Cytochemical, functional, and proliferative characteristics of promonocytes and monocytes from patients with monocytic leukemia

This article deals with a prospective study on the cytochemical, functional, and proliferative characteristics of promonocytes and bone marrow and peripheral blood monocytes of 20 patients with acute monocytic leukemia and 7 patients with chronic monocytic leukemia. The results show a wide variation in the peroxidase and esterase activities in these cells, whereas the percentages of mononuclear phagocytes with Fc gamma and C3b receptors did not differ appreciably from those in normal individuals. A discriminant analysis of these data and corresponding data from normal individuals showed that a below-normal peroxidase activity of circulating monocytes has predictive value for the presence of monocytic leukemia; a below-normal esterase activity has less, but nevertheless some, predictive value in this respect. An increase in the percentage of circulating monocytes, a decrease in the percentage of Fc gamma or C3b receptors, and a decline in the ability to phagocytose bacteria has no predictive value for the presence of monocytic leukemia. The mean percentage of patients' promonocytes that incorporated 3H-thymidine amounted to 80.9%, which is close to the control value in normal individuals. The mean values for the labeling indices of cultured bone marrow and peripheral blood monocytes are 1.0% and 0.74%, respectively; when 3H-thymidine was added to whole blood, the labeling index of the monocytes amounted to 3.6%. These percentages are only a little higher than those found for monocytes of normal individuals. These results indicate that the majority of the circulating monocytes in acute and chronic monocytic leukemia are not actively dividing or blast cells.     

Intrinsic neural circuits between dorsal midbrain neurons that control fear-induced responses and seizure activity and nuclei of the pain inhibitory system elaborating postictal antinociceptive processes: a functional neuroanatomical and neuropharmacological study

The blockade of GABA-mediated Cl(-) influx with pentylenetetrazol (PTZ) was used in the present work to induce seizures in Rattus norvegicus. The aim of this work was to study the involvement of monoamines in the antinociception induced by convulsions elicited by peripheral administration of PTZ (64 mg/kg). The analgesia was measured by the tail-flick test in seven or eight Wistar rats per group. Convulsions were followed by statistically significant increase in the tail-flick latencies (TFL), at least for 120 min of the postictal period. Peripheral administration of methysergide (0.5, 1, 2, and 3 mg/kg) caused a significant decrease in the TFL in seizing animals, as compared to controls, in all postictal periods studied. These findings were corroborated by the pretreatment with ketanserin, a 5-HT(2A/2C)-serotonergic/alpha(1)-noradrenergic receptors antagonist, at the same doses. Peripheral administration of yohimbine (0.5, 1, 2, and 3 mg/kg), alpha(2)-noradrenergic antagonist, also decreased the postictal analgesia either at initial or more terminal periods of the postictal analgesia. These data were corroborated with peripheral administrations of propranolol, a beta-noradrenergic receptor blocker that caused a decrease in the postictal analgesia consistently in later stages (after the first 20-min post-tonic-clonic convulsive reactions) of the post-seizure analgesia, except for the highest dose. These results indicate that monoamines may be involved in the postictal analgesia. The blockade of 5-HT(2A/2C)-serotoninergic, alpha(1)-noradrenergic, or alpha(2)-noradrenergic receptors before tonic clonic seizure-induced analgesia antagonized the increase in the nociceptive threshold caused by seizures in initial steps of the temporal antinociceptive curve, as compared to the blockade of beta-noradrenergic ones. These findings suggest that the recruitment of alpha-noradrenergic receptor and serotonergic receptors was made immediately after convulsions and in other initial periods of the postictal analgesia, as compared to the involvement of beta-noradrenergic receptor. Neurochemical lesions of the locus coeruleus (LC) and neuronal damage of the dorsal raphe nucleus induced a significant decrease of the postictal analgesia, suggesting the involvement of these nuclei in this antinociceptive process. The functional neuroanatomical study of the neural link between the mesencephalic tectum and nuclei of the central pain inhibitory system showed evidence for the interconnection between superior colliculus, both dorsal and ventral periaqueductal gray matter (PAG), and inferior colliculus. Defensive substrates of the inferior colliculus, also involved with wild running and epilepsy, send inputs toward dorsal raphe nucleus and locus coeruleus. Since these nuclei are rich in monoamines and send neural connections toward other monoaminergic nuclei of the brainstem involved with the control of the nociceptive inputs in the dorsal horn of the spinal cord, the present results offer a neuroanatomical and psychopharmacological basis for the antinociceptive processes following tonic-clonic seizures.     

Damage did not independently influence mortality in childhood systemic lupus erythematosus

Objective: To analyze clinical, laboratory and treatment features associated with death in a childhood-onset SLE population. Patients and methods: Patients with childhood-onset SLE followed at the State University of Campinas, Brazil, between 1980 and 2002 were included. Data on clinical and laboratory features of the disease were collected regularly. Logistic regression was used for analyzing association between clinical and laboratory features and death. Kaplan–Meyer tests were used to estimate the survival curves. Results: Of 61 patients identified, six were lost to follow-up during the first year of disease. The mean follow-up period of the remaining 55 patients was 3.25 years (SD=1.2). Mean SLICC/ACR-DI score was 4.9 (SD=3.4). Death occurred in 12 (21.8%) of 55 patients. Direct causes of death were: infection in six (50%), stroke in four (33.3%), and renal insufficiency in two (16.7%). Five patients (41.7%) died during the first 5 years of disease due to infection. Male gender (p=0.004; OR=9.1; 95% CI=7.6–21.0), infection (p=0.001; OR=4.2; 95% CI=1.6–15.2) and nephritis (p=0.02; OR=2.3; 95% CI=1.3–5.2) were independent factors associated with death in the multivariate analysis. The global survival rate adjusted for duration of disease was 93.9% in the first year of disease, 88.9% in the second year, 80.8% in the fifth year and 48.1% in 20 years of follow-up. When comparing survival curves, male gender, the presence of infection during the course of the disease and the presence of nephritis during follow-up had a worse survival. Conclusion: Male gender, the presence of infection and nephritis were independent risk factors for death in our Brazilian cohort. Damage did not independently influence survival in this study.     

The effect of age on functional outcome in mild traumatic brain injury: 6-month report of a prospective multicenter trial

OBJECTIVE: Elderly patients (aged 60 years and older) have been demonstrated to have an increased mortality after isolated traumatic brain injury (TBI); however, the prognosis of those patients surviving their hospitalization is unknown. We hypothesized that surviving elderly patients would also have decreased functional outcome, and this study examined the functional outcome of patients with isolated TBI at discharge and at 6 months posthospitalization. METHODS: This was a multicenter prospective study of all patients with isolated moderate to severe TBI defined as Head Abbreviated Injury Scale score of 3 with an Abbreviated Injury Scale score in any other body area of 1. Patients surviving to discharge gave their consent and were enrolled. Data collected included demographics, Glasgow Coma Scale (GCS) score at admission, and neurosurgical interventions. Outcome data included discharge disposition and Glasgow Outcome Scale score and modified Functional Independence Measure (FIM) score at discharge and at 6 months. RESULTS: Two hundred thirty-five patients were enrolled, with 44 (19%) aged greater than or equal to 65 years. Mechanisms of injury were falls (34%), assaults (28%), motor vehicle collisions (14%), pedestrian (11%), and other (12%). Falls were more common in the older patients and assaults in the younger group. The mean admitting GCS score was 12.8 (95% confidence interval [CI], 12.4-13.3), with older patients having a higher mean GCS score, 14.1 (95% CI, 13.6-14.6) versus 12.5 (95% CI, 12.0-13.1; p = 0.03). There were no differences in the percentage of patients admitted to the intensive care unit or requiring neurosurgical intervention between younger and older patients. Because there were few elderly patients with low GCS scores who survived to discharge, outcome measures focused on those patients with GCS scores of 13 to 15. A greater percentage of elderly were discharged to rehabilitation (28% vs. 16%, p =0.08). The mean discharge FIM score was 10.4 (95% CI, 9.8-11.0) for the elderly versus 11.4 (95% CI, 11.1-11.7) for the young (p =0.001), with 68% elderly and 89% young discharged with total independent scores of 11 to 12. At 6 months, the difference narrowed, but the mean FIM score was still greater for the young group, 11.7 (95% CI, 11.6-11.9) versus 11.0 (95% CI, 10.6-11.4; p < 0.001). CONCLUSION: Functional outcome after isolated mild TBI as measured by the Glasgow Outcome Scale and modified FIM is generally good to excellent for both elderly and younger patients. Older patients required more inpatient rehabilitation and lagged behind their younger counterparts but continued to recover and improve after discharge. Although there were statistically significant differences in the FIM score at both discharge and 6 months, the clinical importance of these small differences in the mean FIM score to the patient's quality of life is less clear. Measurable improvement in functional status during the first 6 months after injury is observed in both groups. Aggressive management and care of older patients with TBI is warranted, and efforts should be made to decrease inpatient mortality. Continued follow-up is ongoing to determine whether these outcomes persist at 12 months.     

The epidemiology of serious and fatal injury in San Diego County over an 11-year period

BACKGROUND: Analysis of the mechanism and severity of injury over time may permit a more focused planning of acute care and trauma prevention programs. METHODS: A retrospective, population-based study examining severe traumatic injury in a single county was undertaken. Three overlapping data sets were used to form a composite injury data set. RESULTS: There were 55,664 patients included in the study. A total of 40,897 (73.5%) patients survived and 14,767 (26.5%) died. Of those patients who died, 8,910 (60.3%) died in the field and were not transported to a trauma center. There was an increase in the mean age of all trauma victims (3 years) and an increase of 5 years in fatally injured patients. The mean Injury Severity Score decreased from 14.7 to 11.6 (p < 0.01); however, Injury Severity Score for fatal patients remained constant (39.7). The overall injury rate remained unchanged (195 per 10(5)), whereas the fatal injury rate decreased by 22% (45.9 per 10(5)) over the 11-year study period. The leading cause of injury was motor vehicle crash, followed by assault. The leading cause of fatal injury was suicide, followed by homicide. CONCLUSION: A combination of three independent injury data sources generated a composite data set of serious and fatal injury. This regional injury analysis was the most comprehensive overview of injury in our region. Important observations included the following: there has been no change in the overall incidence of severe injury within our county; the incidence of fatal traumatic injury has significantly decreased; the leading causes of nonfatal injury do not correlate with the rank order of fatal injury; intentional injury was the leading cause of injury deaths; and scene fatalities represent a poorly studied group of patients who may benefit from primary prevention and injury control research.     

The role of gender in the long-term prognosis of patients with myocardial infarction submitted to fibrinolytic treatment

PURPOSE: To determine the role of gender in short- and long-term survival after a thrombolytic-treated myocardial infarction. METHODS: A total of 686 consecutive patients with ST-elevation acute myocardial infarction, admitted to a single center and treated with intravenous streptokinase, were studied prospectively and consecutively. Assessment of clinical and in-hospital variables permitted comparison of baseline characteristics and both in-hospital and long-term survival between men and women. RESULTS: A significantly (odds ratio=0.48, P=0.009) lower 14-day mortality rate for males (8.5%) relative to females (16%) was noted. However, this difference became non-significant after adjustment for age (odds-ratio male/female=0.62, P=0.097) or age and other variables (odds ratio=0.71, P=0.17). At the end of the follow-up (up to 12 years), survival rates for the whole population were 59.6% and 54.4% for men and women, respectively (chi-square=1.4, P=0.24); excluding in-hospital deaths, the rates were 65.1% and 64.8%, respectively (chi-square=0.21, P=0.65). CONCLUSIONS: In the short-term follow-up, women have a significantly higher mortality relative to men in an unadjusted analysis. This difference became non-significant after adjusting for age, or age and other variables. In the long-term follow-up, sex was not correlated with prognosis.     

Rhombencephalosynapsis: CT and MRI findings

An unusual disorder of cerebellar development, rhombencephalosynapsis is a unique entity which presents with cerebellar fusion and absence of cerebellar vermis on imaging studies, often associated with supratentorial findings. No specific clinical syndrome has been described in these patients so far, and most cases are found in infancy and childhood. MRI and its multiplanar capabilities and high spatial and contrast resolution increased its recognition. Two cases are reported, with emphasis on imaging findings.     

Risk factors for low birthweight in north-east Brazil: the role of caesarean section

Caesarean section (CS) delivery is associated with low birthweight (LBW) in south‐east Brazil. A hospital‐based study was conducted on singleton infants from mothers residing in São Luís, to assess if an association between CS and LBW was found in the northern part of the country, where the CS rate is lower than in the south‐east. A standardised questionnaire was administered to a sample of 2541 mothers in 10 hospitals, representing 94% of all deliveries, from March 1997 to February 1998. In a logistic model, type of delivery was the independent variable, the other variables were treated as confounders, and interaction terms were added between type of delivery and all other factors. LBW was associated with low maternal height, maternal smoking, primiparity, previous LBW, public insurance, preterm birth and CS. The CS rate was 33.7%. The risk of CS was higher for primiparous and married mothers, those with high level of schooling and attended by the same physician during prenatal and delivery care, deliveries held in private hospitals, daylight hours or evenings, and for those mothers who had adequate prenatal care. Because it appears unlikely that only medical reasons are operative, it is a possibility that CS could cause LBW, reflecting abusive indications for elective CS.     

Prognostic Value of Proliferation Index and Expression of the RNA Component of Human Telomerase (hTR) in Papillary Meningiomas

Papillary meningioma is a rare subtype of meningioma that often behaves aggressively. In order to characterize factors that may influence this behavior, we chose to compare MIB-1 labeling index (LI) and telomerase RNA localization (hTR) in papillary meningiomas, meningiomas, and atypical meningiomas. LI is now often used to supplement histologic grade in the evaluation of these lesions. More recent studies indicate that increased expression of hTR is detected in many neoplastic cells, and may play an essential role in cell immortalization. The study group consisted of five papillary meningiomas (and a recurrence in one case), 11 conventional meningiomas, and eight atypical meningiomas. Conventional meningiomas showed either negative or 1+ hTR. Atypical meningiomas showed 1+ hTR. Papillary meningiomas showed the highest hTR (five of six, including recurrence, 2–3+ and one 1+). Generally, the LI was very low for conventional meningiomas (<2%). The LI of atypical meningiomas ranged from 3–19%, mean 12%, and from 5.5–17.5%, mean 11.75% for papillary meningiomas. LI differentiated between meningiomas, and papillary or atypical meningiomas. hTR further delineated papillary (moderate to high) from atypical meningiomas (low). The combined variable of LI and hTR expression could be a useful independent prognostic indicator in patients with papillary meningioma.     

Effects of opioid receptor blockade on defensive behavior elicited by electrical stimulation of the aversive substrates of the inferior colliculus in Rattus norvegicus (Rodentia, Muridae)

RATIONALE: Electrical or chemical stimulation of some structures of the midbrain tectum, such as the dorsal periaqueductal gray matter, deep layers of the superior colliculus and inferior colliculus induce fear and flight behavior. These structures constitute the main neural substrates commanding defensive behavior in brainstem. Many neurotransmitters are implicated in the modulation of aversion at the mesencephalic level. OBJECTIVE: The aim of this work is to investigate the involvement of opioid mechanisms in modulation of defensive behavior in dorsal mesencephalon. METHODS: Male Wistar rats were fixed in a stereotaxic frame and a chemitrode was implanted into the midbrain, targeted to the central nucleus of the inferior colliculus. In the present study, the effects of peripheral and central administration of naloxone, naltrexone or naloxonazine on aversive thresholds (freezing and escape reactions) elicited by electrical stimulation of the midbrain tectum were determined. RESULTS: Peripherally and centrally administered naloxone caused a significant increase in the freezing and flight thresholds elicited by electrical stimulation of the aversive substrates of the inferior colliculus. These effects were confirmed by peripheral and central administration of naltrexone and by microinjections of naloxonazine in inferior colliculus. CONCLUSIONS: These findings suggest that endogenous opioids are involved in the modulation of the aversive behavior elicited by midbrain tectum stimulation. Since microinjections of naloxonazine in the central nucleus of the inferior colliculus caused a significant increase in the aversive thresholds elicited by electrical stimulation of this structure, it is possible that micro1 opioid receptor located in this nucleus may be critically implicated in this neural circuitry.