Cardiogenic shock: thrombolysis or angioplasty?

Cardiogenic shock (CGS) occurs in 3 to 20% of patients presenting with acute myocardial infarction (MI), and it generally involves dysfunction of at least 40% of the total myocardial mass. Prior to the advent of balloon angioplasty and thrombolysis, in-hospital mortality was greater than 75%. This mortality rate has been consistent in reported series despite the advent of cardiac intensive care units, vasopressor, inotropic, and vasodilator therapy. Intra-aortic balloon counterpulsation therapy provides hemodynamic improvement, and it may provide some mortality benefit when used in conjunction with appropriate revascularization. Survival studies have shown that patency of the infarct-related artery is a strong predictor of survival. No randomized trials have been completed to examine which reperfusion therapy best treats this emergent situation. Subgroup analysis of large scale, multicenter trials, although underpowered, has shown no improvement in mortality with use of thrombolytic agents, leading many to advise use of mechanical intervention. In patients who present with acute MI with contraindications to thrombolysis, primary angioplasty is the treatment of choice. At selected centers, primary angioplasty is comparable to or better than thrombolytic therapy for patients presenting with acute MI, with or without CGS. Studies examining angioplasty in patients with CGS have shown high procedural success rates (75%) and reduced in-hospital mortality (44%), particularly in those patients with successful revascularization. Emergency bypass surgery may improve survival, but it is costly, unavailable to many, and often leads to excessive delays in therapy. If available, we believe that primary angioplasty is the treatment of choice for patients with CGS.     

Immunoproteins in human brain tumor cyst fluids

Quantitation of the concentration of immunoproteins in serum, and cystic fluids from six patients (three with cerebral astrocytoma and three with cerebellar hemangioblastoma) has been determined. The values for total protein, albumin, immunoproteins IgG, IgA, and IgM, and C3C (complement) in cyst fluid more closely correspond to serum than to cerebrospinal fluid values. Values for cyst fluid, cerebrospinal fluid, and serum were determined using albumin ratios in order to compare relative differences between fluids from these three compartments. Our data suggests that: 1) the major protein content of brain tumor cyst fluid is consequential to a transudative process from serum, and 2) that immunoglobulins IgG and IgA are present in higher concentrations in human brain tumor cyst fluids in comparison to IgM concentrations. These studies further question the concept of the brain as an "immunological privileged site", and may be of direct relevance to the investigation of the use of immunotherapeutic modalities as an adjunct after surgical tumor removal.     

Experimental tests of three-dimensional model of urinary concentrating mechanism.

Recently, a new model of the urinary concentrating process has been proposed that takes into account the three-dimensional architecture of the renal medulla. Under the assumptions of the model, computer simulations predicted significant axial osmolality gradients in the inner medulla without active transport by the inner medullary loop of Henle. Two of the model assumptions (which constitute hypotheses for this study) were: (1) the osmotic water permeability of the initial part of the inner medullary collecting duct (initial IMCD) is very low even in the presence of vasopressin; and (2) there is significant lateral separation of structures such that thin descending limbs are far from the collecting ducts at the same inner medullary level. The first hypothesis was addressed by perfusing rat initial IMCD segments in vitro and measuring osmotic water permeability. With the osmotic gradient oriented as predicted by the model (lumen greater than bath), vasopressin increased the osmotic water permeability from 286 to 852 microns/s. Three additional series of experiments confirmed the high water permeability in the presence of vasopressin. The second hypothesis was addressed by morphometric analysis of histologic cross-sections of the rat renal medulla. Mean distances of descending limbs to the nearest adjacent collecting duct were very small throughout the inner medulla (less than 6 microns) and substantially less than in the outer medulla (28 microns). It was concluded that the data are inconsistent with both hypotheses and therefore do not support the feasibility of the "three-dimensional" model of the renal inner medulla. The axial distributions of loops of Henle and collecting ducts in the rat renal medulla are also reported.     

Role of macrophages in onion-bulb formation in localized hypertrophic mononeuritis (LHM).

A unique pathogenetic process for onion-bulb (Ob) formation is disclosed with disclosed with immunohistochemistry and electron microscopy. Biopsy of a swollen segment of tibial nerve from a 42 year-old white female histologically demonstrated diffuse and angiocentric lymphocytic infiltrate in both endo- and perineurium with occasional lymphofollicular formation. Extensive Ob formation of nerve fibers was most striking with or without associated lymphocytes. Axis-cylinders were intact in the majority of Ob. Immunocytochemically, Ob are composed of alternately laminated leaflets of Schwann cells (S100+) and mononuclear macrophage (HAM56+/LeuMl+/Muramidase+) processes but no perineurial (EMA+) cells. Immunohistochemical evidence of antigen presentation (HLA-DR/LN3+/Ia+) was confined to macrophages. Electron microscopy insinuates that intricate interactions between macrophages and Schwann cells exists. Putative inhibition of remyelination along with proliferation of Schwann cells most probably is secondary to the effects of macrophages secretory products. No direct participation of B or T lymphocytes was detected in Ob. Thus, modified macrophages may emit a factor for concomitantly promoting proliferation of Schwann cells and an enzyme for myelin breakdown. In addition, only a few macrophages could be detected in some Ob and could be easily overlooked or misinterpreted as "vacuolated fibroblasts", if no immunohistochemical correlation is made, as modified macrophages making the external leaflets of Ob are more vacuolated.     

Tumorigenicity of 7, 12-dimethylbenz[a]anthracene, its hydroxy-methylated derivatives and selected dihydrodiols in the newborn mouse

The newborn mouse lung adenoma model has been shown to be asensitive test for studying the tumor-igenicity of bay regiondiol epoxides and their precursor dihydrodiols. When a totaldose of 28 nmol of 7, 12-dimethylbenz[a]anthracene (DMBA) orits derivatives was injected i.p. into the preweaning mice,it was found that the 3, 4-dihydrodiols of both DMBA and 7-hy-droxymethyl-12-methylbenz[a]anthracenecaused 13.3 and 4.1 times more lung adenomas than DMBA, respectively.The mice treated with the 5, 6- and 8, 9-dihydro-diols of DMBA,7-hydroxymethyl-12-methylbenz[a]-anthracene and its 5, 6- 8,9-and 10,11-dihydrodiols, 7-methyl-12-hydroxymethylbenz[a]an-thraceneand 7,12-dihydroxymethylbenz[a]anthracene developed a levelof lung adenomas/mouse less than Mold higher than that foundin the DMSO-treated control group. Liver tumors also developedin some of the mice. The percentage of mice with liver tumorsalso indicated that the 3, 4-dihydrodiols of both DMBA and 7-hydroxymethyl-12-methylbenz[a]anthracenewere more tumorigenic than DMBA itself. These data indicatethat the 3, 4-dihydrodiols of both DMBA and its 7-hydroxymethylderivative may be proximate carcinogenic metabolites of DMBAin the newborn mouse.     

Effects of support group intervention in postnatally distressed women. A controlled study in Taiwan

Objective: The symptoms of depression experienced by women during the postnatal period may have profound effects on the lifelong health of both the mother and the child. In this randomized controlled study, we systematically evaluated the effects of weekly supportive group meetings for women with postnatal distress. Methods: Sixty postnatally distressed women were randomly assigned to support (n=30) and control (n=30) groups. Women assigned to the support group participated in four supportive group sessions that comprised discussions concerning transition to motherhood, postnatal stress management, communication skills, and life planning. Results: Subjects who attended the support sessions had significantly decreased scores on the Beck Depression Inventory (BDI) and the Perceived Stress Scale (PSS), and significantly increased scores on the Interpersonal Support Evaluation List (ISEL) as evaluated at the end of the fourth weekly session. In contrast, no significant changes were observed in the control group during this period. Conclusion: This is the first controlled study to provide evidence that participation in support groups for postnatally distressed women provides quantifiable psychosocial benefits.     

Unexpected recurrent seizures following repeated spinal injections of tetracaine--a case report

A 36-year-old male patient was scheduled to undergo ureteroscopic lithotomy because of left ureteral stone under spinal anesthesia. After receiving a renewed spinal anesthesia with 8 mg tetracaine to compensate for the first attempt (with 10 mg tetracaine), which proved to be a failure, he was soon seized with episodic seizure attacks. Central nervous system toxicity of the local anesthetic might be the cause of the seizure. We brought forward this case for discussion for warning that the possibility of systemic toxicity of local anesthetic might exist despite a seemingly undisputable spinal anesthesia.     

Effects of intermittent exposure to aflatoxin B1 on DNA and RNA adduct formation in rat liver: dose-response and temporal patterns.

We studied the effects of intermittent exposure to aflatoxin B1 (AFB1) on hepatic DNA and RNA adduct formation. Fisher-344 male rats were fed 0.01, 0.04, 0.4, or 1.6 ppm of AFB1 intermittently for 8, 12, 16, and 20 weeks, alternating with 4 weeks of dosing and 4 weeks of rest. Other groups of rats were fed 1.6 ppm of AFB1 continuously for 4, 8, 12, and 16 weeks. Control rats received AFB1-free NIH-31 meal diet. AFB1-DNA and -RNA adducts were measured by HPLC with fluorescence detection. The data are presented as total DNA or RNA adducts. The DNA and RNA adduct levels increased or decreased depending on the cycles of dosing and rest. Rats removed from treatment 1 month after 1 or 2 dosing cycles (8 and 16 weeks of intermittent exposure) showed approximately a twofold decrease in DNA adduct levels and a two- to elevenfold decrease in RNA adduct levels compared with rats euthanized immediately after the last dosing cycle (12 and 20 weeks of intermittent exposure). Our data indicate that DNA and RNA adducts increased linearly, from 0.01 ppm to 1.6 ppm of AFB1 after 12 and 20 weeks of intermittent treatment. A linear dose response was also apparent for DNA but not for RNA adducts after 8 and 16 weeks of treatment. As biomarkers of exposure, AFB1-RNA adducts were three to nine times more sensitive than AFB1-DNA adducts but showed greater variability. These results suggest that binding of AFB1 to hepatic DNA is a linear function of the dose, regardless of the way this is administered. The dose-response relationship for RNA adducts depends on the length of the no-dosing cycles and on the turnover rate of RNA.     

Recombinant human relaxin as a cervical ripening agent

Objective The aim of this study was to investigate the efficacy and safety of recombinant human relaxin (rhRIx) as a cervical ripening agent in women with an unfavourable cervix before induction of labour at term.
Design A multi-centre, double-blind, placebo-controlled trial performed in Edinburgh, Glasgow and Oxford. Women were treated with 0, 1, 2 or 4 mg of rhRIx in a gel vehicle administered intravaginally. Analysis of variance tests were performed on all continuous variables, and Cochran Mantel-Haenszel tests employed for all discrete variables.
Participants Ninety-six women at 37 to 42 weeks of gestation with a singleton pregnancy and a modified Bishop score of 4 were recruited.
Results There was no significant difference in the change in modified Bishop score between the four treatment groups. The lengths of the first and second stages of labour were similar in all 4 groups. PGE₂ and oxytocin requirements were similar in all groups, as was the mode of delivery. There was no evidence that relaxin was absorbed systemically when given in this way.
Conclusion Recombinant human relaxin 1 to 4 mg, administered as an intravaginal gel, has no effect as a cervical ripening agent before induction of labour at term.     

ANALYSIS OF APOPTOSIS BY DNA END LABELING METHOD (TDT) IN LEUKEMIA CELL LINES HL-60 AND U937

Apoptosisisakindofcelldeathrecognizablebyaseriesofspecializedchangesinmorphological,biochemicalandmolecularbiologicalforms.Apoptosisisanactiveprocessofcelldestruction,characterizedbycellshrinkage,chromatinaggregationwitheXtensivegenomicfragmentation,crescentbodyformingbychromosomepyknosisalongthenuclearmargin.Intheapoptosis,endouncleaseasedependentCa2 andMg2 isactivated,thisenzymemakechromosomedegradedatthelinkersectionstofragmentsequivalenttosingleandmultiplenucleosomes.Thelatterarerevealeda…