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J Nesbitt

Publications and source records attributed to J Nesbitt.

11 recordsLinked to original sources
PubMed2001

A three-step strategy of induction chemotherapy then chemoradiation followed by surgery in patients with potentially resectable carcinoma of the esophagus or gastroesophageal junction.

BACKGROUND: Patients with locoregional carcinoma of the esophagus or gastroesophageal junction have a poor survival rate after surgery. Preoperative chemotherapy or chemoradiotherapy has not improved the outcome for these patients. Our study was designed to assess the feasibility of preoperative induction combination chemotherapy in addition to chemoradiotherapy to improve the curative resection rate, local control, and survival. PATIENTS AND METHODS Patients having histologic proof of localized carcinoma (either squamous cell carcinoma or adenocarcinoma) of the esophagus or gastroesophageal junction underwent full classification including endoscopic ultrasonography (EUS). Patients first received up to two courses of induction chemotherapy consisting of 5-fluorouracil at 750 mg/m(2)/day as continuous infusion on Days 1--5, cisplatin at 15 mg/m(2)/day as an intravenous bolus on Days 1--5, and paclitaxel at 200 mg/m(2) as a 24-hour intravenous infusion on Day 1. The second course was repeated on Day 29. This was followed by radiotherapy (45 grays in 25 fractions) and concurrent admission of 5-fluorouracil (300 mg/m(2)/day as a continuous infusion 5 days/week) and cisplatin (20 mg/m(2) on Days 1--5 of radiotherapy). After chemoradiotherapy, patients underwent surgery. The feasibility of this approach, curative resection rates, patient survival, and patterns of failure were assessed. RESULTS: Thirty-seven of 38 patients enrolled were evaluable for toxicity and survival. Adenocarcinoma and distal esophageal location of carcinoma were observed frequently. Thirty-five (95%) of the 37 patients underwent surgery, all of whom had an R0 (curative) resection. A pathologic complete response was noted in 11 (30%) of the 37 total patients. In addition, 5 patients (14%) had only microscopic carcinoma. According to EUS classification, 31 (89%) of the 35 patients who underwent surgery had a T3 carcinoma whereas according to pathologic classification only 3 (9%) had a T3 carcinoma (P </= 0.01). Similarly, according to EUS classification, 23 patients (66%) had an N1 carcinoma, whereas according to pathologic classification only 7 patients (20%) had an N1 carcinoma (P < or = 0.01). At a median follow-up of 20 months (minimum follow-up, 13+ months; maximum follow-up, 36+ months), the median survival duration for the 37 patients had not yet been reached. In addition, there were two deaths related to surgery. CONCLUSIONS: These data show that the three-step strategy of preoperative paclitaxel-based induction chemotherapy then chemoradiotherapy followed by surgery is feasible and appears quite active in patients having locoregional carcinoma of the esophagus or gastroesophageal junction. Future investigations should focus on substituting cisplatin with less toxic agents and including more systemic therapy with newer classes of agents.

Adenocarcinoma↗
PubMed2000

Zanamivir use during transmission of amantadine-resistant influenza A in a nursing home.

OBJECTIVE: To describe the use of zanamivir during an influenza A outbreak. POPULATION: Residents of a 176-bed long-term-care facility for the elderly in Newmarket, Ontario, Canada, 90% of whom received influenza vaccine in the fall of 1998. OUTBREAK: When respiratory illness due to influenza A was confirmed, infection control measures and amantadine prophylaxis were initiated. Despite these measures, transmission of influenza A continued. INTERVENTION: Zanamivir inhalations, 10 mg daily for prophylaxis and 10 mg twice daily for treatment of influenza. RESULTS: There were 13 definite and 66 probable outbreak-associated cases of influenza A. Twelve (15%) cases developed pneumonia, 7 (9%) were hospitalized, and 2 (2.6%) died. All 12 culture-positive cases yielded influenza A/Sydney/H3N2/05/97-like virus, a 1998/99 vaccine component. The three isolates obtained prior to the initiation of amantadine were amantadine-susceptible; all nine obtained after prophylaxis was instituted were amantadine-resistant. One hundred twenty-nine (92%) of 140 residents who were offered zanamivir accepted it and were able to attempt inhalations. Of these 129, 78% (100) had no difficulty in complying with inhalations. Difficulty with inhalations was associated with decreased functional and mental status. Fifteen (58%) of 26 residents fully dependent in activities of daily living had difficulty compared to 14 (14%) of 100 others (P<.001). Twenty-two (45%) of 49 residents not oriented to person, place, or time had difficulty compared to 7 (10%) of 77 others (P<.001). In the 2 weeks after zanamivir prophylaxis, only 2 new cases of respiratory illness occurred, neither confirmed as influenza. No side effects were identified in 128 zanamivir-treated residents. CONCLUSION: A minority of nursing home residents have difficulty following instructions for zanamivir inhalations. Zanamivir was well tolerated, and its use was temporally associated with termination of an outbreak that amantadine had failed to control.

Activities of Daily Living↗
PubMed1999

Preparation of nuclear extracts from myelinating Schwann cells.

Myelination of peripheral nerve fibres is performed by Schwann cells and is associated with the coordinate upregulation of lipid synthesis and multiple genes encoding myelin-specific proteins. Both the decision to enter into a myelinating phenotype and subsequently, the quantity of myelin that each Schwann cell elaborates appear to be controlled by axonal signals. Understanding of the relevant signaling pathways and the downstream transcription factors and cis elements that confer myelin gene expression is notably limited. In large part, this has resulted directly from a lack of methods for obtaining nuclear extracts from myelinating Schwann cells thus precluding the application of numerous powerful molecular techniques. In this report, we describe a method that overcomes this limitation for the myelinating Schwann cells in the sciatic nerves of the mouse. During the evolution of the method, its effectiveness was monitored using an oligonucleotide containing the binding site for KROX-20, a transcription factor known to be present in myelinating Schwann cells. Following technical development, the optimized protocol has proven to be entirely reliable and thus novel experimental strategies now can be applied to the investigation of the molecular mechanisms controlling gene expression in peripheral nerves.

Animals↗
PubMed1998

A multidisciplinary approach to therapy for unresectable malignant thymoma.

BACKGROUND: The therapeutic outcome for unresectable, locally advanced, malignant thymoma has been poor. OBJECTIVE: To improve tumor resectability and patient survival rates by studying a multimodal approach to therapy for unresectable malignant thymoma. DESIGN: Prospective cohort study. SETTING: Tertiary care cancer center. PARTICIPANTS: All eligible patients had newly diagnosed, histologically proven, unresectable malignant thymoma. INTERVENTION: The treatment regimen consisted of induction chemotherapy (three courses of cyclophosphamide, doxorubicin, cisplatin, and prednisone), surgical resection, postoperative radiation therapy, and consolidation chemotherapy (three courses of cyclophosphamide, doxorubicin, cisplatin, and prednisone). Tissue samples were taken at the time of surgical resection for assessment of tumor necrosis and Ki-67 expression. MEASUREMENTS: Tumor response and resectability (both overall and after induction chemotherapy) and disease-free survival rate in patients who received multimodal therapy. RESULTS: 13 patients were consecutively enrolled from February 1990 to December 1996, and 12 evaluable patients were assessed for response. Disease responded to induction chemotherapy completely in 3 patients (25%) and partially in 8 patients (67%); 1 patient had a minor response (8%). Eleven patients had surgical resection; 1 refused surgery. Tumors were removed completely in 9 (82%) and incompletely in 2 (18%) of 11 patients who had been receiving radiation therapy and consolidation chemotherapy. All 12 patients are alive (100% at 7 years), with a median follow-up of 43 months, and 10 patients are disease free (73% disease-free survival at 7 years). A high correlation was seen between tumor necrosis after induction chemotherapy and Ki-67 expression (r=-0.88). CONCLUSIONS: Aggressive multimodal treatment is highly effective and may cure locally advanced, unresectable malignant thymoma.

Adult↗
PubMed1996

Patients with limited-stage small-cell lung cancer treated with concurrent twice-daily chest radiotherapy and etoposide/cisplatin followed by cyclophosphamide, doxorubicin, and vincristine.

PURPOSE: A phase II trial in patients with limited-stage small-cell lung cancer treated with induction etoposide/cisplatin plus twice-daily chest radiotherapy was conducted in an attempt to increase response rates and prolong survival. PATIENTS AND METHODS: Fifty-four previously untreated patients with limited-stage small-cell cancer were treated with etoposide/cisplatin and concurrent radiotherapy at 1.5 Gy twice daily for 3 weeks to a total dose of 45 Gy. Patients then received three more cycles of etoposide/cisplatin followed by four cycles of vincristine, doxorubicin, and cyclophosphamide or an individualized chemotherapy regimen. RESULTS: Nine patients are alive and free of cancer a median of 4 years (range, 2 to 7) from the start of treatment. Thirty-eight have had progression of their cancer at a median of 1.2 years (range, 0.5 to 5.4) and all have died of small-cell cancer. Thirteen of these 38 patients' (34%) only site of initial relapse was in the CNS and all died of CNS metastases. Five patients died during therapy or from its complications and two patients died of causes other than relapsed small-cell lung cancer and toxicity. The median survival time is 21.3 months, with an actual survival rate of 83% at 1 year, and actuarial survival rates of 43% at 2 years and 19% at 5 years. CONCLUSION: This combined modality regimen for patients with limited-stage small-cell lung cancer results in a 2-year survival rate of 43%, but the principal cause of death in these patients is still relapse of the original cancer. Isolated CNS metastases caused more than 30% of the cancer deaths.

Adult↗
PubMed1995

Stability of ursodiol in an extemporaneously compounded oral liquid.

The stability of ursodiol in an extemporaneous oral liquid formulation refrigerated at 4 degrees C for 35 days was studied. A suspension was prepared by opening commercially available 300-mg capsules of ursodiol, adding Glycerin, USP, to form a paste, and then adding Simple Syrup, NF. A control solution was prepared from analytical-grade ursodiol powder in simple syrup. The final concentration of ursodiol in both formulations was 60 mg/mL. Three samples of each preparation were stored in 2-oz, amber glass prescription bottles in the dark at 4 degrees C. Immediately after preparation and at 7, 14, 21, 28, and 35 days, samples were visually inspected, tested for pH, and assayed in duplicate by high-performance liquid chromatography. Stability was defined as the retention of more than 90% of the initial concentration. On day 35, the mean percentage of the initial ursodiol concentration remaining was 96.5% in the suspension made from powder-filled capsules, and 100.6% in the suspension made from analytical-grade powder. The color, odor, and pH of the samples did not change appreciably over the study period. An extemporaneously compounded oral liquid preparation of ursodiol in simple syrup was stable under the conditions studied for up to 35 days.

Administration, Oral↗
PubMed1990

The vasopressin response to severe birth asphyxia.

Serial measurements of urinary arginine vasopressin (AVP) were made in six severely birth asphyxiated newborn infants. In five infants serial plasma concentrations were also evaluated. There was a strong negative correlation between plasma AVP and plasma osmolality in these infants (r = -0.52, P = 0.0012). In neither the individual babies nor the group as a whole was there a significant correlation between plasma AVP and the urinary excretion of AVP even if the latter was standardised for creatinine content. Normal development at follow up was only observed in two asphyxiated infants who had consistently low urinary arginine vasopressin levels in the first days of life. Infants with consistently high urinary vasopressin concentrations either died or were severely abnormal in their subsequent development.

Apgar Score↗
PubMed1989

Coumarin necrosis of the penis.

Coumarin-induced necrosis of the skin and subcutaneous tissue is an uncommon but well recognized complication of anticoagulant therapy. Although any area of skin may be involved necrosis of the penis is rare. We report a case of penile necrosis associated with coumarin therapy and review the literature.

Coumarins↗