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Biomedical subjects

A G Robinson

Publications and source records attributed to A G Robinson.

At least 19 recordsLinked to original sources
PubMed1999

Valve surgery in octogenarians.

OBJECTIVE: To review the outcomes of octogenarians undergoing valve operations. PATIENTS AND METHODS: One hundred and twenty-five consecutive patients aged 80 years and over received valve operations between 1990 and 1996 at the Toronto General Hospital, Toronto, Ontario. All hospital survivors were prospectively followed for a mean of 36.6 months (range 0.1 to 89.9). RESULTS: One hundred and two patients received aortic valve operations, 18 patients received mitral procedures and five patients underwent double valve operations. Significant aortic stenosis was present in 95 of 102 patients (93%) receiving isolated aortic valve surgery, and mitral regurgitation was present in 16 of 18 patients (89%) undergoing mitral valve operations. Overall in-hospital mortality was 6.4% (n=8) and the perioperative infarction rate was 1.6% (n=2). In-hospital mortality was higher for mitral valve patients at 17% (n=3) than for aortic valve patients at 4% (n=4) (P=0.06). For the group overall, the six-year actuarial survival rate was 71.6+/-6%. The actuarial freedom from valve-related death was 97.1+/-2% at three years. Concomitant coronary artery disease was not significantly associated with perioperative mortality. Survivors had significantly improved New York Heart Association functional class status. CONCLUSION: In carefully selected patients aged 80 years and over, aortic valve surgery carries a low perioperative mortality with good intermediate term survival and benefits. Octogenarians undergoing mitral valve procedures experience higher perioperative mortality. Although the number of participants was small for this study, it does appear that coexistent coronary artery disease should not be the sole reason for denial of surgery because it has less of an impact on short and intermediate term survival than other factors.

Age Factors↗
PubMed1997

Diabetes insipidus.

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Diabetes Insipidus↗
PubMed1996

The central oxytocin pulse generator: a pacemaker for the ovarian cycle.

During luteolysis in sheep, episodic pulses of oxytocin (OT), contributed by the neurohypophysis and the corpus luteum (CL), stimulate uterine luteolytic pulses of prostaglandin (PG) F2 alpha via endometrial OT receptors. To distinguish relative contributions of neurohypophysial and luteal OT, ovariectomized sheep were given estradiol-17 beta (E) and progesterone (P) to stimulate levels during the cycle. In intact sheep, luteectomy was performed to exclude the CL as a source of OT and to initiate P withdrawal. In ovariectomized sheep, E (1 microgram/h) for 12 to 36 h) superimposed on basal E(0.05 microgram/h), caused a series of 4 to 6 episodes of high frequency pulses of OT, each episode lasting 1 to 2 h at intervals of 3 h, and commencing at 24 h. Withdrawal of P (500 micrograms/h), superimposed on basal E in ovariectomized sheep, or luteectomy in intact sheep, evoked similar episodes of high frequency pulses of OT beginning at 24 h. We conclude that (1) an increase in E levels, or the return of E action following P withdrawal, causes intermittent increases in the frequency of the central OT pulse generator. (2) high frequency pulses of OT initiate subluteolytic levels of uterine PGF2 alpha which trigger a supplemental release of luteal OT; (3) luteal OT amplifies the secretion of uterine PGF2 alpha which initiates luteolysis and causes more luteal OT to be secreted; and (4) in addition to the established hypothalamic-anterior pituitary-gonadal axis for initiating the ovarian cycle (via the gonadotrophins), there is now evidence for a hypothalamic-posterior pituitary-gonadal axis for terminating the ovarian cycle (via OT).

Animals↗
PubMed1995

The central oxytocin pulse generator: a pacemaker for luteolysis.

Oxytocin (OT) is released from the neurohypophysis into the jugular vein of sheep in small 1-2 min pulses (ca. 10 pg/ml) in both cyclic and ovariectomized sheep. In intact cycling sheep, additional hour long bursts of OT (up to 200 pg/ml) occur in peripheral blood during luteolysis at intervals of 6 to 9 hrs which appear to regulate large luteolytic pulses of uterine prostaglandin F2a (PGF2a). Since the ovine corpus luteum (CL) also synthesizes OT, experiments were performed to distinguish between the relative contributions of the neurohypophysis and the CL to the large bursts of OT secreted during luteolysis. Two models were used. First, ovariectomized sheep were given exogenous E and/or P by constant infusion to simulate levels during the estrous cycle. Second, in tact cycling sheep, the CL was surgically excised during the luteal phase to exclude the CL as a source of OT and, at the same time, subject the animals to the withdrawal of P. Pulses of OT in jugular vein plasma were determined by RIA or biometry of the uterus. The findings are summarized as follows: In ovariectomized sheep, maintained on low E (0.05 g/hr) to preserve the OT pulse generator, infusion of E (1 microgram, 2 micrograms or 4 micrograms/hr) for 12 to 36 hr, caused a series (4 to 6) of rapid increases in OT pulse frequency each lasting 1 to 2 hrs at intervals of 3 hrs. The time of onset of high frequency pulses was dose-dependent. Withdrawal of 10 day infusions of P (500 micrograms/hr) superimposed on low E (0.05 microgram/hr) also evoked a series of high frequency episodes of OT pulses beginning 24 hrs after P withdrawal. In intact sheep, surgical removal of the CL resulted in a series of high frequency pulses similar in duration and frequency to those following the withdrawal of P in the ovariectomized animal. We conclude that: (1) an increase in E or returning E action causes the OT pulse generator to alter its frequency intermittently thus producing a series of 4 to 6 episodes of high frequency pulses of OT. (2) Similar changes can be evoked by withdrawal of P either by terminating an infusion of P in the presence of E in the ovariectomized sheep or by surgically removing the CL from the ovary in the intact sheep. (3) At the end of the reproductive cycle, the central OT pulse generator appears to act as a pacemaker which, acting on the endometrial OT receptors, triggers a series of pulses of PGF2a from the uterus and hence causes regression of the CL. In the sheep and other ruminants, an intermittent supplemental secretion of OT from the CL, triggered via the central OT pulse generator, may also be required to amplify the luteolytic pulses of PGF2a from the uterus. (4) In addition to the well established interaction of ovarian steroid hormones, and the hypothalamic pituitary system for the initiation of the reproductive cycle via the gonadotrophins, there is now good evidence for an interaction of ovarian steroids and the posterior pituitary for terminating the reproductive cycle.

Animals↗
PubMed1994

Control of posterior pituitary vasopressin content: implications for the regulation of the vasopressin gene.

Axon terminals in the posterior pituitary store large quantities of the hormone vasopressin (AVP), buffering the synthesizing neurons in the hypothalamus against acute changes in physiological demand for hormone release. The dynamics of pituitary AVP content reflect the competing processes of release and synthesis. This report demonstrates substantial increases in pituitary AVP content in the maturing rat. Between 7-10 weeks of age, the total pituitary AVP content in the rat increases from 957 +/- 72 to 1667 +/- 160 ng. Cross-sectional data indicate a parallel relationship between body weight and pituitary AVP content. Nevertheless, weight maintenance does not affect age-related increases in AVP content. Decreasing demand for hormone release and synthesis by inducing hyponatremia blocks subsequent pituitary accumulation. After withdrawing the hyponatremic experimental conditions, animals resume accumulation of pituitary AVP, but do not catch up to age-matched controls. This indicates that increases in pituitary AVP content do not result from a feedback signal from the neural lobe, but rather, pituitary AVP levels passively reflect changes in hormone release and compensatory synthesis.

Aging↗
PubMed1994

Diabetes insipidus.

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Benzothiadiazines↗
PubMed1993

c-fos expression in vasopressin and oxytocin neurons reveals functional heterogeneity within magnocellular neurons.

The c-fos protein is rapidly induced in hypothalamic magnocellular nuclei following hemorrhage. We used specific antibodies directed against c-fos and either vasopressin (AVP) or oxytocin (OT) neurophysin to investigate c-fos activation in individual AVP and OT neurons. AVP and OT neurons expressed c-fos in response to hypovolemic stimuli. Following a protocol of incremental hemorrhage, AVP and OT neurons expressed c-fos with a graded response that correlated with stimulus intensity. As the volume of hemorrhage increased, there was an increase in the number of cells expressing c-fos as well as in the amount of c-fos immunoreactivity per cell. These increases correlated with the amount of hormone released into the peripheral blood. In addition, a differential pattern of activation for AVP neurons occurred in response to hemorrhagic stimuli. AVP neurons in the supraoptic nucleus (SON) had a lower threshold for response than those in the paraventricular nucleus (PVN). For OT, activation required a greater blood loss than AVP and c-fos expression encompassed both SON and PVN neurons. We conclude that c-fos expression is proportional to stimulus intensity and reveals functional heterogeneity among magnocellular neurons.

Animals↗
PubMed1993

The diagnosis and management of diabetes insipidus during medical emergencies.

The abrupt presentation of hypertonic polyuria, polydipsia and hypernatremia, reflects vasopressin deficiency owing to multiple potential etiologies. Diabetes insipidus becomes an emergency and leads to severe hyperosmolality and dehydration when fluid intake does not match obligate losses. Decreased mental alertness may impair the ability to sense thirst or to obtain access to fluids, thus placing patients postoperatively or posttrauma at particular risk of complicated diabetes insipidus. Intravenously administered DDAVP and hydration with hypotonic fluids is the preferred therapy in the acute setting. As diabetes insipidus may be of unpredictable duration, the need for ongoing medical therapy must be frequently reassessed.

Diabetes Insipidus↗
PubMed1992

Models of neurohypophyseal homeostasis.

Rats subject to prolonged (3-6 days) hypernatremia show significantly decreased pituitary vasopressin content as well as increased levels of hypothalamic vasopressin mRNA; these values return to baseline levels after the stimulus is removed. In this paper, we tested whether a single cellular mechanism for regulation of synthesis could account for the experimental observations of both pituitary hormone depletion-repletion and hypothalamic mRNA content. We developed several "minimal" models of vasopressin synthesis in which control of hormone synthesis was regulated exclusively by transcription, translation, or mRNA decay and tested each model to see which best emulated the dynamics of neuro-hypophyseal vasopressin content and hypothalamic vasopressin mRNA. Experimental data provided parameters for pituitary content, baseline and stimulated release rates, mRNA decay, transcription, and translation. Models based exclusively on translation and mRNA decay failed to produce predictions similar to experimental observations. Of the models tested, the transcription model provided predictions most consistent with laboratory data, although some quantitative differences remain. The results of the computer modeling strongly suggest that transcription represents the predominant means by which magnocellular neurons regulate vasopressin synthesis.

Animals↗
PubMed1992

Transient hyponatremia after damage to the neurohypophyseal tracts.

Section of the neurohypophyseal stalk classically produces a triphasic response: diabetes insipidus (1st phase), hyponatremia or normonatremia (2nd phase), and diabetes insipidus (3rd phase). Transient hyponatremia without diabetes insipidus has been reported after transsphenoidal pituitary surgery. We report two additional cases of transient hyponatremia which occurred 6-8 days after pituitary surgery. We hypothesize that this outcome may be due to partial section or damage of the hypothalamiconeurohypophyseal tracts. The remaining intact vasopressin neurons function normally to protect against the diabetes insipidus of the first and third phase, but leak of vasopressin from the damaged tracts and posterior pituitary is sufficient to cause what can be described as an isolated second phase. To study this hypothesis in rats, partial damage to the hypothalamicneurohypophyseal tracts was produced by radiofrequency lesions. The lesions did not affect anterior pituitary function. A variety of responses in posterior pituitary function occurred, including classic triphasic response in 2 rats and transient hyponatremia in 20 of 35 lesioned animals. The mean sodium nadir was 128.7 +/- 1.5 mEq/l in comparison to the sham-operated value of 140.0 +/- 0.4 mEq/l. Of the 20 rats exhibiting transient hyponatremia, 12 went on to develop diabetes insipidus, and 8 recovered. In the recovered group, the transient hyponatremia occurred 1-3 days after lesioning and returned to normal by day 7 which corresponds to the timing of the second phase of the triphasic response in rats. Hyponatremia was accompanied by vasopressin levels inappropriate for the plasma sodium level, inappropriately concentrated urine, water retention, and natriuresis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1991

Postoperative computed tomographic evaluation of patients with large pituitary tumors treated with operative decompression and radiation therapy.

Thirty consecutive patients who underwent operative decompression and radiation therapy for large sellar and suprasellar pituitary tumors (greater than or equal to 2 cm) were studied in terms of the serial computed tomographic (CT) changes. There were 23 men and 7 women. The mean age was 49.6 +/- 2.5 years, and the mean follow-up was 45.3 +/- 3.9 months. Twenty-eight of the 30 patients had transsphenoidal surgery, and 27 had hormonally inactive tumors. Radiation therapy was begun within 1 month of surgery with a mean dose of 4855 +/- 70 cGy. Postoperative CT scans were obtained within 1 month of surgery and at 6- to 12-month intervals thereafter. Fourteen patients (45%) had no suprasellar tumor visualized in either the early postoperative CT scans or on subsequent scans. Eleven patients (35%) had a persistent suprasellar mass during the early postoperative period that resolved on serial CT evaluation. The mean time for resolution was 10.4 +/- 1.2 months. Six patients (20%) had a persistent suprasellar mass on serial CT evaluation. A persistent postoperative mass that subsequently resolved in many of the patients was thought to be caused by the gradual retraction of the postoperative packing and hematoma, as well as the effect of radiation on any residual tumor.

Combined Modality Therapy↗
PubMed1991

Vasopressin transport regulation is coupled to the synthesis rate.

Vasopressin is synthesized in the perikarya of magnocellular neurons and is transported down long axons to the storage terminals of the posterior pituitary. To maintain stable pituitary stores following vasopressin secretion, the hypothalamus must synthesize and transport an amount of new vasopressin, equivalent to the amount released. Vasopressin release and synthesis rate can be chronically upregulated or suppressed relative to basal levels, depending on the demand for vasopressin. We studied whether vasopressin transport was similarly regulated during situations of varying demand. During chronic hyponatremia, when synthesis of vasopressin was reduced to undetectable levels, transport of vasopressin was also markedly decreased, as evidenced by continued presence of vasopressin in the transport system. Upregulation of transport was demonstrated by measuring pituitary accumulation of vasopressin in rats whose pituitary stores were initially depleted by hypernatremia and in whom subsequent release was suppressed by hyponatremia. In hypernatremic rats, transport of vasopressin was increased fivefold over baseline as determined by pituitary accumulation, and this elevated rate persisted for 7 days in the absence of release. This study demonstrates that axonal transport of vasopressin is a regulated process and is linked to synthesis rate rather than release.

Animals↗
PubMed1990

Hyponatremia in rats induces downregulation of vasopressin synthesis.

Hyponatremia due to inappropriate secretion of vasopressin is a common disorder in human pathophysiology, but vasopressin synthesis during hypoosmolality has not been investigated. We used a new method to quantitate synthesis of vasopressin in rats after 3, 7, and 14 d of hyponatremia induced by administering dDAVP (a vasopressin agonist) and a liquid diet. Vasopressin synthesis was completely turned off by 7 d. Vasopressin mRNA levels in the hypothalamus paralleled the reduction in synthesis and were reduced to levels of only 10-15% of the content in control rats. When hyponatremia was corrected by withdrawal of dDAVP, vasopressin mRNA slowly returned to normal over 7 d. The observation that vasopressin synthesis can be so completely turned off leads to several conclusions: under normal physiological conditions the neurohypophysis is chronically upregulated; there must be an osmotic threshold for initiation of vasopressin synthesis (and release); the large store of hormone in the posterior pituitary is essential for vasopressin to be available during times of decreased synthesis; and, finally, some nonosmolar stimulus for synthesis must be present during clinical disorders when vasopressin is secreted (and synthesized) despite hypoosmolality.

Animals↗
PubMed1989

Total translation of vasopressin and oxytocin in neurohypophysis of rats.

There is a paucity of information about total translation rate of vasopressin and oxytocin. Because the site of synthesis of the neurohypophysial hormones is anatomically separate from the site of storage, we were able to measure total translation by blocking transport of newly synthesized hormone and measuring accumulation in the areas of synthesis in the hypothalamus. Colchicine administered into the third ventricle in doses as low as 3.5 micrograms/rat blocked transport for 18 h. The linear increase in vasopressin and oxytocin content over 18 h indicated a stable rate of synthesis, which was 1.2 and 1.9 pmol/h for vasopressin and 1.4-2.5 pmol/h for oxytocin. The molar correlation for synthesis of total neurophysin to total hormone was 1.16. Infusion of oxytocin and vasopressin into rats indicated that this level of synthesis of hormone was essential under steady-state conditions to maintain plasma levels in the low physiological range of approximately 3 pg/ml for oxytocin and 1 pg/ml for vasopressin. The data on total synthesis of the neurohypophysial hormones provide a reference for studies in which physiological replacement is required and also provide the technique and base-line data to determine how translation of vasopressin and oxytocin is regulated when neurohypophysial function is altered.

Animals↗
PubMed1989

Changes in the metabolic clearance of vasopressin and in plasma vasopressinase throughout human pregnancy.

Metabolic clearance rates (MCR) of arginine vasopressin (AVP) were measured serially in five women starting before conception, during gestational weeks 7-8 (early), 22-24 (middle), and 36-38 (late pregnancy), and again 10-12 wk postpartum. Hormonal disposal rates were determined after water loading to suppress endogenous AVP release using a constant infusion method designed to achieve three different steady-state concentrations of plasma AVP (PAVP) on each test occasion. Dose schedules were altered in mid- and late pregnancy to obtain comparable AVP levels at each stage of the protocol. Prehydration decreased plasma osmolality sufficiently to suppress AVP release, as circulating AVP-neurophysin measured serially in three of the women was undetectable. The MCR of AVP was similar before conception (0.75 +/- 0.31, 0.79 +/- 0.34, and 0.76 +/- 0.28 liters/min at PAVP of 2.6 +/- 1.9, 4.7 +/- 2.4, and 8.3 +/- 3.9 pg/ml), in early pregnancy (0.89 +/- 0.34, 0.97 +/- 0.04, and 0.95 +/- 0.40 liters/min at PAVP of 2.2 +/- 2.1, 3.9 +/- 3.2, and 7.9 +/- 3.4 pg/ml), and postpartum (0.70 +/- 0.21, 0.69 +/- 0.24, and 0.75 +/- 0.20 liters/min at PAVP 3.5 +/- 1.8, 5.1 +/- 3.7, and 9.1 +/- 4.2 pg/ml). Values at mid-pregnancy (2.8 +/- 1.3, 3.0 +/- 1.2, and 2.7 +/- 1.2 liters/min at PAVP 2.3 +/- 2.2, 4.0 +/- 3.6, and 7.7 +/- 3.9 pg/ml) and late pregnancy (3.2 +/- 1.4, 3.3 +/- 1.4, and 2.9 +/- 1.2 liters/min at PAVP 1.9 +/- 2.0, 3.8 +/- 2.6, and 7.4 +/- 4.1 pg/ml) increased 3-4-fold (all P less than 0.01). Plasma vasopressinase, undetectable at 7-8 gestational wk, increased markedly by mid- and slightly more by late gestation. Finally, relationships between PAVP and urine osmolality were similar before, during, and after pregnancy. We conclude that marked increments in the MCR of AVP occur between gestational weeks 7 and 8 and mid-pregnancy, which parallel the period of greatest rise in both trophoblastic mass and plasma vasopressinase. There was no evidence of a renal resistance to AVP during gestation.

Aminopeptidases↗