Biomedical subjects
Publications and source records attributed to J E Cox.
The scintigraphic findings in a rare case of bilateral renal malakoplakia are presented. Markedly increased Ga-67 activity was present in both kidneys in sites corresponding to focal cortical defects on Tc-99m gluceptate (glucoheptonate) imaging. Interestingly, there was no abnormal renal activity with In-111 leukocyte scanning.
We compared suppression of intake of 30% sucrose produced by continuous aortal (near celiac) and intravenous infusions of cholecystokinin octapeptide (CCK-8). Adult, male Sprague-Dawley rats received 21-min infusions of saline or 100-1,600 ng CCK-8. Sucrose was available for 20 min, beginning 1 min after onset of infusions. Significant reductions in intake were produced by near-celiac infusions of 400, 800, and 1,600 ng CCK-8, but only the two highest doses affected intake when infused intravenously. In a second experiment, which replicated previous observations, near-celiac bolus infusions of 70 ng CCK-8 significantly reduced sucrose intake but intravenous infusions did not. Behavioral observations indicated that although bolus infusions produced immediate disruption of feeding, suggesting an aversive effect, effects of continuous CCK-8 infusions on temporal intake patterns were consistent with enhancement of satiety. These data provide further evidence that CCK-8 acts on a site within the upper gastrointestinal tract to produce satiety.
We report transient focal abnormalities on MR in a patient having frequent electrographic seizures that were not obvious clinically. Marked mass effect (confirmed with volumetric studies) and abnormal T2 signal intensity in the right hippocampal region correlated with electroencephalographic ictal activity and with increased positron-emitting radiotracer uptake in the medial temporal lobe. The follow-up MR 2 months later, after electroencephalography findings normalized, revealed no hippocampal abnormalities.
In two experiments I examined whether intraduodenal sucrose and glucose would enhance inhibition of sham feeding by cholecystokinin-8 (CCK-8). In the first experiment, adult male Sprague-Dawley rats received infusions of 0.88 M (30%, wt/vol) sucrose or normal saline at 0.51 ml/min for the first 7.67 min of 30-min sham-feeding tests. Tests began 10 min after intraperitoneal injections of saline or 0.5, 1, or 2 micrograms/kg CCK-8. When sucrose was infused, all doses of CCK-8 reduced sham feeding of 0.88 M sucrose by 60% or more, but with saline infusions, only the highest dose was effective. In the second experiment, rats received 30-min infusions of 0.3 M (5.4%) or 0.6 M (10.8%) glucose or equimolar saline at 0.388 ml/min. Although 1 microgram/kg CCK-8 was ineffective in the absence of infusions, it significantly reduced intake in combination with both concentrations of glucose and hypertonic (0.6 M) saline. Behavioral observations indicated that reductions in intake were attributable primarily to decreased meal length and slower intake. These results suggest that an intestinal signal may contribute to the previously reported ability of preloads to potentiate CCK satiety.
A method was developed and applied for the assessment of tobacco-specific N-nitrosamines (TSNA) in indoor air polluted with tobacco smoke. Air samples were collected on Cambridge filters treated with 0.01 M potassium bisulfate, extracted with dichloromethane and enriched by column chromatography. The fraction containing the TSNA was concentrated and placed on a thermal desorption cartridge packed with Tenax GR. The sample was thermally desorbed and analyzed by capillary GC using a thermal energy analyzer. When the method was applied in a test laboratory in which one, two and four cigarettes were smoked during 30 min, linearity was observed. Field studies included sampling in bars, restaurants and trains. The concentration of N'-nitrosonornicotine (NNN) ranged from not detected to 23 pg/l, that of N'-nitrosoanatabine ranged from not detected to 9 pg/l, while 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was detected in concentrations ranging from 1 to 29 pg/l. This means an exposure to NNN and NNK of 0.1-0.3 cigarette equivalents. Thus, non-smokers can be exposed to highly carcinogenic TSNA.
Use of supercritical carbon dioxide extraction in the analysis of smokeless tobacco for tobacco-specific N-nitrosamines revealed the presence of higher levels of 4-(methylnitros-amino)-1-(3-pyridyl)-1-butanone (NNK) than had been determined with conventional methods. Whether human saliva may be similarly capable of releasing apparently bound NNK during chewing or snuff dipping was tested by incubating smokeless tobacco with enzymatically active saliva and with heat-treated saliva respectively. Enzymatically active human saliva was found to liberate up to twice the amount of the highly carcinogenic NNK than did heat-treated saliva. This is of major consequence for the cancer risk assessment of snuff dippers and tobacco chewers.
This study tested the role of melatonin in the regulation of seasonal physiological change in the pony stallion. Four 3-year-old, Welsh Mountain pony stallions were housed initially under the prevailing short-day photoperiod in December (8 of light [L]:16 h of darkness [D]) before being transferred to long days (16L:8D) on 13 January for the remaining 22 weeks of the study. On Day 76 (11 weeks later) the stallions began an 11-week period of daily melatonin treatment (20 mg orally, 8 h after lights on). Marked changes in mean plasma testosterone, beta-endorphin and cortisol concentrations occurred in response to long days and to subsequent melatonin treatment. Photostimulation produced a sharp rise in overall mean daily testosterone to a peak of 6.74 nmol/litre by Day 30. Values then fell to a nadir (3.17 nmol/litre) by Day 85, suggesting a role for melatonin in the termination of breeding activity in the horse. Cortisol and beta-endorphin values remained low throughout the first 11 weeks, but by Day 105 (Day 30 of melatonin treatment) concentrations had risen sharply, attaining a peak on Day 125 (510 pg beta-endorphin/ml, 50 ng cortisol/ml). Concentrations of both hormones had fallen by Day 77 of melatonin treatment (Day 152), perhaps as a result of refractoriness. Parallelism between beta-endorphin and cortisol suggests a pituitary origin for peripheral beta-endorphin. Diurnal variation in cortisol was observed under long days but no change in beta-endorphin was detected. Long days and melatonin treatment stimulated shedding of the winter and summer coats respectively, whereas growth rate was increased (2.03 kg/week) during the period of melatonin treatment relative to that of long days only (0.37 kg/week). The study provides evidence that the diurnal pattern of melatonin secretion mediates the reproductive and non-sexual responses to photoperiodic change in pony stallions.
The effect of long-term treatment of stallions with a powerful gonadotrophin-releasing hormone (GnRH) analogue was investigated. In the first part of the study, 9 sexually mature pony stallions were allocated to 1 of 3 groups, each of which was treated with 240 micrograms or 60 micrograms Buserelin per day administered by subcutaneously sited osmotic pumps or 30-50 micrograms Buserelin per day via solid, slow-release implants injected subcutaneously. Peripheral blood plasma and serum samples were collected frequently and assayed for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and testosterone. No significant differences were seen between either high of low dose rates: in all treatment groups, serum and plasma concentrations of FSH, LH and testosterone rose sharply following insertion of pumps ofr implant. The levels remained elevated for 3-10 days in most animals, after which they returned to pre-treatment of lower values. In a second experiment, single implants, formulated to deliver 120 micrograms Buserelin per day for 28 days, were injected subcutaneously in to 2 pony stallions on 4 occasions at 5-day intervals. Gonadotrophin and testosterone secretions were temporarily stimulated in response to the first implant, but thereafter returned to pre-treatment or lower levels and showed no further stimulation following injection of subsequent implants. In a third experiment designed to establish the effects on libido and spermatogenesis of chronic treatment with levels of Buserelin (shown previously to depress gonadotrophin concentrations in stallions), 3 fertile pony stallions received subcutaneous implants at 2- to 5-week intervals for 12 months. Three untreated pony stallions acted as controls. Weekly blood samples were collected from both groups to monitor levels of FSH, LH, testosterone and oestrone sulphate. Semen was collected daily for 6-10 days both before treatment and at 3-month intervals thereafter in order to establish daily sperm output (DSO) and assess libido. Gonadotrophin, testosterone and oestrone sulphate levels were all lower in the treated group compared with either pre-treatment or control values. DSO was reduced by at least 50% throughout the treatment period in treated stallions but 7 months after insertion of the last implant it had returned to pre-treatment values. No significant effects on other semen characteristics were noted and there were no noticeable changes in libido of treated animals throughout the period of the experiment.
I previously reported that cholecystokinin octapeptide (CCK-8) had little effect on feeding motivation as indexed by runway performance, but that substantial impairment resulted from the interaction of CCK-8 and prefeeding of sucrose. If the sucrose was sham-fed, potentiation of the effect of CCK-8 was seen only after large doses. The current experiments examined whether synergy between 1 microgram/kg CCK-8 and prefeeding could be reproduced using gastric, duodenal, or hepatic-portal infusions. Gastric and duodenal infusions of 30% sucrose were effective; in conjunction with CCK-8 they decreased running speed as substantially as prefeeding did. The duodenal effect was specific. Glucose appeared to be as effective as sucrose, whereas equi-osmotic saline and mannitol were not. Intraportal glucose was relatively ineffective; interaction with CCK-8 was seen only after very large infusions, and the resulting running speeds did not approach those seen after prefeeding or gastrointestinal infusions. These results suggest that decreased feeding motivation after 1 microgram/kg CCK-8 develops through synergy between this peptide and a carbohydrate-sensitive signal generated within the small intestine.
An analytical procedure was developed for the analysis of 1,3-butadiene, acrolein, isoprene, benzene and toluene in the gas phase of cigarette smoke and environmental tobacco smoke (ETS) utilizing cryogenic gas chromatography-mass selective detection (GC-MSD). The MSD was operated in the selective ion monitoring (SIM) mode. The compounds of interest eluted in less than 15 min. The gas phase of freshly generated mainstream smoke was introduced into the GC-MSD via a 10-port gas sampling valve on a puff-by-puff basis. This method minimizes the ageing of tobacco smoke. The levels of 1,3-butadiene in the mainstream smoke ranged from 16 to 75 micrograms/cigarette. The gas phase of sidestream smoke was trapped in methanol using three midget impingers at -78 degrees C. The amount of 1,3-butadiene in the sidestream smoke ranged from 205-361 micrograms/cigarette. The concentration of 1,3-butadiene in ETS in a smoke-filled bar amounted to 2.7-4.5 micrograms/m3.
The long term effect of a single injection of 6,000 iu of human chorionic gonadotrophin (hCG) was studied in two pony stallions. Peripheral plasma samples were analysed for testosterone and oestrone sulphate. Testosterone concentrations were markedly elevated for five days after injection in both stallions. No adverse effects of these high concentrations were observed on concentrations later in the experiment. There was an initial increase in oestrone sulphate in one stallion, after which concentrations decreased to below pre-injection levels. The other stallion (whose initial oestrone sulphate concentrations were somewhat higher) showed no rise in response to hCG but did show a significant decline from five days after injection. Whether this suppression is an effect of the high testosterone concentrations remains to be determined.
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Electrolytes, metabolites, cortisol and reproductive hormones were measured in maternal plasma taken at least twice daily from three cases of bovine hydrops before, during and after parturition induced by dexamethasone or prostaglandin. Caesarean operations were required for two of the cases. Maternal plasma electrolytes remained within the normal range, but average potassium and creatinine concentrations were higher (9.2 and 0.68 mmol/litre, respectively) than normal (4.7 and 0.42 mmol/litre) in samples of amniotic fluid obtained at calving. Sodium (100 mmol/litre) and chloride (67 mmol/litre) in allantoic fluid were also higher than normal (53 and 20 mmol/litre, respectively). Conversely, creatinine concentrations were lower than normal in allantoic fluid (2.2 vs 13.8 mmol/litre). Oestradiol concentrations were lower than normal in maternal plasma (ranges: less than 20 to 140 pg/ml vs 30 to 440 pg/ml); maximum prostaglandin F metabolite (PGFM) concentrations were slightly elevated (ranges 1.1 to 2.0 ng/ml vs 0.4 to 0.9 ng/ml). Progesterone and cortisol concentrations remained within the normal range; the latter hormone increased markedly in parallel with raised PGFM concentrations. In two cases, the concentrations of reproductive hormones tended to be lower in the amniotic fluid than in the allantoic fluid. For example, progesterone concentrations were 42.8 and 14.9 ng/ml in the amniotic fluids vs 64.2 and 29.8 ng/ml in the allantoic fluids of the two cows; PGFM concentrations were 27.7 and 4.3 ng/ml vs 34.6 and 5.0 ng/ml, and oestradiol concentrations were 1.5 and 3.5 ng/ml vs 1.1 and 6.4 ng/ml in the two fluids, respectively.
An analytical procedure was devised for the determination of selected gas phase constituents in cigarette smoke utilizing capillary gas chromatography and mass selective detection (GC-MSD); the MSD was used in the selective ion monitoring mode (SIM). The gas of freshly generated mainstream smoke was analyzed via a 10-port gas sampling valve on a puff-by-puff basis. Benzene, toluene, and 1,3-butadiene were found in the range of 6-73, 5-88, and 16-75 micrograms/cigarette, respectively. The gas phase of sidestream smoke was trapped in methanol using 3 midget impingers at -78 degrees C. Benzene in sidestream smoke was found in the range of 490-840 micrograms/cigarette; toluene and 1,3-butadiene levels were 1,090-1,690 and 300-470 micrograms/cigarette, respectively. Environmental tobacco smoke (ETS), sampled in a smoke-filled bar, was analyzed using the cold trap method. The concentrations of benzene and toluene in this indoor air were found to be 26-36 and 41-80 micrograms/m3, respectively, while 1,3-butadiene was present at 3.3-4.5 micrograms/m3.
Six horses with monorchidism, identified at surgery for cryptorchidectomy, are reported. All six presented with a single scrotal testis. Following surgical removal of one testis, they were either hormonally, anatomically or behaviourally determined to be geldings. Three other horses reported in the literature are reviewed. Of these nine cases of monorchidism, eight were thought to be caused by testicular degeneration and one by testicular agenesis. The vaginal process was present in all of the former and absent in the latter. The left side was involved in five of these eight horses. In seven, the epididymis was absent and, in the remaining two, only the epididymal tail was present. The condition was thought to be congenital in the six horses in this series. A surgical approach to identify accurately monorchid horses is described.
The administration of 0.5 mg of long-acting adrenocorticotrophic hormone (ACTH, Synacthen-Depot) twice daily for 5.5 d to four adult rams during the breeding season had no consistent effect on plasma follicle stimulating hormone (FSH) concentrations. In contrast, it suppressed both plasma luteinizing hormone (LH) and testosterone concentrations. The responses to injections of 5 ug of gonadotrophin releasing hormone (GnRH), as measured by maximum concentrations reached and areas under the response curves, were also suppressed. These findings suggest that ACTH exerts its suppressive efects on LH at the pituitary level.
The administration of 0.5 mg of long-acting adrenocorticotrophic hormone (ACTH, Synacthen-Depot) twice daily for 5.5 d to four rams outside the breeding season caused marked rises in plasma cortisol without any evidence of adrenal depletion. This treatment also caused marked rises in basal plasma follicle stimulating hormone (FSH) concentrations which remained high even after cessation of treatment. Plasma FSH responses to 5 ug of gonadotrophin releasing hormone (GnRH) were consistently observed and ACTH treatment increased the FSH response to GnRH. In contrast, spontaneous fluctuations in the plasma luteinizing hormone (LH) and testosterone concentrations were abolished by ACTH treatment. The quantity of testosterone released after GnRH (estimated by the maximum values reached and by the area under the response curve) was also suppressed while that of LH was only slightly lower. A comparison of the results of this experiment with those obtained in rams during the breeding season showed that the effects of ACTH on LH and testosterone were more marked during the breeding season. In contrast, the effect of ACTH on FSH is to increase the latter during the nonbreeding season, whereas no effect was observed during the breeding season.
Twice daily for 5.5 d, 0.5 ug of long-acting adrenocorticotrophic hormone (ACTH, Synacthen-Depot) was administered to four rams castrated 17 d earlier. There was a progressive diminution in basal plasma follicle stimulating hormone (FSH) during and after treatment. ACTH also suppressed basal plasma luteinizing hormone (LH) concentrations and the maximum LH values reached and the quantity of LH released in response to the injection of 5 ug of gonadotrophin releasing hormone (GnRH). There was, however, evidence that the LH concentrations returned to pretreatment levels after ACTH treatment ceased. This experiment demonstrated that the effects of ACTH on LH are modulated by castration, but throughout this series of experiments ACTH always depressed LH activity. In contrast, FSH is affected by ACTH in different ways, depending on the season and the presence or absence of a testis.