Oxidative DNA damage in reconstituting T cells is associated with relapse and inferior survival after allo-SCT.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the only curative treatment option for a number of hematologic malignancies. Its therapeutic potential relies on the potency of donor T cells to eliminate residual malignant cells, the so-called graft-versus-leukemia (GVL) effect. Disease relapse remains the most frequent treatment failure and is associated with poor outcome. Therefore, it is inevitable to decipher mechanisms that weaken GVL. In recent years, studies of tumor biology have revealed that metabolic remodeling of the micromilieu can critically regulate immune responses. Accumulation of reactive oxygen species leads to a metabolic condition known as oxidative stress, which can severely hamper T cells. Currently, only a few studies, mainly using preclinical models, have demonstrated the occurrence of oxidative stress after allo-SCTs. Therefore, we sought to investigate oxidative stress in a well-characterized group of patients who underwent allo-SCT and its impact on reconstituting T cells. We identified high concentrations of serum 8-hydroxydeoxyguanosine (8-OHdG) as an established biomarker for oxidative stress. 8-OHdG is one of the major products of DNA oxidation, which is normally rapidly removed. After allo-SCT, T cells accumulated oxidative DNA damage. High cellular 8-OHdG content (8-OHdGhi) was associated not only with signs of enhanced T-cell activation but also premature exhaustion. The inability of 8-OHdGhi T cells to efficiently target malignant cells or produce cytotoxic granzyme B and interferon gamma was associated with a significantly increased relapse risk and a shorter overall survival. Taken together, our novel findings could give reason to focus on bolstering DNA repair in reconstituting T cells as a means to improve GVL efficacy.

Prevalence of disorders in preweaned dairy calves from 731 dairies in Germany: A cross-sectional study.

The objective of this cross-sectional study was to determine the prevalence of disorders in preweaned calves in 3 regions in Germany, exemplary for structural diversity in dairy farming. A farm visit was performed on a single occasion on 731 dairy farms in the northern, eastern, and southern regions of Germany between December 2016 and July 2019. Farms differed in herd size, geographical location, and management. In the northern region, the farms had a median of 90 milking cows and were often run as full-time family businesses, partly with external workers. The eastern region tended to have larger farms (a median of 251 milking cows), which were often large-scale agricultural enterprises with employees. In the southern region, the farms had a median of 39 milking cows and were often traditional family businesses, some of these being part-time businesses. Clinical examinations were performed on 14,164 preweaned dairy calves (median 12 calves per farm) by trained veterinarians. A complete data set was available for 13,656 calves. Almost half (42.0%) of the evaluated calves were classified as being affected by at least 1 of the common calf disorders. Omphalitis (O, 20.9%; n = 2,876) and diarrhea (D, 18.5%; n = 2,670) were the most frequently recorded diagnoses, whereas respiratory diseases (RD) were observed to a lesser extent (8.7%; n = 1,100). A striking feature was the fact that 7.1% (n = 987) of the calves were affected by more than 1 disorder at the same time (multimorbidity, M). The following combinations of disorders were frequently observed: O and D (n = 596), O and RD (n = 164), and D and RD (n = 140). Disorders such as O and D, as well as M, were predominantly observed in calves aged 2 wk. A gradual increase in the frequency of RD was observed with age. For all disorders except RD, male calves were more often affected than females. Omphalitis was predominantly diagnosed in the summer months, whereas RD, D, and M were more common in the fall. We detected several statistically significant differences in the prevalence of clinical signs and disorders in preweaned dairy calves between the 3 exemplary regions. The prevalence of RD was higher in the south (10.8%) than in the north (8.2%) and east (7.4%). In the north (33.2%), O was observed more frequently than in the other regions (east: 18.9%; south: 10.5%), whereas D was found less frequently in the north (13.8%) than in the east (21.6%) and south (20.0%).

[Nasal, pulmonary, and abomasal aspergillosis (Aspergillus fumigatus) in a calf]. / Nasale, pulmonale und abomasale Aspergillose (Aspergillus fumigatus) bei einem Kalb.

This study presents a case of nasal aspergillosis in a 17-days old calf (German Fleckvieh): it had been admitted moribund to the Clinic for Ruminants of the University of Munich, and died after a short time. Pathologically, the calf was diagnosed with purulent-necrotizing rhinitis, necrotizing pneumonia, and diphtheroid-necrotizing abomasitis. Histologically, fungal elements were found in all the localizations mentioned before, and mycologically, Aspergillus fumigatus was cultured from nasal cavity. Pathogenesis is discussed.

[Squamous cell carcinomas of the ear: factors of gravity and surgical treatment, about 30 cases]. / Carcinomes spinocellulaires de l'oreille : facteurs de gravité et traitement chirurgical, à propos de 30 cas.

INTRODUCTION: Squamous cell carcinomas (SCC) of the ear are known for their aggressiveness. The aim of this study was to investigate factors of gravity while freeing the therapeutic requirements. PATIENTS AND METHODS: This is a retrospective study of 28 patients (30 ears) operated for SCC. The characteristics of the lesion, the presence of metastasis, treatment modalities and histologic findings were collected. Local recurrences and metastasis are identified with a mean follow-up time of 37months (17-110months). RESULTS: The lesion size was less than 2cm in 19 cases (63.3%) and greater than or equal to 2cm in 11 cases (36.7%). Macroscopic resection margins were 5, 7 or 10mm. The resections were histologically incomplete in 4 cases (13%) requiring further surgery. Six cases had local recurrence (20%): three with pulmonary or lymph node metastases (10%) and one death (3.3%). In these 6 cases of recurrence, the surgical margins were 6.3mm on average, the initial lesion measured always greater than 2cm (100%). Three quarters of incomplete resections have recurrent despite a surgical revision in healthy margin. CONCLUSION: Our study confirms the data of literature, namely the pejorative character of a lesion greater than 2cm and incomplete resection. The HAS recommendations seem minimal regarding the ear. In case of injury by more than 2cm and with a proximal location on the ear pinna, only amputation of the ear allows satisfactory cancer control.

Setaria tundra in a roe deer (Capreolus capreolus) in the Donau-Ries district of Bavaria, Germany.

INTRODUCTION: Setaria tundra is known as a common parasite of sylvatic ungulates in Northern latitudes. Although mostly considered of low pathogenicity, severe disease outbreaks and remarkable economic losses have been observed in reindeer (Rangifer tarandus tarandus). Host density and climatic factors are major drivers of the expansion of Setaria spp. facilitating their development and spread. Five adult specimens of S. tundra were retrieved from a male roe deer in Bavaria, Germany. Deoxyribonucleic acid (DNA) barcoding confirmed morphological identification. Cyclooxygenase 1 gene sequences showed 98,73-99,68 % similarity to sequences of other S. tundra specimens found in deer (Cervidae) and mosquitoes (Culicidae). The results raise awareness for the presence of S. tundra in a hitherto unkown endemic region and represent a starting point for broader investigations to understand the biology and distribution of this parasite in roe deer as well as other potential definitive hosts.

INTRODUCTION: Setaria toundra est connu comme un parasite commun des ongulés sylvatiques aux latitudes septentrionales. Bien que généralement considéré comme faiblement pathogène, de graves épidémies et des pertes économiques significatives ont été observées chez le renne (Rangifer tarandus tarandus). La densité d'hôtes et les facteurs climatiques sont les principaux moteurs de l'expansion de Setaria spp., facilitant leur développement et leur diffusion. Cinq spécimens adultes de S. toundra ont été récupérés sur un chevreuil mâle en Bavière, en Allemagne. Le séquençage de l'acide désoxyribonucléique (ADN) a confirmé l'identification morphologique. Les séquences du gène de la cyclooxygénase 1 ont montré une similarité de 98,73 à 99,68 % avec les séquences d'autres spécimens de S. toundra trouvés chez les cerfs (Cervidae) et les moustiques (Culicidae). Les résultats sensibilisent à la présence de S. toundra dans une région endémique jusqu'alors inconnue et représentent un point de départ pour des investigations plus larges pour comprendre la biologie et la distribution de ce parasite chez le chevreuil ainsi que d'autres hôtes définitifs potentiels.

CD137 (4-1BB) stimulation leads to metabolic and functional reprogramming of human monocytes/macrophages enhancing their tumoricidal activity.

Immunotherapies have heralded a new era in the cancer treatment. In addition to checkpoint inhibitors, agonistic antibodies against co-stimulatory immune receptors hold the potential to invoke efficient antitumor immunity. Targeting CD137 has gained momentum based on its ability to drive NK- and T-cell-based responses. CD137-engaging mAbs have already entered clinical trials for different types of tumors showing promising results. Despite the efforts to translate CD137-mediated immunotherapy into clinical practice, little remains known regarding the role of CD137 in human monocytes/macrophages.We found CD137 being expressed on monocytes of healthy controls and at even higher levels in patients with multiple myeloma or CLL. CD137HI(GH) monocytes displayed a distinct phenotypic, transcriptomic, and metabolic profile. They possessed an increased phagocytic capacity enabling superior antibody-dependent phagocytosis (ADPC) of multiple myeloma and lymphoma cells that were treated with anti-CD38 or anti-CD20 mAbs. Triggering CD137 promoted both metabolic and tumoricidal activity in an extracellular signal-regulated kinase (ERK)-dependent fashion. In addition, we observed a phenotypic, transcriptomic, and functional skewing towards a M1-like phenotype.Overall, we introduce CD137 as a positive immune checkpoint on human monocytes/macrophages, which can have therapeutic implications especially in view of synergistic effects when combining CD137 agonists with tumor-targeting antibodies.

[Sports-related carotid artery dissection]. / Karotisdissektionen nach Sport.

Sports-related carotid artery dissection are very rare and were described in different kinds of sports. We report on a 45-year old man who suffered bilateral brain infarctions caused by bilateral extracranial internal carotid artery dissection after excessive weight lifting in a gym. As possible trigger factors for the dissections we assumed the abrupt extension of the neck during weight lifting and the frequent Valsalva manoeuvers with massive rise in the pressure in the carotid artery system. The patient underwent angioplasty and stenting of the stenosis of right carotid artery, the primarily occluded left carotid artery recanalized spontaneously. Secondary prevention was established by platelet aggregation inhibitors. The patient recovered completely. The pathogenesis of sports-related dissections is multifactorial. In addition to sporting activities hereditary or acquired structural aberrations in the arterial walls could be discussed. Acute focal neurological symptoms after sport should always focus on carotid or vertebral artery dissection.

Malignant Cutaneous Peripheral Nerve Sheath Tumour with Rhabdomyosarcomatous Differentiation (Triton Tumour) in a Domestic Cat.

Divergent differentiation is encountered frequently within human malignant peripheral nerve sheath tumours (MPNSTs). The new component is often a rhabdomyosarcoma, but in animals this specific form of divergent differentiation within MPNSTs has only been reported once (in a dog). Incisional wedge biopsy of a locally extensive, ventral abdominal wall mass, which extended from the dermis to the subcutis, from a 12-year-old female domestic shorthaired cat, was performed. The tissue was examined with routine haematoxylin and eosin staining and immunohistochemical methods. A malignant neoplasm with spindle and polygonal cell components and progression towards a rhabdomyosarcomatous phenotype was observed. Both neoplastic cell populations exhibited strong expression of vimentin and there was multifocal expression of S100 and desmin. There was strong cytoplasmic labelling for α-sarcomeric actin and muscle actin and weak labelling for myoglobin within the cells positive for desmin. There was multifocal positive nuclear labelling for myogenin. Glial fibrillary acidic protein, α-smooth muscle actin, microphthalmia-associated transcription factor and melanoma antigen recognized by T cells were not expressed. Microscopical features, aided by immunohistochemistry, identified a MPNST with progression towards a rhabdomyosarcomatous phenotype, a so-called 'triton tumour'. A Schwann cell component could account for the divergent patterns of growth, given the plasticity of the neural crest. Nerve sheath tumours have been reported in the skin and subcutis of cats and are a differential diagnosis of feline cutaneous spindle cell neoplasms.

Clinicopathologic Features and Magnetic Resonance Imaging Findings in 24 Cats With Histopathologically Confirmed Neurologic Feline Infectious Peritonitis.

BACKGROUND: Feline infectious peritonitis (FIP) is the most common infectious central nervous system (CNS) disease in the cat and is invariably fatal. Improved means of antemortem diagnosis is required to facilitate clinical decision making. Information regarding the magnetic resonance imaging (MRI) findings of neurologic FIP currently is limited, resulting in the need for better descriptions to optimize its use as a diagnostic tool. OBJECTIVE: To describe the clinicopathologic features and MRI findings in cases of confirmed neurologic FIP. ANIMALS: Twenty-four client-owned cats with histopathologic confirmation of neurologic FIP. METHODS: Archived records from 5 institutions were retrospectively reviewed to identify cases with confirmed neurologic FIP that had undergone antemortem MRI of the CNS. Signalment, clinicopathologic, MRI, and histopathologic findings were evaluated. RESULTS: Three distinct clinical syndromes were identified: T3-L3 myelopathy (3), central vestibular syndrome (7), and multifocal CNS disease (14). Magnetic resonance imaging abnormalities were detected in all cases, including meningeal contrast enhancement (22), ependymal contrast enhancement (20), ventriculomegaly (20), syringomyelia (17), and foramen magnum herniation (14). Cerebrospinal fluid was analysed in 11 cases; all demonstrated a marked increase in total protein concentration and total nucleated cell count. All 24 cats were euthanized with a median survival time of 14 days (range, 2-115) from onset of clinical signs. Histopathologic analysis identified perivascular pyogranulomatous infiltrates, lymphoplasmacytic infiltrates, or both affecting the leptomeninges (16), choroid plexuses (16), and periventricular parenchyma (13). CONCLUSIONS AND CLINICAL IMPORTANCE: Magnetic resonance imaging is a sensitive means of detecting neurologic FIP, particularly in combination with a compatible signalment, clinical presentation, and CSF analysis.

Retrospective evaluation of COX-2 expression, histological and clinical factors as prognostic indicators in dogs with renal cell carcinomas undergoing nephrectomy.

Limited veterinary literature is available regarding prognostic markers for canine renal cell carcinoma (CRCC). We retrospectively evaluated COX-2 expression, histological and clinical features associated with prognosis of CRCC. Sixty-four cases post-nephrectomy were included, 54 had histopathological assessment and 30 had COX-2 immunostaining performed. Eight dogs (13%) had metastatic disease at initial diagnosis. Twenty-seven dogs (42%) received adjuvant therapy after nephrectomy. On univariate analysis, COX-2 expression, mitotic index (MI), histologic type, vascular invasion, neoplastic invasiveness and metastasis at diagnosis were significantly associated with overall median survival time (MST). COX-2 score (COX-2 score > 3 MST 420 days versus 1176 days if COX-2 score <3; P = 0.011) and MI (MI > 30 MST 120 days versus 540 days for MI < 30; P = 0.003) were the only variables associated with CRCC outcome on multivariate analysis. The addition of MI and COX-2 immunostaining to standard histopathological evaluation would help predicting outcome in CRCC patients.

WITHDRAWN: Clinical Signs, Neuroanatomical Distribution and Histopathological Characterisation of Meningoencephalitis in Wild Red Foxes (Vulpes vulpes) Associated with a Novel fox Circovirus.

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Existence of bovine neonatal pancytopenia before the year 2005? Retrospective evaluation of 215 cases of haemorrhagic diathesis in cattle.

Haemorrhagic diathesis (HD) in cattle is a relatively rare syndrome that can have many different causes. With the occurrence of bovine neonatal pancytopenia (BNP) in 2007, the number of cases of HD in cattle has increased. This led to an enhanced interest in diseases presenting with bleeding disorders. The possible causes of HD in cattle, the clinical findings, and the course of various diseases are described and evaluated. Furthermore, we determined whether cases of BNP occurred before the introduction of the vaccine Pregsure BVD since its widespread use was associated with the syndrome. Records of 215 cases of HD in cattle that had been referred to the Clinic for Ruminants with Ambulatory and Herd Health Services at the Centre for Clinical Veterinary Medicine, Ludwig Maximilian University, Munich, between 1982 and 2014 were evaluated. The two most commonly diagnosed diseases were BNP (n = 95) and septicaemia (n = 35), with fatality rates of 82% and 66%, respectively. In 27 (13%) cases, no clear cause for the HD could be designated. Statistically significant differences were found with regard to the course of the various disorders and the clinical findings. A receiver operating characteristic analysis of thrombocyte counts of affected animals at the time of arrival at the clinic did not provide any predictive information on disease outcome. Two cases of HD occurred before the introduction of Pregsure BVD (1989, 1991). In both cases, clinical, haematological, and pathological findings were identical to BNP. The cause of HD in these two cases could not be determined retrospectively.

Analysis of adenovirus gene transfer into adult neural stem cells.

Adult neural stem cells (aNSCs) represent an attractive source for the production of specific types of neurons in degenerative CNS diseases and for the development of new regenerative gene therapies. However, the use of adult NSCs for transplantation and gene replacement strategies requires efficient gene expression in the cells. Due to the low pathogenicity of adenovirus (Ad) for humans, its large delivery capacity, and long-term transgene expression, Ad vectors are widely used. Here, we tested the potential of the Ad vector system to transduce adult NSCs. Analysis of Ad receptor expression in primary aNSCs revealed a complete lack of the coxsackie-adenovirus receptor and no or low expression of alphanu- and beta5-integrins, respectively, on mRNA and protein level. Consistently, transduction at different multiplicities of infection using an Ad vector expressing the enhanced green fluorescent protein (GFP) showed that adult NSCs are particularly resistant to Ad infection even at highest MOI (1000) in contrast to differentiated types of neural cells.

Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial.

BACKGROUND: Omega3 fatty acids may inhibit neuronal signal transduction pathways in a manner similar to that of lithium carbonate and valproate, 2 effective treatments for bipolar disorder. The present study was performed to examine whether omega3 fatty acids also exhibit mood-stabilizing properties in bipolar disorder. METHODS: A 4-month, double-blind, placebo-controlled study, comparing omega3 fatty acids (9.6 g/d) vs placebo (olive oil), in addition to usual treatment, in 30 patients with bipolar disorder. RESULTS: A Kaplan-Meier survival analysis of the cohort found that the omega3 fatty acid patient group had a significantly longer period of remission than the placebo group (P = .002; Mantel-Cox). In addition, for nearly every other outcome measure, the omega3 fatty acid group performed better than the placebo group. CONCLUSION: Omega3 fatty acids were well tolerated and improved the short-term course of illness in this preliminary study of patients with bipolar disorder.

Experimental analysis of the mechanical behavior of the viscoelastic porcine pancreas and preliminary case study on the human pancreas.

The aim of this article is to study the mechanical properties of the pancreas. Up to now, the mechanical properties of the pancreas are not sufficiently characterized. The possibility of intraoperative mechanical testing of pathological pancreata will allow the classification of pancreatic diseases in the future. The application of mechanical parameters instead of the intraoperative frozen section analysis shortens waiting times in the operating room. This study proves the general applicability of shear rheology for the determination of the mechanical properties of pancreas and the assessment of graft quality for transplantation. Porcine and human pancreas samples were examined ex vivo and a nonlinear viscoelastic behavior was observed. Pancreas was found to be more viscous than liver but both abdominal organs showed a similar flow behavior. The shear deformation dependence of healthy human pancreas was similar to porcine pancreas. An increase in the post-mortem time led to an increase in the complex modulus for a post-mortem time up to 8.5 days. Histological investigations showed that an increased amount of collagen coincides with the stiffening of the pancreatic tissue.

Thermal properties of human skin related to nondestructive measurement of epidermal thickness.

The thermal and physical properties of skin are reviewed briefly in the light of their relationship to skin functions and their influence on temperature measurement and related methodology. Thermal conductivity and epidermal thickness have a direct bearing on the majority of skin functions as these significantly affect heating rates, thermal pain thresholds, and blister formation, as will be seen from the experimental data. The accumulated data on both temperature and pain threshold are used to estimate epidermal thickness in the intact individual. The procedure to accomplish this end utilizes the measured thermal pain threshold, surface temperature, exposure time, and incident energy on a standardized skin site (volar surface of the forearm) to obtain conductivity values. These values are then used in a two-layer system heat flow equation to determine epidermal thickness in other skin sites (fingers) referred to the standard area. Systematic exposures to various materials at high temperatures in contact-burn studies provide data for checking the reliability of this procedure by alternative computations and comparison with predicted tissue temperatures derived from earlier work. Certainly, blister formation and physical measurement of the excised epidermis would provide direct verification of the accuracy of the procedure but these measures have not been undertaken. It is quite possible that over a period of time verification data could be accumulated incidentally in the clinic where skin grafting procedures are carried out. For this purpose only relatively simple measurements of skin temperature and pain threshold, as described herein, would be required to be performed on skin graft donors to provide epidermal thickness measurements for comparison with direct measurements of excised skin immediately after removal.

Alterations in parathyroid dynamics in lithium-treated subjects.

Chronic lithium (Li) therapy, used extensively in the treatment of bipolar affective disorders, is one of psychiatry's most effective treatments. The data on the effects of Li on baseline PTH and calcium (Ca) levels are conflicting. A clear resetting of the PTH set-point to the right was documented in vitro; however, the effect of Li on the Ca-PTH axis has not been rigorously studied in vivo. In this study, we used a Ca and citrate infusion protocol to fully characterize PTH dynamics in seven female patients, 40 +/- 11 yr old, on chronic Li therapy for 5.23 +/- 4.0 yr, compared with seven controls, 41 +/- 16 yr old (mean +/- SD). Baseline ionized Ca (Cai) and intact PTH levels were 5.2 +/- 0.06 mg/dL and 38.4 +/- 5.7 pg/mL in the Li group and 4.9 +/- 0.06 mg/dL and 21.2 +/- 5.0 pg/mL in the controls, (mean +/- SEM) P = 0.008 and 0.042, respectively. We defined an inverse sigmoidal curve between Cai and the intact biologically active PTH molecule (iPTH) for the two study groups and demonstrated a significant shift in the iPTH set-point to the right in the Li-treated patients, compared with controls. The set-point was 5.08 +/- 0.04 for the former group and 4.88 +/- 0.04 mg/dL for the latter, P = 0.004. Patients on Li had significantly higher Cai levels during citrate and Ca infusions, P = 0.0008 and 0.012, respectively; however, iPTH levels were not significantly different between the two study groups during either infusion. The shift in the iPTH set-point to the right in the Li-treated patients and the similar iPTH levels, despite higher serum Cai levels during both infusions, establish the presence of a clear alteration in PTH dynamics in patients on chronic Li therapy.

The effect of lithium on calcium-induced changes in adrenocorticotrophin levels.

The calcium receptor (CaR) plays a central role in calcium (Ca) sensing by the parathyroid gland and other organs, including the brain. Chronic lithium (Li) therapy causes a significant alteration in Ca-sensing by the CaR-expressing parathyroid chief cells through an unknown mechanism, shifting the PTH set-point (the level of Ca that half-maximally suppresses PTH secretion) to the right. Ca is known to stimulate ACTH levels in normal subjects, and baseline ACTH levels are increased in patients with bipolar disorder. Because the stimulation of ACTH secretion by Ca likely involves the CaR, the aim of this study was to investigate the effects of Li on Ca-induced changes in ACTH levels, using Ca and citrate infusions in seven Li-treated patients and seven controls. During the Ca infusion, increments in serum-ionized Ca concentration (Ca(i)) were accompanied by increments in ACTH levels that were significantly greater in the Li-treated group, P = 0.014, by ANOVA. Also, cortisol levels increased significantly in the Li-treated, but not the control group, during the Ca infusion, P < 0.0001. There was a statistically significant shift in the midpoint of the Ca(i)/ACTH curve, to the right, in the Li-treated group, compared with the controls (P = 0.042), that was largely caused by an effect of Li on Ca(i). However, for comparable levels of Ca(i), there were no significant differences in the levels of ACTH between the two groups. Therefore, within the physiological range of Ca, there was no effect of Li on Ca(i)-induced change in ACTH levels.

Erythrocyte choline concentrations in psychiatric disorders.

Erythrocyte choline has been used as a potential indirect measure of cholinergic function in the central nervous system (CNS). We review the literature and present some new data on erythrocyte choline concentrations in patients with neuropsychiatric disorders. Our data and most of the reviewed studies report modest elevations in mean erythrocyte choline values in patients with affective illnesses, psychoses, dementia, and other neuropsychiatric disorders when compared to controls. Within each disorder, the increased mean erythrocyte choline concentrations are due to subgroups of patients with especially high values. These subgroups of patients with elevated erythrocyte choline levels appear to have clinical characteristics that distinguish them from patients with normal choline values. Finally, the dramatic rise in erythrocyte choline concentration produced by lithium therapy is reviewed, and the implication of this effect, in particular, the possibility that pretreatment or posttreatment erythrocyte choline concentrations may predict response to lithium, is discussed.

Erythrocyte choline concentration in bipolar disorder: a predictor of clinical course and medication response.

Erythrocyte choline concentrations were measured in hospitalized patients with bipolar disorder, manic phase, and control subjects. There was a significant elevation in mean erythrocyte choline in the patients with mania. This elevation in erythrocyte choline was due to a subgroup of patients with especially high values. Significant clinical differences were apparent between the patients with "high" and those with "low" erythrocyte choline concentrations. The subgroup of manic patients with elevated erythrocyte choline had a more severe illness at admission, a worse outcome at discharge, and required significantly more neuroleptic during hospitalization than their low choline counterparts; that is, they were less likely to respond well to lithium alone. Furthermore, the bipolar patients with low erythrocyte choline concentrations, as a whole, had more than four times as many previous manic episodes than depressive episodes, while the patients with high choline values had approximately the same number of past manias and depressions. These results are discussed in light of the evidence implicating cholinergic neurotransmission in the pathophysiology of affective disorders. In addition, the design of future clinical studies of erythrocyte choline and its possible clinical utility are discussed.