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Biomedical subjects

L Sanders

Publications and source records attributed to L Sanders.

At least 55 records · Page 3Linked to original sources

Addressing the public's concerns about human immunodeficiency virus transmission in health-care settings.

BACKGROUND: The 1990 report of a cluster of patients infected with the human immunodeficiency virus (HIV) associated with a Florida dentist with acquired immunodeficiency syndrome attracted considerable media coverage and legislative attention. A number of polls found that the public favored mandatory HIV-antibody testing of health-care workers. The Centers for Disease Control and Prevention, Atlanta, Ga, conducted a two-phase study to understand how public concerns regarding potential HIV transmission in health-care settings can be addressed by the medical and public health communities. METHODS: Sixteen focus group discussions in nine US cities were conducted to explore the public's perceptions, concerns, and behavioral responses regarding HIV transmission in health-care settings. Using this information, a questionnaire was developed and administered to a nationwide probability telephone sample of 1150 adults. RESULTS: Concern about contracting HIV in health-care settings was highest for emergency department treatment and lowest for treatment by a personal physician. Two factors directly related to patient care, ie, the health-care professional's willingness to discuss acquired immunodeficiency syndrome and the presence of acquired immunodeficiency syndrome educational materials in the waiting room, were considered useful factors for determining potential risk of transmission of HIV in a health-care setting. CONCLUSIONS: Public concern about the potential for HIV transmission in health-care settings remains high. Active steps on the part of health-care professionals, such as providing educational materials and initiating discussions about infection control procedures and about HIV and acquired immunodeficiency syndrome, could likely have positive effects in terms of alleviating these concerns.

Adolescent↗

Both beta 1- and beta 2-adrenoceptors mediate catecholamine-evoked arrhythmias in isolated human right atrium.

The involvement of beta 1- and beta 2-adrenoceptors in catecholamine-evoked arrhythmias was investigated in isolated human right atrial appendages obtained from 22 patients chronically treated with beta blockers (usually beta 1-selective) and 9 patients not treated with beta blockers. A simple experimental model that assesses the incidence of arrhythmic contractions as a function of heart rate (pacing) is introduced. beta 1-adrenoceptors were activated by (-)-noradrenaline during beta 2-adrenoceptor blockade with 50 nmol/l ICI 118551. beta 2-adrenoceptors were activated by (-)-adrenaline during beta 1-adrenoceptor blockade with 300 nmol/l CGP 20712A. Both (-)-noradrenaline and (-)-adrenaline caused arrhythmic contractions whose incidence was greater at low than at high pacing rates. CGP 20712A (300 nmol/l) blocked the (-)-noradrenaline-evoked contractions in 1/1 atrial strip from 1/1 patient not treated with a beta blocker and 17/17 atrial strips from 15/15 patients chronically treated with beta blockers. ICI 118551 (50 nmol/l) blocked the (-)-adrenaline-evoked contractions in 3/4 atrial strips from 3/4 patients not treated with beta blockers and 17/20 atrial strips from 15/18 patients chronically treated with beta blockers. The incidence of arrhythmic contractions evoked by both (-)-noradrenaline and (-)-adrenaline was higher in chronically beta blocked patients than in non beta blocked patients. We conclude that both beta 1- and beta 2-adrenoceptors mediate atrial arrhythmias and that the generation of these arrhythmias is facilitated by chronic beta 1-adrenoceptor blockade.

Adrenergic beta-1 Receptor Antagonists↗

A 5-HT4-like receptor in human left atrium.

The effects of 5-hydroxytryptamine (5-HT) on left atrial preparations obtained from 5 patients with terminal heart failure who were undergoing heart transplant surgery were investigated. The preparations were paced under isometric conditions. In the presence of (-)-pindolol 1 mumol/l (to block beta-adrenoceptors) and cocaine 6 mumol/l (to block tissue uptake of 5-HT) 5-HT increased contractile force with a pEC50 of 7.0. The maximum effect of 5-HT amounted to 24.5% of that caused by a maximally effective concentration of (-)-isoprenaline (200 mumol/l) and 25% of that caused by 6.75 mmol/l CaCl2. The effects of 5-HT were competitively antagonised by 3 alpha-tropanyl-1H-indole-3-carboxylate (ICS 205-930) with a pKB of 6.8. The effects of 5-HT on cyclic AMP levels and cyclic AMP-dependent protein kinase activity were also studied using left atrial tissues from one of the patients; 5-HT increased the cyclic AMP content and stimulated the kinase. The results are consistent with the existence of a human left atrial 5-HT receptor which is similar to the recently identified human right atrial 5-HT receptor that resembles the 5-HT4 receptor. The left atrial 5-HT4-like receptor is functional in tissues obtained from patients with terminal heart failure.

Adult↗

Interurban migration and the dynamics of a system of cities: 1. The stochastic framework with an application to the French urban system.

"A stochastic framework for the modelling of interurban migration is presented. The model is an extension of a recently developed master-equation approach to interregional migration. The population dynamics of the French urban system, described by a set of 78 cities, is investigated within the period 1954-82. The importance of synergy effects (self-reinforcing collective effects) as well as socioeconomic macrovariables for the understanding of urban dynamics becomes obvious. A forecasting of urban dynamics...[up to the year 2002 confirms] this result and [gives] further insight into the nested structure of urban systems."

Demography↗

Visceral metastases from melanoma: findings on MR imaging.

Typical ocular and CNS melanomas are hyperintense on T1-weighted MR images and hypointense on T2-weighted MR images. We performed MR imaging in 48 patients with melanoma metastatic to visceral organs. Images were reviewed retrospectively in order to determine whether there were predominant MR features specific for visceral melanoma and to see if visceral metastases have MR characteristics similar to metastases in the CNS. Eleven patients also were examined after injection of gadopentetate dimeglumine to evaluate the enhancement characteristics of these tumors. Two hundred sixty-one lesions were found. Lesions were classified according to their signal intensities relative to uninvolved liver on T1-weighted, T2-weighted, and short TI inversion recovery (STIR) pulse sequences. Most commonly, lesions were either hypointense or isointense on T1-weighted sequences and hyperintense on T2-weighted and STIR sequences (185 lesions). Less frequently, lesions were hyperintense on T1-weighted sequences and hypointense or isointense on T2-weighted and STIR sequences (59 lesions). A mixed pattern was seen on T1- and T2-weighted sequences in 17 lesions. The patterns did not correlate with lesion size. Of the three sequences studied by subjective comparison, the STIR sequence in our series had the highest sensitivity for lesion detection and yielded the highest lesion conspicuity. Injection of gadopentetate dimeglumine in 11 patients did not increase either the number or the conspicuity of lesions seen. Our results show that visceral metastases from melanoma have a wide variety of appearances on MR images. The STIR sequence appears to be optimal, and the metastases do not enhance with gadopentetate dimeglumine.

Abdominal Neoplasms↗

A 5-HT4-like receptor in human right atrium.

The effects of 5-carboxamidotryptamine (5-CT) and the gastrokinetic benzamides renzapride and cisapride on contractile force were investigated using isolated paced right atrial appendages from patients treated with beta-adrenoceptor blocking agents who were undergoing open heart surgery. These effects were compared to those of 5-hydroxytryptamine (5-HT). The effects of the drugs on atrial cyclic AMP levels and cyclic AMP-dependent protein kinase ratios were also investigated. The drugs all increased contractile force of rank order of potency was 5-HT greater than renzapride greater than cisapride greater than 5-CT. The maximum responses, expressed as a fraction of the response to 200 mumol/l (-)-isoprenaline, were 5-HT 0.6, 5-CT 0.6, renzapride 0.4 and cisapride greater than or equal to 0.2, suggesting that the latter two are partial agonists. 5-HT, 5-CT and renzapride but not cisapride caused significant shortening of time to peak force. The effects of the four drugs were blocked by mumolar concentrations of ICS 205-930, suggesting an involvement of 5-HT4 receptors. As expected of partial agonists both renzapride and cisapride caused simple competitive antagonism of the positive inotropic effects of 5-HT. The estimated equilibrium dissociation constants pKP (-log mol/l KP) were 6.7 for renzapride and 6.2 for cisapride. 5-CT at concentrations up to 10 mumol/l did not antagonise the effects of 5-HT. In the presence of (+/-)-propranolol 0.4 mumol/l, 5-HT 10 mumol/l, 5-CT 100 mumol/l, renzapride 10 mumol/l and cisapride 40 mumol/l significantly increased cyclic AMP levels. 5-HT and renzapride also significantly increased cyclic AMP-dependent protein kinase activity, whereas 5-CT caused only marginal stimulation and cisapride was ineffective. The results confirm the existence of a human right atrial 5-HT receptor that is similar in nature to, but not necessarily identical with, the 5-HT4 receptor of mouse embryonic colliculi neurones. The main difference is that in human right atrium the benzamides are less potent and efficacious than 5-HT and that cisapride is less potent and less efficacious than renzapride while in mouse embryonic colliculi these two benzamides are equipotent with and more efficacious agonists than 5-HT. We designate the human right atrial 5-HT receptor 5-HT4-like. The human right atrial 5-HT4-like receptor greatly resembles porcine sinoatrial and left atrial 5-HT4-like receptors and also appears to be similar to 5-HT4-like receptors of guinea-pig ileum and rat oesophagus.

Benzamides↗

Relationship of hospitalized stroke rate and in-hospital mortality to the decline in US stroke mortality.

Data from the National Hospital Discharge Survey was used to estimate the admission rate and in-hospital mortality for US stroke patients from 1970 to 1987. Over this period the hospital admission rate increased from 5.0 per 1,000 population to 5.5 per 1,000, while the in-hospital mortality fell from 18.6 to 10.0% of discharges. When patients experiencing general or late effects or transient ischemic attacks were excluded, the hospital admission rate increased from 2.8 to 4.8 per 1,000 and in-hospital mortality fell from 26 to 12% of discharges. Admission rates increased from 1970 to 1987 for both hemorrhagic strokes and cerebral infarctions, but fell for ill-defined cerebrovascular events, presumably reflecting increased use of computed tomography and magnetic resonance imaging during this period. Mortality for hemorrhagic strokes decreased from 45 to 30% of discharges, mortality for infarctions decreased from 24 to 13% and mortality for ill-defined events fell from 24 to 17%. There are several limitations with the use of the National Hospital Discharge Survey data to estimate changes in hospital admission rates and in-hospital mortality. However, these data suggest a greater role for decreasing case fatality in explaining nationwide declines in stroke mortality rates than has generally been acknowledged.

Acute Disease↗

A 5-hydroxytryptamine receptor in human atrium.

1. The effects of 5-hydroxytryptamine (5-HT) were investigated on right atrial appendages obtained from patients treated with beta-adrenoceptor blocking agents who were undergoing open heart surgery. Atrial strips were paced under isometric conditions. 2. 5-HT increased contractile force to approximately one half of the force produced by a saturating concentration of (-)-isoprenaline. Both 5-HT and (-)-isoprenaline accelerated the onset of relaxation, as indicated by an abbreviation of time to peak force. 3. The effects of 5-HT were resistant to blockade by 0.4 microM (+/-)-propranolol, 1 microM (-)-pindolol, 0.4 microM methiothepin, 4 microM yohimbine, 0.4 microM ketanserin, 10 microM phenoxybenzamine, 1 microM methysergide, 2 microM MDL 72222 and 20 microM granisetron. 4. Cocaine 6 microM potentiated the effects of 5-HT, increasing the pEC50 from 6.6 to 7.4. The inotropic potency of 5-HT is five times greater than that of (-)-noradrenaline. 5. ICS 205930 antagonized competitively the effects of 5-HT with a pKB of 6.7. 6. In the presence of 0.4 microM (+/-)-propranolol, 10 microM 5-HT increased both adenosine 3':5' cyclic-monophosphate (cyclic AMP) levels and cyclic AMP-dependent protein kinase activity by approximately one half and two thirds respectively, of the corresponding effects of 200 microM (-)-isoprenaline. 7. Both the increase in cyclic AMP levels and the stimulation of protein kinase activity are consistent with the inotropic effects of 5-HT being mediated by cyclic AMP-dependent phosphorylation of Ca2+ channels and of proteins involved in contraction and relaxation. 8. The human atrial 5-HT receptor resembles the neuronal 'so called' 5-HT4 receptor of rodents both in increasing cyclic AMP levels and in its affinity for ICS 205930.

Cocaine↗

Expression of cyr61, a growth factor-inducible immediate-early gene.

A set of immediate-early genes that are rapidly activated by serum or purified platelet-derived growth factor in mouse 3T3 fibroblasts has been previously identified. Among these genes, several are related to known or putative transcription factors and growth factors, supporting the notion that some of these genes encode regulatory molecules important to cell growth. We show here that a member of this set of genes, cyr61 (originally identified by its cDNA 3CH61), encodes a 379-amino-acid polypeptide rich in cysteine residues. cyr61 can be induced through protein kinase C-dependent and -independent pathways. Unlike many immediate-early genes that are transiently expressed, the cyr61 mRNA is accumulated from the G0/G1 transition through mid-G1. This expression pattern is due to persistent transcription, while the mRNA is rapidly turned over during the G0/G1 transition and in mid-G1 at the same rate. In logarithmically growing cells, the cyr61 mRNA level is constant throughout the cell cycle. Cyr61 contains an N-terminal secretory signal sequence; however, it is not detected in the culture medium by immunoprecipitation. Cyr61 is synthesized maximally at 1 to 2 h after serum stimulation and has a short half-life within the cell.

Amino Acid Sequence↗

Effects of dilevalol on human atrial muscle.

The beta 1- and beta 2-adrenoceptor agonist effects of dilevalol on human heart tissue were studied in vitro. The receptors were studied independently of one another through the use of selective antagonists. Human right atrial appendages were generally cut into four strips which were then set up in parallel in an organ bath system. All tissues were incubated either with 300 nM CGP 20712A to block beta 1-adrenoceptors, or with 50 nM ICI 118551, to block beta 2-adrenoceptors. Alpha-adrenoceptors and tissue uptake of catecholamines were blocked using 5 microM phenoxybenzamine. The atrial strips from one patient were then exposed either to vehicle or to cumulative additions of dilevalol, (+)- pindolol or salbutamol (10(-8) to 10(-5) M) and the resulting force of contraction was expressed as a percentage of the inotropic response obtained with a saturating dose of (-)-isoprenaline. The beta-antagonist effects of the three substances were also studied, by running a dose-response curve to noradrenaline or adrenaline as appropriate following the addition of the substance of interest. Neither dilevalol nor (+)-pindolol had any intrinsic sympathomimetic activity at the atrial beta 1- or beta 2-adrenoceptors. Both dilevalol and (+)-pindolol caused marked antagonism of the atrial beta-adrenoceptors. They caused similar blockade of the beta 2-adrenoceptors but not of the beta 1-adrenoceptors.

Albuterol↗

Babinski's sign in medieval, Renaissance, and baroque art.

In 1896, Joseph François Babinski first described his well-known sign of dorsiflexion of the big toe on stimulating the sole of the foot. However, unknown to Babinski, several painters had previously demonstrated this phenomenon in their paintings. Sandro Botticelli (1445-1510), a Florentine Renaissance painter, demonstrated this reflex in his Madonna and Child with Angels 400 years before the publication of Babinski's discovery. Botticelli used live infants as models for his paintings. Gentile da Fabriano (d 1427) in his Adoration of the Kings, demonstrates a similar response of toe extension in the infant Jesus when one of the Magi kisses the baby's foot. Similarly, Jacob Schick von Kempter, a 16th century German painter, in his Coronation of the Virgin demonstrates the extensor plantar response in the infant. Correggio (1492-1534), in northern Italy captured the extension and flare of the baby's toes in his Madonna and Child with Mary Magdalen. Raphael (1483-1520) presented the extensor plantar responses in the child when sole pressure is applied in Small Cowper Madonna. Leonardo da Vinci, with his nude model drawings (1503-1507) seemed to have been aware of this response. There is no indication that any of these artists fully understood the physiology behind the response; therefore, the value of this sign in neurologic disease must still rely on Babinski's demonstration several hundred years after its initial demonstration in artistic literature.

Child↗

Isolation of rat Schwann cell lines: use of SV40 T antigen gene regulated by synthetic metallothionein promoters.

Synthetic promoter elements from the mouse metallothionein-I promoter controlling the expression of SV40 T antigen have been tested for their efficacy in cloning rat Schwann cell lines that retained the characteristic properties of these cells and could be passed in culture indefinitely. The constructed promoters contained either four (MT4) or five (MT5) copies of a metal regulatory element 5' to the CAAT and TATA elements from the HSV-1 thymidine kinase gene. Characterization of these promoters in transient expression assays and transformation assays showed that both MT5 and MT4 were approximately 10-fold and 15-fold, respectively, weaker than the wild-type MT-I promoter in the presence of heavy metal inducer. However, in the absence of inducer, the basal activity of both MT5 and MT4 was barely detectable and much lower than that of MT-I. Schwann cells were transfected with plasmids containing the SV40 T antigen gene under the control of the different metallothionein promoters and cell lines were established from each. Only with the MT5 and MT4 promoters were lines obtained that resembled secondary Schwann cells in culture in their morphology, generation time, and demonstration of contact inhibition. In the presence of zinc, the expression of T antigen in the lines derived with MT5 and MT4 was about 10-fold lower than that derived with MT-I. On removal of the inducer this level was reduced, and in one cell line T antigen was undetectable. Concomitant with the reduction in T antigen expression there was an increased expression of Po, a protein specific to myelin-forming Schwann cells, and a decreased expression of glial fibrillary acidic protein, a protein expressed only in nonmyelin-forming Schwann cells. These cell lines, therefore, closely resemble untransfected Schwann cells in culture.

Animals↗

High-performance liquid chromatographic assay of biphenyl metabolism by hepatocytes cultured in an embryo/hepatocyte co-culture medium.

A high-performance liquid chromatographic method has been modified for the evaluation of both Phase I and II metabolism of biphenyl by hepatocytes maintained in an embryo/hepatocyte co-culture medium. Extracts of the media, before and after hydrolysis of conjugates, are directly injected onto the HPLC and the major hydroxylated metabolites plus unmetabolized biphenyl are detected by fluorescence after separation under gradient or isocratic conditions. The method is almost free of interferences and is relatively simple and rapid. In the case of the monohydroxylated derivatives, the minimum media concentrations which can be measured are 7 to 20 nM (0.07 to 0.2 pmol on-column). Recoveries from culture medium to which known amounts of biphenyl and metabolites had been added were quantitative (90-103%) and the reproducibility good (interassay CV less than 5%). The assay was applied to cultures of hepatocytes derived from rabbit and from phenobarbital induced and noninduced rat.

Animals↗

MRI of multilocular cystic nephroma.

We report the magnetic resonance imaging (MRI) findings in 2 patients with multilocular cystic nephromas. Both underwent MRI immediately prior to resection. The images accurately reflected the morphology of the tumors: in each, the capsule was hypointense on all pulse sequences. Varied intensities of signal from the fluid in the visualized locules presumably represented differing concentrations of old hemorrhage and protein. In one case soft tissue elements became hyperintense on T2-weighted images. We speculate that MRI of multilocular cystic nephromas will produce imaging features that are highly suggestive, but not always pathognomonic, of the disease.

Adult↗

Role of scintigraphy in focally abnormal sonograms of fatty livers.

Fatty infiltration of the liver may cause a range of focal abnormalities on hepatic sonography which may simulate hepatic nodular lesions. Discrete deposits of fat or islands of normal tissue which are uninvolved by fatty infiltration may stand out as potential space-occupying lesions on the sonograms. Twelve patients with such focally abnormal ultrasound images were referred for liver scintigraphy with 133Xe and 99mTc colloidal SPECT studies to clarify the issue. These examinations helped identify, in nine of 12 patients, the innocent nature of the sonographic abnormalities which were simply related to the fat deposition process. Further, [99mTc]RBC scans defined the additional pathologic process in three patients in whom actual space-occupying lesions were indeed present in the liver. Scintigraphy has an important role to play in the understanding of focal hepatic ultrasound abnormalities particularly in unsuspected hepatic steatosis.

Aged↗