Historical documentation of lead toxicity prior to the 20th century in English literature.

Lead is a heavy metal that remains a persistent environmental toxin. Although there have been a substantial number of reviews published on the health effects of lead, these reviews have predominantly focused on recent publications and rarely look at older, more historical articles. Old documents on lead can provide useful insight in establishing the historical context of lead usage and its modes of toxicity. The objective of this review is to explore historical understandings and uses of lead prior to the 20th century. One hundred eighty-eight English language articles that were published before the year 1900 were included in this review. Major themes in historical documentation of lead toxicology include lead's use in medical treatments, symptoms of lead poisoning, treatments for lead poisoning, occupational lead poisonings, and lead contamination in food and drinking water. The results of this review indicate that lead's usage was widespread throughout the 19th century, and its toxic properties were well-known. Common symptoms of lead poisoning and suggested treatments were identified during this time period. This review provides important insight into the knowledge and uses of lead before the 20th century and can serve as a resource for researchers looking at the history of lead.

Longitudinal changes of tau PET imaging in relation to hypometabolism in prodromal and Alzheimer's disease dementia.

The development of tau-specific positron emission tomography (PET) tracers allows imaging in vivo the regional load of tau pathology in Alzheimer's disease (AD) and other tauopathies. Eighteen patients with baseline investigations enroled in a 17-month follow-up study, including 16 with AD (10 had mild cognitive impairment and a positive amyloid PET scan, that is, prodromal AD, and six had AD dementia) and two with corticobasal syndrome. All patients underwent PET scans with [18F]THK5317 (tau deposition) and [18F]FDG (glucose metabolism) at baseline and follow-up, neuropsychological assessment at baseline and follow-up and a scan with [11C]PIB (amyloid-ß deposition) at baseline only. At a group level, patients with AD (prodromal or dementia) showed unchanged [18F]THK5317 retention over time, in contrast to significant decreases in [18F]FDG uptake in temporoparietal areas. The pattern of changes in [18F]THK5317 retention was heterogeneous across all patients, with qualitative differences both between the two AD groups (prodromal and dementia) and among individual patients. High [18F]THK5317 retention was significantly associated over time with low episodic memory encoding scores, while low [18F]FDG uptake was significantly associated over time with both low global cognition and episodic memory encoding scores. Both patients with corticobasal syndrome had a negative [11C]PIB scan, high [18F]THK5317 retention with a different regional distribution from that in AD, and a homogeneous pattern of increased [18F]THK5317 retention in the basal ganglia over time. These findings highlight the heterogeneous propagation of tau pathology among patients with symptomatic AD, in contrast to the homogeneous changes seen in glucose metabolism, which better tracked clinical progression.

Overlapping expression of serotonin transporters and neurokinin-1 receptors in posttraumatic stress disorder: a multi-tracer PET study.

The brain serotonergic system is colocalized and interacts with the neuropeptidergic substance P/neurokinin-1 (SP/NK1) system. Both these neurochemical systems have independently been implicated in stress and anxiety, but interactions between them might be crucial for human anxiety conditions. Here, we examined the serotonin and substance P/neurokinin-1 (SP/NK1) systems individually as well as their overlapping expression in 16 patients with posttraumatic stress disorder (PTSD) and 16 healthy controls. Participants were imaged with the highly selective radiotracers [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (DASB) and [(11)C]GR205171 assessing serotonin transporter (SERT) and NK1 receptor availability, respectively. Voxel-wise analyses in the amygdala, our a priori-defined region of interest, revealed increased number of NK1 receptors, but not SERT in the PTSD group. Symptom severity, as indexed by the Clinician-administered PTSD Scale, was negatively related to SERT availability in the amygdala, and NK1 receptor levels moderated this relationship. Exploratory, voxel-wise whole-brain analyses revealed increased SERT availability in the precentral gyrus and posterior cingulate cortex of PTSD patients. Patients, relative to controls, displayed lower degree of overlapping expression between SERT and NK1 receptors in the putamen, thalamus, insula and lateral orbitofrontal gyrus, lower overlap being associated with higher PTSD symptom severity. Expression overlap also explained more of the symptomatology than did either system individually, underscoring the importance of taking interactions between the neurochemical systems into account. Thus, our results suggest that aberrant serotonergic-SP/NK1 couplings contribute to the pathophysiology of PTSD and, consequently, that normalization of these couplings may be therapeutically important.

Increased neurokinin-1 receptor availability in the amygdala in social anxiety disorder: a positron emission tomography study with [11C]GR205171.

The neurokinin-1 (NK1) receptor is abundantly expressed in the fear circuitry of the brain, including the amygdala, where it modulates stress and anxiety. Despite its proposed involvement in psychopathology, only a few studies of NK1 receptor availability in human subjects with anxiety disorders exist. Here, we compared NK1 receptor availability in patients with social anxiety disorder (SAD; n = 17) and healthy controls (n = 17) using positron emission tomography and the radiotracer [11C]GR205171. The Patlak Graphical plot using a cerebellar reference region was used to model the influx parameter, Ki measuring NK1 receptor availability. Voxel-wise statistical parametric mapping analyses revealed increased NK1 receptor availability specifically in the right amygdala in SAD patients relative to controls. Thus, we demonstrate that exaggerated social anxiety is related to enhanced NK1 receptor availability in the amygdala. This finding supports the contribution of NK1 receptors not only in animal models of stress and anxiety but also in humans with anxiety disorders.

Chest pain in family practice. Diagnosis and long-term outcome in a community setting.

OBJECTIVE: To describe diagnostic distribution and outcome of chest pain among patients attending an urban family practice. DESIGN: Retrospective, descriptive chart review. SETTING: Primary care practice. PARTICIPANTS: All patients contacts for chest pain at Fossvogur Health Centre in the years 1989 and 1990 (193 contacts with 189 patients) were examined. One patient died before follow up and two could not be reached for follow up; they were excluded from the study. Of the 190 contacts and 186 patients studied, one patient who had two contacts with the clinic died during the study. MAIN OUTCOME MEASURES: Age and sex distribution, physical examination, investigations, diagnosis, and treatment; well-being of every patient was checked 3 to 4 years after initial contact. We asked about evolution of symptoms and looked for possible misdiagnosis. RESULTS: Musculoskeletal pain was diagnosed in 48.9% of contacts, heart diseases in 17.9% and 9.5% had undiagnosed chest pain. The history was the main diagnostic tool for patients with musculoskeletal diseases, while patients with heart diseases were examined more carefully and underwent more diagnostic procedures. Follow up showed that no serious disease had been missed in spite of restrictive use of laboratory investigations. CONCLUSIONS: The working methods of family doctors who examined patients with chest pain in this health centre can differentiate between patients with serious diseases and those with benign conditions.

Evidence for a food additive as a cause of ketosis-prone diabetes.

A comprehensive survey of ketosis-prone diabetes showed a 29% preponderance of males and a trend for the time of diagnosis to coincide with epidemics of viral diseases. There was a significantly increased incidence between July and January in the age group diagnosed at 0-14 years but this seasonal trend was not shown in a group of boys diagnosed at this age who were all born in the month of October. The incidence of diabetes in this group of boys was very much higher than would be expected (p less than 0.00001). HLA histocompatibility types and virus infections were considered as possible causes of this striking finding but there seemed to be at least one additional seasonal factor acting prenatally. Circumstantial evidence suggested that this additional factor is the N-nitroso-compound content of processed mutton traditionally consumed in Iceland in the two weeks from December 23. Recently produced Icelandic smoked/cured mutton contains considerable concentrations of N-nitroso-compounds. This work implies that a common food additive contributes to the production of ketosis-prone diabetes, not in the consumer but in the progeny.