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Biomedical subjects

W Jones

Publications and source records attributed to W Jones.

At least 73 records · Page 4Linked to original sources
PubMed1995

Elevated protease activities in human amnion and chorion correlate with preterm premature rupture of membranes.

OBJECTIVES: The mechanism(s) of preterm premature rupture of fetal membranes resulting in preterm birth remains unknown. Studies suggest that fetal membranes are susceptible to weakening by protease attack and that collagenases may be active at the site of rupture. In this study fetal membranes from women delivered after preterm premature rupture of membranes were compared with control membranes and analyzed qualitatively and quantitatively for protease activities. STUDY DESIGN: Fourteen membranes from women with preterm premature rupture of membranes and nine membranes from women delivered preterm without premature rupture of membranes or otherwise normal women delivered at term vaginally or by cesarean section were studied. Zymogram gel electrophoresis with gelatin incorporation was used to assess the number and apparent molecular weights of protease activities. Functional and quantitative studies of protease activity were measured by fluorescent substrate cleavage. RESULTS: Zymogram gel electrophoresis studies demonstrated the presence of five to seven different protease bands in preterm premature rupture of membranes samples, whereas control membranes demonstrated only one to three protease bands. Fluorescent studies of protease activity demonstrated a 10- to 40-fold increase in activity in membranes from women with preterm premature rupture of membranes compared with normal control membranes. Studies with protease inhibitors suggest that most of the activity is due to metalloproteinases. CONCLUSION: In membranes from women with preterm premature rupture of membranes there appears to be a general increase in the amount of protease activity and increased numbers of putatively different proteases. Increased activity or deregulated protease control may mediate preterm premature rupture of membranes and be a potentially remediable cause of preterm birth.

Amnion↗
PubMed1995

How consistently do RNs perform the procedure of collecting specimens for measurement of gastric pHi and CO2?

Gastric Tonometry is an important tool being used more frequently in the Intensive Care Unit (ICU). Tonometry is used to collect normal saline which has equilibrated with the stomach contents and is used in combination with a sample of arterial blood to calculate intragastric PaCO2 and intramucosal pH (pHi). These values are indicative of gastric perfusion. Correct performance of each of the 5 procedural steps to instill and then collect the normal saline is paramount for accuracy of the CO2 and pHi results. The aim of this study was to examine how consistently nurses perform the procedure. Study participants comprised two groups of 15 registered nurses (RNs) chosen at random from the nurses employed in the ICU at Liverpool Hospital (NSW, Australia). The first group of RNs were asked to answer a questionnaire before and after performing the tonometry procedure under simulated conditions. The second group were asked to perform the tonometry procedure only. Each participant was observed by one of the researchers whilst performing all of the procedural steps. Regardless of critical care experience of participants or the number of years since registration a s a nurse, error rates in performing the specimen collection/procedure were as high as 34%. This study is designed to examine the previously unaddressed area of how accurately nursing staff follow systematic instructions to collect the mucosal sample.

Bias↗
PubMed1995

Small area variation in the utilization of mental health services: implications for health planning and allocation of resources.

OBJECTIVE: To determine the variables associated with utilization of mental health services and to develop a planning model to predict service utilization that incorporates these factors. METHOD: A regression analysis of service utilization and demographic characteristics was used to assess the relative importance of alternative service, supply of psychiatrists and demographics in explaining variations of services use. A model using socioeconomic factors was applied to the population to predict need. RESULTS: The percentage of divorced males was the only factor significantly and positively correlated with the utilization of hospital inpatient and provincial psychiatric beds. Predicted need exceeds utilization in 7 out of 10 areas for all services. CONCLUSIONS: Small area variations in inpatient psychiatric utilization is correlated with community characteristics, not supply of psychiatrists or utilization of alternative services. A model has been developed using census data to allocate resources according to need.

Adult↗
PubMed1995

New developments in EPG3 software.

New developments in EPG3 software are described including: a three-dimensional display of the electrodes on the palate in the form of a wire frame representation; a facility for annotating EPG3 files; and a new data management system. Recent methods of EPG data reduction are also described, including numerical indices for representing tongue-palate contact profiles. A new clinical version of the Reading EPG system, EPG4, is introduced.

Electrodiagnosis↗
PubMed1995

Late generalized tuberculosis: unusual features of an often overlooked disease.

Late generalized tuberculosis--ie, disseminated tuberculosis occurring long after the primary infection-- is an often unrecognized cause of severe illness in patients with relative immunocompromise, such as the elderly, alcoholics, or those with chronic illnesses. It has become increasingly recognized in the elderly as a cause of a gradual debilitating illness, often with vague constitutional symptoms. We describe three cases of late generalized tuberculosis in patients seen on a single medical service over a 6-month period. Each case presents a unique features of extrapulmonary tuberculosis that escaped diagnosis for some time, and each of these elderly patients had a protracted and wasting illness. We present these cases and the ensuing discussion to reemphasize to clinicians that late generalized tuberculosis may be experiencing increased prevalence among the elderly and that diagnosis requires a heightened suspicion. A history of past tuberculosis infection is not always present, but the diagnosis should be entertained in any elderly patient with a chronic debilitating illness.

Aged↗
PubMed1995

Adinazolam-SR in panic disorder with agoraphobia: relationship of daily dose to efficacy.

BACKGROUND: We report the results from a multicenter, double-blind, randomized, fixed-dose study designed to evaluate the relationship between daily dose and efficacy of adinazolam-SR in patients with panic disorder with agoraphobia. METHOD: Patients (N = 315) were randomized to one of four treatment groups (placebo, N = 83; 30-mg group, N = 79; 60-mg group, N = 81; and 90-mg group, N = 72) and then treated twice daily for 4 weeks. All treatment groups were comparable demographically. Primary efficacy measures included total number of panic attacks, global improvement score using the Clinical Global Impressions (CGI) scale, phobic anxiety dimension of the Symptom Checklist-90 phobic cluster, overall phobia state using the Phobia Scale, and severity of illness on the CGI. RESULTS: The 60- and 90-mg/day adinazolam-SR treatment groups showed superior results when compared with the placebo group at Week 4 while the 30-mg group did not. Treatment with adinazolam-SR was well tolerated, with sedation the only treatment-emergent symptom that occurred more frequently in patients treated with adinazolam-SR than placebo. CONCLUSION: These results suggest that adinazolam-SR at doses of 60-mg/day or greater administered twice daily is a safe and effective treatment in selected patients with panic disorder with agoraphobia.

Adolescent↗
PubMed1995

Mortality preventable by medical intervention: ethnic and regional differences in Texas.

An examination of mortality from 12 causes of death was tabulated for the state of Texas for residents in the Lower Rio Grande Valley; for residents of border counties; for residents of Dallas, Harris, and Tarrant counties, along with residents of east Texas from 1980 to 1989. The ninth revised edition of the International Classification of Diseases was used to categorize causes of mortality. The mortality data were obtained from mortality data tapes obtained from the Texas Department of Health and archived at the University of Texas School of Public Health. From 1980 to 1989, an average of 1543 deaths per year was attributed to these 12 selected causes in Texas. Thirty-two percent of deaths were due to hypertensive heart disease, 30% to pneumonia and bronchitis, 11% to cervical cancer, and 6% to rheumatic fever. Pneumonia and bronchitis were the leading causes of death among those aged 15 to 44 years.

Adolescent↗
PubMed1994

Bacterial vaginosis is associated with prematurity and vaginal fluid mucinase and sialidase: results of a controlled trial of topical clindamycin cream.

OBJECTIVE: The pathogenesis of preterm birth and other adverse pregnancy outcomes linked with reproductive tract infection remains poorly understood. Mucolytic enzymes, including mucinases and sialidases (neuraminidase), are recognized virulence factors among enteropathogens and bacteria that cause periodontal infection. Perturbation of maternal cervicovaginal mucosa membrane host defenses by such enzyme-producing microorganisms may increase the risk of subclinical intrauterine infection during pregnancy and thus increase risks of preterm birth. STUDY DESIGN: We prospectively evaluated vaginal fluid mucinase and sialidase and selected cervicovaginal bacteria along with pregnancy outcomes in 271 women. Within this study, women with bacterial vaginosis (16 to 27 week' gestation) were treated with 2% clinadmycin vaginal cream or placebo. Enzyme, microbial findings, treatment effects, and pregnancy outcomes were compared among drug- and placebo-treated women and control women without bacterial vaginosis. RESULTS: Presence of bacterial vaginosis at intake was associated with increased risk of preterm birth (relative risk 3.3, 95% confidence interval 1.2 to 9.1, p = 0.02), premature rupture of membranes (relative risk 3.8, 95% confidence interval 1.6 to 9.0, p = 0.002), and preterm premature rupture of membranes. Mucinase and sialidase activities were more commonly identified, and they occurred in higher concentrations, if present, in women with bacterial vaginosis (mucinase: 44.3% with bacterial vaginosis vs 27.4% without, p = 0.007; sialidase: 45% with bacterial vaginosis vs 12% without p < 0.001). Sialidase activity was associated with bacterial vaginosis-linked organisms (Gardnerella vaginalis, Mobiluncus spp, and Mycoplasma hominis) and Chlamydia trachomatis and yeast species; mucinase activity was associated only with bacterial vaginosis-linked microorganisms. Clindamycin, 2% cream, was effective treatment for bacterial vaginosis and temporarily reduced mucinase and sialidase activities. Topical treatment of bacterial vaginosis did not reduce risks of perinatal morbidity. Women with persistent or recurrent sialidase 8 weeks after treatment were at increased risk of preterm birth (15.6% vs 7.4%) premature rupture of membranes (30% vs 15%), and low birth weight (20% vs 3%, relative risk 6.8, 95% confidence interval 1.6 to 28.1). CONCLUSIONS: Persistence of sialidase-producing vaginal microorganisms in numbers sufficient to increase vaginal fluid sialidase activity may be a risk factor for possibly preventable subclinical intrauterine infection and preterm birth. This study confirms and further informs our understanding of the association of bacterial vaginosis and preterm birth; studies to evaluate whether systemic treatment for bacterial vaginosis can effectively reduce vaginal mucolytic enzymes and risks of prematurity and other morbid outcomes are continuing.

Administration, Topical↗
PubMed1994

Intraperitoneal Taxol (paclitaxel) in the management of ovarian cancer.

In an effort to examine the safety and pharmacology of the intraperitoneal (i.p.) delivery of paclitaxel, 25 patients (24 with ovarian cancer) were treated in a phase I dose escalation trial. The drug was administered in normal saline every 3 to 4 weeks, starting at a dose of 25 mg/m2. The dose-limiting toxicity at doses at or above 175 mg/m2 was abdominal pain. A 3-log pharmacokinetic advantage for peritoneal cavity exposure to paclitaxel, compared with the systemic compartment, was observed. High levels of drug persisted within the cavity for longer than 48 hours following a single treatment. In addition, significant paclitaxel concentrations were found in the systemic compartment after i.p. treatment, despite the pharmacokinetic advantage demonstrated for cavity exposure. Several patients exhibited clinical and laboratory evidence of an antitumor response. On the basis of these data, further exploration of a potential role for i.p. paclitaxel in the management of ovarian cancer appears justified.

Dexamethasone↗
PubMed1993

Biochemical and functional properties of recombinant human sickle hemoglobin expressed in yeast.

Previous studies had indicated that recombinant and natural human sickle hemoglobin had similar chemical properties (Martin de Llano, J. J., Schneewind, O., Stetler, G., and Manning, J. M. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 918-922). In the present study, additional biochemical and physiological characterization of some primary through quaternary structural features of recombinant sickle hemoglobin are described. The molecular weight of the purified recombinant sickle hemoglobin was identical to natural sickle hemoglobin as determined by mass spectrometry, thus excluding extensive post-translational modification in the yeast system. Carboxypeptidases A and B together catalyzed the release of COOH-terminal amino acids at the same rate for recombinant and natural hemoglobin S, consistent with identity in their primary and secondary structures in this region of the molecule. The tryptic peptide maps of natural and recombinant hemoglobins were practically indistinguishable, indicating the same internal protein sequences for recombinant and natural hemoglobins. As a probe of the secondary structure of recombinant sickle Hb, the reactivity of the SH group of Cys-93(beta) was investigated for the glutathione sickle hemoglobin adduct, which has significant anti-gelling and anti-sickling properties. The position of glutathione at Cys-93(beta) was established by direct mass spectrometric analysis of enzyme digests; reduction of this derivative to the unmodified chains was also observed by mass spectrometry and by isoelectric focusing. The oxygen equilibrium curves of recombinant and natural sickle hemoglobin at high protein concentration were superimposable with identical Hill coefficients of 3.3. The response of recombinant sickle hemoglobin to chloride with respect to a lowered oxygen affinity was identical to that of natural sickle hemoglobin. The gelation properties of recombinant and natural sickle hemoglobins were identical at the high hemoglobin concentrations that occur in the red cell. Therefore, the yeast expression system synthesizes a completely functional recombinant sickle hemoglobin with the same biochemical and physiological properties as natural sickle hemoglobin with respect to features characteristic of its primary through quaternary structures.

Amino Acids↗
PubMed1993

Intraperitoneal chemotherapy in the management of ovarian cancer.

During the past decade, intraperitoneal therapy of ovarian cancer has evolved from a pharmacologic model into an established treatment technique for women with this malignancy. Approximately 40% of patients with small-volume residual ovarian cancer (microscopic disease or macroscopic tumor, < or = 0.5 cm in maximum tumor diameter), after an objective response to initial organoplatinum-based systemic chemotherapy, may have a surgically documented complete response to platinum-based intraperitoneal chemotherapy. Patients who have not responded to systemic platinum administration rarely will respond to the drug given intraperitoneally, despite the presence of only small-volume residual disease when this regional treatment strategy is used. Other agents with antineoplastic activity after intraperitoneal administration in women with ovarian cancer include mitoxantrone, taxol, alpha-interferon and gamma-interferon, and interleukin-2. Although intraperitoneal therapy currently is being examined as a component of the initial chemotherapeutic program for patients with ovarian cancer, a precise role for regional drug delivery in this clinical setting remains to be defined.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Epithelial ovarian cancer in the elderly. The Memorial Sloan-Kettering Cancer Center experience.

BACKGROUND: There is evidence of differences between older (> or = 65 years of age) and younger (< 65 years of age) women with ovarian cancer. METHODS: To evaluate differences in the care of older versus younger patients with ovarian cancer, a retrospective review was conducted of the records of 146 patients who had their initial surgery for ovarian cancer at the Memorial Sloan-Kettering Cancer Center from January 1987-January 1991. RESULTS: There was a significant difference in stage at presentation between the older (48 patients) and younger (98 patients) populations (Stage I/II: older 10%; younger 25%; P < 0.05). Although there was no statistically significant difference in the distributions of patients according to tumor grade between the two groups, 10% of the younger patients had ovarian cancer of low malignant potential, compared to only 2% of older patients (P < 0.1). Forty-six percent of the younger patients entered an intensive initial chemotherapy trial compared to only 17% of the older patients (P < 0.001), principally due to comorbid medical conditions (e.g., heart disease). Finally, whereas the relative number of younger to older patients with ovarian cancer undergoing initial surgery at this institution was 2:1, the relative number of totally new patients to the service (including referral for initial treatment or salvage programs) was 4:1 (P < 0.001), suggesting that older patients with ovarian cancer are less likely to be referred for secondary experimental programs than for initial treatment. CONCLUSIONS: These data suggest that there are major differences between the presentation and treatment strategies of older compared to younger patients with ovarian cancer.

Adult↗
PubMed1993

Evidence for persistence of mitoxantrone within the peritoneal cavity following intraperitoneal delivery.

In clinical trials examining the intraperitoneal (ip) administration of mitoxantrone as therapy of platinum-refractory small-volume residual ovarian cancer, the characteristic "blue color" of the agent has been demonstrated to stain the surface of the peritoneal cavity and to persist for > or = 1 month following the last course of therapy. To determine if this blue staining material contains potentially cytotoxic concentrations of mitoxantrone, we analyzed tissue obtained at exploratory laparotomy in six women who had last received the agent administered ip from 6-22 weeks prior to surgery. Concentrations of mitoxantrone ranged from < 0.1 to 13.8 micrograms/g of tissue examined. Since any mitoxantrone present on the peritoneal surface will be highly protein bound, any residual drug may not have cytotoxic potential. The dose-response curves of mitoxantrone in a human clonogenic cytotoxicity assay against the RPMI 2780/S human ovarian cell line were virtually identical when the cells were incubated in either 5 or 50% fetal bovine serum, suggesting that protein binding will not significantly impair mitoxantrone-induced tumor cell killing. We conclude that the ip administration of mitoxantrone may lead to prolonged exposure of surface tumor to the high local concentrations of the active cytotoxic agent. This effect may contribute significantly to the antineoplastic potential of ip mitoxantrone in patients with small-volume residual ovarian cancer.

Dose-Response Relationship, Drug↗
PubMed1993

The use of recombinant human erythropoietin to prevent carboplatin-induced anemia.

Anemia is a frequent and potentially serious toxicity associated with the use of carboplatin, particularly when this agent is administered in the salvage setting. In an effort to evaluate a possible role for human erythropoietin (rh-E) in preventing or minimizing carboplatin-induced anemia we analyzed the impact of the agent on anemia and transfusion requirements of women with ovarian cancer who were treated on one of two nonrandomized trials employing identical second-line carboplatin-based intraperitoneal regimens, with the only difference in the regimens being the addition of rh-E (Study 1, without rh-E; Study 2, with rh-E). There was a statistically significant difference in the incidence of documented nadir hemoglobin levels of < 9 g/dl (Study 1, 60%; Study 2, 13%; P < 0.005) and < 8 g/dl (Study 1, 33%; Study 3, 6%; P < 0.05). We also observed a threefold reduction in transfusion requirements with the use of rh-E (Study 1, 23%; Study 2, 6%), but this difference was not statistically significant with the limited sample size evaluated. In this nonrandomized comparison of two identical chemotherapy programs we have demonstrated that rh-E significantly reduced the incidence and severity of anemia associated with carboplatin-based chemotherapy. A randomized trial examining the potential impact of rh-E on carboplatin-induced anemia and transfusion requirements is warranted.

Adult↗
PubMed1993

Salvage intraperitoneal mitoxantrone therapy of ovarian cancer: influence of increasing the volume of treatment.

Despite the demonstrated activity of intraperitoneal mitoxantrone in patients with small volume-platinum-refractory ovarian cancer, previous reports have revealed that many patients fail to achieve adequate distribution of the cytotoxic drug throughout the peritoneal cavity when delivered in a "standard" 2-liter treatment volume. In an effort to improve the distribution and therapeutic efficacy of intraperitoneal mitoxantrone, 22 patients with platinum-refractory ovarian cancer were treated with the drug at a dose of 10 mg/m2 given in 2 liters of normal saline followed by an additional 1-2 liters every 2 weeks for eight cycles. The surgically defined complete response rate in 17 patients evaluable for response with platinum-refractory ovarian cancer was 24%, with an overall response rate of 29%. Of 18 in which the influence of treatment volume could be examined (4 patients developed catheter failure), 12 (67%) were able to tolerate a 4-liter treatment volume for > 80% of courses, with a total of 15 patients (83%) receiving treatment with a minimum of a 3-liter treatment volume. We conclude that it is possible to safely increase the intraperitoneal treatment volume to 3-4 liters in most patients undergoing this therapeutic strategy. While the impact on therapeutic efficacy of expanding the volume employed for cytotoxic drug delivery remains to be defined, in theory this approach may optimize the opportunity for agents achieving high-intraperitoneal concentrations to produce their maximal cytotoxic effect.

Adult↗
PubMed1993

Impact of age on survival of patients with ovarian cancer.

In an effort to determine if there are significant differences in outcome between elderly (> or = 65 years of age) and younger (< 65 years of age) women with epithelial ovarian cancer we examined the survival of patients with this malignancy who underwent their initial surgical evaluation at the Memorial Sloan-Kettering Cancer Center from January 1987-January 1991. The actuarial median overall survival for the 98 younger patients has not been reached but will exceed 4 years, compared to a median survival of 24 months for the 48 elderly patients (P < 0.0001). For individuals with advanced (stages 3-4) disease, excluding patients with tumors of low malignant potential, the median survival for the younger patient population has also not been reached and will exceed 4 years, compared to 21 months for the older population (P < 0.0001). Even in the limited number of patients with local/regional (stages 1-2) ovarian cancer, there was a statistically significant superior survival for the younger group of patients (P < 0.02). With a single exception, all deaths were believed to be due principally to disease progression, rather than to an unrelated comorbid medical event. We conclude that elderly patients with ovarian cancer experience a significantly inferior survival than younger individuals with this malignancy. Evaluation of larger populations will be required to confirm the results of this analysis and to probe for explanations for the striking survival differences we have observed.

Adult↗