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Biomedical subjects

W Jones

Publications and source records attributed to W Jones.

At least 127 records · Page 7Linked to original sources
PubMed1991

Intraperitoneal cisplatin and cytarabine in the treatment of refractory or recurrent ovarian carcinoma.

Preclinical evaluation has suggested impressive concentration-dependent cytotoxic synergy between cisplatin and cytarabine in ovarian carcinoma. To further evaluate the clinical relevance of these observations, 39 patients with refractory or recurrent ovarian carcinoma were entered onto a phase II trial of intraperitoneal (IP) cisplatin (100 to 105 mg/m2 per course) plus cytarabine (600 to 900 mg per course). Treatment was administered over 2 or 3 days for a maximum of five monthly courses, followed by surgical reevaluation in patients without clinical evidence of disease. The 3-day regimen was discontinued secondary to the development of severe thrombocytopenia (five of 12 courses platelets decreased to less than 50,000/mm3). Additional toxicities included abdominal pain (moderate to severe at some time during therapy in 46% of patients), fever without evidence of infection (44%), and bacterial peritonitis (10%). Three patients declined surgical reassessment. Fourteen of 36 (39%; 95% confidence interval [CI], 23% to 55%) assessable patients demonstrated surgically defined responses, including 12 of 23 (52%; 95% CI, 32% to 72%) patients with tumor nodules less than 1 cm in diameter and only two of 13 (15%; 95% CI, 0% to 34%) patients with any lesion greater than 1 cm. There were seven (30%; 95% CI, 11% to 49%) surgically defined complete responses (CRs) in patients with less than 1 cm disease and none in patients with larger tumor nodules. IP cisplatin/cytarabine results in a high surgically defined response rate in patients with minimal residual ovarian carcinoma, but activity is low in patients with bulky intraabdominal disease.

Adult↗
PubMed1991

Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin.

In an effort to critically define the incidence and clinical characteristics of secondary responses to cisplatin-based therapy in patients with ovarian cancer previously treated with a cisplatin-based program, a retrospective review was undertaken of patients at the Memorial Sloan-Kettering Cancer Center who received greater than or equal to two cisplatin/carboplatin-based programs. Eighty-two patients were identified who met the entry criteria of having had a cisplatin-free interval (CFI) of more than 4 months between the completion of their first regimen and the institution of a second cisplatin/carboplatin program. Of the 72 assessable patients (10 had no measurable disease, and a laparotomy was not performed to assess response), 31 (43%) responded, including 10 surgically defined complete responses (S-CRs). The overall response rates (and S-CR rate), based on duration of CFI, were 5 to 12 months, 27% (5%); 13 to 24 months, 33% (11%); and more than 24 months, 59% (22%). Twenty-nine patients (35%) received noncisplatin/carboplatin-containing treatments between the cisplatin programs. Patients without any treatment for more than 24 months from the completion of their initial therapy experienced a 77% (17 of 22) response rate and a 32% (seven of 22) S-CR rate. In conclusion, secondary responses to cisplatin/carboplatin-based treatment are common in patients with ovarian cancer who have previously responded to the agents and increase in frequency with greater distance from the initial therapy.

Adult↗
PubMed1991

Phase II trial of weekly or biweekly intraperitoneal mitoxantrone in epithelial ovarian cancer.

Previous experimental and clinical evaluation has suggested that ovarian cancer is sensitive to the cytotoxic effects of mitoxantrone at concentrations achievable within the peritoneal cavity after intraperitoneal (IP) administration. Unfortunately, the use of the drug delivered IP at high doses (20 mg/m2 in 2 L normal saline [NS]) on a monthly schedule is compromised by severe local effects secondary to the irritant properties of the drug. To reduce toxicity and take advantage of minimal systemic drug exposure following IP administration, we treated 28 patients with a lower drug concentration of mitoxantrone (10 mg/m2 in 2 L NS), but on a weekly or every other week schedule (total, 12 courses). Compared with the monthly program, this regimen caused less pain, allowed for a higher cumulative dose of mitoxantrone to be delivered, and resulted in less serious treatment-related morbidity. Four of 13 assessable patients (31%) whose largest tumor was less than or equal to 1 cm in diameter demonstrated a surgically defined response. All responding patients had failed previously or exhibited a minimal response to cisplatin. Despite the improved toxicity profile of this regimen, the overall response rate was similar to the monthly program, probably secondary to inadequate IP drug distribution in many patients. Future investigative efforts using IP mitoxantrone as therapy for ovarian cancer might focus on developing methods to improve drug delivery to all sites of tumor within the peritoneal cavity (eg, intraoperative therapy, increased treatment volumes, and antiinflammatory agents to reduce adhesion formation).

Adult↗
PubMed1991

Visual display of tongue-palate contact: electropalatography in the assessment and remediation of speech disorders.

The technique of electropalatography (EPG) records the location and timing of tongue contacts with the hard palate during continuous speech. Recent developments in hardware and software design of the Reading electropalatograph are described and applications of the technique in assessment and remediation of a variety of speech disorders are outlined. In assessment, it is shown that EPG can provide insights into possible origins of auditorily perceived errors, and case descriptions illustrate how this information can lead to a more rationalised approach to treatment. In therapy, the provision of real-time visual feedback of tongue movement can be effective in the remediation of certain types of intractable speech problems. Finally, the importance of techniques such as EPG in the objective evaluation of treatment procedures is discussed in the light of the increasing demand for accountability within the speech therapy service.

Adolescent↗
PubMed1991

The uninsured and patient dumping: recent policy responses in indigent care.

This article discusses the uninsured population and the phenomenon known as "patient dumping"--the transfer of a patient from one hospital (typically a private hospital) to a public hospital because of the patient's lack of insurance or inability to pay. The uninsured are the most vulnerable to patient dumping. The growth of patient dumping, a profile of the uninsured who are most likely to be a minority, and an analysis of federal and state policy responses to patient dumping are all discussed. The need for reform of the American health care system is highlighted and the Canadian health system is suggested as an alternative model.

Delivery of Health Care↗
PubMed1990

Induction of the endogenous whey acidic protein (Wap) gene and a Wap-myc hybrid gene in primary murine mammary organoids.

In rodents, the whey acidic protein (Wap) is the major whey protein expressed in mammary glands in response to lactogenic hormones. The regulation of the Wap gene differs from that of other milk protein genes, with one consequence being that little or no Wap expression is detectable in cell culture. Here we describe the efficient in vitro induction of the Wap gene in mammary organoids isolated from midpregnant mice. Mammary organoids were isolated as intact epithelial subcomponents which retained the glandular microarchitecture. If organoids were cultured in contact with a monolayer of 3T3-L1 adipocytes, significant levels of Wap mRNA were induced upon hormonal stimulation, with the highest level of Wap mRNA being induced by a combination of hydrocortisone, prolactin, and insulin. Dissociation of the three-dimensional organization abrogated Wap inducibility. Organoids cultured on plastic or hydrated type I collagen did not transcribe Wap mRNA even after hormonal stimulation. Addition of hormones was required to maintain low levels of Wap mRNA in organoids cultured on reconstituted basement membrane, however, Wap mRNA was not induced. Organoid-adipocyte interactions as well as cell-cell interactions inherent in the structure of organoids promote hormone-dependent Wap mRNA expression. In order to study the Wap promoter region in vitro, we cocultured organoids from transgenic mice harboring a chimeric Wap-myc gene with 3T3-L1 adipocytes. Lactogenic hormones induced the Wap-myc transgene in vitro. The kinetics of induction were similar for both the transgene and the endogenous Wap gene indicating that the 2.5-kb regulatory Wap region present in the hybrid gene contains the sequence elements required for hormone-induced gene expression in vitro.

Adipose Tissue↗
PubMed1990

Optimizing bone screw pullout force.

Stability of internal fixation by plate and screw depends on the interface of bone and screw threads. Bone-screw thread design was tested in a synthetic bone model to determine maximum bone-screw pullout force. The model was confirmed to provide reproducible results in a clinically relevant range. Consistent material properties were reflected in the relatively small standard deviations in pullout force, which were less than 10% of mean values. As expected, major diameter was an important determinant of pullout force in a roughly linear manner. Pitch was important with a finer thread giving greater purchase. Minor diameter and the ratio of major to minor diameter had a small but significant effect on pullout force. This study was significant for establishing a good bone-screw testing model and suggesting important thread parameters in selecting or manufacturing a bone screw to optimize its holding power.

Biomechanical Phenomena↗
PubMed1990

Phase II trial of intraperitoneal mitoxantrone in the management of refractory ovarian cancer.

To define both the toxicity and efficacy of intraperitoneal mitoxantrone in the treatment of refractory ovarian carcinoma, 31 patients were entered onto a phase II trial of this agent delivered in a 2 L treatment volume on a monthly basis. Due to excessive local pain at the initial dose level (30 mg/m2), the amount of drug delivered with each treatment course was reduced to 20 mg/m2. Despite this reduction, 74% of patients required narcotic analgesia during treatment. In addition, there were four episodes of bowel obstruction (one requiring surgical intervention) during therapy, and two patients developed bowel obstruction and intraabdominal abscesses following the completion of treatment. Six of 18 evaluable patients (33%) whose largest tumor diameter was less than or equal to 1 cm at protocol initiation experienced surgically documented responses, compared with one of 11 patients (9%) whose largest tumor was greater than 1 cm in diameter. If the two patients exhibiting what we called a mixed response to treatment are included, seven of 21 patients previously treated with intraperitoneal cisplatin responded to this treatment program, including four patients who had failed to respond to intraperitoneal cisplatin. No responding patient has demonstrated clinical evidence of relapse with a median follow-up of 7 months (range, 3+ to 13+ months) from response laparotomy. Intraperitoneal mitoxantrone is an active treatment program in patients with small-volume refractory ovarian carcinoma, but local toxicity can be severe. Due to the toxicity encountered with this specific program, its use cannot be recommended for standard clinical practice. However, in view of the activity observed in refractory ovarian carcinoma, including responses in patients who had previously failed intraperitoneal cisplatin, it is important to continue to explore alternative therapeutic regimens using intraperitoneal mitoxantrone to reduce local toxicity while maintaining or improving efficacy.

Carcinoma↗
PubMed1990

Determinants of health services utilization among the black and white elderly.

Andersen's (1968) behavioral model was used to assess whether factors predictive of health services utilization are the same or different for elderly blacks and whites. We hypothesized that because the black elderly have fewer resources, lower psychological well-being, and are in worse health, situational and attitudinal factors suggested by the model have different effects for blacks and whites. Using three measures of utilization--physician contact, hospital contact, and nights hospitalized--our findings show some support for differential effects, particularly in the case of physician contact. Neither resource factors such as health insurance nor psychological well-being were predictive of utilization within the black population. We conclude with some suggestions for future research.

Black or African American↗
PubMed1990

Consensus statement on the investigation and management of testicular seminoma 1989.

In the past 10 years, many developments have allowed us to understand more fully the natural history and routes of spread of testicular seminoma. The development of radiological tests such as CT scanning has allowed us to better assess the extent of disease. The availability of serum tumor markers AFP and beta HCG has facilitated the recognition of the presence of occult non-seminomatous elements. These developments plus the knowledge that seminoma is sensitive to cisplatin containing chemotherapy and that it is exquisitely sensitivity to radiation therapy resulted in further improvement in therapy. Overall we now expect 97 to 98% of patients will be cured of their disease. Currently, a number of issues in the management of seminoma remain controversial. These controversies however impact on very small proportion of patients with seminoma. Between 5 and 10% of patients have stage IID, III, or IV disease and 10 to 20% of these patients ie: 1 or 2% of the total population actually die from testicular seminoma. Thus it is for patients with advanced disease that we seek to define the nature of optimal chemotherapy, that is the most effective yet least toxic regimen. For those 1 or 2% of patients dying of seminoma we seek to identify prognostic factors to identify these patients and better treatments for them. Refinements in the application of radiation therapy for early stage disease, should allow some reduction in the morbidity of radiation without compromising control rates. Testicular seminoma its investigation and management, serves as a model for understanding other malignant processes and for orderly ways in which to refine the therapeutic ratio in the management of disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

The privatization of treatment services for alcohol abusers: effect on the black community.

This article discusses the "new wave" of privatization of treatment services for alcohol abusers. Despite the prevalence of alcohol abuse among ethnic minorities, the problem is still only marginally accepted as a focus for public health services. Instead of a consolidated effort or an integrated network, there are territorial fights among providers, a mistargeting of audiences, and a lack of any effort directed toward preventive health care. Recent research indicates that 68.5% of private sector employees are now covered by alcohol abuse treatment benefits as compared with only 36.2% in 1982. The growing number of employee assistance programs also has addressed the financial problems associated with long-term treatment in the work environment. Unfortunately these efforts are only directed at those in the society who are employed. As minority employment is much lower than that of the majority, minorities have not received the benefits of employer-financed treatment. This article assesses the growing privatization of treatment services and the failure of public alcohol prevention and rehabilitation programs to provide needed treatment for American minorities.

Black or African American↗
PubMed1989

Early diagnosis of testicular cancer.

Tumour markers, ultrasound, CT scanning and new cytotoxic therapy have revolutionised the management of testicular cancer; with early outpatient referral the condition can often be cured.

Diagnosis, Differential↗
PubMed1989

Transition-state stabilization by adenosine deaminase: 1,6-addition of water to purine ribonucleoside, the enzyme's affinity for 6-hydroxy-1,6-dihydropurine ribonucleoside, and the effective concentration of substrate water at the active site.

Positions of equilibria of highly unfavorable addition reactions, whose products are present at concentrations below the limits of detection, can be determined from equilibria of combination of anionic nucleophiles with quaternized enamines. Applied to the newly prepared 1-methylpurinium ribonucleoside cation, this method yields approximate equilibrium constants of 2 X 10(-9) M-1 for addition of water and 4 X 10(-5) M-1 for addition of N-acetylcysteine to neutral purine ribonucleoside, in dilute aqueous solution. Positions of 13C magnetic resonances and UV absorption maxima of the above complexes and comparison with those of adenosine deaminase complexes strongly suggest that purine ribonucleoside is bound by adenosine deaminase as the 1,6 covalent hydrate, not as a covalently bonded complex formed by addition of a thiol group at the active site. The favorable position of equilibrium of the hydration reaction on the enzyme, together with its extremely unfavorable position in free solution, indicates that the effective activity of substrate water at the active site is in the neighborhood of 10(10) M. The Ki value of the active diastereomer of 6-hydroxy-1,6-dihydropurine ribonucleoside is estimated as 1.6 X 10(-13) M, more than 8 orders of magnitude lower than the apparent dissociation constants of enzyme complexes with the substrate adenosine or the product inosine. The enzyme's remarkable affinity for this hydrated species, which is vanishingly rare in free solution, seems understandable in terms of the hydrate's close resemblance to a hydrated intermediate approaching the transition state in direct water attack on adenosine.

Adenosine Deaminase↗
PubMed1989

Expression and ontogeny of murine CD2.

CD2 was first defined as the erythrocyte rosetting protein on the surface of human T cells. Recently, the rat and murine homologues have been identified by cDNA cloning. In this report we demonstrate that CD2 is expressed on the surface of most adult murine peripheral lymphocytes and thymocytes by indirect immunofluorescence using an anti-murine CD2 antiserum. The expression of CD2 on murine B cells was unexpected since in rat and human species it has been defined as a T cell-specific marker. Furthermore, CD2 appears very early on fetal thymocytes during development. The level of surface expression increases from day 13 of gestation to day 17, after which the surface density appears to reach a steady state. Thus, CD2 is expressed on day-13 thymocytes at the same stage that Thy-1, Pgp1 and the TcR gamma/delta/CD3 complex have been shown to be expressed.

Animals↗