Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient

"OBJECTIVE: To update the 2002 version of ""Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient."" DESIGN: A Task Force comprising 17 members of the Society of Critical Medicine with particular expertise in the use of neuromuscular-blocking agents; a Grading of Recommendations Assessment, Development, and Evaluation expert; and a medical writer met via teleconference and three face-to-face meetings and communicated via e-mail to examine the evidence and develop these practice guidelines. Annually, all members completed conflict of interest statements; no conflicts were identified. This activity was funded by the Society for Critical Care Medicine, and no industry support was provided. METHODS: Using the Grading of Recommendations Assessment, Development, and Evaluation system, the Grading of Recommendations Assessment, Development, and Evaluation expert on the Task Force created profiles for the evidence related to six of the 21 questions and assigned quality-of-evidence scores to these and the additional 15 questions for which insufficient evidence was available to create a profile. Task Force members reviewed this material and all available evidence and provided recommendations, suggestions, or good practice statements for these 21 questions. RESULTS: The Task Force developed a single strong recommendation: we recommend scheduled eye care that includes lubricating drops or gel and eyelid closure for patients receiving continuous infusions of neuromuscular-blocking agents. The Task Force developed 10 weak recommendations. 1) We suggest that a neuromuscular-blocking agent be administered by continuous intravenous infusion early in the course of acute respiratory distress syndrome for patients with a PaO2/FIO2 less than 150. 2) We suggest against the routine administration of an neuromuscular-blocking agents to mechanically ventilated patients with status asthmaticus. 3) We suggest a trial of a neuromuscular-blocking agents in life-threatening situations associated with profound hypoxemia, respiratory acidosis, or hemodynamic compromise. 4) We suggest that neuromuscular-blocking agents may be used to manage overt shivering in therapeutic hypothermia. 5) We suggest that peripheral nerve stimulation with train-of-four monitoring may be a useful tool for monitoring the depth of neuromuscular blockade but only if it is incorporated into a more inclusive assessment of the patient that includes clinical assessment. 6) We suggest against the use of peripheral nerve stimulation with train of four alone for monitoring the depth of neuromuscular blockade in patients receiving continuous infusion of neuromuscular-blocking agents. 7) We suggest that patients receiving a continuous infusion of neuromuscular-blocking agent receive a structured physiotherapy regimen. 8) We suggest that clinicians target a blood glucose level of less than 180 mg/dL in patients receiving neuromuscular-blocking agents. 9) We suggest that clinicians not use actual body weight and instead use a consistent weight (ideal body weight or adjusted body weight) when calculating neuromuscular-blocking agents doses for obese patients. 10) We suggest that neuromuscular-blocking agents be discontinued at the end of life or when life support is withdrawn. In situations in which evidence was lacking or insufficient and the study results were equivocal or optimal clinical practice varies, the Task Force made no recommendations for nine of the topics. 1) We make no recommendation as to whether neuromuscular blockade is beneficial or harmful when used in patients with acute brain injury and raised intracranial pressure. 2) We make no recommendation on the routine use of neuromuscular-blocking agents for patients undergoing therapeutic hypothermia following cardiac arrest. 3) We make no recommendation on the use of peripheral nerve stimulation to monitor degree of block in patients undergoing therapeutic hypothermia. 4) We make no recommendation on the use of neuromuscular blockade to improve the accuracy of intravascular-volume assessment in mechanically ventilated patients. 5) We make no recommendation concerning the use of electroencephalogram-derived parameters as a measure of sedation during continuous administration of neuromuscular-blocking agents. 6) We make no recommendation regarding nutritional requirements specific to patients receiving infusions of neuromuscular-blocking agents. 7) We make no recommendation concerning the use of one measure of consistent weight over another when calculating neuromuscular-blocking agent doses in obese patients. 8) We make no recommendation on the use of neuromuscular-blocking agents in pregnant patients. 9) We make no recommendation on which muscle group should be monitored in patients with myasthenia gravis receiving neuromuscular-blocking agents. Finally, in situations in which evidence was lacking or insufficient but expert consensus was unanimous, the Task Force developed six good practice statements. 1) If peripheral nerve stimulation is used, optimal clinical practice suggests that it should be done in conjunction with assessment of other clinical findings (e.g., triggering of the ventilator and degree of shivering) to assess the degree of neuromuscular blockade in patients undergoing therapeutic hypothermia. 2) Optimal clinical practice suggests that a protocol should include guidance on neuromuscular-blocking agent administration in patients undergoing therapeutic hypothermia. 3) Optimal clinical practice suggests that analgesic and sedative drugs should be used prior to and during neuromuscular blockade, with the goal of achieving deep sedation. 4) Optimal clinical practice suggests that clinicians at the bedside implement measure to attenuate the risk of unintended extubation in patients receiving neuromuscular-blocking agents. 5) Optimal clinical practice suggests that a reduced dose of an neuromuscular-blocking agent be used for patients with myasthenia gravis and that the dose should be based on peripheral nerve stimulation with train-of-four monitoring. 6) Optimal clinical practice suggests that neuromuscular-blocking agents be discontinued prior to the clinical determination of brain death."

Effects of hyperandrogenemia and increased adiposity on reproductive and metabolic parameters in young adult female monkeys.

Many patients with hyperandrogenemia are overweight or obese, which exacerbates morbidities associated with polycystic ovary syndrome (PCOS). To examine the ability of testosterone (T) to generate PCOS-like symptoms, monkeys received T or cholesterol (control) implants (n = 6/group) beginning prepubertally. As previously reported, T-treated animals had increased neuroendocrine drive to the reproductive axis [increased luteinizing hormone (LH) pulse frequency] at 5 yr, without remarkable changes in ovarian or metabolic features. To examine the combined effects of T and obesity, at 5.5 yr (human equivalent age: 17 yr), monkeys were placed on a high-calorie, high-fat diet typical of Western cultures [Western style diet (WSD)], which increased body fat from <2% (pre-WSD) to 15-19% (14 mo WSD). By 6 mo on WSD, LH pulse frequency in the controls increased to that of T-treated animals, whereas LH pulse amplitude decreased in both groups and remained low. The numbers of antral follicles present during the early follicular phase increased in both groups on the WSD, but maximal follicular size decreased by 50%. During the late follicular phase, T-treated females had greater numbers of small antral follicles than controls. T-treated monkeys also had lower progesterone during the luteal phase of the menstrual cycle. Although fasting insulin did not vary between groups, T-treated animals had decreased insulin sensitivity after 1 yr on WSD. Thus, while WSD consumption alone led to some features characteristic of PCOS, T + WSD caused a more severe phenotype with regard to insulin insensitivity, increased numbers of antral follicles at midcycle, and decreased circulating luteal phase progesterone levels.

Elevated androgens during puberty in female rhesus monkeys lead to increased neuronal drive to the reproductive axis: a possible component of polycystic ovary syndrome.

BACKGROUND: Hyperandrogenemia is associated with several clinical disorders in which both reproductive dysfunction and metabolic changes may coexist [i.e. polycystic ovary syndrome (PCOS), obesity and congenital adrenal hyperplasia]. Moreover, there is growing evidence that the elevated levels of circulating androgens in obese girls may lead to an increased neuroendocrine drive to the reproductive axis, similar to that associated with PCOS. METHODS: To test whether androgen exposure in the childhood and adolescent period could lead to pubertal alterations in LH secretory patterns, female rhesus monkeys received subcutaneous testosterone implants prepubertally beginning at 1 year of age, maintaining a 3.7-fold increase (P = 0.001) in circulating testosterone levels over cholesterol-implant controls (n = 6/group) into the post-pubertal period. In early adulthood, pulsatile secretion of LH was measured over 12 h during the early follicular phase of a menstrual cycle, and responsiveness of the pituitary to gonadotrophin-releasing hormone was determined. In addition, ultrasounds were performed to assess ovarian morphology and glucose tolerance testing was performed to assess insulin sensitivity. RESULTS: The timing of menarche was similar between groups. Testosterone-treated animals had a significantly greater LH pulse frequency during the early follicular phase compared with controls (P = 0.039) when measured at 5 years of age. There was a larger LH response to GnRH when testosterone-treated animals were 4 years of age (P = 0.042), but not when the animals were 5 years old (P = 0.57). No differences were seen in insulin sensitivity or ovarian morphology, and the groups showed similar rates of ovulation in early adulthood. CONCLUSIONS: Exposure to increased levels of androgens over the course of pubertal development appears to trigger physiological changes in the neural drive to the reproductive axis that resemble those of obese hyperandrogenemic girls in early adulthood and are characteristic of PCOS.

Bell clapper impact dynamics and the voicing of a carillon.

The periodic re-voicing of the bell clappers of the Australian National Carillon in Canberra provided an opportunity for the study of the acoustic effects of this operation. After prolonged playing, the impact of the pear-shaped clapper on a bell produces a significant flat area on both the clapper and the inside surface of the bell. This deformation significantly decreases the duration of the impact event and has the effect of increasing the relative amplitude of higher modes in the bell sound, making it "brighter" or even "clangy." This effect is studied by comparing the spectral envelope of the sounds of several bells before and after voicing. Theoretical analysis shows that the clapper actually strikes the bell and remains in contact with the bell surface until it is ejected by a displacement pulse that has traveled around the complete circumference of the bell. The contact time, typically about 1 ms, is therefore much longer than the effective impact time, which is only a few tenths of a millisecond. Both the impact time and the contact time are reduced by the presence of a flat on the clapper.

Temporary monocular blindness associated with acute carotid thrombosis: a case report.

We report upon a patient with multiple, progressive episodes of temporary monocular blindness associated with acute thrombosis and a critical internal carotid artery stenosis. Carotid angiography demonstrated an anatomically compelling situation consisting of a critical reduction of flow distal to a preocclusive internal carotid artery stenosis accompanied by intraluminal thrombus. The patient was managed successfully by urgent thrombectomy and carotid endarterectomy. This case report highlights principles in management of patients with the unstable neurologic condition of temporary monocular blindness associated with an anatomically compelling situation demonstrated on angiography.

Patient characteristics and ICU organizational factors that influence frequency of pulmonary artery catheterization.

CONTEXT: Hemodynamic monitoring of patients with a pulmonary artery catheter is controversial because there are few data confirming its effectiveness, and patient and intensive care unit (ICU) organizational factors associated with its use are unknown. OBJECTIVE: To determine pulmonary artery catheter use in relationship to type of ICU organization and staffing, and patient characteristics, including severity of illness and insurance coverage. DESIGN, SETTING, AND PATIENTS: Retrospective database study of 10,217 nonoperative patients who received treatment at 34 medical, mixed medical and surgical, and surgical ICUs at 27 hospitals during 1998 (patients were enrolled in Project IMPACT). MAIN OUTCOME MEASURES: Pulmonary artery catheter use based on severity of illness measured by the Simplified Acute Physiology Score, resuscitation status at ICU admission, and ICU organizational variables, including type, size, and model. RESULTS: A pulmonary artery catheter was used for 831 patients (8.1%) in the ICU. In multivariate analysis adjusted for severity of illness, age, diagnosis, and do-not-resuscitate status, full-time ICU physician staffing was associated with a two-thirds reduction in the probability of catheter use (odds ratio [OR], 0.36; 95% confidence interval [CI], 0.28-0.45). Higher catheter use was associated with white race (OR, 1.38; 95% CI, 1.10-1.72) and private insurance coverage (OR, 1.33; 95% CI, 1.10-1.60). Admission to a surgical ICU was associated with a 2-fold increase in probability of catheter use (OR, 2.17; 95% CI, 1.70-2.76) compared with either medical or mixed medical and surgical ICUs. CONCLUSION: Organizational characteristics of ICUs, insurance reimbursement, and race, as well as clinical variables, are associated with variation in practice patterns regarding pulmonary artery catheter use. Understanding such influences, combined with studies measuring clinical and economic outcomes, can contribute to the development of policies for the rational use of pulmonary artery catheters. JAMA. 2000;283:2559-2567

Immediate causes of death of demented and non-demented elderly.

OBJECTIVE: To investigate the immediate causes of death, in autopsied demented and non-demented elderly. DESIGN: Retrospective clinicopathologic correlations. SETTING: Acute and intermediate care geriatric hospital. PARTICIPANTS: 342 hospitalized demented and non-demented elderly (mean age 84.94 +/- 6.9 years) who underwent consecutive postmortem examinations: 120 demented patients with either vascular dementia (VaD, n = 34), mixed dementia (MD, n = 65) or Alzheimer's disease (AD, n=21) neuropathologically confirmed and 222 nondemented elderly. RESULTS: Primary causes of death were similar in both demented and non-demented patients; the commonest were cardiovascular disease and bronchopneumonia. Cardiac causes of death and especially cardiac failure were more frequent in VaD than in AD or MD (respectively P = 0.027 and 0.005). Dementia was an underlying but never a primary cause of death. CONCLUSIONS: Immediate causes of death are similar in elderly demented and non-demented patients.

Refolding rate of stability-enhanced cytochrome c is independent of thermodynamic driving force.

N52I iso-2 cytochrome c is a variant of yeast iso-2 cytochrome c in which asparagine substitutes for isoleucine 52 in an alpha helical segment composed of residues 49-56. The N52I substitution results in a significant increase in both stability and cooperativity of equilibrium unfolding, and acts as a "global suppressor" of destabilizing mutations. The equilibrium m-value for denaturant-induced unfolding of N52I iso-2 increases by 30%, a surprisingly large amount for a single residue substitution. The folding/unfolding kinetics for N52I iso-2 have been measured by stopped-flow mixing and by manual mixing, and are compared to the kinetics of folding/unfolding of wild-type protein, iso-2 cytochrome c. The results show that the observable folding rate and the guanidine hydrochloride dependence of the folding rate are the same for iso-2 and N52I iso-2, despite the greater thermodynamic stability of N52I iso-2. Thus, there is no linear free-energy relationship between mutation-induced changes in stability and observable refolding rates. However, for N52I iso-2 the unfolding rate is slower and the guanidine hydrochloride dependence of the unfolding rate is smaller than for iso-2. The differences in the denaturant dependence of the unfolding rates suggest that the N52I substitution decreases the change in the solvent accessible hydrophobic surface between the native state and the transition state. Two aspects of the results are inconsistent with a two-state folding/unfolding mechanism and imply the presence of folding intermediates: (1) observable refolding rate constants calculated from the two-state mechanism by combining equilibrium data and unfolding rate measurements deviate from the observed refolding rate constants; (2) kinetically unresolved signal changes ("burst phase") are observed for both N52I iso-2 and iso-2 refolding. The "burst phase" amplitude is larger for N52I iso-2 than for iso-2, suggesting that the intermediates formed during the "burst phase" are stabilized by the N52I substitution.

Coronary artery bypass surgery in women.

Coronary artery disease remains a predominant cause of morbidity and mortality in women. Some studies indicate that there exists a degree of gender bias in the distribution of surgical therapy for coronary artery disease. Numerous studies have demonstrated that female patients have a higher operative mortality rate when undergoing coronary artery bypass surgery. The reasons for this appear to be many including an increased number of comorbid factors in female patients, instability at the time of surgery, and smaller coronary artery size resulting in more technical difficulties and greater risk of incomplete revascularization. Once past the perioperative time period, however, female patients have survival and functional benefits from surgery equivalent to those of men. Increased awareness of clinical manifestations of coronary artery disease in women and careful selection of patients for surgical therapy is warranted.

Rhodanese folding is controlled by the partitioning of its folding intermediates.

Rhodanese is used widely as a model for protein folding, since the enzyme as usually studied refolds poorly unless the process is assisted. Here, the influence of the partitioning of the folding intermediates of bovine rhodanese on the efficiency of its refolding has been investigated. Metastable intermediates can be formed during unfolding of the enzyme. The stabilities of these intermediates and the native protein with respect to chemical unfolding can be greatly increased by high concentrations of glycerol. The concentration dependence of the protein folding kinetics indicates that associative processes occur during renaturation. It is suggested that, during enzyme refolding, rhodanese undergoes fast collapse to an intermediate state I' which partitions to at least two other states (I" and I"'). One of these states (I"') is able to refold to the native enzyme, while the other state (I") is in equilibrium with I' and is prone to slow irreversible aggregation. Stabilization of I" against irreversible aggregation by glycerol results in increased yield of the protein refolding and a complex temperature dependence of the protein renaturation. The nature of the I" type intermediate has been investigated. Based on the fact that extensive hydrophobic surfaces are exposed during formation of the intermediates, it is suggested that partial dissociation of the two structural domains of rhodanese is an early event in unfolding. Interactions of different folding intermediates of rhodanese with the chaperonin GroEL were investigated, and the results suggest that the more extensively unfolded intermediates bind tighter than those that appear later on the rhodanese refolding pathway.

Ovarian metastatic melanoma. A diagnostic pitfall in histopathologic examination.

Malignant melanoma metastasis to the ovary is exceptional. This observation relates the case of a 33 year-old woman who presented with a voluminous unilateral, histologically poorly differentiated, ovarian mass, and discusses the differential diagnosis. Immunohistochemical studies demonstrated strong positivity for S-100 protein, HMB-45 and vimentin. We emphasize the unpredictable clinical and biologic behavior of malignant melanomas and the necessity to perform immunohistochemical study by S-100 protein and HMB-45 in a poorly differentiated metastasis to the ovary, histologically compatible with malignant melanoma; even in the absence of intracytoplasmic pigment and clinical antecedent of cutaneous malignant melanoma.

Thermodynamic cycles as probes of structure in unfolded proteins.

The relationship between structure and stability has been investigated for the folded forms and the unfolded forms of iso-2 cytochrome c and a variant protein with a stability-enhancing mutation, N52I iso-2. Differential scanning calorimetry has been used to measure the reversible unfolding transitions for the proteins in both heme oxidation states. Reduction potentials have been measured as a function of temperature for the folded forms of the proteins. The combination of measurements of thermal stability and reduction potential gives three sides of a thermodynamic cycle and allows prediction of the reduction potential of the thermally unfolded state. The free energies of electron binding for the thermally unfolded proteins differ from those expected for a fully unfolded protein, suggesting that residual structure modulates the reduction potential. At temperatures near 50 degrees C the N52I mutation has a small but significant effect on oxidation state-sensitive structure in the thermally unfolded protein. Inspection of the high-resolution X-ray crystallographic structures of iso-2 and N52I iso-2 shows that the effects of the N52I mutation and oxidation state on native protein stability are correlated with changes in the mobility of specific polypeptide chain segments and with altered hydrogen bonding involving a conserved water molecule. However, there is no clear explanation of oxidation state or mutation-induced differences in stability of the proteins in terms of observed changes in structure and mobility of the folded forms of the proteins alone.

Accurate placement of central venous catheters using a 16-cm catheter.

We determine if use of 16-cm central venous catheters (CVC) minimizes dangerous intracardiac catheter placements. We conducted a prospective study in a large community teaching hospital. Consecutive patients (n = 127) who required a CVC via either the internal jugular (IJV) or the subclavian vein (SCV) were assessed using 16 (n = 102) or 20-cm (n = 25) catheters. The main outcome measurements were (1) intracardiac placement of central venous catheters, and (2) relationship of right- or left-sided internal jugular or subclavian vein insertions to intracardiac catheter placement. Use of a 20-cm CVC resulted in 14 of 25 (56%) intracardiac placements compared with 11 of 102 (11%) using a 16-cm catheter (p < 0.0001). All intracardiac placements with the 16-cm CVC were from right-sided approaches: IJV 7 of 38 (16%), SCV 4 of 18 (18%). Use of a 16-cm CVC to access the central circulation from either the SCV or the IJV results in a significantly greater proportion of safe catheter placements than using longer CVCs, and it should become the standard of care.

Prolyl isomerase as a probe of stability of slow-folding intermediates.

Catalysis of slow folding reactions by peptidyl prolyl cis-trans isomerase (PPI) provides estimates of stabilities of intermediates in folding of normal and mutational variants of yeast iso-2 cytochrome c. A two-state model postulating a rapid preequilibration of intermediates with the unfolded protein is employed to calculate the stabilization free energy of the intermediate from the catalytic efficiency (kcat/Km) of PPI toward slow folding species. Stability measurements have been made for two distinct slow-folding intermediates: the absorbance-detected (IIS) and fluorescence-detected (IIIS) intermediates. Mutation-induced changes in the stability of the intermediates and in the activation free energy for slow folding are compared to changes in equilibrium thermodynamic stability. The results show that (1) for iso-2 the absorbance-detected intermediates (IIS) are slightly more stable than the fluorescence-detected intermediates (IIIS), (2) most mutations have different effects on equilibrium stability and the stability of the IIS or IIIS intermediates, and (3) for both slow folding reactions the mutation-induced changes in the activation free energy are small compared to the magnitude of the activation free energy barrier. Differential effects of mutations on equilibrium stability and the stability of intermediates provides a means of assessing the sequence-encoded structural specificity for folding. Mutations with different effects on intermediate stability and equilibrium stability change the encoded folding information and may alter folding pathways and/or lead to different three-dimensional structures. Identification of mutations which stabilize a folding intermediate relative to the native conformation provides an empirical approach to the design of thermodynamically stable forms of folding intermediates.

Reengineering medical treatment facilities for TRICARE: the Medical Group Practice Model.

The purpose of this article is to propose a model for reengineering military community hospitals, as well as medical centers, to adapt to the extraordinarily rapid and complex changes that are being made to the Military Health Services System. This article analyzes the changes taking place and discusses how a particular organizational model, the Medical Group Practice Model, can enhance quality and patient satisfaction in a capitated managed care environment. The phased implementation, structure, and performance management of the model are described, as is the model's advantages and disadvantages.

Accurate placement of central venous catheters: a prospective, randomized, multicenter trial.

OBJECTIVES: a) To define the frequency of dangerous (intracardiac) central venous catheter placement in a multicenter study of large community hospital intensive care units (ICUs) and to evaluate physician responses to this finding. b) To validate right atrial electrocardiography as a technique to assure adherence with recent Food and Drug Administration (FDA) guidelines regarding the location of central venous catheter tips. c) To conduct a literature review of vascular cannulation and its associated potentially lethal complications. DESIGN: Prospective, randomized, blinded, multicenter study. SETTING: Multidisciplinary ICUs in five large community teaching hospitals. PATIENTS: Consecutive patients (n = 112) who required a central venous catheter by either internal jugular vein or subclavian vein at four separate hospitals were assessed using 30-cm catheters. Consecutive patients (n = 50) in a fifth hospital who subsequently required a central venous catheter via the internal jugular vein or subclavian vein route were prospectively randomized to receive a 20-cm central venous catheter with either conventional surface-landmark guidance, or with the right atrial electrocardiography-guided technique. MAIN OUTCOME MEASURES: a) Occurrence rate of malpositioned central venous catheters. b) Ability of right atrial electrocardiography to aid in the accurate placement of central venous catheters. RESULTS: a) Using conventional placement techniques with a 30-cm catheter, 53 (47%) of 112 initial central venous catheter placements resulted in location of the catheter tip within the heart. Catheter tips were not repositioned to locations outside the right atrium after this finding was identified on initial post-procedure films. b) Using the right atrial electrocardiography technique to place 20-cm central venous catheters resulted in no catheter tip locations within the heart (0/25) vs. 14 (56%) of 25 (p < .0001) intracardiac placements using conventional techniques. c) The literature suggests that serious mechanical complications of central venous catheterization, although uncommon, are associated with a high mortality rate. Deaths are associated with intracardiac placement. CONCLUSIONS: a) The FDA guidelines regarding catheter tip location (catheter tip should not be in the right atrium) have not been widely publicized. b) The average safe insertion depth for a central venous catheter from the left or right internal jugular vein or subclavian vein is 16.5 cm for the majority of adult patients; a central venous catheter should not be routinely inserted to a depth of > 20 cm. Catheters longer than this size are rarely needed, and potentially dangerous. Catheter tip location is important to document following central venous catheter insertion. Thirty-centimeter central venous catheters should not be used when accessing the central circulation via internal jugular or subclavian veins. c) Right atrial electrocardiography is a technique that assures initial tip position outside the heart in accordance with FDA guidelines. This technique would virtually eliminate the major risk of death (i.e., cardiac perforation) associated with this procedure. d) Recently available, 15- and 16-cm central venous catheters have significant potential to minimize intracardiac placement of central venous catheters by either the internal jugular or subclavian vein route and may become the standard of care.

[Postmortem diagnosis of cardiac amyloidosis in the aged. Anatomoclinical correlation]. / Diagnostic post-mortem de l'amyloïdose cardiaque du vieillard. Corrélation anatomoclinique.

The absence of specific clinical signs makes the diagnosis of cardiac amyloidosis difficult. Moreover, it is established that this condition, the prevalence of which increases with age, aggravates the prognosis of cardiac failure. The present study was undertaken to identify the clinical or paraclinical signs enabling more accurate diagnosis of this disease. Analysis of 2589 autopsy reports from the University Institutes of Geriatrics of Geneva between January 1972 and January 1990 recensed 58 cases of microscopic cardiac amyloidosis, but this diagnosis was not made in any of these patients before death. Of the potential indicators, the good specificity but poor sensitivity of atrial fibrillation and low voltage electrocardiogram was confirmed. On the other hand, the author's research found the association of radiological cardiomegaly and a raised erythrocyte sedimentation rate in nearly 70% of cases of cardiac amyloidosis with a false positive rate of only 10% in a control group.

A flow procedure to determine oxygen binding isotherms for low affinity and easily oxidized hemoglobins.

1. The determination of binding isotherms for low affinity hemoglobins is particularly difficult because of rapid autoxidation. 2. In carp Hb (pH 6 + IHP, 25 degrees C), one-quarter of the hemes are oxidized within 3 min, preventing the accurate determination of even P50 or X. 3. We circumvent this problem by rapidly flowing HbO2, initially at pH 9 (X = 1.4 microM), against a low pH buffer to bring the system rapidly to equilibrium in the low affinity form. Diode-array spectrophotometry allows a complete spectrum to be obtained less than 5 sec, after flow ceases, before significant oxidation has occurred. In tandem with the stopped flow apparatus is an oxygen electrode to measure O2 activity. 4. At 22 degrees C, the half-saturation oxygen activity (X) is 227 microM, and the Hill number is 0.91, for carp Hb (T state) implying significant differences in the O2 affinities of the alpha and beta chain hemes or, two different T states.

[Cardiovascular polymorbidity as a function of psycho-organic status. A series of 904 pathological and neuropathological comparisons]. / Polymorbidité cardiovasculaire en fonction de l'état psycho-organique. Série de 904 confrontations pathologiques et neuropathologiques.

In the past decades, the recognition of polymorbidity as an important characteristic of geriatric medicine lead to important improvements in the multidisciplinary approach of the elderly. Coexistence of somatic and psychiatric diseases with various forms of etiopathogenic relations has been described early in this century. Dementia may be caused, aggravated, revealed or randomly accompanied by somatic diseases and inversely. However, very few attempts have been made in order to analyze the significance of these associations. This study is meant to give a better epidemiological knowledge of the relation between cardiovascular diseases and cerebral aging. This could lead to a better diagnostic approach and to a more complete physiopathological conception of dementia. 904 autopsy reports (patients who died between 1972 and 1986 in the Hôpital de Gériatrie of Genova) have been reviewed and classified in three groups according to neuropathological findings: 335 subjects with vascular encephalopathy of various types, 382 patients with degenerative diseases of Alzheimer type and 187 patients with normal brain. The subjects of these three groups had not all been considered demented. For each patient, age, sex, cause of death and 14 cardiovascular items have been appointed. The patients of the Alzheimer group died older and were more often women than those of the two other groups. The subjects of the vascular group died older than those of the normal group and were more often men than those of the two other groups. Stoke was considered to be the cause of death in 3% of the vascular patients whereas, by definition, it was absent from the two other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of clinical maneuvers on sonographically determined internal jugular vein size during venous cannulation.

We sought to define variations in internal jugular vein (IJV) anatomy and the effect of recommended cannulation maneuvers on a population of ICU patients. Maneuvers that decreased IJV lumen cross-sectional area were carotid artery palpation (1.48 to 0.82 cm2, p less than .05) and advancement of the needle (1.57 to 0.75 cm2, p less than .001). The head-down (modified Trendelenburg) position increased IJV lumen cross-sectional area (1.18 to 1.62 cm2, p less than .05). There was wide variability in IJV anatomic features, although most patients had patent veins.