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Biomedical subjects

J Allen

Publications and source records attributed to J Allen.

At least 271 records · Page 15Linked to original sources

Continuity equation and Gorlin formula compared with directly observed orifice area in native and prosthetic aortic valves.

Orifice areas calculated by the continuity and Gorlin equations have been shown to correlate well in vivo. The continuity equation, however, gives underestimates compared with the Gorlin formula and it is not clear which is the more accurate. Both equations have therefore been tested against maximal orifice area measured by planimetry in eight prepared native aortic valves and four bioprostheses. A computer controlled, ventricular flow simulator (cycled at 70 beats/min) was used at five different stroke volumes that gave cardiac outputs of 2.8 to 7.0 l/min. The mean difference between measured and estimated orifice area was zero for the continuity equation, but -0.14 cm2 for the conventional Gorlin formula. Thus the Gorlin formula tended to give overestimates compared with both measured area and area estimated by the continuity equation, probably because of the effect of pressure recovery. When predictive equations derived from these data were tested, residual standard deviations were around 0.3 cm2 at all stroke volumes for the continuity equation, around 0.2 cm2 for the invasive Gorlin formula, and between 0.2 and 0.4 cm2 for the modified Gorlin formula. These results suggest that estimates of orifice area in an individual valve as judged by any of the equations tested should be seen as a guide to rather than as a precise measure of actual orific area.

Anthropometry↗

Can autism be detected at 18 months? The needle, the haystack, and the CHAT.

Autism is currently detected only at about three years of age. This study aimed to establish if detection of autism was possible at 18 months of age. We screened 41 18-month-old toddlers who were at high genetic risk for developing autism, and 50 randomly selected 18-month-olds, using a new instrument, the CHAT, administered by GPs or health visitors. More than 80% of the randomly selected 18-month-old toddlers passed on all items, and none failed on more than one of pretend play, protodeclarative pointing, joint-attention, social interest, and social play. Four children in the high-risk group failed on two or more of these five key types of behaviour. At follow-up at 30 months of age, the 87 children who had passed four or more of these key types of behaviour at 18 months of age had continued to develop normally. The four toddlers who had failed on two or more of these key types of behaviour at 18 months received a diagnosis of autism by 30 months.

Age Factors↗

Need for achievement and performance on measures of behavioral fluency.

This investigation was designed to assess the relationship between a validated personality characteristic, need for achievement (nAch), and performance on measures of behavioral fluency. To infer this relationship, 50 neurologically intact college undergraduates were administered a questionnaire assessing nAch and a battery of tests including a short form of the WAIS and measures of behavioral fluency (i.e., verbal fluency). Statistical analysis indicated that subjects high on nAch obtained higher scores than subjects low on nAch on the measures of figural fluency and the WAIS Verbal Scale. No significant difference on verbal fluency was seen between the two groups. Secondly, the group high on nAch also had a higher mean Verbal IQ but not a higher mean Performance IQ as measured by a short form of the WAIS than did subjects scoring low on nAch.

Achievement↗

Effects of hypoxia on morphological and biochemical characteristics of renal epithelial cell and tubule cultures.

Apoptotic cell death plays an important role in the pathogenesis of renal atrophy in diseases of the kidney involving chronic mild ischemia. The present study constitutes an in vitro model of these diseases and assesses the modes of cell death involved after hypoxic treatment of renal epithelium. Cultures of MDCK cells or primary cultures of rat renal parenchymal tubules were treated in either a physiological or a hypoxic atmosphere. Cultures were collected before treatment and at 24 h and 48 h, for morphological and biochemical studies. Both apoptosis and necrosis were observed at significantly increased levels by 48 h of hypoxia in the MDCK cell cultures. DNA gel electrophoresis patterns supported these findings. Experiments using tubule cultures demonstrated that, during the 48 h of study, tubular epithelial cells in the center of the control tubule structures died by apoptosis, possibly as a result of mild oxygen and/or nutrient depletion. With added hypoxic treatment, however, the entire tubule structure became necrotic. Results are similar to those found during in vivo studies, thus providing in vitro models that may be developed further to define factors in the pathogenesis of some renal diseases.

Animals↗

Pharmacological characterization of in vivo [3H]lfenprodil binding sites in the mouse brain.

Intravenous injection of 5 muCi of [3H]ifenprodil to mice resulted in an accumulation of radioactivity in the whole brain which was maximal at 5 min postinjection and then declined in a biphasic manner. When whole brain radioactivity was measured 2 h after [3H]ifenprodil injection, more than 65% of the incorporated label was displaced by i.p. administration (30 min before the radiotracer) of the ifenprodil chemical congener +/-alpha-(4-chlorophenyl)-4-(4- fluorophenylmethyl)-1-piperidine ethanol (SL 82.0715) (10 mg/kg). At this time, most of the radioactivity (80%) present in the brain comigrated with authentic [3H]ifenprodil. When administered 30 min before the radiotracer, several sigma ligands inhibited in vivo [3H]ifenprodil binding to the mouse brain with the following rank order of potency (ID50, mg/kg, i.p.): haloperidol (0.27) greater than ifenprodil (0.83) greater than SL 82.0715 (1.37) greater than BMY 14,802 (5.5) greater than 1,3-di-O-tolylguanidine (18). GBR 12909 (20 mg/kg, i.p.) and phencyclidine (30 mg/kg, i.p.) also inhibited this binding by 71 and 59%, respectively. In contrast, the N-methyl-D-aspartate receptor channel blockers 1-[1-(2-thienyl)cyclohexyl] piperidine and MK-801 (10 mg/kg, i.p.) failed to affect [3H]ifenprodil binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The hematopoietically expressed vav proto-oncogene shares homology with the dbl GDP-GTP exchange factor, the bcr gene and a yeast gene (CDC24) involved in cytoskeletal organization.

The vav proto-oncogene encodes a protein of unknown function that is rendered oncogenic by loss of a short N-terminal domain. A correction reported here to the vav sequence reveals that a central domain of some 230 amino acids is similar to the products of three genes: the human dbl oncogene, now known to encode a GDP-GTP exchange factor for the Ras-like polypeptide CDC42Hs; the CDC24 gene of Saccharomyces cerevisiae, which participates with CDC42Sc in organization of the cytoskeleton for budding; and the human bcr gene, which recombines with the abl oncogene in certain forms of leukemia. Furthermore, the N-terminal portion of Vav (and of CDC24) is similar to that of certain proteins that associate with filamentous structures. These similarities suggest that Vav, and perhaps also Bcr, may function as a GDP-GTP exchange factor for a Ras-like molecule such as CDC42Hs, and that its action may coordinate cytoplasmic architecture with the cell cycle. Reported evidence that the vav proto-oncogene is widely expressed in hematopoietic cells but not other cell types is extended here by detection of vav mRNA in 49 of 50 murine hematopoietic cell lines representing diverse hematopoietic lineages, and by in situ hybridization in embryos showing expression confined to the only hematopoietic tissue, fetal liver. Thus, like Dbl in other cell types, Vav may function throughout the hematopoietic compartment to govern a Ras-like signal transduction pathway.

Amino Acid Sequence↗

Increased plasma interleukin-6 concentrations in alcoholic hepatitis.

Interleukin-6 (hepatocyte stimulating factor) is a 26 kd cytokine that plays a major role in the acute phase response, especially the hepatic aspects of the acute phase response. Patients with alcoholic hepatitis manifest many aspects of the acute phase response. In this 6-month study we evaluated serial plasma interleukin-6 levels in 30 consecutive patients with moderate to severe alcoholic hepatitis. Mean admission plasma interleukin-6 activity was markedly increased (49.8 +/- 8.5 U/ml, normal less than 5 U/ml) in patients with alcoholic hepatitis, and levels decreased with clinical improvement to 15.6 +/- 6.1 U/ml at 6 months. Admission interleukin-6 activity correlated significantly (r = 0.82) with the severity of liver disease as assessed by the discriminant function of Maddrey. Also measured were selected assays postulated to be regulated by interleukin-6, including serum albumin (2.3 +/- 0.1 gm/dl), which was significantly depressed; alpha 1-acid glycoprotein (52 +/- 5 mg/dl), which was within normal limits; and IgA (827 +/- 70 mg/dl) and C-reactive protein (3.03 +/- 0.51 mg/dl), which were significantly elevated. Interleukin-6 activity fell over time in a pattern similar to that of bilirubin and C-reactive protein. We suggest that plasma interleukin-6 may not only regulate many aspects of the acute phase response but also may be a marker of inflammation and severity of disease in alcoholic hepatitis.

Hepatitis, Alcoholic↗

Cloning, expression and characterization of a cDNA encoding a lipase from Rhizopus delemar.

A lambda gt11 cDNA library was constructed in Escherichia coli using poly(A)-selected mRNA from the fungus, Rhizopus (Rp.) delemar. Lipase-producing members of the library were identified by means of a phenotypic score wherein the release of fatty acids by lipase causes a characteristic color change in the growth medium. One such isolate contained a 1287-bp insert (LIP cDNA) which hybridizes to 1.25- to 1.35-kb mRNA species from Rp. delemar. The lipase produced in E. coli containing the LIP cDNA exhibits the same substrate selectivity as the authentic fungal enzyme, hydrolyzing ester bonds at the stereospecific numbering (sn) sn-1 and sn-3, but not the sn-2, positions of triglycerides. The complete nucleotide sequence of the LIP cDNA was determined. By reference to the N-terminal sequence of authentic Rp. delemar lipase, the lipase-encoding region was identified within this fragment. The LIP cDNA encodes a putative preprolipase consisting of a 26-amino-acid(aa) signal sequence, a 97-aa propeptide, and a 269-aa mature enzyme. The predicted mature lipase has the same molecular weight and aa composition as that of Rp. delemar, is highly homologous to that produced by the fungus Rhizomucor miehei, and contains the consensus pentapeptide (Gly-Xaa-Ser-Yaa-Gly) which is conserved among lipolytic enzymes. It is concluded that the LIP cDNA is an essentially full-length analogue of the lipase-encoding gene of Rp. delemar. The lipase encoded by the LIP cDNA occupies a cytoplasmic location when synthesized in E. coli. Unprocessed forms of the lipase accumulate in E. coli.

Amino Acid Sequence↗

Stunned left ventricular myocardium after exercise treadmill testing in coronary artery disease.

Myocardial stunning (postischemic ventricular dysfunction) occurs in dogs after coronary stenosis following treadmill exercise. Less data are available in humans regarding development of stunned myocardium after exercise. Regional wall motion changes were evaluated in 22 patients with known coronary artery disease using 2-dimensional echocardiography and exercise treadmill testing. Wall motion was scored as 1 = normal, 2 = hypokinetic, 3 = akinetic, 4 = dyskinetic. At least 1 left ventricular segment with normal resting function developed an increase in wall motion score at 15 or 30 minutes compared with values at rest. The wall motion score in the midportion of the ventricular septum increased from 1.0 at rest to 1.6 (p less than 0.004) at 30 minutes after exercise; the basal inferior wall score worsened from 1.0 at rest to 1.9 (p less than 0.01) at 30 minutes after exercise. Coronary angiographic data in these patients revealed that left anterior descending narrowing correlated best with left ventricular septal wall motion abnormalities, whereas right coronary artery and circumflex narrowing best correlated with inferior and posterior wall motion abnormalities. Eight normal adult volunteers with no history of myocardial ischemia also underwent 2-dimensional echocardiography and exercise testing. No wall motion abnormalities were observed at any time after exercise. The present study suggests that in patients with coronary artery disease, exercise treadmill testing may induce regional wall motion abnormalities of the left ventricle that persist greater than or equal to 30 minutes after exercise, an observation consistent with the phenomenon of stunned myocardium.

Adult↗

Implementation and evaluation of a strategic parasite control program for captive exotic ungulates.

A parasite control program was designed for greater than 1,200 exotic ungulates maintained in mixed-species enclosures at the San Diego Wild Animal Park. Three strategically-timed anthelmintic treatments were given during 1988-1989, and their success was evaluated by monitoring pretreatment and posttreatment fecal egg counts. Adequate parasite control was achieved for animals in 52 ungulate species, as evidenced by low pretreatment egg counts and the absence of egg-shedding after treatment. However, animals belonging to 11 species in the subfamilies Antilopinae, Hippotraginae, and Caprinae were identified as important targets for more intensive control efforts because they shed either greater than 100 eggs/g of feces before treatment, or greater than 0 eggs/g after treatment, at 2 or more sampling periods. These results and observations were used to generate management recommendations and illustrate how a model parasite control program can be developed for collections of exotic ungulates.

Animals↗

Nursing-led group modalities in a psychiatric inpatient setting: a program evaluation.

This examination of group practice activities conducted by nurses in an inpatient setting combined retrospective examination of practices and concurrent analysis of what is actually done on the units. The most striking finding of this evaluation of institutional nursing-led or co-led group activities was the significant decline in the number of groups. Second, and a related finding, was the need to standardize the format for documenting group activities and outlining the scope and function of these groups. And finally, the need for concise evaluation criteria and measures to document the achievement of stated patient outcomes was very apparent.

Adolescent↗

Quantitative testicular biopsy in spinal cord injured men: comparison to fertile controls.

Spermatogenic abnormalities have been reported in the majority of spinal cord injured men on routine testicular biopsy. However, given the interim advances in their urological and rehabilitative care, a quantitative assessment of the germinal epithelium after spinal cord injury and comparison of these parameters to normal controls are warranted. Incisional testicular biopsy was performed in 14 spinal cord injured men. Quantitative micrometric techniques were applied to assess spermatogenesis and the results were compared to a normative data base of testicular biopsies previously obtained from a group of 15 fertile volunteers. From a minimum of 10 randomly selected round seminiferous tubules per subject the mean number of Sertoli cells, mature spermatids, tubular diameter and tubular wall thickness were determined in both groups and statistically analyzed. In the spinal cord injury group the mean number of spermatids per tubule was significantly lower and the mean number of Sertoli cells per tubule was significantly higher than in fertile controls (p less than 0.05). Moreover, the mean Sertoli cell-to-spermatid ratio per seminiferous tubule was significantly higher in the spinal cord injury group and discriminated between spinal cord injured men and controls, with a sensitivity of 93% and specificity of 100% (p less than 0.0001). Half of the spinal cord injury group showed a mean tubular spermatid density of less than 10. Compared to the fertile population, spinal cord injured men show significant differences in quantitative parameters of the germinal epithelium that may contribute to the reproductive dysfunction.

Adolescent↗

The long-term use of zidovudine in patients with severe immune-mediated thrombocytopenia secondary to infection with HIV.

Various treatments for HIV-related thrombocytopenia have been reported. Since etiologies of the thrombocytopenia may differ with regard to risk group treatment outcomes may also vary. We have recently studied the long-term use of zidovudine in individuals with sexually transmitted HIV infection and severe thrombocytopenia. Twenty-five men, median age 34 years (range, 23-51 years), were treated with zidovudine (1000 mg/day) for a median duration of 12 months (range, 2.5- less than 26 months). Nineteen patients (76%) had had episodes of symptomatic bleeding secondary to thrombocytopenia prior to study entry. All patients bleeding symptoms resolved with therapy. Six (24%) achieved a complete response, with normalization of platelet counts, while 11 patients (44%) achieved a partial response, giving an overall response rate of 68%. The median time to partial or complete normalization of platelet counts was 12 weeks (range, 4-62 weeks). Toxicities were minimal during the study period. Only one patient developed an AIDS-defining diagnosis while on therapy. We conclude that patients with sexually transmitted HIV infection and immune thrombocytopenia may need a prolonged period of therapy with zidovudine to achieve a platelet response. Other treatment modalities may be required for the 30% of patients who do not respond to zidovudine.

Adult↗

The clinical expression of bullous pemphigoid is not determined by the specificity of the target antigen.

The major bullous pemphigoid (BP) antigen is a 220-240-kDa polypeptide, although some BP sera recognize bands of 180-200 kDa or lower molecular weight. We have investigated to what extent this heterogeneity of the target antigen accounts for the clinical diversity of BP. Immunoblotting studies against extracts of salt-separated epidermis were performed on sera from 39 patients with BP. The blotting patters obtained were correlated with the clinical findings, with particular reference to prodromal itching, lesion morphology and severity, mucosal involvement, presence of milia, dapsone responsiveness and disease duration. The results confirm that the major BP antigen is a 220-kDa polypeptide, and that the 180-kDa polypeptide is a second and sometimes the sole BP antigen identified in immunoblots. Rarely, multiple bands of lower molecular weight were found. There was no correlation between the pattern of BP antigens detected in immunoblots and the clinical presentation and course of BP. There was considerable clinical diversity even among the nine patients showing specificity for a single 220-kDa target antigen. Although two patients with a single 180-kDa antigen specificity had a disease of unusually long duration, factors other than antigen specificity must determine the clinical expression of BP.

Aged↗

Recombinant interferon beta: a phase I-II trial in children with recurrent brain tumors.

A multicenter phase I-II trial of intravenous (IV) human recombinant interferon beta (rIFN-beta; Betaseron; Triton Bioscience Inc, Almeda, CA) was conducted in children with recurrent or progressive primary brain and spinal cord tumors. A total of 29 patients were enrolled: high-grade astrocytoma (12), brainstem glioma (nine), and primitive neuroectadermal tumor (three), ependymoma (two), germ cell (two), and spinal cord astrocytoma (one). Betaseron was given by IV infusion over 30 minutes 3 times per week (Monday-Wednesday-Friday [MWF]). Four dose levels were studied, and at least three patients were entered at each dose level. The treatment plan began with a three-step dose escalation for each patient over 6 weeks (initiation phase). The dose-escalation schema for the four dose levels was: 50-100-200, 100-200-400, 200-300-500, and 300-400-600 x 10(6) (M) IU/m2. Patients experiencing an objective response or stable disease after 6 weeks entered the maintenance phase at the final escalated dose, ie, 200, 400, 500, or 600 mlU/m2 (MWF). Common transient effects included chills, fever, and fatigue. Dose-limiting toxicities were hematologic, hepatic, and CNS. The maintenance maximum-tolerable dose (MTD) was 500 mlU/m2, ie, dose level 3. Response was assessed at completion of the initiation phase and at 2-month intervals during the maintenance phase. Objective partial responses were seen in patients with high-grade astrocytoma (two) and brain-stem glioma (two). Thus, four of 21 (19%) assessable patients had partial responses for a median of 4 months. Eight patients had stable disease for a median of 5+ (2 to 14+) months. Antineoplastic activity has been identified in children with high-grade astrocytomas and brainstem gliomas in a dose-intensive regimen.

Brain Neoplasms↗