Choice of anaesthesia for category-1 caesarean section in women with anticipated difficult tracheal intubation: the use of decision analysis.

A predicted difficult airway is sometimes considered a contra-indication to rapid sequence induction of general anaesthesia, even in an urgent case such as a category-1 caesarean section for fetal distress. However, formally assessing the risk is difficult because of the rarity and urgency of such cases. We have used decision analysis to quantify the time taken to establish anaesthesia, and probability of failure, of three possible anaesthetic methods, based on a systematic review of the literature. We considered rapid sequence induction of general anaesthesia with videolaryngoscopy, awake fibreoptic intubation and rapid spinal anaesthesia. Our results show a shorter mean (95% CI) time to induction of 100 (87-114) s using rapid sequence induction compared with 9 (7-11) min for awake fibreoptic intubation (p < 0.0001) and 6.3 (5.4-7.2) min for spinal anaesthesia (p < 0.0001). We calculate the risk of ultimate failed airway control after rapid sequence induction to be 21 (0-53) per 100,000 cases, and postulate that some mothers may accept such a risk in order to reduce potential fetal harm from an extended time interval until delivery. Although rapid sequence induction may not be the anaesthetic technique of choice for all cases in the circumstance of a category-1 caesarean section for fetal distress with a predicted difficult airway, we suggest that it is an acceptable option.

Measurement of the positive muon lifetime and determination of the Fermi constant to part-per-million precision.

We report a measurement of the positive muon lifetime to a precision of 1.0 ppm; it is the most precise particle lifetime ever measured. The experiment used a time-structured, low-energy muon beam and a segmented plastic scintillator array to record more than 2×10(12) decays. Two different stopping target configurations were employed in independent data-taking periods. The combined results give τ(µ(+)) (MuLan)=2 196 980.3(2.2) ps, more than 15 times as precise as any previous experiment. The muon lifetime gives the most precise value for the Fermi constant: G(F) (MuLan)=1.166 378 8(7)×10(-5) GeV(-2) (0.6 ppm). It is also used to extract the µ(-)p singlet capture rate, which determines the proton's weak induced pseudoscalar coupling g(P).

Pre-operative vitamin B infusion and prevention of nitrous oxide-induced homocysteine increase.

SUMMARY: Nitrous oxide inactivates vitamin B(12) with detrimental consequences for folate and methionine metabolism, detectable by an increase in total plasma homocysteine. We hypothesised that a pre-operative vitamin B(12) and folate infusion prevents nitrous oxide-induced homocysteine increase. Sixty-three healthy patients having elective surgery were randomly allocated to receive either B-vitamin plus nitrous oxide; placebo plus nitrous oxide or placebo plus air. Fifty-nine patients completed the study. After intravenous B-vitamin infusion, plasma vitamin B(12) and folate concentrations increased 35-fold and 12-fold, respectively, on the first postoperative measurement. Patients who received B-vitamins developed a similar increase (18%) in homocysteine after nitrous oxide (1.9 micromolxl(-1); 95% CI 0.2-3.6 micromolxl(-1)) as those who did not (22%; 2.7 micromolxl(-1); 95% CI 0.6-4.8 micromolxl(-1)). Patients not receiving nitrous oxide had no homocysteine change (0.5 micromolxl(-1); 95% CI -0.8-1.9 micromolxl(-1)), indicating that pre-operative intravenous B-vitamins may not prevent nitrous oxide-induced hyperhomocysteinaemia.

Rapid killing of single neurons by irradiation of intracellularly injected dye.

A simple technique for rapidly killing all or part of single neurons consists of filling the cell with Lucifer Yellow CH and irradiating all or part of it with intense blue light. Such treatment kills the irradiated part of the cell within a few minutes. Adjacent cells are not affected.

Functional properties of individual neuronal branches isolated in situ by laser photoinactivation.

The functional properties of an isolated dendritic branch of an identified sensory interneuron in the cricket were studied. The branch responded to wind stimuli directed at the animal and displayed a distinct directional sensitivity to those stimuli. A technique was used that allows a neuron to be specifically lesioned in a semi-intact preparation during intracellular recording. Lesioning was achieved by dye-sensitized photoinactivation with a laser epi-illumination stereomicroscope.

Getting to precision psychopharmacology: Combining clinical and genetic information to predict fat gain from aripiprazole.

INTRODUCTION: All atypical antipsychotics are associated with some degree of weight gain. We applied a novel statistical approach to identify moderators of aripiprazole-induced fat gain using clinical and genetic data from a randomized clinical trial (RCT) of treatment resistant depression in older adults. MATERIALS AND METHODS: Adults aged ≥60 years with non-response to a prospective trial of venlafaxine were randomized to 12 weeks of aripiprazole augmentation (n = 91) or placebo (n = 90). Dual energy x-ray absorptiometry (DEXA) measured adiposity at baseline and 12 weeks. Independent moderators of total body fat gain were used to generate two combined multiple moderators, one including clinical data alone and one including both clinical and genetic data to characterize individuals who gained fat during aripiprazole augmentation. RESULTS: The value of the combined genetic + clinical multiple moderator (Mcg) was 0.57 [95% CI 0.46, 0.68] (effect size: 0.57), compared to the combined clinical moderator (Mc) value of 0.49 [0.34, 0.63] (effect size: 0.49). Individuals who gained adiposity in this study were more likely to be female and younger in age, have lower weight, fasting glucose and lipids at baseline and positive for the HTR2C polymorphism. DISCUSSION: These results demonstrate a combined multiple moderator approach, including both clinical and genetic moderators, can be applied to existing clinical trial data to understand adverse treatment effects. This method allowed for more specific characterization of individuals at risk for the outcome of interest. Further work is needed to identify additional genetic moderators and to validate the approach.

Pathology of ilioinguinal neuropathy produced by mesh entrapment: case report and literature review.

Ilioinguinal neuropathy is a well-described complication of mesh inguinal herniorrhaphy. We report the first human case, to our knowledge, of ilioinguinal nerve mesh entrapment with neuropathological changes that suggest an inflammatory cause for this chronic pain syndrome.

Neural coding. Neurons cleverer than we thought?

Neurons may encode information in more subtle ways than their average firing rate; encoding by more complex features of a neuron's firing pattern may allow more efficient information transmission.

Neuroendocrine responses to glucose ingestion in man. Specificity, temporal relationships, and quantitative aspects.

The mechanisms of postprandial glucose counterregulation-those that blunt late decrements in plasma glucose, prevent hypoglycemia, and restore euglycemia-have not been fully defined. To begin to clarify these mechanisms, we measured neuroendocrine and metabolic responses to the ingestion of glucose (75 g), xylose (62.5 g), mannitol (20 g), and water in ten normal human subjects to determine for each response the magnitude, temporal relationships, and specificity for glucose ingestion. Measurements were made at 10-min intervals over 5 h. By multivariate analysis of variance, the plasma glucose (P < 0.0001), insulin (P < 0.0001), glucagon (P < 0.03), epinephrine (P < 0.0004), and growth hormone (P < 0.01) curves, as well as the blood lactate (P < 0.0001), glycerol (P < 0.001), and beta-hydroxybutyrate (P < 0.0001) curves following glucose ingestion differed significantly from those following water ingestion. However, the growth hormone curves did not differ after correction for differences at base line. In contrast, the plasma norepinephrine (P < 0.31) and cortisol (P < 0.24) curves were similar after ingestion of all four test solutions, although early and sustained increments in norepinephrine occurred after all four test solutions. Thus, among the potentially important glucose regulatory factors, only transient increments in insulin, transient decrements in glucagon, and late increments in epinephrine are specific for glucose ingestion. They do not follow ingestion of water, xylose, or mannitol. Following glucose ingestion, plasma glucose rose to peak levels of 156+/-6 mg/dl at 46+/-4 min, returned to base line at 177+/-4 min, reached nadirs of 63+/-3 mg/dl at 232+/-12 min, and rose to levels comparable to base line at 305 min, which was the final sampling point. Plasma insulin rose to peak levels of 150+/-17 muU/ml (P < 0.001) at 67+/-8 min. At the time glucose returned to base line, insulin levels (49+/-12 muU/ml) remained fourfold higher than base line (P < 0.01); thereafter they declined but never fell below base line. Plasma glucagon decreased from 95+/-14 pg/ml to nadirs of 67+/-11 pg/ml (P < 0.001) at 84+/-9 min and then rose progressively to peak levels of 114+/-17 pg/ml (P < 0.001 vs. nadirs) at 265+/-12 min. Plasma epinephrine, which was 18+/-4 pg/ml at base line, did not change initially and then rose to peak levels of 119+/-20 pg/ml (P < 0.001) at 271+/-13 min. These data indicate that the glucose counterregulatory process late after glucose ingestion is not solely due to the dissipation of insulin and that sympathetic neural norepinephrine, growth hormone, and cortisol do not play critical roles. They are consistent with, but do not establish, physiologic roles for the counterregulatory hormones-glucagon, epinephrine, or both-in that process.

Three novel brain tropomyosin isoforms are expressed from the rat alpha-tropomyosin gene through the use of alternative promoters and alternative RNA processing.

cDNA clones encoding three novel tropomyosins, termed TMBr-1, TMBr-2, and TMBr-3, were isolated and characterized from a rat brain cDNA library. All are derived from a single gene, which was previously found to express striated muscle alpha-tropomyosin and a number of other tropomyosin isoforms via an alternative splicing mechanism (N. Ruiz-Opazo and B. Nadal-Ginard, J. Biol. Chem. 262:4755-4765, 1987; D. F. Wieczorek, C. W. J. Smith, and B. Nadal-Ginard, Mol. Cell. Biol. 8:679-694, 1988). The derived amino acid sequences revealed that TMBr-1 contains 281 amino acids, TMBr-2 contains 251 amino acids, and TMBr-3 contains 245 amino acids. All three proteins contain a region that is identical to amino acids 81 through 258 of skeletal muscle alpha-tropomyosin. TMBr-1 is identical to striated muscle alpha-tropomyosin from amino acids 1 through 258 but contains a novel COOH-terminal region from amino acids 259 through 281. TMBr-2 and TMBr-3 both contain identical NH2-terminal sequences from amino acids 1 through 44 which were found to be expressed from a novel promoter. TMBr-3 contains the same COOH-terminal region as TMBr-1, whereas TMBr-2 contains a second novel COOH-terminal region. The genomic organization of the exons encoding TMBr-1, TMBr-2, and TMBr-3 were determined. These studies revealed a previously uncharacterized promoter located in the internal region of the alpha-TM gene as well as two novel COOH-terminal coding exons. The alpha-TM gene is a complex transcription unit containing 15 exons including two alternative promoters, two internal mutually exclusive exon cassettes, and four alternatively spliced 3' exons that encode four different COOH-terminal coding regions. A total of nine distinct mRNAs are known to be expressed from the alpha-TM gene in a cell type-specific manner in tissues such as striated muscle, smooth muscle, kidney, liver, brain, and fibroblasts. The mRNAs encoding TMBr-1, TMBr-2, and TMBr-3 were found to be expressed only in brain tissue, with TMBr-3 being expressed at much greater levels than TMBr-1 and TMBr-2. The individual structural characteristics of each brain alpha-tropomyosin isoform and their possible functions are discussed.

Genetic causes of familial hypercholesterolaemia in patients in the UK: relation to plasma lipid levels and coronary heart disease risk.

AIMS: To determine the relative frequency of mutations in three different genes (low-density lipoprotein receptor (LDLR), APOB, PCSK9), and to examine their effect in development of coronary heart disease (CHD) in patients with clinically defined definite familial hypercholesterolaemia in UK. PATIENTS AND METHODS: 409 patients with familial hypercholesterolaemia patients (158 with CHD) were studied. The LDLR was partially screened by single-strand conformational polymorphism (SSCP) (exons 3, 4, 6-10 and 14) and by using a commercial kit for gross deletions or rearrangements. APOB (p.R3500Q) and PCSK9 (p.D374Y) were detected by specific assays. Coding exons of PCSK9 were screened by SSCP. RESULTS: Mutations were detected in 253 (61.9%) PATIENTS: 236 (57.7%) carried LDLR, 10 (2.4%) carried APOB p.Q3500 and 7 (1.7%) PCSK9 p.Y374. No additional mutations were identified in PCSK9. After adjusting for age, sex, smoking and systolic blood pressure, compared to those with no detectable mutation, the odds ratio of having CHD in those with an LDLR mutation was 1.84 (95% CI 1.10 to 3.06), for APOB 3.40 (0.71 to 16.36), and for PCSK9 19.96 (1.88 to 211.5; p = 0.001 overall). The high risk in patients carrying LDLR and PCSK9 p.Y374 was partly explained by their higher pretreatment cholesterol levels (LDLR, PCSK9 and no mutation, 10.29 (1.85), 13.12 and 9.85 (1.90) mmol/l, respectively, p = 0.001). The post-statin treatment lipid profile in PCSK9 p.Y374 carriers was worse than in patients with no identified mutation (LDL-C, 6.77 (1.82) mmol/l v 4.19 (1.26) mmol/l, p = 0.001, HDL-C 1.09 (0.27) mmol/l v 1.36 (0.36) mmol/l, p = 0.03). CONCLUSIONS: The higher CHD risk in patients carrying PCSK9 p.Y347 or a detected LDLR mutation supports the usefulness of DNA testing in the diagnosis and management of patients with familial hypercholesterolaemia. Mutations in PCSK9 appear uncommon in patients with familial hypercholesterolaemia in UK.

PM2.5 constituents and related air quality variables as predictors of survival in a cohort of U.S. military veterans.

Air quality data on trace metals, other constituents of PM2.5, and criteria air pollutants were used to examine relationships with long-term mortality in a cohort of male U.S. military veterans, along with data on vehicular traffic density (annual vehicle-miles traveled per unit of land area). The analysis used county-level environmental data for the period 1997-2002 and cohort mortality for 1997-2001. The proportional hazards model included individual data on age, race, smoking, body mass index, height, blood pressure, and selected interactions; contextual variables also controlled for climate, education, and income. In single-pollutant models, traffic density appears to be the most important predictor of survival, but potential contributions are also seen for NO2, NO3-, elemental carbon, nickel, and vanadium. The effects of the other main constituents of PM2.5, of crustal particles, and of peak levels of CO, O3, or SO2 appear to be less important. Traffic density is also consistently the most important environmental predictor in multiple-pollutant models, with combined relative risks up to about 1.2. However, from these findings it is not possible to discern which aspects of traffic (pollution, noise, stress) may be the most relevant to public health or whether an area-based predictor such as traffic density may have an inherent advantage over localized measures of ambient air quality. It is also possible that traffic density could be a marker for unmeasured pollutants or for geographic gradients per se. Pending resolution of these issues, including replication in other cohorts, it will be difficult to formulate additional cost-effective pollution control strategies that are likely to benefit public health.

Promoting effects of polychlorinated biphenyls (Aroclor 1254) and polychlorinated dibenzofuran-free Aroclor 1254 on diethylnitrosamine-induced tumorigenesis in the rat.

The hepatic tumor-promoting activity of a commercial polychlorinated biphenyl mixture, Aroclor 1254 (AR 1254), with and without its intrinsic polychlorinated dibenzofuran (PCDF) impurities, was investigated. Male Sprague-Dawley non-inbred albino rats were treated with 66 microgram diethylnitrosamine (DENA)/ml drinking water for 5 weeks and subsequently given a control diet or a diet supplemented (100 ppm for 18 wk) with either AR 1254 or AR 1254 from which the PCDF moieties were removed (AR 1254-PCDF). Of those animals receiving DENA alone, 16% exhibited hepatocellular carcinomas. Of those rats treated with DENA followed by administration of AR 1254 or AR 1254-PCDF, 64 or 84%, respectively, developed hepatocellular carcinomas. Thus promotion with either AR 1254 or AR 1254-PCDF significantly (P less than 0.05) increased the incidence of DENA-initiated hepatocellular carcinomas. Administration of AR 1254 or AR 1254-PCDF alone did not induce hepatic tumors. Therefore, PCDF impurities were not necessary for the promoting activity of AR 1254.

Ultrastructural analysis of a murine model of congenital hydrocephalus produced by overexpression of transforming growth factor-beta1 in the central nervous system.

The purpose of this study was to elucidate using transmission electron microscopy (TEM) the ultrastructural changes that occur within the cortical gray matter of a novel reproducible model of congenital hydrocephalus in mice created to overexpress the cytokine transforming growth factor-beta1 (TGF-beta1) in the central nervous system. Brain tissue was obtained from mice from a colony engineered to overexpress TGF-beta1 at two days postpartum and compared to a wild-type aged-matched control. This tissue was fixed using a solution containing 1.25% paraformaldehyde and 1.25% glutaraldehyde in phosphate buffer at least 3-4 h and then cut into 40-50 microm sections. Randomly selected thin sections were stained with uranyl acetate and lead citrate, and then analyzed using a JEOL-100CX or 1200EX transmission electron microscope at accelerating voltage 80 kV. Dramatic neuronal and glial pathology was observed throughout the cortical neuropil in TGF-beta1 mice. The most striking change in the hydrocephalic mice was severe edema with extracellular fluid, possibly due to cerebrospinal fluid (CSF) penetration into the cortex. In addition, severe disruption of the cytoplasmic matrix was seen throughout the cortex, with damage to cellular organelles and particularly severe damage to mitochondria. Our results suggest that congenital hydrocephalus may be associated with significant damage to cortical tissue.

Angle- and velocity-specific alterations in torque and semg activity of the quadriceps and hamstrings during isokinetic extension-flexion movements.

The purpose of this study was to investigate the effect of movement velocity (100 degrees, 200 degrees , 300 degrees s(-1), and 400 degrees s(-1)) and joint position (0 degrees - 15 degrees [L0], 25 degrees - 40 degees [L25], 55 degrees - 70 degrees [L55], and 75 degrees - 90 degrees [L75]) on peak torque (PT) parameters and surface electromyography (SEMG) of the knee-joint muscles during reciprocal isokinetic extension and flexion movements. Thirteen subjects (age = 22.7 +/- 2.1 years, mean height = 161.1 +/- 6.6 cm, mean weight = 63.5 +/- 5.8 kg) participated in the study. Bipolar surface electrodes were placed over the vastus medialis, vastus lateralis, biceps femoris, and medial hamstrings for determination of the root mean square (SEMGrms) and median frequency (SEMGmf) of the SEMG. Peak torque, angle of peak torque (PTang), percentage of peak torque (PTper), SEMGrms, and SEMGmf were analyzed using separate repeated measures analysis of variance (ANOVA). The following main results, significant at p < or = 0.05 or better, were found: The PTang was influenced by movement velocity (in extension there was a decrease in PTang moving from 300 degrees x s(-1) to 400 degrees x s(-1) and inflexion there was an increase in PTang moving from 300 degrees x s(-1) to 400 degrees x s(-1)). Secondly, a greater percentage of peak torque (PTper) was maintained during knee flexion than knee extension. And thirdly, both the quadriceps and hamstrings exhibited changing amplitudes and spectral frequencies based on joint position and movement velocity. There was a trend of decreasing SEMGrms for the quadriceps as the knee moved into extension, and a lower SEMGmf during early (L75) and end stages of knee extension (L0). For the hamstrings, SEMGrms was lowest at the more shortened position (L75) and highest near the mid-position (L25); the lowest SEMGmf occurred at the more lengthened position (L0) and the highest occurred at the more shortened position (L75). Finally, velocity influenced hamstrings and quadriceps muscle amplitude such that SEMGrms was highest at the slower velocities and lowest at the higher velocities. Velocity had no impact on quadriceps spectral properties (p > 0.05), but had a cyclic effect on hamstrings spectral properties. Changes in amplitude and frequency spectrum in tested muscles could be explained, in part, by neural drive to these muscles. Data support the hypothesis of lower activation levels of the quadriceps muscle in the extended position espoused by several authors as a way to protect the knee-joint in the knee-extended position.

Coactivation patterns of the medial and lateral hamstrings based on joint position and movement velocity during isokinetic movements.

The purpose of this investigation was to determine the effect of movement velocity (100 degrees x s(-1), 200 degrees x s(-1), 300 degees x s(-1), and 400 degrees x s(-1)) and joint position (0 degrees - 20 degrees [L0] 30 degrees - 50 degrees [L30], and 70 degrees - 90 degrees [L70] knee flexion) on reciprocal coactivation patterns of the medial and lateral hamstrings as determined by the amplitude and frequency spectrum of surface electromyography (SEMG). Thirteen female subjects (age = 22.7 +/- 2.1 years, mean height = 161.1 +/- 6.6 cm, mean weight = 63.5 +/- 5.8 kg) participated in the study. Bipolar surface electrodes were placed over the biceps femoris (BF) and medial hamstrings (MH) for determination of the root mean square (SEMGrms) and median frequency (SEMGmf) of the SEMG. Normalized SEMGrms values for the MH and BF were determined as a percentage of agonist SEMGrms activity for the same muscle during its agonist phase. Data were analyzed using separate 2 x 3 x 4 (muscle x position x angular velocity) repeated measures analysis of variance (ANOVA). For SEMGrms, there were significant muscle (p < 0.01) and position (p < or = 0.0001) main effects. Post-hoc analyses indicated the BF displayed greater muscle amplitude than the MH and that there was greater muscle amplitude at the L0 position (as the knee approached terminal extension). No velocity effect was noted (p > 0.05). For SEMGmf there were muscle x position (p < or = 0.05) and muscle x position x velocity (p < or = 0.01) interaction effects. Post-hoc analyses indicated the BF displayed a higher frequency spectrum than the MH at the L0 position. Secondly, velocity affected the BF and MH frequency spectrum such that values for both the MH and BF were lowest at 200 degrees x s(-1) and highest at 300 degrees x s(-1) (BF) and 400 degrees x s(-1) (MH). Velocity had little impact on the frequency spectrum in the midrange of the ROM (L30 position). Higher SEMGrms and SEMGmf values for the BF could be explained by the locking or screw home mechanism of the knee, and a way in which the human motor control system provides the limb with a dynamic braking system to control both extension and lateral rotational forces during the final stage of knee extension. It would appear that the way in which the body performs this function is not only to increase the amplitude of BF muscle firing but also to shift toward the recruitment of more fast-twitch motor units.

Activation of type I and type II cyclic AMP-dependent protein kinases by 2,8-disubstituted derivatives of cyclic AMP.

Derivatives of cyclic AMP with substituents in both the 2-position (methyl or butyl) and the 8-position (bromo, benzylthio, p-chlorophenylthio or azido) and their singly modified parent compounds were examined for their abilities to activate type I isozymes of cyclic AMP-dependent protein kinases from rabbit and porcine muscle and type II isozymes of cyclic AMP-dependent protein kinases from bovine brain and heart. The specificity of 2-n-butyl-cyclic AMP for type II was substantially reduced or eliminated by the addition of 8-substituents. The lack of specificity of 2-methyl-cyclic AMP for either type I or II was not changed by the addition of 8-substituents.

Rate of change in aortic valve area during a cardiac cycle can predict the rate of hemodynamic progression of aortic stenosis.

BACKGROUND: The ability to predict the rate of hemodynamic progression in an individual patient with valvular aortic stenosis has been elusive. The purpose of the present study was to evaluate whether the rate of change in aortic valve area (AVA) measured during the ejection phase of a cardiac cycle predicts the rate of hemodynamic progression in patients with asymptomatic aortic stenosis. METHODS AND RESULTS: In 84 adults with initially asymptomatic aortic stenosis and a baseline AVA of > or =0.9 cm(2), annual echocardiographic data were obtained prospectively (mean follow-up 2.8+/-1.3 years). With the initial echocardiogram, the ratio of AVA measured at mid-acceleration and mid-deceleration to the AVA at peak velocity was calculated. The primary outcome variable was the annual rate of change in AVA (rate of progression), with rate of progression classified as rapid (a reduction in AVA of > or =0.2 cm(2)/y) or slow (<0.2 cm(2)/y). Rapid progression was significantly associated with an AVA ratio of > or =1.25 (P=0.004, risk ratio 3.1, 95% CI 1.2 to 7.9). The sensitivity, specificity, and positive predictive value of AVA ratio of > or =1.25 for the prediction o rapid progression of valvar aortic stenosis was 64%, 72%, and 80% respectively. The decrease in ejection fraction measured from the initial to final echocardiogram was small but greater for patients with an AVA ratio of > or =1.25 (-4+/-7% versus +2+/-7%, P<0.001). CONCLUSIONS: A flow-dependent change in AVA can be measured during a routine transthoracic echocardiographic study. The rate of change in AVA is an additional measure of disease severity and may be used to predict an individual's risk for subsequent rapid disease progression.

Muscle capillary basement membrane width and its relationship to diabetes mellitus in monozygotic twins.

Quadriceps (Q) and gastrocnemius (G) muscle capillary basement membrane width (CBMW) were measured in 18 pairs of monozygotic (MZ) twins. Thirteen of these twin pairs were discordant for insulin-dependent diabetes (IDD) and five pairs were concordant for either IDD (two pairs) or for non-insulin-dependent diabetes (NIDD). In 12 of the 13 nondiabetic (ND) twin mates of IDD, 50 oral glucose tolerance tests performed in the years before or after determination of CBMW revealed mean blood glucose levels in the 36-52 percentile range, compared with normal controls. The mean (+/-SD) age at the onset of IDD in discordant twins was 18.7 +/- 10.1 (range 8-37) yr and the mean duration of discordance at the time of biopsy was 13.6 +/- 8.3 (range 3-32) yr. CBMW data were compared within each twin (Q versus G) and between twin mates and age- and sex-matched controls. Overall, CBMW of IDD twins was greater than that of their ND twin mates. Differences between IDD and ND twins, however, were much more marked in gastrocnemius (1859 +/- 643 versus 1222 +/- 307 A, P less than 0.0003) than in quadriceps (1291 +/- 319 versus 1112 +/- 302 A; P less than 0.04). CBMW in gastrocnemius was significantly thicker than that in the quadriceps of IDD twins (t = 4.55, P less than 0.0008) but not in their ND twin mates (t = 1.15, P less than 0.27). CMBW was significantly thicker in IDD than in their ND twin mates (in quadriceps and/or gastrocnemius) in 10 of the 12 twin pairs.(ABSTRACT TRUNCATED AT 250 WORDS)