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Biomedical subjects

M Germine

Publications and source records attributed to M Germine.

14 recordsLinked to original sources

Plasma levels of gamma-aminobutyric acid and panic disorder.

Low levels of gamma-aminobutyric acid (GABA) in plasma have been associated with the presence of mood disorders in patients with major depressive disorder. We examined plasma GABA in patients with panic disorder, a disorder that is often comorbid with major depression, and in a group of control subjects. Patients with panic disorder had plasma GABA levels that did not differ significantly from levels in controls subjects. These data support the specificity of low plasma GABA as a marker for mood disorders.

Adult↗

Effects of tryptophan depletion on responses to yohimbine in healthy human subjects.

There is considerable evidence that both the norepinephrine (NE) and serotonin (5-HT) systems are involved in the regulation of human anxiety and fear responses. To assess the modulating effects of central 5-HT levels on NE function, 11 healthy human subjects were studied with placebo-controlled challenge tests involving tryptophan depletion followed by administration of the alpha-2-adrenergic antagonist yohimbine 0.4 mg/kg IV. Five of the 11 subjects reported a marked increase in feelings of nervousness (> or = 25 mm on a 100 mm analog scale) following the combination test, while 1/11 had this response to yohimbine alone. No subjects had an increase in nervousness during other control tests. The increase in nervousness after the tryptophan depletion-yohimbine test was statistically significant for the whole group, but there were no other unique changes in behavioral, physiologic or biochemical (MHPG, cortisol) variables with this test. These data are discussed in terms of possible functional interactions between the 5-HT and NE neurotransmitter systems.

Adrenergic alpha-Antagonists↗

Response to meta-chlorophenylpiperazine in panic disorder patients and healthy subjects: influence of reduction in intravenous dosage.

As a further test of the hypothesis of serotonin hypersensitivity in panic disorder (PD), the serotonin agonist meta-chlorophenylpiperazine (MCPP) was administered intravenously in a dose of 0.05 mg/kg to 27 PD patients and 22 normal control subjects. This is one-half the dose used in our previous study of PD patients, where the dose may have been too high to provide evidence of hypersensitivity to the agent. Responses of anxiety and nervousness were statistically indistinguishable by analysis of variance in the two groups, replicating our previous findings. Panic attack symptom score (PASS) ratings were significantly higher in the PD group, compared with a trend toward higher PASS ratings in the 0.1 mg/kg study. Cortisol, human growth hormone, and male prolactin responses showed no significant differences in the two groups by analysis of variance. Prolactin responses were significantly blunted in the female patients. The unexpected blunted prolactin response to MCPP in female PD patients may reflect a nonspecific blunting of prolactin response to stress. The PASS data provide some evidence of serotonergic hypersensitivity in PD.

Adult↗

Information and psychopathology.

Our current understanding of mental processes in health and disease is limited by the absence of a practical model describing the physiology of the mind as an informational system. The mind is described here as a physical system with four functional dimensions that can be interrelated mathematically on the basis of information theory. These variables describe the information processing activities of the mind, and include: a) a state function (g), which is the number of potential states that the system can occupy at a given time and relates to the complexity and activity of the brain; b) a power function (P), the number of state changes per unit time; c) time (t); and d) the relative entropy of the system (R), which describes the ordering of mental states in time. Using these variables, the evolution of states of mind can be described as a trajectory in a multidimensional phase space representing all possible mental states. Ego functions constrain the field of brain states within this space, thereby giving rise to the information content of consciousness and to the individual psyche. Functional mental disorders, as disorders of the psyche, are dysfunctions in the ordering processes that give rise to conscious information.

Brain↗

Dynamic SPECT imaging after injection of the benzodiazepine receptor ligand [123I]iomazenil in healthy human subjects.

Previous work suggests that iomazenil (formerly known as Ro 16-0154) is a useful ligand for static imaging of the benzodiazepine (BZ) receptor with single photon emission computed tomography (SPECT). The present study evaluated the feasibility of dynamic SPECT imaging of cerebral radioactivity following intravenous [123I]iomazenil injection in healthy human subjects, in preparation for future receptor quantitation studies. Maximal brain uptake was reached approximately 25-30 minutes after i.v. administration of the radioligand and represented approximately 12% of the injected dose. The regional distribution of radioactive densities was consistent with the known distribution of BZ receptors in human brain, with highest uptake localized over the occipital area. Washout of cortical radioactivity was regionally variable but relatively slow, with a half-life of approximately 4 hours after the time of peak radioactivity. In summary, [123I]iomazenil is a promising SPECT radioligand for the BZ receptor, with high brain uptake, relatively slow washout of radioactivity, and appropriate regional distribution.

Adult↗

Dynamic SPECT imaging of dopamine D2 receptors in human subjects with iodine-123-IBZM.

We studied the uptake, distribution, metabolism and washout of the dopamine D2 receptor ligand [123I]IBZM in healthy subjects (n = 12) with dynamic brain SPECT. The highest radioactivity level was detected in the striatum. Operationally-defined striatal "specific" uptake peaked at 69 min postinjection of radioligand and showed a gradual decline of 15% per hour thereafter. "Specific" uptake at maximal counts represented 53% of the total striatal radioactivity. Two subjects received haloperidol (20 micrograms/kg i.v.) 80 min postinjection of radioligand. Haloperidol caused a 2.6-fold increase in the rate of washout of specific striatal activity in comparison to that in the 10 control subjects and was consistent with drug-induced displacement of radioligand from the dopamine D2 receptor. Two classes of metabolites were detected in plasma and urine: a polar fraction, not extracted by ethyl acetate, and a nonpolar, extractable fraction consisting of parent compound and two compounds having shorter retention times on reversed-phase HPLC. Greater than half the plasma parent was metabolized within 10-15 min after administration. The volume of distribution, estimated from the peak arterial plasma concentration at 50-75 sec, was 7.7-10.2 l; the free (nonprotein bound) fraction of [123I]IBZM after in vitro incubation with blood or plasma was 4.4% +/- 0.4%. These results suggest that [123I]IBZM exhibits uptake in brain regions with high D2 receptor density and shows a relatively stable washout during which drugs affecting dopaminergic transmission may be administered.

Adult↗

Consciousness and synchronicity.

The brain is described as a system whose states are subject to quantum uncertainty. Conscious observation brings individual states into being from the multiple states possible at a given instant. This gives rise to information, which is the content of consciousness. Synchronicity is the principle by which a single state is generated by conscious observation throughout the brain at a given instant. It is the equivalent of the non-local interaction in quantum theory. Both psychodynamic and cognitive applications of the proposed model are described.

Cognition↗

Deconvoluted X-ray diffraction analysis of bone and mixtures of bone and particulate hydroxyapatite.

Recent evidence suggests that bone phosphate exists almost entirely as hydroxyapatite (HA). The relative deficiency of calcium and presence of substantial HPO2-4 in bone phosphate indicates modification of the ideal HA structure, however. An inability to resolve closely spaced lines in fine grained materials, coupled with the limited periodicity of the thin mineral crystals of bone have prevented definitive characterization of the structure of bone mineral using standard X-ray diffraction (XRD) techniques. We have applied computer deconvolution XRD techniques to aid in the resolution of component overlapped profiles from bone, synthetic hydroxyapatite (HA) and mixtures of bone and synthetic HA resulting from implantation studies. In the course of this resolution process separate profiles were resolved from the (002) profile of bone derived HA. The ratio of integrated intensities of these profiles to the intensity of the profile of synthetic HA appears to provide an approximate measure of the ratio of bone to synthetic HA in a given sample. The finding of shoulders on the (002) peak of bone provides the basis for resolution into separate profiles. The asymmetry of these shoulders in mature bone cannot be attributed to crystallinity, particle size, or computer artifact. The same finding has been previously reported in hydrolyzed, deproteinated bone. Further work will be needed to resolve the question of whether the structural heterogeneity implied by profile geometry is the result of multiple HA phases, surface layer structure involving hydrolysis and calcium absences, or some other factor.

Animals↗

Sepiolite asbestos from Franklin, New Jersey: a case study in medical geology.

Asbestiform sepiolite has been found in a zinc deposit at Franklin, New Jersey. The host rock is Precambrian Franklin marble. Pseudomorphous foliated texture and cross-cutting relationships indicate replacement of talc by sepiolite. Sepiolite is manganoan, while talc contains little manganese, suggesting differences in manganese substitution in these minerals and providing evidence against solid-state replacement. Sepiolite from Franklin is of moderate crystallinity and consists of soft, flexible mass-fiber. Comparison with other sepiolite samples suggests that increased crystallinity among sepiolites parallels increased fiber length, while disorder appears to be associated with flexibility. Length and aspect ratio (length/width) distributions support toxicological equation of asbestiform sepiolite with the regulated asbestos minerals. The data presented here suggest that talc can be unstable in a low-temperature hydrothermal environment, altering under certain conditions to form sepiolite. In a wider context, sepiolite may be expected to precipitate at the end-stages of hydrothermal mineralization in some talc deposits and in carbonate and calc-silicate rocks. Many occurrences of sepiolite in these rocks may have been overlooked due to similarities with other minerals. The fact that sepiolite has been previously unrecognized and misidentified at Franklin is a case in point. Since there is evidence suggesting that sepiolite is fibrogenic and carcinogenic, its potential occurrence in consumer talcs and crushed-stone products has environmental health implications. Similarities in composition and other analytical parameters may cause sepiolite to be mistaken for fibrous talc or chrysotile in environmental samples.

Geological Phenomena↗