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Biomedical subjects

J Jeffrey

Publications and source records attributed to J Jeffrey.

At least 19 recordsLinked to original sources
PubMed2004

Is electrosurgical loop excision with negative margins sufficient treatment for cervical ACIS?

OBJECTIVES: A recent clinical practice guideline supports the conservative management of adenocarcinoma in situ of the cervix (ACIS) diagnosed or suspected before treatment. However, patients may be diagnosed with unsuspected ACIS found in a loop electrosurgical excisional procedure (LEEP) specimen done for squamous dysplasia. To assess the outcome in this group of patients, we retrospectively analyzed all our cases of cervical ACIS and endocervical glandular dysplasia (EGD) to determine if LEEP was sufficient treatment. STUDY METHOD: A retrospective review of all patients treated for ACIS-EGD from 1990 to 2003 at Kingston General Hospital Colposcopy Clinic was undertaken. Sixty patients were identified. RESULTS: Of the 60 patients, 31 were diagnosed with ACIS-EGD only from the LEEP specimen. Twenty-two patients had ACIS and nine had EGD. Seven had further surgical procedures (five hysterectomies and two cold knife cone biopsies CKC) for positive LEEP margins. All seven of these specimens were disease free. Three of 31 LEEP patients were not compliant with colposcopic follow up. The remaining 28 patients were followed in our colposcopy clinic or by their family doctor for 6-107 months (median: 42; mean: 51) and have remained free of persistent or recurrent ACIS-EGD. CONCLUSION: Colposcopic follow-up with cytology and endocervical curettage (ECC) is acceptable for patients with ACIS-EGD found unexpectantly in LEEP specimens with negative margins. This is an alternative to proceeding to repeat LEEP, cold-knife conization, or simple hysterectomy, especially in patients desiring conservative management or preservation of fertility. Patients with positive margins, however, require further histologic evaluation.

Adenocarcinoma↗
PubMed2002

Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix.

PURPOSE: To test the hypothesis that cisplatin (CDDP) administered concurrently with standard radiotherapy (RT) would improve pelvic control and survival in patients with advanced squamous cell cancer of the cervix. PATIENTS AND METHODS: A total of 259 patients with International Federation of Gynecology and Obstetrics stage IB to IVA squamous cell cervical cancer with central disease greater-than-or-equal 5 cm or histologically confirmed pelvic lymph node involvement were randomized to receive RT (external-beam RT plus brachytherapy) plus weekly CDDP chemotherapy (40 mg/m(2)) (arm 1) or the same RT without chemotherapy (arm 2). RESULTS: A total of 253 patients were available for analysis. Median follow-up was 82 months. No significant difference was found in progression-free survival (P =.33). No significant difference in 3- and 5-year survival rates was found (69% v 66% and 62% v 58%, respectively; P =.42). The hazard ratio for survival (arm 2 to arm 1) was 1.10 (95% confidence interval, 0.75 to 1.62). CONCLUSION: This study did not show a benefit to either pelvic control or survival by adding concurrent weekly CDDP chemotherapy in a dose of 40 mg/m(2) to radical RT as given in this trial. Careful attention to RT details is important for achieving optimum outcome for patients with this disease.

Adult↗
PubMed2001

Diagnostic accuracy of fine-needle aspiration biopsy is determined by physician training in sampling technique.

BACKGROUND: Fine-needle aspiration biopsy (FNAB) has been used with variable success as a diagnostic test for benign and malignant breast lesions. The goal of this study was to examine the effects of training physicians in the fine-needle aspiration sampling-technique on the diagnostic accuracy of FNAB of palpable breast masses. The settings for this study were private physicians' offices and university clinics of primary care physicians, surgeons, and cytopathologists. METHODS: We reviewed 1043 consecutive FNAB specimens of the breast obtained during 1 year (1992): 729 FNABs were performed by formally trained physicians (at least 150 FNABs performed previously under supervision during fellowship training or the equivalent) who had done at least 100 FNABs during the year; 314 FNABs were performed by physicians without formal training who had done a median of only 2 FNABs during the year (range, 1-43 FNABs). All FNAB specimens were reviewed microscopically and evaluated for cellularity and type of material present, for diagnostic accuracy, and for the rate of surgical intervention. A minimum of 2 years of follow-up was obtained by matching all cases to the population-based Northern California Cancer Registry. FNAB specimens were correlated with histologic specimens when they were available. RESULTS: Using FNAB, the formally trained physicians missed 2% of cancers, whereas the physicians without formal training missed 25%. Among the patients with benign lesions seen by the formally trained physicians, 8% went on to surgery, whereas 30% of those seen by physicians without formal training did so. Specimens obtained by the formally trained physicians were significantly more cellular and were significantly less likely to be nondiagnostic. CONCLUSIONS: FNAB, when performed by physicians who are well trained in the technique, is a highly accurate, cost-effective diagnostic method that carries minimal morbidity and could replace a large number of surgical biopsies. When performed by physicians without adequate training, FNAB is often misleading and potentially harmful.

Adult↗
PubMed2001

The effectiveness of a thermal mattress in stabilizing and maintaining body temperature during the transport of very low-birth weight newborns.

The purpose of this study was to determine the effectiveness of a thermal mattress in stabilizing and maintaining body temperature during the transport of newborns who weigh less than 1,500 g. We compared 91 infants who were transported without a thermal mattress from April 1995 to March 1996 with 100 infants who were transported with the use of a transport thermal mattress (TTM) from April 1998 to October 1999. Temperature data were collected on arrival to the referring hospital, on departure from the referring hospital, and on arrival to the tertiary neonatal intensive care unit. The findings support that, over time, infants who were transported on a TTM had a greater increase or greater stability in body temperature, in comparison with infants who were not transported on a TTM (t = 5.1, p <.001). The data also supported that infants on a TTM maintained body temperature during stabilization and transport (F = 12.33, p =.001) better than the no mattress group did (F = 3.6, p =.061). Use of the TTM in the prevention of hypothermia in unstable environmental conditions can be extended to other areas within the hospital when thermoregulation of the premature infant is a concern, especially that of very low-birth weight infants. However, hyperthermia may also be a concern; body temperature should be monitored to watch for it.

Analysis of Variance↗
PubMed2001

Mechanism of action of 1-beta-D-2,6-diaminopurine dioxolane, a prodrug of the human immunodeficiency virus type 1 inhibitor 1-beta-D-dioxolane guanosine.

(-)-beta-D-2,6-Diaminopurine dioxolane (DAPD), is a nucleoside reverse transcriptase (RT) inhibitor with activity against human immunodeficiency virus type 1 (HIV-1). DAPD, which was designed as a water-soluble prodrug, is deaminated by adenosine deaminase to give (-)-beta-D-dioxolane guanine (DXG). By using calf adenosine deaminase a K(m) value of 15 +/- 0.7 microM was determined for DAPD, which was similar to the K(m) value for adenosine. However, the k(cat) for DAPD was 540-fold slower than the k(cat) for adenosine. In CEM cells and peripheral blood mononuclear cells exposed to DAPD or DXG, only the 5'-triphosphate of DXG (DXG-TP) was detected. DXG-TP is a potent alternative substrate inhibitor of HIV-1 RT. Rapid transient kinetic studies show the efficiency of incorporation for DXG-TP to be lower than that measured for the natural substrate, 2'-deoxyguanosine 5'-triphosphate. DXG-TP is a weak inhibitor of human DNA polymerases alpha and beta. Against the large subunit of human DNA polymerase gamma a K(i) value of 4.3 +/- 0.4 microM was determined for DXG-TP. DXG showed little or no cytotoxicity and no mitochondrial toxicity at the concentrations tested.

Adenosine Deaminase Inhibitors↗
PubMed1998

Safety and tolerability of cyclosporine and cyclosporine microemulsion during 18 months of follow-up in stable renal transplant recipients: a report of the Canadian Neoral Renal Study Group.

BACKGROUND: There has been concern that the increased drug exposure associated with treatment with cyclosporine microemulsion (CsA-ME) would lead to an increase in adverse events. METHODS: The long-term safety and tolerability of conventional cyclosporine (CsA) and CsA-ME were compared in a randomized, multicenter, pharmacoepidemiologic study involving 1097 stable renal transplant patients after 18 months of follow-up. RESULTS: No significant difference was seen in change in serum creatinine or calculated creatinine clearance between the two groups. Episodes of deterioration in renal function (change in serum creatinine > or = 20%) were categorized with the following results for CsA-ME versus CsA, respectively: acute rejection, 4.5% vs. 4.5%; chronic rejection, 8% vs. 11%; CsA nephrotoxicity, 12% vs. 7% (P=0.008); transient changes, 17% vs. 12%; other causes, 4% vs. 6%. During the first 6 months of the study, a transient increase in the incidence of gastrointestinal and neurological adverse events was seen in the CsA-ME group compared with the CsA group. Up to 18 months, patients in the CsA group reported significantly fewer hearing and vestibular disorders, but more cardiovascular problems than those in the CsA-ME group (P=0.035). CONCLUSIONS: Tolerance to CsA and CsA-ME was similar. Renal function over 18 months was not adversely affected by the increased drug exposure with CsA-ME, although there was a transient increase in nephrotoxicity. The frequency of acute and chronic rejection did not change.

Administration, Oral↗
PubMed1997

Quality of life, hope, and uncertainty of cardiac patients and their spouses before coronary artery bypass surgery.

The relationships among quality of life, uncertainty, and hope for 21 patients and their spouses before bypass surgery were examined in this study. The instruments used included: Ferrans' and Powers' Quality of Life Index, Mishel's Uncertainty in Illness Scale, and the Herth Hope Index. Greater uncertainty was associated with lower quality of life and hope scores for patients and spouses. Spouses were more uncertain about the patients' cardiac disease and had higher quality of life scores than the patients. Female patients had more uncertainty about their disease. Patients with poor left ventricle function had lower quality of life. Implications for practice include the need to incorporate the spouse into the plan of care. Also, the presence of uncertainty in the waiting period for surgery for both patients and their spouses, and its negative association with quality of life, reinforces the importance of pre-admission intervention with this population.

Adult↗
PubMed1997

The role of the nurse with families of patients in ICU: the nurses' perspective.

Although nurses are often charged with the responsibility of helping families cope with the stress that results when a loved one is hospitalized in a critical care unit, there is little research investigating how critical care nurses perceive their role with families. The objectives of this study were to (a) describe critical care nurses' role expectations and perceived role performance with respect to patients' families, and (b) describe the relationship between nurses' role expectations and their perceived role performance. Forty-seven nurses were surveyed in this descriptive, correlational study. There was a moderately strong correlation (r = .60, p < .0001) between role expectations and role performance. However, family-focused interventions requiring less time and less intense communication skills were performed more often than those requiring more time and greater skill in communication. Thus, certain family needs may be met inconsistently due to varied perceptions among nurses regarding their responsibility to families. The findings are discussed in relation to concepts from role theory.

Adult↗
PubMed1995

Phase II study to evaluate the toxicity and efficacy of concurrent cisplatin and radiation therapy in the treatment of patients with locally advanced squamous cell carcinoma of the cervix.

Sixty patients presenting with poor prognosis squamous cell cancer of the cervix have been studied in a phase II clinical trial. Patients were treated with radiotherapy and concurrent cisplatin chemotherapy every 10 days. Treatment was well tolerated with all patients completing radiotherapy as prescribed. There was one case of grade 4 acute bowel toxicity. Significant late morbidity was acceptable for this group of patients being restricted to two cases (3.3%) of grade 4 toxicity to the bowel. Pelvic control rates of 78% have been observed. There have been no pelvic recurrences after 26 months, although recurrences beyond the pelvis have occurred up to 4 years later. Actuarial 4-year survival is encouraging at 60%.

Actuarial Analysis↗
PubMed1995

A targeted mutation at the known collagenase cleavage site in mouse type I collagen impairs tissue remodeling.

Degradation of type I collagen, the most abundant collagen, is initiated by collagenase cleavage at a highly conserved site between Gly775 and Ile776 of the alpha 1 (I) chain. Mutations at or around this site render type I collagen resistant to collagenase digestion in vitro. We show here that mice carrying a collagenase-resistant mutant Col1a-1 transgene die late in embryo-genesis, ascribable to overexpression of the transgene, since the same mutation introduced into the endogenous Col1a-1 gene by gene targeting permitted normal development of mutant mice to young adulthood. With increasing age, animals carrying the targeted mutation developed marked fibrosis of the dermis similar to that in human scleroderma. Postpartum involution of the uterus in the mutant mice was also impaired, with persistence of collagenous nodules in the uterine wall. Although type I collagen from the homozygous mutant mice was resistant to cleavage by human or rat fibroblast collagenases at the helical site, only the rat collagenase cleaved collagen trimers at an additional, novel site in the nonhelical N-telopeptide domain. Our results suggest that cleavage by murine collagenase at the N-telopeptide site could account for resorption of type I collagen during embryonic and early adult life. During intense collagen resorption, however, such as in the immediate postpartum uterus and in the dermis later in life, cleavage at the helical site is essential for normal collagen turnover. Thus, type I collagen is degraded by at least two differentially controlled mechanisms involving collagenases with distinct, but overlapping, substrate specificities.

Amino Acid Sequence↗
PubMed1994

Improving quality of care based on evaluation of the Western Ontario Provincial Lithotripsy Program by patients and their families.

A survey is an effective method for evaluating quality of care and generating cost-effective ideas for quality improvement. This article describes a survey of 138 patients and their families to evaluate the quality of care provided by a regional lithotripsy program. Although patients and their families generally gave high ratings to the care they received, areas for improvement were documented. The results were ultimately used to support change in nursing practice and care of patients and their families. The survey process described incorporates principles of research, quality assurance, and quality improvement.

Attitude to Health↗
PubMed1994

Uncertainty and quality of life of adults hospitalized with life-threatening ventricular arrhythmias.

Advances in the management of ventricular arrhythmias have improved patient survival, but not the uncertainty faced by those living with these arrhythmias. Managing the uncertainty in illness is considered essential to the maintenance of well-being and, therefore, quality of life. The purpose of this study was to determine the relationship between uncertainty and quality of life for adults with recurrent ventricular arrhythmias. Using a descriptive correlational design, 22 adults hospitalized with life-threatening ventricular arrhythmias completed questionnaires prior to discharge from the hospital. Data were collected using a demographic questionnaire, the Mishel Uncertainty in Illness Scale, the Quality of Life Index-Cardiac Version, and a single item self-rating scale for amount of worry. Results from the study indicated that greater quality of life for the health and functioning domain was significantly correlated with lower overall uncertainty and less ambiguity. Greater worry about the arrhythmia was associated with increased uncertainty and ambiguity, and poorer quality of life for the health and functioning domain. The results provide support for the aversive nature and negative impact of uncertainty on quality of life for patients with ventricular arrhythmias. Conclusions address clinical and research implications of these findings.

Adult↗
PubMed1994

L-Tryptophan in supraphysiologic concentrations stimulates collagenase gene expression in human skin fibroblasts.

BACKGROUND: Collagenase plays a critical role in regulating connective tissue breakdown in physiologic and pathologic processes. The expression of collagenase is modulated by a variety of biologic and pharmacologic agents. L-tryptophan is an essential amino acid with diverse biologic effects not shared by other amino acids. EXPERIMENTAL DESIGN: In this study, we examined the effects of L-tryptophan on collagenase gene expression in normal human skin fibroblasts using Northern hybridizations and transient transfection assays. RESULTS: The results indicate that L-tryptophan at supraphysiologic concentrations caused a marked increase in collagenase gene expression. The increase in collagenase mRNA levels was reversible, time- and dose-dependent, and was accompanied by enhancement of procollagenase synthesis and secretion. Parallel accumulation of mRNA for tissue inhibitor of metalloproteinase was also noted, whereas stromelysin mRNA levels remained undetectable. The enhancement of collagenase mRNA was specific for L-tryptophan, and was abrogated by alpha-amanitin or dexamethasone. The apparent half-life of collagenase mRNA transcripts was similar in cultures exposed to interleukin-1 beta or L-tryptophan. In contrast to interleukin-1 beta, L-tryptophan-induced increase in collagenase mRNA was not preceeded by expression of c-jun or c-fos. Transient transfection of human skin fibroblasts with a collagenase promoter, chloramphenicol acetyl transferase construct indicated marked dose-dependent increase in promoter activity with L-tryptophan. CONCLUSIONS: These results demonstrate that L-tryptophan in supraphysiologic concentrations is a potent inducer of collagenase gene expression in vitro at a transcriptional level by human skin fibroblasts.

Adult↗
PubMed1993

Spontaneously hypertensive rats (SHR) readily learn to vary but not repeat instrumental responses.

When spontaneously hypertensive rats (SHR) and Wystar-Kyoto normotensive control rats (WKY) were rewarded in a 12-arm radial maze (Experiment 1), the SHRs varied their arm choices more, making fewer repetition errors than the WKYs. Similarly when rewards depended on variable sequences of responses on two levers in an operant chamber (Experiment 2), SHRs' sequences were more variable than those of WKYs. A requirement for response variability was then combined with a requirement to repeat selected responses in the radial maze (Experiment 3) and operant chamber (Experiment 4). WKYs learned to repeat more readily than the SHRs, whereas SHRs varied more readily. Thus, when subjects had to repeat responses, SHRs were at a disadvantage, but when variability was adaptive, SHRs excelled. The high variability of SHRs, together with their difficulty in learning to repeat, may have parallels in children diagnosed with attention deficit disorder with hyperactivity (ADDH).

Animals↗
PubMed1992

Cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide in advanced ovarian cancer: a randomized phase III study of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: Given the potential for improved tolerance, a trial was initiated to compare the toxicity and efficacy of a standard regimen of cisplatin-cyclophosphamide (75 mg/m2 and 600 mg/m2, respectively) with an experimental regimen of carboplatin-cyclophosphamide (300 mg/m2 and 600 mg/m2, respectively) in women with postoperative macroscopic residual ovarian cancer. PATIENTS AND METHODS: Between 1985 and 1989, 447 (417 eligible) patients were randomized. Treatment arms were well balanced; most patients had stage III (82%), grade 3 (54%) tumors with bulky residual (greater than 2 cm in 59%), and good performance status (Eastern Cooperative Oncology Group [ECOG] 0 or 1, 77%). Response was assessed after six 4-week cycles. RESULTS: The treatments were equally deliverable, with 76% of patients completing their allocated regimen. The reported reasons for failure to complete treatment differed; toxicity/refusal predominated on the cisplatin arm, and progressive disease predominated on the carboplatin arm (P = .0092). Cisplatin-treated patients were more likely to develop neuropathy and nephropathy, and carboplatin patients experienced myelosuppression, particularly thrombocytopenia. Efficacy was similar, with no significant differences for the cisplatin and carboplatin arms in clinical response rate (57% v 59% in those with measurable disease), pathologic response rate (52% v 54% in those suitable for relaparotomy), time to progression (median, 56 v 58 weeks), or overall survival (median, 100 weeks v 110 weeks). Time to progression and survival were predicted by residual disease size, performance status, and treatment center (with those treated at centers that accrued more patients doing better). CONCLUSION: Neither regimen is optimal in that relapse remains the norm. It may be inappropriate to expect that any single regimen can be an effective therapy for all patients with advanced ovarian cancer. Both cisplatin and carboplatin are likely to have a role in future treatment strategies.

Adult↗
PubMed1988

Biochemical changes in rhesus monkey during the first days after streptozotocin administration are indicative of selective beta cell destruction.

Hormonal and glycemic changes in 22 rhesus monkeys were characterized during the first days after treatment with streptozotocin (STZ) (45 to 55 mg/kg, administered intravenously [IV]). Almost half (10/22) of the monkeys developed insulin-dependent diabetes mellitus (STZ-IDDM) within five days following injection. Four of the remaining monkeys did not become insulin dependent for at least 6 months after STZ treatment, during which time they were considered non-insulin-dependent, and eight monkeys never required exogenous insulin. In the STZ-IDDM group, plasma immunoreactive c-peptide (IRC-P) levels fell by three hours after STZ from a mean +/- SEM of 252 +/- 82 to 101 +/- 45 pg/mL, as glucose and immunoreactive glucagon (IRG) levels increased from 65 +/- 3 and 120 +/- 37, respectively, to 336 +/- 43 mg/dL and 234 +/- 52 pg/mL, respectively. Between six and 30 hours after treatment, IRC-P increased to a peak of 1,561 +/- 360 pg/mL before falling permanently to less than 60 pg/mL by 66 hours. During this period, glucose and IRG responded in a reciprocal fashion by falling and then increasing to levels above 300 mg/dL and 300 pg/mL, respectively, by 66 hours. In the non-insulin-dependent diabetes mellitus (STZ-NIDDM) group, no clear reciprocal relationship between IRC-P and glucose and IRG was obtained. In nine additional monkeys subjected to total pancreatectomy (Px), IRC-P and IRG levels fell immediately and permanently by greater than 90% and 75%, respectively. Levels of immunoreactive somatostatin increased steadily over the initial 96 hours following STZ, but did so both STZ-IDDM and Px monkey groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗