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J R Jacobs

Publications and source records attributed to J R Jacobs.

At least 55 records · Page 3Linked to original sources
PubMed1995

Apoptosis of the midline glia during Drosophila embryogenesis: a correlation with axon contact.

We have examined cell death within lineages in the midline of Drosophila embryos. Approximately 50% of cells within the anterior, middle and posterior midline glial (MGA, MGM and MGP) lineages died by apoptosis after separation of the commissural axon tracts. Glial apoptosis is blocked in embryos deficient for reaper, where greater than wild-type numbers of midline glia (MG) are present after stage 12. Quantitative studies revealed that MG death followed a consistent temporal pattern during embryogenesis. Apoptotic MG were expelled from the central nervous system and were subsequently engulfed by phagocytic haemocytes. MGA and MGM survival was apparently dependent upon proper axonal contact. In embryos mutant for the commissureless gene, a decrease in axon-glia contact correlated with a decrease in MGA and MGM survival and accelerated the time course of MG death. In embryos mutant for the slit gene, MGA and MGM maintained contact with longitudinally and contralaterally projecting axons and MG survival was comparable to that in wild-type embryos. The initial number of MG within individual ventral nerve cord segments was increased by ectopic expression of the rhomboid gene, without changing axon number. Extra MGA and MGM were eliminated from the ventral nerve cord by apoptosis to restore wild-type numbers of midline glia. Ectopic rhomboid expression also shifted MGA and MGM cell death to an earlier stage of embryogenesis. One possible explanation is that axon-glia contact or communication promotes survival of the MG and that MG death may result from a competition for available axon contact.

Animals↗
PubMed1994

Chemotherapy as predictor of compliance.

Patient compliance with the increasingly complex adjuvant therapy protocols has always been of concern, particularly in the head and neck cancer population. The Head and Neck Intergroup recently concluded a phase III prospective randomized trial testing the addition of three courses of cisplatinum containing combination chemotherapy to standard treatment defined as surgery and postoperative radiotherapy for advanced stage III and IV squamous cell carcinoma. The chemotherapy was administered following the surgery prior to the postoperative radiotherapy. Variation from protocol is ranked retrospectively as minor acceptable, major acceptable, and major unacceptable. The incidence of major unacceptable variation from the protocol for radiotherapy immediately following the surgery was 15% vs. 19% in the population that completed all three courses of the chemotherapy (P < 0.10). However, for those patients that completed less than the three courses of chemotherapy, the incidence of major unacceptable variation in radiotherapy was 33% (P < 0.001). This observation was controlled for site, stage, performance status, age, sex, surgical margins and experience of participating institution. We conclude that compliance with a multicourse adjuvant chemotherapy regimen is predictive of subsequent compliance to radiotherapy in the head and neck cancer population.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Mesectodermal cell fate analysis in Drosophila midline mutants.

We have used enhancer traps and antibodies as markers of cell identity to assess the relative contribution of individual mesectodermal cell (MEC) lineages to CNS midline morphogenesis in four mutations that disrupt commissure formation in Drosophila. The absence of commissures, leading to longitudinal tract collapse, was seen in embryos mutant for the genes single-minded and slit. MEC lineages did not survive in single-minded mutant embryos, in contrast to the survival of all MEC lineages in slit mutant embryos. The midline glial cells were displaced and appeared ultrastructurally normal in slit mutant embryos, yet the presence of the MG was not sufficient to generate commissures. Commissure formation requires correct MEC cytoarchitecture, dependent upon slit activity. In fused commissure mutants (rhomboid and Star) neuron number was reduced in the ventral unpaired median neuron (VUM) lineage and the median neuroblast lineage before commissure formation (stage 12). Subsequent to these neuronal defects, the midline glia died by apoptosis (stage 13). Commissure fusion and glial apoptosis may be triggered by the earlier perturbations in MEC neuronal lineages. These studies establish when the respective activities of each gene are required for the development of each MEC lineage.

Alleles↗
PubMed1994

Effects of human milk or formula feeding on the growth, behavior, and protein status of preterm infants discharged from the newborn intensive care unit.

The growth, behavior, and protein status of 59 healthy preterm (mean gestational age 30 wk) infants fed either human milk or one of three infant formulas were studied post-discharge from the hospital. Formula-fed infants received either a standard term formula, a standard preterm formula, or an experimental preterm formula from discharge to 8 wk of age. From 8 to 16 wk, all formula-fed infants received the standard term formula. At 2, 8, and 16 wk, anthropometric, dietary intake, blood biochemistry, amino acid, and Brazelton Neonatal Behavioral Assessment measurements were evaluated. Weights, lengths, and head circumferences were similar for all feeding groups at discharge. After discharge all formula-fed infants were heavier than human milk-fed infants. Length and head circumference values and plasma urea nitrogen and retinol-binding protein concentrations were not different among dietary groups. Formula-fed infants had higher plasma concentrations of numerous amino acids compared with those of human milk-fed infants during the first 8 wk but not at 16 wk. There were no differences among the feeding groups in the Brazelton assessment. This study found little effect on the growth or behavioral or protein status of preterm infants discharged from the hospital who were fed either human milk or formulas designed for term or preterm infants.

Amino Acids↗
PubMed1994

Surgical reporting instrument designed to improve outcome data in head and neck cancer trials.

Precise reporting of surgical staging and operative data in multi-institutional protocol studies could provide a number of benefits: 1) fewer cases would be discarded because of inadequate data, 2) staff review time would be reduced, 3) there would be assurance that participating surgeons were performing similar operations on similar tumors, 4) the resulting precision in stratification should improve the likelihood of achieving accurate comparison of the treatment options under study, and 5) by comparing the surgical parameters with local-regional control of disease, the specific factors that have a statistically significant correlation with outcome could be identified. This paper presents a computer-based, anatomically oriented reporting instrument that should improve the reliability of surgical data available to multi-institutional protocols.

Clinical Trials as Topic↗
PubMed1994

Carotid artery reconstruction using superficial femoral arterial grafts.

The indications, consequences, and value of resection of the carotid artery as part of an extended neck dissection has been discussed for many years. Many of the earlier reports have focused on the sequelae of carotid artery ligation and tests to predict patient tolerance for the procedure. Efforts to reconstruct the carotid artery have been limited primarily to vein grafts. The authors report on 11 cases of reconstruction of the carotid artery using the patient's superficial femoral artery. The femoral artery itself is reconstructed using a Gore-Tex graft. Free autografts of the superficial femoral artery in the carotid location have been found to be an excellent size match, mechanically stronger than a vein graft, and tolerant of bacterial contamination. Arteriography in 1 case with 14 months' follow-up demonstrates long-term patency.

Blood Vessel Prosthesis↗
PubMed1993

Is a surgical resection leaving positive margins of benefit to the patient with locally advanced squamous cell carcinoma of the head and neck: a comparative study using the intergroup study 0034 and the Radiation Therapy Oncology Group head and neck database.

PURPOSE: The purpose of this study was to determine whether or not for patients with squamous cell carcinomas of the head and neck, a surgical resection leaving positive margins followed by postoperative adjuvant therapy improves the outcome compared to a matched group of patients treated with definitive radiotherapy alone. METHODS AND MATERIALS: From January 1985 through January 1990 a consortium of national cooperative groups (Radiation Therapy Oncology Group, Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, Northern California Oncology Group, Southeast Group, and Southwest Oncology Group) conducted a phase III clinical trial testing the efficacy of adjuvant chemotherapy for patients with resectable, squamous cell carcinomas of the head and neck. One hundred and nine patients were excluded from this study due to positive surgical margins. These patients have been followed prospectively with regards to local/regional tumor control, development of distant metastases, and survival. The postoperative treatment of these patients was not specified by the protocol but the majority of patients received postoperative radiotherapy +/- chemotherapy. These patients were compared with a matched group of patients from the Radiation Therapy Oncology Group head and neck database of patients treated with definitive radiotherapy alone using a standard fractionation schema. Matching parameters included primary tumor site, T-stage, N-stage, Karnofsky performance status, and age. RESULTS: Actuarial curves are presented for local/regional control and survival. At 4 years the local/regional control rate is 44% for the positive margin patients compared to 24% for the patients from the data base (p = 0.007). However, there is no significant difference between the survival curves (p = 0.76) with respective median survivals being 18.1 months vs. 17.9 months and 4-year survivals being 29% vs. 25%. CONCLUSION: While an incomplete excision followed by postoperative therapy does not seem to improve survival compared to treatment with radiotherapy alone, it appears to yield significantly better local/regional control. This would argue for its applicability in selected palliative settings. A follow-up, Phase III trial for patients with advanced tumors may be warranted to test traditional resectability criteria.

Actuarial Analysis↗
PubMed1993

Effect of hypothermia and sampling site on blood esmolol concentrations.

Esmolol hydrochloride was administered by constant-rate continuous infusion to 10 patients undergoing hypothermic cardiopulmonary bypass for coronary artery revascularization surgery. After a suitable loading dose, the esmolol infusion was started approximately 30 minutes before bypass and was stopped 10 minutes after termination of bypass. Esmolol concentrations were measured in arterial and venous blood samples collected before and after bypass and in samples taken from the inflow and outflow ports of the membrane oxygenator during bypass. Blood esmolol concentrations increased during hypothermia in a manner that correlated significantly and inversely with temperature. All patients were separated from the extracorporeal circulation without difficulty, and the average arterial esmolol concentration was slightly below the prebypass concentration within minutes of discontinuing bypass. Esmolol disappeared from the blood rapidly on terminating the infusion. There was no difference between esmolol concentrations measured simultaneously from the inflow and outflow ports of the membrane oxygenator during bypass, but radial arterial esmolol concentrations before and after bypass were on average about sevenfold higher than forearm venous esmolol concentrations during the esmolol infusion. The results of this study lead to two important conclusions: (1) in vivo clearance of esmolol demonstrates acute temperature dependence and (2) esmolol is removed irreversibly as it passes through the microcirculation of the hand, making measurement of peripheral esmolol concentrations markedly dependent on sampling site (arterial versus venous).

Adrenergic beta-Antagonists↗
PubMed1993

Perturbed glial scaffold formation precedes axon tract malformation in Drosophila mutants.

The longitudinal glia (LG), progeny of a single glioblast, form a scaffold that presages the formation of longitudinal tracts in the ventral nerve cord (VNC) of the Drosophila embryo. The LG are used as a substrate during the extension of the first axons of the longitudinal tract. I have examined the differentiation of the LG in six mutations in which the longitudinal tracts were absent, displaced, or interrupted to determine whether the axon tract malformations may be attributable to disruptions in the LG scaffold. Embryos mutant for the gene prospero had no longitudinal tracts, and glial differentiation remained arrested at a preaxonogenic state. Two mutants of the Polycomb group also lacked longitudinal tracts; here the glia failed to form an oriented scaffold, but cytological differentiation of the LG was unperturbed. The longitudinal tracts in embryos mutant for slit fused at the VNC midline and scaffold formation was normal, except that it was medially displaced. Longitudinal tracts had intersegmental interruptions in embryos mutant for hindsight and midline. In hindsight, there were intersegmental gaps in the glial scaffold. In midline, the glial scaffold retracted after initial extension. LG morphogenesis during axonogenesis was abnormal in midline. Commitment to glial identity and glial differentiation also occurred before scaffold formation. In all mutants examined, the early distribution of the glycoprotein neuroglian was perturbed. This was indicative of early alterations in VNC pattern present before LG scaffold formation began. Therefore, some changes in scaffold formation may have reflected changes in the placement and differentiation of other cells of the VNC. In all mutants, alterations in scaffold formation preceded longitudinal axon tract formation.

Animals↗
PubMed1993

Midazolam and fentanyl continuous infusion anesthesia for cardiac surgery: a comparison of computer-assisted versus manual infusion systems.

Continuous infusion of intravenous anesthetics can be achieved either by a manually controlled infusion (MCI) pump, or by a computer-assisted continuous infusion (CACI) pharmacokinetic model-driven infusion system. Randomized double-blind comparisons of the two infusion systems for general anesthesia were performed in 24 patients undergoing coronary artery bypass grafting. Patients were allocated to receive continuous infusions of midazolam and fentanyl by either a MCI device or CACI. Midazolam and fentanyl infusions were independently titrated to maintain hemodynamic stability, defined as mean arterial pressure (MAP) and heart rate (HR) within 20% of baseline values. As directed by the study design, comparable hemodynamic control was achieved in both groups. Mean plasma fentanyl concentrations measured at specific timepoints were similar between groups. The plasma midazolam level for induction was 196 +/- 139 ng/mL in the CACI group and 300 +/- 128 ng/mL in the MCI group, and the fentanyl level was similar in both groups, 6.7 +/- 1.9 ng/mL in CACI and 6.3 +/- 4.6 ng/mL in the MCI group. The drug levels were lower (P < or = .05) for midazolam during maintenance of anesthesia and similar for fentanyl during the maintenance of anesthesia. In the MCI group, the average duration of anesthesia was 246.5 +/- 35.0 minutes, with a mean total fentanyl dose of 30.27 +/- 11.14 micrograms/kg. In the CACI group, the average duration of anesthesia was 230.8 +/- 44.1 minutes, with a mean total fentanyl dose of 34.61 +/- 5.40 micrograms/kg (P > 0.05 for comparisons between groups for duration of anesthesia and total fentanyl dose).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗
PubMed1993

Plasma concentration of fentanyl, with 70% nitrous oxide, to prevent movement at skin incision.

BACKGROUND: The Cp50 (minimal steady state plasma concentration of an intravenous analgesic/anesthetic required to prevent a somatic response in 50% of patients following skin incision) and the Cp50-BAR (minimal plasma concentration of an analgesic/anesthetic required to prevent either a somatic, hemodynamic, or autonomic response in 50% of patients following skin incision) have been recently proposed as a measure, like minimum alveolar concentration (MAC; and MAC-BAR), to establish the relative potency of intravenous analgesics. This study was conducted to establish the Cp50 for fentanyl. METHODS: Unpremedicated patients were administered fentanyl (in the presence of 70% N2O) via computer-assisted continuous infusion, a pharmacokinetic model-driven infusion device. After induction of anesthesia with fentanyl, the randomized target fentanyl concentration was entered into computer-assisted continuous infusion. This target fentanyl concentration was maintained until skin incision. Before induction, prior to skin incision, and immediately after skin incision, arterial blood samples were obtained for measurement of fentanyl and norepinephrine concentrations. At skin incision, patients were observed for a somatic, hemodynamic, or autonomic response. Only patients in whom the pre- and postincision fentanyl concentrations were within +/- 30% were included in the calculation of the Cp50. The Cp50 was calculated using logistic regression. RESULTS: The Cp50 for fentanyl was 3.26 ng/ml, and the Cp50-BAR was 4.17 ng/ml. CONCLUSIONS: Comparing these results with the previously published Cp50 of alfentanil, the potency of fentanyl relative to alfentanil is 1:58. Establishing the Cp50, once effect site equilibration has occurred, will allow pharmacodynamic comparisons between the opioids at equipotent concentrations.

Adult↗
PubMed1993

Algorithm to control "effect compartment" drug concentrations in pharmacokinetic model-driven drug delivery.

In most computer-controlled pharmacokinetic model-driven drug infusion pumps, simulation of a linear compartmental pharmacokinetic model is used to compute the rate of intravenous drug infusion required to achieve setpoint central compartment (plasma) drug concentrations. For many drugs, it has been suggested that it is the drug concentration in a hypothetical "effect" compartment, rather than in the plasma, that should be manipulated to achieve maximum control over pharmacologic action. Controlling the effect compartment drug concentration is algorithmically more difficult than controlling the central compartment drug concentration because of the time delay between administration of drug into the central compartment and its subsequent appearance in the effect compartment. Presented in this paper is a model-based dosing algorithm for use in pharmacokinetic model-driven drug infusion devices that target the theoretical effect compartment drug concentration.

Algorithms↗
PubMed1993

Implications of positive surgical margins.

The recently concluded Head and Neck Intergroup trial tested the addition of three courses of cis-platinum containing chemotherapy to standard treatment of surgery and postoperative radiotherapy for patients with advanced operable squamous cell carcinoma of the head and neck. Only patients with negative surgical margins were eligible for the trial. One hundred twelve patients with positive surgical margins were dropped from the trial but continued to be followed. These patients received a variety of treatments. Positive surgical margins were most often seen in nonglottic primaries and with increasing frequency as the N stage increased. Patients with positive margins who achieved a complete clinical response to subsequent treatment had a median survival of 33.8 months vs. 9.1 months for those with less than a complete clinical response. The addition of chemotherapy did not significantly alter the median survival of the positive margin patients.

Adult↗
PubMed1993

Evaluation of the effect of alfentanil on the minimum alveolar concentration of halothane in horses.

The effect of 3 plasma concentrations of alfentanil on the minimum alveolar concentration (MAC) of halothane in horses was evaluated. Five healthy geldings were anesthetized on 3 occasions, using halothane in oxygen administered through a mask. After induction of anesthesia, horses were instrumented for measurement of blood pressure, airway pressure, and end-tidal halothane concentrations. Blood samples, for measurement of pH and blood gas tensions, were taken from the facial artery. Positive pressure ventilation was begun, maintaining PaCO2 at 49.1 +/- 3.3 mm of Hg and airway pressure at 20 +/- 2 cm of H2O. The MAC was determined in triplicate, using a supramaximal electrical stimulus of the oral mucous membranes. Alfentanil infusion was then begun, using a computer-driven infusion pump to achieve and maintain 1 of 3 plasma concentrations of alfentanil. Starting at 30 minutes after the beginning of the infusion, MAC was redetermined in duplicate. Mean +/- SD measured plasma alfentanil concentration during the infusions were 94.8 +/- 29.0, 170.7 +/- 29.2 and 390.9 +/- 107.4 ng/ml. Significant changes in MAC were not observed for any concentration of alfentanil. Blood pressure was increased by infusion of alfentanil and was dose-related, but heart rate did not change. Pharmacokinetic variables of alfentanil were determined after its infusion and were not significantly different among the 3 doses.

Alfentanil↗
PubMed1992

A comparison of gastrostomy techniques in patients with advanced head and neck cancer.

Patients with advanced head and neck carcinomas often suffer from impaired deglutition and require prolonged enteral feedings during therapy. This retrospective study analyzed 75 patients managed with three different gastrostomy techniques. Thirty patients received a percutaneous endoscopic gastrostomy; 28 patients had an open tube gastrostomy using a Foley or Malecot catheter through a purse-string stay suture; and 17 patients received an open-tube gastrostomy with a 1-cm Dacron-cuffed Silastic catheter enclosed in a 3-cm Witzel tunnel with the cuff buried in the subperitoneal pocket. The complication rate for 100 days of tube use was 0.21 for cuffed Silastic gastrostomy, 0.35 for open tube gastrostomy, and 1.41 for the percutaneous endoscopic gastrostomy group. We conclude that the cuffed Silastic gastrostomy technique is superior in this patient population.

Enteral Nutrition↗
PubMed1992

DNA ploidy of primary and metastatic squamous cell head and neck cancers.

Regional metastases are a major determinant in the treatment outcome of patients with squamous cell carcinoma of the head and neck. Metastases do not respond as well to cytotoxic therapy as do primary tumors. DNA diploid tumors or tumor components also respond poorly to intermittent cytotoxic therapy. In our series of 497 patients with squamous cell carcinoma of the head and neck, the percentage of pure DNA diploid tumors and the mean DNA indexes in 497 primary tumors and 82 regional metastases were 34% and 1.54 and 50% and 1.34, respectively. Paired comparisons were performed in 61 patients and revealed a statistically significant increase in the frequency of DNA diploid tumors (27.4% to 41.2%) in associated lymph node metastases. The clinical observation that patients with squamous cell carcinoma of the head and neck and regional lymph node metastases have a poorer prognosis and a poorer response to cytotoxic therapy may in part be explained by the increased incidence of DNA diploid tumors in their regional lymph nodes, and the poorer response of such tumors to cytotoxic therapy.

Carcinoma, Squamous Cell↗
PubMed1992

Adjuvant chemotherapy for resectable squamous cell carcinomas of the head and neck: report on Intergroup Study 0034.

To test the efficacy of sequential chemotherapy as an adjuvant to surgery and postoperative radiotherapy for patients with locally-advanced but operable squamous cell cancers of the head and neck region, a randomized clinical trial was conducted under the auspices of the Head and Neck Intergroup (Radiation Therapy Oncology Group, Southwest Oncology Group, Eastern Oncology Group, Cancer and Leukemia Group B, Northern California Oncology Group, and Southeast Group). Eligible patients had completely resected tumors of the oral cavity, oropharynx, hypopharynx, or larynx. They were then randomized to receive either three cycles of cis-platinum and 5-FU chemotherapy followed by postoperative radiotherapy (CT/RT) or postoperative radiotherapy alone (RT). Patients were categorized as having either "low-risk" or "high-risk" treatment volumes depending on whether the surgical margin was greater than or equal to 5 mm, there was extracapsular nodal extension, and/or there was carcinoma-in-situ at the surgical margins. Radiation doses of 50-54 Gy were given to "low-risk" volumes and 60 Gy were given to "high-risk" volumes. A total of 442 analyzable patients were entered into this study with the mean-time-at-risk being 45.7 months at the time of the present analysis. The 4-year actuarial survival rate was 44% on the RT arm and 48% on the CT/RT arm (p = n.s.). Disease-free survival at 4 years was 38% on the RT arm compared to 46% on the CT/RT arm (p = n.s.). At 4 years the local/regional failure rate was 29% vs. 26% for the RT and CT/RT arms, respectively (p = n.s.). The incidence of first failure in the neck nodes was 10% on the RT arm compared to 5% on the CT/RT arm (p = 0.03 without adjusting for multiple testing) and the overall incidence of distant metastases was 23% on the RT arm compared to 15% on the CT/RT arm (p = 0.03). Treatment related toxicity is discussed in detail, but, in general, the chemotherapy was satisfactorily tolerated and did not affect the ability to deliver the subsequent radiotherapy. Implications for future clinical trials are discussed.

Antineoplastic Combined Chemotherapy Protocols↗