Providing public health services through an integrated delivery system.

This article examines a recently implemented strategy to transfer responsibility for local public health service delivery from a county health department to a hospital-based integrated delivery system. Innovative quality management efforts at both local and state levels offer opportunities for sustained improvement in the availability and adequacy of public health services under this arrangement.

Maternal serum screening for alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin between 11 and 15 weeks of pregnancy to detect fetal chromosome abnormalities.

OBJECTIVE: The purpose of this prospective study was to assess the value of maternal serum screening between 11 and 15 weeks of gestation to detect fetal Down syndrome. STUDY DESIGN: Blood samples were collected on 993 women between 11 and 15 weeks' gestation before amniocentesis. Ninety percent were > or = 35 years old. Samples were coded and assayed for alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin. Medians were established at each week between 11 and 15 from 836 normal, singleton pregnancies. RESULTS: We used a computer-generated cut-off risk for Down syndrome of one in 365 at term; nine of 11 (82%) Down syndrome pregnancies were identified. There were 23% false-positive results in women > or = 35 years old and 6% in those < 35 years. CONCLUSION: These results suggest that maternal serum screening between 11 and 15 weeks may provide an acceptable alternative to screening between 16 and 20 weeks.

Racial differences in maternal serum human chorionic gonadotropin and unconjugated oestriol levels.

We assayed maternal serum samples from 134 black and 268 white women from 16 to 18 weeks of gestation for intact human chorionic gonadotropin (hCG), and unconjugated oestriol (uE3). Serum from women with high (> or = 2.5 MOMs) or low (risk for Down syndrome > or = 1/365) maternal serum alpha-fetoprotein (MSAFP) levels were excluded. After correcting for maternal weight, we found that median hCG levels were 16 per cent higher in black women but uE3 levels were not significantly different. These results confirm three other studies for hCG and one study for uE3. Corrections are recommended for both maternal serum hCG and AFP before calculating the risk for Down syndrome in black women.

Reduced fetal hepatic alpha-fetoprotein levels in Down's syndrome.

In the majority of pregnancies involving a Down's syndrome (DS) fetus, the level of alpha-fetoprotein (AFP) measured in maternal serum and amniotic fluid is reduced to about 70 per cent of the level attained in normal pregnancies. Causes of this decrease may include the production of an altered AFP molecule with modified turnover or transport properties, or a reduction in the level of AFP synthesis. We examined hepatic AFP mRNA transcripts and compared AFP polypeptide isoforms in liver tissue samples obtained from a group of DS and normal abortuses. No differences was detected in the structure of the AFP mRNA transcript or in the charge or mass of AFP polypeptides in the two sample groups. However, the hepatic AFP level, expressed as microgram AFP/mg protein, was significantly lower in a group of 28 DS cases relative to a group of 47 normal controls (p = 0.04). This difference in hepatic AFP concentration did not appear to be the result of a general reduction in the level of total protein or total RNA production. The greatest difference between the AFP levels of the DS and normal groups was observed in the earliest samples examined (i.e., at 17-19 weeks of age) where the median AFP levels differed by about 20 per cent.

Case management offers opportunities.

Insurance companies and independent utilization management firms often provide medical and disability case-management services. Hospitals, home health-care agencies and freestanding outpatient centers could also provide these services to help employers manage their high-cost cases effectively. The authors outline the steps a provider should take to implement such a program.

Pulmonary pathology of Rocky Mountain spotted fever (RMSF) in children.

Despite infrequent respiratory symptoms, histopathologic changes were identified in the lungs of 15 of 16 children dying of Rocky Mountain spotted fever (RMSF). Gross examination demonstrated increased lung weight, edema, congestion, focal hemorrhage, and bronchopneumonia in a few cases. Paraffin sections were stained with hematoxylin and eosin and phosphotungstic acid-hematoxylin, and available blocks were examined by direct immunofluoresence for Rickettsia rickettsii. Cases and controls matched for age and sex were randomized and examined blindly for pathologic changes. In addition, morphometric measurements of mean alveolar septal thickness were made in each case. The histopathologic findings include (1) diffuse interstitial mononuclear (lymphocyte and macrophage) inflammatory infiltrate in 15/16 cases of RMSF (5/10 controls), (2) pulmonary edema and intraalveolar hemorrhage in 11/16 cases of RMSF (2/10 controls), and (3) vasculitis of small pulmonary venules and arterioles in 5/16 RMSF cases (0/10 controls). Rickettsia rickettsii were identified in 4/8 RMSF cases by direct fluorescent antibody technique. Although pulmonary disease is not always clinically apparent in children with RMSF, involvement of the pulmonary microcirculation is a frequent event in fatal cases and may contribute to the development of non-cardiogenic pulmonary edema.

Cloning and characterization of recA genes froM Proteus vulgaris, Erwinia carotovora, Shigella flexneri, and Escherichia coli B/r.

The recA genes of Proteus vulgaris, Erwinia carotovora, Shigella flexneri and Escherichia coli B/r have been isolated and introduced into Escherichia coli K-12. All the heterologous genes restore resistance to killing by UV irradiation and the mutagen 4-nitroquinoline-1-oxide in RecA- E. coli K-12 hosts. Recombination proficiency is also restored as measured by formation of Lac+ recombinants from duplicated mutant lacZ genes and the ability to propagate phage lambda derivatives requiring host recombination functions for growth (Fec-). The cloned heterologous genes increase the spontaneous induction of lambda prophage in lysogens of a recA strain. Addition of mitomycin C stimulates phage production in cells carrying the E. coli B/r and S. flexneri recA genes, but little or no stimulation is seen in cells carrying the E. carotovora and P. vulgaris recA genes. After treatment with nalidixic acid, the heterologous RecA proteins are synthesized at elevated levels, a result consistent with their regulation by the E. coli K-12 LexA repressor. Southern hybridization and preliminary restriction analysis indicate divergence among the coding sequences, but antibodies prepared against the E. coli K-12 RecA protein cross-react with the heterologous enzymes, indicating structural conservation among these proteins.

Homologous pairing of single-stranded circular DNAs catalyzed by recA protein.

RecA protein catalyzes annealing between pairs of circular single-stranded DNA molecules containing complementary sequences varying in length from 3550 nucleotides to 181 nucleotides. The reaction requires ATP and catalytic amounts of recA protein. Molecules containing large complementary inserts are annealed by recA protein to form large multimeric aggregates that migrate slowly in agarose gels. In contrast the products formed from circular molecules containing short complementary regions are principally dimeric structures. We have used electron microscopy, thermal denaturation and kinetic studies to analyze these reaction products. Our results indicate that recA protein catalyzes multiple nucleation events between complementary DNA sequences in the absence of a free end and when these sequences are flanked by extensive noncomplementary regions.

On the enzymatic basis for mutagenesis by manganese.

The effects of manganese on DNA synthesis fidelity are measured using T4 DNA polymerase. When the nucleotide analogue 2-aminopurine deoxyribonucleoside triphosphate competes against dATP at thymine sites on template DNA, the aminopurine misincorporation frequency increases from 6.3% in the presence of Mg2+ to 29.2% in the presence of Mn2+. The major cause of the increased error rate is an approximate 4-fold increase in the frequency of aminopurine misinsertions. Exonucleolytic proofreading of aminopurine is similar in the presence of Mn2+ and Mg2+. However, the excision frequency of the correct nucleotide, dAMP, is increased 2-fold with Mn2+. In experiments in which insertion and incorporation velocities of aminopurine and adenine are measured independently of each other, a 5- to 10-fold decrease in the Michaelis constant for aminopurine is observed in the presence of Mn2+ compared to a 2-fold decrease in the Km for adenine. In contrast to the marked differential reduction in the ratio of aminopurine to adenine Km values, the maximum insertion velocities of both nucleotides are reduced by similar amounts (40-fold). We suggest that the mutagenic action of Mn2+ can be attributed primarily to a significant differential increase in binding of mispaired relative to correctly paired nucleotides to the polymerase-template complex. The resulting increase in the ratio of residence times for mispaired compared with correctly paired nucleotides on the complex results in their increased frequency of misinsertion. A smaller contributing factor to Mn2+-induced mutagenesis is a loss of proofreading specificity. We propose that the losses in both the specificities of nucleotide insertion and excision (proofreading) share a common molecular origin in which nucleotides are bound in the presence of Mn2+ in distorted configurations at the polymerase insertion and excision active sites resulting in increased nonspecific enzyme-substrate binding forces at the expense of template-substrate base pair specific hydrogen bonds.

Phenylethylamine-like properties of baclofen.

Baclofen therapy resulted in improvement of dyskinesias only in patients with trunkal tardive dyskinesia. However, the appearance of undesirable side effects did not warrant continuation of treatment with this drug. Baclofen did not have any therapeutic effect in schizophrenia and moreover a trend towards a worsening of the psychiatric conditions with irritability, assaultiveness and prominent auditory hallucinations was observed. The effects of baclofen on tardive dyskinesia and schizophrenia can be explained in terms of its phenylethylamine-like properties.

Clockwise and counterclockwise pinwheel colony morphologies of Bacillus subtilis are correlated with the helix hand of the strain.

Helical macrofiber-producing strains of Bacillus subtilis grown on fresh complex medium semisolid surfaces formed "pinwheel"-shaped colonies. Clockwise pinwheel projections arose from colonies of strains that produce right-handed helical macrofibers in fluid cultures. Most strains able to make left-handed helical macrofibers in fluid grew as disorganized wavy colonies without directed projections. A phage-resistant left-handed mutant was found that produces very tight colonies with pinwheel projections that lie counterclockwise relative to the colony. The pinwheel colony morphology is interpreted therefore in terms of the cell surface organization and helical growth.

Physiological influences on cell division patterns in the div IV-B1 MINIcell-producing mutant of Bacillus subtilis.

The proportion of abnormal divisions resulting in minicells is influenced by growth stage and medium composition.

DNA Complementary to Ribosomal RNA: Relation between Genomic Proportion and Ploidy.

Ten Nicotiana species were assayed for the proportion of DNA that is complementary to ribosomal RNA. This proportion varies from 0.27 to 0.9 percent, with tetraploid species having lower values than the diploid species. The tetraploid species have about twice as much DNA per cell as do diploid species. Thus, the absolute number of genes for ribosomal RNA varies less than the proportion of complementary DNA. Further, the number of genes for the RNA in 80S ribosomes varies less among species than does that for the RNA in 70S ribosomes. The data indicate that loss of DNA complementary to ribosomal RNA is associated with tetraploidy in the genus Nicotiana.