The impact of ionizing radiation on placental trophoblasts.

INTRODUCTION: Exposure to low-dose radiation is widespread and attributable to natural sources. However, occupational, medical, accidental, and terrorist-related exposures remain a significant threat. Information on radiation injury to the feto-placental unit is scant and largely observational. We hypothesized that radiation causes trophoblast injury, and alters the expression of injury-related transcripts in vitro or in vivo, thus affecting fetal growth. METHODS: Primary human trophoblasts (PHTs), BeWo or NCCIT cells were irradiated in vitro, and cell number and viability were determined. Pregnant C57Bl/6HNsd mice were externally irradiated on E13.5, and placentas examined on E17.5. RNA expression was analyzed using microarrays and RT-qPCR. The experiments were repeated in the presence of the gramicidin S (GS)-derived nitroxide JP4-039, used to mitigate radiation-induced cell injury. RESULTS: We found that survival of in vitro-irradiated PHT cell was better than that of irradiated BeWo trophoblast cell line or the radiosensitive NCCIT mixed germ cell tumor line. Radiation altered the expression of several trophoblast genes, with a most dramatic effect on CDKN1A (p21, CIP1). Mice exposed to radiation at E13.5 exhibited a 25% reduction in mean weight by E17.5, and a 9% reduction in placental weight, which was associated with relatively small changes in placental gene expression. JP4-039 had a minimal effect on feto-placental growth or on gene expression in irradiated PHT cells or mouse placenta. DISCUSSION AND CONCLUSION: While radiation affects placental trophoblasts, the established placenta is fairly resistant to radiation, and changes in this tissue may not fully account for fetal growth restriction induced by ionizing radiation.

Prevalence of periodontal pathogens in subgingival lesions, atherosclerotic plaques and healthy blood vessels: a preliminary study.

BACKGROUND AND OBJECTIVE: Previous studies have reported different periodontal bacteria in atherosclerotic lesions, but their involvement in plaque formation remains unclear. The aim of the present study was to investigate the presence of 20 periodontal bacteria in atherosclerotic samples and healthy blood vessels (used as controls) and to clarify their relationship in regard to clinical and bacteriological periodontal status. MATERIAL AND METHODS: The day before vascular surgery the patients had a thorough periodontal examination and bacteriological samples were taken from periodontally diseased sites. Atheromatous plaques, internal mammary arteries and saphenous veins were harvested during surgery. A DNA-DNA hybridization procedure was used to screen periodontal and vascular samples for the 20 selected bacterial species. RESULTS: Periodontal samples from the severe periodontitis group were found to have a higher prevalence and biomass of bacterial species than the moderate periodontitis group. In vessel samples, the prevalence of the same 20 bacterial species analyzed together was similar in the two groups, except for saphenous veins. CONCLUSION: The presence of periodontal pathogens in atherosclerotic plaques and in apparently healthy vessels appeared to reflect a higher level of bacteremia rather than infection of endothelial cells.

Combined intravenous and intra-arterial recombinant tissue plasminogen activator in acute ischemic stroke.

BACKGROUND AND PURPOSE: A retrospective analysis was performed on 20 consecutive patients who presented with severe acute ischemic stroke and were evaluated for a combined intravenous (IV) and local intra-arterial (IA) recombinant tissue plasminogen activator (rtPA) thrombolytic approach within 3 hours of onset. METHODS: Twenty consecutive patients with carotid artery distribution strokes were evaluated and treated using a combined IV and IA rtPA approach over a 14-month period (September 1998 to October 1999). rtPA (0.6 mg/kg) was given intravenously (maximum dose 60 mg); 15% of the IV dose was given as bolus, followed by a continuous infusion over 30 minutes. A maximal IA dose, up to 0.3 mg/kg or 24 mg, whichever was less, was given over a maximum of 2 hours. IV treatment was initiated within 3 hours in 19 of 20 patients. All 20 patients underwent angiography, and 16 of 20 patients received local IA rtPA. RESULTS: The median baseline National Institutes of Health Stroke Scale (NIHSS) score for the 20 patients was 21 (range 11 to 31). The median time from stroke onset to IV treatment was 2 hours and 2 minutes, and median time to initiation of IA treatment was 3 hours and 30 minutes. Ten patients (50%) recovered to a modified Rankin Scale (mRS) of 0 or 1; 3 patients (15%), to an mRS of 2; and 5 patients (25%), to an mRS of 4 or 5. One patient (5%) developed a symptomatic intracerebral hemorrhage and eventually died. One other patient (5%) expired because of complications from the stroke. CONCLUSIONS: We believe that the greater-than-expected proportion of favorable outcomes in these patients with severe ischemic stroke reflects the short time to initiation of both IV and IA thrombolysis.

Thrombolytic therapy for pulmonary embolism. Frequency of intracranial hemorrhage and associated risk factors.

STUDY OBJECTIVES: To determine the risk factors and frequency of intracranial hemorrhage among patients undergoing thrombolysis for pulmonary embolism. DESIGN: A retrospective descriptive and controlled analysis. SETTING: Hospitalized patients at centers in the United States, Canada, and Italy. PATIENTS: All had evidence of pulmonary embolism on perfusion scans or angiography. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Data were analyzed on 312 patients from five previously reported studies of pulmonary embolism thrombolysis. The frequency of intracranial hemorrhage up to 14 days after pulmonary embolism thrombolysis was 6 of 312 or 1.9% (95% confidence interval, 0.7 to 4.1%). Two of six intracranial hemorrhages were fatal. Two of the six patients received thrombolysis in violation of the protocol because they had pre-existing, known intracranial disease. Average diastolic BP at the time of hospital admission was significantly elevated in patients who developed an intracranial hemorrhage (90.3 +/- 15.1 mm Hg) compared with those who did not (77.6 +/- 10.9 mm Hg; p = 0.04). Other baseline characteristics and laboratory data were similar in both groups. Decreased level of consciousness, hemiparesis, and visual field deficits were the most common clinical signs of intracranial hemorrhage. CONCLUSIONS: Intracranial hemorrhage after pulmonary embolism thrombolysis is an infrequent but often grave complication. Meticulous patient screening before administering thrombolysis is imperative. Diastolic hypertension at the time of hospital admission is a risk factor for intracranial hemorrhage after pulmonary embolism thrombolysis.

Variability in length of hospitalization for stroke. The role of managed care in an elderly population.

OBJECTIVES: To measure hospital stay for acute stroke care and to describe health services and demographic factors associated with longer length of stay (LOS). DESIGN: Observational, retrospective consecutive case series. SETTING: Large tertiary-care teaching hospital in Massachusetts. PATIENTS: The patient population comprised 745 patients aged 65 years and older admitted with ischemic stroke from 1982 through 1995. MAIN OUTCOME MEASURES: Hospital LOS (1-5, 6-10, and >10 days) as well as total charges and discharge location. RESULTS: Median LOS was 7 days (range, 1-289 days), and median total charges were $8740 (range, $522-$135172); LOS explained 62% of the variance in total charges. Insurance status was a major factor in determining LOS: after possible confounders were controlled for, patients enrolled in a health maintenance organization were significantly less likely to have long hospital stays (odds ratio [OR], 0.45; 95% confidence interval, 0.31-0.66) than were conventional Medicare enrollees, while the LOS of patients with other insurance coverage was no different from that of Medicare patients. Longer LOS was significantly associated with greater comorbidity (OR, 1.52 for a Charlson comorbidity index >2), institutionalization prior to hospital admission (OR, 1.83), and unmarried status (OR, 1.37) and was inversely associated with year of admission (OR, 0.30 in years 1991-1995 vs 1982-1986). Age, sex, and race were not associated with LOS. Discharge to a nursing home or inpatient rehabilitation site was not associated with type of insurance coverage (OR, 1.10; 95% confidence interval, 0.72-1.69 for patients in a health maintenance organization vs conventional Medicare patients). CONCLUSIONS: There is marked variability in length of hospital stay for ischemic stroke among the elderly, even after underlying patient differences are controlled for. Managed care may result in increased efficiency of in-hospital care and improved discharge planning for these patients; further study of the ultimate clinical outcomes of such care is needed.

Apolipoprotein E epsilon 4 is associated with the presence and earlier onset of hemorrhage in cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy is an important cause of intracerebral hemorrhage in the elderly. The epsilon 4 allele of the apolipoprotein E gene, recently established as a genetic risk for Alzheimer's disease, has also been suggested as a possible risk factor for cerebral amyloid angiopathy. We sought to determine whether this allele is specifically associated with hemorrhages related to amyloid angiopathy and whether it correlates with the age at which first amyloid angiopathy-related hemorrhage occurs. METHODS: Forty-five consecutive patients presenting with lobar hemorrhage were prospectively classified according to clinical, radiological, and when available, pathological features and evaluated for apolipoprotein E genotype. They were compared with 1899 elderly patients from a population-based sample and with 18 consecutive patients with hemorrhages in deep regions typical of a hypertensive mechanism. RESULTS: Patients with multiple hemorrhages confined to the lobar territory demonstrated a greater than twofold overrepresentation (P < .001) in frequency of the apolipoprotein E epsilon 4 allele compared with the population-based sample. Apolipoprotein E genotypes of patients with hemorrhages in deep territories resembled the population sample. Among patients with strictly lobar hemorrhages, carriers of the epsilon 4 allele had their first hemorrhage more than 5 years earlier than noncarriers (mean age at first hemorrhage, 73.4 +/- 8.0 versus 78.9 +/- 7.4 years; P = .033). These effects were independent of the accompanying presence of Alzheimer's disease. CONCLUSIONS: The data support a specific role for apolipoprotein E epsilon 4 in accelerating the process that leads to amyloid angiopathy-related hemorrhage.

Fluvoxamine maleate in the treatment of depression: a single-center, double-blind, placebo-controlled comparison with imipramine in outpatients.

The efficacy and safety of fluvoxamine maleate, a selective serotonin reuptake inhibitor, was compared with placebo and imipramine in patients with major depressive disorder. Previous literature has cited a dose range of 100 to 300 mg/day of fluvoxamine maleate for the treatment of major depression; however, this study demonstrates that a dose range of 50 to 150 mg/day is as effective as imipramine (80-240 mg/day). After a 1- to 2-week, single-blind, placebo washout phase, 150 depressed outpatients were randomized to double-blind treatment with fluvoxamine maleate (50-150 mg/day), imipramine (80-240 mg/day), or placebo for 6 weeks. Fluvoxamine produced a significant therapeutic benefit over placebo (p < or = 0.05) as assessed by the total score on the Hamilton Rating Scale for Depression; imipramine (80-240 mg/day) produced similar results. The secondary outcome variables (i.e., Clinical Global Impression severity of illness item and 56-Item Hopkins Symptom Checklist depression factor) also showed significant differences between fluvoxamine maleate and placebo during three of the four final weeks of the study. Both fluvoxamine maleate and imipramine appeared to be safe and well tolerated by the majority of patients. As expected from the pharmacology of these agents, the imipramine groups reported more anticholinergic effects (dry mouth, dizziness, and urinary retention) and electrocardiographic effects, whereas the fluvoxamine group reported more nausea, somnolence, and abnormal ejaculation. The majority of these adverse events were mild to moderate and, with the exception of dry mouth (imipramine) and abnormal ejaculation (fluvoxamine), were transient. The data clearly demonstrate the antidepressant activity and tolerability of fluvoxamine maleate (50-150 mg/day) as compared with placebo; it is also as effective as the tricyclic antidepressant imipramine (80-240 mg/day) in patients with major depressive disorder.

Electrocardiographic findings during extended clinical trials of fluvoxamine in depression: one years experience.

INTRODUCTION: Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), is used to treat depression. No significant effect on the electrocardiogram (ECG) has been reported during short-term controlled studies of SSRI's. We report a long-term (1 year) multi-center, double-blind controlled study of the ECG during treatment of depression with fluvoxamine (FX), active control medication (TCA), and placebo (PLA). METHOD: Initially ECGs were obtained from 1840 physically healthy, depressed outpatients who were treated with FX, TCA, or PLA for 6 weeks. A subset of these patients continued treatment for up to one year. Complete sets of ECGs were obtained from 462 of these patients. Patients whose depression was substantially improved in the initial 6-week study ("responder") received the same medication. Non-responders received a blinded active medication. Pre-treatment, intra-study, and past-treatment ECGs were recorded according to protocol. One blinded electrocardiographer measured and analyzed all ECG data. The effects of each medication upon the ECG were measured and compared. RESULTS: Of the 462 patients, 311 used FX, 100 used TCA and 51 used PLA. Analyses of ECG data for each treatment focused on changes in ECG measurements; % of normal ECGs, and % of individual ECG findings. The ECG changes during FX treatment were less than or not significantly different from the ECG changes with PLA treatment. The changes with TCA were as expected. CONCLUSIONS: Fluvoxamine treatment of depression for one year was not associated with any significant effect on the ECG.

Salicylic Acid in Rice (Biosynthesis, Conjugation, and Possible Role).

Salicylic acid (SA) is a natural inducer of disease resistance in some dicotyledonous plants. Rice seedlings (Oryza sativa L.) had the highest levels of SA among all plants tested for SA content (between 0.01 and 37.19 [mu]g/g fresh weight). The second leaf of rice seedlings had slightly lower SA levels than any younger leaves. To investigate the role of SA in rice disease resistance, we examined the levels of SA in rice (cv M-201) after inoculation with bacterial and fungal pathogens. SA levels did not increase after inoculation with either the avirulent pathogen Pseudomonas syringae D20 or with the rice pathogens Magnaporthe grisea, the causal agent of rice blast, and Rhizoctonia solani, the causal agent of sheath blight. However, leaf SA levels in 28 rice varieties showed a correlation with generalized blast resistance, indicating that SA may play a role as a constitutive defense compound. Biosynthesis and metabolism of SA in rice was studied and compared to that of tobacco. Rice shoots converted [14C]cinnamic acid to SA and the lignin precursors p-coumaric and ferulic acids, whereas [14C]benzoic acid was readily converted to SA. The data suggest that in rice, as in tobacco, SA is synthesized from cinnamic acid via benzoic acid. In rice shoots, SA is largely present as a free acid; however, exogenously supplied SA was converted to [beta]-O-D-glucosylSA by an SA-inducible glucosyltransferase (SA-GTase). A 7-fold induction of SA-GTase activity was observed after 6 h of feeding 1 mM SA. Both rice roots and shoots showed similar patterns of SA-GTase induction by SA, with maximal induction after feeding with 1 mM SA.

Plasmapheresis in fulminant acute disseminated encephalomyelitis.

We describe two patients with fulminant acute disseminated encephalomyelitis (ADEM) treated with plasmapheresis after they failed to improve on steroids. Both patients improved concomitant with the plasma exchange. These are the first reported cases of fulminant ADEM with extensive white matter abnormalities on imaging studies treated with a regimen of plasmapheresis and steroids. Plasmapheresis may be beneficial in this disorder.

Communication of the monitoring and evaluation process through the use of storyboards and story notebooks.

In preparation for the 1993 Joint Commission on Accreditation of Health Care Organizations (JCAHO) survey, Audie L. Murphy Memorial Veterans Hospital Nursing Service was faced with determining the best approach to presenting their Total Quality Improvement/Total Quality Management (TQI/TQM) process. Nursing Service management and staff, Quality Improvement Clinicians, and medical staff used the Storyboard concept and the accompanying Story Notebooks to organize and to communicate their TQI/TQM process and findings. This concept was extremely beneficial, enabling staff to successfully present the multidisciplinary TQI/TQM data to the JCAHO surveyors.

Excess morbidity associated with interhospital transport.

A prospective study was performed to determine whether excess morbidity occurred in critically ill and injured pediatric patients during interhospital transport compared with morbidity in a control group. Control observations were made during the first 2 hours of pediatric intensive care unit (PICU) care of patients emergently admitted from within the same institution and not requiring interhospital transport. The first 2 PICU hours of control patients corresponded to the interval of transport in those who required interhospital transfer. Transport care was provided by nonspecialized teams from referring hospitals. Morbidity occurred in 20.9% of 177 transported patients, exceeding the morbidity rate of 11.3% in 195 control patients (P < .05). The difference in morbidity was due to intensive care-related adverse events (eg, plugged or dislodged endotracheal tubes, loss of intravenous access) in 15.3% and 3.6% of transported and control patients, respectively (P < .05). Physiologic deterioration occurred at similar rates of 7.9% and 8.7% in transported and control patients, respectively (P > .05). Slightly greater pre-ICU severity of illness in transported than control patients (median Pediatric Risk of Mortality Score = 10 and 7, respectively, P < .05) and greater pre-ICU therapy relative to severity (P < .05) in control patients are potential confounding sources of the morbidity differences. If patients are stratified into subgroups of similar pre-ICU severity, an excess of intensive care-related adverse events in transported patients remains evident in the severe subgroup (P < .05). Further investigation is warranted to determine whether specialized transport teams can reduce the excess morbidity associated with interhospital transport of critically ill and injured pediatric patients.

[Widows and neighbors, cornfields and magueys. The impact of population increase in the Toluca Valley: the case of Tenango del Valle during the eighteenth century]. / Viudas y vecinos, milpas y magueyes. El impacto del auge de la poblacion en el Valle de Toluca: el caso de Tenango del Valle en el siglo XVIII.

PIP: The author examines the effect of rapid population growth due to migration on the parish of Tenango del Valle, Mexico, during the eighteenth century. She gives special consideration to the impact on quality of life in indigenous villages, especially for widows and female heads of households who were impoverished as a result of discriminatory land transactions. Data are mainly from the parish register for 1770.^ieng

See-saw nystagmus and brainstem infarction: MRI findings.

A patient with see-saw nystagmus had a lesion localized by Magnetic Resonance Imaging (MRI) to the paramedian ventral midbrain with involvement of the right interstitial nucleus of Cajal. This the first MRI study of see-saw nystagmus associated with a presumed brainstem vascular event. Our findings support animal and human studies suggesting that dysfunction of the interstitial nucleus of Cajal or its connections is central in this disorder.

Plasma propranolol levels and their effect on plasma thioridazine and haloperidol concentrations.

The relationship between chronic oral dosage with a long-acting formulation of propranolol and plasma propranolol levels 22 to 23 hours later is described in 12 adult male patients with organic brain disease. Separately, the effects on plasma levels of thioridazine plus metabolites with concomitant rising dose long-acting propranolol administration were studied in five patients. Significant dose-related increases in levels of thioridazine and metabolites were found when long-acting propranolol was given. No changes in haloperidol levels were found in three patients studied in a similar protocol.

Therapeutic effects of pindolol on behavioral disturbances associated with organic brain disease: a double-blind study.

A double-blind, placebo-controlled crossover study was conducted to examine the effects of pindolol for the treatment of 11 patients with impulsive, explosive behaviors and other emotional-behavioral abnormalities as a consequence of brain disease or injury. Pindolol treatment was associated with significant therapeutic benefits without sedation and without the use-limiting side effects that occur with propranolol.

Propranolol treatment of assaultive patients with organic brain disease. A double-blind crossover, placebo-controlled study.

A double-blind, placebo-controlled crossover study was conducted to examine the effects of long-acting propranolol in the treatment of violent behavior associated with organic brain disease in 10 patients whose symptoms had proved refractory to various conventional medications. Long-acting propranolol treatment was associated with reductions of assaultive behavior without apparent sedative effects. Cautions are noted regarding potential undesirable side effects which may necessitate careful patient monitoring during treatment.

A comparison of differential white blood cell counts using manual technic and the Coulter S-Plus IV.

The results of 100-cell and 500-cell manual differential white blood cell counts were compared with those obtained using a Coulter S-Plus IV electronic particle counter. Significant (P less than 0.001) correlations were observed between the manual and instrument-derived data for percentages of granulocytes and lymphocytes.