Risk Factors for Neonatal Infection

A retrospective case-control study was designed to assess risk factors for neonatal infection. Nonprivate patients (8,215) who delivered in a period from January 1, 1983 to June 30, 1988 were studied. Ninety three cases of conjunctivitis (incidence 2.4/1,000), 104 cases of pneumonia (incidence 2.8/1,000), and 50 cases of sepsis (incidence 1.3/1,000) were identified. Group B streptococcus was cultured from septic neonates in 46%. Calculated Odds ratio's indicated prematurity/low birth-weight (OR 6.9) and antepartum fetal tachycardia (OR 6.3) as important risk factors for pneumonia/sepsis. Prematurity/low birth-weight (OR 3.0) and an abnormal presentation in the birth canal (OR 2.8) were identified as risk factors for conjunctivitis. After testing all the risk factors found by univariate analysis in a logistic regression model tachycardia (chi 2 35.21, p less than 0.001) remained an independent predictor for neonatal pneumonia/sepsis and abnormal vaginal presentation (chi 2 7.58, p 0.006) for conjunctivitis.     

GENOTYPIC INFLUENCE ON PLASMA DIPEPTIDYL CARBOXYPEPTIDASE-1 ACTIVITY IN HYPERTENSIVES

1. Plasma dipeptidyl carboxypeptidase-1 (DCP1; angiotensin I-converting enzyme, kininase II; EC 3.4.15.1) tracks with the deletion allele in genotypes of a 287 bp insertion/deletion (I/D) polymorphism of its gene, DCP1, in healthy Caucasian populations. The aim of the present study was to see whether genotype has a similar influence on plasma DCP1 in hypertensives. 2. The study involved 35 Caucasian patients with severe, familial essential hypertension, who were not being treated with DCP1 inhibitors, and 94 normotensives. Genotyping for the I/D polymorphism was performed by polymerase chain reaction and plasma DCP1 activity was measured by rate of hydrolysis of both [³H]-Hip-Gly-Gly and Hip-His-Leu. 3. Plasma DCP1 activity (nmol Gly-Gly/min per mL; mean ± s.e.m.) was 67 ± 2, 82 ± 4 and 91 ± 6 in II, ID and DD hypertensives, respectively, which was similar to values of 68 ± 4, 82 ± 3 and 94 ± 3 in normotensives (P= 0.0001 by one-way analysis of variance). Results for the His-Leu assay indicated similar tracking with genotype. 4. The Michaelis constant (μmol Hip-Gly-Gly/mL; mean ± s.e.m., n= 10) for DD subjects was the same as for II subjects (10.6 ± 1.6 vs 11.1 ± 2.3; P = 0.86). 5. In conclusion, in severely hypertensive Caucasian subjects, plasma DCP1 activity is subject to a similar genotypic influence in hypertensives as has been reported previously in normotensives. Furthermore, the plasma DCP1 enzyme itself appears to be functionally similar for each genotype.     

Hepatocellular Carcinoma: Comparison of Clinical Features among Ethnic Groups in an Area of Low Prevalence

We retrospectively surveyed the clinical features of 73 cases of hepatocellular carcinoma at two hospitals over a 12-yr period. The population was heterogeneous, with 39% representing immigrants from regions of high hepatitis B and hepatocellular carcinoma prevalence. The yearly incidence of cases was constant over the 12 yr. Patient data were analyzed by grouping into three broad categories based on origin from known high, medium, or low prevalence hepatocellular carcinoma zones. In this fashion, differences in clinical presentation were observed. Asians (N = 12) were younger, invariably presented with pain; 82% had markers of hepatitis B and did not have features of chronic liver disease. In contrast, Westerners (N = 45) were older by more than a decade. One-quarter were HBV positive and almost two-thirds were alcoholic. The clinical presentation of this group was more varied, over one-third presenting with features of decompensated liver disease or variceal bleeds. Mediterranean patients (N = 16) had features intermediary between the two other groups. A logistic regression model clinically separated patients with hepatitis B-related hepatocellular carcinoma from those with alcohol-related hepatocellular carcinoma, suggesting different ongoing pathogenetic influences.     

Effects of Chronic Ethanol on Currents Carried through Calcium Channels in Aplysia

Voltage clamp techniques were used to monitor the effects of chronic exposure to ethanol (EtOH) on current carried through calcium channels in an identified neuron of cultured abdominal ganglia from Aplysia californica. Exposure to 200 mM EtOH for periods up to 3 weeks did not change the baseline characteristics of current carried through calcium channels, nor did it alter its acute sensitivity to either 100 mM or 300 mM EtOH challenge. The currents that we examined were equivalent when carried by calcium or barium, and EtOH had similar effects on currents carried by these two ions. The population of voltage-dependent calcium channels studied here does not show development of tolerance after chronic exposure to EtOH.     

NO EFFECT OF KININS ON DNA SYNTHESIS IN LNCaP PROSTATE CANCER CELLS

1. Prostate has kininogenase activity and expresses members of the tissue kallikrein gene family. The present study examined the effect of exogenous and endogenous kinins on growth of LNCaP prostate adenocarcinoma cells. 2. Rate of DNA synthesis was measured by incorporation over 4 h of [³H]-thymidine into a TCA insoluble fraction of LNCaP cells that had been cultured for 24 h. 3. Increased [³H]-thymidine incorporation was seen in response to 10 nmol/L testosterone (4– 103 ± 5 s.e.%), dihydrotestosterone (+ 113 ± 14%) and R 1881 (+64 ± 10%) (P± 0.001; n = 4). 4. In contrast 0.05, 5 and 1000 nmol/L lysyl-bradykinin had no effect (15 ± 4, 10 ± 9 and 5 ± 3 s.e.%, respectively; n = 7). Des-Arg⁹[Leu⁸]-bradykinin (a B₁ receptor antagonist) and/or d-Arg-[Hyp³,Thi^5,8,d-Phe⁷]-bradykinin (a B₂ receptor antagonist), 1 nmol/L, and indomethacin, 5 μmol/L, also had little or no effect. 5. In conclusion, kallidin and endogenous kinins and prostaglandins have little or no effect on DNA synthesis and therefore on the growth of LNCaP cells in comparison to the two-fold stimulation produced by androgens.     

Syntaxin 1A Co-Associates with Native Rat Brain and Cloned Large Conductance, Calcium-Activated Potassium Channels in situ

Large conductance, calcium-activated potassium channels (BK_Ca channels) are regulated by several distinct mechanisms, including phosphorylation/dephosphorylation events and protein-protein interactions. In this study, we have examined the interaction between BK_Ca channels and syntaxin 1A, a soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) that is reported to modulate the activity and/or localization of different classes of ion channels. Using a reciprocal co-immunoprecipitation strategy, we observed that native BK_Ca channels in rat hippocampus co-associate with syntaxin 1A, but not the closely related homologue syntaxin 3. This BK_Ca channel-syntaxin 1A interaction could be further demonstrated in a non-neuronal cell line (human embryonic kidney (HEK) 293 cells) following co-expression of rat syntaxin 1A and BK_Ca channels cloned from either mouse brain or bovine aorta. However, co-expression of these same channels with syntaxin 3 did not lead to a detectable protein-protein interaction. Immunofluorescent co-staining of HEK 293 cells expressing BK_Ca channels and syntaxin 1A demonstrated overlapping distribution of these two proteins in situ . Functionally, co-expression of BK_Ca channels with syntaxin 1A, but not syntaxin 3, was observed to enhance channel gating and kinetics at low concentrations (1–4 μ m ) of free cytosolic calcium, but not at higher concentrations (≤ 10 μ m ), as judged by macroscopic current recordings in excised membrane patches. Interactions between BK_Ca channels and neighbouring membrane proteins may thus play important roles in regulating the activity and/or distribution of these channels within specialized cellular compartments.     

Flow Measurement at the Pump Head of Centrifugal Pumps: Comparison of Ultrasonic Transit Time and Ultrasonic Doppler Systems

Abstract: Determination of blood flow is essential for monitoring rotary blood pumps. However, accurate measurement directly adjacent to the pump housing is difficult because of the highly irregular flow profiles near the fast spinning rotor. Therefore, a specially adapted flow probe based on the ultrasound transit time (USTT) principle was designed to evaluate the flow in centrifugal blood pumps. The probe can be directly mounted at the housing and creates 2 crossed measuring ultrasound beams. The mean value, Q_m, of the 2 output signals corresponds to the blood flow and the difference, Q_d, correlates to the vorticity of the flow profile in the pump outflow tract. In vitro measurements obtained an accuracy for mean flow values of better than ±0.6 L/min in extreme working points and for vorticity values even as high as Q_d= 3.5 L/min. Because of vorticity, however, the output signal contained considerable noise, and that required the application of a 10 Hz filter. Positioning of the ultrasound (US) beams parallel to the axial direction of the pump was superior to radial positioning. Additional measurement of the flow profile demonstrated that a large vorticity occurred (up to Q_dequal to 3.5 L/min), and this vorticity was highly dependent upon the afterload of the pump. In vivo experiments demonstrated the reliability of the method. We concluded that USTT flow measurement can determine blood flow immediately adjacent to the pump housing with sufficient accuracy, and these measurements are superior to those from US-Doppler systems (which cannot handle the vorticity accurately enough) and electromagnetic devices (which lack zero stability).     

Treatment of warts

ABSTRACT: Warts are caused by human papilloma viruses (HPV) and more than 80 types of HPV have been described. Although some HPV types in the anogenital area can lead to dysplasia and cancer, most HPV infections cause histologically benign warts. Clinically, warts produce much morbidity, mainly due to their resistance to most standard therapies. Although the choice of therapy depends partly on the location of the warts, i.e., anogenital vs. non-anogenital, most treatments in the past have been anti-wart but not antiviral. Therefore, removal of the wart was often followed by a recurrence in a few weeks due to sub-clinical or latent HPV infections surrounding the wart. Such non-antiviral therapies included a variety of acids, podophyllin, podophyllotoxin, chemotherapeutic agents, retinoids, topical sensitizers, a spectrum of surgical techniques, and cryotherapy. Two drugs approved for anogenital warts have antiviral and immunomodulatory activity, interferon and imiquimod, although imiquimod is much more convenient to use. While neither of these antiviral agents is approved for non-anogenital warts, they do appear to have efficacy in these warts when used as adjunctive therapy. Experimental therapies for warts are currently under study and include topical cidofovir and both prophylactic and therapeutic HPV vaccines.     

Sensitivity of coherent oscillations in rat hippocampus to AC electric fields

The sensitivity of brain tissue to weak extracellular electric fields is important in assessing potential public health risks of extremely low frequency (ELF) fields, and potential roles of endogenous fields in brain function. Here we determine the effect of applied electric fields on membrane potentials and coherent network oscillations. Applied DC electric fields change transmembrane potentials in CA3 pyramidal cell somata by 0.18 mV per V m⁻¹ applied. AC sinusoidal electric fields have smaller effects on transmembrane potentials: sensitivity drops as an exponential decay function of frequency. At 50 and 60 Hz it is ∼0.4 that for DC fields. Effects of fields of ≤ 16 V m⁻¹ peak-to-peak (p-p) did not outlast application. Kainic acid (100 n m ) induced coherent network oscillations in the beta and gamma bands (15–100 Hz). Applied fields of ≥ 6 V m⁻¹ p-p (2.1 V m⁻¹ r.m.s.) shifted the gamma peak in the power spectrum to centre on the applied field frequency or a subharmonic. Statistically significant effects on the timing of pyramidal cell firing within the oscillation appeared at distinct thresholds: at 50 Hz, 1 V m⁻¹ p-p (354 mV m⁻¹ r.m.s.) had statistically significant effects in 71% of slices, and 0.5 V m⁻¹ p-p (177 mV m⁻¹ r.m.s.) in 20%. These threshold fields are consistent with current environmental guidelines. They correspond to changes in somatic potential of ∼70 μV, below membrane potential noise levels for neurons, demonstrating the emergent properties of neuronal networks can be more sensitive than measurable effects in single neurons.     

Haemodynamic characteristics of hypertension induced by prenatal cortisol exposure in sheep

1. Administration of glucocorticoids to ewes early in pregnancy results in offspring with hypertension in adulthood. The hypertension in female offspring exposed to dexamethasone is associated with increased cardiac output, but whether this is also true in cortisol-exposed offspring is unknown.
2. Systemic haemodynamic variables were measured under basal conditions in castrated male and female adult sheep exposed to cortisol (5 mg/h) or saline (0.19 mL/h) from 26 to 28 days of gestation. To examine the contribution of the autonomic nervous system to maintenance of basal arterial pressure in established hypertension in cortisol-exposed sheep, responses to adrenoceptor blockade (intravenous infusion of 0.15 mg/kg per h phentolamine plus 0.4 mg/kg per h propranolol) and ganglionic blockade (intravenous infusion of 125 mg/h hexamethonium) were examined in castrated male offspring.
3. Mean arterial pressure and calculated systemic vascular resistance were 9% and 17% greater, whereas cardiac output tended to be 8% less, in cortisol-compared with saline-exposed sheep. These effects were not sex dependent. The depressor response to ganglionic blockade and the initial phase of the depressor response to adrenoceptor blockade were greater in cortisol-compared with saline-exposed sheep.
4. These results indicate that hypertension in offspring exposed prenatally to cortisol is associated with increased total peripheral resistance, mimicking observations in human patients with chronic hypertension. Furthermore, the increased vascular resistance appears to be dependent, at least in part, on an increased effect of sympathetic vasomotor drive. Taken together with previous findings, the present observations suggest that prenatal cortisol and dexamethasone programme altered adult cardiovascular function via distinct mechanistic pathways.