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Biomedical subjects

S Harding

Publications and source records attributed to S Harding.

At least 91 records · Page 5Linked to original sources

Alcohol consumption following bidirectional shifts in body weight in rats.

Weight restriction has frequently been used to induce consumption of pharmacologically significant amounts of alcohol by rats. When previously weight-restricted rats are fed ad lib., however, their alcohol consumption is substantially reduced. This could occur because weight restriction per se causes increased alcohol consumption, or because the stimulus conditions (in this case, largely interoceptive) that were originally associated with drinking have changed, resulting in a stimulus generalization decrement. The present experiment was designed to discriminate between these two possibilities. Two groups of animals, one at free-feeding weight (FFW) and one at 80% FFW were initially trained to drink alcohol in a limited access paradigm. Each group was then divided into two, such that one half remained at its original weight and the other was gradually shifted to the reverse feeding condition in a double cross-over design. When alcohol consumption was again stable the experimental groups were returned to their original weights. If the weight restriction hypothesis were true, animals should drink more when weight-reduced and less when at FFW. According to the stimulus generalization decrement hypothesis, drinking should decrease with any shift from their initial weight. The direction of the results was such as to support the weight restriction hypothesis, but the magnitude of the changes was greater than would be expected on the basis of the respective control groups, and the effects were often transient. In these ways the results more closely resembled positive and negative contrast effects that have traditionally been described following shifts in amount of reinforcement. Possible mechanisms and the importance of an animal's history as a determinant of alcohol consumption are discussed.

Alcohol Drinking↗

The relationship of conjunctival and arterial blood gas oxygen measurements.

Conjunctival oxymetry (CjO2) measures peripheral tissue oxygen at the conjunctival level. CjO2 changes can indicate pulmonary or circulatory conditions leading to shock. Literature review does not define 'normal' CjO2/ABG PaO2 ratios. We designed a study to measure these ratios. Twenty-two healthy patients undergoing cardiac catheterization had simultaneous PcjO2 and PaO2 measurements completed. The range of conjunctival oxygen measurements was from 34 to 68 mmHg with a mean of 50.5 mmHg. The PaO2 readings ranged from 65 to 93 mmHg with a mean of 77.1 mmHg. The average PcjO2/PaO2 ratio was 0.656 with a range of 0.47-0.93. Thus the PcjO2 is on average 66% of the arterial blood gas PaO2. This ratio of 0.66 can serve as a base for further clinical studies in which PcjO2 is looked at in patients with pulmonary or circulatory illnesses or injuries.

Adult↗

Use of conjunctival oxygen monitoring in cardiac patients in the emergency unit.

Conjunctival oxygen monitoring (PcjO2) measures conjunctival tissue organ. It has proved useful in helping to evaluate hypovolemic multiple trauma patients, carotid artery surgery patients, as well as others. Little has been written about its use during medical resuscitations. This report reviews its accident and emergency department use in 13 cardiac arrest/life-threatening cardiac dysrhythmia patients. Nine patients expired and four patients survived. Accident and emergency department PcjO2 values in the group which expired averaged 6.3. Those patients who survived averaged 35.4. Subjects who maintained PcjO2 values below 20 did not survive. Furthermore, PcjO2 values taken within the first 8 min of accident and emergency department resuscitation appear to indicate outcome. Conjunctival oxygen monitoring may be useful in monitoring critically ill cardiac patients in the accident and emergency department.

Arrhythmias, Cardiac↗

Training increases [3H]fucose incorporation in chick brain only if followed by memory storage.

Incorporation of [3H]fucose into glycoproteins is increased in the forebrain base and anterior forebrain roof of day-old chicks following passive avoidance training. In chicks trained but rendered apparently amnestic by immediate transcranial electroshock, the increased incorporation by comparison with untrained-shocked birds was abolished. If the electroshock was delayed by 10 min, the chicks showed recall for the task and fucose incorporation was increased by comparison with untrained but shocked or trained and immediate-shocked birds. We conclude that the increased incorporation of [3H]fucose is not a result of any concomitant of training but is directly associated with engram formation.

Amnesia↗

Effects of positive end expiratory pressure and counterpressurization on circulating prostaglandins in the dog.

The effects of the application of positive end expiratory pressure (PEEP) ventilation, with and without body counterpressure (CP), on circulating prostaglandin-like substances (PGL) were studied in chloralose anesthetized dogs. The normal respiratory movements were paralysed with succinylcholine chloride. Arterial levels of PGL were continuously bioassayed using Vane's blood superfusion method. PEEPs of 10 and 20 mm Hg elicited PEEP-related increases in functional residual capacity and circulating PGL levels and decreases in blood pressure, left ventricular dP/dt, and heart rate. The PGL appeared to be PGE or prostacyclin in character. When PEEP and CP were simultaneously applied, the increments or decrements of indices described above were reduced. It is concluded that increases in the levels of circulating PGL are attributable, at least in part, to hyperexpansion of the lungs during PEEP and that some of the cardiovascular deterioration observed during and after PEEP may be the result of the vasodilating and cardiodepressing effects of PGL.

Animals↗

Major differences in the concanavalin A binding glycoproteins of postsynaptic densities from rat forebrain and cerebellum.

A highly purified fraction of postsynaptic densities (PSDs) was isolated from rat forebrain and cerebellum. The glycoproteins in the PSDs from the two brain regions were compared by probing nitrocellulose blots with concanavalin A. This approach revealed the presence of 8, previously undetected PSD glycoproteins and a 230K M, glycoprotein unique to forebrain PSDs and 260K Mr glycoprotein unique to cerebellar PSDs. There were also variations in the relative abundances of glycoproteins common to both brain regions. These observations may indicate that individual PSDs differ in their complement of major glycoproteins.

Animals↗

Post-traumatic fungal endophthalmitis caused by Exophiala jeanselmei.

Fungal endophthalmitis caused by dematiacious fungi is an uncommon occurrence. We report a case of fungal endophthalmitis caused by Exophiala jeanselmei following penetrating injury. This is a previously unreported etiologic agent in endophthalmitis. The infection was treated with intravitreal and intravenous amphotericin B in combination with oral 5-fluorocytosine. Although the organism was eradicated, vision was lost due to total retinal detachment.

Adult↗

Aspergillosis presenting as a corticosteroid-responsive optic neuropathy.

A case of orbital aspergillosis presenting as a steroid response of optic neuropathy is presented. The invasive and aggressive nature of this infection in the presence of systemic corticosteroids is documented by serial CT scans and necropsy examination. The authors urge inclusion of aspergilloma in the differential diagnosis of a steroid responsive optic neuropathy.

Adrenal Cortex Hormones↗

Increased incorporation of [3H]lysine into synaptic membranes of the visual cortex following first exposure of dark-reared rats to light is confined to particular polypeptides.

The incorporation of [3H]lysine into separated polypeptides of synaptic-membrane fractions prepared from the visual cortices of dark-reared rats and littermates exposed to light for 1 h was examined. Increased incorporation of [3H]lysine was found in synaptic membranes from light-exposed compared to dark-reared rats in polypeptides of four molecular weights: 100,000, 71,000, 44,000, and 38,000. The 44,000-molecular-weight peak has been suggested to be actin on the basis of its comigration with pure brain actin. These results indicate that increased incorporation of [3H]lysine into synaptic membranes of the visual cortex, following first exposure of dark-reared rats to light, is confined to particular polypeptides.

Animals↗

Increased alcohol consumption in weight-reduced rats is modulated by the renin-angiotensin system.

Weight reduction and food restriction increase the self-administration of alcohol and other drugs of abuse, but the underlying physiological mechanisms have not been identified. Because weight reduction alters angiotensin (ANG) II activity, and ANG II is known to modulate alcohol intake, ANG II may play a role in the enhanced alcohol consumption of food-deprived weight-reduced rats and in the drop in alcohol intake when these rats are refed. Two groups of rats were reduced to and maintained at 80% of their free feeding weights and offered daily 40 min access to a 6% (w/v) alcohol solution and water. Water was available ad lib. After alcohol intake stabilized, one group was given daily injections of the angiotensin converting enzyme inhibitor captopril (5.0 mg/kg) for 6 days while the other group received the saline vehicle. Following this, each group continued to receive either captopril or vehicle injections but was returned to ad lib feeding. Captopril did not alter alcohol intake when the rats were food-deprived and weight-reduced, but did significantly attenuate the decline in alcohol consumption compared to the vehicle group when both groups were refed and regaining weight. These findings suggest that the increase in alcohol intake with food restriction and its decline following refeeding are, in part, related to changes in ANG II activity.

Alcohol Drinking↗

The reduction in alcohol intake produced by enalapril is not attenuated by centrally administered angiotensin inhibitors.

Angiotensin-converting enzyme (ACE) inhibitors, which prevent the conversion of angiotensin I to angiotensin II, reduce alcohol intake when injected peripherally. The mechanism by which ACE inhibitors produce this effect on alcohol intake is unknown. A rise in the biosynthesis of angiotensin II in the periphery is known to reduce alcohol intake. In this experiment, we examine the possibility that the reduction in alcohol intake produced by an ACE inhibitor, enalapril, is mediated by a rise in angiotensin II in the brain. Enalapril, 20 mg/kg, injected intraperitoneally, produced a 40% reduction in alcohol intake. This reduction was not attenuated by the concurrent administration into the lateral ventricle of either the ACE inhibitors captopril or ceranapril (1, 10, or 25 micrograms), or the angiotensin II receptor antagonist Sar1-Thr8-Angiotensin II (5 micrograms). These findings suggest that the ACE inhibitors do not reduce alcohol intake by raising angiotensin II in the brain.

Alcohol Drinking↗

Glucose and the insulin-releasing drug tolbutamide attenuate the effects of morphine and angiotensin on alcohol consumption.

Animals studies have shown that insulin injections reduce alcohol intake, implicating glucoregulatory processes in alcohol consumption. Angiotensin (ANG) II reduces alcohol intake and promotes glycogen breakdown in the liver but no studies have assessed the role of glucoregulatory processes in ANG II's effect. Similarly, glucose injections attenuate the analgesic and cognitive effects of opiates, yet no studies have assessed the effect of glucose on the well-documented ability of opiates to enhance alcohol consumption. The present experiments further examine the role of glucoregulatory processes in alcohol intake by assessing the effect of glucose injections on morphine-enhanced alcohol consumption and by evaluating the effect of the insulin-releasing drug, tolbutamide, on ANG II-reduced alcohol consumption. Adult male Wistar rats acquired alcohol drinking using the limited access procedure that offers daily 40-min access to both 6% w/v alcohol and water and ensures reliable alcohol drinking in bouts large enough to produce pharmacologically relevant intakes. Experiment 1: after intake stabilized, four groups of rats were first pretreated with vehicle injections and in the next phase, three of the four groups received either 50, 100, or 200 mg/kg glucose intraperitoneally (i.p.) prior to access to alcohol. Neither the vehicle injections nor any of the glucose doses had an effect on alcohol intake. In the final phase all groups continued to receive their respective glucose doses or vehicle but were now also treated with 5 mg/kg morphine sulphate i.p. prior to alcohol access. Morphine stimulated alcohol intake to a similar degree in all groups except the 200 mg/kg group, which showed a significant attenuation in morphine-enhanced alcohol intake. Experiment 2: after intake stabilized, different groups of rats were pretreated with vehicle injections and in the next phase received either 5, 25, 50, or 100 mg/kg tolbutamide or vehicle subcutaneously (s.c.) prior to alcohol access. The vehicle injections did not alter alcohol intake, and only the 100 mg/kg dose of tolbutamide produced a reduction in alcohol intake. In the final phase the groups continued to receive their respective doses of tolbutamide or vehicle but were also treated with 400 micrograms/kg ANG II s.c. immediately prior to alcohol access. ANG II reduced alcohol intake a similar extent in the groups pretreated with 5-50 mg/kg tolbutamide. However, the 100 mg/kg dose of tolbutamide significantly attenuated ANG II's ability to reduce alcohol intake. These results demonstrate that manipulations that engage glucoregulatory processes can influence the mechanism(s) by which morphine and angiotensin respectively increase and decrease alcohol drinking.

Alcohol Drinking↗

Cancer incidence among first generation Scottish, Irish, West Indian and South Asian migrants living in England and Wales.

OBJECTIVES: To examine the incidence of cancers among persons born in Scotland, Northern Ireland, the Irish Republic, Caribbean Commonwealth and Indian subcontinent and living in England and Wales. METHODS: Longitudinal Study of 1% of population of England and Wales followed from 1971 to 1989. Standardised incidence ratios (SIRs) were derived for commonly occurring cancers and all cancers using the age-sex-specific rates for all females and all males in the Longitudinal Study. RESULTS: The incidence of all malignant neoplasms among West Indians (females SIR = 67, male SIR = 70) and Indians (female SIR = 32, male SIR = 52) was low. Among South Asians, this pattern was consistent for Hindus, Sikhs and Moslems. Scottish females showed raised incidence of lung cancer (SIR = 149) and those from the Irish Republic of oral cavity and pharynx (SIR = 321), oesophageal (SIR = 219) and liver (SIR = 373) cancers. Among Northern Irish females, incidence of lung cancer (SIR = 193) was raised. West Indian and South Asian females showed low incidence of breast cancer (SIR = 55 and 45, respectively). High incidence of laryngeal (SIR = 229) and renal (SIR = 203) cancers was observed for Scottish males and of oral cancer (SIR = 259) for males from the Irish Republic. At ages 15-64, raised incidence of prostate cancer (SIR = 129) and of leukaemia (SIR = 252) was also observed for men from the Irish Republic. Northern Irish males showed raised incidence of stomach cancer (SIR = 200). CONCLUSION: This study describes patterns of cancer incidence among migrant groups, most of which reflect environmental influences. This has challenging implications for sensitive targeting of primary interventions. It is important not to be complacent about lower risks of main cancers among West Indians and South Asians. In all Longitudinal Study members, breast cancer was the most common malignancy among females and lung cancer among males. This was also true for all migrant groups with the exception of Northern Irish women for whom lung cancer was the most common.

Adolescent↗