Gestational age and intrauterine growth retardation among white and black very low birthweight infants: a population-based cohort study

Summary. Very low birthweight (VLBW) is a commonly used endpoint in perinatal epidemiology, but the population of VLBW infants comprises a wide range of gestational ages and rates of fetal growth. We used data from a population-based study of all 1072 black and white VLBW liveborn infants born in 29 counties in Georgia between April 1986 and March 1988. Less than 1% of the VLBW infants were ≥ 37 weeks gestation; most were 29–32 weeks (26%) or 25 to 28 weeks (40%); 12% were 22 weeks or less. All infants 33 weeks gestation or greater were growth retarded. The population of VLBW infants seems to comprise three groups: approximately 11% very immature infants of 22 weeks or less; the majority of infants, born between 23 and 30 weeks, 90% of which are of normal weight for their gestational age; and a group of less premature, growth-retarded infants from 31 to 36 weeks. We found little or no difference in the distribution of gestational age or the percentage of intrauterine growth rates (IUGR) between black and white infants. In the USA the VLBW rate among black infants is over three times greater than that among white infants and consequently the rates of the three types of VLBW among black infants are likely to be triple those among white infants.     

Randomised comparison of CHOEP versus alternating hCHOP/IVEP for high-grade non-Hodgkin's lymphomas: Treatment results and prognostic factor analysis in a multi-centre trial

Background: With CHOP, the standard protocol of recent decades,about 30% of long-term survival has been reported. A numberof studies using more aggressive multidrug regimens or alternatingchemotherapies have recently suggested higher CR rates and increasedsurvival. In 1989 we reported similar results with a combined-modalitytreatment administering 6 cycles of CHOP supplemented with etoposideand an involved field irradiation for patients in PR or CR. Patients and methods: To confirm the efficacy of this approach,we initiated a prospective randomised trial comparing 4 cyclesof CHOP-VP 16 (CHOEP) with 4 cycles of two alternating regimens,‘hCHOP and IVEP’. One hundred seventy-five patientswith high-grade non-Hodgkin's lymphomas stages II-IV were stratifiedfor age, stage and LDH and randomised to receive either fourcycles of cyclophosphamide, doxorubicin, vincristine, etoposide,prednisolone (CHOEP) in arm A or four cycles of chemotherapywith a dose-intensified CHOP (hCHOP) alternating with ifosfamide,etoposide, vindesine, prednisolone (IVEP) in arm B. After fourcycles of chemotherapy an involved field irradiation with atotal dose of 35 Gy was given to all patients demonstrated tobe in complete or partial remission. Results: Of the 185 randomised patients, 175 were eligible and171 evaluable for response and survival. One hundred forty-sixof the 171 patients (85%) achieved complete remission (CR) with87% and 84% CRs in arms A and B, respectively. With a medianfollow-up of 36 months the estimated overall survival at 2 yearsis 66% and 73% for arms A and B. The percentage of all patientsin first CR is estimated to be 59% and 55% at 2 years for armsA and B, respectively. None of the differences in CR rate, survival,or relapse-free survival are statistically significant. Multivariateanalysis of subgroups incorporating the factors of sex, age,performance status, stage, B symptoms, bulky disease, LDH andhistology revealed that only stage and LDH were factors whichindependently affected outcome. The estimated 2-year survivalrate of patients with stages II, III and IV is predicted tobe 84%, 62% and 52%, respectively. Patients with LDH >250U/I have an estimated survival of 52% at 2 years versus 84%for patients with LDH     

Nucleic acid spot hybridization with nonradioactive labeled probes in screening for human papillomavirus DNA sequences

We examined 161 human tissue samples using the spot hybridization technique with nonradioactive labeled DNA probes of human papillomavirus (HPV). Whole cells were spotted on nitrocellulose filters; DNA of the cells was denatured and fixed to the filter. Then the DNA spots were hybridized to nonradioactive labeled DNA and monitored by a sandwich immunoenzymatic reaction. This technique is simple, sensitive, specific, requires no special equipment, and can be used in clinical settings. HPV DNA was found in 92% of samples in which, on the basis of histologic and colposcopic criteria, its presence was suspected, as well as in 31 samples where it was not suspected.     

The pharmacology of GR203040, a novel, potent and selective non-peptide tachykinin NK1 receptor antagonist.

1. The in vitro and in vivo pharmacology of GR203040 ((2S, 3S)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-y l)-amine), a novel, highly potent and selective non-peptide tachykinin NK1 receptor antagonist, was investigated in the present study. 2. GR203040 potently inhibited [3H]-substance P binding to human NK1 receptors expressed in Chinese hamster ovary (CHO) and U373 MG astrocytoma cells, and NK1 receptors in ferret and gerbil cortex (pKi values of 10.3, 10.5, 10.1 and 10.1 respectively). GR203040 had lower affinity at rat NK1 receptors (pKi = 8.6) and little affinity for human NK2 receptors (pKi < 5.0) in CHO cells and NK3 receptors in guinea-pig cortex (pKi < 6.0). With the exception of the histamine H1 receptor (pIC50 = 7.5). GR203040 had little affinity (pIC50 < 6.0) at all non-NK1 receptors and ion channels examined. Furthermore, GR203040 produced only weak inhibition of Na+ currents in SH-SY5Y neuroblastoma and superior cervical ganglion cells (pIC50 values < 4.0). GR203040 produced only weak antagonism of Ca(2+)-evoked contractions of rat isolated portal vein (pKn = 4.1). The enantiomer of GR203040, GR205608 (2R, 3R)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-y l)-amine), had 10,000 fold lower affinity at the human NK1 receptor expressed in CHO cells (pKi = 6.3). 3. In gerbil ex vivo binding experiments, GR203040 produced a dose-dependent inhibition of the binding of [3H]-substance P to cerebral cortical membranes (ED50 = 15 micrograms kg-1 s.c. and 0.42 mg kg-1 p.o.). At 10 micrograms kg-1 s.c., the inhibition of [3H]-substance P binding was maintained for > 6 h. In the rat, GR203040 was less potent (ED50 = 15.4 mg kg-1 s.c.) probably reflecting, at least in part, its lower affinity at the rat NK1 receptor. 4. In guinea-pig isolated ileum and dog isolated middle cerebral and basilar arteries, GR203040 produced a rightward displacement of the concentration-effect curves to substance P methyl ester (SPOMe) with suppression of the maximum agonist response (apparent pKB values of 11.9, 11.2 and 11.1 respectively). 5. In anaesthetized rabbits, GR203040 antagonized reductions in carotid arterial vascular resistance evoked by SPOMe, injected via the lingual artery (DR10 (i.e. the dose producing a dose-ratio of 10) = 1.1 micrograms kg-1, i.v.). At a dose 20 fold greater than its DR10 value (i.e. 22 micrograms kg-1, i.v.), significant antagonism was evident more than 2 h after GR203040 administration. 6. In anaesthetized rats, GR203040 (3 and 10 mg kg-1, i.v.) produced a dose-dependent inhibition of plasma protein extravasation in dura mater, conjunctiva, eyelid and lip in response to electrical stimulation of the trigeminal ganglion. 7. It is concluded that GR203040 is one of the most potent and selective NK1 receptor antagonists yet described, and as such, has considerable potential as a pharmacological tool to characterize the physiological and pathological roles of substance P and NK1 receptors. GR203040 may also have potential as a novel therapeutic agent for the treatment of conditions such as migraine, emesis and pain.     

A series of novel, highly potent and selective agonists for the kappa-opioid receptor.

1. This paper describes the opioid receptor pharmacology and in vivo activity of several novel benzene-acetamidopiperidine and benzeneacetamidopiperazine analogues. 2. These compounds all showed potent, naloxone-reversible, full agonist activity in the field-stimulated rabbit vas deferens, indicating that they are kappa-opioid agonists; but showed very little activity in the rat or hamster vas deferens, indicating good selectivity with regard to mu- and delta-opioid receptors. 3. They were all potent antinociceptive agents, the most potent compound, GR 103545, having an ED50 value in the mouse abdominal constriction test of 0.25 micrograms kg-1 s.c. The compounds also produced sedation and diuresis, but had little effect on respiration rate or gastrointestinal motility. 4. It is concluded that the seven novel compounds described are all potent and selective agonists for the kappa-opioid receptor.     

Fetal lumbar spine: measuring axial growth with US

Ultrasound (US) can be used to visualize vertebral segments, suggesting a quantitative means of studying vertebral column growth in utero and thus a means of detecting developmental abnormalities. US images of the lumbar spine were obtained in 128 clinically normal fetuses between the gestational age of 11 through 41 weeks. A large-aperture, dynamically focused US system capable of regional magnification was used. Average lumbar spacing was calculated from distance between centrums of at least four lumbar bodies. The average distance between lumbar centrums increased nearly linearly throughout the second and third trimesters (r2 = 0.98). Enhanced anatomic display implies new capabilities for recognizing developmental abnormalities antenatally.     

Pneumatic retinopexy versus scleral buckle. Preferences of Vitreous Society members, 1990.

A survey was conducted among the 1990 members of the Vitreous Society in order to measure their acceptance of pneumatic retinopexy. They were asked which treatment they would prefer should they suffer a hypothetical detachment. The choices were limited to pneumatic retinopexy or scleral buckling (encircling or segmental). The majority of respondents selected a scleral buckling procedure for a phakic retinal detachment with two adjacent superior temporal quadrant tears. Surgeons who had been in practice for 10 years or less (median for entire group = 10 years) were significantly more likely to select a pneumatic retinopexy procedure. As the details of the hypothetical detachment became more complicated with myopia, additional tears, vitreous hemorrhage, or lattice degeneration with a positive family history, the respondents selected a scleral buckling procedure with greater frequency, and the differences between the choices of the surgeons became nonsignificant. This survey shows that many surgeons feel pneumatic retinopexy is an acceptable alternative to buckling surgery in select cases. There were no trends by geographic location.     

Novel mutations in the thymidine kinase and DNA polymerase genes of acyclovir and foscarnet resistant herpes simplex viruses infecting an immunocompromised patient.

BACKGROUND: Mutations in the thymidine kinase (TK) and DNA polymerase (pol) genes of herpes simplex virus (HSV) may confer resistance to antiviral drugs, particularly in the context of immunosuppression induced by infection with the human immunodeficiency virus (HIV). OBJECTIVES: To characterise the HSV type 2 (HSV-2) TK and DNA pol genes in an immunocompromised patient with clinical resistance to both acyclovir and foscarnet. STUDY DESIGN: The TK and DNA pol genes of isolates obtained over a 2-year period from an AIDS patient with severe genital herpes infection were characterised both phenotypically and genotypically. RESULTS: HSV strains that were acyclovir resistant/foscarnet sensitive, acyclovir sensitive/foscarnet sensitive and acyclovir resistant/foscarnet resistant were isolated during this time. The TK gene of all the acyclovir resistant isolates contained a large 969 bp deletion which extended into a downstream untranslated region. The foscarnet resistance was associated with an S725G mutation in a conserved region (region II) of the herpesvirus DNA pol gene. CONCLUSIONS: Clinical and virological suppression of the infection was not always associated with subsequent reactivation with wild-type virus. Mutations of the nature we describe have not previously been reported occurring simultaneously in HSV strains isolated from patients treated with acyclovir and foscarnet.