Systematic quality control for management of ST elevation acute myocardial infarction in setting of local network.

AIM: Adherence to evidence based guidelines, assessed by measuring key indicators, allows to detect, evaluate and improve quality of care. Since 2004 in Carlo Poma Hospital, following the introduction of a network for ST-elevation myocardial infarction (STEMI) management, the authors carried out a clinical database in order to measure quality of care in STEMI patients. MATERIALS AND METHODS: A real time upgradable database was developed, to assess clinical practice in myocardial infarction management. The authors evaluated prevalence and control of risk factors, pharmacological therapies and interventional procedures, pathways and delays to care. RESULTS: From 1 February 2004 to 31 January 2008, 1,714 consecutive patients with myocardial infarction were admitted in the Intensive Care Unit (ICU). Primary percutaneous coronary intervention (PCI) was performed in 85% of STEMI patients. Door to balloon time was greater than 90 min in only 17% of patients, of whom 88% coming from emergency department and 12% transferred by 118. CONCLUSION: In the authors' experience quality indicators proved useful in the management of myocardial infarction. Implementation of 118 and improvement of pre-hospital diagnosis in setting of local network can reduce time to treatment.

Changes in the distribution of a histone in dorsal root ganglion neurons during development.

The isolation and cellular localization of a basic protein (histone) from central nervous tissue have been previously reported. In the tissues previously studied (nervous tissue, testis, liver, spleen, kidney, ovary), the basic protein was restricted in distribution to the nuclei of neurons and spermatogonia. In the present study, the temporal appearance of the histone within neurons and the changes in its distribution during ontogenesis were examined. The reaction between a fluorescent immune gamma-globulin prepared against this purified tissue-specific histone and the neurons from the dorsal root ganglia of the rat was investigated. The dorsal root ganglia examined were those from fetuses, 2-, 10-, and 40-day-old rats, and from adult rats. At the earliest stages, only the nucleoli reacted. Subsequently, threads of fluorescent material were seen to emerge from the nucleoli. The extent of this reaction between the immune globulin and the threads within the nuclei continued to increase with maturation. No changes in fluorescence localization during development could be seen in the nuclei of neurons in the cerebellum or brain stem. The role that this tissue-specific histone may play in cell function is discussed.

[Mortality triplicates in acute myocardial infarction patients affected by chronic renal failure]. / L'insufficienza renale triplica il rischio di morte intraospedaliera nell'Infarto del Miocardio.

In order to calculate the cardiovascular risk in patients with chronic renal failure (CRF), we retrospectively analyzed 1482 acute myocardial infarctions (AMIs) treated in the ICU at C. Poma General Hospital, Mantua, Italy, from 1 December 2004 to 31 July 2007. Of these patients, 133 suffered from CRF at hospital admission (eGFR <40 mL/min/1.73 m2 body surface and/or serum creatinine >2 mg/dL). During hospitalization for AMI, the CRF-affected patients showed a 2.7 times higher relative risk of mortality than patients without CRF (Yates chi square 14.46; p = 0.0001432). The evaluated comorbidities (hypertension, type 2 diabetes, supra-aortic vascular stenosis >70%, previous PTCA, COPD, previous AMI, previous coronary artery bypass and chronic obliterative peripheral arteriopathy) increased the relative risk of death 1.2- to 3.76-fold in those affected. In accord with recent evidence in the international literature, our results point to the importance of early assessment of CRF for the prognosis of patients with AMI.

Cardiac function and intracellular Ca2+ handling proteins are not impaired by high-saturated-fat diet-induced obesity.

Obesity is often associated with changes in cardiac function; however, the mechanisms responsible for functional abnormalities have not yet been fully clarified. Considering the lack of information regarding high-saturated-fat diet-induced obesity, heart function, and the proteins involved in myocardial calcium (Ca2+) handling, the aim of this study was to test the hypothesis that this dietary model of obesity leads to cardiac dysfunction resulting from alterations in the regulatory proteins of intracellular Ca2+ homeostasis. Male Wistar rats were distributed into two groups: control (C, n=18; standard diet) and obese (Ob, n=19; high-saturated-fat diet), which were fed for 33 weeks. Cardiac structure and function were evaluated using echocardiographic and isolated papillary muscle analyses. Myocardial protein expressions of sarcoplasmic reticulum Ca2+-ATPase, phospholamban (PLB), PLB serine-16 phosphorylation, PLB threonine-17 phosphorylation, ryanodine receptor, calsequestrin, Na+/Ca2+ exchanger, and L-type Ca2+ channel were assessed by western blot. Obese rats presented 104% increase in the adiposity index (C: 4.5±1.4 vs Ob: 9.2±1.5%) and obesity-related comorbidities compared to control rats. The left atrium diameter (C: 5.0±0.4 vs Ob: 5.5±0.5 mm) and posterior wall shortening velocity (C: 36.7±3.4 vs Ob: 41.8±3.8 mm/s) were higher in the obese group than in the control. The papillary muscle function was similar between the groups at baseline and after inotropic and lusitropic maneuvers. Obesity did not lead to changes in myocardial Ca2+ handling proteins expression. In conclusion, the hypothesis was not confirmed, since the high-saturated-fat diet-induced obese rats did not present cardiac dysfunction or impaired intracellular Ca2+ handling proteins.

Performance and clinical comparison between left ventricular quadripolar and bipolar leads in cardiac resynchronization therapy: Observational research.

AIM: To evaluate Attain Performa (Medtronic, Dublin, Ireland) quadripolar lead performance in clinical practice and, secondarily, to compare its long term clinical outcomes vs bipolar leads for left ventricular (LV) pacing. METHODS AND RESULTS: We retrospectively analyzed clinical, procedural and follow-up data of 215 patients implanted with a quadripolar lead. One hundred and twenty one patients implanted with bipolar lead were selected to compare long-term clinical outcomes. The quadripolar lead was implanted in the target vein in 196 patients (91%) without acute dislodgements. In 50% of patients the chosen final pacing configuration at implant would not have been available with bipolar leads. A dedicated quadripolar pacing vector was chosen more frequently when the LV tip location was apical than otherwise (65.6% vs 42.7%, p=0.003). After a median follow-up of 14 months, the LV pacing threshold was less than 2.5V at 0.4ms in 98 patients (90%) with a safety margin between phrenic nerve and LV pacing threshold >3V in 97 patients (89%). We observed a slight trend toward a lower risk of heart failure worsening and a lower incidence of ventricular arrhythmias and pulmonary congestion in patients implanted with quadripolar leads compared with the control group. CONCLUSION: Quadripolar leads improve the management of phrenic nerve stimulation at no trade-off with pacing threshold and lead stability. Quadripolar leads seems to be associated with a lower incidence of VT/VF and pulmonary congestion, when compared with bipolar leads, but further investigations are necessary to confirm that this positive effect is associated with better LV reverse remodeling.

No reflow in patients undergoing primary angioplasty for acute myocardial infarction at high risk: incidence and predictive factors.

AIM: Percutaneous coronary intervention (PCI) is a consolidated therapeutic strategy for the treatment of acute myocardial infarction (AMI), but achieving a TIMI 3 flow does not always correspond to true tissue reperfusion. The aim of the study was to evaluate the incidence and predictive factors of no reflow in patients undergoing primary angioplasty (PCI) for AMI at high risk, in the setting of a provincial cardiological emergency network. METHODS: We retrospectively analyzed the ECGs of 360 consecutive patients undergoing primary PCI, between 2001-2004, recorded before and 90 min after the procedure, and compared them with the angiographic data. RESULTS: The patients were divided into 2 groups: group A (reperfused) with a >50% reduction in ST and group B (no reflow) with a <50% reduction in ST but a TIMI 3 flow in the epicardial vessel. The 2 groups were comparable in terms of mean age, sex, diabetes and AMI site. However, there were statistically significant differences between the groups in terms of precoronary time, Killip class IV, ejection fraction, mean leukocyte count, C-reactive protein, and the periprocedural administration of abciximab. Total mortality was 6%: 14% in group B vs 3% in group A. CONCLUSIONS: Our data show that a fair percentage of patients (24%) with a TIMI 3 flow after PCI during ST-elevation MI do not show ECG signs of effective reperfusion and have a higher in-hospital mortality rate. Precoronary time and the inflammatory phlogistic substrate are important independent predictors of no reflow. Pretreatment with abciximab, particularly if it is not periprocedural, can prevent the occurrence of no reflow.

[Coronary disease: early intervention saves lives. Treatment of acute myocardial infarction in Mantova: results of thirty months of work after the implementation of a province network]. / Malattia coronarica: l'intervento precoce salva la vita. Terapia dell'infarto miocardico acuto a Mantova, risultati di trenta mesi di attivita' dopo l'attivazione di una rete provinciale.

BACKGROUND: Since June 2001, in the province of Mantova, we have undertaken a program for the management of acute myocardial infarction based on the early assessment of patient risk profiles, concerning telematic connections among care centers and on the optimization of in-hospital and out of hospital critical pathways for access to care. MATERIALS AND METHODS: Our network provides connections among the following centers: advanced life support ambulances, seven hospitals, three coronary care units, one cath lab on call 24 h a day for primary angioplasty, and one thoracic surgery division. This program, through its strong telematic platform, allows the early assessment of myocardial infarction and provides primary angioplasty to all high-risk patients, as fibrinolytic treatment is reserved only for low-risk patients admitted in peripheral hospitals. RESULTS: Two hundred and eighty patients with acute myocardial infarction were treated with angioplasty; 224 patients (80%) underwent primary angioplasty, 36 patients (13%) facilitated angioplasty and 20 patients (7%) rescue angioplasty. One hundred and thirty-two patients (47%) were first admitted to Mantova Hospital; 78 patients (28%) were referred to Mantova from peripheral hospitals and 70 patients (25%) were directly transported to the cath lab by advanced life support ambulances. Procedural success was obtained in 98% of patients, with 0.4% intraprocedural mortality. In-hospital mortality was 5.7%, while mortality in cardiogenic shock patients was 36%. The recurrence of acute myocardial infarction occurred in 1% of patients and major bleeding occurred in 2.2% of patients. One patient with cardiogenic shock died during transport. Mean door to balloon time was 67 min with a 42% reduction in the 3rd recruitment period. CONCLUSIONS: This program, developed in the setting of a provincial network for the management of acute myocardial infarction, provided primary angioplasty to all high-risk patients, with a high procedural success rate. Within a few months, time to treatment was minimized by the use of telematic facilities.

Reversibility of human myopathy caused by vitamin E deficiency.

Although a neuromuscular syndrome has been induced experimentally by vitamin E deficiency, a human syndrome has not yet been documented. This report describes a 7-year-old boy with severe malabsorption since birth who presented with progressive external ophthalmoplegia, proximal muscle weakness, peripheral neuropathy, hyporeflexia, and bilateral Babinski signs. Abnormalities on neurologic examination included elevated creatine phosphokinase and aldolase, slowed distal sensory latencies, type II muscle fiber atrophy, and a plasma vitamin E level of 8 microgram per deciliter (normal, 550-1500 microgram per deciliter). Treatment with oral water-solubilized vitamin E (400 IU daily; greater than 50 times the normal daily intake) was begun, with repeat laboratory studies at 3-month intervals. Over a 16-month period, plasma vitamin E content gradually increased to 350 microgram per deciliter, associated with declining sarcoplasmic enzyme activities and clinical improvement.

Prognostic implications of hyperglycemia and reduced cerebral blood flow in childhood near-drowning.

We retrospectively examined the clinical courses of 20 children with severe near-drowning and divided their outcomes into 3 groups: normal (4), persistent vegetative state (9), and dead (7). We reviewed serial blood glucose levels and cerebral blood flow measured by stable xenon computed tomography within the 1st 48 hours of admission to determine whether they were predictive of outcome. Total, frontal gray, frontal white, and temporal and parietal gray matter cerebral blood flows were significantly decreased in children who died compared with those who completely recovered. Only 1/2 the children surviving in a vegetative state had decreased flows compared with those who recovered. An elevated initial blood glucose was highly predictive of those patients who died (mean, 511 +/- 110 mg%) or those with vegetative survival (465 +/- 104 mg%) compared with those who recovered completely (238 +/- 170 mg%). The predictive value of initial blood glucose alone (68%) or CBF alone (50%) was similar to that of clinical rating scales or immersion/resuscitation times. The combination of blood glucose with CBF improved predictability to 79%. Our results suggest that CBF measurements are predictive of eventual death but cannot differentiate normal from vegetative survival. Combining multiple laboratory studies may be of value in predetermining the eventual outcome in near-drowning.

Bacterial meningitis in children: pathophysiology and treatment.

Recent studies of the pathophysiology of bacterial meningitis have suggested that the development of neuronal injury is related to the release of vasoactive substances or alteration of blood-brain barrier permeability. Cerebral edema, increased intracranial pressure (ICP), systemic hypotension, decreased cerebral perfusion pressure, vascular inflammation, thrombosis, and a variety of other vascular changes may result in global or regional reductions in cerebral blood flow (CBF), which contribute to this insult. Approximately one-third of infants and children with bacterial meningitis will have markedly reduced CBF, and even in those children with normal total flow, regional hypoperfusion is common. Reduced CBF is associated with cerebral edema and a poor prognosis. A poor prognosis also is associated with reduced cerebral perfusion pressure. This occurs early in the course of meningitis and is primarily due to increased ICP rather than systemic hypotension. Autoregulation is preserved, suggesting that local ischemic tissue injury is more related to factors such as regional edema formation, focal vascular pathology, or specific intrinsic flow/metabolic abnormalities than to a reduction in systemic blood pressure. In contrast with other acute CNS insults, CBF/PCO2 reactivity is well preserved in many patients with meningitis; this raises the possibility that hyperventilation may cause further ischemic injury in those patients with marginal CBF. Although it is still unclear that treatment of increased ICP will affect outcome, we propose a treatment paradigm based on the results of neuroimaging studies and ICP measurements.

Hyperkinesis and food additives: testing the Feingold hypothesis.

Teacher ratings, objective classroom and laboratory observational data, attention-concentration, and other psychological measures obtained on 36 school-age, hyperactive boys under experimental and control diet conditions yielded no support for the Feingold hypothesis. Parental ratings revealed positive behavioral changes for the experimental diet; however, they seemed primarily attributable to one diet sequence. Parents' behavioral ratings on ten hyperactive, preschool boys indicated a positive response to the experimental diet; again, laboratory observations showed no diet effect.

Individual herpes simplex virus 1 glycoproteins display characteristic rates of maturation from precursor to mature form both in infected cells and in cells that constitutively express the glycoproteins.

Pulse-chase experiments in conjunction with quantitative immunoprecipitation have been used to study the time-course of conversion from precursor to mature form of herpes simplex virus 1 glycoproteins C, D and B (gC, gD, and gB). The experimental systems employed were two infected cell lines and cells that constitutively express gD or gB. The relative rates of conversion among the glycoproteins did not vary in the systems used; the rate of maturation of gC was about two-fold higher than that of gD which, in turn, was about one and a half-fold higher than that of gB. Treatment with phosphonoacetate which inhibits viral DNA synthesis and hence virion morphogenesis induced a striking increase in the time course of conversion of immature gC, gD, and gB to fully glycosylated forms when measured late in the infection. The model of HSV glycoproteins maturation as integral components of the virion envelope is discussed.

Human herpesvirus 6 envelope glycoproteins B and H-L complex are undetectable on the plasma membrane of infected lymphocytes.

Membrane immunofluorescence analysis of cells infected with either variant (A or B) of human herpesvirus 6 revealed a typical punctate staining, after labeling with several HHV-6-positive human sera or with two monoclonal antibodies directed to gB and gH. Immunoprecipitation studies showed a sharp difference in glycoprotein content in whole-cell extracts versus on the cell surface, suggesting the occurrence of gB in the extracellular virions juxtaposed to plasma membranes. By immunoelectron microscopy, the extracellular virions still attached to the cell surface appeared consistently and specifically labeled, whereas the plasma membrane was always unlabeled, independent of viral variant, antibody, or target cell used. These findings may reflect an atypical maturation pathway of HHV-6, and could have important implications in the control of cellular immune response to HHV-6-infected lymphocytes.

Selection of a monoclonal antibody specific for variant B human herpesvirus 6-infected mononuclear cells.

A monoclonal antibody, designated as MAb 6E2, specific for human herpesvirus 6 variant B (HHV-6B) was derived from the spleen of a mouse immunized with lysates of HHV-6B(Z29) cord blood mononuclear cells. MAb 6E2 reacts by immunofluorescence with all the HIV-6B strains tested (Z29, CV, Hashimoto and SF) and fails to react with variant A prototypes, GS and U1102. The immunofluorescence staining was punctate and localized to the cytoplasm. The protein reacting with MAb 6E2 was identified as protein 48,000 in apparent M(r) value by immunoaffinity chromatography of lysates of HHV-6B-infected mononuclear cells.

A phase-II clinical trial of 4'-epi-doxorubicin in advanced solid tumors.

Sixty-six patients with advanced solid tumors were treated with 4'-epi-doxorubicin at a dose of 90 mg/m2 by rapid IV injection every 21 days until the disease had progressed or to a maximum cumulative dose of 540 mg/m2. Myelosuppression, nausea and vomiting, and alopecia were the almost frequent side effects, but their incidence seemed lower than that after a comparable dosage of doxorubicin. After a cumulative dose of 540 mg/m2 a significant decrease of QRS complex deflection on the electrocardiogram was detected, but no case of congestive heart failure was observed. Partial remission and minor remission were achieved, respectively, in nine (15%) and five (9%) out of 59 evaluable patients for a median duration of 6 months. Partial remission occurred in anthracycline-sensitive tumors like breast cancer (4 of 13), lung cancer (1 of 17), head and neck cancer (1 of 8), gastric cancer (2 of 4), and ovarian cancer (1 of 1).

A distinctive neurologic syndrome after induced profound hypothermia.

Four patients suffered a distinctive neurologic syndrome after undergoing profound hypothermia and complete circulatory arrest for congenital heart lesion repair. Symptom onset was delayed 24-120 hours postoperatively. The syndrome consists of choreoathetosis and oral-facial dyskinesias, hypotonia, affective changes, and pseudobulbar signs (CHAP). Precise anatomic localization is uncertain. Magnetic resonance imaging of 2 patients did not reveal basal ganglia lesions. Pathogenesis is obscure.

Reflex sympathetic dystrophy syndrome in children.

We report 3 children with reflex sympathetic dystrophy syndrome, review the literature, and discuss current concepts of diagnosis and management. In this disorder, pain, tenderness, swelling, vasomotor instability, and dystrophic skin changes frequently develop after minor injury. The clinical diagnosis is supported by osteopenia detected on radiographs and either increased or decreased radionuclide uptake on bone scan of the affected extremity. Treatment with a graduated program of physical therapy and transcutaneous electrical nerve stimulation is beneficial in almost all patients. In contrast to adults, the prognosis of childhood reflex sympathetic dystrophy syndrome is favorable; most children recover completely after one episode.

CBF and CBF/PCO2 reactivity in childhood strangulation.

Four children with self-inflicted strangulation injuries had cerebral blood flow determined by stable xenon computed tomography (XeCTCBF) within 24 hours of admission. All had suffered a severe hypoxic-ischemic cerebral injury; 3 initially had fixed pupils, all were apneic with varying bradyarrhythmias, and the initial mean arterial pH was 7.26 (+/- 0.18). The initial blood glucose values were greater than 300 mg/dl (334 and 351 mg/dl) in the 2 patients who died compared to the 2 who survived (104 and 295 mg/dl). The cardiac index was depressed during the first several days of hospitalization in the 2 patients who died (less than 2.0 L/min/m2) compared to the 2 who survived. Total CBF was normal (63 +/- 8 ml/min/100 gm) and local variations in CBF were present. PCO2 reactivity was determined by hyperventilating the 4 patients for 20 min from an end tidal PCO2 of 39 +/- 3 torr to 29 +/- 1 torr and then repeating the XeCTCBF study. Marked regional variability in the CBF/PCO2 response was observed, ranging from 0.5-5.5 ml/min/100 gm/torr PCO2. In the 2 patients who died, the CBF/PCO2 was decreased (1.2 ml/min/100 gm/torr PCO2) compared to the 2 patients who survived (2.1 ml/min/100 gm/torr PCO2). Although CBF was normal in these 4 children, the hyperventilation response was depressed, variable, and even paradoxical which may be important in the evolution of further brain injury and is a critical factor in deciding whether hyperventilation may be of clinical benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

Anencephaly: clinical determination of brain death and neuropathologic studies.

Twelve liveborn anencephalic infants were serially examined to determine if they would meet our clinical criteria for whole brain death within a 7-day period: Protocol 1 infants (6) received intensive care including intubation from birth; and Protocol 2 infants (6) received intensive care during the period in which death was imminent. Brain death was determined by absence of brainstem function, including loss of all cranial nerve responses and sustained apnea (PCO2 greater than 60 torr) for 48 hours with confirmation of findings by an outside consulting child neurologist. The initial examinations of these 12 infants revealed spontaneous movements and startle myoclonus (12), suck, root, and gag responses (7), increased tone (8), deep tendon reflexes (9), absent pupillary responses (9), absent oculocephalic and corneal responses (6), absent auditory/Moro responses (7), and nonvisualization of the optic nerve (8). Mild depression of neurologic function occurred during the first several days of life; subsequently, the infants' responses were easier to elicit and more sustained. Only 2 infants met the clinical criteria for brain death. Neuropathologic findings indicated that observed complex motor responses were not based upon cortical activity because no infant had a normally-formed cerebrum. Brainstem neuronal activity may have accounted for these motor responses in some patients but even at this level neurons were scanty or absent. Our findings suggest that, although rare, clinical brain death can be determined in liveborn anencephalic infants; ophthalmologic and otologic developmental abnormalities may confound examination of cranial nerve function; and absence of cortical neurons supports the widely held opinion that these infants do not experience sensation.

Proton magnetic resonance spectroscopy in children with acute central nervous system injury.

Single voxel proton magnetic resonance spectroscopy (1H-MRS) was used in 30 infants and children with acute central nervous system injuries to determine the value of changes in specific metabolite ratios in predicting outcome. The mean age of all patients was 38 +/- 52 months and the mean time of study after insult was 7 +/- 5 days. 1H-MRS was determined in the occipital gray and parietal white matter (8 cm3 volume, STEAM sequence with TE = 20 ms, TR = 3,000 ms). Data were expressed as ratios of different metabolite peak areas including N-acetylaspartate (NA), choline-containing compounds (Ch), creatine and phosphocreatine (Cr), and lactate (Lac). Statistically significant differences were observed when patients with good/moderate (G/M) outcomes (n = 17; mean age: 46 months) were compared to patients with bad outcomes (n = 10; mean age: 26 months). NA/Cr and NA/Ch were significantly lower in the bad outcome group (NA/Cr = 1.15 +/- 0.38; NA/Ch = 1.18 +/- 0.52) compared to the G/M group (NA/Cr = 1.41 +/- 0.28, P < .05; NA/Ch = 1.98 +/- 0.81, P < .01). Lactate was present in 80% of bad outcome patients and in none of the G/M group (P < .0001). Using a linear discriminant analysis and combining 4 clinical variables (Glasgow Coma Scale score, initial pH and glucose, number of days unconscious at time of 1H-MRS) allows classification of 94% of patients into their correct outcome group. Use of spectroscopy variables (NA/Cr, NA/Ch, Ch/Cr, presence of lactate) alone correctly classified 81% of patients. The combination of clinical and 1H-MRS variables correctly classified 100% of patients. Our findings suggest that 1H-MRS adds information which, in combination with clinical examination, may be useful in outcome assessment in children with serious acute central nervous system injury.