The potential of insulin-like growth factor-I as a therapeutic for the treatment of neuromuscular disorders.
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Biomedical subjects
Publications and source records attributed to E Yu.
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BACKGROUND: A prospective, single-treatment-arm, Phase I/II trial was performed to determine the tumor response to an accelerated regimen and assess the feasibility and toxic effects of this approach in patients with inoperable non-small cell lung cancer (NSCLC). METHODS: Thirty-seven previously untreated patients with inoperable NSCLC who had no evidence of metastatic disease entered the study. All patients were able to walk and had disease that was measurable or assessable. Patients with palpable supraclavicular disease and weight loss were also eligible. Radiation therapy consisted of an altered fractionation regimen with a concomitant boost technique. The original lung volume received a dose of 40 Gy in 20 daily fractions to the computerized axial tomography (CT)-defined primary tumor and mediastinal nodes. The boost dose (10 Gy) was administered concomitantly with the last five fractions of the original volume treatments, with an interfraction interval of 6-8 hours. The maximal allowed dose to the cord was 46 Gy. RESULTS: At a median follow-up of 36 months, complete response was achieved in 29% (9 of 31) of the patients and a partial response in 42% (13 of 31). The overall survival rate at 36 months was 10% (median survival time, 8 months). Survival rates were 25%, 8%, and 0% for the complete responders, partial responders, and nonresponders, respectively. Local failure alone was observed in 35.5% of all patients, local and distant failure in 42%, and distant failure only in 13%. Treatments were well tolerated, and all patients were able to complete the planned regimen. Grade 1 and 2 esophagitis occurred in 65% and 26% of the patients, respectively. The clinical condition of two patients (6%) was compatible with radiation pneumonitis. Moist desquamation of the skin occurred in two patients, but most had either mild (55%) or moderate (19%) skin erythema. Late complications have been limited to radiologically detected lung fibrosis. CONCLUSIONS: The accelerated fractionation schedule used in this trial was well tolerated with shortening of overall treatment time. Local tumor control and overall survival are similar to those resulting from conventional fractionation without an increase in normal tissue effects. These results are encouraging, and additional studies testing higher tumor doses are warranted.
To evaluate the distribution of alpha-smooth muscle actin (alpha-SMA) positive cells in various liver diseases, we undertook an immunohistochemical study of liver diseases including chronic persistent hepatitis, chronic active hepatitis, liver cirrhosis, intrahepatic cholelithiasis and hepatocellular carcinoma. As a control, fetal livers (gestational age: 22-26 weeks) showed alpha-SMA positive cells along the blood vessels of the portal area, terminal hepatic venules and at perisinusoidal spaces. Perisinusoidal alpha-SMA positive cells were bipolar shaped and had round nuclei. In chronic persistent hepatitis, a few alpha-SMA positive cells were admixed with the inflammatory infiltrates mostly along the intact limiting plate. They were also detected multifocally in a linear pattern along the dilated sinusoid. In chronic active hepatitis, very strong alpha-SMA staining was detected at the site of piecemeal necrosis and adjacent lobules. A-SMA expression was decreased in some cases after interferon treatment. In cases of transplanted liver biopsies, expression of intralobular alpha-SMA was diffusely increased but showed no correlation with degree of acute rejection. Cirrhotic livers revealed strong alpha-SMA positivity in fibrous septae as well as in the perisinusoidal space of intact hepatocytes at the leading edge of fibrosis. Interlobular bile ducts were concentrically circumscribed by alpha-SMA positive cells in cases of intrahepatic cholelithiasis. In trabecular type hepatocellular carcinomas, most sinusoidal lining cells were positive for alpha-SMA. Most intralobular alpha-SMA positive cells represent, if not all, perisinusoidal cells (PSCs) which are involved in intralobular fibrogenesis in various liver diseases.(ABSTRACT TRUNCATED AT 250 WORDS)
To investigate the development of the reticular network of the thymus with aging and under pathologic conditions, we performed reticulin stains on the following samples; 5 fetal thymi (22 to 33 weeks of gestational age) and 35 postnatal thymi (less than 1 month to 33 years of age). The latter included 1 hyperplastic thymus, 4 pathologically involuted thymi and 1 physiologically involuted thymus as well as 29 normal thymi. Reticulin fibers were invariably seen along the capsule and interlobular septae of all the thymi. In fetal thymi, reticulin fibers circumscribed only cortical blood vessels and Hassall's corpuscles. Postnatal thymi from the children aged less than 1 month showed discontinuous reticulin fibers along the blood vessels of the corticomedullary junction. With aging, the amount of reticulin fibers increased and formed a "fibroreticular network(FRN)" from the branching point of the interlobular septae along the corticomedullary junction. It completely circumscribed the outer medulla in fully developed thymi. In the hyperplastic thymus, the reticular network retained its original structure. Both pathologically and physiologically involuted thymi revealed irregularly collapsed reticulin fibers. These findings suggest that the reticular network of the thymus consists of FRNs as well as capsule and interlobular septae and matures with aging before involution.
Jarcho-Levin syndrome (JLS) is a condition manifested by malformations of vertebral bodes and related ribs. There are two major subtypes spondylocostal dysostosis and spondylothoracic dysostosis, with different survival rates, associated malformations, and inheritance patterns. We have experienced an autopsy case of a premature female fetus with multiple congenital anomalies. She was 30 weeks of gestational age, born as the second baby of twins and expired shortly after birth. A post-mortem examination revealed multiple abnormalities including cervicothoracic hemivertebrae, a diminished number of right-sided ribs, and pulmonary hypoplasia with left diaphragmatic hernia. In addition, there were anomalous rotation of the foregut, unfused pancreas and anomalous drainage of the superior vena cava. Chromosomal analysis showed 46, XX, del(4)(q ter).
The DSM-IV work groups are the first to be given the opportunity to document carefully all stages of deliberations and make decisions based on carefully constructed and data-based criteria. The 5-year process has encouraged the use of detailed literature reviews and allowed members of the working groups to generate data from both MacArthur analyses and field trials to make the most appropriate decisions possible. The Substance Use Disorders Work Group was faced with a potentially infinite number of questions that could be asked. The guidelines presented at the beginning of this article, especially the focus on areas in which data are already available or might potentially be generated from a field trial, allowed our Work Group to focus on a limited number of questions. With rare exceptions, each of these areas was evaluated by the thorough literature reviews that have formed the chapters that make up this section of the Sourcebook. Our goals are relatively straightforward. It is important that clinicians, researchers, administrators, and those who will work the DSM-IV process have full access to the state of the literature that existed in the late 1980s and early 1990s, and the decision-making process that was used to address the issues that affected the DSM-IV. It is hoped that this article will not only help readers to understand both how and why the DSM-IV Substance Use Disorders Work Group made the relevant decisions, but will also encourage active research to answer more fully the potentially important questions raised in these reviews.
AutoAnalysis is a new method for detecting and quantitating the trityl cation released each cycle on automated DNA synthesizers. The trityl (dimethoxytrityl) cation is removed from the growing oligonucleotide after each base addition and is a useful measure of synthesis efficiency. The traditional absorbance method of collecting each trityl effluent with a fraction collector, followed by dilution with an acid solution and careful quantitation by UV/VIS spectroscopy is costly, tedious and prone to error. The absorbance method for trityl cation analysis must usually wait until the synthesis is complete. Interruption of a failed operation, for a variety of reasons, such as an empty reagent reservoir, is thus not possible. Taking advantage of the conductive properties of the trityl cation, immediate and real-time quantitation is now possible by integrating the total conductance of the flowing stream during the detritylation step after each nucleoside addition in DNA synthesis. A conductivity cell is mounted downstream, past the synthesis column. The conductivity signal is processed and displayed as the current average stepwise yield and overall yield. If the yield drops below a pre-set threshold value because of a failure situation, the synthesizer will interrupt, preserving reagents. AutoAnalysis allows trityl monitoring with complete automation on the Applied Biosystems Models 392 and 394 DNA/RNA Synthesizers.
We report a primary choriocarcinoma of the urinary bladder in a 63-year-old man who presented with painless hematuria. He was diagnosed as having an invasive carcinoma and underwent a total cystectomy. The tumor was diffusely hemorrhagic and occupied the dome of the bladder. Histologically, it consisted of cyto-and syncytiotrophoblasts with extensive hemorrhage. No coexisting transitional cell carcinoma component was present. By immunohistochemistry, the tumor expressed beta-hCG and low-molecular weight cytokeratin intensely while it was negative for CEA or EMA. The post-cystectomy serum beta-hCG was 237mlU/ml, and decreased later. The pertinent literature is reviewed and diagnostic criteria are discussed.
We compared the power required to achieve a retinal burn with the dye yellow laser (wavelength 577 nm) and the argon green laser (wavelength 514 nm) in 49 eyes of 38 patients with proliferative diabetic retinopathy who underwent panretinal photocoagulation. All eyes were treated with both lasers. The dye laser required on average 35.7% less power to achieve a retinal burn than the argon laser (p = 0.0001). With both lasers more power was needed in patients older than 55 years than in those aged 55 years or less and in patients with light skin versus those with dark skin (p less than 0.02). The lower power required with the dye yellow laser allows facilitated photocoagulation in patients in whom treatment with the argon green laser would be problematic.
We report the prevalence rates for dementia and Alzheimer's disease (AD) obtained from a probability sample survey of 5,055 noninstitutionalized older persons in Shanghai, China. A two-stage procedure was used for case finding and case identification. A Chinese version of the Mini-Mental State Examination was used to determine cases of possible dementia. Three different cutoff points on this mental status test were used depending on the respondent's level of education. Clinical evaluations, based on functional assessments and psychiatric interview, medical and neurological examinations, three standardized mental status tests, and a selected group of psychometric tests, were made in the second stage of the study to ascertain the clinical diagnosis of dementia and AD utilizing the Diagnostic and Statistical Manual for Mental Disorders, edition 3 and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, respectively. The prevalence rate of dementia in persons 65 years and older was 4.6%. Clinically diagnosed AD accounted for 65% of the subjects with dementia. These findings indicate that the prevalence of dementia in Shanghai is very much higher than figures published earlier for China and Japan, and at the lower part of the range of values reported for community residents in the United States and other Western countries, but less than half of that reported in the recently published survey of the elderly in East Boston. Increasing age, gender (female), and low education are each highly significant and independent risk factors for dementia. One hypothesis to explain the increased prevalence in elderly women who had received no formal education invokes the possibility of an effect of early deprivation, perhaps lowering brain "reserve," allowing the symptoms of dementia to appear at an earlier date during disease progression.
Partial exchange transfusions are performed in sickle cell patients for a variety of reasons. An algorithm to plan a nonautomated exchange in patients with sickle cell syndromes was developed and validated by a study of 40 such procedures. Formulas that can be used to explore alternatives, by assessing at any point during the exchange the current concentration of sickleable cells and the hematocrit, were devised: a computer program in BASIC is available for maximum versatility. The two most important determinants of the exchange are the patient's initial hematocrit and the desired final concentration of sickleable cells; the rate and type of exchange (continuous or discontinuous) are not important. The final hematocrit depends on the type of blood product used. An exchange can be performed with packed red blood cells (PRBC), whole blood (or its equivalent, PRBC reconstituted with albumin), or it can be started with PRBC and continued with whole blood. Whole blood decreases the concentration of sickeleable cells rapidly and increases the hematocrit slowly; it does not markedly increase the viscosity. PRBCs decrease the concentration of sickleable cells more slowly and increase the hematocrit faster; thus, they may increase the blood viscosity to dangerous levels.
The effects of various eicosanoids on cytoplasmic calcium and the release of amylase were examined in isolated rat parotid cells. Arachidonate and several of its metabolites increased amylase release and elevated cytoplasmic calcium. Melittin, a stimulator of arachidonate mobilization, and lyso-phosphatidylcholine also released amylase and elevated calcium. These results suggest that the metabolites of arachidonate may have an important role in amylase secretion.
The Mini-Mental State Examination of Folstein et al was translated into and culturally adapted to Chinese and Finnish and used in dementia surveys involving probability samples of 2187 Shanghai elderly, aged 65 to 74 years, and 525 Finns of the same age group. The mean scores of these two groups were statistically different owing to the lower scores of Shanghai subjects who had no formal education. When this subset of 579 subjects was eliminated from the analysis, the distribution of total scores was almost identical in the two populations, suggesting that the Mini-Mental State Examination can be used in disease populations, provided education is taken into account. However, there remained cultural differences in regard to individual test items; the Chinese had better recall but did not do as well as Finnish or US subjects when asked to copy a figure.
A dementia screening survey was carried out in Shanghai using a culturally adapted Chinese version of the Mini-Mental State Examination. A probability sample of 5055 community-dwelling elderly in Shanghai was surveyed, 1497 aged 55-64, 2187 aged 65-74, and 1371 aged 75 and over. In the 73.3% of the subjects who had gone to school, using the age and education adjustments suggested by Kittner et al. (1986), [Kittner et al. J Chron Dis 39: 163-170; 1986] suitable cutoff scores could readily be selected to identify the subjects who should be examined intensively for the presence of dementia. However, in the 26.7% who had not gone to school, there was a significant increase in low scores on the mental status test as well as a different error pattern, reflecting the lack of formal education. Methods for following cognitive changes in illiterate individuals need further development.
1. We previously reported that parotid gland secretion is decreased in rats deprived of vitamin D (Glijer, Peterfy & Tenenhouse, 1985). In the present study we examine whether this effect is a direct result of the absence of vitamin D or due to the secondary systemic effects of vitamin D deficiency. 2. Offspring of rats maintained on a calcium-supplemented (1.2%), vitamin-D-deficient diet were weaned onto the same diet and examined after 8 weeks. Using this method it was possible to maintain serum calcium and parathyroid hormone concentrations within normal limits. Serum 25-hydroxyvitamin D (25(OH)D3) was not detectable, but 1,25-dihydroxyvitamin D (1,25(OH)2D3) concentrations were normal. 3. Pilocarpine-stimulated flow of parotid saliva was reduced 57% in vitamin-D-deprived animals, but amylase secretion was unchanged. Treatment with vitamin D3 returned flow rates to normal. 4. The concentration of calcium in parotid saliva was normal in vitamin-D-deprived rats, although total parotid calcium output was reduced 57%. 5. Pilocarpine-stimulated salivary flow from submandibular gland, a tissue which does not possess 1,25(OH)2D3 receptors, was normal in vitamin-D-deprived rats. 6. Heart rate and arterial blood pressure changes in response to I.V. pilocarpine administration were identical in normal and vitamin-D-deficient rats. 7. Auriculotemporal nerve-stimulated flow of parotid saliva was also reduced by 50% and administration of vitamin D3 to these rats corrected this abnormality. 8. It is concluded that fluid and electrolyte secretion from parotid gland is directly dependent on vitamin D; abnormal parotid gland function seen in vitamin-D-deficient rats is not due to secondary hypocalcaemia or hyperparathyroidism, nor can it be explained by haemodynamic changes evoked during systemic administration of pilocarpine. We further conclude that the metabolite of vitamin D responsible for this effect is not 1,25(OH)2D3.
Sixteen patients with various types of cancer who developed pain along the axial spine were prospectively studied by magnetic resonance imaging (MRI). The studies were performed with a Fonar Beta-3000 (Fonar Co., Melville, NY) permanent magnet operating at 0.3 Tesla (T). Detailed neurologic examinations were followed by bone x-rays, bone scans, and MRI. In 12 patients there were focal neurologic findings. Bone x-rays and bone scans were diagnostic for metastatic disease in 10 cases; MRIs were consistent with metastatic spinal-epidural disease in all 16 patients. Magnetic resonance imaging revealed bone involvement in three patients whose x-rays and bone scans were both negative indicating a higher degree of sensitivity. In six patients thecal compression was obvious on MRI; in three of these previous myelograms had been interpreted as negative. These early results suggest that MRI can serve as a useful tool for diagnosing early spinal-epidural metastases.
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We reviewed the clinical and roentgenographic findings of forty-seven non-unions of a fracture of the scaphoid in forty-six symptomatic patients in order to assess the incidence and severity of degenerative changes of the wrist. The duration of non-union ranged from five to fifty-three years. Three roentgenographic patterns were seen: twenty-three lesions had sclerosis, cyst formation, or resorptive changes confined to the scaphoid bone (Group I); fourteen had radioscaphoid arthritis (Group II); and ten had generalized arthritis of the wrist (Group III). The duration of Group-I non-unions averaged 8.2 years; Group-II, 17.0 years; and Group-III non-unions, 31.6 years. Fracture displacement and carpal instability correlated with the severity of degenerative changes. Lunate dorsiflexion of 10 degrees or more was a useful guide to carpal instability. Few of the forty-seven non-unions were undisplaced, stable, or free of arthritis after ten years. Based on the high probability of arthritis, we recommend that all displaced ununited scaphoid fractures be reduced and grafted, regardless of symptoms, before degenerative changes occur. Asymptomatic patients with an undisplaced, stable non-union should be advised of the possibility of late degenerative changes.