Atypical imaging features of multiple sclerosis lesions include size >2 cm, mass effect, oedema and/or ring enhancement. This constellation is often referred to as 'tumefactive multiple sclerosis'. Previous series emphasize their unifocal and clinically isolated nature, however, evolution of these lesions is not well defined. Biopsy may be required for diagnosis. We describe clinical and radiographic features in 168 patients with biopsy confirmed CNS inflammatory demyelinating disease (IDD). Lesions were analysed on pre- and post-biopsy magnetic resonance imaging (MRI) for location, size, mass effect/oedema, enhancement, multifocality and fulfilment of Barkhof criteria. Clinical data were correlated to MRI. Female to male ratio was 1.2: 1, median age at onset, 37 years, duration between symptom onset and biopsy, 7.1 weeks and total disease duration, 3.9 years. Clinical course prior to biopsy was a first neurological event in 61%, relapsing-remitting in 29% and progressive in 4%. Presentations were typically polysymptomatic, with motor, cognitive and sensory symptoms predominating. Aphasia, agnosia, seizures and visual field defects were observed. At follow-up, 70% developed definite multiple sclerosis, and 14% had an isolated demyelinating syndrome. Median time to second attack was 4.8 years, and median EDSS at follow-up was 3.0. Multiple lesions were present in 70% on pre-biopsy MRI, and in 83% by last MRI, with Barkhof criteria fulfilled in 46% prior to biopsy and 55% by follow-up. Only 17% of cases remained unifocal. Median largest lesion size on T2-weighted images was 4 cm (range 0.5-12), with a discernible size of 2.1 cm (range 0.5-7.5). Biopsied lesions demonstrated mass effect in 45% and oedema in 77%. A strong association was found between lesion size, and presence of mass effect and/or oedema (P < 0.001). Ring enhancement was frequent. Most tumefactive features did not correlate with gender, course or diagnosis. Although lesion size >5 cm was associated with a slightly higher EDSS at last follow-up, long-term prognosis in patients with disease duration >10 years was better (EDSS 1.5) compared with a population-based multiple sclerosis cohort matched for disease duration (EDSS 3.5; P < 0.001). Given the retrospective nature of the study, the precise reason for biopsy could not always be determined. This study underscores the diagnostically challenging nature of CNS IDDs that present with atypical clinical or radiographic features. Most have multifocal disease at onset, and develop RRMS by follow-up. Although increased awareness of this broad spectrum may obviate need for biopsy in many circumstances, an important role for diagnostic brain biopsy may be required in some cases.

Research data indicates a persistence of elevated muscle glycogen concentration 3 days post-supercompensation in resting athletes. This study expands our earlier findings by determining whether muscle glycogen remains elevated 3, 5, or 7 days post-supercompensation. Seventeen trained male cyclists underwent one bout of exhaustive exercise to deplete muscle glycogen. This was followed by a 3-day consumption of a high carbohydrate/low protein/low fat diet (85:08:07%). Three post-loading phases followed with subjects randomly assigned to either a 3-day, 5-day, or 7-day post-loading maintenance diet of 60% carbohydrate and limited physical activity. Biopsies (50-150 mg) of the vastus lateralis were obtained pre-load (BASELINE), at peak-load (PEAK), and either at 3-day, 5-day, or 7-day post-load (POST). On average, PEAK to POST muscle glycogen concentrations decreased 34, 20 and 46% respectively for the 3-, 5-, and 7-day POST groups. Only the 7-day post-load group's PEAK to POST mean muscle glycogen concentration decreased significantly. In addition, multi-regression analysis indicated that the PEAK glycogen level was the main determinant of the number of days that glycogen levels remained significantly greater than BASELINE. Thus, trained athletes-supercompensated glycogen levels can remain higher than normal for up to 5 days post-loading. The amount of carbohydrate consumed, the level of physical activity, and the magnitude of the glycogen supercompensation determine the interval for which the glycogen levels are elevated.

The aims of the present investigation are fourfold: (i) to review the range of non-invasive methods that may be used to diagnose acute cardiac allograft rejection; (ii) to review the use of the bioptome in sampling the donor heart endomyocardium; (iii) to review the light microscopic and histological grading of acute cardiac rejection; (iv) to characterise the mononuclear populations in endomyocardial biopsy samples and correlate the findings with the light microscopic appearances of the same biopsy specimens.

Sarcoidosis is a multisystem, inflammatory granulomatous disease that rarely involves breast tissue. The pathophysiology of this chronic granulomatous condition is not well understood but is thought to be multifactorial, involving environmental influences causing an amplified immune response. A key histomorphology feature in sarcoidosis is the presence of non-necrotizing granulomas. In this case, we report a 41-year-old African-American man with a known history of sarcoidosis of the lung who presented with gynecomastia and bilateral breast tenderness with palpable nodules. Subsequent biopsy and microscopic examination of the breast nodules revealed diffuse involvement with non-necrotizing granulomas in both breasts. A final diagnosis of extensive sarcoidosis involving breast tissue was rendered after excluding other causes of non-necrotizing granulomas. The patient underwent a bilateral mastectomy to remove the breast nodules. This case discusses sarcoidosis involving an unusual site.

The purpose of this investigation was to determine the effects of a four day creatine load and simultaneous energy restriction on muscle creatine content, exercise performance, and body composition in 24 male recreational resistance trainers, age 18-26. Sixteen subjects were randomly divided into placebo (Pl, n=8) and creatine supplement (CrS, n=8) groups. Control (C, n=8) subjects of the same age were recruited separately g à d-1 to complete the performance and body composition tests while consuming their normal diet. The CrS group was administered 20 g à d-1 of creatine monohydrate (Cr) mixed with 5 g à d-1 of sucrose, while the Pl group was administered 25 of sucrose. Both CrS and Pl consumed a formula diet of 75.3 kJ (18 kcal) à kg-1 à d-1 for 4 d. Testing before and after energy restriction consisted of a repeated sprint cycle performance test (10 sprints of 6s, with 30s rest), hydrostatic weighing, and resting needle muscle biopsy. Testing revealed that subjects in CrS and Pl demonstrated significant decreases in body weight and % body fat (%BF) with no difference between groups. However, Pl demonstrated a significantly greater % loss in FFM (2.4 ± 0.25%) compared to CrS (1.4 ± 0.4%) (p<0.05). The muscle fuel stores of CrS and Pl responded significantly to the diet. Significant increases in muscle total Cr (p<0.01), free Cr (p<0.01), and CrP (p<0.05) of 16.5%, 16.8%, and 16% respectively were demonstrated by CrS over the energy restriction period, while Pl demonstrated significant decreases of 7.2% and 8.2% respectively in muscle total Cr (p<0.01) and free Cr (p<0.05). There were no significant differences between groups for performance during the cycle test, however, there were trends toward group by time interactions for performance enhancement in CrS relative to Pl, as total work (p=0.078) and work capacity (p=0.058) increased 3.8 ± 2.2% in CrS and decreased 0.5 ± 0.4% in Pl. It was concluded that short-term energy restriction resulted in decreased muscle Cr storage, and that Cr supplementation during energy restriction increased muscle Cr and CrP stores. Consumption of Cr allowed CrS to lose a significantly lower % FFM compared to Pl. Cr supplementation resulted in trends toward improved performance in CrS relative to Pl after energy restriction, but did not influence losses in body weight or %BF. / Master of Science

Eight competitive cyclists performed two cycling trials, one following a high carbohydrate diet (H-CHO) and the other following a low carbohydrate diet (L-CHO). Trials consisted of repeated 60s maximal effort sprints to fatigue at a workload designed to elicit 125-135% VO_2peak at 90rpm. Three min of recovery separated sprints. Muscle biopsies taken at rest (biopsy 1), 85% max interval rpm (biopsy 2), and 70% max interval rpm (biopsy 3) revealed a main effect of diet on muscle glycogen levels: 609 ± 38 HCHO vs. 390 ± 42 mmol/kgdw L-CHO at biopsy 1, 383 ± 29 vs. 252 ± 28 mmol/kgdw at biopsy 2, and 346 ± 29 vs. 196 ± 18 mmol/kgdw at biopsy 3 (p<0.01). Similar decreases in muscle glycogen (45%), creatine phosphate (CP) (35%), and sarcoplasmic reticulum (SR) Ca²⁺-uptake (56%) were shown in both trials from biopsy 1 to 3. SR Ca²⁺-release decreased by 53% in H-CHO subjects and 36% in L-CHO subjects. Total exercise time tended to be longer in H-CHO than L-CHO subjects (57.5 ± 10 vs. 42.0 ± .89min) (p=0.09). H-CHO subjects exercised significantly longer than L-CHO subjects from biopsy 2 to 3 (33.6 ± 10 vs. 18 ± 3.6min) (p< 0.05). Results suggest that fatigue from 40- 60min of intermittent 60s high intensity cycling intervals is associated with reductions in muscle glycogen, CP, and SR function, and that the latter part of performance is impaired by low muscle glycogen. These data do not support a relationship between muscle glycogen status and SR function in intermittent high intensity exercise. / Master of Science

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24993号 / 医博第5027号 / 新制||医||1069(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 滝田 順子, 教授 岩田 想, 教授 万代 昌紀 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

No description available.

No description available.