PubMed Health⌕ Search

Biomedical subjects

T Sweeney

Publications and source records attributed to T Sweeney.

At least 19 recordsLinked to original sources
PubMed1999

Effect of immunization against melatonin on prolactin concentrations and the timing of reproductive transitions in ewes.

The objective of this experiment was to develop a procedure for immunizing ewes against melatonin that would alter the effects of changing photoperiod on seasonal reproduction and prolactin secretion. Ewes were immunized against human serum albumin (HSA) as controls (n = 9) or a melatonin-human serum albumin conjugate (0.25 mg; n = 10) on December 14th (Day 0) and boosted 9 times. They were maintained on natural photoperiod and then transferred indoors and exposed to long days for 35 d, followed by short days for 146 d, long days for 93 d, and short days for a further 123 d. Antibody titers to melatonin (at a serum dilution of 1:1,250) were significantly higher in immunized ewes (27.3 +/- 6.6%) than controls (0.7 +/- 0.1%; P < 0.001). At the end of the experiment, antibody titers in immunized ewes (at dilution of 1:50) were higher in blood (43.7 +/- 8.2%) than in cerebrospinal fluid (10.8 +/- 3.9%; P < 0.05), and highly correlated (r2 = 0.746). Onset of the breeding season was advanced slightly after the second transfer from long to short days in immunized ewes (April 12 +/- 3 d) compared with controls (April 25 +/- 3 d; P < 0.05). Mean serum prolactin concentrations were lower (P < 0.05) in melatonin-immunized ewes compared with controls on natural photoperiod, after transfer from long to short days, during long days, and after the second transfer from long to short days. In conclusion, despite melatonin-immunization increasing antibody titers in blood and cerebrospinal fluid, and decreasing prolactin concentrations over much of the experiment, minimal effects on the timing of reproductive transitions in the ewes were evident. This discrepancy between the response of the prolactin and reproductive axes to melatonin immunization supports the hypothesis of a dual site of action of melatonin, with melatonin acting in the pituitary gland to mediate the effects of photoperiod on prolactin secretion and in the mediobasal hypothalamus to affect reproductive responses.

Animals↗
PubMed1999

Protein inhalation powders: spray drying vs spray freeze drying.

PURPOSE: To develop a new technique, spray freeze drying, for preparing protein aerosol powders. Also, to compare the spray freeze-dried powders with spray-dried powders in terms of physical properties and aerosol performance. METHODS: Protein powders were characterized using particle size analysis, thermogravimetric analysis, scanning electron microscopy, X-ray powder diffractometry, and specific surface area measurement. Aerosol performance of the powders was evaluated after blending with lactose carriers using a multi-stage liquid impinger or an Anderson cascade impactor. Two recombinant therapeutic proteins currently used for treating respiratory tract-related diseases, deoxyribonuclase (rhDNase) and anti-IgE monoclonal antibody (anti-IgE MAb), were employed and formulated with different carbohydrate excipients. RESULTS: Through the same atomization but the different drying process, spray drying (SD) produced small (approximately 3 microns), dense particles, but SFD resulted in large (approximately 8-10 microns), porous particles. The fine particle fraction (FPF) of the spray freeze-dried powder was significantly better than that of the spray-dried powder, attributed to better aerodynamic properties. Powders collected from different stages of the cascade impactor were characterized, which confirmed the concept of aerodynamic particle size. Protein formulation played a major role in affecting the powder's aerosol performance, especially for the carbohydrate excipient of a high crystallization tendency. CONCLUSIONS: Spray freeze drying, as opposed to spray drying, produced protein particles with light and porous characteristics, which offered powders with superior aerosol performance due to favorable aerodynamic properties.

Administration, Inhalation↗
PubMed1999

Seasonal variation in long-day stimulation of prolactin secretion in ewes.

Whereas ewes initiate reproductive activity in response to a photoperiod signal initiated after the winter solstice of 35 long days (35 LD) followed by short days, the reproductive axis fails to respond to this signal between the autumn equinox and the winter solstice. The aim of experiment 1 was to determine whether the prolactin axis, like the reproductive axis, is unresponsive to a 35 LD photoperiod signal followed by continuous exposure to short days between the autumn equinox and the winter solstice. Whereas the 35 LD signal from September 21 (</= 6 h increase in day length) failed to influence prolactin secretion, all other long-day treatments (> 6 h increase in day length) initiated a rise in prolactin in at least 75% of ewes in each group (p < 0.05). The aim of experiment 2 was to determine whether ewes failed to secrete prolactin during a 35 LD photoperiod from September 21 because they did not recognize a 6-h increase in day length at any time of year as a stimulatory photoperiod signal or because hypothalamic/pituitary regulation of prolactin synthesis or secretion is compromised in September. The results demonstrated that while hypothalamic regulation of prolactin secretion and pituitary stores of prolactin were normal at all times of year examined, the ability of ewes to secrete prolactin in response to a long-day photoperiod signal appears to be dependent on photoperiodic history rather than the time of year of the photoperiodic challenge.

Animals↗
PubMed1999

Effect of long-term immunization against inhibin on sperm output in bulls.

To determine the effect of neutralization of inhibin on sperm output, 12 Holstein bulls were paired by birth date and weight on Day 1 of age. Each bull was actively immunized against bovine inhibin alpha1-26 gly-tyr (bINH) conjugated to human alpha globulin (HAG, n = 6 bulls) or HAG alone (controls, n = 6) at 60 days of age; booster immunizations were administered at 90, 104, 124, 270, and 395 days of age. Body weights and scrotal circumferences were measured at the time of primary immunization and at 10 days after each booster. In addition, jugular blood was obtained at 60, 70, 100, 114, 134, 280, and 405 days of age, during the 3-wk sperm collection period, and during a 6-h blood-sampling period after sperm collection to determine bINH antibody titer and concentrations of FSH, LH, testosterone, and estradiol. Beginning at 405 days of age, sperm output was measured 3 days/wk for 3 wk with two successive ejaculates collected each day for a total of 18 ejaculates per bull. During Days 60-405 of age, the increase in titer of bINH antibodies, scrotal circumference, and serum concentration of FSH was greater (p < 0.01) for the bINH-immunized compared with control bulls. There were significant (p < 0.01) pair x treatment interactions for sperm output and serum FSH and LH concentrations. Specifically, bINH-immunized bulls for four of the six pairs had nearly 50% greater serum FSH concentrations and sperm output. For the remaining two pairs, sperm output was lower and FSH was either lower or only marginally higher in the bINH-immunized bulls compared with controls. Also, the control bulls for the two remaining pairs produced more sperm than all but one bINH-immunized bull, and had markedly higher serum LH concentrations than all other bulls. To summarize, enhancement of sperm output after immunization against inhibin depends on the subsequent increment in FSH concentrations. We conclude that inhibin suppresses spermatogenesis. Thus, methods to immunoneutralize inhibin may have merit as a therapeutic route to enhance sperm production in reproductively maturing bulls.

Aging↗
PubMed1999

Primary aorto-duodenal fistula secondary to infected abdominal aortic aneurysms: the role of local debridement and extra-anatomic bypass.

Gastrointestinal bleeding secondary to spontaneous rupture of an infected abdominal aortic aneurysm into the duodenum is a rare and highly lethal clinical occurrence, representing roughly a third of all primary aortoduodenal fistulas. Diagnosis is problematic due to the subtleties in the clinical presentation and course, and surgical treatment is usually delayed, representing a challenge even for the experienced vascular surgeon. The overall mortality is over 30% and the operative approaches are still controversial. Two cases of ruptured infrarenal aortic aneurysms complicated with aortoduodenal fistula were recently treated at our institution. Bacterial aortitis was documented by arterial wall cultures positive for Klebsiella and Salmonella species respectively. The clinical courses and outcomes of the two patients (one survivor ) treated with retroperitoneal debridement and extra-anatomic bypass and a review of the modern surgical treatment are herein described.

Aged↗
PubMed1997

Influence of previous photoperiodic exposure on the reproductive response to a specific photoperiod signal in ewes.

Two experiments were carried out to determine whether the reproductive response of ewes to a specific photoperiodic signal depends on the time of year that the signal is given, and, if so, whether this dependence can be attributed to the photoperiodic history of the ewes. The aim of experiment 1 was to expand upon previous findings that the reproductive response to a specific photoperiodic challenge in ewes previously maintained on natural photoperiod varies with time of year. Ewes were transferred at one of three times of year from natural photoperiod to photochambers and were immediately exposed to 35 long days (18L:6D) followed by continuous exposure to short days (8.5L: 15.5D); this treatment is referred to as LD-->SD. The three times of year when long days started corresponded to the beginning of the breeding season, the mid-breeding season, and early anestrus (September 21, December 21, March 21, respectively). In ewes exposed to LD-->SD beginning in September, the breeding season and subsequent anestrous season was not altered. In ewes exposed to LD-->SD beginning in December, the transition to anestrus was advanced (p < 0.05) relative to that in controls maintained in simulated natural photoperiod. Subsequently, half of these ewes resumed reproductive activity within 180 days; this occurred 131 +/- 8 days after transfer to short days. In contrast, all ewes exposed to LD-->SD beginning in March resumed reproductive activity; this began 100 +/- 3 days after transfer to short days (p < 0.05 versus December group). The purpose of experiment 2 was to assess the extent to which the difference in response to a photoperiodic challenge can be attributed to photoperiodic history. Ewes were maintained on short days from the winter solstice interrupted with 35 long days from March 21, June 21, September 21, or December 21. The majority of ewes exhibited an onset of reproductive activity after exposure to LD-->SD at the different times of year, and there was no group difference in latency to onset of reproductive activity. The duration of reproductive activity, however, was longer (p < 0.05) in ewes exposed to LD-->SD beginning in June than in the other groups. Thus we conclude that the seasonal difference in the ability of the photoperiodic challenge of long followed by short days to induce reproductive activity in ewes previously maintained outdoors can be attributed, in large measure, to photoperiodic history. Other factors, such as phase of the endogenous rhythm, however, may influence the duration of reproductive activity resulting from this photoperiodic challenge.

Analysis of Variance↗
PubMed1997

Variation in the ability of a long day followed by a short day photoperiod signal to initiate reproductive activity in ewes at different times of the year.

Three experiments examined the importance of the time and duration of exposure to a long day followed by a short day photoperiod signal in initiating reproductive activity in ewes. In Expt 1, ewes were maintained on short days (8.5 h light:15.5 h dark) from 21 December interrupted with either 105 long days (18 h light:6 h dark; LD) from 9 February or 35 LD from 9 February, 16 March or 20 April. Exposure to long days followed by short days advanced the onset of reproductive activity in comparison to control ewes maintained on simulated natural photoperiod. Exposure to long days for 105 days delayed the onset of reproductive activity (August 2 +/- 3 days; P < 0.05) compared with 35 days beginning on the same date (July 13 +/- 5 days). The interval from the end of the long day signal to the onset of reproductive activity was shorter (P < 0.001) however, after 105 LD than after 35 LD. In Expt 2, control ewes were moved from natural photoperiod to simulated natural photoperiod on 1 November and subsequently exposed to short days from 21 December. Four other groups were also exposed to this basic photoperiodic signal sequence but it was interrupted with either 70 LD from 16 November, or 35 LD from 16 November, 21 December or 20 April. More ewes (P < 0.05) initiated reproductive activity after exposure to 70 LD from 16 November and 35 LD from 21 December or 20 April compared with control ewes maintained on short days or ewes given 35 LD from 16 November. The interval from the end of long days to the onset of reproductive activity was less (P < 0.01) in ewes given 70 LD than in ewes given 35 LD. In Expt 3, ewes on natural photoperiod were given either 90 LD from 21 September, 35 LD from 21 September, 26 October, 30 November, 4 January or 8 February followed by short days. The majority of ewes that received long followed by short days after the winter solstice resumed reproductive activity. However, all photoperiod signals given between the autumn equinox and the winter solstice failed to initiate reproductive activity in ewes during the experiment. Thus we conclude that, in ewes, the reproductive neuroendocrine axis is insensitive to long days followed by short days between the autumn equinox and the winter solstice. The reproductive axis of ewes regains sensitivity to the inductive effects of long days followed by short days at a time close to the winter solstice. Between the winter and summer solstices, long days followed by short days maintain the anoestrous state and provide the cue for initiation of reproductive activity.

Animals↗
PubMed1997

Ontogeny of anti-müllerian hormone, 3 beta-hydroxysteroid dehydrogenase and androgen receptor expression during ovine total gonadal development.

Anti-müllerian hormone (AMH) and androgenic steroids are key factors regulating the masculinisation of the internal and external genitalia during fetal development. AMH is produced in Sertoli cells and causes regression of the müllerian ducts in the male. 3 beta-Hydroxysteroid dehydrogenase (3 beta-HSD) is one of the key steroidogenic enzymes regulating testosterone production in Leydig cells. The objective of this experiment was to elucidate the development of the ovine fetal testes by identifying the spatio-temporal expression of AMH, 3 beta-HSD and androgen receptor expression within them. Fetuses from days 30 and 40 of gestation were fixed intact, while the gonads were dissected from the fetuses on days 70, 100 and 130 of gestation. Tissue was fixed in Bouin's fixative for 6 h, processed into paraffin wax and sections immunostained using rabbit anti-human AMH, 3 beta-HSD or androgen receptor antibodies. While seminiferous cords were absent on day 30 of gestation, pre-cord organisation was apparent and the gonad could be clearly distinguished from surrounding tissue by the presence of AMH and 3 beta-HSD immunopositive cells. Androgen receptor expression was not apparent at this stage. By day 40 of gestation the testis was organised into distinct seminiferous cords and intense immunostaining for AMH and 3 beta-HSD was present in Sertoli cells within the cords and Leydig cells in the interstitium respectively. Androgen receptor immunopositive cells were present in the interstititum but cells destined to develop into rete testis were immunonegative. By day 70 of gestation, the rete testis was organised in the centre of the testis and was strongly androgen receptor immunopositive. AMH and 3 beta-HSD expression was present in Sertoli and Leydig cells respectively. The expression of AMH, 3 beta-HSD and androgen receptor in the 100 and 130 day gestation fetuses was similar to that identified in the 70 day fetuses. In conclusion, Sertoli and Leydig precursor cells are present in the gonad prior to seminiferous cord formation and contain AMH and 3 beta-HSD at all stages of gestation examined. While androgen receptor immunoexpression was present in nuclei of interstitial cells from day 40 of gestation and in the rete testis from day 70 of gestation, Sertoli cells were immunonegative for androgen receptor at all of the stages examined.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

'Hamster-like' cycles in testicular size in the absence of gonadotrophin secretion in HPD rams exposed to long-term changes in photoperiod and treatment with melatonin.

Long term changes in the secretion of FSH, LH and testosterone, and the size of the testis were measured in groups of hypothalamo-pituitary disconnected Soay rams (HPD rams, n = 8) and control Soay rams (HPD-sham operated and unoperated, total n = 8) while exposed to an artificial lighting regimen of alternating 16-weekly periods of long days (16L: 8D) and short days (8L: 16D), and when treated with a constant-release implant of melatonin given under long days (total study: 136 weeks). Short term provocation tests using NMDA (glutamate receptor agonist), GnRH and LH were used to assess functionality of the hypothalamus, pituitary gland and testis, respectively. Control rams expressed normal photoperiod-induced cycles in the reproductive axis. Blood concentrations of FSH, LH and testosterone were significantly increased under short days, and decreased under long days with parallel changes in testicular diameter. Treatment with implants of melatonin under long days mimicked the effect of short days and induced rapid reactivation of the reproductive axis. In the HPD rams the blood concentrations of FSH, LH and testosterone declined immediately after the HPD surgery and values remained close to the lower limit of detection of the radioimmunoassays throughout the experiment. LH pulses were absent in the HPD rams and NMDA failed to induce LH secretion consistent with functional disconnection of the pituitary gland from the hypothalamus. The testes regressed to a significantly smaller size in the HPD rams compared with controls even at the nadir of the sexual cycle (testis diameter: 30.2 +/- 0.7 vs 41.3 +/- 0.8 mm, HPD vs control rams, respectively). A low amplitude cycle in testicular diameter (peak to nadir: 5.0 +/- 0.7 mm) persisted in the HPD rams with a temporal pattern opposite to the controls (growth under long days instead of short days; 'hamster like'). In the HPD rams, the treatment with melatonin blocked the long day-associated increase in testicular size, without effects on FSH, LH and testosterone secretion, pituitary responsiveness to GnRH (LH increment) or testicular responsiveness to LH (testosterone increment). This was in contrast to the cyclical changes in all parameters induced by melatonin in the control rams. At post-mortem, the reproductive tract in HPD rams was markedly regressed compared with the controls. The efficiency of spermatogenesis was reduced with few germ cells maturing beyond primary spermatocytes. Immunocytochemical staining, however, revealed the maintenance of androgen receptor expression in Sertoli cells, pertibular cells and Leydig cells, and steroid activity as measured by 17 alpha-hydroxylase expression in Leydig cells. Overall, the absence of photoperiod-induced changes in gonadotrophin secretion in the HPD rams illustrates the dependence on regulation by the hypothalamus, presumably through the secretion of GnRH. The residual cycle in the size of the testes in the HPD rams was closely correlated with the photoperiod-induced changes in prolactin secretion which persisted in these animals (summary of previous published data included). The combined results support the view that melatonin acts in the hypothalamus to mediate effects of photoperiod on gonadotrophin secretion and in the pituitary gland to mediate effects on prolactin secretion (dual site hypothesis), and that FSH, LH and prolactin act synergistically to regulate the long-term cycle in testicular activity in the ram.

Animals↗
PubMed1979

Obturator canal bypass grafts for septic lesions of the femoral artery.

Infection of the femoral artery results in false aneurysm formation and hemorrhage unless appropriate reconstructive measures are taken. We reviewed ten such cases managed by obturator canal bypass with autogenous saphenous vein. The graft maintained viability of the extremity in every case in the early postoperative period. One death occurred related to cardiac disease, and there was one late failure. This experience confirms the usefulness of the obturator canal as a method for bypass of the infected femoral artery.

Adolescent↗
PubMed1975

Compensatory hypertrophy of the ileum after gastroduodenojejunal exclusion.

One theory of compensatory hypertrophy of the gut suggests that ileal growth after jejunectomy results from exposure of the ileum to villus-enlarging factors emanating from the papilla of Vater. This hypothesis was tested by examination of the ileum after bypass of pancreatobiliary secretions to the colon. Hypertrophy of the ileum occurred after esophagoileostomy and gastroduodenojejunal exclusion, suggesting that adaptive growth of the gut depends on additional factors. There is evidence to support several theories of compensatory hypertrophy. A hypothesis seeking to reconcile the conflicting notions of intraluminal and hormonal stimuli is suggested.

Ampulla of Vater↗
PubMed1975

The hepatorenal syndrome: recovery after portacaval shunt.

Reversal of the morbid hepato-renal syndrome has been achieved in a cirrhotic patient with ascites following successful side-to-side portacaval shunt. The hepatorenal syndrome is defined as progressive unresponsive renal failure with previously normal kidneys in the presence of impaired hepatic function. Although the etiologic mechanism has not been defined, it is suggested the relationship of increased intrahepatic sinusoidal pressure on the thoracic duct and subsequent decreased lymph flow are interrelated to increased levels of aldosterone and manifested by (chylous) ascites. Laboratory and clinical evidence suggest that cirrhotics with ascites have remarkably high levels of aldosterone secretion via the rennin-angiotensin-adrenal cortex mechanism. This is the group that develops hepatorenal syndrome. Reduction of the intrahepatic pressure and decompression of the portal hypertension can be successfully achieved with a side-to-side shunt which should return the aldosterone-rennin-angiotensin axis to normal and subsequently reverse the hepatorenal syndrome.

Acute Kidney Injury↗