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The contractile apparatus of striated muscle in the course of atrophy and regeneration. I. Myosin and actin filaments in the denervated rat soleus.

The ultrastructure of the contractile apparatus of the rat soleus muscle during the course of denervation atrophy was investigated. It was found that the ratio of thin the thick filaments increased in myofibrils of atrophying muscle fibers. Elevation of the ratio was observed as early as the second day after denervation, and became more pronounced with the progress of atrophy. Parallel measurements of the amounts of actin and myosin in the myofibrils and in the muscle protein extracts revealed a lower proportion of myosin heavy chains to actin in the fractions from denervated muscles, compared with the control values. Both the electron-microscopic observations and the biochemical evaluation of the actin content of the muscle, suggests that the elevated ratio of thin of thick filaments seen in the course of the muscle atrophy appears as the results of an earlier and more intensive disappearance of thick filaments. Thin filaments disappeared more slowly, in parallel to the decrease in muscle weight. On the basis of the results presented a mechanism of progress of "simple atrophy" of muscle in suggested.

Actins↗

Residual insulin positivity and pancreatic atrophy in relation to duration of chronic type 1 (insulin-dependent) diabetes mellitus and microangiopathy.

The relationship of residual insulin positivity in chronic Type 1 (insulin-dependent) diabetes and atrophy of the exocrine pancreas to duration of diabetes, age at onset and microangiopathy was studied in 26 patients (disease duration 2 to 54 years, mean 26 years). Islets containing insulin cells were found in 13/26 pancreata. In 5/13 pancreata insulin positive cells were detected in only one lobule, while in 8/13 insulin positivity was multifocal. All patients with diabetes duration less than 11 years had residual insulin cells; whereas, the rate of insulin positivity was near 40% with diabetes duration of more than 11 and 21 years, respectively. Survival of insulin cells was not clearly related to age at onset. HLA-DR expression on insulin cells was seen in one case. Insulitis was lacking. Pancreatic volume determined in 18 patients ranged from 14-110 ml (age adjusted mean 56.3 ml) and was significantly less than that of control subjects (age adjusted, mean 89.9 ml, p less than 0.0001). Computerized morphometry of the exocrine pancreas revealed severe acinar atrophy due to a reduction in size of acinar cells. Acinar atrophy correlated neither with the degree of insulin positivity, disease duration nor severity of microangiopathy. The findings suggest that in about 40% of patients with Type 1 diabetes a small population of insulin cells may escape autoimmune destruction, irrespective of disease duration or age at onset. Though exocrine atrophy and insulin deficiency are associated, the variable extent of pancreatic atrophy could not be related to such factors as amount of surviving insulin cells, duration of diabetes or microangiopathy.

Aging↗

Environmental-occupational risk factors and familial associations in multiple system atrophy: a preliminary investigation.

We studied 60 patients with multiple system atrophy and autonomic failure and 60 control subjects matched for age, sex and race. Their psychosocial history, pedigree and occupation were obtained by personal interview. An inventory of autonomic and neurologic symptoms was obtained from 148 first-degree relatives of the patients and 80 controls by a self-administered questionnaire. Patients with multiple system atrophy had significantly more potential exposures to metal dusts and fumes, plastic monomers and additives, organic solvents, and pesticides than the control population. The potential exposures were determined in most subjects by their reported usual occupation. Clinical symptoms of multiple system atrophy were reported by a significantly larger group of patients' relatives than controls. These findings are possibly consistent with the hypothesis that multiple system atrophy develops as a result of a genetically determined selective vulnerability in the nervous system. Specific neuronal systems may become targets for environmental insults or toxins, and the disease state may occur when ageing neuronal systems can no longer sustain functional capacity. This preliminary study supports the need to further explore possible environmental, occupational, and familial contributions to the aetiology of multiple system atrophy.

Environment↗

Results of transplanting developing third molars as part of orthodontics space management. Part 2: results following the orthodontic treatment of transplanted developing third molars in cases of aplasia and premature loss of teeth with atrophy of the alveolar process.

MATERIAL AND METHODS: The aim of this study was to assess the effects of atrophy of the alveolar process and subsequent orthodontic treatment on the transplantation results of developing third molars. The material consisted of 35 teeth transplanted to an atrophied alveolar process. 19 of these teeth were treated orthodontically subsequent to transplantation. The control group consisted of 61 developing molars transplanted to a new extraction socket. The transplanted teeth were followed up clinically and radiographically for a mean period of 3.2 years. RESULTS: The success rate was 85% for transplants to new extraction sockets and 84% for transplants to atrophied jaw sections with subsequent orthodontic treatment. In contrast, transplants to atrophied jaw sections without subsequent orthodontic treatment showed a significantly (p < or = 0.001) lower success rate of only 37.5%. These poorer results were due to persistent infraocclusion and ankylosis. CONCLUSIONS: Even in cases with atrophy of the alveolar process, a transplantation with subsequent orthodontic treatment represents a promising treatment concept, whereas teeth without subsequent orthodontic treatment showed a lower success rate. Orthodontic tooth movement had no negative effect on the healing rates of transplanted developing third molars.

Adolescent↗

Functional correlates of callosal atrophy in relapsing-remitting multiple sclerosis patients. A preliminary MRI study.

In multiple sclerosis (MS), periventricular lesions produce atrophy of the corpus callosum (CC), as evidenced by magnetic resonance imaging (MRI). We investigated whether CC atrophy in relapsing-remitting MS patients is related to functional deficits. We compared 14 mildly disabled (mean Expanded Disability Status Scale score 2.7) relapsing-remitting MS patients with 14 age- und sex-matched controls. CC size was determined using sagittal T1-weighted MRI. The function of the CC was studied using a neuropsychological battery and neurophysiological evaluation based on visual stimulation using a divided visual field paradigm. The total area of the CC in patients (mean 5.3 cm2) was significantly (P = 0.002) smaller than in controls (mean 6.6 cm2). Patients showed left ear extinction using the dichotic listening test and impaired name learning, which was correlated with atrophy of the splenium. There were no differences in interhemispheric transfer time between patients and controls. Marked atrophy of the CC can be encountered in relapsing-remitting MS patients. The associated cerebral disconnection correlated with atrophy of expected regions of the CC, thus supporting topographical organization.

Adult↗

Prevention of denervation atrophy in muscle: mammalian neurotrophic factor is not transferrin.

Atrophy in a denervated muscle results from the disuse caused by paralysis of the muscle, and from the loss of special neurotrophic substances. Daily injections of proteins extracted from rats' sciatic nerves have been shown to prevent the non-disuse atrophy of rats' muscles denervated for 7 days. The trophic factor from chicken sciatic nerve which stimulates differentiation in aneural chick muscle in vitro has been purified and found to be closely similar to transferrin. We undertook to determine whether the trophic properties of mammalian nerve extract on denervated rats' muscles in vivo were due to the presence of serum transferrin in the extract. Atrophy was measured as the reduction in cross-sectional areas of type IIB fibers in the extensor digitorum longus muscle. Muscles denervated for 7 days and injected daily with 1 of several doses of iron-conjugated rat transferrin exhibited a rate of atrophy equivalent to that in denervated muscles that either were not treated or were injected with saline. Denervated muscles injected with crude extract of rats' sciatic nerves had significantly less atrophy than their controls. Removal of transferrin from the crude extract by immunoaffinity chromatography did not diminish its ameliorative effects on denervated muscle. Therefore, the trophic action of mammalian nerve extract on denervated rats' muscles in vivo is not due to the presence of serum transferrin in the extract.

Animals↗

Skeletal muscle myosin heavy chain expression in rats with monocrotaline-induced cardiac hypertrophy and failure. Relation to blood flow and degree of muscle atrophy.

BACKGROUND: In congestive heart failure (CHF) the skeletal muscle of the lower limbs develops a myopathy characterised by atrophy and shift from the slow to the fast type fibres. The mechanisms responsible for these changes are not clear yet. OBJECTIVES: We investigated the influence of blood flow and degree of muscle atrophy on the myosin heavy chains (MHC) composition of the soleus and extensor digitorum longus (EDL) of rats with right ventricle hypertrophy and failure. METHODS: CHF was induced in 16 rats by injecting 30 mg/kg monocrotaline. Eight animals had the same dose of monocrotaline but resulting in compensated right ventricle hypertrophy. Two age- and diet-matched groups of control animals (nine and five respectively) were also studied. The relative percentage of MHC1 (slow isoform), MHC2a (fast oxidative) and MHC2b (fast glycolytic) was determined by densitometric scan after electrophoretic separation. The relative weights of soleus and EDL (muscle weight/body weight) were taken as an index of muscle atrophy. Skeletal muscle blood flow was measured by injecting fluorescent micropheres. RESULTS: CHF and Control (Con) rats showed similar degree of atrophy both in soleus (0.40 +/- 0.06 vs. 0.44 +/- 0.06 p = NS), and EDL (0.47 +/- 0.04 vs. 0.45 +/- 0.02, p = 0.09). In CHF rats these two muscles showed a statistically significant MHCs redistribution toward the fast type isozymes. In fact in EDL of CHF rats MHC2a was 30.5 +/- 6.1% vs. 35.8 +/- 8.6% of the Con (p < 0.05). MHC2b was however higher (68.5 +/- 6.6% vs. 61.0 +/- 9.6%, p = 0.017). In the soleus of CHF rats MHC1 was decreased (87.6 +/- 3.4% vs. 91.9 +/- 5.2%, p = 0.02), while MHC2a was increased (12.04 +/- 3.5% vs. 7.9 +/- 5.2%; p = 0.028). Similar changes were not found in the muscles of the compensated hypertrophy animals. No correlation was found between MHC pattern and the relative muscle weight in the CHF animals. Soleus blood flow in CHF rats was significantly lower than that of Con (0.11 +/- 0.03 ml/min/g vs. 0.22 +/- 0.03 p < 0.05), while no differences were found in EDL (0.06 +/- 0.02 ml/min/g vs. 0.08 +/- 0.02, p = NS). CONCLUSIONS: In rats with CHF a skeletal muscle myopathy characterised by a shift of the MHCs toward the fast type isoforms occurs. The magnitude of the shift correlates neither with the degree of atrophy, nor with the skeletal muscle blood flow, suggesting that these two factors do not play a pivotal role in the pathogenesis of the myopathy.

Animals↗

Age-related thymic atrophy in the guinea pig.

We have characterized age-related thymic atrophy in the guinea pig, including identification of antibodies that allow immunohistochemical assessment of thymopoiesis. Age-related thymic atrophy in guinea pigs more closely resembles what occurs in humans histologically and in thymus weight, cellularity, and percent functional area than do other rodent models. The guinea pig model is thus particularly well-suited to study the role of the thymic perivascular space in age-related thymic atrophy. We next tested the hypothesis that dietary supplementation with Vitamin C could prevent or delay age-related thymic atrophy. Thymus histology, weight, cellularity, and percent functional area did not differ at 12 months between groups that received 3, 30, or 150 mg Vitamin C daily from 4 months of age. Thus long-term supplementation with up to 130 mg/kg/day Vitamin C is insufficient to influence the time course and extent of age-related thymic atrophy in guinea pigs.

Aging↗

Changes in facial form relative to progressive atrophy of the edentulous jaws.

The surgical and prosthodontic rehabilitation of the edentulous patient aims to restore oral function and facial form. Planning treatment requires an understanding of the effect of progressive jaw atrophy, and the concomitant effect on the soft tissues of the face. This study examined 179 Caucasians at different stages of jaw atrophy according to the Cawood and Howell classification; various standard anthropological measurements of the face, according to Farkas, were also taken. We have demonstrated that changes in the soft tissues are related to the degree of underlying jaw atrophy. This has important implications when planning surgical and prosthodontic rehabilitation of the edentulous patient. Early stages of jaw atrophy (Class II, III & IV) result in the collapse of the circumoral musculature causing a narrowing of the mouth, loss of lip support, inversion of the lips and contraction of the cheeks. Late changes of jaw atrophy (Class V & VI) result in changes in vertical facial proportion causing a decrease in lower facial height and an increase in chin prominence. These late skeletal changes accentuate the earlier soft tissue facial effects.

Adolescent↗

Does conventional HRT protect from urogenital atrophy? A prospective study.

Urogenital atrophy is a poorly defined entity. This prospective study looked at the effect of conventional HRT on urogenital atrophy. One hundred and sixty-three women were studied in a 12-month period. The incidence of urinary symptoms and clinical evidence of urogenital atrophy was found to be similar in both the 'HRT group' and the 'no HRT group'. This can be explained by the new oestrogen receptor theory. Conventional HRT does not seem to protect women from urogenital atrophy and receptor specific oestrogen therapy may be required to address the problem of urogenital atrophy and postmenopausal urinary symptoms.

Journal Article↗

Cerebral atrophy in Parkinson's disease with and without dementia: a comparison with Alzheimer's disease, dementia with Lewy bodies and controls.

Parkinson's disease is a common neurodegenerative disorder primarily characterized by rigidity, tremor and bradykinesia. Cognitive impairment and neuropsychiatric symptoms are frequent in Parkinson's disease, with a 70% cumulative incidence of dementia. The aim of this cross-sectional study was to establish the pattern of cerebral atrophy on MRI in Parkinson's disease patients with dementia. We used voxel-based morphometry (VBM) to provide an unbiased means of investigating brain volume loss. Whole brain structural T1-weighted MRI scans from Parkinson's disease patients with dementia (PDD, n = 26), Parkinson's disease patients without dementia (n = 31), Alzheimer's disease patients (n = 28), patients with dementia with Lewy bodies (DLB, n = 17) and control subjects (n = 36) were acquired. Images were analysed using SPM99 and the optimized method of VBM. Reduced grey matter volume in PDD patients compared with controls was observed bilaterally in the temporal lobe, including the hippocampus and parahippocampal gyrus, and in the occipital lobe, the right frontal lobe and the left parietal lobe, as well as some subcortical regions. Parkinson's disease patients without dementia showed reduced grey matter volume in the frontal lobe compared with control subjects. There was significant grey matter atrophy bilaterally in the occipital lobe of PDD patients compared with Parkinson's disease patients. In addition, significant temporal lobe atrophy, including the hippocampus and parahippocampal gyrus was detected in Alzheimer's disease relative to PDD. No significant volumetric differences were observed in PDD compared with DLB. Thus, Parkinson's disease involves grey matter loss in frontal areas. In PDD, this extends to temporal, occipital and subcortical areas, with occipital atrophy in PDD being the only difference between the two groups. This provides important information about the pattern of cerebral atrophy in Parkinson's disease and PDD.

Aged↗

Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes.

While brain atrophy occurs early in the clinical course of multiple sclerosis, exactly how early, which tissues are affected and the rate at which early atrophy occurs are unclear. Regional brain atrophy was investigated in 58 patients recruited within 3 months of onset of a clinically isolated syndrome (CIS) suggestive of multiple sclerosis, who were followed-up for 3 years. At 3 years, 31 subjects had developed multiple sclerosis as defined by the McDonald criteria, while 27 had not (13 had MRI-visible brain lesions and 14 did not). In those who developed multiple sclerosis, the mean decrease in grey matter fractional volume (GMF, as a fraction of total intracranial volume) was -0.017 (-3.3%) and was significantly larger than in the combined lesion-positive and lesion-negative CIS subjects [-0.005 (-1.1%), P = 0.001]. No decrease in white matter fractional volumes (WMF) was seen. Change in GMF correlated only modestly with the change in T2 lesion volume from baseline to year 3 (r = -0.428, P = 0.004). These results suggest that progressive grey matter, but not white matter, atrophy is seen in the earliest clinically observable stages of relapse onset multiple sclerosis, and this is only moderately related to lesion accumulation. Longer-term follow-up is required to determine whether early grey matter atrophy is associated with subsequent disability or cognitive impairment.

Adolescent↗

Central brain atrophy in childhood AIDS encephalopathy.

OBJECTIVE: To determine differential patterns of brain atrophy in pediatric AIDS encephalopathy. DESIGN: We measured the bicaudate, bifrontal, and ventricle-brain ratio in brain magnetic resonance imaging scans of 42 control children, nine children with progressive AIDS encephalopathy, 25 AIDS children without progressive encephalopathy, and 23 children with cerebral atrophy of other causes. RESULTS: When compared with controls, encephalopathy patients showed significantly increased bicaudate and ventricle-brain ratios, but no significant increase in bifrontal ratio, whereas children with brain atrophy from causes other than AIDS showed increases in all three ratios. CONCLUSION: Children with AIDS encephalopathy demonstrate a specific pattern of brain atrophy distinct from other etiologies: a central atrophy, primarily affecting the subcortical white matter or the basal ganglia regions.

AIDS Dementia Complex↗

Helicobacter pylori serology in chronic gastritis with antral atrophy and negative histology for Helicobacter-like organisms.

It has been suggested that there may be a correlation between Helicobacter pylori (Hp) infection and precancerous lesions of the stomach. However, histological evaluation of bacterial colonization in chronic atrophic gastritis shows a relatively low prevalence of the microorganism, which does not support the hypothesis. The aim of our study was to investigate the Hp serology in 95 patients with chronic gastritis with antral atrophy, with (27 cases) and without (68 cases) intestinal metaplasia, and without Helicobacter-like organisms in antral and corpus biopsy specimens. For all subjects, serum anti-Hp immunoglobulin IgG was identified by a fluorescent immunoenzymatic method (Helori-test; Eurospital), and mucosal atrophy and activity were graded histologically (Sydney System score). The serum Hp-antibody status documented the presence of current bacterial infections in 64 of 95 (67.4%) patients and previous infections in another 17 subjects. In only 14.7% of cases was there no evidence of current or previous infection. These subjects had less severe mucosal atrophy and lower inflammatory scores. In addition, there were no cases of intestinal metaplasia in such subjects. The high prevalence of Hp infection confirms the primary role of the microorganism in the pathogenesis of chronic gastritis with antral atrophy, although the bacterium is no longer present in the advanced stages of such disease. The histological evaluation of Hp colonization following the criteria of the Sydney System appears from our study to underestimate the true prevalence of the infection in the stomach when there is mucosal atrophy.

Adult↗

Microvascular free-flap correction of severe hemifacial atrophy.

Romberg's disease is a progressive hemifacial atrophy of unknown etiology. Microsurgical reconstruction, focusing on the correction of facial asymmetry and restoration of contour, has become the "gold standard." We report our experience with 15 patients involving 16 free-tissue transfers with a minimum of 1 year of follow-up who were treated from July of 1989 to January of 1993. All patients were classified as having severe atrophy. There were 7 males and 8 females in the series. Distribution of disease was a coup de sabre type or segmental pattern in 6 patients, whereas 9 patients had a hemifacial distribution. Fourteen patients had unilateral disease (7 right and 7 left), and 1 patient had bilateral atrophy. The average age of onset of disease was 11.9 years. The average duration of atrophy was 6.7 years. No patient was operated on with a quiescent interval of less than 2 years. Average age at operation was 28.7 years, with a range from 6 to 46 years. Follow-up ranged from 1 to 4.5 years. Two patients had facial hematomas as the only complication. No flaps were lost. Flap revisions consisting of minor contour corrections were performed in 10 patients. Limited recurrence of facial atrophy was seen in a single patient 2 years postoperatively. All patients rated their improvement as excellent. The deepithelialized extended parascapular flap with large fascial extensions of dorsal thoracic fascia is our procedure of choice. This fascia can be folded into variable thicknesses to correct subtle contour defects of the upper lip, medial canthus, eyelids, and ear that have reportedly been difficult to reconstruct.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Free anterolateral thigh adipofascial flap for hemifacial atrophy.

Though the etiology of hemifacial atrophy is still unknown, the aim of its reconstruction is cosmetic amelioration of the defect. Among many techniques introduced, microsurgical reconstruction has become the gold standard to restore the symmetry of the face. Seven free anterolateral thigh adipofascial flaps were used to reconstruct hemifacial atrophy between September 1999 and May 2005. There were 1 male and 6 females in the series. All the patients had unilateral disease (6 right and 1 left). The average age of onset of disease was 11.9 years. The average duration of atrophy was 6.7 years. The patients' average age was 25 years (range, 21 to 32 years), and the average follow-up period was 12.6 months (range, 6 to 36). The size of the transferred flap ranged from 8 x 6 cm to 12 x 13 cm. All adipofascial flaps survived completely. No complications occurred. The result is stable, and no recurrence of facial atrophy was seen in the patients after follow-up. One patient received minor revision because of the bulky reconstructed face. The esthetic appearance of the reconstructed face was acceptable. Despite a variable vascular anatomy that can give rise to some surgical challenge in raising the anterolateral thigh adipofascial flap, the authors conclude that this is a safe and reliable adipofascial flap for hemifacial atrophy.

Adult↗

Diagnostic accuracy of the serum profile of gastric mucosa in relation to histological and morphometric diagnosis of atrophy.

BACKGROUND: Histology is the gold standard for diagnosis of atrophy but is hampered by observer variation. A reliable method to overcome this issue is morphometric analysis of gastric mucosa. Serum pepsinogens and gastrin have been proposed in the diagnostic work-up of gastric atrophy although diagnostic accuracy of these tests is considered unsatisfactory. AIM: To evaluate the diagnostic accuracy of gastric serum profile in relation both to morphological and morphometric diagnosis of gastric atrophy. METHODS: Ninety-four dyspeptic out-patients underwent upper endoscopy and evaluation of serum levels of PGI, PGII and 17-gastrin. Diagnostic accuracy of gastric serum profile was tested by receiver operating characteristic curves and by evaluation of sensitivity and specificity in relation to both histology and morphometric analyses. RESULTS: As far as concern to histological evaluation, only PGI/PGII ratio showed an acceptable diagnostic accuracy in discrimination of gastric atrophy, while, when morphometric analysis was considered as reference, both serum PGI level and PGI/PGII ratio showed an excellent performance. However, both PGI and PGI/PGII ratio showed low sensitivity and high specificity. CONCLUSIONS: Serological gastric profile corresponds better with the morphometric diagnosis of atrophy, even if, because of the low sensitivity, today this could only be used as screening test of chronic atrophic gastritis.

Adult↗

Brain stem auditory evoked potentials in patients with multiple system atrophy with progressive autonomic failure (Shy-Drager syndrome).

Brain stem potentials from three groups of patients, namely those with pure progressive autonomic failure, Parkinson's disease and multisystem atrophy with progressive autonomic failure (Shy-Drager syndrome) were compared with each other and a group of normal subjects. In virtually all the patients with multisystem atrophy with progressive autonomic failure the brain stem potentials were abnormal in contrast to normal findings with Parkinson's disease. The closely associated group of patients with progressive autonomic failure alone also revealed no abnormalities of the BAEP. This separation of the two groups, Parkinson's disease and progressive autonomic failure from multisystem atrophy with progressive autonomic failure is important clinically as multiple system atrophy of the Shy-Drager type has extra-pyramidal features closely resembling Parkinsonism or a late onset cerebellar degeneration. From the abnormalities of the brain stem response in multisystem atrophy with progressive autonomic failure, it is clear that some disruption of the auditory pathway occurs in the ponto-medullary region as in nearly all patients there is a significant delay or reduction in the amplitude of components of the response generated beyond this region. The most likely area involved is the superior olivary complex.

Aged↗