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Biomedical subjects

I Smith

Publications and source records attributed to I Smith.

At least 19 recordsLinked to original sources
PubMed1992

Cancer-cell traffic in the liver. I. Growth kinetics of cancer cells after portal-vein delivery.

Following the intrasplenic injection of B16F10 melanoma cells into mice, at first single cells, and later multicellular tumor foci were observed at different times in the liver. Cell numbers and tumor volumes were determined over the next 12 days, by confocal microscopy of thick liver sections. Fifteen minutes after injection, approximately 20% of the melanoma cells were identified in the liver microvasculature; after 48 hr, only 0.68% of these retained morphologic integrity; by 5 days only 0.13% of the originally detected cells incorporated BUdR; and, by 12 days, these subsequently grew into tumor nodules. Tumor volume changes with time were not exponential and, following a non-replicative period during the first 2 1/2 days, the volume doubling times increased from approximately 8 to 39 hr at 12 days. BUdR incorporation indicated that this was probably due to a diminishing proliferative fraction in the cancer-cell population. When animals were killed at 12 days, tumor foci were centered on the liver sinusoids and appeared to represent expansive growth of arrested cells, with no evidence of parenchymal invasion by migrating cancer cells, in spite of the absence of a subendothelial basement membrane. Our direct observations indicate that, in this model system, the post-delivery phase of hepatic colonization is characterized by high levels of inefficiency with respect to cancer-cell survival, growth and extravasation.

Animals↗
PubMed1992

Induction of transforming growth factor beta 1 in human breast cancer in vivo following tamoxifen treatment.

We have investigated the ability of tamoxifen to regulate members of the transforming growth factor beta (TGF-beta) family in human breast cancers in vivo. Using immunohistochemical techniques, we find that 3 months of tamoxifen treatment causes a consistent induction of extracellular TGF-beta 1 in breast cancer biopsies, compared with matched pretreatment samples from the same patient. The induced TGF-beta is localized between and around stromal fibroblasts and appears to be derived from these cells. Lower levels of TGF-beta 1,-beta 2, and -beta 3 seen in epithelial cells were not altered by tamoxifen treatment. The increased stromal staining of TGF-beta 1 occurred in estrogen receptor-negative as well as estrogen receptor-positive tumors. These results provide in vivo evidence for a novel, estrogen receptor-independent mechanism of action for tamoxifen, involving the stromal induction of a potent growth inhibitor for epithelial cells.

Biomarkers, Tumor↗
PubMed1992

Tryptophan and serotonin metabolism in familial erythrophagocytic lymphohistiocytosis.

Reduced concentrations of tryptophan and 5-hydroxyindoleacetic acid (the major CSF metabolite of serotonin) were found in the cerebrospinal fluid of two children with familial erythrophagocytic lymphohistiocytosis. This was associated with elevated cerebrospinal fluid neopterin concentrations indicating increased macrophage activity within the central nervous system. In one child, cytotoxic therapy induced a complete clinical remission and an increase of tryptophan and 5-hydroxyindoleacetic acid concentrations to normal; during a subsequent relapse, concentrations of these analytes again fell below normal. In the other child, in whom therapy produced only a transient improvement, tryptophan and 5-hydroxyindoleacetic acid concentrations remained low and the child died. It is likely that increased activity of indoleamine 2,3-dioxygenase induced by the activation of macrophages was responsible for the disturbance in serotonin and tryptophan homeostasis within the brain. Excessive tryptophan catabolism and the disturbance of serotonin turnover may play a role in the aetiology of the neurological symptoms seen in familial erythrophagocytic lymphohistiocytosis.

Aging↗
PubMed1992

Familial glucocorticoid deficiency with achalasia of the cardia associated with mixed neuropathy, long-tract degeneration and mild dementia.

This paper describes the progress of two previously reported brothers with familial glucocorticoid deficiency, achalasia of the cardia, and alacrima. In their early 'teens both boys developed polyneuropathy with sensory, motor and autonomic components, Parkinsonism, and signs of both dorsal column and pyramidal tract damage. The older boy also showed signs of dementia. Red cell folate levels were markedly reduced but plasma and CSF folate were normal. Serum B12 and erythrocyte concentrations were at or below the lower limit of normal CSF levels of homovanillic acid and 5-hydroxyindole acetic acid (the major metabolites of dopamine and serotonin in brain) were low, indicating impaired turnover of the two amines within the nervous system. Positron emission photometry scans in the older boy showed low binding of c-methyl-spiperone and reduced uptake of 18-F-L-fluorodopa in the striatum, confirming the impairment in dopamine metabolism and suggesting both reduced synthesis and reduced receptor density. Treatment with L-dopa up to 800 mg/day (along with carbidopa 200 mg/day) corrected the low CSF homovanillic acid levels and produced some improvement in the Parkinsonism but no other obvious clinical benefit. Empirical treatment with hydroxycobalamin (1000 micrograms three times a week) and folinic acid (15 mg/day) was without clinical effect. The cause of the neurological disorder, low red-cell folate concentrations, and amine disturbance remains unknown, as does the pathogenesis of the adrenocortical failure.

Adolescent↗
PubMed1992

The Fifth Edition of the Addiction Severity Index.

The Addiction Severity Index (ASI) is 12 years old and has been revised to include a new section on family history of alcohol, drug, and psychiatric problems. New items were added in existing sections to assess route of drug administration; additional illegal activities; emotional, physical, and sexual abuse; quality of the recovery environment; and history of close personal relationships. No changes were made in the composite scoring to maintain comparability with previous editions. This article discusses the clinical and research uses of the ASI over the past 12 years, emphasizing some special circumstances that affect its administration. The article then describes the rationale for and description of the changes made in the ASI. The final section provides "normative data" on the composite scores and severity ratings for samples of opiate, alcohol, and cocaine abusers as well as drug abusing inmates, pregnant women, homeless men, and psychiatrically ill substance abusers.

Adolescent↗
PubMed1992

Effects of ketorolac and bupivacaine on recovery after outpatient arthroscopy.

The effects of intraarticular bupivacaine, systemic ketorolac, and a combination of both treatments on postoperative pain and mobilization were evaluated in 60 healthy outpatients undergoing arthroscopic knee surgery under general anesthesia. After induction of anesthesia, patients received 2 mL of either ketorolac (60 mg) or saline solution (1 mL IV and 1 mL IM). On completion of surgery, the patient's knee joint was injected with 30 mL of either 0.5% bupivacaine or saline solution, according to a randomized, double-blind protocol. Only one patient (6%) receiving both medications complained of pain on awakening, compared with seven patients receiving either bupivacaine (37%) or ketorolac (41%) alone. Postoperative fentanyl was required by significantly fewer patients receiving combined therapy (n = 4, 21%) than either bupivacaine (n = 13, 62%) or ketorolac (n = 12, 60%) alone; however, there were no significant differences among the three treatment groups in terms of perioperative pain, nausea, or sedation visual analogue scale scores. Similarly, there were no differences in the times to ambulation or discharge or in analgesic requirements at home. In conclusion, a combination of systemic ketorolac and intraarticular bupivacaine decreased analgesic requirements and pain on awakening after arthroscopic surgery. However, the use of ketorolac alone or in combination with bupivacaine offered no advantage over bupivacaine alone with respect to recovery times after outpatient arthroscopy.

Adult↗
PubMed1992

Use of the laryngeal mask airway as an alternative to a face mask during outpatient arthroscopy.

The laryngeal mask airway (LMA) has recently become available in the United States, and several authors have suggested that it is superior to an anesthesia mask. To test this hypothesis, 64 patients undergoing outpatient arthroscopic knee surgery were randomly assigned to have anesthesia maintained via either a laryngeal mask airway (LMA) (n = 31) or a standard face mask (n = 33). Anesthesia was induced with fentanyl 1 microgram.kg-1 and propofol 2 mg.kg-1 and maintained with a variable-rate propofol infusion (50-180 micrograms.kg-1 x min) and nitrous oxide 67% in oxygen. The LMA was inserted without difficulty by inexperienced anesthesiologists in 90% of the patients. Problems associated with airway management were more common in patients in the face mask (control) group. Episodes of hemoglobin oxygen desaturation (< 95%) occurred in 52% of patients in the face mask group compared to only 13% in the LMA group (P < 0.05). Intraoperative airway manipulations were required in 15% of face mask patients (vs. 3% of the LMA group), and difficulties in maintaining an airway were reported by 24% of the resident anesthesiologists caring for patients in the face mask group (vs. none in the LMA group) (P < 0.05). Insertion of the LMA was not associated with any acute changes in hemodynamic values. Intraoperative hemodynamic values and anesthetic requirements did not differ significantly between the two treatment groups. There were no significant differences in the emergence and recovery times or in the incidence of postoperative sore throats between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

An attempt to standardize APTT reagents used to monitor heparin therapy.

Citrated samples from 100 patients on i.v. heparin and 20 normal patients were tested with three batches each of three activated partial thromboplastin time (APTT) reagents: Thrombosil I (Ortho); Automated APTT (Organon Teknika) and Actin FSL (Baxter). The ratio of APTT over the geometric mean normal APTT for each heparinized sample was calculated. One batch of reagent arbitrarily chosen as a reference gave the ratios APTRREF (y). The remaining reagents to be standardized against the reference system gave the ratios APTRTEST (x). The best correlation between systems was given by log vs log x. Standard curves were prepared from the APTT ratios of the 20 normal patients and 65 of the heparinized samples. On plotting log APTRTEST vs log APTRREF the y intercept was close to zero so x was expressed in terms of y using; log x = HSI. log y, where HSI (Heparin Sensitivity Index) = slope. The APTRTEST results of the remaining 35 heparinized samples were transformed using; APTRTRANS = (APTRTEST)HSI.APTRTRANS was then compared to APTRREF to determine whether the transformation brought the results closer to the reference. We conclude that although some improvement was found by using the transform, it was not possible to mathematically relate APTT results due to a high degree of variation between results using different reagents. A standard APTT reagent for the monitoring of heparin therapy is recommended. A separate APTT reagent may be required for the screening of factor deficiencies and lupus anticoagulants.

Animals↗
PubMed1992

A simple and rapid method for the detection and identification of mycobacteria using mycobactin.

A system was developed for the identification of mycobacteria such as Mycobacterium tuberculosis and M. avium, by thin layer chromatography of 55Fe-labelled mycobactin. Approximately 2 x 10(3) mycobacteria were detected within 24 h and little operator time or skill was required. M. avium, M. intracellulare and M. scrofulaceum were found to have lower requirements for iron than other mycobacteria and this may influence their growth in host organisms.

Chromatography, Thin Layer↗
PubMed1992

Rising IQ scores in British children: recent evidence.

Between 1987 and 1990 IQ scores for 333 5-year-old white school children were obtained using the Wechsler Pre-School and Primary Scale of Intelligence (WPPSI) and the results were compared with 112 children assessed in 1967. The mean full scale IQ score of 113.3 was 8 points higher than the mean of 105.1 in the 1967 study. These findings indicate that the rate of increase of IQ scores was comparable and probably higher than that reported in the U.S.A. for the period 1932-78. It is important that this large increase is taken into account for correct interpretation of IQ test results.

Child, Preschool↗
PubMed1992

Sin, a stage-specific repressor of cellular differentiation.

Sin is a Bacillus subtilis DNA-binding protein which is essential for competence, motility, and autolysin production but also, if expressed on a multicopy plasmid, is inhibitory to sporulation and alkaline protease synthesis. We have now examined the physiological role of Sin in sporulation and found that this protein specifically represses three stage II sporulation genes (spoIIA, spoIIE, and spoIIG) but not the earlier-acting stage 0 sporulation genes. sin loss-of-function mutations cause higher expression of stage II genes and result in a higher frequency of sporulation, in general. Sin binds to the upstream promoter region of spoIIA in vitro and may thus gate entry into sporulation by directly repressing the transcription of stage II genes. In vivo levels of Sin increase rather than decrease at the time of stage II gene induction, suggesting that posttranslational modification may play a role in downregulation of negative Sin function.

Bacillus subtilis↗
PubMed1992

Bacillus subtilis early sporulation genes kinA, spo0F, and spo0A are transcribed by the RNA polymerase containing sigma H.

The Bacillus subtilis genes kinA (spoIIJ), spo0F, and spo0A encode components of the sporulation signal transduction pathway. Recent work has suggested that these genes are transcribed by a minor form of RNA polymerase, E sigma H (sigma H is the product of spo0H, another early sporulation gene). We directly tested this hypothesis by performing in vitro transcription assays with reconstituted E sigma H and a set of plasmids containing the kinA, spo0F, and spo0A promoter regions. We were able to obtain distinct transcripts of the expected sizes with all three genes by using linearized or supercoiled templates. Furthermore, primer extension experiments indicate that the transcription start sites for the three genes in vitro and in vivo are the same. In addition, we measured steady-state levels of kinA, spo0F, and spo0A mRNAs during growth in sporulation medium; all of them were increased at or near the beginning of the stationary phase.

Bacillus subtilis↗
PubMed1992

Congenital hypothyroidism detected by neonatal screening: relationship between biochemical severity and early clinical features.

The relationships between biochemical severity of hypothyroidism (as judged by plasma thyroxine) and the clinical and radiographic findings at diagnosis were evaluated in 449 infants born in 1982-4 with congenital hypothyroidism identified by neonatal screening. Details of pregnancy, delivery, and the neonatal period were also examined and compared with the findings in a normal population of 36,727 infants born in 1988. Infants with plasma thyroxine values of 30 nmol/l or less had a significantly higher incidence of prolonged jaundice, feeding difficulties, lethargy, umbilical hernia and macroglossia, showed more severe delay of bone maturation on a knee radiograph, and had a higher proportion of thyroid agenesis on isotope scan. In contrast, an ectopic or hypoplastic gland was more common in infants with plasma thyroxine values above 30 nmol/l. Prevalence of illness in pregnancy and mode of delivery was not related to severity of hypothyroidism and were similar to figures for the normal population. Induction of labour, gestation over 40 weeks, and birth weight above 3500 g were significantly more common in the hypothyroid infants. Perinatal illness and congenital malformations were more common in the infants with low plasma thyroxine values at diagnosis.

Adult↗
PubMed1992

Violent visual hallucinations and aggression in frontal lobe dysfunction: clinical manifestations of deep orbitofrontal foci.

Three patients from different racial, social, and economic backgrounds were studied because of sudden intrusive thoughts: visions or intrusions of threatening scenes--violent, aggressive, and sometimes horrifying--that lasted from seconds to minutes. Apart from the association with intense anxiety, fear, and aggression, there was no association with oculomotor, motor, sensory, or autonomic dysfunction or altered conscious state. Patients had abnormal intermittent discharges that arose from frontal areas and probably did not spread further. Carbamazepine was useful in two cases. The authors suggest that violent, brief hallucinations with no other epileptic sign may be manifestations of frontal lobe seizures.

Adult↗
PubMed1992

Comparison of induction, maintenance, and recovery characteristics of sevoflurane-N2O and propofol-sevoflurane-N2O with propofol-isoflurane-N2O anesthesia.

Induction of, maintenance of, and recovery from sevoflurane anesthesia were compared with propofol and isoflurane anesthesia when administered with nitrous oxide to patients undergoing gynecologic surgery. Seventy-five healthy (ASA I or II), consenting patients were randomly assigned to receive either (I) propofol for induction of anesthesia and isoflurane-nitrous oxide for maintenance (control), (II) propofol for induction and sevoflurane-nitrous oxide for maintenance, or (III) sevoflurane-nitrous oxide for induction and maintenance of anesthesia. Inhaled induction of anesthesia with sevoflurane-nitrous oxide was rapid (109 +/- 25 s to loss of consciousness) and without any untoward hemodynamic changes or episodes of coughing and laryngospasm. Mean arterial blood pressure after induction of anesthesia with propofol (71 +/- 11, 73 +/- 12 mm Hg for groups I and II, respectively) was lower than when sevoflurane (80 +/- 14 mm Hg) was used. The emergence time after discontinuation of isoflurane-nitrous oxide (6.7 +/- 2.2 min) was significantly longer than after propofol-sevoflurane-nitrous oxide or sevoflurane-nitrous oxide alone (4.1 +/- 2.2 and 4.0 +/- 2.0 min for groups II and III, respectively). However, later recovery events did not differ between groups. Serum fluoride levels increased after administration of sevoflurane but not isoflurane. The levels of fluoride ions correlated with the degree of exposure to sevoflurane in MAC-hours. In conclusion, induction of anesthesia with either propofol or sevoflurane-nitrous oxide was rapid and without significant side effects. Emergence and early recovery after maintenance of anesthesia with sevoflurane-nitrous oxide was significantly faster than that after an isoflurane-nitrous oxide combination.

Adult↗