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Biomedical subjects

L M Katz

Publications and source records attributed to L M Katz.

At least 19 recordsLinked to original sources
PubMed2001

Brain energetics of cardiopulmonary cerebral resuscitation.

Recovery of normal brain energetic conditions during and after resuscitation from cardiac arrest is critical for survival and good neurologic outcome. This review emphasizes the glucose-driven metabolic processes during and after ischemia and on the post-resuscitation development of secondary energy derangements. It also explores some potential therapeutic interventions designed to attenuate these energy derangements. The article summarizes some bench research and is not intended to provide treatment strategies for clinical application.

Brain↗
PubMed2000

Cardiopulmonary and cerebral resuscitation.

The future of cardiopulmonary resuscitation lies in new technologies for monitoring and generating vital organ perfusion during cardiac arrest and the post-resuscitation phase and in pharmacologic agents that will enhance ROSC and reverse ischemia-reperfusion injury. ROSC is the first step toward survival, so interventions that improve ROSC deserve further investigation. Long-term survival with good neurologic recovery is the critical endpoint. Interventions recommended for clinical practice must therefore demonstrate improved long-term survival. The resources required to provide many of the interventions discussed in this article, principally invasive perfusion technologies, cannot be justified unless there is clear benefit. The allocation of such resources to provide intensive resuscitation and post-resuscitation support will need to be addressed from medical and societal viewpoints.

Anti-Arrhythmia Agents↗
PubMed2000

Bovine hemoglobin-based oxygen carrier (HBOC-201) for resuscitation of uncontrolled, exsanguinating liver injury in swine. Carolina Resuscitation Research Group.

In the setting of rapidly exsanguinating hemorrhage, resuscitation with intravenous (i.v.) crystalloid solution may not sustain survival before availability of allogenic blood transfusion and surgery. This study tested the hypothesis that bovine hemoglobin-based oxygen carrier, HBOC-201, would improve resuscitation and extend early survival from exsanguinating hemorrhage. This study simulated the prehospital scenario of rapidly exsanguinating hemorrhage with prolonged prehospital time and lack of blood availability. Severe hemorrhagic shock was induced in swine by using multiple liver lacerations. At 9 min after the onset of bleeding, swine were randomized to receive approximately 10 mL/kg/min of i.v. lactated Ringer's solution (n = 10) or HBOC-201 (n = 7) to achieve a mean aortic pressure (MAP) of 60 mmHg. Thereafter, infusion rate was adjusted to maintain MAP at 60 mmHg for up to 2 h. All animals were initially successfully resuscitated. The results showed 2-h survival was 1 of 10 with lactated Ringer's and 7 of 7 with HBOC-201 (P = 0.0004). Nine lactated Ringer's swine had cardiovascular collapse at 36 +/- 10 min. Lactate at 30 min was 18 +/- 3 mmol/L with lactated Ringer's and 12 +/- 2 mmol/L with HBOC-201 (P < 0.05). Hematocrit was <1% in 9 of 10 lactated Ringer's and 6 of 7 HBOC-201 animals. These data indicate that HBOC-201 improved early survival and stabilized hemodynamic and metabolic parameters vs. lactated Ringer's in this swine model of liver injury with uncontrolled, lethal hemorrhage that simulates the prehospital care environment where allogenic blood is unavailable.

Animals↗
PubMed2000

Effects of training on maximum oxygen consumption of ponies.

OBJECTIVES: To establish maximum oxygen consumption VO2max) in ponies of different body weights, characterize the effects of training of short duration on VO2max, and compare these effects to those of similarly trained Thoroughbreds. ANIMALS: 5 small ponies, 4 mid-sized ponies, and 6 Thoroughbreds. PROCEDURE: All horses were trained for 4 weeks. Horses were trained every other day for 10 minutes on a 10% incline at a combination of speeds equated with 40, 60, 80, and 100% of VO2max. At the beginning and end of the training program, each horse performed a standard incremental exercise test in which VO2max was determined. Cardiac output (Q), stroke volume (SV), and arteriovenous oxygen content difference (C [a-v] O2) were measured in the 2 groups of ponies but not in the Thoroughbreds. RESULTS: Prior to training, mean VO2max for each group was 82.6 = 2.9, 97.4 +/- 13.2, and 130.6 +/- 10.4 ml/kg/min, respectively. Following training, mean VO2max increased to 92.3 +/- 6.0, 107.8 +/- 12.8, and 142.9 +/- 10.7 ml/kg/min. Improvement in VO2max was significant in all 3 groups. For the 2 groups of ponies, this improvement was mediated by an increase in Q; this variable was not measured in the Thoroughbreds. Body weight decreased significantly in the Thoroughbreds but not in the ponies. CONCLUSIONS AND CLINICAL RELEVANCE: Ponies have a lower VO2max than Thoroughbreds, and larger ponies have a greater VO2max than smaller ponies. Although mass-specific VO2max changed similarly in all groups, response to training may have differed between Thoroughbreds and ponies, because there were different effects on body weight.

Animals↗
PubMed1999

Repeated manual evacuation for treatment of rectal tears in four horses.

Horses with tears that involve all layers of the rectum except the mesocolon (grade IIIb) have a poor prognosis for survival because of the difficulty in treating these wounds and the propensity for them to progress to full perforations (grade IV). Most treatments for grade-IIIb rectal tears involve surgery of some kind, but not all grade-IIIb rectal tears require surgical intervention. We report on 4 horses with grade-IIIb rectal tears that were evaluated via palpation per rectum and endoscopy. Two of 4 horses were admitted with signs consistent with shock and endotoxemia, and evaluation of all peritoneal fluid samples was indicative of nonseptic peritonitis. Horses were treated via administration of antibiotics and anti-inflammatory drugs and repeated manual evacuation of the terminal portion of the small colon and rectum. Treatment centered on preventing further enlargement of the rectal tear by eliminating the storage function of the terminal portion of the small colon and rectum. None of our horses had worsening of the original injury, and horses were discharged within 2 weeks of admission with full resolution of the rectal tear. Outcomes in the horses of our report indicate that repeated manual evacuation can be successful for treatment of horses with grade-IIIb rectal tears.

Animals↗
PubMed1999

Spectral analysis of heart rate variability and pulmonary responses to topical applications of 2% aminophylline-based thigh cream.

OBJECTIVE: Noninvasive assessment of the immediate and delayed cardiopulmonary response to a 2% aminophylline-based topical thigh reducing cream. DESIGN: Prospective, double-blind, randomized, counterbalanced study with application of: no cream (NC), placebo cream (PC) or 2% aminophylline cream (AC). SUBJECTS: Nine healthy women (aged: 23+/-3 y; weight: 58+/-3 kg; height: 165+/-7 cm; body fat: 19+/-6%; estimated maximal aerobic fitness VO2max): 40+/-4 ml/kg/min). MEASUREMENTS: Medical history, skin patch test, skinfolds, YMCA submaximal cycle ergometry test, psychological evaluations (POMS and Speilberger STAI-1). Pulmonary function and spectral analysis on heart rate variability, measured immediately post-and 4 h post-treatment, on three separate days within a three-week period. RESULTS: Pulmonary function did not change. The averaged R-R interval (ms) was significantly lower for the immediate post AC treatment, but returned to baseline in 4 h. CONCLUSION: Application of a 2% aminophylline-based thigh cream does not affect pulmonary function, however, it may cause a temporary, transient reduction in the averaged R-R interval.

Administration, Cutaneous↗
PubMed1999

Efficacy of a 1-week regimen of ranitidine bismuth citrate in combination with metronidazole and clarithromycin for Helicobacter pylori eradication.

BACKGROUND: In order to improve the efficacy and simplicity of the FDA-approved regimen of ranitidine bismuth citrate (RBC) and clarithromycin dual therapy, we added an inexpensive antibiotic (metronidazole), changed the dosage scheme to twice daily dosing, and decreased the duration of therapy to 1 week. METHODS: This was an open label study in which subjects with previously untreated Helicobacter pylori infection documented by serology or endoscopy and confirmed by the 13C-urea breath test received a 1-week course of RBC 400 mg b.d., metronidazole 500 mg b.d. and clarithromycin 500 mg b.d. A repeat breath test was performed 4-6 weeks after completing therapy. RESULTS: Forty-seven out of 50 subjects completed the protocol. Intention-to-treat and per protocol cure rates were 86% and 91%, respectively. The regimen was well tolerated. Study drugs were stopped in two patients due to side-effects. The most common side-effect was self-limited diarrhoea. CONCLUSION: Twice daily RBC-based triple therapy with metronidazole and clarithromycin for 1 week is well tolerated and effective in eradicating H. pylori infection.

Anti-Bacterial Agents↗
PubMed1999

Differences in the ventilatory responses of horses and ponies to exercise of varying intensities.

Horses exercising at > or = approximately 90% VO2max develop arterial hypoxaemia with concurrent hypercapnoea, whereas ponies exercising at comparative levels become hypocapnoeic and maintain arterial oxygen tensions close to resting values. We sought to investigate the possibility that these differences relate to the ventilatory responses of these animals to exercise. Six Thoroughbred horses weighing mean +/- s.e. 501 +/- 27 kg and 5 ponies weighing mean +/- s.e. 164 +/- 18 kg exercised for 2 min on a 10% slope at speeds calculated to require 60% VO2max and for at least 1 min at speeds calculated to require 115% VO2max. Oxygen consumption (VO2), arterial oxygen (PaO2) and carbon dioxide (PaCO2) tensions, acid-base balance, tidal volume (VT), minute ventilation (VE), peak inspiratory (VImax) and expiratory (VEmax) flow, and maximal changes in transpulmonary pressures (delta PtPmax) were measured immediately before exercise and in the last 15 s of exercise at each intensity. The results confirmed that, unlike horses, ponies do not become hypoxaemic or hypercapnoeic during exercise. Despite having a higher delta PtPmax, higher VImax and VEmax and VE/kg0.75 at the same relative intensities, horses were less capable of mounting an appropriate ventilatory response to exercise. This was reflected by lower mass specific and metabolic weight-based ventilations at similar absolute workloads, and their higher PaCO2 and arterial HCO3-[, and lower ventilatory equivalent for oxygen (VE/VO2). This suggests that horses become hypoxaemic and hypercapnoeic at work loads > or = approximately 90% VO2max because their metabolic demand surpasses the capacity of their ventilatory system to meet this demand. Because ponies are less capable athletes, they can match their ventilatory response to their metabolic requirements.

Acid-Base Equilibrium↗
PubMed1998

Glucose plus insulin infusion improves cerebral outcome after asphyxial cardiac arrest.

Hyperglycemia before ischemia worsens cerebral outcome. The aim of this study was to determine the cerebral effects of giving glucose with or without insulin after asphyxial cardiac arrest. Rats underwent 8 min of asphyxial cardiac arrest. After arrest, Group 1 received NaCl; Group 2, insulin; Group 3, glucose; and Group 4, glucose plus insulin, all intravenously. Neurological deficit (ND) scores were 14+/-10%, 22+/-12%, 12+/-10% and 2+/-2% in Groups 1-4, respectively, 72 h after reperfusion. Overall histological damage (HD) scores were 4, 2, 3 and 1, respectively. Group 4 fared significantly better than group 1 on both scores. Glucose after asphyxial cardiac arrest in rats produces no increased brain damage while glucose plus insulin improves cerebral outcome.

Animals↗
PubMed1998

Electron spin resonance measure of brain antioxidant activity during ischemia/reperfusion.

An electron spin resonance technique was used to measure cerebral antioxidant activity during asphyxial cardiac arrest and reperfusion. There were significant decreases in ascorbate (48%), glutathione (44%), total thiols (42%), protein thiols (38%) and alpha-tocopherol (26%) in the hippocampus 10 min after reperfusion (p < 0.05 vs respective baselines) but not during asphyxial cardiac arrest. The levels of antioxidants returned to baseline values by 120 min after reperfusion. The results support the hypothesis that reperfusion from asphyxial cardiac arrest, but not arrest alone, produced a significant oxidative stress as reflected by a depletion of both water and lipid soluble antioxidants. Furthermore, antioxidant depletion was transient, with normal antioxidant levels observed 120 min, 24 h and 72 h after reperfusion.

Analysis of Variance↗
PubMed1996

Inhibition of GH in maternal separation may be mediated through altered serotonergic activity at 5-HT2A and 5-HT2C receptors.

The hyposecretion of growth hormone (GH) in maternal separation (MS) of rat pups is remarkably similar to the specific suppression of GH secretion to evocative tests in infants diagnosed with Reactive Attachment Disorder of Infancy (RADI). Growth hormone-releasing factor (GRF) and somatostatin (SS) provide opposing regulation of GH secretion, and both are modified by noradrenergic and serotonergic stimuli in neonatal and adult rats. In this study, GRF administration reversed MS-induced suppression of GH secretion in 10-day-old pups, but this action of GRF was prevented by pretreatment with cyproheptadine (Cypro), a serotonergic antagonist. The normalization of GH secretion after return to the dam was not altered by pretreatment with SS. Indirect 5-HT agonists, fluoxetine (FLX) and 5-HTP, both stimulated GH secretion in 10-day-old pups. All mixed serotonin- and 5-HT1A-receptor agonists suppressed GH secretion in 10-day-old pups. Antagonists Cypro and ketanserin (Ket) suppressed FLX-induced GH secretion. In contrast, only Cypro suppressed 5-HTP-induced GH secretion. Maternal separation inhibited GH secretion stimulated by 5-HTP, but not by FLX. The serotonergic pathway acting on 5-HT2A receptors may be obligatory for GRF-mediated stimulation and is sensitive to inhibition by Cypro. In addition, a Ket-sensitive serotonergic parallel pathway acting on 5-HT2C receptors may also stimulate GH secretion by acting on GRF or SS. However, only the obligate 5-HT2A pathway appears to be suppressed in MS. These data and observations by others indicate that specific suppression of GH secretion in MS may derive from a reduction in GRF release through noradrenergic neurons, possibly impinging upon serotonergic terminals in the hypothalamus. This study may also provide insight into mechanisms by which GH secretion is suppressed in humans with RADI.

Animals↗
PubMed1996

Cerebral resuscitation from cardiac arrest: treatment potentials.

In 1961, in Pittsburgh, PA, "cerebral" was added to the cardiopulmonary resuscitation system (CPR --> CPCR). Cerebral recovery is dependent on arrest and cardiopulmonary resuscitation times, and numerous factors related to basic, advanced, and prolonged life support. Postischemic-anoxic encephalopathy (the cerebral postresuscitation disease or syndrome) is complex and multifactorial. The prevention or mitigation of this syndrome requires that there be development and trials of special, multifaceted, combination treatments. The selection of therapies to mitigate the postresuscitation syndrome should continue to be based on mechanistic rationale. Therapy based on a single mechanism, however, is unlikely to be maximally effective. For logistic reasons, the limit for neurologic recovery after 5 mins of arrest must be extended to achieve functionally and histologically normal human brains after 10 to 20 mins of circulatory arrest. This goal has been approached, but not quite reached. Treatment effects on process variables give clues, but long-term outcome evaluation is needed for documentation of efficacy and to improve clinical results. Goals have crystallized for clinically relevant cardiac arrest-intensive care outcome models in large animals. These studies are expensive, but essential, because positive treatment effects cannot always be confirmed in the rat forebrain ischemia model. Except for a still-elusive breakthrough effect, randomized clinical trials of CPCR are limited in their ability to statistically document the effectiveness of treatments found to be beneficial in controlled outcome models in large animals. Clinical studies of feasibility, side effects, and acceptability are essential. Hypertensive reperfusion overcomes multifocal no-reflow and improves outcome. Physical combination treatments, such as mild resuscitative (early postarrest) hypothermia (34 degrees C) plus cerebral blood flow promotion (e.g., with hypertension, hemodilution, and normocapnia), each having multiple beneficial effects, achieved complete functional and near-complete histologic recovery of the dog brain after 11 mins of normothermic, ventricular fibrillation cardiac arrest. Calcium entry blockers appear promising as a treatment for postischemic-anoxic encephalopathy. However, the majority of single or multiple drug treatments explored so far have failed to improve neurologic outcome. Assembling and evaluating combination treatments in further animal studies and determining clinical feasibility inside and outside hospitals are challenges for the near future. Treatments without permanent beneficial effects may at least extend the therapeutic window. All of these investigations will require coordinated efforts by multiple research groups, pursuing systematic, multilevel research--from cell cultures to rats, to large animals, and to clinical trials. There are still many gaps in our knowledge about optimizing extracerebral life support for cerebral outcome.

Animals↗
PubMed1996

Resuscitative hypothermia.

Resuscitative (postinsult) hypothermia is less well studied than protective-preservative (pre- and intra-arrest) hypothermia. The latter is in wide clinical use, particularly for protecting the brain during cardiac surgery. Resuscitative hypothermia was explored in the 1950s and then lay dormant until the 1980s when it was revived. This change occurred through the discoveries of brain damage mitigating effects after cardiac arrest in dogs, and after forebrain ischemia in rats, of mild (34 degrees C) hypothermia (which is safe), and of benefits derived from moderate hypothermia (30 degrees C) after traumatic brain injury or focal brain ischemia in various species. The idea that protection-preservation or resuscitation by hypothermia is mainly explained by its ability to reduce cerebral oxygen demand has been replaced by an increasingly documented synergism of many beneficial mechanisms. Deleterious chemical cascades during and after these insults are suppressed even by mild hypothermia. Prolonged moderate hypothermia carries some risks, e.g., arrhythmias, infection and coagulopathies. These side effects need further study. In global brain ischemia, protective-preservative mild hypothermia provides lasting mitigation of brain damage. Resuscitative mild hypothermia, however, may be beneficial in terms of long-term outcome or may merely delay the inevitable loss of selectively vulnerable neurons. Even if the latter is true, mild hypothermia may extend the therapeutic window for other interventions. This extension of the therapeutic window requires further documentation. After normothermic cardiac arrest of 11 mins in dogs, mild resuscitative hypothermia from 15 mins to 12 hours after reperfusion plus cerebral blood flow promotion normalized functional recovery with the least histologic damage seen thus far. Optimal duration of, and rewarming methods from, resuscitative hypothermia need clarification. The earliest possible induction of mild hypothermia after cardiac arrest seems desirable. Head-neck surface cooling alone is too slow. Among many clinically feasible rapid cooling methods, carotid cold flush and peritoneal cooling look promising. After traumatic brain injury or focal brain ischemia, which seem to still benefit from even later cooling, surface cooling methods may be adequate. Resuscitative hypothermia after cardiac arrest, traumatic brain injury, or focal brain ischemia should be considered for clinical trials.

Animals↗
PubMed1995

Guidelines for clinical trials in systemic sclerosis (scleroderma). I. Disease-modifying interventions. The American College of Rheumatology Committee on Design and Outcomes in Clinical Trials in Systemic Sclerosis.

OBJECTIVE: To develop guidelines for therapeutic trials designed to improve the overall course of systemic sclerosis (SSc), that is, to reduce the development of significant organ damage or death. METHODS: A committee developed general guidelines for patient inclusion and exclusion criteria, randomization, blinding of patients and physicians, controls, duration of the trial, investigator training, responses, samples size, study dropouts, statistical analyses, data management, and safety monitoring. Delphi and nominal group techniques were used. RESULTS: Briefly, patients with diffuse cutaneous SSc of less than 24 months' duration should be included because they are at greatest risk for the development of severe organ damage and death. Patients should be excluded if they have other connective tissue diseases, SSc-like illnesses related to exposures or ingestions, severe existing internal organ damage, an unacceptable risk of side effects, or concurrent therapies that might independently influence the outcome. Randomized, double-blind, placebo-controlled trials are preferred. The treatment and followup period must be long enough to permit observation of any disease modification, which is likely to require 18-36 months, unless an extraordinarily effective therapy is identified. Responses selected should be quantitative, consistently and accurately reflect activity of SSc in major target organs (not solely the skin), be sensitive to change, and be standardized, with limited variability. An example of a set of responses is given. Surrogate responses are desirable, but none have been validated as correlating with organ damage. CONCLUSION: Guidelines have been established for trials of disease-modifying interventions in SSc. These guidelines will need to be altered as additional information becomes available. Any given protocol will be individualized based on the nature of the intervention and objectives of the study. Nonetheless, each study team should develop a protocol that meets the spirit of these guidelines.

Clinical Protocols↗