Lifestyle determinants and mortality in German vegetarians and health-conscious persons: results of a 21-year follow-up.

BACKGROUND: The long-term observation of vegetarians in affluent countries can provide insight into the relative effects of a vegetarian diet and lifestyle factors on mortality. METHODS: A cohort study of vegetarians and health-conscious persons in Germany was followed-up prospectively for 21 years, including 1,225 vegetarians and 679 health-conscious nonvegetarians. Standardized mortality ratios compared with the German general population were calculated for all causes and specific causes. Within the cohort, Poisson regression modeling was used to investigate the joint effects of several risk factors on overall and cause-specific mortality. RESULTS: Standardized mortality ratios for all-cause mortality was significantly below 100: 59 [95% confidence interval (95% CI), 54-64], predominantly due to a deficit of deaths from circulatory diseases. Within the cohort, vegetarian compared with nonvegetarian diet had no effect on overall mortality [rate ratio (RR), 1.10; 95% CI, 0.89-1.36], whereas moderate and high physical activity significantly reduced risk of death (RR, 0.62, 0.64), adjusted for age, sex, smoking, alcohol intake, body mass index, and educational level. Vegetarian diet was however associated with a reduced RR of 0.70 (95% CI, 0.41-1.18) for ischemic heart disease, which could partly be related to avoidance of meat. CONCLUSIONS: Both vegetarians and nonvegetarian health-conscious persons in this study have reduced mortality compared with the general population. Within the study, low prevalence of smoking and moderate or high level of physical activity but not strictly vegetarian diet was associated with reduced overall mortality. The nonsignificant reduction in mortality from ischemic heart diseases in vegetarians compared with health-conscious persons could be explained in part by avoidance of meat intake.     

Two-tiered DNA-based diagnosis of transthyretin amyloidosis reveals two novel point mutations

We analyzed 11 consecutive unrelated cases of polyneuropathy due to transthyretin amyloidosis. Direct sequencing of the promoter region, exons, and splice junctions revealed that each patient was heterozygous for a mutation: six patients had valine 30 substituted by methionine (V30----M; Portuguese-Japanese type), one had threonine 60 substituted by alanine (T60----A; Appalachian type), and two had serine 77 substituted by tyrosine (S77----Y; Illinois type). In addition, two patients had previously undescribed mutation: phenylalanine 33 substituted by leucine (F33----L) and phenylalanine 64 substituted by leucine (F64----L). From present information, the probands of these novel mutations do not exhibit any pathology that clearly distinguishes them from individuals with the other mutations. The mutations extend the range of mutations associated with amyloidotic polyneuropathy. In our 11 patients, the different mutations did not seem to correlate with distinct clinical phenotypes. We developed PASA assays (PCR amplification of specific alleles) for each of the five mutations. PASA can be used by any diagnostic laboratory that can perform PCR to rapidly detect any of the known mutations. The minority of samples with an undescribed mutation can be sent to a specialty laboratory for delineation of the mutation by direct genomic sequencing. The presently described combination of methods may have widespread utility in the diagnosis of genetic disease.     

MORPHOMETRY AND PATHOLOGY OF THE PARASPINOUS MUSCLES IN IDIOPATHIC SCOLIOSIS

Muscle biopsies from the apex of both sides of the curve of 31 patients with idiopathic scoliosis showed abnormalities in fiber-type distribution in 68 per cent and in fiber size in 55 per cent. There was no preference for either side. Type 1 fiber predominance was as common as type 1 fiber deficiency. Atrophy occurred in 33 per cent and affected mainly type 1 fibers: atrophy of type 2 fibers was rare. Hypertrophy was limited to type 2 fibers, and occurred in 26 per cent. The strength factor for type 1 fibers exceeded that for type 2. Type 2A fibers were no larger than 2B fibers: there was a large type 2A predominance, more so on the convex side. Most of the muscle changes appear to be secondary and compensatory: none suggests a pathogenesis for the curve.     

Rare diseases mimicking acute vertebrobasilar artery thrombosis

Acute ischaemia of the vertebrobasilar circulation leads to a variety of clinical manifestation and is mostly due to cardiogenic or artery-to-artery embolism. We describe four neurological emergency situations involving vertebrobasilar artery aclusion of other origins: basilar migraine, extrinsic compression by rheumatoid inflammatory tissue, generalized vasculitis in subacute rheumatic fever and basilar artery dissection. The differential diagnosis of acute vertebrobasilar artery occlusion may have an important impact on patient management.     

Normal intracortical excitability in developmental stuttering.

Persistent developmental stuttering (PDS) shares clinical features with task-specific dystonias. In these dystonias, intracortical inhibition is abnormally weak. We therefore sought to determine intracortical inhibition and intracortical facilitation in PDS. In 18 subjects with PDS since childhood (mean age, 39.4 [SD 13.0] years) and 18 speech-fluent controls (43.6 [14.3] years), we investigated resting and active motor thresholds as well as intracortical inhibition and facilitation of the optimal representation of the abductor digiti minimi of the dominant hand using transcranial magnetic stimulation. In PDS, the resting and active motor thresholds were increased, whereas intracortical inhibition and facilitation were normal. Normal intracortical excitability makes a pathophysiological analogy between focal dystonia and PDS less likely. The enhanced motor threshold suggests reduced motor cortical neuronal membrane excitability in PDS.     

Screening for glaucomatous visual field loss. The effect of patient reliability

Eighty-eight glaucoma patients and 252 normal subjects underwent C-30-2 testing on the Humphrey Field Analyzer. The effect of fixation losses, high false-positive and false-negative response rates on visual field test results was assessed using the mirror image method of detecting asymmetry across the horizontal meridian, and the Humphrey STATPAC pattern standard deviation (PSD) and mean deviation (MD). Glaucoma patients with poor fixation (greater than or equal to 20%) had less depressed fields and fewer localized defects than those with good fixation. Fixation loss did not affect measures of localized defects or generalized depression among normal subjects. High false-positive rates (greater than or equal to 10%) were associated with less-depressed visual fields among glaucoma patients and normal subjects. Visual fields were depressed by an average of 9 dB for glaucoma patients and 7 dB for normal subjects with high false-negative rates (greater than or equal to 33%), when compared with those with low false-negative rates. Apparent localized defects were observed among normal subjects with high false-negative rates. Most of these defects were located in the superior nasal and adjacent arcuate area.     

Phage-displayed recombinant single-chain antibody fragments with high affinity for cholesteryl ester transfer protein (CETP): cDNA cloning, characterization and CETP quantification.

Cholesteryl ester transfer protein (CETP) greatly affects the metabolism of all lipoprotein classes including low-density lipoprotein (LDL) and high-density lipoprotein (HDL), both known to constitute powerful risk factors for coronary artery disease (CAD). We now report the successful first cloning and characterization of single-chain antibody fragments specific for CETP. A recombinant phage display library was generated using spleen mRNA isolated from BALB/c mice that had been immunized with highly purified CETP. Screening of the library yielded two single-chain antibody fragments with high affinity for CETP, termed 1CL8 and 1CL10, displaying respective KD values of 4.36 x 10(-9) M and 4.64 x 10(-9) M as determined by affinity sensor technology. Amino acid sequence comparison indicated the complementarity-determining regions of the respective heavy chains to be responsible for CETP high affinity binding. Fragment 1CL8 was successfully employed in clinical chemical quantification systems that uncovered an association in humans between plasma CETP concentration and total body fat mass (r=0.50, p<0.002). Because of the demonstrated superb CETP capturing capacity, combined with high binding affinity to CETP, ready access and unlimited supply, 1CL8 and 1CL10 are expected to prove powerful tools for studies on the role of CETP in atherogenesis.     

Congenital defects of lower limbs and associated malformations: A population based study

As part of a detailed study of limb defects and associated patterns of congenital malformations, cases with lower limb deficiencies were analysed separately. We identified a total of 130 cases with deficiencies of the lower limbs without defects of the upper limbs. This gives an incidence of 1.07/10,000 livebirths, or 1/9,337 for this group of limb defects. Most common were femur deficiencies and deficiencies of the foot. A preponderance of males was found in the group of transverse defects of the leg (fibula/tibia deficiencies) and central axis deficiencies, while females had significantly more often longitudinal tibia defects and preaxial ray defects. © 1993 Wiley-Liss, Inc.