Toe transplantation for reconstruction of the hand.
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Biomedical subjects
Publications and source records attributed to D B Jones.
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The eosinophilic variant of acute myelomonocytic leukemia (AMML) is highly associated with characteristic abnormalities of chromosome 16. Leukemias developing secondary to chemotherapy frequently show abnormalities of chromosomes 5 and 7. This report describes a secondary AMML, eosinophilic variant (M4Eo), developing in a patient with coexistent mycosis fungoides who had received chemotherapy, including an alkylating agent, and showing characteristic abnormalities of both chromosomes 7 and 16. This is the first reported case of the M4Eo arising secondarily in a patient treated for another hematopoietic malignancy, and the second case of treatment-induced M4Eo to show coexistent abnormalities of chromosomes 7 and 16. Additional cytochemical, ultrastructural, and cell surface marker findings are described supporting malignant transformation of the eosinophilic cell line.
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This study was performed to find the quantitative relationship between basolateral surface alterations of proximal convoluted tubules (PCT) and renal failure in 26 Fisher 344 rats receiving 20 mg/kg of gentamicin twice daily up to 28 days. They were sacrificed on day 14 (renal failure, 13 rats) and day 28 (recovering, 13 rats). Control rats were used for morphologic studies (19) and serum creatinine studies (6 of 19). PCTs (14th and 28th day) were graded as to severity with transmission electron microscopy into grades 1 (normal-mild injury), 2 (moderate injury) and 3 (severe injury) using brush border and basolateral surface alterations. Scanning electron microscopy confirmed these grades using kidney slices and isolated tubular cells. With scanning electron microscopy greater than 3400, PCTs were graded and counted from 14th and 28th day kidneys, day 14 (grade 1, 18%, grade 2, 22%, and grade 3, 60%), day 28 (grade 1, 89% grade 2, 4%, and grade 3, 7%). The basolateral surface contour lengths (BSCL) per length of underlying tubular basement membrane were measured using a computer-assisted digitizer on transmission electron microscopy prints. Control PCTs had a mean BSCL of 268 microns, SD +/- 79, SE +/- 19 per 40 microns of tubular basement membrane. Likewise, the mean BSCL of grade 1 tubules measured 249 microns, SD +/- 87, SE +/- 21; the mean BSCL of grade 2 tubules was 125 microns, SD +/- 40, SE +/- 9 and grade 3 tubules BSCL was 90.5 the BSAI values showed that the 14th day rats had 28% of control BSAI and 28th day rats 80%. 2, grade 3, p less than 0.005). Squaring the mean BSCL of each group gave a basolateral surface area index (BSAI). Combining the percentage of the 3 grades of tubules of 14th and 28th day rats with the BSAI values showed that the 14th day rats had 28% of control BSAI and 28th day rats 80%. Mean serum creatinines (milligrams/deciliters) were: 14th day, 0.86; 28th day, 0.54; and control, 0.39. These data indicate loss of function correlates with lower BSAI (decreased basolateral surface area).
Dietary calcium (CA++) supplementation attenuates gentamicin nephrotoxicity in rats. It has been proposed that this protective effect results from the ability of Ca++ to interfere with gentamicin binding to renal cell membranes. However, calcium supplementation also suppresses parathyroid hormone (PTH) activity, which may affect gentamicin nephrotoxicity by altering renal brush border phospholipid composition or renal calcium handling. We therefore compared gentamicin nephrotoxicity in PTH-stimulated control rats and parathyroidectomized (PTX) rats. Although their pretreatment serum ionized calcium concentration was significantly higher (1.27 +/- 0.01 vs. 0.88 +/- 0.06 mmol/L; P less than 0.001), PTH-stimulated rats had higher peak renal cortical gentamicin concentrations (543 +/- 20 vs. 395 +/- 49 micrograms/gm; P less than 0.025) and serum creatinine concentrations (3.0 +/- 0.8 vs. 0.9 +/- 0.3 mg/dl; P less than 0.05). Structural injury and depression of renal cortical slice uptake of p-aminohippurate were also less severe in PTX rats. Gentamicin treatment also caused increased urinary Ca++ excretion in control rats (from 2.12 +/- 0.64 mumol/mg creatinine per day [pretreatment] to 16.86 +/- 2.07 mumol/mg creatinine per day; P less than 0.001) but not in PTX rats. Control rats ingesting chow containing a standard Ca++ content (1.2%) resembled PTX rats. These results indicate that PTH stimulation exacerbates gentamicin nephrotoxicity. Increased peak renal cortical gentamicin concentrations in PTH-stimulated rats may be caused by increased gentamicin transport across the brush border as a consequence of PTH-mediated alteration of plasma membrane phospholipid composition, turnover, or both.(ABSTRACT TRUNCATED AT 250 WORDS)
We treated 10 patients who had chronic non-A,non-B hepatitis with recombinant human alpha interferon in varying doses (0.5 to 5 million units) daily, every other day, or three times weekly for up to 12 months. In 8 of the 10 patients, elevated serum aminotransferase levels decreased rapidly during therapy and eventually fell into the normal or nearly normal range. In two of these patients, the interferon therapy was stopped after four months, and in both cases, a prompt return of aminotransferase activities to pretreatment values occurred. Prolonged treatment was associated with a sustained improvement in aminotransferase levels; in three cases, biopsy specimens obtained after one year of therapy showed marked improvement in hepatic histology, even though low doses of alpha interferon had been used. These preliminary findings, although not adequately controlled, suggest that long-term, low-dose alpha interferon therapy may be effective in controlling the disease activity in some patients with chronic non-A,non-B hepatitis. A prospective controlled trial is now needed to assess the role of interferon therapy in this disease.
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Frozen sections of human fetal spleen from 12 to 20 wk gestation were examined by using polyclonal antibodies to Ig isotypes, monoclonal antibodies to HLA class II subregion locus products, B and T cells, and follicular dendritic cells. Scattered lymphoid cells in spleen sections from fetuses of 12 to 13 wk gestational age expressed IgM but not IgD. The appearance of lymphoid cells expressing IgD occurred at 14 to 15 wk before the formation of loose clusters of B cells at 16 wk. IgD expression was associated mainly with cells in these clusters, which by 17 wk had become definite follicles. Follicular dendritic cells were not detectable until 20 wk. OKT3-positive T cells were not detected until 17 wk, and at 20 wk constituted 5% of the nucleated cell population. HLA-DR- and DP-positive lymphocytes and macrophages were detectable in fetal spleen from 12 wk onward; DR was expressed on more cells than DP, and the numbers of cells stained by HLA-DR-specific monoclonal antibodies exceeded the number of Ig-positive cells in all spleens examined. HLA-DQ was expressed by consistently fewer cells than HLA-DR and -DP in all spleens tested. The small number of DQ-positive cells in spleens from 12- to 13-wk fetuses had the morphology of macrophages; HLA-DQ expression by lymphoid cells followed a similar pattern to IgD expression and was associated mainly with follicular lymphocytes. It could be demonstrated by double-labeling experiments that all follicular IgM-positive cells in 17- to 20-wk spleens expressed HLA-DP, DQ, and DR antigens: IgM-positive cells in 12- to 16-wk spleens and interfollicular IgM-positive cells in 17- to 20-wk spleens all expressed HLA-DR, but only 59% and 43% expressed DP and DQ, respectively. Ninety-one to 100% of IgD-positive cells in all spleens examined expressed HLA-DQ in addition to DR and DP. In these experiments IgD-negative, DQ-positive cells had the morphologic appearance characteristic of macrophages. These data suggest that class II antigens are differentially expressed on developing lymphoid cells; DR and DP expression occurring in the earliest spleens examined, with expression of DP on a subpopulation of DR-positive cells; IgD and DQ expression appears to be coincident on maturing B cells as they begin to form follicles. An immunoregulatory role for HLA-DQ in B cell development is implicated and remains to be fully investigated.
We assessed the diagnostic value of ocular cytologic examination by reviewing Giemsa-stained smears of conjunctival scrapings. Of 387 patients with a clinical diagnosis of adult chlamydial conjunctivitis, intracytoplasmic inclusions were found in 30 (8%). Both polymorphonuclear leukocytes and lymphocytes were common; the predominant cell type was not useful to differentiate chlamydial from adenoviral conjunctivitis. More sensitive cytologic features included the presence of plasma cells, Leber cells, blastoid cells, and multinucleated cells. Giemsa-stained conjunctival cytologic examination can provide a useful method to support the clinical diagnosis and to direct further laboratory testing.
Calcofluor white (CFW) is a chemofluorescent dye with an affinity for the polysaccharide polymers of amebic cysts. Using CFW staining with fluorescent microscopy, we demonstrated amebic cysts in corneal scrapings and keratectomy specimens from four patients with culture-proved Acanthamoeba keratitis and from one in whom CFW was the only positive laboratory test. Calcofluor white staining is simple, rapid, and highly reliable in the diagnosis of Acanthamoeba keratitis.
ADP-induced platelet aggregation was measured in 15 Type 1 (insulin-dependent) diabetic patients, 15 Type 2 (non-insulin-dependent) diabetic patients and in 15 non-diabetic control subjects. Simultaneous measurements were made of fasting blood glucose, glycosylated haemoglobin, serum insulin, total plasma cholesterol, cholesterol in the lipoprotein subfractions, total triglycerides and platelet phospholipid fatty acid levels. Regression analysis of aggregation against the biochemical variables within the three groups revealed that there was no significant difference in the associations with aggregation between the groups. When the data was pooled, blood glucose (p less than 0.01) and glycosylated haemoglobin (p less than 0.05) demonstrated significant associations with aggregation. Multiple regression analysis was then applied; only blood glucose (p less than 0.05) had an independent effect on aggregation. Platelet aggregation in diabetic patients and non-diabetic patients appears to be related directly only to blood glucose levels.
Fifty-two patients with Fredrickson Type IIb or Type IV hyperlipidaemia, in whom diet had not achieved satisfactory lipid levels, completed a double blind randomised study of acipimox versus placebo. The patients were given acipimox, 250 mg three times daily or placebo for a three month period, and plasma lipids and glucose were monitored. The patients receiving acipimox showed a fall in the mean concentration of plasma triglyceride compared to placebo (0.74 mmol/l) and this was most marked in patients whose initial plasma triglyceride levels were greater than 3 mmol/l (1.0 mmol/l, confidence limits 0.18, 1.82). Acipimox was well tolerated, and could be a useful addition to the drugs available for the treatment of patients with hypertriglyceridaemia.
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We have identified seven patients with clinical and serological features suggestive of Epstein-Barr viral (EBV) stromal keratitis. Four had discrete, sharply demarcated, multifocal, pleomorphic or ring-shaped granular anterior stromal opacities with normal intervening stroma, seemingly distinct from adenoviral or herpes simplex stromal keratitis. Two had soft, blotchy, pleomorphic, multifocal infiltrates, predominantly involving the peripheral cornea at all depths, and with minimal neovascularization, resembling syphilitic stromal keratitis. One patient had features or both forms of keratitis. OUr experience suggests that EBV may be more commonly associated with stromal keratitis than recognized previously.
Seventy-one nonimmunocompromised patients with herpes zoster ophthalmicus, presenting within seven days of onset of characteristic skin eruption, were enrolled in a prospective, longitudinal, randomized, double-masked, placebo-controlled trial with oral acyclovir. In a previous interim report we noted more prompt resolution of dermatomal signs and symptoms with acyclovir treatment. There was also a reduction of viral shedding in acyclovir-treated patients coupled with a trend to greater rate of microdissemination of the virus in placebo-treated patients (Cobo LM, et al. Ophthalmology 1985; 92:1574-83). While further substantiating these findings, we report that a ten-day course of treatment with oral acyclovir (600 mg, five times a day) is well-tolerated and significantly reduces the incidence and severity of the most common complications of herpes zoster ophthalmicus: dendritiform keratopathy, stromal keratitis, and uveitis. While this acyclovir treatment regimen reduces the zoster-related pain during the acute phase of the disease, especially in patients treated within 72 hours of onset of skin lesions, it has no evident effect on either incidence, severity, or duration of post-herpetic neuralgia in the patients studied.
The distribution of iron and iron binding proteins (IBP) have been compared with control spleen tissue in an attempt to establish a pattern of staining restricted to Hodgkin's disease (HD). All but one of the HD spleens examined stained for ferritin, which was largely present in red pulp dendritic macrophages (DM). In spleens histologically involved with HD heavy deposits of ferritin were seen around tumour nodules. Staining for ferritin increased with involvement of the spleen in HD but DM still represented the bulk of positive cells. However, ferritin positive DM were frequently seen in control spleens, and often in large numbers. Staining of ferric iron by Perls technique was less prominent than ferritin but this observation was also true of the non-HD spleens studied. Patterns of staining with transferrin were equivalent in both groups of spleens with DM being the most frequently positive cell type. Polymorphous macrophages showing erythrophagocytosis were present in the red pulp sinuses of all groups of spleens and although these cells have been considered as precursors of the Reed-Sternberg cell their presence seemed related to total splenic ferritin regardless of the disease process. These cells marked as macrophages and their presence was not restricted to HD. The results show that there is no particular appearance of iron or IBP distribution which is restricted to HD spleens. However, staining for ferritin and iron increased in HD spleens with tumour involvement and could contribute to circulatory abnormalities in this disease.
We measured the platelet total phospholipid fatty acid profiles of 20 insulin treated (Type I) diabetics, 20 non-insulin treated (Type II) diabetics and 20 matched non-diabetic controls to determine the relationship between the omega 6 and omega 3 series of fatty acids in diabetes. A significant inverse correlation between linoleic acid and arachidonic acid occurred in the normal subjects (r = -0.61; P less than 0.001) but was not seen in the Type I diabetics (r = -0.13; P = NS) or in the Type II diabetics (r = -0.27; P = NS). No significant correlation was seen between linolenic acid and eicosapentaenoic acid in the normal controls (r = -0.34; P = NS) or in the Type I diabetics (r = 0.21; P = NS) or in the Type II diabetics (r = -0.20; P = NS). The results suggest that a functional impairment of platelet delta 5 and delta 6 desaturase may occur in diabetes which disrupts the normal equilibrium between linoleic acid and arachidonic acid. However, the level of eicosapentaenoic acid appears to be less dependent on conversion from linolenic acid. Our findings are of importance to studies designed to reduce platelet aggregation in diabetics and non-diabetics by manipulation of the levels of the precursor fatty acids of thromboxane.
Limited joint mobility (LJM) of the small joints of the hands was studied in 63 adult insulin-dependent diabetics to determine whether LJM might serve as an indicator to the presence of diabetic retinopathy in diabetics of long duration. In 123 non-diabetic controls, and in the 63 diabetics, the prevalence of LJM increased with age. In the diabetics, LJM was not associated with retinopathy, long-term glycaemic control or HLA type. The hypothesis that LJM is useful as a predictor of the development of retinopathy in young diabetics does not extend to older diabetics of long duration. LJM and retinopathy may have a different pathophysiology.