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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

Direct costs of glaucoma and severity of the disease: a multinational long term study of resource utilisation in Europe.

BACKGROUND: Resource utilisation and direct costs associated with glaucoma progression in Europe are unknown. As population progressively ages, the economic impact of the disease will increase. METHODS: From a total of 1655 consecutive cases, the records of 194 patients were selected and stratified by disease severity. Record selection was based on diagnoses of primary open angle glaucoma, glaucoma suspect, ocular hypertension, or normal tension glaucoma; 5 years minimum follow up were required. Glaucoma severity was assessed using a six stage glaucoma staging system based on static threshold visual field parameters. Resource utilisation data were abstracted from the charts and unit costs were applied to estimate direct costs to the payer. Resource utilisation and estimated direct cost of treatment, per person year, were calculated. RESULTS: A statistically significant increasing linear trend (p = 0.018) in direct cost as disease severity worsened was demonstrated. The direct cost of treatment increased by an estimated 86 for each incremental step ranging from 455 euro per person year for stage 0 to 969 euro per person year for stage 4 disease. Medication costs ranged from 42% to 56% of total direct cost for all stages of disease. CONCLUSIONS: These results demonstrate for the first time in Europe that resource utilisation and direct medical costs of glaucoma management increase with worsening disease severity. Based on these findings, managing glaucoma and effectively delaying disease progression would be expected to significantly reduce the economic burden of this disease. These data are relevant to general practitioners and healthcare administrators who have a direct influence on the distribution of resources.

Adult↗

Endotoxin-induced digital vasoconstriction in horses: associated changes in plasma concentrations of vasoconstrictor mediators.

REASONS FOR PERFORMING STUDY: Lipopolysaccharide (LPS) infusion reduces digital perfusion, but the mediators responsible remain undetermined. OBJECTIVES: To identify vasoconstrictor mediators released following LPS infusion and relate their appearance in plasma to digital blood flow alterations. METHODS: Blood flow in the lateral digital vessels of 6 Thoroughbred horses, following a 30 min infusion of LPS (E. coli 055:B5; 30 ng/kg), was measured using Doppler ultrasonography. Concomitant measurements of hoof wall and coronary band surface temperatures (HWST and CBST) were made. Serial blood samples were collected and plasma LPS, tumour necrosis factor alpha (TNFalpha), 5-HT, thromboxane B2 (TxB2) and endothelin measured. RESULTS: Plasma LPS concentrations reached a maximum of 13.2 pg/ml during the infusion, followed by an increase in plasma TNFalpha concentration. Digital arterial and venous blood flow decreased by 43 and 63%, respectively; HWST and CBST similarly decreased. Systemic blood pressure remained unaltered. Plasma concentrations of TxB2 and 5-HT increased, coinciding with the onset of digital hypoperfusion. Plasma endothelin concentrations remained unchanged. CONCLUSIONS: The temporal relationship between the onset of digital hypoperfusion and increases in plasma 5-HT and TxB2 concentrations is consistent with these platelet-derived mediators being associated with LPS-induced laminitis. POTENTIAL RELEVANCE: These experimental data support the use of anti-platelet therapy in the prevention of laminitis associated with endotoxaemic conditions.

Animals↗

Serological responses to Cryptosporidium antigens among users of surface- vs. ground-water sources.

Cryptosporidium oocysts are commonly detected in surface-derived drinking water. However, the public health significance of these findings is unclear. This study compared serological responses to two Cryptosporidium antigen groups for blood donors and college students using chlorinated and filtered river water vs. ground-water sources. The surface water received agricultural and domestic sewage discharges upstream. Participants from the surface-water city had a higher relative prevalence (RP) of a serological response to the 15/17-kDa antigen group (72.3 vs. 52.4%, RP = 1.36, P < 0.001) and to the 27-kDa antigen group (82.6 vs. 72.5%, RP = 1.14, P < 0.02). Multivariate logistic regression analysis found that the people with a shorter duration of residence or drinking bottled water also had a lower seropositivity for each marker. Use of private wells was associated with a higher prevalence of response to the 15/17-kDa markers. Seroconversion to the 15/17-kDa antigen group was more common in the residents of the city using surface water. These findings are consistent with an increased risk of Cryptosporidium infection for users of surface-derived drinking water compared with users of municipal ground-water-derived drinking water. Users of private well water may also have an increased risk of infection.

Adult↗

Characterisation of the response of equine digital arteries and veins to substance P.

Substance P (SP), a potent vasodilator, has been detected in equine digital sensory-motor nerves. The aim of the study was to characterise the functional responses of equine digital blood vessels to exogenous SP. Pre-constricted equine digital arteries (EDA) and veins (EDV) vasodilated in a biphasic, endothelium- and concentration-dependent manner to SP. A nitric oxide (NO) synthase inhibitor Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME; 300 microm) inhibited both phases of the relaxation response curve of EDAs to SP by >70%. In EDVs, the first relaxant phase to SP was largely L-NAME-resistant, whereas the second phase was inhibited by 60%. Both L-NAME and a cyclo-oxygenase inhibitor (ibuprofen; 10 microm) were required to inhibit EDV relaxation to SP by > or =80%. Experiments determining the receptor mediated responses to physiological concentrations of SP (1 nm) revealed that the relaxant responses of both EDA and EDV were inhibited by a neurokinin-1 (NK1) receptor antagonist (CP-96 345; 10 nm). In conclusion, SP is an endothelium-dependent vasodilator of both EDA and EDV. NO is the predominant pathway activated in EDA, whereas both prostacyclin and NO pathways are involved in EDVs. NK1 receptors appear to mediate responses to low concentrations of SP.

Animals↗

Regulation of caspases and XIAP in the brain after asphyxial cardiac arrest in rats.

The aim of this study was to determine whether hypoxic-ischemia from asphyxial cardiac arrest activates brain caspases-1 and -3, and the anti-apoptotic protein, XIAP. Asphyxial cardiac arrest in rats was used to induce hypoxic-ischemia. A pan-caspase inhibitor (zVAD) was given in the treatment group. At 72 h after reperfusion, caspase-3 and XIAP expression were present in multiple vulnerable brain regions, whereas caspase-1 was predominantly found in the CA1 hippocampus. zVAD significantly reduced expression of caspases and XIAP and the number of ischemic neurons in the CA1 hippocampus while neurological deficit scores were improved. We conclude that hypoxic-ischemia increases caspases-1 and-3, and XIAP expression. Treatment with zVAD significantly decreases caspase and XIAP expression in these brain regions and improves neurological outcome.

Amino Acid Chloromethyl Ketones↗

Selective aortic arch perfusion with hemoglobin-based oxygen carrier-201 for resuscitation from exsanguinating cardiac arrest in swine.

OBJECTIVE: The prospects for resuscitation after blunt traumatic cardiac arrest are dismal. Selective aortic arch perfusion (SAAP) with a hemoglobin-based oxygen carrier (HBOC-201) offers a potentially effective therapy. This study evaluated the acute cardiovascular and metabolic effects of SAAP with HBOC-201 in an exsanguination model of cardiac arrest. DESIGN: Randomized, controlled, laboratory investigation. SETTING: University research laboratory. SUBJECTS: Domestic swine, 25-39 kg. INTERVENTIONS: Partial resection of four liver lobes rapidly led to profound hemorrhagic shock and subsequent cardiac arrest at 10-13 mins. At 15 mins, swine were randomized to receive either SAAP with oxygenated lactated Ringer's (LR) solution (n = 6) or SAAP with oxygenated HBOC-201 (n = 6) at a rate of 10 mL x kg(-1) x min(-1) until return of spontaneous circulation with a mean aortic pressure of 60 mm Hg (8.0 kPa) was achieved. Epinephrine (0.005 mg/kg) was given via intra-aortic route every 30 secs as needed to promote return of spontaneous circulation beginning at 18 mins after onset of liver injury (3 mins after beginning SAAP). MEASUREMENTS AND MAIN RESULTS: Mean aortic pressure, cardiac output, total blood loss, and time of arrest were similar for both groups before SAAP therapy. In the SAAP-HBOC group, return of spontaneous circulation with a sustained mean aortic pressure of 60 mm Hg (8.0 kPa) was achieved in six of six swine at 1.9 +/- 0.3 mins of SAAP, and none of these swine required epinephrine. In the SAAP-LR group, no swine (from a total of six) achieved return of spontaneous circulation before intra-aortic epinephrine administration, and only two of six swine had brief return of spontaneous circulation with an mean aortic pressure of 60 mm Hg (8.0 kPa) after intra-aortic epinephrine that was sustained for <10 mins. One-hour survival was five of six in the SAAP-HBOC group and none of six in the SAAP-LR group (p <.05, Fisher's exact test). CONCLUSION: SAAP with oxygenated HBOC-201 rapidly restored viable cardiovascular function after exsanguinating cardiac arrest in this swine model of liver injury with profound hemorrhagic shock.

Animals↗

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↗

Neurotensin analog NT69L induces rapid and prolonged hypothermia after hypoxic ischemia.

OBJECTIVE: To determine whether the neurotensin analog NT69L, administered systemically, could induce mild brain hypothermia after asphyxial cardiac arrest (ACA) in rats. METHODS: The study design was experimental, blinded, randomized, and approved by the animal use committee. All rats had continuous monitoring of brain temperature and sustained 8 minutes of ACA, resuscitation, and either saline or NT69L intravenously after return of spontaneous circulation (ROSC). Rats surviving 14 days after ACA had a neurological deficit score (NDS) and a Morris Water Maze (MWM) test. RESULTS: Seven of eight rats in each group survived 14 days. Brain temperature was less than 35 degrees C 13.1 +/- 3 minutes (mean +/- standard deviation) after NT69L vs controls that remained 37.5 degrees C at the same ambient temperature (p < 0.05 ANOVA). The NT69L group remained below 35 degrees C for 300 +/- 100 minutes while the controls remained at 37.5 +/- 0.5 degrees C. The NDS in the NT69L rats was 3 +/- 3% vs controls 26 +/- 8% (p < 0.05, Kruskal-Wallis, 0% = normal, 100% = brain dead). The NT69L rats performed better on the MWM vs the controls (22 +/- 8 sec vs 45 +/- 26 sec, respectively, p < 0.05 ANOVA). CONCLUSIONS: NT69L induced rapid and prolonged mild brain hypothermia after ACA in this rat model and reduced neurological deficits.

Analysis of Variance↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗