Depression correlated with cellular immunity in systemic immunodeficient Epstein-Barr virus syndrome (SIDES).

We conducted studies on the peripheral blood of 12 depressed patients with previous diagnoses of mood and/or personality disorders. These patients, and other depressives we observed informally, were resistant to infectious mononucleosis during an epidemic of that illness. All 12 had serologic evidence of a chronic or recrudescent viremia caused by the Epstein-Barr virus (EBV), the infectious agent in infectious mononucleosis. Additional evidence that EBV viremia may be causally related to depression was provided by a strong correlation between the intensity of depressive symptoms and the cellular immune response to the EBV infection.

Generation, observation, and free radical reactivity of aliphatic bisketenes: the solution to a long-standing problem.

[reaction: see text] Bisketenes O=C=CH(CH(2))(n)()CH=C=O (1b,c,d, n = 4, 3, 6) and (E)-O=C=CHCH=CHCH=C=O (E-13) were generated in solution by dehydrochlorination of bis(acyl chlorides) and by photochemical Wolff rearrangements and identified by their characteristic IR signals. The bisketenes react with aminoxyl radicals to give tetraaddition products for 1b and conjugate 1,6-diaddition for E-13.

Radical additions of TEMPO to ketenes: correlation of free radical and nucleophilic reactivity.

[reaction: see text] Tetramethylpiperidinyloxy (TEMPO, TO*) reacts with a variety of ketenes R1R2C=C=O by rate-limiting attack on carbonyl carbon to give the 1,2-bis(adducts) R1R2C(OT)CO2T. The alpha,beta-unsaturated ketenes (E)-PhCH=CHCH=C=O (8b) and PhC=CCH=C=O (8c) give the 1,4-bis(adducts) PhCH(OT)CH=CHCO2T and PhC(OT)=C=CHCO2T. The ketenes may be generated in situ for these reactions in the presence of TEMPO by either dehydrochlorination of R1R2CHCOCl with Et3N or Wolff rearrangement. Ketenes PhCH=C=O (8a), 8b, and 8c had not previously been observed as long-lived species at room temperature, but when formed by photochemical Wolff rearrangement, these could be characterized in solution by conventional IR spectroscopy and used for kinetic studies for reaction with TEMPO using UV detection. The reactions of six ketenes with TEMPO in hydrocarbon solvents follow second-order kinetics, with a range of 2.5 x 10(5) in the rate constants, which are correlated with unit slope with the corresponding rate constants for hydration.

Effects of estradiol on platelet aggregation in mouse mesenteric arterioles and ex vivo.

Mice were implanted subcutaneously with a pellet containing 0.5 mg estradiol or with a placebo. Eight to 12 days later platelet aggregation was produced in mesenteric arterioles by injuring their endothelium in vivo with a noxious light/dye stimulus. The time between the onset of the noxious stimulus and the appearance of platelet aggregates was significantly shortened (p less than .01) in the estradiol treated mice. In contrast to this enhancement of aggregation, when platelets were tested ex vivo in platelet rich plasma (PRP), aggregation to sodium arachidonate was inhibited in estradiol treated mice. Aggregation of PRP by ADP was not affected by estradiol treatment of the mice. Thus the enhanced aggregation observed in injured mesenteric arterioles of estradiol treated mice may not reflect direct effects of estradiol on the platelet itself. Rather enhanced aggregation may reflect an effect of estradiol on endothelium or adjacent tissue. The data are discussed in light of other literature concerning estradiol effects in rodents, and in light of literature suggesting that an increased number of thromboembolic events occurs in humans receiving high doses of estrogens.

The Oxford growth study: a district growth surveillance programme 1988-1994.

OBJECTIVES: To develop a method of community based growth assessment. SETTING: Oxford District, United Kingdom. METHODS: A system of growth surveillance involving a community consultant paediatrician, a paediatric endocrinologist, a clinical auxologist, a project coordinator, and the many primary health care teams was started. Letters and meetings were arranged to introduce the programme to general practitioners and health visitors, emphasising the importance of growth assessment in normal child development. They were asked to measure all children as part of their routine developmental checks at 3 and 4.5 years of age. Community growth assessment clinics staffed by an experienced auxologist were established. Children whose heights were more than two standard deviation (SD) scores below the mean or whose height SD score decreased between the two ages were referred to the clinic. Any child whose height was more than 3 SD scores below the mean was referred directly to the paediatric endocrinologist. Those seen in the community clinics were followed up for a year and if their velocity was > 25th centile, karyotype normal, and bone age appropriately delayed, they were discharged to the general practitioner for further follow up. Any child with an annual velocity < 25th centile was referred to the endocrinologist. RESULTS: Of 20,338 children monitored, 260 (1.3%) had heights > -2 SD scores. Seventy six were lost to follow up, 35 were measuring errors, 69 were already seeing a paediatrician, leaving 80 children to be evaluated. Of these, 69 were "short normals" and 11 were newly identified diagnoses. CONCLUSIONS: This system of secondary referral keeps normal healthy children out of hospital, avoids unnecessary over-investigation, reduces travel and anxiety for families, avoids filling specialist clinics with normal children, and provides an inexpensive system of growth surveillance.

Making moral decisions on a double-blinded drug trial in progress without breaking the code: a primer on posterior analysis.

The double blinding of drug trials to prevent bias deprives physicians of information they need in order to comply with their duty to treat patients and do them no harm. This ethical dilemma can be ameliorated with a standard statistical method known as posterior analysis. The clinical researcher can use posterior analysis to calculate the probability that a patient in a double-blinded drug trial is in the placebo group, based on the patient's clinical status. The clinician can also calculate the probability that the drug is safe and efficacious, as compared with the placebo, without breaking the code.

Is RA27/3 rubella immunization a cause of chronic fatigue?

Patients with chronic fatigue syndromes (primary fibrositis syndrome, major affective disorder, etc.) have elevated IgG serum antibodies to multiple common viruses. Only IgG rubella antibodies are positively correlated with the intensity of symptoms and have a height that is clearly significant compared to healthy controls. The lymphotropic properties of the rubella virus could account for the multiple elevated antibodies. Adult women are over-represented in the population of patients with chronic fatigue, and are especially susceptible to developing such symptoms following exposure to attenuated rubella virus. A new more potent strain of live rubella vaccine (strain RA27/3) was introduced in 1979. Within three years reports of patients with chronic fatigue began surfacing in the literature. Considering all this, the possible role of rubella immunization in the etiology of chronic fatigue syndromes deserves further study.

Modeling AIDS and its treatment with immunostimulation.

A mathematical model of AIDS and its response to treatment with immunostimulation therapy is introduced. It correctly predicted the response of an AIDS patient to hyperimmunization with inactivated polio vaccine for a period of four months, indicating that this benign modality will offset the clinical effects of HIV-1 infection for almost a year.

A computer simulation of the natural history of HIV infection: insights and implications.

Computer simulation of the natural history of HIV infection shows that the progression from a silent infection to serious disease need not depend upon any particular biological event but only requires the passage of time. It likewise illustrates why modest efficacy from an antiretroviral agent can go a long way toward treating HIV infection, but a cure will be difficult to develop.

Left-right spatial agnosia and other mental defects that characterize clinical researchers.

There are mathematical rules for determining the logical significance of data, just as there are such rules for determining the statistical significance of data. Logical significance reflects the question a study is asking, whereas statistical significance reflects how well it has been answered. Clinical researchers routinely make an incorrect determination as to their study's logical significance because of a spatial (left-right) agnosia. More diffuse cognitive dysfunctions are encouraged by journals that expect clinicians to report on a study as a prerequisite for communicating their pre-existing opinions. The unwillingness or inability of the clinical community to acknowledge this problem reflects a related anosagnosia.

Pitfalls in the use of surrogate markers for human immunodeficiency virus disease: further evidence on pathogenesis.

The administration of drugs to human immunodeficiency virus patients with a pronounced CD4+ T lymphocytopenia may cause non-specific binding of the murine antibodies used in flow cytometry. This has produced spurious reports of early thymocytes in the circulating blood of human immunodeficiency virus-infected individuals following treatment with an anti-adhesion monoclonal mouse antibody (Cytolin+). Recent clinical experience with Cytolin+ confirms the pathogenic role of leukocyte adhesion pathways in human immunodeficiency virus infection. However, this experience also illustrates how comparisons of viral burden can be misleading. For nine patients with low CD4 counts, Cytolin+ alone reduced the mean ribonucleic acid-polymerase chain reaction by 0.45 log to 39 800 particles per mL. Ten patients with more advanced disease added Cytolin+ to an established regimen of standard antiretroviral drugs. Their mean polymerase chain reaction was only reduced by 0.2 log to 91 501. Yet, 67% of the former patients experienced a major clinical event within seven months, whereas the latter patients remained stable during this time.

Leukocyte adhesion molecules as a cofactor in AIDS: basic science and pilot study.

It is well known that the AIDS pandemic is a consequence of pandemic HIV infection. However, Koch's postulates are not satisfied for two reasons: 1) AIDS cannot be experimentally produced in animals susceptible to HIV infection and 2) some people have AIDS (idiopathic CD4+ T lymphocytopenia) in the absence of HIV infection. It follows that there is a human immunologic cofactor (HIC) that causes AIDS when certain other conditions are satisfied, and the most common of these other conditions (but not the only one) is HIV infection. Results from microbiology make leukocyte adhesion molecules a good candidate for the HIC. We have tested this hypothesis with a pilot study in which a small number of patients with HIV disease were infused with a monoclonal mouse antibody (MmAb) directed against an LFA-1 adhesion epitope, and then with F(ab) and F(ab)2' fragments that bind to the same epitope but are nonimmunogenic. Both agents reduced peripheral viral burden significantly but fragments were more effective in this respect than the MmAb due to the mitogenic properties of the latter. For the same reason, only the MmAb were highly effective in raising circulating levels of single and double-marked CD4+ T lymphocytes, with a correlated resolution of cutaneous anergy.

Assessment of the endoscopic semitendinosus/gracilis autograft procedure with interference screw fixation for reconstruction of the anterior cruciate ligament.

The semitendinosus/gracilis autograft procedure with interference screw fixation was evaluated for clinical effectiveness of anterior cruciate ligament (ACL) reconstruction. Thirty patients underwent the procedure and were evaluated an average of 15 months postoperatively. Results revealed 22 (73%) patients had a standard knee evaluation form score of normal or nearly normal, and 24 (80%) patients returned to strenuous or moderate activity levels. Average Lysholm outcome score was 89, and bilateral KT-2000 differences were <3 mm at follow-up. Functional knee test symmetry index percentage outcome for the one-legged hop test was 92.6% for distance and 98% for time. Length of time (i.e., < or =90 days or > or =91 days) between injury and surgery was independent of outcome. These findings indicate the semitendinosus/gracilis autograft is a viable procedure for reconstruction of the ACL-deficient knee.