Related factors in the progession of microangiopathy in KK mice.
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Biomedical subjects
Publications and source records attributed to D Patel.
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The study was conducted in 2831 pregnant women with no diagnosed complication at the time of registration to obtain normal foetal growth pattern for clinical and ultrasonographic parameters. Normal values for maternal weight, fundal height and abdominal girth for clinical and biparietal diameter, abdominal circumferences and femoral length for ultrasonographic parameters are presented. Clinical and ultrasonographic parameters were compared for their efficacy in prediction of low birth weight. Neither clinical nor ultrasonographic parameters were found to be satisfactory in identifying the foetus at risk of low birth weight. It has been found that clinical parameters for routine monitoring are as effective as ultrasonographic parameters and have the added advantage of being easily replicable at the peripheral level of health care.
This manuscript describes a new method, validated in in vitro models, for quantitating volume flow rate across an orifice with Doppler color flow mapping. Flow through a narrowed orifice is characterized by the convergence of radial streamlines proximal to the orifice. In this color Doppler method, one or more isovelocity surface areas (PISA), delineated by blue and red aliasing velocity interfaces, can be identified proximal to the narrowed orifice. Volume flow rate (in milliliters per second) can then be calculated as PISA (in square centimeters) multiplied by the isovelocity of the PISA (in centimeters per second). Doppler color flow mapping was performed in in vitro models of constant and pulsatile flow through an orifice in a wall. The first proximal isovelocity surface area, with an isovelocity corresponding to the aliasing velocity, that is, one half the Nyquist sampling limit, could be identified as a blue and red color interface proximal to the orifice. Over a range of circular orifice diameters from 3 mm to 16 mm and flow rates from 0.5 to 18.7 L/min, the proximal isovelocity surface area could be imaged in two planes. This PISA was best described by a hemielliptic mathematical model with two different radii measured from long-axis and short-axis views. In the constant flow model, volume flow rate calculated from the Doppler PISA correlated well with actual volume flow rate measured simultaneously with a cylinder and stopwatch (r = 0.98, p less than 0.001, standard error of the estimate [SEE] = 0.36 L/min). In the pulsatile flow model, with jet velocities ranging from 2.6 to 7.7 m/sec and flow volume ranging from 1.0 to 10.3 L/min, calculated volume flow rate also demonstrated an excellent correlation with actual volume flow rate (r = 0.99, p less than 0.001, SEE = 0.53 L/min). Findings from these in vitro models suggest that quantification of the proximal isovelocity surface area by Doppler color flow mapping appears to be a promising technique for estimating volume flow rate across a narrowed orifice. This new color Doppler flow method may have advantages over previous Doppler methods in estimating volume flow rate in various clinical situations, for example, valvular regurgitation and shunt lesions.
As an approach to the development of therapeutically useful peptide pharmaceuticals that can penetrate the blood-brain barrier, we have designed and demonstrated the application of a carrier-targeting system. We have developed a prodrug design strategy that is designed to utilize membrane-bound enzymes whereby release of a bioactive peptide from a highly lipophilic triglyceride peptide-carrier is achieved in situ, thus attaining high localized concentrations of the bioactive peptide. Following localization of such a system, normal peptidase and lipase action is utilized to release the active peptide (deltorphin II) intact and in high concentration. At present, the exact mechanisms are unclear, but the observed results in which analgesia is observed following peripheral administration suggest that the active peptide is able to cross the blood-brain barrier and sustain prolonged periods of analgesia as determined by antinociception tests by release of the bioactive peptide. In vitro tests of binding and bioactivity by the peptide conjugate show essentially no potency in either target or control analogues, but potent antinociceptive effects are observed following peripheral administration.
Keloids are the result of a dysregulated wound-healing process and are characterized by formation of excess scar tissue that proliferates beyond the boundaries of the inciting wound. In this study, we investigated the expression of key proteins involved in regulating apoptosis in keloids. Twenty archival paraffin-embedded keloid samples were randomly selected for an immunoperoxidase assay with antibodies against fas, p53, bcl-2, and bcl-x proteins using the target antigen-retrieval technique. Apoptosis was assessed in keloids and normal skin and in keloid and normal fibroblasts by the TdT-mediated dUTP nick-end labeling (tunel) assay on tissue sections, fibroblast cultures, and by flow cytometry for cell suspensions. We found that 18 of 20 keloids expressed p53 protein; bcl-2 was expressed by keloid fibroblasts in 19 of 20 keloids, and all specimens had prominent fas expression throughout the tissue. The distribution of these three antigens was regional within each lesion and followed a consistent pattern of p53 and bcl-2 expression colocalized to the hypercellular, peripheral areas of each keloid in a perinuclear pattern (p < .001). In contrast, an inverse distribution of fas expression was shown, with staining being more diffuse across the cell surfaces and limited to the central, more hypocellular regions in16 of 17 keloids (p < .001). There was no specific staining pattern in these keloids with antihuman bcl-x. In vitro studies on cultured keloid fibroblasts (derived from six patients) revealed maintenance of the p53+, bcl-2+ phenotype up to passage 10. Neither neonatal nor normal adult skin fibroblasts expressed either antigen but could be induced to express p53 by exposure to adriamycin. Keloid lesions and keloid fibroblasts were found to have lower rates of apoptosis than normal controls. Keloid fibroblasts displayed enhanced apoptosis rates in response to hydrocortisone, gamma interferon, and hypoxia treatment as compared with normal adult fibroblasts. Focal dysregulation of p53 combined with upregulation of bcl-2 may help produce a combination of increased cell proliferation and decreased cell death in the younger, hypercellular areas of the keloid. This phenotype is reversed in the older areas of the keloid and may prevent malignant degeneration, thus favoring normal apoptosis as evidenced by prominent fas expression.
Lipoblastoma is a relatively rare tumor that occurs in infancy and early childhood and arises from embryonic white fat. Although a benign tumor, lipoblastomas tend to recur and may resemble myxoid liposarcoma. The authors report 26 cases over a 15-year period at Texas Children's Hospital. There was a slight female predilection (14F:12M). The most common symptom was a painless mass with or without increasing size. The trunk, extremities, head and neck, retroperitoneum, inguinal canal, peritoneal cavity, and lung were the tumor sites. Most tumors were circumscribed lipoblastomas and the minority were diffuse infiltrative lipoblastomatosis. Reexcision for residual or recurrent tumor was necessary more frequently in patients with lipoblastomatosis. Histopathologic examination and ultrastructural examination revealed cellular neoplasms composed of immature adipocytes with relatively well-defined septa, frequent lipoblasts, a fine vascular network, and often a myxoid appearance resembling myxoid liposarcoma. Cytogenetics was performed in 4 cases with chromosome 8q abnormality being most common. The major concern with lipoblastoma in children is to completely excise the tumor to avoid leaving residual tumor and to prevent recurrences. Confusion with myxoid liposarcoma, well-differentiated liposarcoma, and typical lipomas may occur. Although asymptomatic, lipoblastomas may cause dysfunction of other organ systems due to mass effect. Complete surgical excision with at least 2 years of follow-up is the preferred therapy.
Fourteen patients with AIDS were treated for 23 neurologic complications: four episodes of acute meningoencephalitis; eight episodes of subacute encephalopathy; two cases of progressive multifocal leukoencephalopathy; and nine cases of polyneuropathy. Nine patients were treated with 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), one with 3'-azido-3'-deoxythymidine (AZT), and four initially with DHPG directed against cytomegalovirus (CMV) retinitis or encephalitis and subsequently with AZT against human immunodeficiency virus (HIV) encephalopathy. CMV retinitis was a helpful clinical observation indicating neurologic involvement. DHPG produced improvement in two of three cases of acute meningoencephalitis but was ineffective in cases of subacute encephalopathy or neuropathy. AZT therapy resulted in resolution in both of the two treated cases of acute confusional state and in two of the four treated cases of polyradiculoneuropathy with paraparesis but was ineffective in the late stage of subacute encephalopathy. These results suggest that CMV is important in some cases of acute meningoencephalitis, whereas HIV is a dominant pathogen in subacute dementia and polyneuropathy in patients with AIDS. DHPG may be beneficial in the former, whereas AZT appears to be effective in the latter complications.
We compared clinical and arteriographic features in 27 white and 24 black patients with symptomatic posterior circulation occlusive disease. The degree of arterial stenosis was measured independently by two examiners at 12 sites within the vertebrobasilar territory. Racial comparisons were made based upon the distribution of extra- and intracranial occlusive lesions and symptomatic sites of the lesions. White patients had significantly more angina pectoris, more lesions of the origin of the left vertebral artery and more high grade lesions of the extracranial vertebral arteries. Black patients had significantly higher mean diastolic blood pressure, more diabetes mellitus, more lesions of the distal basilar artery, more high grade lesions of intracranial branch vessels and more symptomatic intracranial branch disease. Race was found to be the only factor increasing the risk of intracranial posterior circulation occlusive disease. Knowledge of the contribution of race to the distribution of posterior circulation lesions will help guide evaluation and treatment strategies for patients with vertebrobasilar occlusive disease.
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