making behavior (r = 0.62, P < 0.01); and 3) several of the nurses' and patients' communicative behaviors were related to patient characteristics such as age, sex, education, and baseline HbA1 levels. CONCLUSIONS: The results suggest that providers' attempts to exert considerable control during consultations with NIDDM patients may be counterproductive and contribute to poorer outcomes. The findings also indicate that patient-centered behaviors (e.g., encouraging the patient's involvement, respecting the patient's opinion, and offering support) facilitate the patient's ability to be an active participant in the consultation.

Reduced cerebrovascular CO(2) reactivity in CADASIL: A transcranial Doppler sonography study.

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukencephalopathy (CADASIL) is a hereditary angiopathy caused by mutations in Notch3. Cerebral microvessels show an accumulation of granular osmiophilic material in the vicinity of degenerating vascular smooth muscle cells. To study cerebrovascular function in CADASIL, we performed measurements on cerebral hemodynamics by using transcranial Doppler sonography. METHODS: Middle cerebral artery (MCA) mean blood flow velocity (MFV), cerebrovascular CO(2) reactivity, and the resistance index were measured by bilateral transcranial Doppler sonography in 29 CADASIL individuals (mean age, 49.0+/-2.4 years) and an equal number of age- and sex-matched control subjects. RESULTS: Compared with control subjects, CO(2) reactivity was reduced in CADASIL (33.4+/-2.7% versus 45.3+/-3.0%; P:<0.01). This difference remained significant when only nondisabled CADASIL individuals (Rankin=0, n=21) were included in the analysis (P:<0.05). CO(2) reactivity was significantly lower in disabled than in nondisabled CADASIL individuals (24.5+/-2.7% versus 36.8+/-3.4%; P:<0.05). MCA MFV was reduced in CADASIL (45.6+/-2.2 cm/s versus 54.2+/-2.4 cm/s; P:<0.05) and correlated negatively with age both in affected individuals (r=-0.314; P:<0.05) and control subjects (r=-0.339; P:<0.05). Resistance index was not significantly altered (59.0+/-1.0% versus 57.7+/-1.2%; P:=0.42). CONCLUSIONS: In CADASIL, there is a reduction of both CO(2) reactivity and basal MCA MFV. The reduced CO(2) reactivity suggests functional impairment of cerebral vasoreactivity probably related to vascular smooth muscle cell dysfunction. The reduction of CO(2) reactivity in nondisabled CADASIL individuals suggests an early role of impaired cerebral vasoreactivity in the evolution of the disease.

Differences in platelet monoamine oxidase activity in subgroups of schizophrenic and depressive disorders.

Platelet monoamine oxidase (MAO) activity was measured in patients with nonaffective schizophrenic disorders (i.e., without prominent symptoms of depressions or manias), and in patients with schizophrenia-related depressions. MAO activity was significantly lower than control values in a subgroup of 16 patients with nonaffective schizophrenic disorders (most of whom were paranoid) characterized by the presence of auditory hallucinations and delusions. Platelet MAO activity was not reduced in 16 other nonaffective schizophrenic patients without auditory hallucinations. Platelet MAO activity was significantly higher than control values in a group of 8 depressed patients with schizophrenia-related depressions characterized by the presence of chronic asocial, eccentric, or bizarre behavior. These findings of differences in platelet MAO activity in clinically defined subgroups of nonaffective schizophrenic disorders and the schizophrenia-related depressive disorders may help to account for some of the discrepancies in findings among the various studies of platelet MAO activity in schizophrenic and affective disorders.