Human brain metabolic response to caffeine and the effects of tolerance

OBJECTIVE: Since there is limited information concerning caffeine's metabolic effects on the human brain, the authors applied a rapid proton echo-planar spectroscopic imaging technique to dynamically measure regional brain metabolic responses to caffeine ingestion. They specifically measured changes in brain lactate due to the combined effects of caffeine's stimulation of glycolysis and reduction of cerebral blood flow. METHOD: Nine heavy caffeine users and nine caffeine-intolerant individuals, who had previously discontinued or substantially curtailed use of caffeinated products because of associated anxiety and discomforting physiological arousal, were studied at baseline and then during 1 hour following ingestion of caffeine citrate (10 mg/kg). To assess state-trait contributions and the effects of caffeine tolerance, five of the caffeine users were restudied after a 1- to 2-month caffeine holiday. RESULTS: The caffeine-intolerant individuals, but not the regular caffeine users, experienced substantial psychological and physiological distress in response to caffeine ingestion. Significant increases in global and regionally specific brain lactate were observed only among the caffeine-intolerant subjects. Reexposure of the regular caffeine users to caffeine after a caffeine holiday resulted in little or no adverse clinical reaction but significant rises in brain lactate which were of a magnitude similar to that observed for the caffeine-intolerant group. CONCLUSIONS: These results provide direct evidence for the loss of caffeine tolerance in the human brain subsequent to caffeine discontinuation and suggest mechanisms for the phenomenon of caffeine intolerance other than its metabolic effects on elevating brain lactate.     

Upper tibial hyperextension fractures in infants: another occult toddler''s fracture

Our study describes a newly designed stapedotomy prosthesis which consists of two components: (1) a platinum ribbon, and (2) a Teflon shaft. The first innovation is a flattened 'tab' on the posterior aspect of the platinum ribbon. The second innovation concerns the dual diameter cylinder-like shaft. Our prosthesis was implanted into 25 individuals, who underwent stapedotomy for stapes fixation, and the results are shown and discussed. Our innovations offer a proper and safe insertion of the prosthesis into the oval window associated with excellent manipulation and handling. At the same time, maximum visualization of the surgical field is achieved, while the stepped-down design of the shaft prevents the prosthesis protruding into the vestibule.     

Combination antiretroviral therapy and recent declines in AIDS incidence and mortality

The reasons for recent declines in AIDS incidence and mortality may include advances in treatment, but these may be confounded by earlier declines in the incidence of human immunodeficiency virus (HIV) infection. To determine whether the declines in AIDS and mortality may, in part, stem from wider use of combination antiretroviral therapy, 622 HIV-positive men with well-characterized dates of seroconversion were followed. In this group, combination therapy came into widespread use in only 1996. In a Cox proportional hazards model, the 1996 calendar period was significantly associated with slower progression to AIDS (relative hazard [RH]=0. 19, 95% confidence interval [CI], 0.05-0.69, P=.01) and death (RH=0. 45, 95% CI, 0.21-0.95, P=.04). Declines in incidence of HIV infection, changes in HIV virulence, and end-point underreporting cannot fully explain the decline in AIDS and death in 1996. The introduction of combination antiretroviral therapy as the standard of care may already have had measurable effects.     

The use of ceramic onlays for restoring the occlusal surface of the teeth

Computer-aided milling of ceramic insertions helped more effectively repair the masticatory surface of teeth, minimize the incidence of errors, rule out the laboratory stage of making the insertions and the technological errors made at this stage, retain physical and mechanical characteristics of ceramics, optimize marginal adherence of the insertion to the tooth, retain the height of the lower part of the face, and thus prevent the maxillodental dysfunction.     

The yeast mic2 mutant is defective in the formation of mannosyl-diinositolphosphorylceramide

Three transmembrane glutamic acid residues play essential roles in the metal-tetracycline/H+ antiporter Tet(K) of Staphylococcus aureus [Fujihira et al., FEBS Lett. 391 (1996) 243-246]. In the putative hydrophilic loop region of the Tet(K) and Tet(L) proteins, six acidic residues are conserved. Asp74, Asp200, Asp318 and Glu381 are located on the putative cytoplasmic side, and Asp39 and Glu345 on the putative periplasmic side. These residues were replaced by a neutral amino acid residue or a charge-conserved one. In contrast to the transmembrane glutamic acid residues, the replacement of the two glutamic acid residues (Glu345 and Glu381) did not affect the tetracycline resistance level. Out of the other four aspartic acid residues, the only essential residue is Asp318, any replacement of which resulted in complete loss of the tetracycline resistance and transport activity. Asp318 is located in cytoplasmic loop 10-11 in the putative 14-transmembrane-segment topology of Tet(K). In the case of the tetracycline exporters of Gram-negative bacteria, the only essential acidic residue in the cytoplasmic loop region is located in loop 2-3 [Yamaguchi et al., Biochemistry 31 (1992) 8344-8348]. It may be a general role for tetracycline efflux proteins that three transmembrane and one cytoplasmic acidic residues are mandatory for the tetracycline transport function.     

Hemifield-specific visual recognition memory impairments in patients with unilateral temporal lobe removals

Recent evidence on visual neglect suggests that each hemisphere maintains a retinotopically organized representation of the visual world contralateral to the current fixation point and that this representation is based not only on analysis of the current retinal input but, equally importantly, on information retrieved from memory. This idea predicts that unilateral damage to memory systems should produce a lateralized impairment of memory for the retinotopically contralateral visual world. To test this prediction we examined visual recognition memory performance in the left and right visual hemifields of patients who had undergone partial unilateral temporal lobe removals for the relief of epilepsy, either in the left hemisphere (n = 5) or the right (n = 5). The patients were given complex artificial scenes to remember, constructed of independent left and right halves, and were then tested for recognition of the left and the right halves separately. Stimuli were exposed tachistoscopically throughout and fixation was maintained on a central position. Patients made significantly more errors with half-scenes in the hemifield contralateral to their removal than in the ipsilateral hemifield, an increase of 50% in the error rate on average. The effect was seen equally in patients with left and right removals. This finding supports the idea that visual memory retrieval is retinotopically organized.     

Long-term outcome in acute myocardial infarction patients admitted to hospitals with and without on-site cardiac catheterization facilities. MITI Investigators. Myocardial Infarction Triage and Intervention

BACKGROUND: Previous studies have documented the strong association between availability of on-site cardiac catheterization facilities and increased use of coronary angiography in patients with acute myocardial infarction (AMI). Although these studies have shown little influence of the availability of catheterization labs on hospital mortality, no long-term follow-up has been reported. METHODS AND RESULTS: From a cohort of 12,331 AMI patients admitted to 19 Seattle area hospitals, we compared long-term outcome in 7985 patients admitted to hospitals with and 4346 patients admitted to hospitals without on-site catheterization labs. During the index hospitalization, patients admitted to hospitals with on-site catheterization were more likely to undergo coronary angiography (67.1% versus 39.3%, P<.0001), coronary angioplasty (32.5% versus 13.2%, P<.0001), or coronary bypass surgery (12.5% versus 9.5%, P<.0001). At 3-year follow-up, patients admitted to hospitals with on-site catheterization labs were more likely to undergo postdischarge angiography (19.2% versus 15.2%, P=.0001) and coronary angioplasty (11.6% versus 8.2%, P<.0001). This was associated with approximately $2500.00 per patient in higher cumulative costs. Despite this higher rate of procedure use, there was no association between admission to a hospital with on-site catheterization facilities and lower long-term mortality (multivariate hazard ratio, 1.0; 95% CI, 0.93 to 1.1., the hazard being associated with admission to hospitals with on-site catheterization facilities). CONCLUSIONS: In an urban area with unconstrained patient transfer mechanisms and high overall cardiac procedure use rates, AMI patients admitted to hospitals without on-site catheterization facilities were managed with fewer procedures during hospitalization and follow-up. This more conservative treatment approach was not associated with any observed increase in long-term mortality.     

Reproducibility of in vivo carotid intima-media thickness measurements: a review

The gyrA gene of Campylobacter fetus subsp. fetus, which encodes the A subunit of DNA gyrase, was cloned, and its nucleotide sequence was determined. An open reading frame of 2,586 nucleotides which encodes a polypeptide of 862 amino acids with an Mr of 96,782 was identified. C. fetus subsp. fetus GyrA is most closely related to Campylobacter jejuni GyrA, with 73% homology at the nucleotide level and 78% identity between polypeptides. The next most closely related GyrA was that from Helicobacter pylori, with both DNA homology and amino acid identity of 63%. The gyrA and gyrB (DNA gyrase B subunit) genes were located on the genomic map of C. fetus subsp. fetus ATCC 27374 and shown to be separate. A clinical isolate of C. fetus subsp. fetus and a laboratory-derived mutant of ATCC 27374, both resistant to ciprofloxacin, had identical mutations within the quinolone resistance determining region. In both mutants a G-->T transversion, corresponding to a substitution of Asp-91 to Tyr in GyrA, was linked to ciprofloxacin resistance, giving MICs of 8 to 16 micrograms/ml.