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Biomedical subjects

R Dolan

Publications and source records attributed to R Dolan.

At least 19 recordsLinked to original sources

Measuring the neuromodulatory effects of drugs in man with positron emission tomography.

Cognitive activation in conjunction with pharmacological challenge was used to demonstrate neuromodulation in man. Using positron emission tomography (PET), measurements of regional cerebral blood flow were made during the performance of memory tasks, before and after the administration of apomorphine (dopamine agonist), buspirone (5-HT1A partial agonist) or placebo. Drug effects on memory-induced increases in regional cerebral blood flow were assessed, on a voxel-by-voxel basis, using statistical parametric mapping. Increases of regional cerebral blood flow in response to the memory challenge were attenuated by apomorphine in the dorsolateral prefrontal cortex and augmented in the retrosplenial region of the posterior cingulate. Conversely, buspirone attenuated blood flow increases in the retrosplenial region. These interactions between drugs and a cognitive challenge can best be interpreted as neuromodulatory effects.

Adult

Accessibility of crystallins to HCI gas.

Different crystallins (alpha, beta H, beta L and LMW) were isolated from bovine lenses. Lyophilized samples of single components (homoaggregates) and those of mixtures (heteroaggregates) were exposed to HCI vapor in a high vacuum vapor sorption apparatus. Lyophilized 5-microns sections of bovine lens were similarly exposed to HCI vapors. Sorption and desorption isotherms were obtained at two temperatures on all samples. Fourier transform infrared (FT IR) spectroscopy was conducted on solid samples of crystallin with and without irreversibly sorbed HCI gas. From the IR spectra the nature of interaction between HCI and protein were ascertained. From the sorption parameters, mainly from the irreversibly sorbed HCI, the accessibilities of homo and hetero aggregates were calculated. The accessibilities provided information on the preferential interactions among crystallins. One of the main conclusions derived from this and also from previous ammonia sorption studies is that the supramolecular organization in the lens fibers is not governed solely by the thermodynamically preferential interactions of crystallins, but also by other possibly cytoskeletal organizations of crystallins.

Animals

Citalopram: labelling with carbon-11 and evaluation in rat as a potential radioligand for in vivo PET studies of 5-HT re-uptake sites.

In vivo autoradiography of [N-methyl-3H]citalopram in rat brain shows a differential regional localization which correlates with the localization of 5-HT re-uptake binding sites defined in vitro. A comparison of the biodistribution of [N-methyl-3H]citalopram over 2 h after i.v. injection in (1) control rats (2) rats pre-dosed with either citalopram or paroxetine and (3) rats chemically-lesioned with p-chloroamphetamine provides an estimate of specific binding relative to total binding in vivo. The ratio of binding in certain regions (e.g. cingulate) to binding in a reference tissue (e.g. cerebellum) at 30-120 min post injection is c. 1.4. In view of these results a method was developed for labelling citalopram with carbon-11 (t1/2 = 20.3 min, beta + = 99.8%) to provide a potential radioligand for studies using positron emission tomography. Thus, reaction of nca [11C]iodomethane, prepared from cyclotron-produced [11C]carbon dioxide, with norcitalopram in ethanol containing 2,2,6,6-tetramethyl-piperidine for 5 min at 95 degrees C gives crude [N-methyl-11C]citalopram in 60% radiochemical yield, decay-corrected. HPLC on silica gel provides radiochemically and chemically pure [N-methyl-11C]citalopram, as assessed by TLC, HPLC and MS. This product (isolated radiochemical yield, 49%) is easily formulated for i.v. injection. Up to 2 GBq of formulated product with a specific activity of c. 15 GBq/mumol have been prepared within 40 min from the end of radionuclide production. The described radiosynthesis has also been applied to give the single biologically active (+)-enantiomer of [N-methyl-11C]citalopram rather than the racemate. This product gives enhanced specific signal in the rat following i.v. injection, the ratio of uptake in regions of interest relative to cerebellum approaching 2 at 90 min.

Animals

Positron emission tomography as a research tool in the investigation of psychiatric and psychological disorders.

The principles of positron emission tomography (PET) are described, and illustrations of how these can be applied to clinical psychiatric questions relating to schizophrenia and depression are delineated. The metabolic changes in the frontal lobes which have been described in both depression and schizophrenia and depression are reviewed and discussed. More recent PET techniques allow several serial measurements of changes in regional blood flow in response to either a pharmacological challenge or a specific psychological task. This method provides a promising new approach to the study of the dopaminergic system in schizophrenia. New tracer methods of quantitating changes in in vivo concentrations of opioid receptors allow direct pharmacological access to the endogenous opioid system in the brain. Observations of regional cortical differences in opioid receptor concentration in relation to the medial and lateral pain systems are described. In addition, changes in receptor occupancy during sleep using [11C]diprenorphine and changes in the mu-specific tracer [11C]carfentanil in temporal lobe epilepsy are discussed.

Brain

Predictors of post-traumatic stress disorder following physical trauma: an examination of the stressor criterion.

A prospective study documenting psychopathology was undertaken in 48 subjects exposed to a range of physical trauma, but whose injuries were of similar severity. No support was found for the DSM-III-R view correlating the severity of the stressor with the development of post-traumatic stress disorder (PTSD). Distress post injury (high scores on the impact of event scale), indicative of difficulty with cognitive assimilation of the traumatic event, was found to be highly predictive of psychiatric morbidity and PTSD at 6 months.

Accidents, Traffic

Attributions and self-esteem in depression and chronic fatigue syndromes.

There is considerable overlap in symptomatology between chronic fatigue syndrome (CFS) and affective disorder. We report a comparison of depressive phenomenology and attributional style between a group of CFS subjects seen in a specialized medical setting, which included a high proportion with depression diagnosed by Research Diagnostic Criteria (RDC), and depressed controls seen in a specialized psychiatric setting. Significant symptomatic differences between the depressed CFS group and depressed controls were observed for features such as self-esteem and guilt as well as attribution of illness. All the CFS groups tended to attribute their symptoms to external causes whereas the depressed controls experienced inward attribution. This may have resulted from differences in the severity of mood disorder between the samples, but it is also suggested that an outward style of attribution protects the depressed CFS patients from cognitive changes associated with low mood but at the expense of greater vulnerability towards somatic symptoms such as fatigue.

Adult

Urinary Charcot-Leyden crystals in the hypereosinophilic syndrome with acute renal failure.

A 48-year-old man with idiopathic hypereosinophilic syndrome (IHS) developed blast crisis along with a fulminant autoimmune hemolytic anemia. Hemoglobinuria and anuric acute renal failure (ARF) ensued. Urinalysis revealed countless Charcot-Leyden crysals (CLC). This is the only known report of Charcot-Leyden crystalluria. The CLC protein (lysophospholipase) should normally undergo glomerular filtration and catabolism by the tubules during reabsorption. Its abundant presence in the urine of our patient may reflect impairment of tubular reabsorption, saturation of the tubular reabsorptive process by excessive CLC load through residual functioning glomeruli, or a combination thereof. The extreme degree of hypereosinophilia suggests a massive load of CLC protein and acute tubular necrosis implies impaired tubular function, so both mechanisms should have been operative. At the autopsy, no eosinophilic infiltrates were present in the kidneys, which points against a local spillage of CLC protein into the tubules.

Acute Kidney Injury

Camel production in Kenya and its constraints. I. Productivity.

Initial results from an ongoing study of the productivity in three herds of camels are presented. The effects of different management systems, traditional nomadic vs. commercial ranching, on growth, fertility and early mortality are described as well as the differences in the genetic potential of two types of indigenous camels.

Age Factors

Camel production in Kenya and its constraints. II. Tick infestation.

The tick loads and tick species infesting an experimental herd, a Rendille pastoralists' herd and two ranch herds of camels, in four different areas of Kenya are described. The tick species most commonly observed were Hyalomma rufipes, Hyalomma dromedarii and Rhipicephalus pulchellus.

Animals

A simple classification of different types of trypanosomiasis occurring in four camel herds in selected areas of Kenya.

Camels from herds in four different areas of Kenya were sampled at regular intervals over periods of 9-15 months and examined for the presence of trypanosomiasis. Five hundred and eight camels divided into three age categories were studied. Trypanosomiasis caused by T. evansi, T. brucei and T. congolense was shown to be present in varying degrees in all the herds. Camels were divided into 5 types according to mortality, the presence or absence of circulating trypanosomes and antibody, and the presence or absence of emaciation and anaemia. Herd profiles were constructed according to the percentage of the different types over the whole of their respective study periods. Results indicated that camels in some herds show a calf-hood resistance to trypanosomiasis in endemic areas and that the disease may be present in a relatively stable situation. Some of the implications of these results are discussed.

Animals

The effect of conditioning the medium in DRosophila, in relation to frequency-dependent selection.

In the context of frequency-dependent selection, the effect of conditioning the medium, by the previous culture of larvae of a given strain, on the survival of subsequent larvae of the same or different strains was measured. Six strains were sued, some inbred and some lines selected for low or high sternopleural bristles. The survival of larvae was not significantly less when the food had been conditioned by the same strain rather than by another strain, nor did conditioning by one strain have any special effect on the survival of another. The survival of lines on medium conditioned by the same strain was not less than on fresh medium, and in some cases was significantly greater.

Alcohol Oxidoreductases