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Biomedical subjects

P Richardson

Publications and source records attributed to P Richardson.

At least 19 recordsLinked to original sources

Crescentic glomerulonephritis and eosinophilic interstitial infiltrates in a patient with hypereosinophilic syndrome.

Crescentic glomerulonephritis with immune complex deposition and acute eosinophilic interstitial nephritis developed in a patient with the hypereosinophilic syndrome. Acute renal failure ensued but was rapidly reversed by high-dose oral prednisone. Confounding factors and unusual findings are described with a review of recent literature. This mode of presentation has not previously been reported.

Acute Disease

Changing populations in the public sector: responding to the needs of Texas youth.

Treatment of sexually abused and abusing youth requires careful program planning and implementation. Led by its Quality Improvement Council and with considerable staff involvement, Waco Center for Youth in Waco, Texas developed a dual-track approach to treatment of this underserved, often misunderstood, adolescent client population. The sexual abuse survivors' program focuses on the issues of trust, safety, self-esteem, assertiveness, and education. The sex offender program is built on the concepts of self-responsibility; diminishing cognitive distortions; identification of stressors, and their relationship to the offending cycle; and relapse prevention. The staff of Waco Center for Youth are engaged in ongoing analysis of behavioral indicators for successful treatment of sexually abused and abusing adolescents.

Adolescent

Choroid coat extract and ciliary neurotrophic factor strongly promote neurite outgrowth in the embryonic chick retina.

Previous studies have shown that extracts from the target optic tectum stimulate neurite outgrowth from retinal explants. The present study indicates that the choroid coat is an even richer source of retinotrophic activity. We thus studied the effects of recombinant rat ciliary neurotrophic factor (CNTF) on primary cultures of dissociated chick ciliary ganglion neurons and retinal explants for a comparison with choroid coat extract from the E18 chick. For our assays, E9 ciliary neurons were incubated in collagen gels and retinal explants were cultured on collagen gels with the addition of the trophic factors and maintained for two or four days. Survival of ciliary neurons per area as well as maximal neurite length in retinal cultures were determined. Growth responses occurred in a dose-dependent manner both to CNTF and choroid extract. Immunofluorescence examination of cells and developing processes showed 200 kdal neurofilament positivity demonstrating that the cells studied were neurons with neurites. It is concluded that a trophic activity of the choroid as well as the recombinant CNTF stimulate retinal neuron survival and neurite extension. The results suggest that CNTF may have developmental functions in the establishment of the visual pathways.

Animals

Peripheral nerve injury.

Knowledge of the actions of conventional neurotrophic factors on peripheral neurons is accumulating rapidly, and growth factors that were discovered outside the nervous system have been found to have neurotrophic actions. The nature and initiation of proximal neuronal responses to nerve injury, the interactions of Schwann cells and growth cones, and the functions of macrophages in the peripheral nervous system are all areas of active investigation. Results of the surgical treatment of injuries to the brachial plexus and spinal accessory nerve are reported.

Accessory Nerve

Modulation and high frequency expression of autoantibody-associated cross-reactive idiotypes linked to the VHI subgroup in CD5-expressing B lymphocytes from patients with chronic lymphocytic leukaemia (B-CLL).

Leukaemic B cells from patients with chronic lymphocytic leukaemia (B-CLL) are known to express the pan T-cell marker CD5 and a restricted set of immunoglobulin (Ig) variable region heavy (VH) and light (VL) chains encoded by germline or minimally mutated germline genes. We have studied surface expression of certain VH and VK gene products on peripheral blood B lymphocytes from 23 patients with B-CLL, using a panel of monoclonal antibodies (MoAbs) recognizing germline encoded cross-reactive idiotypes (CRI) associated with VHI (G6, G8), VHIII (B6, D12), VKIIIb (17-109) and an epitope linked to the VKIII light chain subgroup (C7). While only 1.7-3.2% of peripheral blood B lymphocytes from normal individuals expressed the VHI-associated CRI (VHI-CRI), these CRI were expressed on virtually all the leukaemic B cells from 17-22% of the CLL patients. The VHIII-associated CRI (VHIII-CRI), however, were found in 8.5-13% of the CLL B cells. Fifty per cent of the IgMK-expressing CLL cells (7/14) expressed the VKIII light chain subgroup of which only one expressed the VKIIIb-associated CRI (VKIIIb-CRI), 17-109. The anti-VHI-associated CRI antibodies were used to study their regulatory effect on in vitro Ig synthesis by the leukaemic cells. A significant suppression of spontaneous and mitogen-driven Ig production was observed in all cases studied. These results demonstrate an over-expression of VHI and VKIII gene products in B-CLL and suggest that B cells expressing these CRI are particularly susceptible to lymphoproliferative stimuli. The anti-CRI antibodies can be used to modulate Ig production by the leukaemic cells and may be of potential value for selective immunotherapy.

Aged

First steps in the development of an information and counselling service for women with an abnormal smear result.

A study was conducted to develop and evaluate an information leaflet and to investigate the acceptability of a counselling service for women with an abnormal smear result. A newly constructed information leaflet which addressed concerns related to receipt of an abnormal smear result and its medical management was compared for ease of readability with five other leaflets in current use and found to be superior. 144 women were given the leaflet either prior to a colposcopy examination or outpatient ablative treatment and randomly assigned to two recruitment strategies to examine the acceptability of a counselling interview. There was no significant difference between the two strategies and an uptake rate of 80% suggested that women welcomed such an opportunity. An interview evaluation schedule yielded a 98% positive response rate which indicated that the women were satisfied with the counsellor and found the interview useful. Significant differences emerged before and after medical intervention. Patients reported less anxiety, improved mood, and less distress related to the smear result and subsequent medical procedures immediately after the medical interventions (P less than 0.001).

Anxiety

Bilateral congenital mydriasis.

A single case of bilateral congenital mydriasis is described. A review of the literature is presented and possible modes of inheritance are discussed.

Child, Preschool

Time dependence of lung mechanics in preterm lambs.

The passive exhalation flow-volume plots of preterm lambs exhibit curvature. To explain this curvature, we proposed two mathematical models that could predict the measured passive exhalation flow-volume data well. One model takes into account the flow and volume dependence of resistance and compliance. The second model emphasizes the time dependence of lung mechanics and considers the respiratory system viscoelastic properties and the analogy of the lung to two electronic resistor-capacitor circuits connected in parallel. We attempted to determine which of the two models is more valid by analyzing passive exhalation flow-volume data that were obtained while briefly obstructing flow midway through deflation. In 14 preterm lambs (130 d gestation), the flow of exhaled gas increased from 76 +/- 35 mL/s when measured just before obstruction to 90 +/- 30 mL/s when measured immediately after release of the obstruction (p less than 0.0001). This finding suggests that a time-dependent phenomenon was taking place during obstruction and is inconsistent with the model based upon the flow and volume dependence of resistance and compliance. We made similar measurements in four near-term (143-146 d gestation) and four full-term lambs (9-12 d of age). Their flow-volume curves were relatively linear, and they showed no increases in flow after removal of the obstruction. The results of this study strongly suggest that time-dependent phenomena caused the curvilinearity in the passive exhalation flow-volume plots of preterm lambs. We suspect that the time-dependent phenomena is associated with the premature lung and with parenchymal lung disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance

Seminoma of the testis in a patient with 48,XXYY variant of Klinefelter's syndrome.

We believe this is the first reported case of seminoma in a patient with the 48,XXYY variant form of Klinefelter's syndrome. Moreover, the seminoma in this patient occurred in a normally descended testis. We report this case because patients with 48,XXYY Klinefelter's syndrome are often confined to institutions, where the diagnosis of testicular tumor may not be recognized as readily.

Adult

Cellular origins of serum complement receptor type 2 in normal individuals and in hypogammaglobulinaemia.

A soluble form of complement receptor 2 (sCR2) is found in normal human serum. Amounts present are about 30-90 ng/ml, which is of the same order as reported for soluble CR1. Although B cells express surface CR2 and are the main peripheral blood source of sCR2 they do not appear to be the major tissue source of serum sCR2. Serum levels of sCR2 of patients with hypogammaglobulinaemia were not significantly different from those of normal individuals even in the case of two brothers with Bruton's X-linked agammaglobulinaemia (XLA) lacking (CD19+) B cells. On gel filtration through Sephacryl S-300 the sCR2 from XLA serum behaved exactly like sCR2 from normal serum or sCR2 affinity purified from cell supernates of a B lymphoblastoid line or from the T-ALL line MOLT-4. In all cases a single peak appeared at the same point in the chromatogram. Possible alternative sources of serum sCR2 are follicular dendritic cells (FDC) which are known to express CR2 strongly and T6+ lymphocytes within the thymus. Peripheral T cells from adults have not been reported to express CR2. However, investigation showed that cells from the Bruton's XLA cases produced small amounts of sCR2 in culture and although no CD21 was detected on the surface of the mononuclear cells by flow cytometry, the more sensitive direct antibody rosette test readily detected CD21. Further studies showed that non-B cells from control samples of cord blood or blood of young children also weakly expressed CD21.

Agammaglobulinemia

A novel dialysing seton: short-term biocompatibility.

A novel dialysing seton made from haemodialysis tubes was implanted into eleven rabbit eyes to establish its biocompatibility. The animals were observed for up to 67 days after implantation. The cannulae were well tolerated clinically. Tissue obtained at seven different time periods was studied by light and electron microscopy and showed only a mild inflammatory reaction of the same grade as or less than that surrounding nylon sutures used to close the scleral trapdoors. The eye containing the seton had consistently lower intraocular pressure compared to the sham-operated fellow eye for up to 24 days. This effect declined over the ensuing five weeks.

Animals

Value of CT in determining the need for angiography when findings of mediastinal hemorrhage on chest radiographs are equivocal.

The role of CT in determining the need for angiography in patients with possible thoracic vascular injury resulting from blunt trauma is controversial. During a 24-month period, we prospectively evaluated the results of CT to screen 90 patients with a history of decelerating thoracic trauma for evidence of mediastinal hemorrhage or great vessel abnormality. All patients either had equivocally abnormal mediastinal contours on chest radiographs (64%) or had technically suboptimal chest radiographs owing to body habitus or restriction to the supine projection (36%). Patients with unequivocal signs of mediastinal hemorrhage on chest radiographs underwent immediate arteriography without prior CT. Thoracic CT was interpreted as normal in 63 (77%) patients and no further imaging was performed. Five patients had technically suboptimal CT studies, and CT scans were interpreted as equivocal in six. These 11 patients had normal arteriograms. Sixteen CT scans (18%) demonstrated evidence of mediastinal hemorrhage and/or great vessel contour abnormality. Four (27%) of 15 patients who underwent arteriography had injury to the great vessels. One patient refused to undergo angiography. In 11 patients with CT evidence of mediastinal hemorrhage, major vascular injury was not seen on arteriography. These results suggest a valuable role for CT in determining the need for arteriography to detect potential great vessel injury in patients with blunt decelerating thoracic trauma and equivocally abnormal mediastinal contours on chest radiographs.

Adult

Lovastatin decreases coenzyme Q levels in humans.

Lovastatin is clinically used to treat patients with hypercholesterolemia and successfully lowers cholesterol levels. The mechanism of action of lovastatin is inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, an enzyme involved in the biosynthesis of cholesterol from acetyl-CoA. Inhibition of this enzyme could also inhibit the intrinsic biosynthesis of coenzyme Q10 (CoQ10), but there have not been definitive data on whether lovastatin reduces levels of CoQ10 as it does cholesterol. The clinical use of lovastatin is to reduce a risk of cardiac disease, and if lovastatin were to reduce levels of CoQ10, this reduction would constitute a new risk of cardiac disease, since it is established that CoQ10 is indispensable for cardiac function. We have conducted three related protocols to determine whether lovastatin does indeed inhibit the biosynthesis of CoQ10. One protocol was done on rats, and is reported in the preceding paper [Willis, R. A., Folkers, K., Tucker, J. L., Ye, C.-Q., Xia, L.-J. & Tamagawa, H. (1990) Proc. Natl. Acad. Sci. USA 87, 8928-8930]. The other two protocols are reported here. One involved patients in a hospital, and the other involved a volunteer who permitted extraordinary monitoring of CoQ10 and cholesterol levels and cardiac function. All data from the three protocols revealed that lovastatin does indeed lower levels of CoQ10. The five hospitalized patients, 43-72 years old, revealed increased cardiac disease from lovastatin, which was life-threatening for patients having class IV cardiomyopathy before lovastatin or after taking lovastatin. Oral administration of CoQ10 increased blood levels of CoQ10 and was generally accompanied by an improvement in cardiac function. Although a successful drug, lovastatin does have side effects, particularly including liver dysfunction, which presumably can be caused by the lovastatin-induced deficiency of CoQ10.

Adolescent

Testosterone reduces the bioactivity of luteinizing hormone (LH) in man.

The effect of testosterone on LH bioactivity was investigated in six adult men (aged 40-56 years) with primary hypogonadism. Two men received a 400 mg testosterone implant, another two 800 mg, and the final two patients received both doses in consecutive courses separated by at least 4 weeks. Plasma samples, obtained before and at 1, 2, 4, 8, 16 and 24 weeks after treatment, were analysed for bioactive LH by the mouse Leydig cell bioassay, and immunoreactive LH and testosterone (T) by standard radioimmunoassays. The bioactive to immunoreactive (B:I) LH ratio, an index of LH biopotency, was calculated and the results compared with those from a group (n = 17) of healthy adult men. Before treatment, both bioactive and immunoreactive LH levels in the patients were higher and T levels lower than in the normal men (P less than 0.001). The mean +/- SD B:I LH ratio (3.5 +/- 0.6) in the patients was greater (P less than 0.05) than in the controls (2.7 +/- 0.7), indicating that in primary testicular failure, increased amounts of LH with enhanced bioactivity are secreted. Following T administration, a dose-related increase in circulating T and a reciprocal decrease in LH levels was observed between 1 and 16 weeks of treatment. However, there was a more pronounced decline in bioactive rather than immunoreactive LH levels, so that the B:I LH ratios decreased (P less than 0.001) from basal values after treatment. There was a negative correlation (r = -0.82, P less than 0.001) between circulating T levels and B:I LH ratios; the stronger the feedback signal, the lower the B:I LH ratio. It is concluded that testosterone negative feedback modifies not only the quantity but also the biological quality of secreted LH.

Adult

Oncogenic transformation by vrel requires an amino-terminal activation domain.

The mechanism by which the products of the v-rel oncogene, the corresponding c-rel proto-oncogene, and the related dorsal gene of Drosophila melanogaster exert their effects is not clear. Here we show that the v-rel, chicken c-rel, and dorsal proteins activated gene expression when fused to LexA sequences and bound to DNA upstream of target genes in Saccharomyces cerevisiae. We have defined two distinct activation regions in the c-rel protein. Region I, located in the amino-terminal half of rel and dorsal proteins, contains no stretches of glutamines, prolines, or acidic amino acids and therefore may be a novel activation domain. Lesions in the v-rel protein that diminished or abolished oncogenic transformation of avian spleen cells correspondingly affected transcription activation by region I. Region II, located in the carboxy terminus of the c-rel protein, is highly acidic. Region II is not present in the v-rel protein or in a transforming mutant derivative of the c-rel protein. Our results show that the oncogenicity of Rel proteins requires activation region I and suggest that the biological function of rel and dorsal proteins depends on transcription activation by this region.

Amino Acid Sequence