Ocular motility anomalies in developmental misdirection of the optic chiasm.
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Adult↗
Biomedical subjects
C Harris
Publications and source records attributed to C Harris.
Growth kinetics and chemoprevention of aberrant crypts in the rat colon.
Single and multiple colonic crypts exhibiting dysplasia that are detectable in situ by staining of rat colon with methylene blue are called aberrant crypts (AC) and may serve as an intermediate marker for colon cancer. In a characterization study, we have established the kinetics of AC growth and development over a period of 20 d following injection of rats with the carcinogen azoxymethane (AOM). AC are not present at 5 d post-injection, but are a constant feature at 10 d and thereafter. Multiple AC, presumably clonal, begin to evolve at 10 d and are consistent by 20 d, forming incipient microadenomata. We have examined 20 candidate chemopreventive agents for inhibition of AC. All agents were given in AIN-76 diet, at two dose levels, with injections of AOM. AC were measured after 5 weeks of growth. Among the most active AC-inhibiting agents were BHA, DFMO, quercetin, diallyl sulfide, 18 beta-glycyrrhetinic acid, and ascorbyl palmitate. In a post-initiation study, the differentiating agent sodium butyrate was ineffective, but piroxicam was highly effective in modulating AC growth. Further, piroxicam inhibited AC development at all stages of growth from single to polycryptal clusters of AC. The AC assay shows marked sensitivity and specificity for screening agents for chemoprevention of colon cancer.
Animals↗
Unusual patterns of Histoplasma capsulatum meningitis and progressive multifocal leukoencephalopathy in a patient with the acquired immunodeficiency virus.
Disseminated histoplasmosis (DH) and progressive multifocal leukoencephalopathy occur in acquired immunodeficiency syndrome (AIDS). At autopsy, DH patients with central nervous system involvement almost always show extensive involvement of the lungs and reticuloendothelial system in addition to the brain, and progressive multifocal leukoencephalopathy is manifest as multiple demyelinating lesions in several locations in the brain. We describe an AIDS patient with a long history of aggressively treated DH who died with DH in the brain only; fungus was not found elsewhere at autopsy. In addition, there was a papovavirus infection restricted to the cerebellum with predominant involvement of the internal granular cell layer; again, demyelinating lesions were not found elsewhere in the brain. Each of these patterns of brain involvement is rare. As the incidence of AIDS increases and patients are treated aggressively, the frequency of unusual neuropathologic patterns of opportunistic infections may be expected to increase.
Acquired Immunodeficiency Syndrome↗
Functional aphonia in young people.
The study reviewed the case histories of 14 young aphonics. A questionnaire was completed by the five speech therapists involved with these cases. The patients were all initially examined by E.N.T. specialists and then treated by speech therapy. All the patients were 'cured' by speech therapy, that is the voice returned to its premorbid state. This study looks at common characteristics of presentation, different approaches to management, and the patterns of voice return.
Adolescent↗
The objective assessment of abnormal eye movements in infants and young children.
Recordings of eye movements from infants and young children can be of clinical value in patients with certain neuro-ophthalmological problems. This requires that the characteristics of normal eye movements in this same age-group are known. Using an electro-oculographic technique in a specially developed laboratory we have been able to assess the saccades, binocular and monocular smooth pursuit, binocular and monocular optokinetic nystagmus (OKN), and sustained vestibular rotation in infants and young children; these recordings were performed in one session lasting approximately 35 minutes. The recordings from four children with abnormal eye movements (delayed visual maturation, hemicerebral cyst, congenital ocular motor apraxia, and gaze-paretic nystagmus) are briefly reported and compared to normal eye movements of age-related children. The limitations of this procedure are discussed.
Adolescent↗
The prescriber must have full responsibility.
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Attitude of Health Personnel↗
Physician-hospital networking: avoiding a shotgun wedding.
The erosion of the traditional market is forcing hospitals and physicians to reevaluate their historical relationships. One method for addressing the potential conflicts created by current pressures is the formation of physician-hospital networks. These entities are formed and function on the basis of mutual interests and responsiveness to change.
Economic Competition↗
Junior doctors, nurses, and drips.
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Education, Nursing↗
Fetotoxic alterations in the normal ontogenies of rat microsomal and lysosomal enzymes.
The activity patterns during development for acid phosphatase (Ac-P), alkaline phosphatase (A1-P), beta-glucuronidase (beta G), and UDP-glucuronyltransferase (UDPGT) have been determined in various tissues of the rat for corn oil and distilled water controls as well as in animals prenatally exposed to four fetotoxic chemicals. Postnatal assays were performed on both sexes separately. In control animals, tissue-specific differences between male and female activity levels were found for UDPGT. In the liver of mature offspring, enzyme activity was greater in males than in females. Although no sex difference was observed in the intestine, the kidneys of females exhibited higher values than those of males. An original computer-assisted methodology is presented, designed (a) to permit a mathematical description for the complex curves exhibited by these ontogeny profiles, and (b) to assess the statistical significance of chemical-induced alterations in these complex developmental patterns, specifically, to target sensitive periods and subtle changes near the fetotoxic threshold. Oral administration (days 6-18 of gestation) of 3,3',4,4'-tetrachlorobiphenyl (4CB) to pregnant females resulted in an induction of liver UDPGT activity in offspring postnatally, and some alterations in the perinatal pattern of beta G in the same tissue. This treatment also produced differences in the intestinal patterns of Ac-P and male UDPGT. No significant changes were observed in offspring exposed to diethylstilbestrol (DES). Treatment with zeranol (ZN) caused reductions in activity over the entire postnatal period for beta G in liver, brain, intestine, and kidney, for A1-P in brain, and for Ac-P in the intestine. Cadmium-treated dams gave birth to offspring that exhibited slightly altered ontogenies only in intestine for UDPGT and AcP. The alterations in these developmental profiles indicate periods of increased sensitivity, and may be useful in directing more specific studies into the fetotoxic mechanisms of these compounds.
Acid Phosphatase↗
Morphological differences elicited by two weak acids, retinoic and valproic, in rat embryos grown in vitro.
We compared in rat whole-embryo culture the morphological changes elicited by valproic acid (VPA) with those elicited by trans-retinoic acid (RA). Rat embryos explanted on day 9.5 of gestation were treated on day 10 with RA or VPA at concentrations producing equivalent reductions in embryonic protein. The concentrations selected for morphological assessment by scanning and transmission electron microscopy, 2.3 and 800 microM, respectively, for RA and VPA, produced approximately a 50% incidence of abnormally open anterior neuropores in initial range-finding experiments in the culture system. Protein and DNA analyses were also performed on corresponding groups of embryos at three different doses. With concurrent control groups used as reference standards, the two treatment groups were compared for differences in external and internal morphology, protein and DNA contents, and growth indices. While certain variables responded similarly in the two treatment groups, e.g., the growth variables, protein and DNA contents, each drug produced selective morphological effects. Whereas treatment with RA produced underdeveloped branchial arches, symmetrically cleft cranial defects resulting in openings in rhombencephalic and prosencephalic regions, and exteriorized neural tissue in the caudal neuropore region, VPA produced irregular clefts with wavy margins along the entire length of the neural tube, and an open caudal neuropore without eversion of the neuroepithelium, while producing no detectable effect on the branchial arches. The similar effects of these two drugs on protein and DNA contents suggest comparable degrees of overall toxicity; however, the dissimilar effects on neural tube and branchial arches, coupled with the large difference in concentration of the drug required to produce the effects, add to the evidence that their mechanisms for elicitation of abnormal development are qualitatively different.
Animals↗
Role of glutathione and hsp 70 in the acquisition of thermotolerance in postimplantation rat embryos.
Studies were initiated to determine the extent to which reduced glutathione (GSH) may be involved in the capacity of cultured rat embryos to develop heat-induced tolerance to the deleterious effects of exposure to high temperatures (heat shock). Investigations of the modulation of dysmorphogenic responses of embryos to heat shock (43 degrees C, 30 min) as well as to the expression of the hsp70 gene and subsequent formation of hsps indicated that the acquisition of thermotolerance by rat embryos could be significantly influenced by the inhibition of GSH synthesis. Treatment of conceptuses with L-buthionine-S,R-sulfoximine (BSO) reduced intracellular GSH concentrations and compromised the capacity of embryos to mount a thermotolerance response as assessed by alterations in indices of growth and development. Embryonic thermotolerance elicited by preexposure to 42 degrees C for 30 min was accompanied by increases in GSH to levels greater than those measured in control embryos at 37 degrees C just prior to the subsequent 43 degrees C heat exposure. Expression of hsp70 mRNA was detectable soon after elevation of the temperature to 42 degrees C and reached its highest level of accumulation 1.5 hr after the 43 degrees C heat shock. BSO treatment had little if any effect on hsp70 message levels or on the synthesis of hsp70. The fact that BSO-treatment attenuated the thermotolerance response but did not produce a decrease in hsp70 RNA or the synthesis of hsp70 suggests that hsp70 alone is not sufficient to confer thermotolerance upon cultured rat embryos.
Animals↗
Cytochrome P450-dependent bioactivation of prodysmorphogens in cultured conceptuses.
These investigations were undertaken to determine the extent to which tissues of cultured rat conceptuses contain cytochrome P450 isoforms in sufficient quantities to significantly influence the capacity of certain chemicals to elicit dysmorphogenic effects in vitro. Investigations with highly sensitive probe substrates/inhibitors and with immunologic methods enabled the detection of at least four separate P450 isoforms in tissues of the visceral yolk sac, ectoplacental cone, and embryo proper. One of the isoforms was identified as P450IA1 and was found to be inducible by polycyclic aromatic hydrocarbons in all three tissues. Other isoforms exhibited properties differing from characterized adult rat hepatic isoforms. Each of the isoforms was detectable in conceptuses on gestational days 10, 11, 12, and 14 and was present in the highest concentrations in the visceral yolk sac. Conceptal P450IA1 catalyzed the conversion of dysmorphogenically inactive 2-acetylaminofluorene to 7-hydroxy-2-acetylaminofluorene, a proximate dysmorphogen. Investigations with microinjections suggested that visceral yolk sac hydroxylation was largely responsible for the bioactivation reaction in vitro. The same isoform exhibited no capacity to influence the dysmorphogenic activity of cyclophosphamide. The results demonstrated that tissues of cultured rat conceptuses may contain P450 isoforms in sufficient amounts to markedly influence the dysmorphogenic activity of substrates of the corresponding isoforms.
Animals↗
The will and the ways: development and validation of an individual-differences measure of hope.
Defining hope as a cognitive set that is composed of a reciprocally derived sense of successful (a) agency (goal-directed determination) and (b) pathways (planning of ways to meet goals), an individual-differences measure is developed. Studies demonstrate acceptable internal consistency and test-retest reliability, and the factor structure identifies the agency and pathways components of the Hope Scale. Convergent and discriminant validity are documented, along with evidence suggesting that Hope Scale scores augmented the prediction of goal-related activities and coping strategies beyond other self-report measures. Construct validational support is provided in regard to predicted goal-setting behaviors; moreover, the hypothesized goal appraisal processes that accompany the various levels of hope are corroborated.
Adaptation, Psychological↗
Pharmacokinetic study of lomefloxacin and its effect on the faecal flora of volunteers.
In a volunteer pharmacokinetic study mean peak serum concentrations of lomefloxacin of 7.19 mg/l were obtained 1.5 h after an oral dose of 400 mg. Women had higher concentrations than men. Urinary excretion was 34% in 6 h and 63% in 24 h and the mean peak concentration was 699 mg/l. Saliva concentrations were 37% of those in serum. Lomefloxacin was detectable in the faeces up to seven days after the last dose. The major effect of lomefloxacin on the faecal flora of volunteers following a four day course of 400 mg once daily was the elimination of strains of Enterobacteriaceae and an increase in the numbers of Gram-positive cocci, mainly streptococci. There was no effect on anaerobic bacteria or yeasts. Lomefloxacin was well tolerated and no side effects were recorded. No bacterial resistance was detected after treatment.
4-Quinolones↗
Headache in HIV-1-related disorders.
To define the causes, clinical significance and characteristics of headaches in HIV-1-related disorders, we studied 49 consecutive HIV-1 infected patients who presented with headache. Work-up included CT scans, cerebrospinal fluid examinations (in the absence of a contraindication) and serologic studies. Overall, 40 of 49 patients (82 percent) had an identifiable serious cause of headache. Cryptococcal meningitis (39 percent) and CNS toxoplasmosis (16 percent) were the leading headache etiologies. Serious causes were more likely in patients diagnosed with AIDS prior to presentation but also occurred in most patients in early stages of infection. Based on this study, we suggest that patients with HIV-1 infection must be managed with a high index of suspicion when they present with new onset headaches.
Adult↗
Efficacy of acemannan in treatment of canine and feline spontaneous neoplasms.
Forty-three dogs and cats with spontaneous tumors were treated with the immunostimulating polysaccharide acemannan by intraperitoneal and intralesional routes of administration. Tumors from 26 of these animals showed histopathological evidence of immunological attack as shown by marked necrosis or lymphocytic infiltration. Thirteen showed moderate to marked tumor necrosis or liquefaction. Twenty-one demonstrated lymphoid infiltration, and seven demonstrated encapsulation. Twelve animals showed obvious clinical improvement as assessed by tumor shrinkage, tumor necrosis, or prolonged survival; these included five of seven animals with fibrosarcomas. It is believed that acemannan exerts its antitumor activity through macrophage activation and the release of tumor necrosis factor, interleukin-1, and interferon.
Adjuvants, Immunologic↗
More on nasal vs. oral suctioning in newborn infants.
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Humans↗
The evaluation of patients with human immunodeficiency virus-related disorders and brain mass lesions.
In patients at risk for acquired immunodeficiency syndrome who present with a mass lesion, a dilemma arises as to whether to treat empirically for toxoplasmosis or perform a brain biopsy. We present data that further define the indications for performing brain biopsy vs empiric treatment. We reviewed charts on 59 patients with acquired immunodeficiency syndrome--related disorders and cerebral mass lesions. Thirty-two patients met diagnostic criteria for toxoplasmosis. Bayesian analysis demonstrated that the prior probability of toxoplasmosis was increased by the presence of contrast enhancement on computed tomographic scans (0.68) and toxoplasmosis titers greater than 1:64 (0.81). Features associated with decreasing probabilities of toxoplasmosis included the absence of contrast enhancement on computed tomographic scans (0.29) and toxoplasmosis titers less than or equal to 1:64 (0.14). Ten percent of patients had complications of brain biopsy. Treatment with pyrimethamine and sulfadiazine produced complications in 29% and serious complications in 8% of treated patients. These data favor empiric therapy for patients with typical features of toxoplasmosis and brain biopsy for defined subsets of patients with atypical features.
Bayes Theorem↗