A new transthyretin variant (Glu61Gly) associated with cardiomyopathy.

We report the identification of a new transthyretin (TTR) gene mutation and variant protein, Glu61Gly, in a 55-year-old man with progressive cardiomyopathy, mild peripheral neuropathy and bilateral carpal tunnel syndrome. A diagnosis of TTR-associated familial amyloidosis (ATTR) was considered after an endomyocardial biopsy revealed amyloid deposits in the heart of a patient who had no family history of amyloidosis and no evidence of a plasma cell dyscrasia. Serum screening for a TTR variant by isoelectric focusing (IEF) was positive and prompted further studies to identify the genetic abnormality and to characterize the amyloidogenic protein. Direct DNA sequence analysis of all four coding regions in the TTR gene demonstrated heterozygosity in exon 3. Near equal amounts of guanine (G) and adenine (A) were observed at the second base position of codon 61. The wild-type (GAG) and mutated (GGG) sequences found in codon 61 correspond to glutamic acid (Glu) and glycine (Gly) residues, amino acids which differ in mass by -72 Da. Mass spectrometric analyses of TTR immunoprecipitated from serum showed the presence of both wild-type and variant proteins. The observed mass results for the wild-type and variant proteins were consistent with the predicted values calculated from the genetic analysis data.     

Decreased pain with lower flexural rigidity of uncemented femoral prostheses

One hundred one consecutive uncemented hip arthroplasties (87 patients) were analyzed radiographically at 1-year follow up to relate mechanical factors to hip pain as determined by clinical pain scores. The average area moment of inertia and flexural rigidity were greater for the bone than the metal prosthesis for each type of prosthesis (AML, HG, PCA). Normalization of the flexural rigidity ratio (bone to prosthesis) for patient weight yielded a Spearman correlation coefficient of 0.232, significant at P = .02, suggesting that both applied stress and bending stiffness have an effect on pain. No relationship was seen between pain and AP, or average gap between prostheses and bone.     

A juvenile animal model to study the growth potential of bowel segments in the urinary tract

A juvenile animal model has been developed to study the growth potential of ileum in the urinary tract. Patch ileocystoplasties of known surface area were constructed in dogs of Group 1. Nonrefluxing ileal nipple valves of known length were created to replace one ureter in dogs of Group 2. After the juvenile animals grew and at minimum doubled their weight, they were reoperated and augmentation surface areas were remeasured at various physiologic intravesical pressures. Nipple valve lengths were remeasured after cystograms ruled out reflux. Results show that the bowel augmentation and an identical control segment increased in surface area proportionate to animal growth and that hydrostatic dilation caused further surface area increase. Nipple valves did not grow and in fact shortened, but remained nonrefluxing. The conclusion is that in the pediatric population, consideration should be given to downscaling the size of bladder augmentations or diversions in anticipation of future bowel growth, but that one should not shorten the ileal nipple valves.     

Rat model of distraction osteogenesis

Prior studies of distraction osteogenesis in dog and rabbit models have shown predominantly intramembranous bone formation. Other models of fracture healing normally display mixtures of both endochondral and intramembranous bone formation. We have established a rat model of tibial lengthening that reliably reproduces the pattern of zonal osteogenesis previously observed in dog and rabbit models. A distraction rate of 0.25 mm twice a day with a 0-day latency period produced intramembranous bone with zones of progressive mineralization from collagen. With this protocol, rats bridged the distraction gap with a 25% increase in the tibial bone length. After 20 days of distraction and 50 days of consolidation, the three-point bending stiffness, as a percentage of the contralateral control, reached a level equivalent to that measured in the canine model for a 15% lengthening (28-day distraction and 84-day consolidation). Radiodensitometric analysis of the regenerate bones measured 97% of the unaffected contralateral tibial densities, and mineral analyses demonstrated that calcium and phosphorus levels in the regenerate bone reached 78% of contralateral tibial levels by day 70. We concluded that a rat model of distraction ostegenesis will be useful for a wide range of studies involving rapid intramembranous bone formation.     

Resuscitation training for cardiac patients and their relatives--its effect on anxiety.

It is feared by many doctors that teaching basic life support (BLS) to high risk cardiac patients or a member of the family increases their anxiety. We trained a group of patients with recurrent ventricular tachycardia in BLS together with a friend or family member. Measurement of anxiety before and three months after training demonstrated a reduction in anxiety in both groups. This suggests that basic life support training can be targeted to high risk groups without fear of increasing anxiety.     

Stimulation-induced setting of postural muscle tone in the decerebrate rat

These studies demonstrate the presence of pontomedullary areas in the rat brainstem which, when stimulated electrically, serve to set postural muscle tone in the hindlimbs. Low amplitude stimulation of the dorsal tegmental field (DTF) was found to inhibit postural muscle tone and, in some rats, was found to decrease mean arterial pressure. Low amplitude stimulation of the ventral tegmental field (VTF) was found to increase postural muscle tone and, in all cases tested, was found to increase mean arterial pressure.     

Treatment of experimental osteomyelitis by surgical debridement and the implantation of bioerodable,polyanhydride-gentamicin beads

Osteomyelitis was induced in the radius in 77 rabbits and confirmed by histological examination and culture. At 4 weeks, the wounds were debrided and the animals were treated with (a) fatty acid dimersebacic acid beads (a bioerodable composite) impregnated with 20% or (b) 10% gentamicin sulfate, (c) placebo beads and intramuscular gentamicin sulfate. (d) placebo beads alone, or (e) debridement only. After 4 weeks, eradication of infection was determined by histological examination and culture. Osteomyelitis was eradicated in 93% of the animals treated with the beads and 20% gentamicin, in 67% of those treated with the beads arid 10% gentamicin, in 25% of those treated with placebo beads and intramuscular gentamicin, in 7% of those treated with placebo beads alone, and in 12.5% of those treated with debridement only (p values from <0.001 to 0.02). Fatty acid dimer-sehacie acid beads with gentamicin were then implanted in noninfected rabbits, and gentamicin sulfate concentrations in bone, serum, urine, and wound exudate were measured. Gentamicin sulfate was detectable in bone for as long as 8 weeks after implantation. Levels as high as 4,746 g/ml were present in the wound exudate for the first 7 days. Levels in the serum peaked at 1.03 μg/ml. Urine levels peaked at 135 μg/ml.     

Complications of the Kock pouch

Over the past 41/2 years, 395 consecutive Kock pouch procedures have been performed by the urology faculty at the University of Southern California School of Medicine as an alternative to conventional cutaneous urinary diversion. This article reviews the early and late complications experienced in the 386 patients surviving the operation and describes in detail modifications in surgical technique designed to reduce the complication rate and the subsequent need for re-operation. We remain convinced that construction from ileum of a low-pressure, high-capacity internal reservoir with continent and nonrefluxing valves as originally described by Kock remains the ultimate technique for patients requiring permanent urinary diversion or for those requiring conversion from a pre-existing form of diversion.