Mitochondrial function and mitochondrial DNA in a series of 64 patients suspected of having mitochondrial myopathy

Biochemical results concerning 64 patients suspected of mitochondrial myopathies are presented. Four clinical groups were studied including 21 encephalomyopathies, 42 ocular myopathies, 8 isolated myopathies and 3 cardiomyopathies. In 26 cases, the coexistence of a normal mitochondrial DNA and a mutated mitochondrial DNA (heteroplasmy) was found (19 simple deletions, 4 multiple deletions and 3 punctual mutations) and all cases presented with ocular disorders (excepted 2 cases with MERRF). Furthermore, 1 complex I deficiency (1 ocular myopathy), 1 complex IV deficiency (1 adult encephalomyopathy type Leigh), 3 complexes I + IV deficiencies (2 cases with a cardiomyopathy and 1 familial MELAS) and 2 pyruvate (1 adult from of Leigh's encephalomyopathy) dehydrogenase deficiencies (clinically and genetically different) did not show evidence of mitochondrial DNA mutation.     

Variability in hand surface representations in areas 3b and 1 in adult owl and squirrel monkeys

Detailed microelectrode maps of the hand representation were derived in cortical areas 3b and 1 from a series of normal adult owl and squirrel monkeys. While overlap relationships were maintained, and all maps were internally topographic, many map features varied significantly when examined in detail. Variable features of the hand representations among different monkeys included a) the overall shapes and sizes of hand surface representations; b) the actual and proportional areas of representations of different skin surfaces and the cortical magnifications of representations of specific skin surfaces, which commonly varied severalfold in area 3b and manyfold in area 1; c) the topographic relationships among skin surface representations, with skin surfaces that were represented adjacently in some monkeys represented in locations many hundreds of microns apart in others; d) the internal orderliness of representations; e) the completeness of representations of the dorsal hand surfaces; and f) the skin surfaces represented along the borders of the hand representation. Owl monkey maps were, in general, internally more strictly topographic than squirrel monkey maps. In both species, area 3b was more strictly topographic and less variable than was area 1. The degree of individual variability revealed in these experiments is difficult to reconcile with the hypothesis that details of cortical maps are ontogenetically specified during a period in early life. Instead, we propose that differences in the details of cortical map structure are the consequence of individual differences in lifelong use of the hands. This conclusion is consistent with earlier studies of the consequences of peripheral nerve transection and digital amputation, which revealed that cortical maps are dynamically maintained and are alterable as a function of use or nerve injury in these monkeys (Merzenich et al., '83a,b, '84a; Merzenich, '86; Jenkins et al., '84; Jenkins and Merzenich, '87).     

Distortion-product emissions and auditory sensitivity in human ears with normal hearing and cochlear hearing loss.

Distortion product emissions (DPEs) at 2f1-f2 frequencies were measured in 53 human ears; 21 of them exhibited cochlear hearing loss. DPEs were obtained as a function of stimulus level (DPE growth curves) at seven frequency regions between 707 Hz and 5656 Hz. Several distinctly different shapes or patterns of DPE growth curves were observed. These included single-segment monotonic growth curves with and without saturation at moderate and high stimulus levels, diphasic growth curves with nulls at moderate stimulus levels, and non-monotonic growth curves with negative slopes at high stimulus levels. Low-level, irregularly shaped segments were more frequent in normal-hearing ears, suggestive of normal low-level active nonlinearities from the outer-hair-cell subsystem. High-level, steeply sloped segments were frequent in hearing-impaired ears, suggestive of residual nonlinearities from a cochlear partition without functional outer hair cells. The stimulus level at which the DPE could just be distinguished from the noise floor, the DPE detection threshold, demonstrated moderate positive correlations (r's from 0.50 to 0.81) with auditory thresholds when all ears, both normal and impaired, were considered together. Those correlations were not strong enough to quantitatively predict auditory thresholds with any great accuracy. However, DPE thresholds were able to predict abnormal auditory sensitivity with some precision. DPE thresholds correctly predicted abnormal auditory sensitivity 79% of the time in the present study, and up to 96% of the time in previous studies. These results suggest that DPE thresholds may prove useful for hearing screening in cases where cooperation from the subject is limited or where corroboration of cochlear hearing loss is required. Different patterns of DPE growth curves suggest underlying micro-mechanical differences between ears, but the differential diagnostic value of those patterns remains to be determined.     

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.     

Antenatal Screening for HPA-la by Flow Cytometry

Summary: regnant women who attended antenatal clinics at King George V Hospital, the Birth Centre or were referred by obstetricians from February to July. 1996 were screened for the platelet antigen HPA-la by flow cytometry. Forty out of 2300 (1.7%) were found to be negative for this antigen . Of the 28 women followed throughout their pregnancy, none developed antibody to HPA-la. Platelet counts performed on samples from 17 babies born to 17 of these mothers were all normal. This study proves the simplicity and rapidity of flow cytometry for platelet antigen screening. The results were comparable with the Solid Phase Red Cell Adherence (SPRCA) method and with PCR. The lack of a plentiful supply of specific antibody and the rarity of fetomaternai alloimmune thrombocytopenia (FMAIT) argue against the introduction of routine screening for maternal HPA-la status at the present time.