Lack of behavioural effects after acute tyrosine depletion in healthy volunteers.

Acute dietary tyrosine depletion has previously been shown to reduce dopamine neurotransmission in both animals and humans. In this study, we investigated the effects of brain dopamine depletion, through acute tyrosine and phenylalanine depletion, on plasma prolactin, mood and neuropsychological function in 12 normal subjects. In a randomized, double-blind, cross-over design, subjects received two amino-acid drinks separated by a week, a nutritionally balanced mixture (Bal) and on the other occasion a tyrosine and phenylalanine deficient mixture (TP-). The plasma ratio of tyrosine and phenylalanine to the other large neutral amino acids decreased significantly on the TP- occasion (-78.7%, p < 0.0001) and there was an increase in plasma prolactin concentration relative to the balanced drink in the seven subjects for whom results were available for both occasions (p < 0.02). Acute tyrosine depletion did not alter mood as measured by visual analogue scale ratings, and measures of memory, attention and behavioural inhibition were also unaffected. Our results are consistent with acute dietary tyrosine depletion causing a reduction in brain dopamine neurotransmission but raise questions about how robust or consistent the effects are on psychological function.

Phenotypic and genotypic characterization of Mycobacterium africanum isolates from West Africa.

The Mycobacterium tuberculosis complex includes M. tuberculosis, M. bovis, M. africanum, and M. microti. Most clinical isolates are M. tuberculosis or M. bovis. These species can be distinguished by phenotypes and genotypes. However, there is no simple definition of M. africanum, and some authors question the validity of this species. We analyzed 17 human isolates from Sierra Leone, identified as M. africanum by biochemical and growth characteristics. We sequenced polymorphic genes and intergenic regions. We amplified DNA from six loci with variable numbers of tandem repeats (VNTRs) and determined the exact number of repeats at each locus in each strain. All M. africanum isolates had the ancestral CTG Leu at katG codon 463. Drug-resistant M. africanum isolates had katG and rpoB mutations similar to those found in drug-resistant M. bovis and M. tuberculosis. Fourteen Sierra Leone M. africanum isolates (designated group A) had katG codon 203 ACC Thr, also found in M. africanumT (the T indicates type strain) from Senegal. Group A isolates clustered with M. africanumT by VNTR analysis. Three M. africanum isolates (group B) had katG codon 203 ACT Thr, found in M. tuberculosisT, and clustered with M. tuberculosisT by VNTR analysis. Phenotypic identification of M. africanum yielded a heterogeneous collection of strains. Genotypic analyses identified a cluster (M. africanum group A) which included M. africanumT and was distinct from the rest of the M. tuberculosis complex. Future studies of M. africanum should include both phenotypic and genotypic analyses.

Randomised, double-blind, placebo-controlled treatment trial of fluoxetine and graded exercise for chronic fatigue syndrome.

BACKGROUND: The Joint Working Group of the Royal Colleges of Physicians, Psychiatrists and General Practitioners (1996) recommended graded exercise and antidepressants for patients with chronic fatigue syndrome. We assessed efficacy and acceptability of these treatments. METHOD: Six-month prospective randomised placebo and therapist contact time controlled trial with allocation to one of four treatment cells: exercise and 20 mg fluoxetine, exercise and placebo drug, appointments only and 20 mg fluoxetine, appointments and placebo drug. Drug treatment was double blind and patients were blind to assignment to exercise or appointments. RESULTS: Ninety-six (71%) of 136 patients completed the trial. Patients were more likely to drop out of exercise than non-exercise treatment (P = 0.05). In an intention to treat analysis, exercise resulted in fewer patients with case level fatigue than appointments only at 26 weeks (12 (18%) v. 4 (6%) respectively P = 0.025) and improvement in functional work capacity at 12 (P = 0.005) and 26 weeks (P = 0.03). Fluoxetine had a significant effect on depression at week 12 only (P = 0.04). Exercise significantly improved health perception (P = 0.012) and fatigue (P = 0.028) at 28 weeks. CONCLUSIONS: Graded exercise produced improvements in functional work capacity and fatigue, while fluoxetine improved depression only.

Continuing measles transmission in students despite school-based outbreak control program.

FRom September 9, 1981 to January 5, 1982, a measles outbreak occurred in Warren County, Pennsylvania. The outbreak persisted for nine weeks following the implementation of a county-wide outbreak control program primarily consisting of identifying and vaccinating susceptible schoolchildren. Forty-six cases occurred among students more than two weeks after control program implementation. All 46 had a school record indicating adequate measles vaccination; 13 had been vaccinated at control program clinics by one jet-injector team (Team A). A seroprevalence survey demonstrated that persons vaccinated by Team a had a significantly higher rate of vaccination failure than children vaccinated by other teams (37.0% vs. 5.9%, p = 5.7 X 10(-7). A case-control study was undertaken to assess possible additional risk factors for developing measles. Individuals with measles were nine times more likely than control individuals to have records of measles immunization that could not be verified with providers or to have been vaccinated at 12 months of age. The most likely reasons that this outbreak was sustained among persons with adequate vaccination histories were: 1) impotent vaccines and/or improper vaccine administration techniques were used by one jet-injector team; 2) several persons with histories of adequate vaccination were really not adequately vaccinated; adn 3) a substantial number of persons had been vaccinated at 12 months of age. There is no evidence from this outbreak that transmission of measles can be sustained among the 2-10% of individuals expected to remain susceptible following a single appropriate measles vaccination.