Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A previously unrecognized autosomal dominant syndrome affecting oral, nasal, vaginal, urethral, anal, bladder, and conjunctival mucosa with cataracts, follicular keratosis, nonscarring alopecia, and terminal lung disease is described in a four-generation kindred of German extraction. Severe photophobia, tearing, and nystagmus in infancy heralds the development of keratitis, corneal vascularization, and lens cataracts. Repeated corneal transplants have failed. Red, periorificial mucosal lesions involving the above structures are noted by 1 year of age and may persist throughout life. Chronic rhinorrhea and repeated upper respiratory infections frequently progress to bilateral pneumonia accompanied by loss of hair, diarrhea, occasional melena, enuresis, pyuria, and hematuria. Spontaneous pneumothorax is frequent, terminating in fibrocystic-type lung disease and cor pulmonale. Women have had repeated abnormal vaginal PAP smears. Histologically the mucosal epithelium shows dyshesion, thinning of the epithelial layer, and dyskeratosis. Mucosal PAP smears show lack of epithelial maturation, cytoplasmic vacuoles and inclusions, and individual cell dyskeratosis. Histochemically there is a lack of cornification and keratinization. Ultrastructural studies show lack of keratohyalin granules, a paucity of desmosomes, intercellular accumulations, cytoplasmic vacuolization, and formation of bands and aggregates of filamentous fibers and structures in the cytoplasm resembling desmosomes and gap junctions. The condition is probably a panepithelial cell defect of desmosomal and gap junction structure most prominently affecting mucosal epithelia associated with an increased susceptibility to a variety of adventitious organisms.
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PMID:Hereditary mucoepithelial dysplasia: a disease apparently of desmosome and gap junction formation. 48 50

A 15-year-old girl with idiopathic intestinal pseudoobstruction is reported. She presented with a long term history of low grade obstructive symptoms, diarrhea, and poor nutrition culminating in an acute obstructive attack leading to exploratory laparotomy. At surgery, the small bowel and colon were dilated, with no mechanical obstruction found. Further evaluation revealed her to have a diffuse disorder of gastrointestinal smooth muscle function involving esophagus, small bowel, and colon. Because medical management failed to control symptom, a gastrojejunostomy was done to bypass a megaduodenum. A third laparotomy was necessary 2 months later because of intractable obstructive symptoms. At this last laparotomy, the afferent loop was taken down and a duodenoplasty and duodenojejunostomy were performed, resulting in clinical improvement. Light and electron microscopic study of the excised small intestine showed marked thinning and degeneraton of the smooth muscle, with replacement by fibrous tissue. The myenteric plexus was normal. This case demonstrates that a degenerative disease of smooth muscle may be one cause of idiopathic intestinal pseudoobstruction.
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PMID:Studies of idiopathic intestinal pseudoobstruction. I. Hereditary hollow visceral myopathy: clinical and pathological studies. 87 34

The rapid-cycling variant of bipolar disorder constitutes about 15%-20% of all bipolar patients, and 72%-82% of these patients exhibit less than adequate response to lithium therapy. Valproate's spectrum of efficacy was examined in 78 patients with rapid-cycling bipolar disorder in a prospective, open, 15.8-month trial. Thirty patients received valproate monotherapy and 48 received combination therapy. Treatment assignment was nonrandomized and based on prior treatment history. A marked acute response was seen in 54% of the patients with mania, 87% of those with mixed states, and 19% of those with depression. Marked prophylactic responses were seen in 72% of manic patients, 94% of mixed states patients, and 33% of depressed patients. In addition, moderate acute antimanic responses were observed in another 31% of the patients, prophylactic antimanic responses in 17%, acute antimixed state responses in 0%, prophylactic antimixed state responses in 0%, acute antidepressant responses in 25%, and prophylactic antidepressant responses in mixed states in 34%. Pattern analysis was conducted to examine the spectrum of efficacy of valproate in various cells (e.g., the cohort of patients who had an acute antimanic response to the drug). Pattern analysis showed that 40% of the patients with a marked prophylactic antimanic response had a marked antidepressant response to valproate. However, among the patients with a marked antidepressant response to valproate, 91% had a marked antimanic response. The most common side effects of valproate in our study, as in earlier studies, were gastrointestinal problems (nausea, stomach cramps, diarrhea), tremors, lethargy, and hair thinning.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Spectrum of efficacy of valproate in 78 rapid-cycling bipolar patients. 154 18

To study the pathophysiology of bone disorder after gastrectomy, 320 patients and 40 Wistar male rats were used. Clinically, patients who had received gastrectomy 1-15 years previously, were examined for skeletal symptoms, serum biochemistry, microdensitometry of second metacarpal bone, and 20 of them were then studied in a calcium infusion test. Using microdensitometry, abnormality of bone metabolism was observed in 38% of the patients. In severe cases, a significant decrease of serum Ca. and increase of alkaline phosphatase were observed (p less than 0.05), 65% complained of joint pain. In the calcium infusion test, severe cases showed a low urinary excretion of Ca, like osteomalacia, and unlike osteoporosis. Experimentally, body weight & amount of food intake decreased and fatty diarrhea was observed in rats after total gastrectomy. Skeletal changes including thinning of the cortex, loss of medullary trabeculation & decrease of bone ash and biochemical changes such as low serum Ca. 25(OH)D3, 24, 25(OH)2D3 and high iPTH levels were observed. Also the bone formation rate was lower than control as detected by tetracycline double labelling method. As low food intake & fatty diarrhea after gastrectomy which result in Ca. & vit. D insufficiency may be the major etiology of bone disorder.
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PMID:[Bone disorder after gastrectomy--clinical & experimental studies]. 226 41

In seven calves we studied experimental invasions by sporocysts of the Sarcocystis cruzi (S. bovicanis) species, isolated from faeces of dingo dogs. Out of clinical changes, an increase in body temperature to 39.6 to 40.5 degrees C is characteristic in the fourth to the eighth week of disease, relaxed attitude of animals, progressive thinning down, anaemia of mucous membranes, diarrhoea and total dehydration. The post-mortem examination completes this observation with generalized hyperplasia of lymphatic nodes to haemorrhagic lymphadenitis and small petechial haematomata on serous coats, particularly on epicardium. Schizonts in the endothelium of capillaries in various organs were evaluated as specific lesions, demonstrated within 26 days from invasion in one calf. From 46 days after invasion we found muscular cysts in three other calves. The titres of sera in all experimental calves obtained with the NFR method are also evaluated as specific. Invaded calves died gradually between the 26th and 59th day, control calves were slaughtered and no sarcocysts were found.
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PMID:[Development of sarcocystosis in experimentally infected calves]. 391 81

Twenty-six patients with metastatic colorectal adenocarcinoma were entered into a Phase I-II study of 5-fluorouracil (5-FUra)-high-dose leucovorin (CF). The starting dose of 5-FUra was 300 mg/sq m with escalation to 750 mg/sq m/week in 6 doses given by rapid i.v. injection midway during a 2-hr infusion of CF, 500 mg/sq m. Partial responses were seen in 9 of 23 patients (6 of 12 who had had previous 5-FUra). Complete normalization of liver enzymes was seen in two of these patients. Side effects were seen sporadically with 5-FUra doses up to 600 mg/sq m. At a 600-mg/sq m 5-FUra dose, 8 of 18 patients had diarrhea, and 2 of 18 had white blood cell counts less than 3000/microliter. At a 750-mg/sq m dose of 5-FUra, 6 of 11 patients had severe diarrhea and 6 of 11 had white blood cell counts less than 3000/microliter. Other toxicities were mild conjunctivitis and lacrimation, thinning of the nails, and alopecia. In bioavailability studies of CF p.o., no plasma CF could be detected. After CF i.v., mean plasma peak was 111.3 +/- 40.3 (S.D.) microM. 5-FUra-CF appears to be effective in patients clinically resistant to 5-FUra. This study is being extended to randomized trial of 5-FUra-CF versus 5-FUra alone.
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PMID:Phase I-II trial of high-dose calcium leucovorin and 5-fluorouracil in advanced colorectal cancer. 633 82

We report three patients with intestinal microvillous dystrophy, two of whom were siblings. The relatively delayed clinical presentation and the lack of classical microvillous inclusions distinguish these cases from the previously described microvillous inclusion disease (MVID). There appears to be an underrecognized spectrum of microvillous disorders leading to fatal intractable secretory diarrhea in infants. In our three cases the diagnosis was suggested by periodic acid-Schiff (PAS) and alkaline phosphatase preparations of a jejunal biopsy specimen showing thinning or absence of brush border staining, which was confirmed by electron microscopy. The latter showed poorly developed and haphazardly arranged microvilli with intracytoplasmic vesicular bodies but no true inclusions. As in MVID, the prognosis of intestinal microvillous dystrophy is poor. The occurrence of the disease in two siblings of consanguinous parents suggests an autosomal recessive inheritance, and like MVID, genetic counselling of affected families is essential.
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PMID:Intestinal microvillous dystrophy: a variant of microvillous inclusion disease or a new entity? 767 89

The role and adverse effects of methotrexate in the treatment of chronic corticosteroid-dependent asthma are discussed. Methotrexate is a folic acid antagonist that has been used as an anti-inflammatory agent in the treatment of arthritis. It also appears to be effective in reducing the corticosteroid requirements in patients with chronic corticosteroid-dependent asthma, a use that was first reported in 1986. Studies of this use of methotrexate in adults support a trial of methotrexate in patients with severe asthma who have been unable to discontinue corticosteroid use despite aggressive management of their asthma and who are experiencing severe corticosteroid toxicity. Experience with methotrexate in children with asthma is limited to case series. Adverse effects associated with the use of methotrexate for treatment of corticosteroid-dependent asthma include nausea, elevated serum aminotransferase, diarrhea, and thinning of hair. While methotrexate appears to reduce corticosteroid requirements in patients with chronic corticosteroid-dependent asthma, its role in asthma therapy still needs to be clarified.
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PMID:Methotrexate for the treatment of chronic corticosteroid-dependent asthma. 825 56

Whereas T lymphocytes are essential for the initiation of acute graft-versus-host disease (aGVHD), it is not at all clear whether they or other cells or noncellular factors actually mediate the characteristic lesions. This report describes the in vivo effects of human NK cells, T cells, and cytokines on the induction of aGVHD in 4 Gy sublethally irradiated C.B-17 scid/scid (SCID) mice. Human NK and T lymphocytes were obtained separately by antibody- and complement-mediated negative selection from the peripheral blood of normal donors and expanded in medium containing rIL-2 and irradiated autologous feeder cells. The characteristics of the two groups of cells were analyzed before injection into SCID mice. Cytofluorometric phenotyping demonstrated that 70-95% of NK-enriched cells expressed CD3-, CD16+, CD56+, and CD8-dim+; ninety-seven per cent of T cells expressed CD3+, TCR-alpha/beta+, CD4+, or CD8-bright+. Analysis of K562 and Daudi cultured target cell lines demonstrated 40-50% higher cytotoxicity by NK-enriched cells as compared with activated T lymphocytes. TNF-alpha cytokine production was greatly increased in activated NK cells (250 pg/ml) as compared with T cells (25 pg/ml) and fresh PBMC (12.5 pg/ml). IFN-gamma was increased in both NK and T cells. After i.v. injection of 1-5 x 10(7) cells into irradiated SCID mice, minor to severe skin lesions, diarrhea, and weight loss occurred in NK- but not the T cell-injected animals. In NK-injected animals, thinning and focal loss of epithelium with pyknotic nuclear change and degeneration and loss of skin appendages were observed. Single cell necrosis, crypt abscess formation, and loss of glandular epithelium developed in the colon of NK but not in T cell-injected animals. These findings are very similar to allogeneic aGVHD in SCID mice injected with C57BL/6 mouse splenocytes. Immunohistological staining with anti-human CD56, CD3, TNF-alpha, and IFN-gamma antibodies demonstrated CD56+ cells in association with TNF-alpha and IFN-gamma secretion in the bowel of NK-injected animals. CD3+ cells were not found in the same tissues. These findings were not observed in T cell-injected and control mice. In summary, aGVHD-like lesions were induced by transplantation of xenogeneic human activated NK cells into SCID mice. We hypothesize that cytokines released from human NK cells play a central role in the pathogenesis of clinical aGVHD.
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PMID:Acute graft-versus-host-like disease induced by transplantation of human activated natural killer cells into SCID mice. 835 98

Controlled clinical trials in renal transplantation have demonstrated that mycophenolate mofetil is well tolerated and has lower renal transplant rejection rates than azathioprine regimens. This study reports on the clinical experiences at two institutions with mycophenolate mofetil (MMF) for severe lupus nephritis. Twelve patients with relapsing or resistant nephritis previously treated with cyclophosphamide therapy and one patient who refused cyclophosphamide as initial therapy for diffuse proliferative nephritis but accepted MMF were included. During combined MMF/prednisone therapy, serum creatinine values remained normal or declined from elevated values: mean change in serum creatinine was -0.26+/-0.46 microM/L, P = 0.039. Proteinuria significantly decreased: mean change in urine protein-to-creatinine ratios was -2.53+/-3.76, P = 0.039. Decreased serum complement component C3 and elevated anti-double-stranded DNA antibody levels at baseline improved in some, but not all, patients. The mean initial dose of MMF was 0.92 g/d (range, 0.5 to 2 g/d). The mean duration of therapy was 12.9 mo (range, 3 to 24 mo). Adverse events included herpes simplex stomatitis associated with severe leukopenia (n = 1), asymptomatic leukopenia (n = 2), nausea/ diarrhea (n = 2), thinning of scalp hair (n = 1), pancreatitis (n = 1), and pneumonia without leukopenia (n = 1). Recurrence of the pancreatitis led to discontinuation of MMF in this patient; all other adverse events resolved with dose reduction. It is concluded that MMF is well tolerated and has possible efficacy in controlling major renal manifestations of systemic lupus erythematosus. Controlled clinical trials are needed to define the role of MMF in the management of lupus nephritis.
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PMID:Mycophenolate mofetil therapy in lupus nephritis: clinical observations. 1020 68


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