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Biomedical subjects

G Scott

Publications and source records attributed to G Scott.

At least 217 records · Page 12Linked to original sources

Osteodysplastic primordial dwarfism: report of a further case with manifestations similar to those of types I and III.

We describe a male infant with microcephalic osteodysplastic primordial dwarfism. The clinical and radiological manifestations most closely resemble those of the patient described by Winter et al. to have manifestations overlapping with both osteodysplastic primordial dwarfism types I and III. The classification of the patient within the spectrum of osteodysplastic primordial dwarfism is discussed and the distinctive neuropathology documented.

Abnormalities, Multiple↗

Goodman and Kruskal's lambda: a new look at an old measure of association.

We examine Goodman and Kruskal's lambda using Efron's approach to regression and analysis of variance (ANOVA) for zero-one outcome data. For a binary response cross-classified by a single nominal predictor, we present a computationally simple ANOVA table in which lambda is analogous to Pearson's R-square. We characterize the relationship between lambda and the commonly used apparent error rate in logistic regression, and show that lambda is based implicitly on a prediction rule for a saturated model with classification level 0.5. This relationship suggests that we can correct the apparent error rate for chance by defining a natural generalization of lambda that we call PRE, the proportional reduction in error. We illustrate the use of lambda and PRE in an analysis of prognostic factors for one-year survival in children with the acquired immunodeficiency syndrome (AIDS).

Acquired Immunodeficiency Syndrome↗

Pharmacokinetics of zidovudine administered intravenously and orally in children with human immunodeficiency virus infection.

Zidovudine pharmacokinetics were determined in 16 children with human immunodeficiency virus infection who were being treated intravenously and orally on an intermittent schedule (every 6 hours). The intravenous doses studied were 80 (n = 3), 120 (n = 4), and 160 (n = 5) mg/m2/dose, infused over 1 hour. Fourteen patients were monitored after an oral dose of zidovudine at 120 (n = 2), 180 (n = 7), or 240 (n = 5) mg/m2/dose. Zidovudine was assayed with a reverse-phase high-pressure liquid chromatography method. Zidovudine disappearance after intravenous administration was rapid and biexponential, with half-lives of 14 and 90 minutes and a total clearance of 641 +/- 161 ml/min/m2. The volume of distribution at steady state was 45 +/- 28 L/m2. These pharmacokinetics parameters are very similar to those reported in adults. When administered orally, zidovudine was rapidly absorbed. The fraction of the oral dose that was bioavailable was 0.68 +/- 0.25, so that a 50% increment in the dose, in the conversion from intravenous to oral administration, resulted in plasma zidovudine concentrations after oral dosing that were nearly identical to those achieved with the 1-hour intravenous infusion. However, a dose of 180 mg/m2 given orally every 6 hours maintained plasma zidovudine concentrations in the target range of 1 mumol/L for less than half of the dosing interval. Other schedules, routes of administration, or oral drug formulations may have to be considered if sustained continuous exposure to micromolar zidovudine concentrations is desired.

Acquired Immunodeficiency Syndrome↗

Penile basal cell carcinoma. Report of a case and review of the literature.

We describe a 69-year-old man with penile basal cell carcinoma and review the literature on this condition. Basal cell carcinomas of the penis are rare, and there are only 26 other reported cases. There is no documented case of metastatic penile basal cell carcinoma. The one reported case of metastatic penile basal cell carcinoma actually represents urethral transitional cell carcinoma. Therefore conservative therapy with local removal is adequate treatment, and more extensive procedures are unnecessary. Ultraviolet light exposure may be an important etiologic factor for basal cell carcinomas located on sun-exposed areas. The occurrence of basal cell carcinomas on non-sun-exposed areas raises the possibility of other, not yet defined, etiologic agents.

Aged↗

Age-related change in anti-carbohydrate antibody levels.

It has been proposed that immunity declines with age. Most evidence for this hypothesis has been obtained from cross-sectional samples of unrelated populations that differ in age, antigen exposure, and morbidity. In the present study, the authors used serum samples collected repeatedly from the same persons in longitudinal studies. Two representative samples of the population in Göteborg, Sweden were obtained; the first was studied at ages 38, 50, and 62 years, and the second at ages 70, 75, 79, and 81 years, respectively. The phosphorylcholine determinant of pneumococcal teichoic acid and the B blood group determinant were selected as model polysaccharide antigens. The results demonstrate a consistent decline in individual antibody levels in the decades before age 70 years but not later. Antibodies to phosphorylcholine and blood group B were highly parallel, suggesting that the decline was a general phenomenon for antibodies to polysaccharide antigens.

ABO Blood-Group System↗

Pontomedullary tears and other gross brainstem injuries after vehicular accidents.

In a series of 988 autopsied victims of road crashes, there were 36 (3.6%) cases of gross primary brainstem injury. These fell into three groups. The first comprised eight cases of pontomedullary tearing without other gross brain injury: in seven of these, there were associated atlanto-occipital dislocations and/or high cervical fracture-dislocations. The usual cause appeared to be facial impact inducing acute hyperextension. Second, there were 17 cases of pontomedullary tearing associated with other brainstem lacerations and/or major damage elsewhere in the brain: in all, there were fractures of the skull base, typically transverse middle fossa fractures. Most of these injuries appeared to be due to facial impacts transmitting force to the anterior skull base, although hyperextension was also a factor in some. There was a third heterogeneous group of 11 cases with brainstem lacerations in sites other than the pontomedullary junction: in some of these it appeared that the impacts had caused skull base fractures by inducing calvarial torsion. In this series, the proportion of motorcyclists (41.7%) was double the expected figure. The use of a helmet modifies the mechanisms of impact head injury; the overall benefits of helmet use are well established, but there is need for more research on helmet design.

Accidents, Traffic↗

Uterine junctional zone: MR study of water content and relaxation properties.

Weighted samples of uterine myometrium, junctional zone, and endometrium were excised for determination of T1 and T2 in a 20-MHz spectrometer and then dried for determination of water content. The remainder of each uterus, examined with special histopathologic stains, demonstrated no significant difference in the number of blood vessels, smooth muscle cells, fibroblasts, elastin, iron, collagen, mucin, polysaccharide, or amyloid. The junctional zone water content (79.28%) was significantly lower than that of endometrium (82.88%, P = .004) and myometrium (81.05%, P = .005). The T1 of the junctional zone (ie, 643) was significantly lower than that of endometrium (ie, 836; P = .004) and myometrium (ie, 709; P = .01). The T2 of the junctional zone (ie, 58) was significantly lower than that of endometrium (ie, 87; P = .003) and myometrium (ie, 67; P = .006). The low signal intensity of the junctional zone on T2-weighted MR images is accounted for by its lower water content and T2, while the brightness on T1-weighted images is due to its reduced T1.

Adult↗

Pseudoepitheliomatous hyperplasia in Spitz nevi. A possible source of confusion with squamous cell carcinoma.

The presence of epithelial hyperplasia in Spitz nevi has been recognized almost from the time of Spitz's first description of the distinctive lesion that bears her name. However, the fact that this hyperplasia can acquire pseudoepitheliomatous features and thus lead to a mistaken diagnosis of squamous cell carcinoma is not widely appreciated. This report describes six examples of this phenomenon.

Adult↗

Synaptic reorganization in the hippocampus induced by abnormal functional activity.

Abnormal functional activity induces long-lasting physiological alterations in neural pathways that may play a role in the development of epilepsy. The cellular mechanisms of these alterations are not well understood. One hypothesis is that abnormal activity causes structural reorganization of neural pathways and promotes epileptogenesis. This report provides morphological evidence that synchronous perforant path activation and kindling of limbic pathways induce axonal growth and synaptic reorganization in the hippocampus, in the absence of overt morphological damage. The results show a previously unrecognized anatomic plasticity associated with synchronous activity and development of epileptic seizures in neural pathways.

Animals↗

Microalbuminuria in non-insulin-dependent diabetes: its prevalence in Indian compared with Europid patients.

Non-insulin-dependent diabetes mellitus is strikingly common in British Indians, but their susceptibility to diabetic complications is unknown. The ratio of albumin to creatinine concentrations was measured in samples of the first urine voided in the morning in 154 Indian and 82 Europid patients with non-insulin-dependent diabetes and in a control group of 129 non-diabetic Indians. The ratio was significantly higher in the Indian patients than in the Europid patients and the Indian controls. There were no significant correlations between the logarithm of the albumin: creatinine ratio and age, known duration of diabetes, haemoglobin A1 concentration, or body mass index within either diabetic group. Hypertension and raised albumin:creatinine ratio were significantly associated, and significant correlations were seen between the logarithm of the albumin:creatinine ratio and systolic and diastolic blood pressures in the Indian but not the Europid diabetics. Because of the high prevalence of diabetes at a relatively early age in Indians, nephropathy may emerge as an important clinical problem.

Adult↗

Increased sodium-lithium countertransport activity in red cells of patients with insulin-dependent diabetes and nephropathy.

Susceptibility to diabetic nephropathy may be related to a predisposition to arterial hypertension. We have studied the activity of sodium-lithium countertransport in red cells, a marker of risk for essential hypertension, in white European adults with insulin-dependent diabetes and diabetic nephropathy, a matched group of patients with diabetes without renal disease, and nondiabetic patients with renal disease. Measures of metabolic control and concentrations of plasma free insulin and growth hormone were similar in the two diabetic groups. The degree of impairment in renal function was similar in the diabetic and nondiabetic patients with renal disease. Body-mass index and plasma potassium concentrations were similar in all three groups. Diastolic blood pressure was elevated to a similar degree in the two groups with renal disease, as compared with that in the diabetic patients without renal disease. The rates of sodium-lithium countertransport in red cells were significantly higher in the diabetic patients with renal disease (mean +/- SD, 0.55 +/- 0.19 mmol of lithium per liter of red cells per hour) than in the diabetic patients without renal disease (0.33 +/- 0.16; P less than 0.005) and in the nondiabetic patients with renal disease (0.31 +/- 0.14; P less than 0.001). Predisposition to hypertension, as indicated by elevated sodium-lithium countertransport activity in red cells, may serve as a marker for the risk of renal disease in patients with insulin-dependent diabetes.

Adult↗

Magnetic resonance imaging of rabbit brain after intracarotid injection of large multivesicular liposomes containing paramagnetic metals and DTPA.

A procedure has been developed for the preparation of large (10- to 80-microns-diameter) multivesicular liposomes that contain magnetic resonance contrast agent (DTPA and either manganese or gadolinium). Blue dextran was observed to induce the formation of the large liposomes with dioleoylphosphatidylcholine and cholesterol (1:1 molar ratio) and with dipalmitoylphosphatidylcholine and cholesterol (1:1 molar ratio). The formation of the large liposomes is dependent upon mixing the blue dextran with the lipid films at temperatures above the transition point of the lipids. Tracer amounts of 153Gd were added to the aqueous phase to permit quantitation of the recovery of encapsulated materials. Liposomes that were prepared using equimolar ratios of phospholipid and cholesterol were stable in serum for more than 12 h. The ultrastructure of the large multivesicular liposomes reveals the existence of individual vesicles (greater than 2 micron diameter) bound together by a multilamellar coating. When injected into the internal carotid artery of the rabbit, the large liposomes became entrapped in the vascular bed primarily in the frontal and occipital regions of brain. The resulting emboli may provide a means to deliver drugs to a specific site in brain, such as a tumor, if the vascular bed of the site can be cannulated precisely.

Animals↗

Basic fibroblast growth factor from human keratinocytes is a natural mitogen for melanocytes.

To survive and proliferate in pure culture, human melanocytes require basic fibroblast growth factor (bFGF) and cAMP. Without these factors, even in the presence of serum, the cells die. Melanocytes cultured in the presence of keratinocytes, however, survive for weeks without added bFGF and cAMP. We show here that the growth factor for melanocytes produced by human keratinocytes is bFGF because its activity can be abolished by neutralizing antibodies to bFGF and by a bFGF synthetic peptide that inhibits the binding of the growth factor to its receptor. The melanocyte mitogen in keratinocytes is cell associated and increases after irradiation with ultraviolet B. Northern blots reveal bFGF gene transcripts in keratinocytes but not melanocytes. These studies demonstrate that bFGF elaborated by keratinocytes in vitro sustains melanocyte growth and survival, and they suggest that keratinocyte-derived bFGF is the natural growth factor for normal human melanocytes in vivo.

Cell Division↗

Paracrine stimulation of melanocytes by keratinocytes through basic fibroblast growth factor.

Melanocytes cultured in the presence of keratinocytes survive for weeks without added basic fibroblast growth factor (bFGF) and cyclic-adenosine-monophosphate (cAMP), the two factors needed for their proliferation in vitro. We show here that the growth factor for melanocytes produced by human keratinocytes is bFGF because its activity can be abolished by neutralizing antibodies to bFGF and by a bFGF synthetic peptide that inhibits the binding of the growth factor to its receptor. The melanocyte mitogen in keratinocytes is cell-associated and increases after irradiation with ultraviolet B (UVB). Northern blots reveal bFGF gene transcripts in keratinocytes but not melanocytes. These studies demonstrate that bFGF elaborated by keratinocytes in vitro sustains melanocyte growth and survival, and they suggest that keratinocyte-derived bFGF is the natural growth factor for normal human melanocytes in vivo.

Epidermal Cells↗

Erythrocytes are essential for development of cerebral vasculopathy resulting from subarachnoid hemorrhage in cats.

In an effort to determine which blood elements play a critical role in the development of cerebral vasospasm, adult cats were subjected to prepontine injection of either autogenous whole blood or erythrocyte-free blood containing latex beads as a substitute morphologic marker. Seven or 10 days later the cats were anesthetized and perfused with fixative, and the basilar arteries were prepared for light and electron microscopy. Successful clot deposition was confirmed by the presence of numerous erythrocytes or latex beads within the adventitia of vessels. In agreement with previous studies, instillation of whole blood produced luminal narrowing associated with profound ultrastructural changes in all layers of the vascular wall. No significant alterations, however, occurred in arteries bathed in erythrocyte-free blood. These findings suggest first, that erythrocytes are essential for the development of the vasculopathy associated with chronic cerebral vasospasm, and second, that the role, if any, of other blood elements is not autonomous.

Animals↗