Lowering platelet count threshold to 10,000/µL for peripherally inserted central catheter placement safely conserves blood products

Annals of Hematology - Despite the low risk of peripherally inserted central catheter (PICC) insertion-related bleeding, the practice of administering prophylactic platelets varies greatly....     

Value and limitations of Holter monitoring and electrophysiologic testing in the evaluation of the treatment of sustained monomorphic ventricular tachycardia

The authors studied the value and limitations of Holter monitoring and electrophysiological investigation in the evaluation of treatment of sustained monomorphic ventricular tachycardia (VT). One hundred and twenty-four consecutive patients were included in the study from January 1981 to February 1988. The etiologies were chronic myocardial infarction (N = 54), dilated cardiomyopathy (N = 24), right ventricular dysplasia (N = 31), and idiopathic VT (N = 15). All the tachycardias could be induced during baseline electrophysiological investigations and presented as complex ventricular arrhythmias on the Holter recordings. The investigations were repeated after treatment which was maintained irrespective of the results, unless the tachycardia which was induced or recorded was over 130 cycles/min and/or poorly tolerated. Recurrence was defined as the recording of VT in the absence of a change of treatment and/or the occurrence of sudden death. The follow-up period averaged 29 +/- 21 months. The Kaplan-Meier method was used to study the prevalence of absence of recurrence and survival rates. We observed 28 recurrences of VT and there were 21 deaths. Eighty-five per cent of patients had normal Holter monitoring after treatment. The prevalence of absence of recurrence was 0.751 when the Holter was normal and 0.485 when an arrhythmia was recorded (p = 0.03). The sensitivity was 25 per cent and the specificity 88 per cent. The survival rates were 0.66 and 0.585 respectively (p = 0.008). Fifty-three per cent of patients remained inducible after treatment with a prevalence of absence of recurrence of 0.572. This value rose to 0.877 when VT could not be induced (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the effect of beta adrenergic antagonists with different ancillary properties on isolated canine and human coronary arteries

Experiments were performed on canine and human isolated coronary arteries to characterise human coronary beta adrenoceptors and to determine whether or not beta blocking agents with different ancillary properties unmask the alpha adrenergic effect of noradrenaline in a similar way. The inhibitory effects of atenolol (a beta1 selective antagonist), epanolol (a beta1 selective antagonist with modest intrinsic sympathetic activity), and propranolol (a non-selective antagonist) were assessed on isoproterenol concentration-response curves. Regression analysis provided slopes not significantly different from unity and similar pA2 values for each agent in both preparations. In a second group of experiments, the effects of noradrenaline (10 mumol.litre-1) were assessed in the absence and presence of beta blockade. At equipotent doses (1 log or 2 log units from the pA2 values) each beta blocking agent unmasked the alpha effect of noradrenaline in the same way. This alpha effect of noradrenaline (10 mumol.litre-1) was completely abolished by prazosin 1 mumol.litre-1 in canine coronary arteries but only partially antagonised in human coronary arteries. Thus the property of a beta blocking agent to unmask the alpha adrenergic effect of adrenaline is mainly related to its affinity for the coronary smooth muscle beta adrenoceptors. These beta adrenoceptors were very similar in both preparations and appear to be mainly beta1. The alpha adrenoceptors seem, nevertheless, to be different and resistant to prazosin in human preparations.     

No loss of genomic imprinting of IGF-II and H19 in placentas of diabetic pregnancies with fetal macrosomia.

OBJECTIVES: Fetal macrosomia is a common complication of maternal diabetes mellitus and is associated with substantial morbidity, but the precise cellular and molecular mechanisms that induce fetal macrosomia are not well understood. The imprinted genes IGF-II and H19 are crucial for placental development and fetal growth. The term placentas from diabetic pregnancies express more insulin-like growth factor II (IGF-II) than those from normal pregnancies. Deregulation of their imprinting status is observed in the macrosomia-associated syndrome, the Beckwith-Wiedemann syndrome. The aim of this study was to determine whether loss of imprinting hence biallelic expression was also a hallmark of macrosomia in diabetic pregnancies. DESIGN AND METHODS: IGF-II and H19 maternal and paternal expressions were studied in placentas from two groups of type 1 diabetic mothers: one with macrosomic babies and the other with babies of normal weight. Maternal or paternal allele specific expressions were defined by using DNA polymorphic markers of the IGF-II and H19 genes. RFLP analysis was performed on PCR products from genomic DNA of the father, the mother and the child, and on RT-PCR products from placental mRNA. RESULTS: RFLP analysis showed that the IGF-II gene remains paternally expressed and the H19 gene remains maternally expressed in all placentas examined, independently of the birth weight status. CONCLUSIONS: These results suggest that, in contrast with Beckwith-Wiedemann syndrome-associated macrosomia, loss of imprinting for IGF-II or H19 is not a common feature of diabetic pregnancies associated with macrosomia.     

Stimulation of gonadotropin release and of ovarian development, by the administration of a gonadoliberin agonist and of dopamine antagonists, in female silver eel pretreated with estradiol

In freshwater or seawater female silver eel, the release of gonadotropin (GTH) accumulated in the pituitary under estradiol (E2) influence could be stimulated by a conjugated treatment with a mammalian gonadoliberin agonist (GnRH-A = des-Gly10, (D-Ala6)-LH-RH ethylamide) and a blocker of dopamine receptor (pimozide). Furthermore, despite the GTH release, no reduction or even a significant increase in pituitary GTH levels were noted, indicating a stimulation of GTH synthesis. In consequence of the endogenous GTH release, a stimulation of ovarian development was induced, as demonstrated by the gonadosomatic index and histological study. Similar results were obtained with a combined treatment with GnRH-A and an inhibitor of catecholamine synthesis (L-alpha-methyl-3,4-dihydroxyphenylalanine). In contrast, no effect was produced by GnRH-A, pimozide, or L-alpha-methyl-DOPA, given alone. The results suggest that a double neuroendocrine mechanism (a lack of GnRH production and a dopaminergic inhibition of GnRH action) is involved in the prepubertal blockage of eel gonadotropic function before the reproductive migration.     

Cloning and sequence analysis of the cDNA for the pituitary glycoprotein hormone alpha-subunit of the European eel.

A cDNA library constructed using mRNAs isolated from pituitary glands of estradiol-treated eels was screened with a cDNA fragment for the rat glycoprotein hormone alpha-subunit. Three out of 10,000 cDNA clones were revealed and subcloned in pUC13 for characterization and sequencing. All three had the same nucleotide sequence except for a single, silent change in the coding sequence for one of them, and for the location of the poly(A) tail. Analysis of the deduced amino acid sequence strongly suggests that these cDNA clones encode the precursor for the eel common glycoprotein hormone alpha-subunit. This precursor would therefore consist of a 93 amino acid apoprotein preceded by a 24 amino acid long signal peptide. Alignment with glycoprotein hormone alpha-subunits from fish and mammals reveals high homology, ranging from 60 to 90%. Particularly, the ten cysteines and the two putative N-linked glycosylation sites were at the same position. Comparison between fish and mammals shows also that two regions are highly conserved, comprising about half of the protein length. This high conservation rate through evolution argues for the importance of these regions in the conservation of biological properties of the alpha-subunits. In contrast, other regions are highly variable and could be responsible for the immunological specificity. Northern blot analysis of pituitary RNA from control and estradiol-treated eels showed that estradiol treatment strongly increases the pituitary content of mRNA encoding the glycoprotein hormone alpha-subunit.     

Metformin-induced resumption of normal menses in 39 of 43 (91%) previously amenorrheic women with the polycystic ovary syndrome

In 43 amenorrheic women with polycystic ovary syndrome (PCOS), 31 (74%) with fasting hyperinsulinemia (> or =20 microU/mL), our aim was to determine whether Metformin (Bristol-Myers Squibb, Princeton, NJ), which reduces hyperinsulinemia, would reverse the endocrinopathy of PCOS, allowing resumption of regular normal menses. A second aim was to assess the effects of weight loss versus other Metformin-induced effects on ovarian function, and to determine if there were different responses to Metformin between those who lost weight and those who did not. A third aim was to assess associations between PCOS, 4G/5G polymorphism in the promoter sequence of the plasminogen activator inhibitor-1 gene (PAI-1 gene), and PAI activity (PAI-Fx). Of the 43 women, 40 (93%) had normal fasting blood glucose and 37 had normal hemoglobin A1C (HgA1C); onlythree (7%) had type 2 diabetes mellitus. Metformin (1.5 to 2.25 g/d) was given for 6.1+/-5.1 months (range, 1.5 to 24), to 16 patients for less than 3 months, to 12 for 3 to 6 months, and to 15 for at least 6 months. On Metformin, 39 of 43 patients (91%) resumed normal menses. The percentage of women resuming normal menses did not differ among treatment duration groups (P<.1) or among dose groups (P>.1). The body mass index (BMI) decreased from 36.4 + 7 Kg/m2 at study entry to 35.1+/-6.7 on Metformin (P=.0008). Of 43 patients, 28 (67%) lost weight (1 to 69 pounds), with nine (21%) losing at least 12 pounds. On Metformin, the median fasting serum insulin decreased from 26 microU/mL to 22 (P=.019), testosterone decreased from 61 ng/dL to 47 (P=.003), and estradiol increased from 41 pg/mL to 71 (P=.0001). Metformin-induced improvements in ovarian function were independent of weight loss (testosterone decrease, P<.002; estradiol increase, P<.0004). The change in response variables on Metformin did not differ (P>.05) between those who lost weight and those who did not, excepting Lp(a), which increased 4 mg/dL in those who lost weight and decreased 9 mg/dL in those who did not (P = .003). The change in response variables on Metformin did not differ among the five quintiles of weight loss, excepting fasting glucose (P<.05), which increased 6 mg/dL in those who lost the least weight on Metformin versus those in the 60th to 80th percentile for weight loss, in whom glucose decreased 33 mg/dL. Although the pretreatment fasting serum insulin was not significantly correlated with testosterone (r=.24, P=.13) or androstenedione (r=.27, P=.09), on Metformin, the change in insulin correlated positively with the change in testosterone (r=.35, P=.047) and with the change in androstenedione (r=.48, P=.01). Patients were more likely than normal controls (83% v 64%, P=.016) to be heterozygous or homozygous for 4G polymorphism of the PAI-1 gene and were also more likely to have high PAI-Fx (> or =22 U/mL, 28% v3%, chi(2)=10.1, P=.001). Metformin reduces the endocrinopathy of PCOS, allowing resumption of normal menses in most (91%) previously amenorrheic women with PCOS.     

Ventricular dysplasia. Nosology and sudden death

The arrhythmia generating dysplasia of the right ventricle is a congenital anomaly suggesting a hereditary substratum. It usually manifests itself as follows: a young patient, with recurrent episodes of ventricular tachycardiac. There is no "pathognomonic sign" of dysplasia. The latter may only be determined by anatomical examination of the heart, macroscopically as well as microscopically. The most difficult differential diagnosis concerns minor or localized forms of dilated idiopathic myocardiopathy or sequelae of myocarditis with ventricular tachycardia originating in the right ventricle. It seems, currently, more appropriate to talk about "arrhythmia generating syndrome of the right ventricle" rather than arrhythmia generating dysplasia of the right ventricle, in these particular cases. The arrhythmia generating syndrome of the right ventricle could cause a sudden death in these young patients, especially during a violent physical exercise or practise of sports. The current nosological classification is based on an experience acquired by comparing a few isolated cases. The search for late potentials by summation-mean measurements and nuclear magnetic resonance could provide a new diagnostic approach.