Striatal uptake of a novel PET ligand, [18F]beta-CFT, is reduced in early Parkinson's disease

[18F] beta-CFT is a novel PET ligand for dopamine reuptake sites. In this study, [18F]beta-CFT uptake was studied in nine patients with early Parkinson's disease (PD) without antiparkinsonian medication and in six age-matched controls. The uptake of [18F]beta-CFT was calculated as a (region-cerebellum)/cerebellum ratio at 150-210 min after injection. The mean uptake in the putamen contralateral to the predominant symptoms (1.04+/-0.40, mean +/- SD; P<0.001) was reduced to 31% of the mean control value. In the "ipsilateral" putamen, the ratio in PD patients (1.50+/-0.50, P<0.001) was reduced to 45% of the control mean (3.33+/-0.61). Individually, all PD patients had [18F]beta-CFT uptake values below 2 SD from the control mean in the contralateral putamen. The decline in [18F]beta-CFT uptake in the caudate nucleus was milder than that seen in the putamen. The uptake was reduced contralaterally (2.19+/-0.47, P<0.01) to 67% and ipsilaterally (2.49+/-0.54, P<0.05) to 77% of the control mean (3.17+/-0.61). In the medial frontal cortex or dorsolateral prefrontal cortex, no significant difference in [18F]beta-CFT uptake between patients and controls was seen. In conclusion, [18F]beta-CFT is a powerful ligand to demonstrate presynaptic dopaminergic defect in PD and shows a clear separation of patient and control values.     

Effects of terbutaline on the pressure volume relationship in fetal rabbit lung.

The pressure-volume relationship in preterm rabbit lung was studied at 28 days of gestation. Injection of 0.1 mg terbutaline, a selective beta2-receptor stimulating drug, significantly increased the volume of air at equivalent low transpulmonary pressures, compared to a saline treated group and an untreated group. These findings indicate an increased pulmonary distensibility of the fetal rabbit lung after terbutaline administration. The mechanism of action is discussed and surfactant mediated effects are suggested to be the probable explanation.     

Conduiturinary diversion and urinary-tract infection. I. Serum antibody titers against Escherichia coli and Proteus mirabilis in relation to urographic findings.

The serum antibody titers against Escherichia coli and/or Proteus mirabilis were elevated in 26 of 80 patients (33%) with a conduit urinary diversion. Urographic findings were abnormal in 44 of these 80 patients (55%). Urography was normal in 59% of the patients with normal antibody titers, but in only 15% of those with elevated titers. Raised antibody levels against E. coli O antigen (greater than 256 before and/or greater than 32 after mercaptoethanol treatment of serum) were associated with wide upper urinary tract or calculi more often than were normal E. coli antibody titers. Raised titers against P. mirabilis (greater than 256 before and/or greater than 32 after mercaptoethanol treatment of serum) were associated with scarring of the renal parenchyma more frequently than were normal titers. A statistically significant association was found between "small" kidney area and raised serum antibody titers against E. coli or P. mirabilis. The frequency of "small" kidney increased with the time lapse after urinary diversion. At 3 to 11 months postoperatively it was 29%, but among the patients with urinary diversion for more than five years the corresponding frequency was 82%. When at least one kidney was "small", the serum creatinine was higher than when both kidneys were of normal size. Patients with raised antibody titers tended also to have high serum creatinine (greater than or equal to 124 mumol/l) more often than those with normal titers (23 vs. 10%). These observations imply a connection between elevation of the antibody titers and destruction of the renal parenchyma in patients with conduit urinary diversion. They illustrate the value of antibody titration in the follow-up of patients with urinary diversion.     

Appendicitis associated with recent barium study.

There have been several reports of "barium-induced" appendicitis in the literature. When confronted with a possible case of this phenomenon, a review of the literature on the subject was carried out. The suggestion is made that there is no evidence to support a cause-effect relationship between barium retained in the appendix and appendicitis. Diseased appendices can be marked by retained barium and a higher likelihood may then exist for the subsequent development of appendicitis. Following the finding of prolonged retention of barium after contrast study, it is recommended that the patient be instructed as to the possibility of developing symptoms of acute appendicitis. Patients who present with symptoms of appendicitis should be questioned as to history of recent barium study, and x-rays should be reviewed with the possibility of finding appendoliths.     

Striatal dopamine transporter binding in neuroleptic-naive patients with schizophrenia studied with positron emission tomography

OBJECTIVE: Recent in vivo imaging studies indicate a dysregulated presynaptic function of the striatal dopaminergic system in patients with schizophrenia. To further explore the basis of this phenomenon, the authors studied brain dopamine transporter binding in vivo in patients with first-episode, never-medicated schizophrenia. METHOD: Nine patients with schizophrenia and nine healthy matched comparison subjects were recruited. Striatal dopamine transporter binding was measured with positron emission tomography and a specific dopamine transporter ligand, [(18)F]CFT, a radiolabeled form of 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane. RESULTS: Average caudate and putamen dopamine transporter binding potentials were almost identical in the patients and comparison subjects, but the patients lacked the right-left asymmetry of the caudate dopamine transporter binding seen in the comparison group. CONCLUSIONS: Average striatal dopamine transporter density is unaltered in neuroleptic-naive patients with schizophrenia. However, patients lack asymmetry in caudate dopamine transporter binding, which conforms with disrupted brain lateralization in this disorder.     

Evaluation of heme oxygenase-1 as a systemic biological marker of sporadic AD

BACKGROUND: Heme oxygenase-1 (HO-1) is a 32-kDa stress protein that catalyzes the degradation of heme to biliverdin. HO-1 immunoreactivity is greatly increased in neurons and astrocytes of the hippocampus and cerebral cortex of individuals with AD and colocalizes to senile plaques and neurofibrillary tangles. METHODS: We investigated whether systemic HO-1 regulation is also deranged in AD patients and whether blood HO-1 measurements provide a peripheral biomarker of the disease. Plasma HO-1 protein levels were measured by competitive ELISA and lymphocyte HO-1 mRNA levels were determined by Northern analysis in patients with early probable sporadic AD, normal elderly controls (NEC), normal younger controls, individuals with age-associated cognitive decline (AACD) not meeting AD criteria, and patients with non-Alzheimer dementia, nondementing neurologic illness, and chronic medical disorders. CSF HO-1 protein concentrations were also determined by ELISA in pathologically confirmed AD and control cases. RESULTS: Mean plasma HO-1 protein concentrations were significantly lower in AD patients (0.85 +/- 0.14 microg/mL) compared with NEC (1.77 +/- 0.34 microg/mL; p < 0.05) and control patients. The AACD group exhibited plasma HO-1 concentrations (1.06 +/- 0.33 microg/mL) intermediate between, but not different from, those of the AD patients and NEC. Lymphocyte HO-1 mRNA levels were lower in the AD cohort relative to NEC (p < 0.001) and individuals with AACD, non-Alzheimer dementia, nondementing neurologic illness, and chronic medical conditions. Lymphocyte HO-1 mRNA levels were also lower in the AACD group relative to NEC (p < 0.05). In comparison with all groups excluding AACD, the sensitivity and specificity of lymphocyte HO-1 mRNA measurement for diagnosis of early sporadic AD are 88% and 75%. Mean CSF HO-1 protein concentrations were lower (p < 0.01) in AD cases (19.07 ng/mL) relative to control values (32.48 ng/mL). CONCLUSIONS: Plasma and CSF HO-1 protein and lymphocyte HO-1 mRNA levels are decreased in subjects with sporadic AD. Quantitative assay for lymphocyte HO-1 mRNA expression may serve as a useful biologic marker in early sporadic AD.     

Otoacoustic emissions as a screening test for hearing impairment in children recovering from acute bacterial meningitis

OBJECTIVES: To study the efficacy of otoacoustic emissions (OAEs) as a screening test for hearing impairment in children with acute bacterial meningitis. Hearing tests were performed before discharge from the hospital in an attempt to improve coverage and avoid delays in the diagnosis of postmeningitic hearing loss. METHODS: Children with bacterial meningitis were recruited from 21 centers. In the 48 hours before discharge from the hospital, all patients underwent a thorough audiologic assessment consisting of transient evoked OAEs, auditory brainstem responses (ABRs), otoscopy, and tympanometry. Hearing loss was defined as ABR threshold >/=30 dB. The results of OAE screening were compared with the gold standard of ABR threshold. RESULTS: Of 124 children recruited, we were able to perform both OAEs and ABRs on 110 children. Seven (6.3%) of the 110 children had ABR threshold >/=30 dB; 2 had sensorineural hearing loss and 5 had conductive hearing loss. At follow-up, hearing loss persisted in both cases of sensorineural hearing loss and no new cases were identified. All 7 children with hearing loss failed the OAE screening test. Ninety-four children with normal hearing thresholds passed the test, and 9 failed. Thus, the screening test had a sensitivity of 1.00 (95% confidence interval, 0.59 to 1.00), a specificity of 0.91 (0.85 to 0.97), a positive predictive value of 0. 44 (0.20 to 0.70), and a negative predictive value of 1.00 (0.96 to 1.00). CONCLUSIONS: OAE screening in children recovering from meningitis was found to be feasible and effective. The test was highly sensitive and reasonably specific. Inpatient OAE screening should allow early diagnosis of postmeningitic hearing loss and prompt auditory rehabilitation.