Accelerated long-term forgetting in patients with acquired brain injury.

OBJECTIVE: Recent research suggests that patients with neurological disorders without overt seizures may also experience accelerated long-term forgetting (ALF). This term describes unimpaired learning and memory performance after standard retention intervals, but an excessive rate of forgetting over delays of days or weeks. The objective of this retrospective study was to investigate ALF in patients with an acquired brain injury (ABI) and to associate memory performance with executive functions. METHODS: Verbal memory performance (short-term recall, 30-min recall, 1-week recall) was assessed in 34 adult patients with ABI and compared to a healthy control group (n = 54) using an auditory word learning and memory test. RESULTS: Repeated measure analysis showed significant effects of time and group as well as interaction effects between time and group regarding recall and recognition performance. Patients with ABI had a significantly impaired 1-week recall and recognition performance compared to the healthy control group. Correlations between recall performance and executive functions were nonsignificant. DISCUSSION: Our results demonstrate that non-epileptic patients with ABI, especially patients with frontal and fronto-temporal lesions, are prone to ALF. Additionally, our data support the assumption that ALF results from a consolidation impairment since verbal recall and recognition were impaired in patients with ABI.

Bullous haemorrhagic dermatitis induced by heparins and other anticoagulants: 94 cases from French pharmacovigilance centres and a literature review.

BACKGROUND: Bullous haemorrhagic dermatitis (BHD) is an uncommon and highly particular side effect of various forms of heparins. METHODS: To better characterise the disease, we collected all cases from French Pharmacovigilance centres recorded over a 20-year period (37 cases) and performed a Medline literature search up to June 2020 (57 cases). RESULTS: In all, 94 patients were identified (male/female ratio: 2.2) of mean age 73.5±12.1 years (31-94). Patients were treated with enoxaparin (n=66), unfractionated heparin (n=11), fondaparinux (n=10), tinzaparin (n=4), bemiparin (n=1), reviparin (n=1), dalteparin (n=1), and 4 with other anticoagulants: warfarin (n=3) and rivaroxaban (n=1). All cases presented with 1 to more than 100 haemorrhagic vesicles and bullae, distant from the injection sites, located mainly on the lower (75%) or upper limbs (69%). The lesions were asymptomatic, except in 5 patients who had pruritic or painful lesions. The interval between treatment initiation and BHD ranged from 6 hours to 30 days (mean: 8.4±7 days). Biopsy (n=53) showed intraepidermal or subcorneal cavity with red cells (n=39) or junctional blisters (n=10), with eosinophilic infiltrate only rarely. Direct immuno-fluorescence was negative in 19/20 cases and indirect immunofluorescence was negative in 8/8. The outcome was favourable in all cases, including in 12 patients for whom heparin was maintained. A 93-year-old patient died of compressive haematomas unrelated to BHD. We found 5 cases similar to BHD due to other anticoagulants. DISCUSSION: This is the largest comprehensive series of this adverse effect due to heparins or, more rarely, to other anticoagulants. Dermatologists must be aware of BHD, since this benign side effect does not necessarily require interruption of treatment. It is rare, considering the large-scale prescription of heparins, and occurs mainly in male patients aged over 70. Although the presentation is highly typical, the physiopathology is difficult to understand, as coagulation parameters are usually normal. Aging, skin fragility or mechanical factors might play a role.

[Types of pain coping in chronic pain patients]. / Typen der Schmerzverarbeitung bei Patienten mit chronischen Schmerzen.

BACKGROUND: The characterization of subtypes of chronic pain patients based on their pain coping profiles may contribute to a better understanding of the pain syndrome, to more specific indications of established treatment options as well as to further development of therapeutic interventions. OBJECTIVE: The aim of this study was to examine whether different subgroups of chronic pain patients emerge when using the German pain coping questionnaire (FESV) to identify homogeneous subgroups of pain coping patterns. Furthermore, the aim was to examine whether these pain coping subgroups differ in terms of sociodemographic characteristics, as well as pain and treatment-related aspects. MATERIAL AND METHODS: A total of 166 inpatients with a chronic pain disorder according to ICD-10 F45.41 were examined as part of the routine assessment within an interdisciplinary pain treatment program. Cognitive and behavioral pain coping and pain-related psychological impairment were measured with the FESV as components of pain coping. Using cluster analyses, homogeneous patient subgroups were generated on the basis of pain coping data. The resulting subgroups were subsequently compared regarding sociodemographic characteristics, pain-related impairment, global psychological distress, depression, anxiety, perceived stress, utilization of social support and motivation for psychotherapy. RESULTS AND CONCLUSION: The results revealed three distinct subgroups regarding pain coping patterns: (1) high impairment and high coping, (2) low impairment and high coping and (3) high impairment and low coping. The subgroups differed significantly in almost all characteristics, except for pain duration and pain intensity. The categorization into the abovementioned pain coping subtypes may assist clinicians in tailoring pain treatment to the needs and characteristics of the individual patients.

[Psychosocial stressors and pain sensitivity in chronic pain disorder with somatic and psychological factors (F45.41)]. / Psychosoziale Stressoren und Schmerzempfindlichkeit bei chronischer Schmerzstörung mit somatischen und psychischen Faktoren (F45.41).

BACKGROUND: Increased pain sensitivity is characteristic for patients with chronic pain disorder with somatic and psychological factors (F45.41). Persistent stress can induce, sustain, and intensify pain sensitivity, thereby modulating pain perception. In this context, it would be favorable to investigate which psychosocial stressors are empirically linked to pain sensitivity. OBJECTIVES: The aim of this study was to examine the relationship between psychosocial stressors and pain sensitivity in a naturalistic sample of patients with chronic pain disorder with somatic and psychological factors (F45.41). MATERIALS AND METHODS: We assessed 166 patients with chronic pain disorder with somatic and psychological factors (F45.41) at entry into an inpatient pain clinic. Pain sensitivity was measured with a pain provocation test (Algopeg) at the middle finger and earlobe. Stressors assessed were exposure to war experiences, adverse childhood experiences, illness-related inability to work, relationship problems, and potentially life-threatening accidents. Correlation analyses and structural equation modeling were used to examine which stressors showed the strongest prediction of pain sensitivity. RESULTS: Patients exhibited generally heightened pain sensitivity. Both exposure to war and illness-related inability to work showed significant bivariate correlations with pain sensitivity. In addition to age, they also predicted a further increase in pain sensitivity in the structural equation model. CONCLUSIONS: Bearing in mind the limitations of this cross-sectional study, these findings may contribute to a better understanding of the link between psychosocial stressors and pain sensitivity.

[Does hypersensitivity to multiple drugs really exist?]. / La polysensibilisation médicamenteuse systémique existe-t-elle ?

BACKGROUND: Multiple-drug hypersensitivity (MDH) in the literature concerns different entities. Our objective was to define its frequency and characteristics in patients examined for cutaneous adverse drug reaction (CADR) before studying genetic predisposition. MATERIALS AND METHODS: From a database comprising all patients referred for CADR between 2000 and 2010, we selected those meeting the following criteria: sensitisation to at least two chemically unrelated substances, as confirmed by positive skin tests or challenge tests. The following were excluded: patients with haematological diseases, HIV or chronic wounds and sensitization to the excipients. RESULTS: Of the 1925 patients included, 11 (0.6%) were classed as polysensitized: eight women and three men, of mean age 62 years, presenting 2.5 episodes of drug hypersensitivity per patient. Four cases of DRESS were noted. DISCUSSION: The strict criteria stipulated for this study enabled us to select patients with MDH, and to affirm that while it does in fact exist, it seems rare. Compared to polysensitized patients described in the literature, we preferred to distinguish between three groups of MDH: one occurring with different substances in separate episodes of CADR, one occurring with different substances during the same episode of CADR, and one occurring during DRESS and correlating with viral replication. CONCLUSION: MDH exists and genetic predisposition could be investigated by studying cytokine polymorphism in such patients. However, because of its rarity, it is impossible to rule out fortuitous association of two episodes of CADR in the same patient.

[Hyperhomocysteinemia and leg ulcers: A prospective study of 68 patients]. / Hyperhomocystéinémie et ulcères de jambes : étude prospective de 68 observations.

BACKGROUND: Homocysteine is a sulphur-containing amino acid derived from methionine. Hyperhomocysteinaemia is now recognised as an independent risk factor for occlusive arterial disease and thrombotic venous disease. The aim of this study was to determine the prevalence of hyperhomocysteinemia in patients with leg ulcers. PATIENTS AND METHODS: We prospectively investigated hospitalised patients for vascular leg ulcers between March 2008 and June 2009 at two dermatology centres. We collected details of cardiovascular disease and determined nutritional status by means of the MNA score. Fasting blood samples were taken and analyzed for homocysteine, albumin, prealbumin, folic acid, vitamin B12, creatinine and a complete blood count. RESULTS: Sixty-eight patients were enrolled in the study: 48 women and 20 men. Fifty-three percent of patients had venous leg ulcers, 18% had arterial leg ulcers and 20% had leg ulcers of mixed origin. The prevalence of hyperhomocysteinemia was 56%, with no differences according to ulcer type or gender. DISCUSSION: While the prevalence of hyperhomocysteinemia in our population of leg ulcer patients was high, this descriptive study does not allow us to establish any causal link between hyperhomocysteinemia and leg ulcers. Moreover, since the literature indicates that homocysteine-lowering therapy does not reduce cardiovascular and thromboembolic risk, there appears to be little call for further trials on hyperhomocysteinaemia and leg ulcers.

Role of a conserved retinoic acid response element in rhombomere restriction of Hoxb-1.

After activation in mesoderm and neuroectoderm, expression of the Hoxb-1 gene is progressively restricted to rhombomere (r) 4 in the hindbrain. Analysis of the chick and mouse Hoxb-1 genes identified positive and negative regulatory regions that cooperate to mediate segment-restricted expression during rhombomere formation. An enhancer generates expression extending into r3 and r5, and a repressor limits this domain to r4. The repressor contains a conserved retinoic acid response element, point mutations in which allow expression to spread into adjacent rhombomeres. Retinoids and their nuclear receptors may therefore participate in sharpening segment-restricted expression of Hoxb-1 during rhombomere boundary formation.

Temperature and moisture are minor drivers of regional-scale soil organic carbon dynamics.

Storing large amounts of organic carbon, soils are a key but uncertain component of the global carbon cycle, and accordingly, of Earth System Models (ESMs). Soil organic carbon (SOC) dynamics are regulated by a complex interplay of drivers. Climate, generally represented by temperature and moisture, is regarded as one of the fundamental controls. Here, we use 54 forest sites in Switzerland, systematically selected to span near-independent gradients in temperature and moisture, to disentangle the effects of climate, soil properties, and landform on SOC dynamics. We estimated two SOC turnover times, based on bulk soil 14C measurements (τ14C) and on a 6-month laboratory soil incubation (τi). In addition, upon incubation, we measured the 14C signature of the CO2 evolved and quantified the cumulated production of dissolved organic carbon (DOC). Our results demonstrate that τi and τ14C capture the dynamics of contrasting fractions of the SOC continuum. The 14C-based τ14C primarily reflects the dynamics of an older, stabilised pool, whereas the incubation-based τi mainly captures fresh readily available SOC. Mean site temperature did not raise as a critical driver of SOC dynamics, and site moisture was only significant for τi. However, soil pH emerged as a key control of both turnover times. The production of DOC was independent of τi and not driven by climate, but primarily by the content of clay and, secondarily by the slope of the site. At the regional scale, soil physicochemical properties and landform appear to override the effect of climate on SOC dynamics.

Similar endothelium-dependent relaxation, but enhanced contractility, of the right gastroepiploic artery as compared with the internal mammary artery.

The right gastroepiploic artery is an alternative coronary bypass graft. The excellent graft function of the internal mammary artery has been related to its physiologic properties, particularly to endothelial function. Isolated artery rings were suspended in organ chambers for recording of isometric tension. Norepinephrine and potassium chloride evoked threefold greater contractions in the gastroepiploic artery than in the mammary artery (p less than 0.01 to 0.05), whereas the sensitivity to the catecholamine was comparable. Acetylcholine induced endothelium-dependent relaxations, but the sensitivity (pD2: 6.7 +/- 0.3) and maximal relaxation (81% +/- 9%) were slightly less in the gastroepiploic artery than in the mammary artery (pD2: 7.6 +/- 0.2; 100% +/- 0%; p less than 0.05). Histamine induced endothelium-dependent relaxations with a similar sensitivity (pD2: 7.5 +/- 0.3 and 7.2 +/- 0.1), whereas the maximal relaxation was slightly enhanced in the gastroepiploic artery. The relaxation to the nitric oxide donor SIN-1 was identical in the two arteries. Thus the right gastroepiploic artery exhibits better contractility than the internal mammary artery but comparable endothelium-dependent and endothelium-independent relaxations. The good endothelial function of the gastroepiploic artery might be important for graft function and patency, whereas the enhanced contractility may facilitate vasospasm, especially in the presence of high circulating levels of catecholamines.

Determinants of early and late results of repair of atrioventricular septal (canal) defects.

The anatomic and functional characteristics of 310 consecutive patients undergoing repair of atrioventricular (AV) septal defects were studied. The characteristics of the six leaflets of the common (139 patients) or two-orifice (171 patients) AV valve are described. Interventricular communications were present in 156 patients and major associated cardiac anomalies in 73 (tetralogy of Fallot 20, double-outlet right ventricle nine, and others). Fifty-one patients (16%) died in hospital. The incremental risk of young age disappeared after 1976. Severity of preoperative AV valve incompetence and New York Heart Association (NYHA) functional class affected hospital mortality. Current risks for patients without major associated cardiac anomalies are 0.6% to 4% for patients in NYHA Class III without an interventricular communication, depending on the degree of preoperative AV valve incompetence, and 5% to 13% for such patients with an interventricular communication. Actuarial survival at 12 1/2 years postoperatively is 95% when preoperative AV valve incompetence is absent or mild and 88% when it is more severe (Grade 3, 4, or 5). Actually, 92% of hospital survivors are alive and in NYHA class I or II. Failure of the AV valve repair occurred in 32 (10%) of the 310 patients and occurred more frequently when AV valve incompetence was severe preoperatively. Its frequency is reduced by current repair techniques, except in patients without interventricular communication.

The DNA content of cerebral cortex neurons. Determinations by cytophotometry and high performance liquid chromatography.

Previous work from our laboratories has indicated that the DNA content of rat cerebral cortex neurons increases postnatally to a level of slightly above 3c, where 2c denotes the diploid DNA complement. We have re-evaluated this concept by using various cytophotometric assays and a novel high performance liquid chromatography (HPLC) technique. The latter consists of digesting the DNA in isolated neuronal nuclei by a mixture of DNA-degrading enzymes followed by analysis of the resulting deoxynucleosides by HPLC. We find that the various methods fall into two groups. The first gives evidence of a postnatal DNA (or histone) increase, while the second does not. The first group (DNA increase) comprises cytofluorometry for DNA following Schiff-type staining with fluorochromes 2,5-bis-(4-aminophenyl)-1,3,4-oxadiazole (BAO) and pararosaniline, ultraviolet absorption scanning for DNA and cytofluorometry for histones following staining with sulfaflavine at pH 8. The second group (no DNA increase) consists of cytofluorometry for DNA following staining with the DNA-complexing agents mithramycin, chromomycin A3, 4',6-diamidino-2-phenylindole (DAPI) and bisbenzimide (Hoechst 33258), as well as the newly developed HPLC technique. Since the HPLC technique measures DNA by a direct chemical approach without interference from other nuclear constituents or from higher order packaging in the chromatin, and detects at least 94-95% of the total DNA contained in neuronal nuclei independent of the developmental stage, we infer that the HPLC technique and, by consequence, the cytochemical assays of the second group reflect true DNA values. Therefore, we propose that cerebral cortex neurons retain a diploid DNA level throughout development.

The internal mammary artery 'string phenomenon'. Analysis of 10 cases.

The internal mammary artery (IMA) string sign has been described as a narrowing of IMA grafts in the late course after coronary artery bypass grafting. It has been assumed that this phenomenon was due to competitive flow in grafts connected to only mildly stenosed coronary arteries. We analyzed 10 cases of IMA string sign operated on between March 1988 and June 1991. Bilateral IMA was used in six cases and unilateral IMA in four. The mean interval between operation and reangiography was 14 +/- 11 months. String sign of the whole length of the IMA was detected in nine cases, and of the distal part between two sequential anastomoses in one. In all cases, the stenosis of the vessel bypassed with the narrowed graft proved to be only mild (50% or less) at reangiography. In all six cases with bilateral IMA grafts, the contralateral IMA was widely patent. These were all connected to highly stenosed or occluded coronary arteries. With respect to this observation, there is a high index of suspicion that the string phenomenon occurs due to competitive flow in only mildly stenosed coronary arteries. We decided, for our strategy in coronary artery surgery, still to aim at complete revascularization using IMAs as much as possible, but to avoid connecting IMA grafts to only mildly or moderately stenosed coronary arteries.

Refinement of the Iowa Self-Assessment Inventory.

Two samples of older respondents (N = 1,153 and N = 420) were used in the refinement of the Iowa Self-Assessment Inventory (ISAI). Factor analyses based on data obtained from these samples resulted in modification of the original six-scale inventory to an inventory of seven scales: economic resources, anxiety/depression, physical health, alienation, mobility, cognitive status, and social support. The original ISAI was shortened from 120 to 56 items.

In vitro analysis of antiangiogenic activity of fungi isolated from clinical cases of equine keratomycosis.

OBJECTIVE: The goal of this project was to explore the possibility that fungal organisms produce metabolites that inhibit angiogenesis. Procedures Fungal cultures were obtained from cases of keratomycosis, grown in Sabouraud's dextrose broth, and sterile filtered for use in experiments. The Matrigel assay was used to screen the filtrate samples for antiangiogenic activity. Matrigel is a basement membrane matrix that supports the differentiation of human umbilical vein endothelial (HUVE) cells into a capillary-like network of tubules. HUVE cells were cultured using standard techniques and passaged at confluence, with all cells being used at passage 3-6. HUVE cells (40 000 cells) were pipetted into each well of a 24-well tissue-culture plate coated with Matrigel. An aliquot of fungal media filtrate was added to each well and the plates allowed to incubate for 18 h, at which time they were evaluated for tubule formation. RESULTS: Two fungal isolates showed inhibition of tubule formation. The addition of 100, 200 and 400 &mgr;L of the fungal media filtrate from the first isolate (Fusarium sp. 99A34574) produced a consistent and dose-dependent inhibition of tubule formation. The second isolate (Aspergillus sp. 271599) did not show inhibition of tubule formation with 100 or 200 &mgr;L added to the wells, however, it did show inhibition at 400 &mgr;L/well. The remaining three isolates did not cause inhibition at any concentration. CONCLUSIONS: Our findings suggest that certain fungal organisms produce metabolites that inhibit tubule formation in vitro, and that these metabolites may play a significant role in altering the host vascular response to fungal infections of the cornea.

Effects of 0.005% latanoprost solution on intraocular pressure in healthy dogs and cats.

OBJECTIVE: To evaluate effects of daily topical ocular administration of latanoprost solution on intraocular pressure (IOP) in healthy cats and dogs. ANIMALS: 9 domestic shorthair cats and 14 dogs. PROCEDURE: Latanoprost solution (0.005%) was administered topically to 1 eye (treated) and vehicle to the other eye (control) of all animals once daily in the morning for 8 days. Intraocular pressure was measured twice daily for the 5 days preceding treatment, and IOP, pupillary diameter, conjunctival hyperemia, and blepharospasm were measured 0, 1, 6, and 12 hours after the first 4 treatments and 0 and 12 hours after the final 4 treatments. Measurements continued twice a day for 5 days after treatment was discontinued. Aqueous flare was measured once daily during and for 5 days after the treatment period. RESULTS: Intraocular pressure and pupillary diameter were significantly decreased in the treated eye of dogs, compared with the control eye. Mild conjunctival hyperemia was also detected, but severity did not differ significantly between eyes. Blepharospasm and aqueous flare were not detected in either eye. Intraocular pressure in cats was not significantly affected by treatment with latanoprost. However, pupillary diameter was significantly decreased in the treated eye, compared with the control eye. Conjunctival hyperemia, aqueous flare, and blepharospasm were not detected in either eye. CONCLUSIONS AND CLINICAL RELEVANCE: Once-daily topical ocular administration of latanoprost solution (0.005%) reduced IOP in healthy dogs without inducing adverse effects but did not affect IOP in healthy cats. Latanoprost may be useful for treating glaucoma in dogs.

[Pre- and postoperative conditions in the self evaluation of 3 groups of surgical patients]. / Prä- und postoperative Befindlichkeit in der Selbstbeurteilung von drei Gruppen chirurgischer Patienten.

This article studies the self-assessed pre/postoperative course of the psychological condition of 3 patient groups (hernia, aorto-coronary bypass and cancer patients) and healthy controls. Some consequences for clinical work are discussed.