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Biomedical subjects

P H Baylis

Publications and source records attributed to P H Baylis.

At least 19 recordsLinked to original sources

Exaggerated vasopressin secretion and attenuated osmoregulated thirst in human survivors of hyperosmolar coma.

AIMS/HYPOTHESIS: To test the hypothesis that subnormal thirst sensation could contribute to the development of the hypernatraemia characteristic of hyperosmolar coma, we studied osmoregulation in survivors of hyperosmolar coma. METHODS: Eight survivors of hyperosmolar coma, eight control subjects with Type II (non-insulin-dependent) diabetes mellitus and eight healthy control subjects underwent water deprivation during which measurements of thirst, plasma osmolality and vasopressin were taken. RESULTS: Water deprivation caused greater peak plasma osmolality in the hyperosmolar coma group (301.7 +/- 2.7 mmol/kg) than in Type II diabetic (294.3 +/- 3.2 mmol/kg, p < 0.01) or control group (296.9 +/- 3.0 mmol/kg, p < 0.01) and a greater increase in plasma vasopressin concentration (hyperosmolar coma, 5.8 +/- 1.3 pmol/l, Type II diabetes, 1.8 +/- 1.3 pmol/l, p < 0.001, control subjects, 2.2 +/- 1.8 pmol/l, p < 0.001). Thirst ratings were lower following water deprivation in the hyperosmolar coma group (3.5 +/- 0.8 cm) than in Type II diabetes (7.7 +/- 1.6 cm, p < 0.001) or control subjects (7.4 +/- 1.3 cm, p <0.001), and the hyperosmolar group patients drank less in 30 min following water deprivation (401 +/- 105 ml) than Type II diabetic (856 +/- 218 ml, p < 0.001) or control subjects (789 +/- 213 ml, p < 0.001). CONCLUSION/INTERPRETATION: Survivors of hyperosmolar coma have subnormal osmoregulated thirst and fluid intake, which might contribute to the hypernatraemic dehydration typical of the condition.

Aged

A review of water balance in ageing in health and disease.

The elderly are at increased risk of changes in body water and sodium, often accompanying comorbid disease states, which are associated with increased mortality. The clinical assessment of the hydration status of an elderly patient is difficult and the elderly care physician relies on both the clinical picture and laboratory investigation. Although still contentious, research suggests that the elderly may appreciate thirst less readily. However, healthy elderly may be able to produce an enhanced vasopressin response to osmotic stimulation compared to their younger counterparts, possibly in response to reduced renal function. The changes in these systems, when combined with coincident disease, place elderly patients at risk of water imbalance and electrolyte disturbance.

Aged

Does positive pressure ventilation increase arginine vasopressin in preterm neonates?

AIM: To examine the effect of intermittent positive pressure ventilation (IPPV) on plasma arginine vasopressin concentration (pAVP) in preterm neonates. METHODS: Thirty five neonates were classified, at the time of blood sampling, into three groups: unstable ventilated; stable ventilated; and stable non-ventilated. A modification of an extraction method for pAVP was developed for use in studies on very small babies, and sampling methods were compared. RESULTS: The pAVP (median, range) was similar in the ventilated (1.85 pmol/l, 0.5 to 3.4) and non-ventilated (2.0, 0.5 to 2.6) stable babies, but was significantly higher (5.7, 1.1 to 25) in the unstable group. There was an inverse correlation between systolic blood pressure and pAVP concentration. CONCLUSIONS: This study shows that in preterm neonates pAVP concentration is affected by the clinical condition and blood pressure, but not by treatment with IPPV.

Adult

Central-peripheral temperature difference, blood pressure, and arginine vasopressin in preterm neonates undergoing volume expansion.

AIM: To examine the effect of intravascular volume expansion for the treatment of hypovolaemia in sick preterm neonates. METHODS: An intravenous infusion of 20 ml per kg of 4.5% albumin was given to 14 preterm neonates. The effects on systolic blood pressure, central peripheral temperature difference (c-pT), and plasma arginine vasopressin concentration (pAVP) were measured. RESULTS: Thirteen babies showed a rise in systolic blood pressure. The six babies with the highest initial values of pAVP and c-pT showed a fall in both of these after infusion. The babies with lower initial pAVP (below 4 pmol/l) showed either a rise (two) or no change (six) after albumin infusion. There was a significant correlation between c-pT and log pAVP before (r2 = 0.61; p < 0.05) and after infusion (r2 = 0.45; p < 0.05). CONCLUSIONS: Plasma AVP concentration is related to c-pT in unwell preterm newborns. This study suggests that clinical assessment of hypovolaemia in preterm newborns is poor and could be improved by using c-pT.

Arginine Vasopressin

Hypothalamic adipsic syndrome: diagnosis and management.

Patients with hypothalamic adipsic syndrome, especially in conjunction with diabetes insipidus, pose management difficulties. They are at risk of both under- and over-hydration. We present 4 patients with hypothalamic adipsic syndromes, due to different causes, illustrating the practical difficulties encountered in this condition. The principles of management, with a sliding scale of water intake related to changes in daily body weight, are discussed.

Adolescent

Atrial natriuretic peptide in preeclampsia: metabolic clearance, sodium excretion and renal hemodynamics.

To further elucidate the role of atrial natriuretic peptide (ANP) in preeclampsia, its metabolic clearance (MCRANP) was determined concomitantly with its effects on sodium excretion (UNa), glomerular filtration rate (GFR), and effective renal plasma flow (ERPF). Ten untreated preeclamptic primigravidae (PET) were studied at 29-37 wk gestation and again 4 mo postpartum (PP). Basal plasma concentration of ANP was significantly increased in PET compared with PP (14.8 +/- 1.9 vs. 4.1 +/- 0.5 pmol/l, respectively; P < 0.0001). MCRANP in PET and PP was 5.0 +/- 0.8 and 4.9 +/- 0.5 l/min [not significant (NS)], respectively. In PET, infusion of ANP produced (basal vs. ANP) a natriuresis (UNa 0.14 +/- 0.02 vs. 0.28 +/- 0.04 mmol/min, P < 0.001) and an increase in GFR (97 +/- 7 vs. 106 +/- 8 ml/min, P < 0.05), with ERPF unchanged (609 +/- 24 vs. 634 +/- 29 ml/min, NS). In PP, ANP infusion also produced a natriuresis (UNa 0.20 +/- 0.02 vs. 0.25 +/- 0.02 mmol/min, P = 0.01), no significant change in GFR (109 +/- 7 vs. 102 +/- 4 ml/min), and a significant reduction in ERPF (514 +/- 22 vs. 409 +/- 18 ml/min, P < 0.0001). Analysis of variance demonstrated a greater natriuretic effect of ANP in PET compared with PP (P < 0.05), similarly a significant difference in the effect of ANP on ERPF (P < 0.01) and GFR (P < 0.05) was seen but not on filtration fraction (P = 0.35).

Adult

Persistent nephrogenic diabetes insipidus following lithium therapy.

We report the case of a patient who developed severe hypernatraemic dehydration following a head injury. Ten years previously he had been diagnosed to have lithium-induced nephrogenic diabetes insipidus, and lithium therapy had been discontinued. He remained thirsty and polyuric despite cessation of lithium and investigations on admission showed him to have normal osmoregulated thirst and vasopressin secretion, with clear evidence of nephrogenic diabetes insipidus. Lithium induced nephrogenic diabetes insipidus is considered to be reversible on cessation of therapy but polyuria persisted in this patient for ten years after lithium was stopped. We discuss the possible renal mechanisms and the implications for management of patients with lithium-induced nephrogenic diabetes insipidus.

Bipolar Disorder

Metastatic prolactinoma: effect of octreotide, cabergoline, carboplatin and etoposide; immunocytochemical analysis of proto-oncogene expression.

A 49-yr-old woman presented with an extensive prolactinoma (serum PRL > 10,000 mU/L, normal range < 450 mU/L). Over a 5-yr period following transsphenoidal surgery and pituitary irradiation, she became increasingly resistant to high doses of bromocriptine and underwent transfrontal surgery followed by stereotactic radiotherapy. In spite of these treatments, serum prolactin estimations rose progressively to > 100,000 mU/L. Magnetic resonance imaging scanning demonstrated a massive cystic tumor invading the temporal lobes, extending into the cervical and thoracic spine, with metastases to cervical lymph nodes. High-dose cabergoline administration resulted in a 30% decrease in serum PRL. Octreotide was administered as a continuous sc infusion with a profound analgesic effect on facial pain but with no effect on tumor progression. She was treated with a course of chemotherapy consisting of carboplatin and etoposide without any noticeable effect. The patient died 6 months following chemotherapy. Immunocytochemical analysis demonstrated positive nuclear staining for WAF-1, Rb protein, c-myc, and p53 both in the original and metastatic tumors. The metastases but not the primary tumor stained for c-jun. Metastatic prolactinoma remains a therapeutic challenge. It is associated with a variable proto-oncogene expression, which may be coincidental or causal. Cabergoline had no advantage over bromocriptine. Octreotide relieved facial pain but did not alter tumor progression. An effective therapy for metastatic prolactinoma remains to be identified.

Antineoplastic Agents, Hormonal

Vasopressin release during orthostatic hypotension after cardiac transplantation.

At the time of cardiac transplantation all nerves from the donor ventricles are cut. These nerves may regrow, but there is no method of measuring any regrowth. Arginine vasopressin (AVP) release was studied during hypotension induced by head-up tilt and lower body negative pressure (LBNP) in transplant recipients and in normal controls. Subjects were tilted to 60 degrees for up to 60 min or until symptomatic. Lower body negative pressure (40 mmHg) was applied for 10 min after 30 min rest. Seven of 17 transplant recipients and 11 of 12 controls became symptomatic during tilt testing, and 9 of 12 controls and 9 of 17 transplant recipients became symptomatic after 10 min of LBNP. Symptoms during tilt did not predict symptoms during LBNP. Resting AVP levels were similar but osmolality was greater in transplant recipients. Resting haematocrit was reduced, and atrial natriuretic peptide increased in transplant recipients, suggesting increased plasma volume. In symptomatic subjects, changes in humoral concentrations were similar when compared between transplant recipients and normals, except that the rise in AVP at the time of symptoms was reduced in transplant recipients, with a comparable drop in blood pressure consistent with persistent cardiac afferent denervation in a subset of transplant recipients.

Adult

The metabolic clearance of atrial natriuretic peptide during human pregnancy.

OBJECTIVE: Our purpose was to determine whether human pregnancy alters the metabolic clearance and natriuretic effect of atrial natriuretic peptide. STUDY DESIGN: The metabolic clearance rate of atrial natriuretic peptide (ANP 99-126) was measured serially in nine normotensive primigravid women studied in early and late pregnancy and again 4 months post partum (nonpregnant). Metabolic clearance of atrial natriuretic peptide was determined by use of a two-tier constant infusion technique (6 and 12 ng/kg/min, respectively). Sodium excretion was determined from 30-minute urine collections taken before and during infusion of atrial natriuretic peptide at both 6 and 12 ng/kg/min. RESULTS: Basal plasma atrial natriuretic peptide levels increased with gestation: in early pregnancy 18.0 +/- 2.7 pg/ml, in late pregnancy 22.6 +/- 4.2 pg/ml, and post partum 19.5 +/- 3.6 pg/ml. Infusion of atrial natriuretic peptide at 6 and 12 ng/kg/min produced two distinct physiologic plasma levels of atrial natriuretic peptide. The metabolic clearance rates for nonpregnant women and those in early and late pregnancy at 6 and 12 ng/kg/min, respectively, were 3.4 +/- 0.4 and 2.9 +/- 0.4 L/min at plasma atrial natriuretic peptide levels of 86.2 +/- 13.2 and 179.8 +/- 42.5 pg/ml, respectively, 4.3 +/- 0.5 and 4.3 +/- 0.5 L/min at plasma atrial natriuretic peptide levels of 61.1 +/- 4.9 and 131 +/- 20.9 pg/ml (p < 0.01, nonpregnant vs early pregnancy), and 3.8 +/- 0.6 and 3.8 +/- 0.5 L/min at plasma atrial natriuretic peptide levels of 72 +/- 8.0 and 136 +/- 18.3 pg/ml (p < 0.05, nonpregnant vs late pregnancy), respectively. Infusion of atrial natriuretic peptide produced natriuresis in both pregnant and nonpregnant states; sodium excretion (basal to atrial natriuretic peptide infusion at 12 ng/kg/min) increased from 133 +/- 19 to 207 +/- 18 mumol/min, 129 +/- 21 to 374 +/- 35 mumol/min, and 128 +/- 20 to 221 +/- 33 mumol/min in nonpregnant women and those in early and late pregnancy, respectively. CONCLUSIONS: The metabolic clearance of atrial natriuretic peptide increased by 16 weeks' gestation and remained elevated thereafter. There appears to be no attenuation of the natriuretic effect of infused atrial natriuretic peptide in normotensive human pregnancy.

Atrial Natriuretic Factor

The short Synacthen and insulin stress tests in the assessment of the hypothalamic-pituitary-adrenal axis.

OBJECTIVE: The best dynamic test for the assessment of the hypothalamic-pituitary-adrenal axis and the interpretation of the cortisol levels, remain a matter of controversy. We aimed to establish normal ranges with current assays, for both the short Synacthen (SST) and insulin stress tests (IST) and then to use these data to examine whether the SST can satisfactorily substitute for the IST in assessment of the hypothalamic-pituitary-adrenal axis. DESIGN: Thirty SSTs and 27 ISTs were performed on different healthy volunteers. The results of all paired tests performed on patients in the last three years are reviewed. SETTING: Programmed Investigation Unit. SUBJECTS: Fifty-seven healthy volunteers and 166 patients. MAIN OUTCOME MEASURES: Basal serum cortisol concentration and cortisol values obtained at 30 and 60 minutes during the SST compared to the maximum obtained with adequate hypoglycemia (plasma glucose < 2 mmol/l) during an IST. RESULTS: From normal data the mean-2SD 30-minute value during the SST was 392 nmol/l and 60-minute value was 497 nmol/l. The maximal cortisol response (mean - 2SD) during the IST was 519 nmol/l. Sixty patients failed the IST, none of whom had a basal cortisol > 450 nmol/l and only six (10%) had a 30-minute cortisol value > 600 nmol/l. The 30-minute value provided a better index than the 60-minute value. The basal, 30 and 60-minute values during the SST all correlated positively and significantly with the maximal cortisol on IST. The correlations persisted for all microadenomas and macroadenomas secreting prolactin, gonadotrophins or growth hormone, patients undergoing either pre or post-adenomectomy evaluation, and in those patients who had received long-term steroids provided that the medication had been reduced and stopped two days prior to admission. CONCLUSIONS: Using a 30-minute cortisol value > 600 nmol/l as a cut-off, the short Synacthen test provides a suitable substitute for the insulin stress test. Adopting this policy will decrease the number of insulin stress tests performed by one-quarter and thus provide a substantial saving without detriment to patient care.

Adrenal Cortex Function Tests

Effect of atrial natriuretic peptide on renal hemodynamics and sodium excretion during human pregnancy.

The effect of infused atrial natriuretic peptide (ANP) on sodium excretion (UNa), glomerular filtration rate (GFR), and effective renal plasma flow (ERPF) was studied in 12 normotensive primigravidae at 32 wk gestation [late pregnancy (LP)] and again 4 mo postpartum [nonpregnant (NP)]. Three 20-min steady-state (renal) clearances of inulin and p-aminohippurate were used to measure GFR and ERPF, respectively, before and after infusion of ANP at 2 pmol.kg-1.min-1. Basal plasma ANP (pANP) was increased in LP compared with NP [7.8 +/- 0.6 vs. 3.3 +/- 0.4 pmol/l (P < 0.0001), respectively]. In LP, infusion of ANP increased pANP from 7.8 +/- 0.6 to 21.8 +/- 1.4 pmol/l (P < 0.00001), which produced a natriuresis [UNa of 0.18 +/- 0.02 vs. 0.25 +/- 0.03 mmol/min (P = 0.03), respectively], with no change in GFR (153 +/- 13 vs. 142 +/- 8 ml/min, P = 0.16) but a significant reduction in ERPF (766 +/- 52 vs. 660 +/- 31 ml/min, P = 0.002). In NP, ANP infusion increased pANP from 3.3 +/- 0.4 to 27.7 +/- 2.5 pmol/l (P < 0.00001), which produced no significant natriuresis [UNa of 0.22 +/- 0.07 vs. 0.26 +/- 0.09 mmol/min (P = 0.15), respectively] and no change in GFR (87 +/- 3 vs. 89 +/- 3 ml/min), but again a reduction in ERPF (486 +/- 17 vs. 414 +/- 9 ml/min, P < 0.001).

Atrial Natriuretic Factor

Thirst induced by a suckling episode during breast feeding and relation with plasma vasopressin, oxytocin and osmoregulation.

OBJECTIVE: There have been anecdotal reports of increased maternal thirst during breast feeding, but the physiological mechanisms remain obscure. We have assessed and quantified the stimulation of maternal thirst during breast feeding (suckling), and correlated the changes with plasma oxytocin and vasopressin levels. DESIGN: A within subject design was used with each subject acting as her own control. Each subject participated in a suckling period and a control non-suckling period the order of which was counterbalanced. SUBJECTS: Ten healthy breastfeeding women ranging from 28 to 52 days post partum. MEASUREMENTS: Thirst (assessed by a visual analogue scale), plasma vasopressin, plasma oxytocin (pOT), plasma osmolality and haematocrit, blood pressure, volume of milk transferred to baby, volume of water drunk immediately following each experimental period. RESULTS: Thirst increased significantly more over a suckling period than over a comparable control period (P = 0.013). The peak level of thirst correlated with the volume of water consumed to satiety following the suckling period (r = 0.7, P = 0.024). As expected, pOT levels rose significantly in response to suckling (P < 0.001). Six women demonstrated a close relation between thirst and oxytocin response during the suckling period. Despite significant changes in thirst during suckling there was no increase in plasma vasopressin or in osmoregulatory parameters. CONCLUSIONS: This study confirms that suckling is a potent stimulus to thirst in the mother, and is not associated with vasopressin release or dependent on any measurable alterations in osmoregulation. What actually stimulates thirst during breast feeding remains unknown, but there are two potential explanations for these observations: (1) suckling sends nerve impulses to the paraventricular and supraoptic nuclei in the hypothalamus which may have afferents within the central nervous system which stimulates a thirst response simultaneous with oxytocin release; (ii) a learned anticipation of thirst may be occurring in a situation associated with expectant fluid loss to preserve homeostasis.

Blood Pressure