Loving openness as a meta-world hypothesis: expanding our vision of mind and medicine

In 1942, Stephen C. Pepper published a seminal book, World Hypothesis, that sought to explain how people create hypotheses about the world. Pepper proposed that there were four basic world hypotheses: (1) formistic (the hypothesis that nature exists as categories); (2) mechanistic (the hypothesis that nature obeys cause-effect relationships); (3) contextual (the hypothesis that processes in nature are relative and context dependent); and (4) organismic (the hypothesis that processes in nature reflect interactive relationships in systems). Most classical and modern theories of science and medicine implicitly adopt one or more of these foundational hypotheses. In 1997, Schwartz and Russek proposed that there were four additional world hypotheses: (5) implicit process (the hypothesis that nature consists of invisible forces and information, such as energy and consciousness); (6) circular causality (the hypothesis that nature consists of circulating interactions that inherently change over time); (7) creative unfolding (the hypothesis that processes in nature reflect flexible designs or plans that have adaptive function); and (8) integrative diversity (the hypothesis that phenomena in nature reflect complex integrations of diverse processes). Theories in postmodern and integrative science implicitly adopt hypotheses 5 through 8. However, underlying the creation of the eight world hypotheses is an implicit meta-world hypothesis which we term loving openness (the hypothesis that phenomena in nature reflect levels of openness and caring). This paper briefly explains the origin and implications of the loving openness meta-world hypothesis for understanding mind-body healing in medicine, the reordering of values in integrative medicine (with a primary focus on caring with humility), and the fostering of a new vision for twenty-first century frontier science, spirituality, and medicine.     

The incidence of T2-weighted MR imaging signal abnormalities in the brain of cocaine-dependent patients is age-related and region-specific.

BACKGROUND AND PURPOSE: Cocaine and its metabolites can produce vasospasm, and cocaine-dependent patients are at increased risk for stroke. Based on previous case reports, we hypothesized that the incidence of hyperintense brain lesions observed on T2-weighted MR images would also be increased in asymptomatic cocaine-dependent individuals. METHODS: Sixty-two male "crack" (smoked) cocaine-dependent participants ranging in age from 25 to 66 years were compared with 116 normal male control participants ranging in age from 25 to 80 years. Those with histories of neurologic symptoms or illnesses were excluded. The severity of hyperintense lesions was rated on a 0- to 3-point scale, and ratings of 3 were used in the data analysis as an indicator of a probable pathologic process. Three regions were separately rated: the cerebral white matter, insular subcortex white matter, and subcortical gray matter (basal ganglia and thalamus region). RESULTS: Significantly increased risk of severe lesions was observed in the two white matter regions of the cocaine-dependent group (odds ratio of 16.7 and 20.3) but not in the subcortial gray matter region (odds ratio of 1.4). In the insula subcortex white matter, the risk of lesions increased with age in the cocaine-dependant sample, but remained essentially absent among normal controls through the age of 80 years. In the cerebral white matter, the relationship of age and risk of lesion among normal participants was similar in shape to that in cocaine-dependent participants, but equivalent risk was seen 20 years earlier among cocaine-dependent participants. CONCLUSIONS: Cocaine-dependent participants had a significantly increased age-related risk of white matter damage. The possible clinical implications of this damage are discussed.     

Ischemic preconditioning attenuates functional, metabolic, and morphologic injury from ischemic acute renal failure in the rat

Ischemic preconditioning has been shown to ameliorate injury due to subsequent ischemia in several organs. However, relatively little is known about preconditioning and the kidney. To address this, rats were randomized to control (C, N = 14), 2 min of ischemic preconditioning (P2 N = 10), 3 periods of 2 min of ischemia separated by 5 min periods of reflow (P2,3 N = 7), or three 5 min periods of ischemia separated by 5 min of reflow (P5,3 N = 6) prior to 45 min of bilateral renal ischemia followed by 24 hours of reperfusion. We observed a lower serum creatinine after 24 hours of reflow in P2, P2, 3 but not P5, 3 rats compared with C. Histology was examined in the C and P2, 3 groups and demonstrated less severe injury in the P2, 3 group. To gain insight into the mechanism by which preconditioning ameliorated ischemic injury, we performed near IR spectroscopy and 31P NMR spectroscopy. Based on near IR spectroscopy, the P2, 3 group had closer coupling of cytochrome aa3 redox state with that of hemoglobin during reflow. In the 31P NMR studies, the changes in ATP and pHi were similar during ischemia, but the P2, 3 group recovered ATP and pHi faster than C. These data suggest that ischemic preconditioning may ameliorate ischemic renal injury as assessed by functional, metabolic and morphological methods. The mechanism(s) by which this occurs requires additional study.     

Long-term outcome of living related liver transplantation for patients with intrapulmonary shunting and strategy for complications

BACKGROUND: In 320 living related liver transplantation performed between June 1990 and September 1997, there were 21 living related liver transplantation for patients with intrapulmonary shunting, manifested by digital clubbing, cyanosis, and dyspnea. We report the long-term outcome for more 6 months and our strategy to overcome complications in these recipients. PATIENTS: A total of 21 patients (age range 2-33 years, 19 children and 2 adults, 6 males and 15 females) were classified into three grades according to shunt ratio calculated by TcMAA pulmonary scintigraphy; 5 in mild group (shunt ratio: less than 20%), 6 in moderated group (20%-40%), and 10 in severe group (more than 40%). The original underlying liver disease was biliary atresia in all patients. RESULTS: Spearmen's correlation coefficient rank test revealed that shunt ratio correlated significantly with PaO2 in room air (P=0.0001), PaO2 in 100% oxygen (P=0.0004), hematocrit (P=0.0276), and period of dyspnea before transplantation (P=0.023). COMPLICATIONS: Wound infection occurred in 80, 66, and 80%, and bile leakage in 20, 0, 40% in mild, moderate, and severe group, respectively. Patients who had portal vein thrombosis, and intracranial complication were classified as severe group and the incidence was 20 and 20%, respectively. The patient actuarial one year survival was 80, 66.7, and 48%, in mild, moderate, and severe group, respectively, although there was no significant difference. All patients who survived improved hepatopulmonary syndrome and the length of period required for the resolution was significantly correlated to the preoperative shunt ratio (P=0.023). COMMENTS: Patients with severe shunting are susceptible to wound infection and bile leak. The trend of higher incidence of portal thrombosis and intracranial complications in the severe group was closely related high hematocrit. Secure surgical technique to reduce bile leak and delayed primary wound closure to reduce wound infection were found to be effective. Anticoagulant therapy by infusing heparin through the portal vein followed by coumadin could prevent fatal portal vein thrombosis without counter risk of fatal cerebral hemorrhage.     

Hypoxia-selective nitrobenzyloxycarbonyl derivatives of 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazines

Some 4- and 2-(nitrobenzyloxycarbonyl)-1, 2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazines (4, 6, and 7) were synthesized and evaluated for their ability to exert preferential toxicity to hypoxic EMT6 mammary carcinoma cells using a colony-forming assay. Of these, the 4,5-dimethoxy-2-nitro analogue 6 (50 microM, 1-h exposure) caused greater than 3 logs of kill of hypoxic cells, with relatively minor toxicity to corresponding aerobic cells. The ability of 4-nitro (4) and 4,5-dimethoxy-2-nitro (6) analogues to reach and kill hypoxic cells of solid tumors was also demonstrated using intradermally implanted EMT6 solid tumors in mice. In addition, a possible source of toxicity to normal tissue, i. e., the activation of the 4-nitrobenzyl derivative 4 by glutathione S-transferase-catalyzed thiolysis, was essentially eliminated by replacing one of the benzylic methylene protons by a methyl group. The 4-nitro (4) and 4,5-dimethoxy-2-nitro (6) analogues also appear to be reduced more easily under acidic conditions (pH 6.0) than under neutral conditions, as measured by differential pulse polarography. Since the pH in hypoxic regions is often lower than that in adjacent aerobic regions, this property should aid in the cytotoxic action of these agents against hypoxic cells of solid tumors.     

Pharmacokinetics of clinafloxacin enantiomers in humans

The pharmacokinetics of R-clinafloxacin and S-clinafloxacin enantiomers of the broad-spectrum fluoroquinolone antibiotic, clinafloxacin, were characterized in selected volunteer subjects and patients after the administration of oral and intravenous doses of racemic drug. The absorption of each enantiomer was rapid and nearly complete after a single, oral 400 mg racemic dose. The mean (+/- SD) bioavailability of R-clinafloxacin was 87.5% +/- 4.8% compared to 86.2% +/- 5.8% for S-clinafloxacin. The mean Cmax of each enantiomer was 1.19 micrograms/mL, with plasma concentrations of each enantiomer remaining above 0.1 microgram/mL for at least 12 hours. No notable differences in the disposition of R-clinafloxacin and S-clinafloxacin were observed. After a single 400 mg intravenous dose of racemic drug, mean (+/- SD) t1/2 was 5.6 +/- 0.3 hours and 5.7 +/- 0.4 hours, plasma Cl was 329 +/- 49 mL/min and 314 +/- 45 mL/min, and Vdss was 138 +/- 18 L and 134 +/- 16 L for R- and S-clinafloxacin, respectively. Two healthy volunteers each received a single 400 mg oral dose of racemic clinafloxacin (alone) and with oral administration of 1 gm probenecid separated by a 1-week washout period between treatments. With probenecid coadministration, the increase in AUC0-infinity was 75% and 83% for R-clinafloxacin and was 71% and 75% for S-clinafloxacin in each subject, respectively. Probenecid increased the total exposure (AUC) of both R-clinafloxacin and S-clinafloxacin, although it had no stereo-selective effects on the disposition of either enantiomer. The antimicrobial potency of the isomers was also evaluated. In vitro susceptibility testing showed that the two compounds were comparable in their inhibitory activities, as all MICs were within twofold for each organism tested. These results demonstrate that in addition to their similar antimicrobial potency, R- and S-clinafloxacin have nearly identical disposition characteristics and are eliminated by similar mechanisms that display no apparent enantioselectivity in man.     

Children's use of CROS hearing aids

Ten children with unilateral hearing loss, aged 7 to 17 years, who were fit with contralateral routing of signal (CROS) hearing aids were followed up for three years to assess the suitability of this type of hearing aid fitting on children. The determination of the success of the fitting was based on follow-up visits, chart review, and response to a questionnaire sent to the parents. The fitting was considered to be successful if the child accepted the aid and if parents and teachers observed substantial improvement in academic performance and/or social behavior. Seven children were considered to be successful users of their CROS aids; one was unavailable for follow-up; one did better with a BICROS aid; and one did not do well with amplification. Our experience suggests that children with unilateral hearing loss can benefit from CROS amplification.     

Medullary carcinoma of the thyroid gland.

Out of the discovery of concurrent multiple endocrine neoplasms has evolved the concept of multiple endocrine adenomatosis (MEA1 and MEA2). Medullary carcinoma of the thyroid gland is the most constant facet of MEA2 and is derived from C-cells of the neural crest. These cells, resembling parafollicular cells of lower animals, elaborate calcitonin which acts as a sensitive signal of the presence of the tumor. Ninety per cent of MCT occurs sporadically; in 10% the tumor presents as an atuosomal dominant trait. Other endocrinopathies, especially pheochromocytomas, are present in 70% of cases. The lesions are "cold" on iodine radioisotope scan. On microscopic examination, the appearance of amyloid is characteristic. Regional lymph node metastasis occurs early. The tumor deserves appropriate aggressive management. Surgical therapy should begin early and vigorously with the minimum procedure being total thyroidectomy. Frequent lymph node metastasis speaks for the need for regional neck dissection extended into the superior mediastinum. The search for, and the treatment of, the frequently associated endocrinopathies is essential. Pheochromocytoma must be suspected and eradicated before treatment of the thyroid tumor. A genetic workup should be included.