Manganese-induced parkinsonism in methcathinone abusers: bio-markers of exposure and follow-up.

BACKGROUND AND PURPOSE: Methcathinone abuse is a new cause of manganism. The psychostimulant is prepared from pseudoephedrine using potassium permanganate as an oxidant. We describe the clinical, biological, neuroimaging characteristics and follow-up results in a large Estonian cohort of intravenous methcathinone users. METHODS: During 2006-2012 we studied 38 methcathinone abusers with a mean age of 33 years. Subjects were rated by the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr (HY), and Schwab and England (SE) rating scales. Twenty-four cases were reassessed 9-70 (20 ±â€…15) months after the initial evaluation. Manganese (Mn) in plasma and hair was analysed by inductively coupled plasma-atom emission spectrometry. Magnetic resonance imaging (MRI) was performed in 11, and single-photon emission computed tomography (SPECT) with iodobenzamide (IBZM) in eight subjects. RESULTS: The average total UPDRS score was 43 ±â€…21. The most severely affected domains in UPDRS Part III were speech and postural stability, the least affected domain was resting tremor. At follow-up there was worsening of HY and SE rating scales. Subjects had a higher mean level of Mn in hair (2.9 ±â€…3.8 ppm) than controls (0.82 ±â€…1.02 ppm), P = 0.02. Plasma Mn concentrations were higher (11.5 ±â€…6.2 ppb) in active than in former users (5.6 ±â€…1.8 ppb), P = 0.006. Active methcathinone users had increased MRI T1-signal intensity in the globus pallidus, substantia nigra and periaquaductal gray matter. IBZM-SPECT showed normal symmetric tracer uptake in striatum. CONCLUSION: Methcathinone abusers develop a distinctive hypokinetic syndrome. Though the biomarkers of Mn exposure are characteristic only of recent abuse, the syndrome is not reversible.

Fibreoptic intubation using three airway conduits in a manikin: the effect of operator experience.

In a randomised cross-over study, 72 anaesthetists (24 Senior House Officers, 24 Specialist Registrars and 24 Consultants) attempted to place a fibreoptic scope in the trachea of a manikin using three airway conduits: the Berman airway, the LMA Classic(trade mark) and the intubating laryngeal mask airway. The time for insertion of the airway conduit, delivery of two breaths and fibreoptic scope placement in the trachea was the primary endpoint. These overall times were significantly shorter (median [interquartile range]) using the LMA Classic (36 [28-45]) than via the intubating laryngeal mask (54 [42-79]) and the Berman airway (45 [33-80]), p < 0.0001. Senior House Officers were significantly slower than both Specialist Registrars and Consultants (p < 0.0001). The LMA Classic was considered to be the easiest conduit to use for fibreoptic scope placement by all grades of anaesthetists. We conclude that the LMA Classic is the most effective conduit for fibreoptic scope placement especially for anaesthetists with limited experience in its use.

A comparison of the Seeing Optical Stylet and the gum elastic bougie in simulated difficult tracheal intubation: a manikin study.

Management of the difficult airway is one of the major challenges that anaesthetists face. The flexible fibreoptic scope is widely available but its use requires a level of skill, training and continued practice that is not universally found in all anaesthetists, particularly trainees. The Seeing Optical Stylet is a new, semirigid fibreoptic stylet 'scope. We compared the Seeing Optical Stylet with a gum elastic bougie in a simulated Cormack and Lehane Grade 3 laryngoscopy in a manikin. Forty-four anaesthetists were timed while intubating the manikin's trachea with both devices. The mean (SD) time taken with the Seeing Optical Stylet was 20.8 (9.3) s and with the bougie 30 (19.8) s (p = 0.001). Oesophageal intubation occurred six times with the bougie but did not occur with the Seeing Optical Stylet (p = 0.011). We conclude that the Seeing Optical Stylet may be superior to the bougie in difficult tracheal intubation. We feel that the results of this manikin trial are sufficiently encouraging to proceed to a clinical trial in patients.

Anaesthetists' records of pre-operative assessment.

The pre-operative anaesthetic records of 195 patients were analysed for the presence of 12 agreed core items of pre-operative assessment. This study showed that anaesthetists recorded 26.8 per cent of this information. In up to one-third of patients the following were recorded: smoking history, family history, gastro-oesophageal reflux, airway assessment, dental assessment, chest examination, heart-sounds and blood pressure. Previous anaesthesia, drug history and allergies were recorded in one to two-thirds of patients. Past medical history was recorded in over two-thirds of patients. With a view to improving the level of record-keeping, a formatted, pre-printed pre-operative assessment record was introduced into practice and two months later the audit was repeated. A small but non-significant improvement in record keeping was observed. An argument is made for the introduction of an interdisciplinary, unified anaesthetic pre-operative record.

YopK of Yersinia pseudotuberculosis controls translocation of Yop effectors across the eukaryotic cell membrane.

Introduction of anti-host factors into eukaryotic cells by extracellular bacteria is a strategy evolved by several Gram-negative pathogens. In these pathogens, the transport of virulence proteins across the bacterial membranes is governed by closely related type III secretion systems. For pathogenic Yersinia, the protein transport across the eukaryotic cell membrane occurs by a polarized mechanism requiring two secreted proteins, YopB and YopD. YopB was recently shown to induce the formation of a pore in the eukaryotic cell membrane, and through this pore, translocation of Yop effectors is believed to occur (Håkansson et al., 1996b). We have previously shown that YopK of Yersinia pseudotuberculosis is required for the development of a systemic infection in mice. Here, we have analysed the role of YopK in the virulence process in more detail. A yopK-mutant strain was found to induce a more rapid YopE-mediated cytotoxic response in HeLa cells as well as in MDCK-1 cells compared to the wild-type strain. We found that this was the result of a cell-contact-dependent increase in translocation of YopE into HeLa cells. In contrast, overexpression of YopK resulted in impaired translocation. In addition, we found that YopK also influenced the YopB-dependent lytic effect on sheep erythrocytes as well as on HeLa cells. A yopK-mutant strain showed a higher lytic activity and the induced pore was larger compared to the corresponding wild-type strain, whereas a strain overexpressing YopK reduced the lytic activity and the apparent pore size was smaller. The secreted YopK protein was found not to be translocated but, similar to YopB, localized to cell-associated bacteria during infection of HeLa cells. Based on these results, we propose a model where YopK controls the translocation of Yop effectors into eukaryotic cells.

Analysis of high-resolution ECG changes during percutaneous transluminal coronary angioplasty.

The authors have hypothesized that low-level, electrocardiographic changes may accompany transient ischemia induced by percutaneous transluminal coronary angioplasty. Altered repolarization may manifest as subclinical changes in ST-T morphology. Changes in depolarization may manifest as low-amplitude notches and slurs, a phenomenon the authors term abnormal intra-QRS potentials. The initial aim of this study was to characterize changes in high-resolution electrocardiograph signals that might be linked to ischemic involvement of the ventricular myocardium.

Pregnancy but not moderate undernutrition attenuates insulin suppression of fat mobilization in sheep.

Nonpregnant and late-pregnant ditocous ewes were fed either to maintain zero energy balance in maternal tissues (fed) or at 50% of this level (underfed) for several weeks. Plasma concentrations of nonesterified fatty acids (NEFA) and glycerol were measured under basal conditions and during infusion of various doses of insulin while maintaining euglycemia (hyperinsulinemic, euglycemic clamp technique). Pregnancy and undernutrition separately increased basal plasma NEFA concentration in an additive manner; plasma glycerol was increased by pregnancy but unaffected by undernutrition. The molar ratio of NEFA to glycerol was significantly greater in underfed ewes. Analysis of dose-response relations between plasma insulin and metabolites during insulin infusions showed that maximally insulin-suppressed concentrations of NEFA and glycerol were significantly greater in pregnant than in nonpregnant ewes but were unaffected by undernutrition. Neither pregnancy nor undernutrition affected the maximally insulin-suppressed NEFA to glycerol ratio, or the plasma insulin concentration for 50% maximal responses to insulin of plasma NEFA, plasma glycerol, or the plasma NEFA to glycerol ratio. Thus, even in ewes at or close to zero energy balance, pregnancy seems to reduce adipose responsiveness but not sensitivity to the antilipolytic effect of insulin. This is another manifestation of the normal development of insulin resistance in maternal tissues during late pregnancy.

Community patterns of psychiatric disorders after the Exxon Valdez oil spill.

OBJECTIVE: This study examined the relationship between exposure to the Exxon Valdez oil spill and subsequent cleanup efforts and the prevalence of generalized anxiety disorder, posttraumatic stress disorder (PTSD), and depressive symptoms in 13 Alaska communities. METHOD: A community survey of 599 men and women was conducted approximately 1 year after the spill occurred. Questions from the National Institute of Mental Health Diagnostic Interview Schedule were used to assess symptoms of generalized anxiety disorder and PTSD. The Center for Epidemiologic Studies Depression (CES-D) Scale was used to assess levels of depressive symptoms. RESULTS: The post-spill (i.e., 1-year) prevalence of generalized anxiety disorder and PTSD for the study communities with all degrees of exposure was 20.2% and 9.4%, respectively. The prevalence of respondents with CES-D Scale scores above 16 and 18 was 16.6% and 14.2%, respectively. When compared with the unexposed group, members of the high-exposure group were 3.6 times as likely to have generalized anxiety disorder, 2.9 times as likely to have PTSD, 1.8 times as likely to have a CES-D Scale score of 16 and above, and 2.1 times as likely to have a CES-D Scale score of 18 and above. Women exposed to this event were particularly vulnerable to these conditions, and Alaska Natives were particularly vulnerable to depressive symptoms after the oil spill. CONCLUSIONS: The results suggest that the oil spill's impact on the psychosocial environment was as significant as its impact on the physical environment. The Exxon Valdez experience suggests a number of implications for the mental health needs of disaster victims, particularly in primary care settings.

Pregnancy and undernutrition alter glucose metabolic responses to insulin in sheep.

Nonpregnant and late-pregnant ditocous ewes were fed either to maintain zero energy balance in maternal tissues (fed) or at 50% of this level (underfed) for several weeks. Whole-body kinetics of glucose metabolism were measured under basal conditions, and the hyperinsulinemic, euglycemic clamp technique was used to define insulin-dose response profiles for several indices of whole-body glucose utilization, and for endogenous glucose production. Pregnancy increased and undernutrition decreased basal glucose entry rate (GER), glucose metabolic clearance rate (GMCR) and insulin-independent glucose utilization (IIGU). The consistent increment in IIGU of pregnant over nonpregnant ewes was comparable to previous estimates of uterine glucose uptake. Pregnancy resulted in higher plasma concentration for 50% maximal responses (ED50) to insulin of GER, GMCR, steady-state glucose infusion rate (SSGIR) to maintain euglycemia and insulin-dependent glucose utilization (IDGU). These changes were especially large in underfed pregnant ewes. Effects on the maximal response to insulin of these variables (Rmax) were relatively small (GMCR, IDGU) or nonsignificant (GER, SSGIR). Maximum insulin-induced suppression of endogenous glucose production was significantly lower due to undernutrition; neither Rmax nor ED50 for this response was affected by pregnancy. Insulin resistance in late-pregnant ewes is primarily due to decreased insulin sensitivity in (presumably) peripheral tissues, implying an alteration of receptor function or of early postreceptor signal transduction.

Ethnic differences in stress, coping, and depressive symptoms after the Exxon Valdez oil spill.

This study assessed levels of depressive symptomatology in a household probability sample of Alaskan Native (N = 188) and Euro-American (N = 371) residents of 13 communities in Alaska. Our objective was to examine ethnic differences in both the association between depressive symptomatology and exposure to the Exxon Valdez oil spill and subsequent cleanup efforts, and in the role of family support as a moderator of exposure to this technological disaster. Level of exposure was significantly associated with mean Center for Epidemiological Studies-Depression Scale scores in both Natives (p less than .05) and Euro-Americans (p less than .01). Both ethnic groups also reported significant declines in traditional relations with increasing levels of exposure (p less than .001). However, Natives had a significantly higher mean Exposure Index score than Euro-Americans and were more likely to report working on cleanup activities, damage to commercial fisheries, and effects of the spill on subsistence activities. Depressive symptomatology was associated with reported participation in cleanup activities and other forms of contact with the oil in Natives, and reported damage to commercial fisheries, use of affected areas, and residence in a community in geographic proximity to the spill in Euro-Americans. Perceived family support was not directly associated with depressive symptoms in either ethnic group, but did serve to buffer the effects of exposure on depressive symptoms in Euro-Americans. The results suggest that cultural differences play an important role in determining the psychosocial impacts of a technological disaster, particularly with respect to exposure, appraisal of an event as stressful, perceived family support as a moderator of stress, and expression of depressive symptomatology.

Relations between maternal and fetal plasma concentrations of placental lactogen and placental and fetal weights in well-fed ewes.

The concentration of ovine placental lactogen (oPL) in maternal plasma varies with litter size and nutritional status, making it difficult to compare these concentrations across studies. In this study, 27 Dorset and Finn-Dorset crossbred ewes with litters of known size and gestational age were used to relate concentrations of oPL in maternal plasma to placental and fetal weights. Fetal oPL concentrations also were correlated to these variables in 12 chronically catheterized singleton fetuses. The concentration of oPL in maternal plasma increased with increasing placental weight across litter sizes ranging from 1 to 3 (r = .716). When expressed per gram of placenta, oPL was greater (P less than .05) in those ewes carrying multiple fetuses. There was no correlation between maternal and fetal oPL in time-matched samples or in average values between individuals for ewes carrying singleton pregnancies. Within the singleton group, placental weight and fetal weight were well correlated (r = .761), as were the concentration of fetal plasma oPL and fetal weight (r = .699). Placental weight plus fetal oPL could explain 81% of the variation seen in fetal weight. These results imply that maternal and fetal oPL release are controlled independently and that fetal oPL affects fetal growth by a mechanism not directly related to placental size.

Distal peripheral polyneuropathy in a great dane.

A spayed female five year old Great Dane dog was diagnosed as having a chronic, progressive, symmetrical distal polyneuropathy and concurrent hypothyroidism. Axonal degeneration and segmental demyelination were evident in teased nerve fiber preparations. Clinical signs included hindlimb weakness and muscle atrophy of the head and distal limbs. Diagnosis was based on clinical, electrophysiological, and nerve and muscle biopsy findings. Thyroxine supplementation for one month was of no benefit. The etiology of the polyneuropathy was not established but several causes were considered. The extent of demyelination in our case was of greater magnitude than described in a previous report of a similar idiopathic distal symmetrical polyneuropathy in a Great Dane.

Respiratory dysfunction in thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, neurologic abnormalities, fever and renal dysfunction. in six of seven consecutive patients with thrombotic thrombocytopenic purpura seen in an eight month period, respiratory impairment was present. Respiratory dysfunction was characterized by tachypnea, hypoxemia nad infiltrates on chest roentgenogram. Five patients required mechanical ventilation. Two patients had cardiogenic pulmonary edema, but they remained hypoxemic despite treatment for pulmonary edema and maintenance of normal pulmonary capillary wedge pressure for more than 36 hours. Four patients died and autopsies revealed pulmonary edema, hemorrhage and hyaline thrombi. Pathologic examination of the heart also showed hyaline thrombi. Information from out patients with thrombotic thrombocytopenic purpura implicates respiratory dysfunction as a component of this disease as well as the classically described pentad. Cardiogenic and noncardiogenic pulmonary edema and possibly bleeding into the lung contributed to pulmonary impairment.