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Biomedical subjects

M C Rogers

Publications and source records attributed to M C Rogers.

At least 19 recordsLinked to original sources
PubMed1997

Gonadotropin-releasing hormone axons target the median eminence: in vitro evidence for diffusible chemoattractive signals from the mediobasal hypothalamus.

The projection of GnRH neurons to the median eminence of the medial basal hypothalamus (MBH) is established early in development and is also seen when preoptic area-derived GnRH cell-containing grafts are placed in the third ventricle of hypogonadal mice. To further study the factors directing GnRH axonal targeting, we cultivated embryonic or postnatal day 1 preoptic area with a coexplant on collagen- and laminin-coated membranes in insert chambers. After 7 days of culture, GnRH-immunoreactive fibers extended significantly farther and in greater number onto the sector of membrane facing a MBH coexplant than in the opposite sector, but not toward coexplants of control tissue. Moreover, such effects were specific, as outgrowth of a general axonal population, immunoreactive for growth-associated protein 43 was not influenced by the presence of the MBH. Preferential GnRH outgrowth toward the MBH was established early and was maintained during 10 days of culture. The importance of substrate-derived guidance was also assessed with confocal microscopy. GnRH axons consistently traveled in the company of growth-associated protein 43-labeled axons, but only erratic associations were seen between GnRH and glial processes extending on the membrane. We suggest that although employing an axonal substrate, GnRH axons follow a diffusible chemoattractive signal(s) secreted by the MBH.

Animals↗
PubMed1995

Neuromodulation of transplanted gonadotropin-releasing hormone neurons in male and female hypogonadal mice with preoptic area brain grafts.

Implantation of normal preoptic area (POA) tissue into the third ventricle of adult hypogonadal (HPG) mice provides a source of GnRH neurons that innervate the host median eminence and stimulate reproductive development in the sterile mutants. To further evaluate graft-host integration, the effects of N-methyl-D,L-aspartic acid (NMA) and opiate antagonists on LH secretion in HPG mice with POA transplants (HPG/POA) were tested. NMA challenges significantly stimulated LH secretion in 10 of 11 HPG/POA females. Only 5 of 12 HPG/POA males responded to the same treatment. Administration of the opiate antagonists naloxone or naloxone methiodide was ineffective in stimulating LH release in any mice, but opiate antagonist pretreatment significantly potentiated the LH secretory response to NMA in female, but not male, HPG/POA mice. A potential anatomical substrate for this facilitation may be the beta-endorphin-immunoreactive innervation of the POA grafts in all HPG/POA brains examined. beta-Endorphin fibers were also present in the median eminence in the vicinity of GnRH outgrowth from the grafts. However, similar innervation patterns in HPG/POA males that did not respond to opioid antagonism suggests that this is not sufficient. We tested whether the sex difference in HPG/POA responsivity to neuromodulation is related to the steroid milieu in the hosts. 17 beta-Estradiol (E2) treatment facilitated the LH secretory response of male HPG/POA to NMA challenges whether animals were castrated and given an E2 capsule prior to graft implantation or one week before testing two months after graft surgery. Intact or vehicle (sesame oil)-treated, castrated HPG/POA males rarely responded to NMA challenges, yet graft-derived GnRH innervation of the hosts' median eminence was comparable in all treatment groups. GnRH challenge testing indicated that pituitary sensitivity of the HPG/POA males was not significantly altered by E2 treatment, suggesting that estrogen acted centrally. These results indicate that the activity of grafted GnRH neurons may be modulated by endogenous opioids of host origin as well as by the hormonal milieu.

Animals↗
PubMed1994

Variation in approval by insurance companies of coverage for autologous bone marrow transplantation for breast cancer.

BACKGROUND: The proper evaluation of new forms of technology depends on the results of clinical trials. However, the treatment of patients in grant-sponsored clinical trials of cancer therapy usually requires that the proposed treatment be approved in advance by an insurance carrier in a process called predetermination. METHODS: We examined the consistency of predetermination decisions by insurance companies for 533 patients enrolled in grant-supported clinical trials of high-dose chemotherapy and autologous bone marrow transplantation (ABMT) for breast cancer from 1989 through 1992. These decisions about coverage were compared with peer-reviewed decision making according to the study protocol and with clinical outcomes. RESULTS: Requests for insurance coverage for ABMT were approved in 77 percent of the cases. Of these patients, 23 percent did not undergo bone marrow transplantation for protocol-based or medical reasons. Insurance coverage for ABMT was denied in response to the other requests, primarily because the therapy was considered experimental; of these patients, 51 percent eventually underwent bone marrow transplantation despite the denial of insurance. In some instances, the patient had to hire an attorney to gain coverage. The frequency of approval was not influenced by the pretreatment clinical characteristics of the patients, the design or phase of the study, the year in which the predetermination request was made, or the response to induction therapy. There was substantial inconsistency in the frequency of approval of coverage both among insurers and between decisions made by some individual insurers, even for patients in the same study protocol. CONCLUSIONS: The predetermination process as applied to patients receiving care in clinical research trials of cancer therapy was arbitrary and capricious. Although most of the patients eventually received financial coverage for entry into clinical trials, the process of predetermination by insurers did not correlate with protocol-based medical decision making, and it was a barrier to obtaining treatment.

Antineoplastic Agents↗
PubMed1994

Zero sum gain.

Explore the source record for details and available documents.

General Surgery↗
PubMed1994

Predictors of acute respiratory failure after bone marrow transplantation in children.

OBJECTIVE: To determine factors associated with acute respiratory failure after bone marrow transplantation which can be identified before the onset of lung disease. DESIGN: Population-based, retrospective study. SETTING: A referral-based pediatric intensive care unit and bone marrow transplant center. PATIENTS: Thirty-nine patients with lung disease (abnormal chest radiograph or a need for supplemental oxygen) were identified from a group of 318 pediatric bone marrow transplant patients from 1978 to 1988. Thirty-four of 39 patients with complete data were further classified into patients with mild lung disease (recovery without needing endotracheal intubation, n = 16) and patients with acute respiratory failure (requirement for endotracheal intubation, n = 18). INTERVENTIONS: Regression analyses were performed to define risk factors for development of respiratory failure (multivariate logistic regression) and for a shortened interval between the identification of lung disease and respiratory failure (Cox proportional hazards analysis). MEASUREMENTS AND MAIN RESULTS: Ninety-three percent (15/16) of patients with mild lung disease survived. Conversely, only 9% (2/23) of patients with respiratory failure survived. Predictors of respiratory failure included graft vs. host disease (odds ratio 28.3, 95% confidence interval 1.9-421, p = .015), a prelung disease (baseline) circulating creatinine concentration of > 1.5 mg/dL (> 132.6 mumol/L) (odds ratio 28.4, 95% confidence interval 1.4-577, p = .029), and male gender (odds ratio 14.6, 95% confidence interval 1-210, p = .049). Predictors of a shortened time to onset of respiratory failure included baseline serum creatinine value of > 1.5 mg/dL (> 132.6 mumol/L) (hazard ratio 6.2, 95% confidence interval 1.5-26.5, p = .013) and baseline total bilirubin concentration > 1.4 mg/dL (> 23.9 mumol/L) (hazard ratio 4.5, 95% confidence interval 0.98-20.7, p = .053). The median time to onset of respiratory failure was 4 days in patients with baseline creatinine values > or = 1.5 mg/dL (> 132.6 mumol/L) and 5 days in patients with baseline bilirubin concentrations > or = 1.4 mg/dL (> 23.9 mumol/L) vs. > 26 days in patients with creatinine < 1.5 mg/dL (< 132.6 mumol/L) and > 29 days in patients with bilirubin < 1.4 mg/dL (< 23.9 mumol/L) (Kaplan-Meier analysis). CONCLUSIONS: Renal and liver dysfunction preceded clinical evidence of lung disease in bone marrow transplant patients who developed respiratory failure. Lung disease leading to respiratory failure and adult respiratory distress syndrome appears to develop as one component of the multiple organ failure syndrome in pediatric bone marrow transplant patients.

Acute Disease↗
PubMed1992

Brain bioenergetics during cardiopulmonary resuscitation in dogs.

Cardiac arrest causes a rapid loss of cerebral adenosine triphosphate [corrected] (ATP) and a decrease in cerebral intracellular pH (pHi). Depending on the efficacy of cardiopulmonary resuscitation (CPR), cerebral blood flow levels (CBF) ranging from near zero to near normal have been reported experimentally. Using 31P magnetic resonance spectroscopy, the authors tested whether experimental CPR with normal levels of cerebral blood flow can rapidly restore cerebral ATP and pHi despite the progressive systemic acidemia associated with CPR. After 6 min of ventricular fibrillation in six dogs anesthetized with fentanyl and pentobarbital, ATP was reduced to undetectable concentrations and pHi decreased from 7.11 +/- 0.02 to 6.28 +/- 0.09 (+/- SE) as measured by 31P magnetic resonance spectroscopy. Application of cyclic chest compression by an inflatable vest placed around the thorax and infusion of epinephrine (40 micrograms/kg bolus plus 8 micrograms/kg/min, intravenously) maintained cerebral perfusion pressure greater than 70 mmHg for 50 min with the dog remaining in the magnet. Prearrest cerebral blood flows were generated. Cerebral pHi recovered to 7.03 +/- 0.03 by 35 min of CPR, whereas arterial pH decreased from 7.41 +/- 0.4 to 7.08 +/- 0.04 and cerebral venous pH decreased from 7.29 +/- 0.03 to 7.01 +/- 0.04. Cerebral ATP levels recovered to 86 +/- 7% (+/- SE) of prearrest concentration by 6 min of CPR. There was no further recovery of ATP, which remained significantly less than control. Therefore, in contrast to hyperemic reperfusion with spontaneous circulation and full ATP recovery, experimental CPR may not be able to restore ATP completely after 6 min of global ischemia despite restoration of CBF and brain pHi to prearrest levels.

Adenosine Triphosphate↗
PubMed1992

Comparison of cerebral blood flow by radionuclide cerebral angiography and by microspheres in cats.

BACKGROUND: Radionuclide cerebral angiography is commonly used as an adjunct to the diagnosis of brain death. Despite its acceptance as a diagnostic tool, it is not clear whether the absence of cerebral blood flow by radionuclide cerebral angiography denotes a complete lack of cerebral blood flow. METHODS: To compare cerebral blood flow estimated by radionuclide cerebral angiography with cerebral blood flow measured by the radiolabeled microsphere technique, we systematically varied cerebral perfusion pressure (mean arterial BP minus intracranial pressure) in anesthetized cats by infusing artificial cerebral spinal fluid into the lateral ventricle to increase intracranial pressure. We measured cerebral blood flow with both techniques as cerebral perfusion pressure was decreased from its baseline of 111 +/- 10 mm Hg to 20, 10, 5, 0, and less than 0 mm Hg, causing a stepwise decrease in cerebral blood flow. RESULTS: We found a correlation by regression analysis (r2 = .47, p less than .05) between radionuclide cerebral angiography and microsphere measurements of cerebral blood flow, when both blood flow measurements were expressed as a percentage of baseline values. However, if 20% of baseline flow was assigned as a cut-off point for critically low cerebral blood flow (based on human studies), radionuclide cerebral angiography was only 33% sensitive to detect critically reduced cerebral blood flow and had a positive predictive accuracy (of low-flow interpretation) of only 60%. Radionuclide cerebral angiography was unable to demonstrate a complete lack of cerebral blood flow, even in two instances when cerebral blood flow by microspheres was less than 0.1% of baseline. CONCLUSIONS: We conclude that the ability of radionuclide cerebral angiography to quantify low cerebral blood flow is poor, and that this technique may not identify severely reduced cerebral blood flow.

Animals↗
PubMed1991

Efficacy of Cushing response during development in sheep.

Mean aortic pressure (MAP) increases (Cushing response) when intracranial pressure (ICP) approaches MAP. We elevated ICP to levels equivalent to normal baseline MAP with infusion of mock cerebrospinal fluid (CSF) into the lateral cerebral ventricles and contrasted responses in near-term fetal sheep, 1-wk-old lambs, and adult sheep anesthetized with pentobarbital sodium. With CSF infusion 1-wk-old lambs and adults produced sustained increases in MAP of 16 +/- 1 and 22 +/- 2 mmHg, respectively, over a 40-min period. However, cerebral blood flow fell 66 and 57%, and cerebral O2 uptake fell 34 and 37%, respectively. In the near-term fetus, MAP increased by 11 +/- 1 mmHg and cerebral blood fell 49% at 3 min of elevated ICP. However, by 15 min MAP had increased further (+17 +/- 2 mmHg) and cerebral blood flow was nearly restored. In contrast to postnatal sheep, cerebral O2 uptake was maintained throughout in the fetus. The mechanism of increased MAP differed among groups. In adults total peripheral resistance fell significantly, whereas in the fetus and lamb it remained constant. Cardiac output increased in each group, but, because of the fall in peripheral resistance, increased cardiac output was relatively more important to the rise in MAP in adults. In addition, marked vasoconstriction occurred in intestines and skin in the fetus. The Cushing response is well-developed in near-term fetal sheep. After birth it may lose its effectiveness in providing for the basal metabolic demand of the brain.

Aging↗
PubMed1990

Age-related effects of compression rate and duration in cardiopulmonary resuscitation.

The effects of various compression rate and duration combinations on chest geometry and cerebral perfusion pressure during cardiopulmonary resuscitation (CPR) were studied in immature swine. Pentobarbital-anesthetized 2- and 8-wk-old piglets received CPR after ventricular fibrillation. At compression rates of 40, 60, 80, 100, 120, and 150/min, duty cycle (compression duration/total cycle time) was increased from 10 to 80% by 10% increments. Mean aortic and sagittal sinus pressures, pulsatile displacement, and deformity of the anterior chest wall were measured. Increasing duty cycle increased cerebral perfusion pressure until chest relaxation time was compromised. Inadequate chest recoil, development of static chest deformation, and limitation of pulsatile chest wall movement occurred in both age groups when relaxation time was very short (150-200 ms in 2-wk-old piglets, 250-300 ms in 8-wk-old piglets). These changes in chest geometry correlated with deterioration of cerebral perfusion pressure only in 8-wk-old piglets. In the younger group, perfusion pressures plateaued but did not deteriorate. These data emphasize the importance of duty cycle in generating cerebral perfusion pressure and indicate that younger animals can tolerate high compression rates except at extremely long duty cycles.

Aging↗
PubMed1990

Intensive management of severe head injury.

Intensive management of patients with severe head injury offers the best hope of minimizing death and functional disability in a young, working population. Secondary neurologic insult can be decreased by cardiorespiratory support and ICP control from the outset. Rapid neurologic assessment, airway management, and support of circulation are the basis of emergency management for head injury. Patients with severe head injury require intensive care management for two major reasons: management of ICP and management of organ system dysfunction. Care should not be withheld because of initially grim (and inaccurate) prognostic assessment. Newer techniques for assessing the adequacy of cerebral circulation may allow refinement of management strategies in the future.

Craniocerebral Trauma↗
PubMed1989

Current concepts in brain resuscitation.

The area of cerebral resuscitation has become an exciting area of research in critical care medicine. It is a complicated field, however, which has seen attempts to protect the brain using a single therapy such as barbiturates ultimately disappoint investigators in the field. It is likely that much more work needs to be done in understanding the intracellular metabolic and biochemical effects of ischemia before therapies can be designed that are likely to be effective. This work might ultimately require knowledge of how ischemia or hypoxia interrupt cellular RNA and DNA machinery before these effective therapies can be developed. Before we are discouraged by the difficulty of the task, however, it is useful to review how much progress has been made in understanding the pathophysiology of ischemic brain injury in the past decade, so that we may be challenged to continue our efforts in this exciting area of critical care medicine.

Animals↗
PubMed1989

The physiology of cardiopulmonary resuscitation.

As the pathophysiology of CPR is understood, ways to alter cerebral blood flow and neurologic outcome following CPR are likely to develop. This review highlights those areas likely to be of clinical importance in the near future.

Calcium Channel Blockers↗
PubMed1989

Cerebral blood flow and evoked potentials during Cushing response in sheep.

We determined how alterations in systemic hemodynamics, characteristic of the Cushing response, are related to changes in cerebral blood flow (CBF), cerebral metabolic rate of O2 (CMRO2), and brain electrical conductive function, as assessed by somatosensory-evoked potentials (SEP) and brain stem auditory-evoked responses (BAER). In three groups of eight pentobarbital-anesthetized sheep, intracranial pressure was gradually elevated to within 50, 25, or 0 mmHg of base-line mean arterial pressure and then held constant for 40 min by intraventricular infusion of mock cerebrospinal fluid. Microsphere-determined CBF fell when cerebral perfusion pressure was less than 50 mmHg. CMRO2 fell when CBF fell greater than 30-40%. Mean aortic pressure and cardiac output increased when CBF fell greater than 40%, i.e., at approximately the level at which CMRO2 fell. Furthermore, the magnitude of the increase in arterial pressure and cardiac output correlated with the reduction of CMRO2. SEP latency did not increase unless CBF fell greater than 55-65%, corresponding to a 20-30% reduction of CMRO2. Increased latency of BAER wave V was associated with a fall in midbrain blood flow of greater than 65-70%. Thus increase in SEP and BAER latencies required reductions of flow greater than those required to elicit a systemic response. This demonstrates that there is a range of intracranial pressure over which the increase in arterial pressure preserves sufficient CBF to sustain minimal electrical conductive function. The best predictor of the onset and magnitude of the Cushing response in adult sheep is the decrease in CMRO2.

Animals↗