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Insomnia is a prevalent condition and a significant source of psychosocial impairments. It is associated with numerous comorbidities that affect quality of life. An adequate assessment is key to developing an efficacious treatment strategy. This paper provides a basic overview of currently available modalities for evaluation and treatment of this condition.

Challenged by the sudden appearance of AIDS as a major public health crisis, the National Institute of Allergy and Infectious Diseases and the Fogarty International Center of the National Institutes of Health (NIH), together with The Rockefeller University, jointly sponsored the conference "Emerging Viruses: The Evolution of Viruses and Viral Diseases" held 1-3 May 1989 in Washington, DC. It was convened to consider the mechanisms of viral emergence [1] and possible strategies for anticipating, detecting, and preventing the emergence of new viral diseases in the future. To provide a broad perspective, participants comprised virologists, infectious disease specialists, theoretical biologists, historians, epidemiologists, ecologists, and molecular biologists (see below for program and participants).

A workshop was held 18 to 19 March 1991 at the National Institutes of Health to address critical issues in research concerning the chronic fatigue syndrome (CFS). Case definition, confounding diagnoses, and medical outcome assessment by laboratory and other means were considered from the perspectives of key medical specialties involved in CFS research. It was recommended that published Centers for Disease Control (CDC) case-definition criteria be modified to exclude fewer patients from analysis because of a history of psychiatric disorder. Specific recommendations were made concerning the inclusion or exclusion of other major confounding diagnoses, and a standard panel of laboratory tests was specified for initial patient evaluation. The workshop emphasized the importance of recognizing other conditions that could explain the patient's symptoms and that may be treatable. It was viewed as essential for the investigator to screen for psychiatric disorder using a combination of self-report instruments followed by at least one structured interview to identify patients who should be excluded from studies or considered as a separate subgroup in data analysis. Because CFS is not a homogeneous abnormality and because there is no single pathogenic mechanism, research progress may depend upon delineation of these and other patient subgroups for separate data analysis. Despite preliminary data, no physical finding or laboratory test was deemed confirmatory of the diagnosis of CFS. For assessment of clinical status, investigators must rely on the use of standardized instruments for patient self-reporting of fatigue, mood disturbance, functional status, sleep disorder, global well-being, and pain. Further research is needed to develop better instruments for quantifying these domains in patients with CFS.

A workshop was held 18 to 19 March 1991 at the National Institutes of Health to address critical issues in research concerning the chronic fatigue syndrome (CFS). Case definition, confounding diagnoses, and medical outcome assessment by laboratory and other means were considered from the perspectives of key medical specialties involved in CFS research. It was recommended that published Centers for Disease Control (CDC) case-definition criteria be modified to exclude fewer patients from analysis because of a history of psychiatric disorder. Specific recommendations were made concerning the inclusion or exclusion of other major confounding diagnoses, and a standard panel of laboratory tests was specified for initial patient evaluation. The workshop emphasized the importance of recognizing other conditions that could explain the patient's symptoms and that may be treatable. It was viewed as essential for the investigator to screen for psychiatric disorder using a combination of self-report instruments followed by at least one structured interview to identify patients who should be excluded from studies or considered as a separate subgroup in data analysis. Because CFS is not a homogeneous abnormality and because there is no single pathogenic mechanism, research progress may depend upon delineation of these and other patient subgroups for separate data analysis. Despite preliminary data, no physical finding or laboratory test was deemed confirmatory of the diagnosis of CFS. For assessment of clinical status, investigators must rely on the use of standardized instruments for patient self-reporting of fatigue, mood disturbance, functional status, sleep disorder, global well-being, and pain. Further research is needed to develop better instruments for quantifying these domains in patients with CFS.

The frequency of resistance to seven different antimicrobial agents was examined in the aerobic gram-negative gut flora of over 600 individuals from hospitals, from laboratories where antibiotics were used, and from urban and rural communities. In a majority (62.5%) of fecal samples from people without a recent history of taking antibiotics, 10% or more of the total organisms were resistant to at least one of the antibiotics. In about 40% of the samples, resistance to more than one drug was present at this level. More than one-third of the samples contained resistant organisms comprising 50% or more of the total flora examined. Organisms with coresistance to multiple drugs were found frequently. Individuals taking antibiotics produced more samples with a higher proportion (greater than 50%) of resistant bacteria, and these samples also had a significantly greater number of different resistance determinants. This extensive study revealed a high prevalence of resistant bacteria in the gut flora of ambulatory and hospitalized individuals whether or not they were taking antibiotics.

A precipitating antigen, rho, was first detected in the blood of persons with rubella and in rubella virus-infected cell culture fluids (1). Partially purified antigens from both sources were examined and shown to have similar properties, although antigen from serum sedimented more heterogeneously, with estimated coefficients from 15 to 21 S, while that from culture fluids sedimented in the 11–14 S region. In each case, antigen was located in the ß-1 zone after electrophoresis in agarose, and at a density of 1.305 g/ml after centrifugation in CsCl. Stability characteristics were typical of protein antigens. Immunofluorescent microscopy revealed that rubella virus induced the appearance of rho antigen scattered throughout the cytoplasm of infected cells. When cells containing antigen were exposed for 24 h to 5 µg/ml actinomycin D rho was no longer detectable, indicating the probable cellular origin of the antigen. Also, titers in medium of infected cultures showed a reduction after actinomycin treatment, but levels of the virus-specified antigen, iota, were relatively unaffected. Rho appears to be a protein common to man and many animals. In vitro, it was induced by rubella virus and by adenovirus. In vivo, rho titers were shown to be elevated after rubella virus infection and, to a lesser extent, after infection with certain other viruses. High titers were also demonstrated in women late in pregnancy and in patients with rheumatoid arthritis. In man and the chimpanzee, the appearance and decline of rho in the blood after rubella virus infection were temporally similar to the patterns of CRP, although rho seemed to be a more sensitive indicator of infection. The data presented indicate that rho is a newly recognized acute phase protein inducible by certain virus infections and by other unidentified stimuli present prominently in pregnancy and rheumatoid arthritis.

Rho, a newly characterized acute-phase protein, was present in high titer in a group of 109 patients with various rheumatic diseases. Statistically significant titer elevations were demonstrated in patients with rheumatoid arthritis (RA), ankylosing spondylitis, and gout. In individual RA patients, serial titers failed to correlate with disease activity or with rheumatic seropositivity. The natural behavior ofrho antigen is contrasted with that of C-reactive protein. Comments are made regarding the possible association of rubella infection with rheumatoid arthritis.

New technologies are being developed which will facilitate measurement of IgG subclass responses to disease and vaccination. To illustrate the potential benefit of determining antibody subclass profiles, special features of the less abundant subclasses are discussed in relation to specific infectious disease problems.

Data bearing on the appearance of measles-specific components in infected-cell nuclei have been reviewed. There is suggestive evidence that nuclear compartmentalization may be host-dependent and that nuclear accumulations may increase when virus release is blocked. It remains uncertain whether the presence of viral components in the nucleus is an incidental or a required stage in measles virus replication. We noted, however, that radioactively labeled measles RNA was demonstrated in nucleoplasmic fractions following short exposures to [3H]-uridine, and that it appeared to accumulate in association with the nucleus late in infection. We recently have been examining nuclei isolated from measles virus infected cells for viral polymerase activity, but none has been demonstrated.

Summary Structural polypeptides of a measles virus strain isolated from a case of subacute sclerosing panencephalitis (SSPE) were compared with those of the Edmonston strain by electrophoresis in acrylamide gel slabs containing sodium dodecyl sulfate. The smallest polypeptide, which appears to be the membrane protein, of the SSPE strain migrated more slowly than the corresponding measles polypeptide, indicating molecular weights of 40,000 and 38,000 daltons, respectively. The five other proteins successfully compared showed identical mobilities. A greater concentration of one of these (66,000 daltons) was seen in SSPE virions.

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Measles virus replication and RNA synthesis in Vero cells are inhibited by actinomycin at concentrations which inhibit cellular RNA synthesis. Drug present from the 2nd to the 24th hr post infection inhibited infectivity but not hemagglutinating activity or cell fusion. Infectivity was much less sensitive to drug added during the second 24-hr period, and 52S RNA was labeled and incorporated into virions during this later time interval.

Summary Studies with inactivated measles virus in guinea pigs showed: The early response to primary antigenic stimulus was production of 19S antibody alone.A 7S antibody component was regularly demonstrated in the later phases of the primary response.The secondary response to the same antigen was characterized by a rapid increase in 7S antibody production and by the absence of 19S.Five of six animals failing to produce detectable hemagglutination inhibition (HI) antibodies during the 1st week of immunization showed an accelerated 19S and 7S antibody responses to an injection given on the 7th day.Antibody responses to challenge with monkey-grown measles virus and chick-grown measles virus appeared identical in animals immunized with chick-grown vaccine. Studies with mumps and DA viruses in monkeys showed: Previous exposure to DA virus did not alter the primary nature of the response to mumps virus.The primary response to mumps infection did not alter the secondary character of the heterologous DA antibody rise.

SummaryFluorescein labeled antibody staining of HEp-2 cell cultures infected with an inoculum of measles virus free of cell debris and other particulate matter revealed the presence of measles virus antigen in cells in metaphase, anaphase and telophase. Mitotic cells were shown to be readily recruited into syncytia induced by measles virus, both in absence and presence of colchicine. These observations contrast with the results of similar studies made in HEp-2 cell cultures infected with Herpes simplex virus and indicate that cells in different stages of the mitotic cycle are not uniformly susceptible to infection with different viruses, or even the same virus.

Measles virus RNA was found in the nuclear fraction of infected Vero cells. 24-hr labeling periods revealed heterogeneously sedimenting 15–50 S RNA associated with a membrane-containing particulate. Viral RNA isolated after shorter labeling periods was larger in size (30–50 S) and associated with both nucleoplasmic and particulate fractions.

RNA has been isolated from measles virions which sediments with a coefficient of 52.2 S when compared with 50 S RNA from SV 5 virions.

Summary Studies of hemagglutination-inhibition reactions of the antigenically related measles soluble (SDA) and envelope-integrated viral (HA) hemagglutinins have shown the following: Eighty units of SDA failed to compete with 4 units of HA for HI antibodies, although in the same experiment SDA required, unit for unit, an antibody concentration of the same magnitude for inhibition as that required by HA.A negative Danysz effect was demonstrated with SDA and a positive effect with viral HA, which indicates that SDA forms a less stable union with antibody than does HA. Reversibility of SDA-antibody combination was proposed as an explanation for the result above.The ratios of SDA inhibition titer to HI titer varied under different circumstances. Factors included time of serum collection relative to disease onset, class of immunoglobulin predominating, and average size and state of aggregation of the HA preparation used for the comparison.

The immune status of children vaccinated prior to 1 year of age was investigated during a measles epidemic in an industrial section of Connecticut. Of the 61 documented cases which occurred in former recipients of live vaccine 46% were children vaccinated prior to the age of 1; children vaccinated before age 1 comprised 1/3 of the total vaccinated population under study. The disproportionately increased number of cases in children vaccinated before their 1st birthday was not statistically significant. Of children vaccinated before age 1 80% had demonstrable measles antibody. The geometric mean antibody titer of those vaccinated in infancy was lower than that of children vaccinated after the age of 1 (p

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Rho is a newly described acute-phase serum protein which increases in titer in response to a variety of inflammatory and infectious diseases. 1 It is present in 100 per cent of sera from pregnant women by the twentieth week of gestation, rises in titer until term, and then falls slowly during the postpartum period. It was barely detectable in some fetal sera and in some amniotic fluid samples near the end of the first half of gestation, and it could not be demonstrated in fetal tissue obtained at that time. Fetal serum titers increase with gestational age, but fetal levels remain below those of maternal sera. Undifferentiated placental tissue and estrogen/progestin do not appear to evoke rho antigen production. The stimulating mechanism during gestation remains unknown.