Much ado about something: a commitment to public safety (with apologies to William Shakespeare).
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Biomedical subjects
Publications and source records attributed to S Davis.
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BACKGROUND: Tunneled central venous catheters (CVCs) and infusion ports have often been considered as the only safe alternative for long-term venous access. The objective of this study was to assess the durability, cost, and infection rate of nontunneled, noncuffed Silastic CVCs. METHODS: We studied a representative cohort of 340 consecutive cancer patients with 359 nontunneled Silastic CVCs inserted and followed up at our center. All patients were evaluated clinically and microbiologically at the time of CVC removal. RESULTS: The mean in-place duration of the catheter for the 359 nontunneled CVCs studied was 109 days (total, 39,147 days of catheter use), and the infection rate was 0.13 per 100 catheter days. When compared with the tunneled Hickman catheter, the insertion cost saving was at least $2322 per CVC. At our institution, the use of nontunneled Silastic catheters with the support of an expert infusion team has resulted in an annual cost saving of at least $7,692,000. Long peripheral CVCs (in the basilic/cephalic vein) had a 26% rate of inflammation at the insertion site compared with only 2.6% for the short subclavian CVCs (P < .01). Most of the exit-site inflammations were sterile, with negative skin and catheter cultures. Neutropenia, bone marrow transplantation, high-dose steroids, and use of vesicant chemotherapeutic agents through the CVC did not predispose the patients to catheter infection. By univariate analysis, acute leukemia was the only risk factor for catheter infection. CONCLUSIONS: Given the low infection rate and long durability of nontunneled silicone CVCs, these catheters could offer a cost-effective and safe alternative to surgically implantable tunneled catheters.
BACKGROUND: Soft tissue sarcomas (STS) comprise a relatively rare group of malignant tumors of the connective tissues. It is estimated that approximately 6000 cases of STS will occur in the United States in 1993. Concerns have been raised in the clinical community that the incidence of STS may be increasing. METHODS: Incidence rates of STS were obtained from the Surveillance, Epidemiology, and End Results program. Cases were restricted by histologic classification to malignant tumors determined a priori to be STS by a pathologist specializing in diseases of soft tissue. Age-, sex- and race-specific rates also were examined. RESULTS: A total of 18,525 newly diagnosed cases of STS were identified for the period 1973 through 1987 in the United States. There was a marked increase in the age-adjusted incidence rate during the interval from 1981 to 1987, with rates increasing from 4.4 x 10(-6) in 1981 to 7.1 x 10(-6) in 1987. However, when patients with Kaposi sarcoma (KS) (International Classification of Diseases for Oncology [ICD-O] code 9140) were eliminated from this analysis, the rates remained relatively unchanged throughout the time period. Additional stratification by age, gender, and race revealed no important differences in this observed lack of a time trend. Gastrointestinal tract cases were examined separately, and no significant changes in incidence rates were observed. CONCLUSIONS: It appears as though the increase in STS during this time period is accounted for primarily by KS, perhaps because of the acquired immune deficiency syndrome epidemic (since single men between the ages of 20 and 59 years accounted for almost 69% of all cases of KS). Additional studies that examine other populations or time periods after 1987 might be useful.
The ciliary neurotrophic factor (CNTF) receptor complex is shown here to include the CNTF binding protein (CNTFR alpha) as well as the components of the leukemia inhibitory factor (LIF) receptor, LIFR beta (the LIF binding protein) and gp130 [the signal transducer of interleukin-6 (IL-6)]. Thus, the conversion of a bipartite LIF receptor into a tripartite CNTF receptor apparently occurs by the addition of the specificity-conferring element CNTFR alpha. Both CNTF and LIF trigger the association of initially separate receptor components, which in turn results in tyrosine phosphorylation of receptor subunits. Unlike the IL-6 receptor complex in which homodimerization of gp130 appears to be critical for signal initiation, signaling by the CNTF and LIF receptor complexes depends on the heterodimerization of gp130 with LIFR beta. Ligand-induced dimerization of signal-transducing receptor components, also seen with receptor tyrosine kinases, may provide a general mechanism for the transmission of a signal across the cell membrane.
Ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) are cytokines that give rise to an identical set of tyrosine-phosphorylated proteins upon addition to responsive cells. One of these proteins is the interleukin-6 signal-transducing molecule gp130, which is required for signal transduction by both CNTF and LIF. Here we identify another prominent tyrosine-phosphorylated protein as LIF receptor (LIFR) beta, which was originally cloned as a LIF-binding protein. Cross-linking experiments with iodinated factors were carried out on a cell line responsive to CNTF and LIF, as well as on COS cells that were cotransfected with various combinations of gp130, LIFR beta, and CNTF receptor (CNTFR) alpha, the previously cloned CNTF-binding protein. These experiments reveal that LIF cross-links to LIFR beta alone, as well as to gp130 when it is coexpressed with LIFR beta. However, cross-linking of CNTF to LIFR beta and gp130 is only observed in the presence of CNTFR alpha. These and other data show that the two known LIF receptor components are recruited by CNTF and CNTFR alpha to form a trimeric CNTF receptor complex.
The alpha component of the receptor for ciliary neurotrophic factor (CNTF) differs from other known growth factor receptors in that it is anchored to cell membranes by a glycosylphosphatidylinositol linkage. One possible function of this type of linkage is to allow for the regulated release of this receptor component. Cell lines not normally responsive to CNTF responded to treatment with a combination of CNTF and a soluble form of the CNTF alpha receptor component. These findings not only demonstrate that the CNTF receptor alpha chain is a required component of the functional CNTF receptor complex but also reveal that it can function in soluble form as part of a heterodimeric ligand. Potential physiological roles for the soluble CNTF receptor are suggested by its presence in cerebrospinal fluid and by its release from skeletal muscle in response to peripheral nerve injury.
Nitric oxide (NO) has been implicated as a mediator of hemodynamic and metabolic changes associated with endotoxemia and inflammation. In vitro studies suggest that NO inhibits hepatocyte protein synthesis but the role of NO in the regulation of hepatic protein synthesis in vivo is not known. In this study, rats were given endotoxin or saline after pretreatment with the NO synthase inhibitor NG-nitro-L-arginine or solvent, and plasma levels of nitrite (NO2), nitrate (NO3), and aspartate aminotransferase and hepatic protein synthesis rate in vivo were measured after 4 and 10 hours. The NG-nitro-L-arginine effectively blocked the increase in serum NO2/NO3 seen in endotoxemia and also inhibited the increase in hepatic protein synthesis in endotoxemic rats. The aspartate aminotransferase levels were elevated in endotoxemic rats pretreated with NG-nitro-L-arginine. Results support previous reports of a protective effect of NO on the liver in endotoxemia and suggest that NO may upregulate hepatic protein synthesis in vivo. Further study is needed to clarify the reason for the apparent difference between the effect of NO on hepatic protein synthesis in vivo and in vitro.
The expression of fragile sites induced by aphidicolin (APC) was evaluated on metaphase chromosomes obtained from the peripheral blood lymphocytes of 26 women with breast cancer and 15 sex- and age-matched normal controls. Both the proportion of damaged cells (P < 0.001) and the mean number of gaps and breaks per cell (0.02 < P < 0.05) were significantly higher in the patient group. There were no differences in either the age-related fragile site levels or the expression of single fragile sites between patients and controls. Our findings indicate an increased genetic instability in women with breast carcinoma.
Recently there have been advances in studies of the molecular biology of the receptor for CNTF. In contrast with the receptors for other known neurotrophic factors, which belong to the family of receptor tyrosine kinases, the CNTF receptor belongs to the family of cytokine receptors. This review will describe the structural features and signaling capabilities of the CNTF receptor, and discuss the implications for the biology of CNTF as well as for other neurotrophic factors and cytokines. This review is an updated version of the review that appears in Current Opinion in Neurobiology 1993, 3:20-24.
Recently there have been advances in studies of the molecular biology of the receptor for CNTF. In contrast with the receptors for other known neurotrophic factors, which belong to the family of receptor tyrosine kinases, the CNTF receptor belongs to the family of cytokine receptors. This review will describe the structural features and signaling capabilities of the CNTF receptor, and discuss the implications for the biology of CNTF as well as for other neurotrophic factors and cytokines.
Thirty-seven (37) consecutive patients with clinical Stage I (T1-2NO, Mo), and Stage II (T1-2N1 Mo) central small-cell lung cancer (SCLC) underwent complete surgical resection of the primary tumor. Ten patients were subsequently pathologically Stage I, 14 patients were Stage II, and 8 were Stage III (T3;N2). The pathologically Stage I, II, and III patients were then treated with chemotherapy consisting of cyclophosphamide (1 g/m2), doxorubicin (50 mg/m2), and vincristine 2 mg (CAV) every 3 weeks for six courses followed by prophylactic cranial irradiation (2000 cGy in 10 fractions). Median survival in Stage I patients is 162 weeks and calculated 5-year survival is 50%; for Stage II patients, median survival is 86 weeks and calculated 5-year survival is 35%. T3;N2 patients have a median survival of 63 weeks; calculated 5-year survival is 21%. Our data suggest surgery plus adjuvant chemotherapy and cranial irradiation results in long-term survival in early central SCLC. These data support the need for randomized surgical trials in Stage I, II, and III central SCLC.
Bill C-30, implemented in February 1992, made a number of significant changes to the Criminal Code provisions concerning the assessment, treatment and disposition of mentally disordered persons charged with a crime, including persons considered to be unfit to stand trial or pleading insanity. The changes deal mainly with procedural law and the civil rights of persons being assessed or held in custody, and put limits on where, how long and for what purpose persons may be detained. The new law abolishes the automatic, indeterminate detention of persons found unfit to stand trial or not criminally responsible on account of mental disorder. The changes may mean that the forensic psychiatric route is now a more "attractive option" for defendants. The new law may create administrative problems for clinicians by leading to increased requests for psychiatric assessments while at the same time constraining the assessment process.
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In this paper, results are presented on the response to an antismoking media campaign designed to encourage women cigarette smokers with young children to call for information on quitting. The intervention campaign used a mix of professionally produced broadcast and print materials that encouraged smokers to call the National Cancer Institute's Cancer Information Service (CIS) for information on quitting. The campaign was implemented in seven media markets in New York state, Pennsylvania, and Delaware; each of these markets was paired with a control market in one of the three states. Response to the campaign was gauged by monitoring calls to the New York and Pennsylvania area CIS offices from smokers residing in intervention and control media markets. Results from the 46-week campaign show that the number of calls for smoking-cessation information was five times greater from intervention markets than from control markets. The campaign also was successful in reaching the target audience of mothers of young children. Twenty-nine percent of calls received from intervention markets were from the target audience compared with 10% from the control markets. Forty-four percent of all calls received from intervention markets came during a 5-week period when time was purchased to air television spots.
This article is an epidemiological analysis of Baltimore homicides between 1986 and 1990. The main findings were that young African-American males between 15 and 34 years of age are at greatest risk of homicide victimization. Homicidal events primarily occurred with handguns, in drug-related circumstances, between acquaintances, and in the western police district area. Questions are raised concerning the expansion of the public health professional's role and the use of epidemiologic data for injury prevention programs. This article is the result of a grant from the Centers for Disease Control and Prevention, Division of Injury Control, to the state of Maryland, Department of Health and Mental Hygiene, and the Baltimore City Health Department.
This study examined the changes over time in the residential status of telephone numbers and the characteristics of households with telephone numbers that changed from nonresidential to residential. The authors determined the status in 1987 of all phone numbers (n = 9,107) that had been found to be nonresidential in six case-control studies conducted between 1979 and 1986 in Washington State. A telephone interview to obtain information on household characteristics was completed for 1,333 of the 1,901 phone numbers that had become residential by 1987. The interviews revealed that households with phone numbers that had previously been nonresidential differed from the general population with respect to household income, the age of household members, and the education of the head of the household. Data for the same area showed that the proportion of all phone numbers that were residential changed differentially according to the prefix (which roughly defines geographic area) during a 12-month period between 1987 and 1988, with some prefixes showing increases in residential phone numbers of more than 20%, while other prefixes decreased or stayed the same over the same period. We conclude that methods of random digit dialing that use two-stage designs or exclude previously dialed numbers may result in biased sampling unless changes over time are considered.