Applications of Doppler-free saturation spectroscopy for edge physics studies (invited).

Doppler-free saturation spectroscopy provides a very powerful method to obtain detailed information about the electronic structure of the atom through measurement of the spectral line profile. This is achieved through a significant decrease in the Doppler broadening and essentially an elimination of the instrument broadening inherent to passive spectroscopic techniques. In this paper we present the technique and associated physics of Doppler-free saturation spectroscopy in addition to how one selects the appropriate transition. Simulations of Hδ spectra are presented to illustrate the increased sensitivity to both electric field and electron density measurements.

Potential mechanisms for failure to eradicate group A streptococci from the pharynx.

OBJECTIVE: To investigate the relative efficacy of orally administered cefadroxil and penicillin V in the treatment of group A streptococcal (GABHS) pharyngitis and the mechanism(s) responsible for failure of antimicrobial therapy to eradicate GABHS from the pharynx. STUDY DESIGN: A prospective, randomized clinical trial was conducted in four pediatric offices in which 462 patients with acute pharyngitis and positive culture for GABHS were randomly assigned to receive cefadroxil (n = 232) or penicillin V (n = 230). RESULTS: Bacteriologic treatment success rates for patients in cefadroxil and penicillin groups were 94% and 86%, respectively. However, among patients classified clinically as likely to have bona fide GABHS pharyngitis, there was no difference in bacteriologic treatment success rates in cefadroxil and penicillin groups (95% and 94%, respectively). Among patients classified clinically as likely to be streptococcal carriers, bacteriologic treatment success rates in cefadroxil and penicillin groups were 92% and 73%, respectively. The presence of beta-lactamase and/or bacteriocin-producing pharyngeal flora had no consistent effect on bacteriologic eradication rates among patients in either penicillin or cefadroxil treatment groups or among patients classified as having either GABHS pharyngitis or streptococcal carriage. CONCLUSIONS: Neither beta-lactamase nor bacteriocin produced by normal pharyngeal flora are related to bacteriologic treatment failures in GABHS pharyngitis. Cefadroxil seems to be more effective than penicillin V in eradicating GABHS from patients classified as more likely to be streptococcal carriers. However, among patients we classified as more likely to have bona fide GABHS pharyngitis, the effectiveness of cefadroxil and penicillin V seems to be comparable.

Estimation and correlation of drug water solubility with pharmacological parameters required for biological activity.

A procedure for estimating the molar water solubility (S) for a series of structurally related drug compounds is presented. HPLC methods for the determination of partition coefficients (P) are combined with semiempirical calculations for S. Multidimensional plots are developed with the physical constants S and P along the x and y axes and with a biological response, e.g. IC50 or ED50, along the z axis. Other attributes, e.g. bioavailability or biodistribution, can be added by color coding, shading, or numbering. Since the methods have a high throughput capability, parameters governing the events leading to pharmacological action [i.e. gastrointestinal dissolution (S), absorption (P), blood level (bioavailability), and biological action (IC50, EC50)] can be correlated for drug series comprising large numbers of compounds.

Perinatal and neonatal issues of substance abuse.

Substance abuse during pregnancy can be teratogenic for the fetus and can cause decreased growth parameters in the newborn infant. Short-term and long-term neurobehavioral problems have been documented also in babies born to substance-abusing mothers. The problem of substance abuse during pregnancy and its effects on the fetus is unique in medicine in that it is 100% preventable. Physicians will need to take an active role in leading society to take action in preventing substance abuse during pregnancy, and emphasis on this action should occur long before the woman becomes pregnant. Until medical schools and residency programs take responsibility for teaching the importance of preventing substance abuse and of identifying the substance-abuser, drug and alcohol use will continue to exact its tragic toll on future generations.

Dentistry's role in the resolution of missing and unidentified persons cases.

The dentist's role in the resolution of missing persons cases is an important one and involves cooperation and assistance. From the beginning of the investigation of a missing child or adult, the submission of complete and accurate records of the dental condition of the particular individual is vital. The dentist that reviews and codes the missing person's dental information before its entry into a missing persons database must be knowledgeable of the logic behind the comparison features of the software used to rank the records. The logic of the comparison may dictate how subjective features are coded. In reviewing the records of the treating dentist, one always must be aware of other sources that may be noted in the records that could provide additional information. The dentist that is responsible for the collection of the dental information from the unidentified remains must be trained in the procedures necessary to collect and document this information. The dentist must be familiar with the legal ramifications and requirements of handling evidence, which may require court testimony. The dentist must be aware of the information that is necessary to substantiate an identification. The examining dentist should be familiar with the American Board of Forensic Odontology's standards and guidelines for the collection, analysis, and terminology used in the identification process. If a particular state does not have a central repository for missing and unidentified persons information, interested and dedicated dentists can encourage agencies and legislators to create one. These repositories have been invaluable in the resolution of cases that have gone on for years. Dentistry can help resolve many of missing persons cases and bring closure to family and friends that wonder and worry.

An overlapping protein-coding region in influenza A virus segment 3 modulates the host response.

Influenza A virus (IAV) infection leads to variable and imperfectly understood pathogenicity. We report that segment 3 of the virus contains a second open reading frame ("X-ORF"), accessed via ribosomal frameshifting. The frameshift product, termed PA-X, comprises the endonuclease domain of the viral PA protein with a C-terminal domain encoded by the X-ORF and functions to repress cellular gene expression. PA-X also modulates IAV virulence in a mouse infection model, acting to decrease pathogenicity. Loss of PA-X expression leads to changes in the kinetics of the global host response, which notably includes increases in inflammatory, apoptotic, and T lymphocyte-signaling pathways. Thus, we have identified a previously unknown IAV protein that modulates the host response to infection, a finding with important implications for understanding IAV pathogenesis.

Oro-facial-digital syndrome II. Transitional type between the Mohr and the Majewski syndromes: report of two new cases.

Two patients with the oro-facial-digital syndrome II or Mohr syndrome presented laryngeal anomalies and hallucal and postaxial polysyndactyly of the feet. Those rare malformations are typically observed in patients with the Majewski syndrome, a lethal, short rib-polydactyly skeletal dysplasia with orofacial findings almost identical to those of the Mohr syndrome. Phenotypic overlap between the Mohr and the Majewski syndromes has already been reported in the literature, and it has been suggested that the two syndromes may be mild and severe expressions of the same autosomal recessive disorder. Our two cases give further support to this hypothesis.

Triphalangeal thumb and brachy-ectrodactyly syndrome. Confirmation of autosomal dominant inheritance.

Two patients with triphalangeal thumbs-ectrodactyly syndrome are described. The first case is a 4-year-old female with triphalangeal thumbs, preaxial polydactyly with rudimentary polydactyly of the 3rd finger of the right hand and ectro-syndactyly of feet. Her stillborn sister had triphalangeal thumbs and ectrodactyly of feet. The mother has triphalangeal thumbs, brachy-syndactyly of the left foot and ectro-syndactyly of the right one. The maternal grandmother has syndactyly of 1st, 2nd, 3rd toes and hypoplasia of the 3rd toe on the right foot. The second case is sporadic and shows triphalangeal thumbs, preaxial polydactyly of the right hand and bilateral lobster-claw feet. Our observations confirm the variability of clinical expression and support the autosomal dominant inheritance of the syndrome.

Soybean oil emulsion administration during parenteral nutrition in the preterm infant: effect on essential fatty acid, lipid, and glucose metabolism.

To examine the effect of a soybean oil emulsion on essential fatty acid, lipid, and glucose metabolism, preterm infants were randomized to receive 0.5 g/kg/d lipid for 5 days (n = 10, group 1) or 0.5 increased to 2.0 g/kg/d over 5 days (n = 11, group 2). Triene/tetraene ratios did not change in group 1, but decreased in group 2. In both groups, plasma phospholipid linoleate (percent and micrograms per milliliter) increased, the increase being greater in group 2. In both groups, percent content of arachidonate and 5,8,11-eicosatrienoate decreased, and that of oleate remained unchanged. In contrast, absolute content of arachidonate and oleate tended to increase, and that of 5,8,11-eicosatrienoate remained unchanged. At a lipid intake of 0.5 g/kg/d, no infants had hyperlipemia. When lipid intake exceeded 1.0 g/kg/d, the frequency of hypertriglyceridemia (triglycerides greater than 200 mg/dL) and free fatty acidemia, with the free fatty acid/molar albumin ratio exceeding 6:1, increased. Plasma glycerol increased slightly, but was substantially less than the rise in enzymatically determined triglycerides. Hyperglycemia was self-limiting and did not require alteration in dextrose intake. Thus, (1) infusion of a soybean oil emulsion at 0.5 to 2.0 g/kg/d maintains essential fatty acid status and phospholipid arachidonate concentrations; (2) significant hyperlipemia occurs when lipid intake exceeds 1.0 g/kg/d; (3) hyperglycemia associated with lipid infusion tends to be self-limiting and may not require alteration in lipid or dextrose intake; and (4) enzymatically determined triglycerides may be used to monitor lipid tolerance, provided that allowance is made for a small but systematic overestimation resulting from the rise in plasma glycerol.

Recombinant outer surface protein C ELISA for the diagnosis of early Lyme disease.

To compare the sensitivity of a new ELISA for IgM antibodies to Borrelia burgdorferi that uses a recombinant outer surface protein C (rOspC) with those of a whole cell (WC) ELISA and an immunoblot assay for the diagnosis of early Lyme disease, serum specimens from 82 consecutive patients with physician-documented erythema migrans were analyzed. To compare the specificities of the three assays, serum specimens from 50 patients without a history of Lyme disease and from an area in which B. burgdorferi is not endemic were analyzed. The sensitivities of the WC ELISA, immunoblot assay, and IgM rOspC ELISA were 28%, 29%, and 46%, respectively, while the specificities were 100%, 100%, and 98%, respectively. The IgM rOspC ELISA is a convenient, readily automated, easily standardized serologic test that is significantly more sensitive for the diagnosis of early Lyme disease than either WC ELISA or immunoblot assay.

Measurement of behavioral, affective, and somatic responses to pediatric bone marrow transplantation: development of the BASES scale.

A new measure to assess behavioral, affective and somatic outcomes in the acute phase of bone marrow transplant is described. The Behavioral Affective and Somatic Experiences Scale (BASES) is a 38 item nurse-report instrument, with five subscales labeled Somatic distress, Compliance, Mood/Behavior, Interactions, and Activity. A series of pilot studies were conducted to refine the content of the BASES scale and to establish its psychometric properties in terms of internal consistency, inter-rater reliability, and validity. Internal consistency (Chronbach's alpha) for the subscales ranged from .742 to .902. Inter-rater reliability was good, with a median correlation between paired nurse observations of .866. A parent report version of the BASES scale has also been developed, and the finding of significant parent-nurse correlations provides preliminary evidence of the validity of the measure. Potential uses of the BASES scale in the pediatric BMT setting are discussed.

Evaluations of enzyme-linked immunosorbent assay procedure for determining specific Epstein-Barr virus serology and of rapid test kits for diagnosis for infectious mononucleosis.

Using the results of Epstein-Barr virus-specific immunofluorescence serology as the "gold standard," we found that the sensitivities of the five rapid test kits varied from 78 to 84% and specificities varied from 89 to 100%. Enzyme-linked immunosorbent assay-determined specific Epstein-Barr virus antibody profiles had a sensitivity and specificity of 98.6 and 95.5%, respectively.

Lyme disease in children in southeastern Connecticut. Pediatric Lyme Disease Study Group.

BACKGROUND: Although the incidence of Lyme disease is highest in children, there are few prospective data on the clinical manifestations and outcomes in children. METHODS: We conducted a prospective, longitudinal, community-based cohort study of children with newly diagnosed Lyme disease in an area of Connecticut in which the disease is highly endemic. We obtained clinical and demographic information and performed serial antibody tests and follow-up evaluations. RESULTS: Over a period of 20 months, 201 consecutive patients were enrolled; their median age was 7 years (range, 1 to 21). The initial clinical manifestations of Lyme disease were a single erythema migrans lesion in 66 percent, multiple erythema migrans lesions in 23 percent, arthritis in 6 percent, facial-nerve palsy in 3 percent, aseptic meningitis in 2 percent, and carditis in 0.5 percent. At presentation, 37 percent of the patients with a single erythema migrans lesion and 89 percent of those with multiple erythema migrans lesions had antibodies against Borrelia burgdorferi. All but 3 of the 201 patients were treated for two to four weeks with conventional antimicrobial therapy, which was administered orally in 96 percent. All had prompt clinical responses. After four weeks, 94 percent were completely asymptomatic (including the two patients whose parents had refused to allow antimicrobial treatment). At follow-up a mean of 25.4 months later, none of the patients had evidence of either chronic or recurrent Lyme disease. Six patients subsequently had a new episode of erythema migrans. CONCLUSIONS: About 90 percent of children with Lyme disease present with erythema migrans, which is an early stage of the disease. The prognosis is excellent for those with early Lyme disease who are treated promptly with conventional courses of antimicrobial agents.

Asymmetric crying facies with microcephaly and mental retardation. An autosomal dominant syndrome with variable expressivity.

An infant boy with asymmetric crying facies, microcephaly, developmental retardation and failure to thrive is reported. His two siblings died in the newborn period because of complex congenital heart defects. The mother and the maternal grandmother have asymmetric crying facies, microcephaly and normal intelligence. A maternal aunt has severe physical and mental retardation, facial asymmetry, microcephaly, and cleft palate. This family allows an expansion of the spectrum of malformations associated with asymmetric crying facies and suggests autosomal dominant inheritance with variable expressivity.

A controlled trial of antimicrobial prophylaxis for Lyme disease after deer-tick bites.

BACKGROUND: Borrelia burgdorferi, which causes Lyme disease, is transmitted by deer ticks (lxodes dammini) in the northeastern and midwestern United States. Although deer-tick bites are common in areas in which the disease is endemic, there is uncertainty about how to manage the care of persons who are bitten. METHODS: To assess the risk of infection with B. burgdorferi and the efficacy of prophylactic antimicrobial treatment after a deer-tick bite, we conducted a double-blind, placebo-controlled trial in an area of southeastern Connecticut in which Lyme disease is endemic. Children and adults who had been bitten by deer ticks were randomly assigned to receive either amoxicillin or placebo for 10 days. Subjects were followed for one year for clinical manifestations of Lyme disease. Serum samples obtained at enrollment and six weeks and three months later were tested for antibodies against B. burgdorferi. RESULTS: Of the 387 subjects, 205 (53 percent) were assigned to receive amoxicillin and 182 (47 percent) to receive placebo. Of 344 deer ticks submitted and analyzed by the polymerase chain reaction, 15 percent were infected with B. burgdorferi. Erythema migrans developed in two subjects, both of whom had received placebo. There were no asymptomatic seroconversions and no late manifestations of Lyme disease. The risk of infection with B. burgdorferi in the placebo-treated subjects was 1.2 percent (95 percent confidence interval, 0.1 to 4.1 percent), which was not significantly different (P = 0.22) from the risk in the amoxicillin-treated subjects (0 percent; 95 percent confidence interval, 0 to 1.5 percent). CONCLUSIONS: Even in an area in which Lyme disease is endemic, the risk of infection with B. burgdorferi after a recognized deer-tick bite is so low that prophylactic antimicrobial treatment is not routinely indicated.

Optical immunoassay test for group A beta-hemolytic streptococcal pharyngitis. An office-based, multicenter investigation.

OBJECTIVE: To compare the accuracy of an optical immunoassay (OIA) for the rapid diagnosis of group A streptococcal pharyngitis with blood agar plate (BAP) culture. DESIGN: Blinded comparison with criterion standard. SETTING: A total of 6 private pediatricians' offices, 3 in Connecticut and 3 in Chicago, III. PATIENTS: A total of 2113 consecutive patients with acute pharyngitis, 983 in Connecticut and 1130 in Chicago. MAIN OUTCOME MEASURES: The sensitivities and specificities of OIA and BAP culture (both performed and interpreted in the office) were determined using a research laboratory's interpretation of a combination of BAP culture and Todd-Hewitt broth (THB) culture of transport tube pledget as criterion standard. RESULTS: Among patients in Connecticut, the sensitivities of the OIA and BAP culture were 94% and 89%, respectively (P=.004), while the specificities were 96% and 99%, respectively (P=.001). Among patients in Chicago, the sensitivities of the OIA and BAP culture were 79% and 72%, respectively (P<.001), while the specificities were 89% and 99%, respectively (P<.001). In each of the 6 pediatricians' offices, the OIA was more sensitive than the BAP culture. Combining the data from Connecticut and Chicago, the overall sensitivities of the OIA and BAP culture were 84% and 78%, respectively (P<.001), while the specificities were 93% and 99%, respectively (P<.001). CONCLUSIONS: The results of this comprehensive office-based investigation suggest that with adequately trained personnel, negative OIA test results may not always need to be routinely confirmed with BAP cultures.