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Background: An infectious syphilis outbreak in Alberta has resulted in increased congenital syphilis (CS) cases. To shed light on potential risk factors, we used administrative data sets to examine care milestones for the prevention of CS among pregnant women diagnosed with syphilis, as well as correlates of women giving birth to infants with CS., Methods: Provincial administrative databases were used to identify and describe pregnant women diagnosed with any stage of infectious or noninfectious syphilis who gave birth in Alberta between January 1, 2017, and December 31, 2019. Data on prenatal care, syphilis screening, and syphilis medication dispensation were used to evaluate the care milestones. Clinical care and maternal demographics were assessed using logistic and linear regression analyses to determine correlates for missed care milestones or a newborn outcome of CS., Results: Of 182 syphilis-infected pregnant women, 63 (34.6%) delivered a newborn with CS. Overall, in the first trimester, 136 (75.1%) women had a health care visit, 72 (39.6%) had a prenatal care visit, 71 (39.0%) were screened for syphilis, and 44 (24.2%) were treated. Gestational time to treatment initiation (adjusted odds ratio, 1.04; 95% confidence interval, 1.02-1.06) and older maternal age at diagnosis (adjusted odds ratio: 1.28, 95% confidence interval, 1.08-1.50) were independently associated with CS outcomes. No variables were found to be independently associated with a health care visit, prenatal screening, or initiation of treatment., Conclusions: Although nearly two-thirds of CS cases were prevented, there remained missed opportunities in the prevention of CS. Early treatment, which relies on timely access to prenatal care and screening, was the most important for the prevention of CS., Competing Interests: Conflict of Interest and Sources of Funding: None declared., (Copyright © 2022 American Sexually Transmitted Diseases Association. All rights reserved.)

Objectives: Despite increasing rates of legalization of medical cannabis worldwide, the current evidence available on its effect on mental health outcomes including anxiety is of mixed results. This study assesses the effect of medical cannabis on generalized anxiety disorder 7-item (GAD-7) scores in adult patients between 2014 and 2019 in Ontario and Alberta, Canada., Methods: An observational cohort study of adults authorized to use medical cannabis. The GAD-7 was administered at the time of the first visit to the clinic and subsequently over the follow-up time period of up to 3.2 years. Overall changes in GAD-7 scores were computed (mean change) and categorized as: no change (<1 point); improvement; or worsening-over time., Results: A total of 37,303 patients had initial GAD-7 scores recorded and 5,075 (13.6%) patients had subsequent GAD-7 follow-up scores. The average age was 54.2 years (SD 15.7 years), 46.0% were male, and 45.6% noted anxiety symptoms at the baseline. Average GAD-7 scores were 9.11 (SD 6.6) at the baseline and after an average of 282 days of follow-up (SD 264) the average final GAD-7 score recorded was 9.04 (SD 6.6): mean change -0.23 (95% CI, -0.28 to -0.17, t [5,074]: -8.19, p -value <0.001). A total of 4,607 patients (90.8%) had no change in GAD-7 score from their initial to final follow-up, 188 (3.7%) had a clinically significant decrease, and 64 (1.3%) noted a clinically significant increase in their GAD-7 scores., Conclusions: Overall, there was a statistically significant decrease in GAD-7 scores over time (in particular, in the 6-12-month period). However, this change did not meet the threshold to be considered clinically significant. Thus, we did not detect clinical improvements or detriment in GAD-7 scores in medically authorized cannabis patients. However, future well-controlled clinical trials are needed to fully examine risks or benefits associated with using medical cannabis to treat anxiety conditions.

Introduction: With the availability of direct-acting antivirals, Hepatitis C (HCV) is now considered a treatable disease. Patients who are co-infected with human immunodeficiency virus (HIV) and HCV represent an ideal patient population to treat for HCV, as (1) patients are routinely taking medication for HIV, and therefore would be able to complete HCV drug regimens, and (2) HIV infection has been shown to increase HCV disease progression., Objective: We sought to determine the occurrence of HCV co-infection among HIV patients in our provincial cohort, determine whether they received treatment for HCV, and identify currently viremic patients who can be linked to care., Materials and Methods: HCV laboratory testing data (HCV antibody and HCV RNA) and HCV medication dispensation data was collected for all HIV positive patients. Current and previous HCV infection and treatment was assessed. Chart reviews were conducted for HCV viremic patients to assess their HIV care and social determinants., Results: Of the 2417 HIV positive patients, 392 (16.2%) were identified as being co-infected with HCV. 198 (50.5%) of the HIV-HCV co-infected patients received HCV treatment and 232 (59.2%) were not viremic on the most recent HCV RNA test. 99 (69.2%) had a suppressed HIV infection suggesting they are active in their HIV care and good candidates for HCV treatment., Conclusion: Despite the availability of direct-acting antivirals, many patients who are co-infected with HIV and HCV are not being treated for HCV. Routine surveillance of HIV-HCV co-infected patients could improve HCV treatment rates in a high-risk population., (Copyright © 2020 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Background: With legal access to medical cannabis in Canada since 2001, there is a need to fully characterize its use at both the individual and population levels. We draw on data from Canada's largest cohort study of medical cannabis to identify the primary reasons for medical cannabis authorization in Canada from 2014 to 2019 in two major provinces: Alberta (AB) and Ontario (ON), and review the extent that evidence supports each indication., Methods: Self-reported baseline assessments were collected from adult patients in ON (n = 61,835) and AB (n = 3410) who were authorized medical cannabis. At baseline, sociodemographic, primary medical information, and validated clinical questionnaires were completed by patients as part of an individual assessment. Patients' reasons for seeking medical cannabis were compared to published reviews and guidelines to assess the level of evidence supporting medical cannabis use for each condition., Results: Medical cannabis use in both AB and ON was similar in both demographic and reason for authorization. The most common reasons for medical cannabis authorization were: (1) pain (AB = 77%, ON = 76%) primarily due to chronic musculoskeletal, arthritic, and neuropathic pain, (2) mental health concerns (AB = 32.9%, ON = 38.7%) due to anxiety and depression, and (3) sleep problems (AB = 28%, ON = 25%). More than 50 other conditions were identified as reasons for obtaining authorization., Conclusion: In both AB and ON, the majority of reasons for medical cannabis authorization are not substantiated by clinical evidence to fully support its efficacy for long-term use. Ongoing epidemiological studies on medical cannabis on these treatments are warranted to fully outline its treatment benefits or risks.

Objective: Silica gel beads have promise as a non-toxic, cost-effective, portable method for storing environmental DNA (eDNA) immobilized on filter membranes. Consequently, many ecological surveys are turning to silica bead filter desiccation rather than ethanol preservation. However, no systematic evaluation of silica bead storage conditions or duration past 1 week has been published. The present study evaluates the quality of filter-immobilized eDNA desiccated with silica gel under different storage conditions for over a year using targeted quantitative real-time polymerase chain reaction (qPCR)-based assays., Results: While the detection of relatively abundant eDNA target was stable over 15 months from either ethanol- or silica gel-preserved filters at - 20 and 4 °C, silica gel out-performed ethanol preservation at 23 °C by preventing a progressive decrease in eDNA sample quality. Silica gel filter desiccation preserved low abundance eDNA equally well up to 1 month regardless of storage temperature (18, 4, or - 20 °C). However only storage at - 20 °C prevented a noticeable decrease in detectability at 5 and 12 months. The results indicate that brief storage of eDNA filters with silica gel beads up to 1 month can be successfully accomplished at a range of temperatures. However, longer-term storage should be at - 20 °C to maximize sample integrity.

Background: Legal access to medical cannabis is increasing world-wide. Despite this, there is a lack of evidence surrounding its efficacy on mental health outcomes, particularly, on depression. This study assesses the effect of medical cannabis on Patient Health Questionnaire (PHQ-9) scores in adult patients between 2014 and 2019 in Ontario and Alberta, Canada., Methods: An observational cohort study of medically authorized cannabis patients in Ontario and Alberta. Overall change in PHQ-9 scores from baseline to follow-up were evaluated (mean change) over a time period of up to 3.2 years., Results: 37,338 patients from the cohort had an initial PHQ-9 score recorded with 5103 (13.7%) patients having follow-up PHQ-9 scores. The average age was 54 yrs. (SD 15.7), 46% male, 50% noted depression at baseline. The average PHQ-9 score at baseline was 10.5 (SD 6.9), following a median follow-up time of 196 days (IQR: 77-451) the average final PHQ-9 score was 10.3 (SD 6.8) with a mean change of - 0.20 (95% CI: - 0.26, - 0.14, p-value < 0.0001). Overall, 4855 (95.1%) had no clinically significant change in their PHQ-9 score following medical cannabis use while 172 (3.4%) reported improvement and 76 (1.5%) reported worsening of their depression symptoms., Conclusions: Although the majority showed no clinically important changes in PHQ-9 scores, a number of patients showed improvement or deteriorations in PHQ-9 scores. Future studies should focus on the parallel use of screening questionnaires to control for PHQ-9 sensitivity and to explore potential factors that may have attributed to the improvement in scores pre- and post- 3-6 month time period.

The coastal tailed frog (Ascaphus truei) is endemic to the Pacific Northwest of North America and is listed as a species of Special Concern under the Canadian Species at Risk Act. Its range is limited to British Columbia where it occurs widely west of the Coast Mountain Ranges extending north almost to the Alaskan Panhandle. The present study focused on surveying within the Cayoosh, Bridge (Shulaps), Seton, Anderson, Carpenter, and Downton Lake drainages. Four years of previous inventory efforts using conventional time-constrained search (TCS) methods detected tailed frog at 23/292 discrete sites (7.9% detection rate) in seven watersheds. Non-invasive environmental DNA (eDNA) methods hold promise for cryptic and low-abundance species detection. We rigorously validated a quantitative real-time polymerase chain reaction (qPCR)-based tool for detecting coastal tailed frog eDNA in water samples. This eASTR4 test is highly specific and sensitive. We applied a two-step targeted eDNA analysis approach on duplicate filtered water samples from a total of 72 sites collected over five days. The first IntegritE-DNA step mitigates false negative results and tests all DNA samples for the ability to support amplification from endogenous plant chloroplast DNA as a measure of sample viability. Three DNA samples failed this step even after inhibitor clean up suggesting that these samples were poor quality and not reliable for targeted species' DNA analyses. All other DNA samples were deemed viable and were then tested for species-specific DNA. Coastal tailed frog eDNA was detected in 55/72 (76%) discrete stream reaches; nine sites with historical known occurrence were all eDNA positive. The false negative rate for TCS compared to eDNA methods was 58%. The results expand known coastal tailed frog distribution to 24 watersheds effectively more than tripling extant occurrences and confirm a previously suspected, apparently isolated coastal tailed frog metapopulation in the Shulaps drainage., Competing Interests: We have read the journal's policy and the authors of this manuscript have the following competing interests: JH is an employee of Hemmera Envirochem Inc. JH was involved with all aspects of the study with the exception of qPCR assay design, validation, data collection, and analysis. A patent is pending on some of the concepts presented in the manuscript (US provisional application number 62/406,802). The patent is owned by the University of Victoria who will handle commercial and academic licensing agreements. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Low sulfur marine diesel (LSMD) is frequently involved in coastal spills and monitoring ecosystem damage, and the effectiveness of cleanup methods remains a challenge. The present study investigates the concentration and composition of polycyclic aromatic hydrocarbons (PAHs) dispersed in LSMD seawater accommodated fractions (WAFs) and assesses the effects of exposure on juvenile coho salmon ( Onchorhynchus kisutch). Three WAFs were prepared with 333, 1067, and 3333 mg/L LSMD. The sum of 50 common PAHs and alkylated PAHs (tPAH50) measured by gas chromatography/triple quadrupole mass spectrometry showed saturation at ∼90 mg/L for all WAFs. These WAFs were diluted 30% for 96 h fish exposures. qPCR was performed on liver and caudal fin from the same genotypically sexed individuals to evaluate PAH exposure, general and oxidative stress, estrogenic activity, and defense against metals. Excluding metal response, our analyses reveal significant changes in gene expression following WAF exposure on juvenile salmon with differential sensitivity between males and females. The 3-methylcholanthrene responsive cytochrome P450-1a ( cyp1a) transcript exhibited the greatest increase in transcript abundance in the caudal fin (10-18-fold) and liver (6-10-fold). This demonstrates that cyp1a is a robust, sex-independent bioindicator of oil exposure in caudal fin, a tissue that is amenable to nonlethal sampling.

Frogs play important ecological roles, and several species are important model organisms for scientific research. The globally distributed Ranidae (true frogs) are the largest frog family, and have substantial evolutionary distance from the model laboratory Xenopus frog species. Unfortunately, there are currently no genomic resources for the former, important group of amphibians. More widely applicable amphibian genomic data is urgently needed as more than two-thirds of known species are currently threatened or are undergoing population declines. We report a 5.8 Gbp (NG50 = 69 kbp) genome assembly of a representative North American bullfrog (Rana [Lithobates] catesbeiana). The genome contains over 22,000 predicted protein-coding genes and 6,223 candidate long noncoding RNAs (lncRNAs). RNA-Seq experiments show thyroid hormone causes widespread transcriptional change among protein-coding and putative lncRNA genes. This initial bullfrog draft genome will serve as a key resource with broad utility including amphibian research, developmental biology, and environmental research.

The development of elbow flexor (biceps) and knee extensor (quadriceps) strength has been followed in a mixed longitudinal study of 50 boys and 50 girls from the age of 8 to 17 years. Sex differences in strength emerged at the time of peak height velocity and were especially marked for the biceps. Data for individual children were aligned to the time of peak height velocity and associations between strength, height, weight and circulating testosterone were investigated using multi-level modelling. The results show that, for girls, quadriceps strength is proportional to height and weight while for boys there is an additional factor which can be fully attributed to increasing levels of testosterone. Testosterone is important in explaining differences in biceps strength between the sexes but an additional factor is also required. It is suggested that, in addition to a direct effect on muscle, testosterone could have a second indirect action on biceps strength by promoting growth in length of the humerus as part of the general development of the male upper limb girdle.

The present study examined two contrasting multilevel model structures to describe the developmental (longitudinal) changes in strength and aerobic power in children: 1) an additive polynomial structure and 2) a multiplicative structure with allometric body size components. On the basis of the maximum log-likelihood criterion, the multiplicative "allometric" model was shown to be superior to the additive polynomial model when fitted to the data from two published longitudinal studies and to provide more plausible solutions within and beyond the range of observations. The multilevel regression analysis of study 1 confirmed that aerobic power develops approximately in proportion to body mass, m1/3. The analyses from study 2 identified a significant increase in quadriceps and biceps strength, in proportion to body size, plus an additional contribution from age, centered at about peak height velocity (PHV). The positive "age" term for boys suggested that at PHV the boys were becoming stronger in the quadriceps and biceps in relation to their body size. In contrast, the girls' age term was either negligible (quadriceps) or negative (biceps), indicating that at PHV the girls' strength was developing in proportion to or, in the case of the biceps, was becoming weaker in relation to their body size.

Xanthine oxidase activity in blood from the ipsilateral femoral vein, and the relationship between xanthine oxidase production and the products of lipid peroxidation, were studied before operation and for 60 min following release of clamps after successful revascularization in two groups of patients with claudication or critical ischaemia. Before revascularization, detectable levels of xanthine oxidase were found only in patients with critical ischaemia. Clamping during bypass surgery led to release of xanthine oxidase in claudicants, but this activity reduced after 60 min. There was no evidence of lipid peroxidation during this time. Xanthine oxidase activity in brachial vein blood was higher than in femoral vein blood in patients with critical ischaemia before revascularization.

Eleven patients with AIDS or AIDS-related complex who developed muscle-related symptoms whilst taking zidovudine were investigated. The clinical details of a further ten patients who did not undergo muscle biopsy are also outlined. The clinical features, quantitative muscle strength testing, electromyographic findings, serial creatine kinase levels, muscle biopsy appearance on light microscopy and the effects of zidovudine withdrawal and rechallenge are described. The spectrum of muscle disease encountered included four cases of frank myopathy diagnosed using clinical, electrophysiological and histological criteria, four patients with mild weakness and myalgia in whom muscle biopsies were normal, three patients with myalgia only and a mild increase in the interstitial cell infiltrate shown by biopsy. The patients presenting with myopathy showed no improvement on withdrawal of zidovudine but responded to immunosuppressive therapy with steroids and, in one case, thalidomide prescribed incidentally. At present, it is not yet possible to clinically define a specific zidovudine-induced myopathy that is distinct from the other effects of HIV infection on muscle structure and function. Our experience suggests that zidovudine may be implicated as a myotoxin in some patients, particularly those with myalgia and mild weakness. In those patients with severe weakness, and with biopsy findings of necrosis and inflammation, the drug effects may be difficult to separate from the primary effects of HIV.

With the advent of functional electrical stimulation (FES) there is the possibility of paraplegic patients regaining some degree of locomotor activity. It is of interest to document the changes in composition histochemistry and size of muscle fibres in such patients both before and after such therapy. We have examined biopsy specimens from quadriceps muscles obtained from 7 male patients, age range 24-47 years, who had been paraplegic for times ranging from 11 months to 9 years and we report the histochemical appearance of the muscle the fibre type composition and the mean fibre areas. In 5 of the 7 subjects there was a marked or complete predominance of fibres which stained as type 2 with the ATPase reaction at pH 9.4. At acid pH these fibres were seen to be predominantly 2B (fast fatigable). The 2 subjects who had been paralysed for the shortest periods had proportions of type 1 fibres which were relatively well preserved. The mean fibre areas of type 2 fibres were below the normal range (2500-7500 microns 2) in every case as were the type 1 fibres in the 4 patients in which these were still present. There was no relationship between the length of time the patient had been paralysed and the mean fibre areas which suggests that atrophy occurs fairly quickly following loss of voluntary control and precedes the loss of type 1 characteristics. Our findings provide an explanation for the rapid onset of fatigue in paraplegic patients taking part in FES programmes since muscles deficient in type 1 fibres will be unable to maintain force for any length of time.

A study was carried out to document the occurrence of rhabdomyolysis and renal complications in patients undergoing vascular reconstruction. Indices of muscle damage and renal function were monitored before, during and for up to 10 days after vascular reconstruction for a variety of conditions ranging from intermittent claudication to acute ischaemia. Seven patients with acute limb ischaemia (group 1) and nine with intermittent claudication (group 2) were studied prospectively. In group 1, median creatine kinase (CK) and myoglobin levels were markedly raised 24-48 h after surgery (CK, 29,370 units/l; myoglobin, 8.17 mg/l). Myoglobin reached its peak concentration and declined more quickly than CK, but both indices gave similar information about the extent of muscle damage. In contrast, patients undergoing elective surgery for claudication showed no significant departure from reference values for myoglobin or CK. All patients in group 1 underwent fasciotomy to relieve raised compartmental pressures and five were treated with alkali and mannitol to produce diuresis. Despite these measures, two patients suffered renal failure (peak creatinine levels 611 and 590 mumol/l) after successful revascularization and subsequently required haemodialysis; these patients did not have diuresis. One of these patients died following a stroke 8 days after surgery; the other survived and was discharged with a normal limb and restored renal function. There was no evidence of muscle damage or renal complications in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

The histology of needle biopsy specimens of skeletal muscle from the vastus lateralis was quantitatively assessed in a group of adults with growth hormone (GH) deficiency, most of whom had hypopituitarism treated with conventional pituitary hormone replacement. The mean age of the 21 patients (16 males and 5 females) was 39 +/- 2 (SEM). Comparisons were made with age- and sex-matched controls following six months double-blind, placebo-controlled treatment with recombinant human GH (rhGH) in the GH-deficient patients. Before treatment, needle muscle biopsies from patients with GH deficiency showed mean type I and II fibre areas of 5,153 +/- 273 and 4,828 +/- 312 microns 2 respectively, which did not differ from the controls (4,482 +/- 306 and 4,699 +/- 310 microns 2). Percentages of type I fibres were similar in the two groups (47.2 +/- 2.5% in GH deficiency and 45.3 +/- 2.2% in controls). No difference in the variability of type I or II fibre areas was demonstrated between the groups. Correlations between the relative contribution to total fibre area by type I fibres (mean fibre area x percent) and maximal oxygen uptake (p = 0.006), and between type II fibres and quadriceps force (p = 0.035) were noted in GH-deficient adults before treatment. Following rhGH treatment, no change was noted in mean fibre areas, variability of fibre areas, or percentage of either fibre type.(ABSTRACT TRUNCATED AT 250 WORDS)

Objectives: The aim of this study was to determine whether there are any changes in skeletal muscle strength and size and body composition following growth hormone (GH) withdrawal in GH deficient young adults., Design: A longitudinal, 1-year, open, uncontrolled study of the changes in skeletal muscle and body composition following GH withdrawal was performed. Endocrine status was reassessed at the end of the study period during an insulin tolerance test. Some measurements were repeated after 2 years of treatment., Patients: Twelve (11 male, one female; age range 14-21) patients who had been diagnosed during childhood as growth hormone deficient took part in the study. Four of the 12 patients were found to have a normal GH response on retesting at the end of the study and their results were analysed as a separate group., Measurements: Quadriceps and forearm flexor maximum voluntary isometric strength, body fat content and serum IGF-1 were measured at 3-monthly intervals over 1 year. Every 6 months muscle size was measured from computerized tomography scans and fibre area from quadriceps needle biopsy samples., Results: For the growth hormone deficient group the 12 month quadriceps strength, size and fibre areas were 94.0% +/- 8.5 (mean +/- SD), 94.5% +/- 6.3 and 85.6% +/- 17.7 respectively of control (baseline) values. Forearm flexor strength and size were 101.4% +/- 7.9 and 92.0% +/- 9.2 of control. Body fat percentage had increased from 19.5% +/- 8.6 to 24.1% +/- 9.5. No change was seen in the non-growth hormone deficient group., Conclusions: Although the changes measured were relatively small they suggest a role for GH in the maintenance of muscle integrity and body composition in the young adult with growth hormone deficiency.

Dual energy x ray absorptiometry and a wide range of blood and urine tests were used to assess the propensity of patients with systemic lupus erythematosus to develop an impairment of bone mineral density. Surprisingly, in this preliminary study no significant differences in bone mineral density were found when patients taking 10 mg or more of prednisolone for six months or longer were compared with those who had never taken prednisolone.

Changes in height and weight during childhood and adolescence are well documented, yet there is comparatively little comprehensive information about muscular development during this time. In a cross-sectional survey standing height, body weight and isometric strength of the elbow flexor and quadriceps muscles have been measured in 267 boys and 284 girls aged from 5 to 17 years. All the children were from private London schools. The mean heights and weights for each age group were between the 50th and 75th centiles for British children. The strength of both muscle groups in the boys and girls rose steadily in each age group from 8 to 12 years, after which there was a rapid increase in strength of both the quadriceps and elbow flexors in boys which continued even when growth in height and body weight had virtually ceased. In the pre-adolescent phase of growth, muscle strength of the elbow flexors and quadriceps increased as a function of height squared and cubed respectively, suggesting that stretch as a result of elongation of the long bones, and for the quadriceps, loading, may be the primary stimuli during this phase. In the postpubertal phase some other stimulus, such as a direct action of hormones on the muscle, must be responsible for the continued increase in strength in the boys.

Proportions of slow (type 1) muscle fibres of the vastus lateralis and percentage body fat were measured in 11 healthy sedentary men. The proportion of slow muscle fibres was inversely related to fatness; at least 40% of the variability in fatness may be related to variation in muscle fibre type. Metabolic evidence in 50 men, provided by the respiratory exchange ratio (RER) during cycle ergometry, indicated that fatter men (or, in the subset of 11 men, those with a low proportion of slow muscle fibres) combusted less fat during work at 100 W than did lean men (or those with a high proportion of slow fibres). The effects of fitness and of body size were excluded in the analysis. The evidence supports the hypothesis that muscle fibre type is an aetiological factor for obesity.

Quadriceps strength and size was measured in a small group of subjects (n = 7) 1 to 5 years after full mobilisation following some form of unilateral lower limb trauma. The mean maximum voluntary isometric force (MVC) was significantly lower for the injured (I) compared to the uninjured (UI) leg (369 N +/- 139 vs. 535 N +/- 131, p less than 0.01). Electrical stimulation superimposed on the voluntary contractions demonstrated that all subjects were able to maximally activate the quadriceps of both legs. Mean quadriceps cross-sectional area (CSA) was significantly lower in the I (64 cm2 +/- 12.8) compared to the UI leg (80 +/- 12.8, p less than 0.01). One subject with marked unilateral weakness and wasting took part in a 3-month strength training study for the injured leg. After training the I/UI ratio had been restored to nearly 100% (94% MVC; 88% CSA). These results would suggest that longer and more intensive physiotherapy is required in the immediate post-injury period to restore muscle strength and size to severely atrophied muscle.

Over 1,000 needle biopsies have been carried out at University College Hospital in London. Needle biopsy has been used by us for histochemical and electron microscopic examination of muscle during the diagnosis and treatment of neuropathic and myopathic disorders, for the diagnosis of mitochondrial myopathies, to study the course of recovery in polymyositis, and for investigations into muscle changes in systemic lupus erythematosus (SLE) and other autoimmune conditions. We have developed a microprocessor system for the measurement of muscle fiber areas, and needle biopsy specimens provide suitable material for such measurements. We have also used needle biopsy specimens for studies of protein turnover using stable isotopes and for trace metal and electrolyte analyses. Needle biopsy is safe and rapid. As the patient usually experiences only minimal discomfort and there is no permanent scar, repeat biopsies are well tolerated allowing follow-up studies after treatment.

The relative concentrations of plasma uric acid and creatinine, the alkaline phosphatase activities and the 24 hour urinary excretion of hydroxyproline together with sexual maturity ratings are reported in a population of normal British schoolchildren studied longitudinally over a three-year period. The children were all of European origin and their ages ranged from 7 to 17 years. Plasma urate rose sharply during puberty in the boys but not in the girls. Plasma creatinine rose in both sexes during maturation. Plasma alkaline phosphatase activity rose to a peak at genital maturity 3(G3) in boys and breast maturity 2(B2) in girls and subsequently fell rapidly in both sexes. The 24-hour urinary secretion of hydroxyproline was high in young boys and rose to a peak during G3 and G4 and then fell rapidly. In girls there was no significant peak in concentrations, although there was a fall during B4 and B5, and levels were higher throughout puberty than those reported for adult females.

We have examined the anatomy and fibre type composition of the human adductor pollicis in muscles taken post mortem. Histochemical staining of muscle fibres showed that type I fibres predominated in all cases with a mean occurrence of 80%. This composition is similar to that of the soleus muscle and unlike that of the quadriceps which has approximately equal proportions of the two fibre types. Comparing the contractile characteristics, however, the adductor pollicis has similar properties to the quadriceps and both are quite distinct from those of the slowly contracting soleus muscle. The lack of correlation between fibre composition, as revealed by histochemical staining, and contractile properties in these muscles must mean that fibres of the same type from different muscles do not necessarily have the same contractile speed. The results also suggest that the type I fibres of the human adductor pollicis are faster than those of both the soleus and quadriceps muscles.

Many children with muscular dystrophy are overweight, and although weight control is pursued in some centres it is unusual to encourage severe dietary restriction for fear that it might lead to accelerated loss of muscle. In this study, two overweight boys with muscular dystrophy were monitored by whole-body nitrogen balance, total body potassium, strength and functional measurements during calorie restriction. Both patients were found to have a transient loss of nitrogen on commencing the low calorie intake: thereafter, weight loss was not found to have any deleterious effect on muscle bulk or function in either patient. It is suggested that controlled weight-reduction in obese children with muscular dystrophy is a safe and practical way of losing excess fat, which can improve mobility and self-esteem, and may possibly effect longevity.

We have examined muscle strength, mitochondrial enzyme activity, histochemistry and fibre size in the quadriceps muscle of 9 patients with severe chronic heart failure. A needle biopsy of the quadriceps muscle was taken with patients at rest. Maximum oxygen uptake was measured during treadmill exercise. Mean maximal oxygen consumption was 11.7 ml.kg-1.min-1. Isometric maximum voluntary contraction was reduced to 55% of the predicted value for weight. Eight biopsies were abnormal. Findings included increased acid phosphatase, increased interstitial cellularity, excess intracellular lipid accumulation, atrophy of both type I and II fibres and variation in size with hypertrophy and atrophy of fibers. Muscle fibre capillary density and the activity of mitochondrial enzymes were normal. Changes in skeletal muscle strength may play a role in the limitation of exercise capacity seen in patients with congestive heart failure.

The type and distribution of mononuclear cell infiltrates in muscle biopsies taken from 9 subjects at differing times after exercise in which the muscle is stretched (eccentric exercise) has been characterised. The appearances are compared to those seen in muscle from patients with inflammatory muscle disease. After exercise infiltrating cells were seen in perivascular, perimysial and endomysial regions, the extent being greater in the later biopsies (9-14 days). The predominant cell type was the macrophage (46-100% of all infiltrating cells), the remainder were T lymphocytes with a predominance of the CD4 positive helper/inducer subset. Approximately one third of the T cells expressed DA2 (class 2) antigen indicating that they were activated. Very few B lymphocytes and no Leu7 positive cells were seen. There was evidence of class 1 expression on some of the damaged muscle fibres. The appearance of the experimentally damaged muscle in normal subjects was very similar to untreated polymyositis suggesting that a proportion of the infiltrating cells seen in this disease may be present as part of a natural response to damage rather than being its cause.

Our purpose was to determine the amount of injury to extensor digitorum longus (EDL) and anterior tibial (ATB) muscles of mice from 1 h to 30 days following passive shortening and lengthening, shortening contractions and lengthening contractions. The shortening-lengthening cycle was of 600 ms duration and was repeated every 5 s for 30 min. Contractions were produced during either the shortening or lengthening phase with stimulation at 100 Hz for 300 ms. The amount of injury was evaluated by the decrease in the number of fibres in a cross-section of the muscle and in the maximum isometric tetanic force (Po). Passively shortened and lengthened and actively shortened EDL and ATB muscles showed no evidence of injury. At 3-5 days after lengthening contractions, EDL and ATB muscles showed an inflammatory response. At 3-5 days, the number of fibres in the cross-section of the injured EDL muscles was 65% of that of the contralateral control EDL muscle, whereas no change was observed in the number of fibres in the injured ATB muscles. By 3 days, the presence of myoblasts, myotubes and central nuclei indicated regeneration of fibres. One hour after shortening contractions, the Po of EDL and ATB muscles decreased to about 75% of the contralateral control value, but recovered completely by 3 days. In contrast, 1 h after lengthening contractions the Po of EDL and ATB muscles decreased to 52 and 40% respectively of the contralateral control value and then both recovered to about 65% within 3 h. For the ATB muscle, the Po showed a secondary decrease to 49% of the contralateral control value at 1 day and for the EDL muscle, to 47% at 3 days. Each muscle recovered gradually and by 30 days the number of fibres and the Po of the injured muscles were not significantly different from values for contralateral control muscles.

Calf and quadriceps muscle size and composition have been examined in 5 control subjects and 12 boys (aged 7-18 years) with Duchenne muscular dystrophy using computed tomography (CT) and quantitative histochemistry of needle biopsy samples of muscle. In assessing the size of leg muscles it was found that in control subjects the muscle cross-sectional area was related to the cross-sectional area of the femur. The calf muscles in the patients were enlarged both relative to the quadriceps and absolutely when related to the cross-sectional area of the femur used as an index of stature. The enlargement of the calf was the result of accumulations of fat and connective tissue in the presence of relatively normal (compared to femur size) amounts of muscle tissue. Although hypertrophied muscle fibres were a feature of the biopsy samples in the calf the extent of this was insufficient to contribute appreciably to the total muscle enlargement.

Skeletal muscle strength and size were measured for 1 year following discontinuation of human growth hormone (hGH) treatment in 11 patients with hypopituitarism. Quadriceps and forearm flexor maximum voluntary isometric strength and size were measured. At the end of the study, endocrine status was reassessed by an insulin tolerance test. Three of the 11 subjects were found to have normal hGH secretion and were not included in the analysis. At 12 months, quadriceps strength, size and fibre areas were 94.0 +/- 8.5%, 94.5 +/- 6.3% and 85.6 +/- 17.7% (mean +/- SD), respectively, of baseline values. Forearm flexor strength and size were 101.4 +/- 7.9% and 92 +/- 9.2% of control values. Although these changes are relatively small, they suggest a role for growth hormone in the maintenance of muscle in the adult.

A cross-sectional study was carried out of 412 healthy and 226 chronically malnourished children in Recife, Brazil. Anthropometric measurements, x-rays of hands and wrists, and biochemical data related to skeletal growth were obtained. Levels of plasma 25 hydroxyvitamin D were measured in both groups of children and both showed higher concentrations than those reported for normal European children. The high levels of 25 hydroxyvitamin D found in these two groups of Brazilian children are probably the result of the intense solar radiation in this part of Brazil and argue against the diet being an important source of vitamin D in poorly nourished children. Some bone abnormalities were seen in the underprivileged group of children but in view of our findings these were more likely to be a result of protein-energy malnutrition than rickets.

A flexible system for the measurement of length and area is described. The system consists of the Reichert Jung MOP-1 area measuring device interfaced with a Commodore PET computer. Its use is illustrated by the planimetric measurement of cross sectional areas in histochemical preparations of normal and diseased muscle. While measurements are being made data can be displayed on the computer screen either in numerical form or as a frequency histogram together with simple statistical analyses. Hard copy can be obtained from an attached printer. Mean values for fibre area in normal human skeletal muscle are reported. An alternative, widely used method of calculating fibre area from the lesser diameter was found to give a consistent underestimate of approximately 30% when compared with our planimetric method. In diseased muscle with abnormally shaped fibres the discrepancy is even larger; such fibres can be identified using a "form factor" which relates the area of a cell to its perimeter. This rapid, accurate and flexible system is also suitable for the measurement of many different types of graphical record.

Seventeen volunteers performed unilateral strength-training of the quadriceps with high-resistance, low-repetition, dynamic exercise, thrice weekly for an average of 5 weeks. Both before and after the training period, bilateral measurements were made of isometric quadriceps strength, quadriceps cross-sectional area (by ultrasound scanning), and thigh circumference. There were no significant changes in the untrained thighs. The trained quadriceps increased their isometric strength by more than they changed their cross-sectional area (mean increments = 15% and 6% respectively). Quadriceps hypertrophy was underestimated by measurements of thigh circumference and could not be predicted from them. We conclude that studies of localized muscle growth require direct measurements of the size of the muscle(s) concerned. Nevertheless, these may still underestimate the improvements in strength produced by high-resistance training.

Case studies are presented for two patients, one with isolated hGH deficiency and one with multiple hormone deficiencies. The patients were studied 3 months before, and 3 and 9 months after discontinuing hGH therapy, at 19 and 18 years of age, respectively. Strength in the quadriceps femoris, cross-sectional area of the quadriceps muscles and cross-sectional muscle fibre area were measured. In the patient with multiple hormone deficiencies, clear decreases in all three parameters were evident after discontinuing hGH treatment. There were no significant changes in the other patient. Reasons for these differences are discussed.

Longitudinal data on changes in the concentrations of plasma inorganic phosphorus and plasma alkaline phosphatase activity in 23 girls and 44 boys during the adolescent growth spurt are reported together with the height velocities, ages and sexual maturity ratings. The average age at the peak of the growth spurt was 12.5 years in the girls and 14.1 years in the boys with mean annual height gains of 7.0 and 9.7 cm/year respectively. In both sexes, plasma alkaline phosphatase activity rose and fell with the growth velocity during the growth spurt. Plasma inorganic phosphorus rose to reach a peak in the 4 months before the peak of the growth spurt in height; this rise was statisically significant in the boys but not in the girls. Values subsequently fell rapidly towards the normal adult concentrations. Plasma calcium, total protein, and albumin concentrations were also followed during this time, but were not at any point significantly different from normal adult values. These findings provide a guide for the interpretation of plasma biochemistry in adolescent patients.

Muscle breakdown and repair were measured by metabolic balance techniques in a patient with polymyositis who was being treated with prednisolone and azathioprine. Changes in body muscle mass that had been estimated from nitrogen and phosphorus balances correlated with antropometric assessments of thigh muscle mass and quadriceps strength. Decline in muscle strength was associated with a net rate of muscle breakdown of 148 g/day. Recovery was associated with a net rate of muscle repair of up to 100 g/day. Early reduction in corticosteroid treatment appeared to enhance the rate of repair. Changes in the isometric contraction force of the quadriceps muscle (but not in clinical symptoms, plasma creatine kinase [CK] or erythrocyte sedimentation rate [ESR] were found to reliably indicate whether the muscle was in a state of breakdown or repair. Treatment of the individual patient may be quantitatively monitored by metabolic balance studies or, more simply, by measurement of muscle strength.

Checking catecholamine stability in whole blood, plasma, and platelets, we found that specimens stored at room temperature or frozen for periods ranging from 1.5 h to three weeks show no significant difference in measured catecholamine concentration. The implications of these findings are discussed.

The natural variability of plasma creatine kinase activity has been examined in patients suffering from muscular dystrophy and in normal subjects. The coefficient of variation of the plasma creatine kinase activities was found to be large (approximately 35%) in both patients with Duchenne muscular dystrophy and normal control subjects. A comparison of the plasma activities of creatine kinase with other muscle-derived enzymes suggests that the cause of this variability is changes in the release of enzymes from muscle. Data obtained concerning the effect of physical activity on plasma creatine kinase activity are contradictory, but several young patients with Duchenne muscular dystrophy and a very high creatine kinase activity (greater than 5000 IU/liter) showed a decreased activity following admission to hospital. An estimate of the rate of efflux of certain kinase from muscle has been made, indicating that young ambulant patients with Duchenne muscular dystrophy have a grossly elevated muscle creatine kinase efflux (495.0 +/- 61.3 IU/kg muscle/hr) compared to control subjects (1.4 +/- 0.5 IU/kg muscle/hr).

The effects of eccentric exercise have been examined in human calf and biceps muscles. Release of muscle creatine kinase and uptake of technetium pyrophosphate have been followed for up to 20 days after the exercise and the results are related to the morphological changes seen in needle biopsy samples. The response to exercise was variable, all subjects developing pain and tenderness in the exercised muscles after 1-2 days and this was followed, in most subjects, by a large increase in plasma creatine kinase 4-6 days after the exercise. This was paralleled by an increased uptake of technetium pyrophosphate into the exercised muscle. Biopsies of the affected muscles showed little or no change in the first 7 days after the exercise but later degenerating fibres were seen, as well as infiltration by mononuclear cells and eventually, by 20 days, signs of regeneration. Very extensive changes were seen in the calf muscle of one subject; changes in the biceps were qualitatively similar but not so severe. In the severely affected calf muscle type II fibres were preferentially damaged. Mononuclear cell infiltration both between and within degenerating fibres was maximal well after the time of peak plasma creatine kinase and it is likely that in eccentrically exercised muscle infiltrating mononuclear cells act to scavenge cellular debris rather than to cause damage to the muscle.

A study of the neuromuscular features of acromegaly was performed in six patients. Clinical assessment was supplemented by quadriceps force measurements, plasma creatine kinase (CK) activities, electromyography (EMG) and nerve conduction studies. Muscle mass was measured by urinary creatinine/height indices (CHI) and cross sectional area (CSA) of thighs and calves on computed tomography. Quadriceps force/unit cross sectional area was derived. Needle biopsies of vastus lateralis were studied by histochemical and ultrastructural methods. Mean fibre area (MFA) and fibre type proportions were measured. Most of the subjects studied had muscle pain and proximal muscle weakness confirmed by quadriceps force measurements. This occurred in the absence of muscle wasting, as shown by cross sectional area measurements and normal or raised creatinine/height indices. "Myopathic" features were demonstrated by needle biopsy in half the patients and occasionally by electromyography and raised plasma creatine kinase activity. Abnormalities on needle biopsy included variation in fibre size, type 2 fibre atrophy and large type 1 MFA relative to type 2 MFA. Electronmicroscopy showed the non-specific findings of increased glycogen accumulation, excess lipofuscin pigment and myofilament loss.

Needle biopsies from vastus lateralis in untreated hypothyroid patients with muscle weakness confirmed by quadriceps force measurements (n = 11) were repeated when the patients had taken L-thyroxine for a mean period of 9.2 months (range 5.3-13.3 months, n = 8) and had been continuously biochemically euthyroid for a mean period of 4.9 months (range 2-11 months). Biopsies were analysed biochemically for mitochondrial function. On light microscopy, histochemical examination, mean fibre areas and fibre percentages of type I and type II fibres were determined. Electronmicroscopy was also performed. Abnormalities on light microscopy occurred in eight patients of which type II fibre atrophy was the commonest and of the remainder two patients showed a myopathic electromyogram (EMG) and a raised plasma creatine kinase activity and one ultrastructural change on biopsy. After treatment resolution of pathological changes was often slow and half the patients had persistent abnormalities when rebiopsied. The type I mean fibre area was significantly increased in the eight hypothyroid females (p less than 0.05) and type II mean fibre areas tended to be low and in females this was significant (p less than 0.05). After treatment the type I mean fibre area was significantly reduced (p = 0.05). The type II mean fibre area also tended to fall but this was not significant (p greater than 0.05). No change in the fibre percentages occurred. A myopathic EMG, a raised plasma creatine kinase activity, ultrastructural changes and low mitochondrial enzyme activities on needle biopsy were other common findings and their significance is discussed.

By means of ultrasound scanning, bilateral measurements of the cross-sectional area of the quadriceps muscle groups were made in 14 young adults with unilateral thigh muscle wasting after knee injury. Needle biopsy specimens from the lateral mass of the muscle were used to estimate the myofibre cross-sectional area for both quadriceps of each subject. 2. The cross-sectional area of the quadriceps of each patient's injured limb was always smaller than that of the contralateral muscle. The wasting was largely localized to the quadriceps, with relative sparing of the other thigh muscles. 3. None of the biopsies showed any abnormality apart from the reduction in fibre size. In each case, the injured limb's reduced quadriceps cross-sectional area was associated with a reduced mean fibre area. 4. The ratio of the cross-sectional area of a muscle to its mean fibre area is a reduced mean fibre area. 4. The ratio of the cross-sectional area of a muscle to its mean fibre area is a function of the number of fibres it contains. The ratio varied considerably from patient to patient but there was close agreement between the values obtained for the two limbs of each patient. 5. The quadriceps wasting produced by knee injury was due to muscle fibre atrophy. There was no evidence for a change in the number of fibres in the muscle.