Mycotic carotid pseudoaneurysm: staged endovascular and surgical repair.

Mycotic carotid pseudoaneurysms are rare and challenging to manage. Traditional surgical approaches are technically demanding and can be associated with a high morbidity and mortality. The use of endovascular stents in infected fields remains controversial, and long-term efficacy has not been fully clarified. We describe a case where a combined staged endovascular and open surgical approach was used to successfully manage a mycotic carotid pseudoaneurysm that developed following dental extraction. A covered endovascular stent was used to temporarily exclude the infected pseudoaneurysm, before proceeding to early definitive surgical management. We suggest that staged endovascular therapy followed by early surgical repair should be considered for this difficult surgical problem.

A multiplanet system of super-Earths orbiting the brightest red dwarf star GJ 887.

The closet exoplanets to the Sun provide opportunities for detailed characterization of planets outside the Solar System. We report the discovery, using radial velocity measurements, of a compact multiplanet system of super-Earth exoplanets orbiting the nearby red dwarf star GJ 887. The two planets have orbital periods of 9.3 and 21.8 days. Assuming an Earth-like albedo, the equilibrium temperature of the 21.8-day planet is ~350 kelvin. The planets are interior to, but close to the inner edge of, the liquid-water habitable zone. We also detect an unconfirmed signal with a period of ~50 days, which could correspond to a third super-Earth in a more temperate orbit. Our observations show that GJ 887 has photometric variability below 500 parts per million, which is unusually quiet for a red dwarf.

Infrapopliteal drug-eluting stents for chronic limb ischemia.

OBJECTIVE: We report our experience with the elective placement of below-knee, drug-eluting stents in patients with chronic limb ischemia. BACKGROUND: Infrapopliteal percutaneous transluminal angioplasty has been associated with a lower rate of procedural success and high rate of restenosis because of the small size of the tibial vessels and the prevalence of calcified and diffuse atherosclerotic disease. Prior published data reports 3-year patency rates below 25%. Bare metal stents have been reported in bailout situations. Drug-eluting stents have markedly reduced restenosis compared to bare metal stents in the coronary vasculature, but there is little data supporting the use of these devices below the knee. METHODS: Elective placement of drug-eluting stents in infrapopliteal lesions was performed on 10 patients with severe (> or =Fontaine Stage IIb) claudication (n = 1) or limb-threatening ischemia (n = 9) (rest pain, nonhealing ulcers and gangrene). RESULTS: A total of 17 drug-eluting stents were electively placed in 12 below-knee arteries in 10 patients, resulting in an average of 1.7 +/- 0.7 stents per patient. The mean lesion length was 24.8 +/- 10.9 mm, the mean total stent length was 38.3 +/- 19.1 mm, and the mean nominal stent diameter was 2.8 +/- 0.3 mm. One patient required target vessel revascularization (TVR) at 3 weeks because of stent thrombosis. TVR was 10% at 12.4 +/- 6.5 months of follow-up. Clinically driven angiography in three different patients was performed at 4, 15, and 16 months and confirmed drug-eluting stent patency in each case. CONCLUSIONS: The use of below-knee drug-eluting stents is feasible and appears to be safe in our small series of complex infrapopliteal lesions causing chronic limb ischemia. The occurrence of a single case of stent thrombosis warrants continued observation in this cohort. Prospective clinical trials will be necessary to confirm the benefits and justify the costs of this strategy for treating patients with infrapopliteal culprit lesions and chronic limb ischemia.

Interaction of vasopressin and oxytocin with human breast carcinoma cells.

The arginine vasopressin and oxytocin content of normal and cancerous human breast tissue were measured using radioimmunoassay. Both peptides were present in amounts greater than that found in the circulation, but no difference between normal and malignant tissues was found. Binding of [3H]oxytocin and [3H]vasopressin were characterized in human breast carcinoma cells (MCF7 cells). Binding of both hormones to MCF7 cells was specific and saturable, the vasopressin receptor found to be of the V1 subtype. Scatchard analyses of the data were linear, indicating a single high affinity, low capacity binding site for each hormone (vasopressin: KD = 47.4 +/- 1.6 nmol/liter, Bmax = 27,300 +/- 6,500 sites/cell; oxytocin: KD = 51.3 +/- 0.4 nmol/liter, Bmax = 87,000 +/- 4,000 sites/cell). The effects of vasopressin and oxytocin on the growth of MCF7 cells were assessed using protein accumulation and cell numbers. Vasopressin at 10-1000 pmol/liter was mitogenic for MCF7 cells, but higher doses (10 nmol/liter) were growth inhibitory. Oxytocin was also mitogenic for MCF7 cells but to a lesser extent than vasopressin. In conclusion, we suggest that vasopressin and possibly oxytocin may be important modulators of the growth of some human breast carcinomas.

Vasoactive intestinal peptide stimulates glycolysis in pituitary tumours; 1H-NMR detection of lactate in vivo.

1H- and 31P-NMR spectroscopy has been applied to rats carrying implanted tumours in vivo, and used to observe simultaneous changes in intracellular pH (pHi) and lactate concentration during the stimulatory action of vasoactive intestinal polypeptide (VIP). A maximal decrease in pHi to a mean of 0.29 units below basal values was recorded. At the same time, 11 min after VIP, a maximal increase in tumour lactate was found, with a mean value of 150% of the basal concentration. The magnitude of these changes was compatible with in vitro measurements of basal lactate concentration and buffering capacity made on the same tumour line. It is concluded that VIP stimulates glycolysis by the tumour cells, resulting in an accumulation of lactate and a consequent fall in pHi.

Renal artery stent placement: utility in lesions difficult to treat with balloon angioplasty.

OBJECTIVES: We assessed the safety and efficacy of stent placement in patients with poorly controlled hypertension and renal artery stenoses, which are difficult to treat with balloon angioplasty alone. BACKGROUND: Preliminary experience with stent placement suggests improved results over balloon angioplasty alone in patients with atherosclerotic renal artery stenosis. METHODS: Balloon-expandable stents were placed in 100 consecutive patients (133 renal arteries) with hypertension and renal artery stenosis. Sixty-seven of the patients had unilateral renal artery stenosis treated and 33 had bilateral renal artery stenoses treated with stents placed in both renal arteries. RESULTS: Angiographic success, as determined by quantitative angiography, was obtained in 132 (99%) of 133 lesions. Early clinical success was achieved in 76% of the patients. Six months after stent placement, the systolic blood pressure was reduced from 173 +/- 25 to 147 +/- 23 mm Hg (p < 0.001); the diastolic pressure from 88 +/- 17 to 76 +/- 12 mm Hg (p < 0.001); and the mean number of antihypertensive medications per patient from 2.6 +/- 1 to 2.0 +/- 0.9 (p < 0.001). Angiographic follow-up at a mean of 8.7 +/- 5.0 months in 67 patients revealed restenosis (>50% diameter narrowing) in 15 (19%) of 80 stented vessels. CONCLUSIONS: Renal artery stenting is an effective treatment for renovascular hypertension, with a low angiographic restenosis rate. Stent placement appears to be a very attractive therapy in patients with lesions difficult to treat with balloon angioplasty such as renal aorto-ostial lesions and restenotic lesions, as well as after a suboptimal balloon angioplasty result.

Coronary stenting in cardiac allograft vasculopathy.

OBJECTIVE: The purpose of this study was to evaluate acute angiographic success, in-hospital complications and long-term outcome after intracoronary stenting in patients with cardiac allograft vasculopathy. BACKGROUND: The application of conventional interventional modalities to treat discrete lesions in patients with cardiac allograft vasculopathy is associated with higher procedural morbidity, mortality and higher restenosis compared to atherosclerotic coronary artery disease. Elective coronary stenting has been shown to lower restenosis rates and improve long-term outcome in selected patients with native coronary artery disease; however, its safety and efficacy in reducing restenosis in patients with cardiac allograft vasculopathy is unknown. METHODS: Ten patients with 19 discrete lesions in a major coronary artery without diffuse distal disease underwent intracoronary stenting using Palmaz-Schatz stents. The average stent size was 3.4 mm, and the stent/artery ratio was 0.99+/-0.07. Eight of ten (80%) patients received antiplatelet therapy (aspirin plus ticlopidine) only. RESULTS: Procedural success was 100% with no in-hospital stent thrombosis, Q-wave myocardial infarction or death. Minimal luminal diameter increased from 0.83+/-0.38 mm to 3.23+/-0.49 mm after stenting. Diameter stenosis decreased from 74.91+/-11.52% to 5.90+/-4.09% after stenting. Follow-up angiography was performed in 8 of 10 (80%) patients and 16 of 19 (84%) lesions. Target lesion revascularization was required in 2 of 10 (20%) patients and 3 of 16 (19%) lesions. Allograft survival was 7 of 10 (70%) at the end of 22+/-11 months follow-up. CONCLUSIONS: Intracoronary stenting can be performed safely with excellent angiographic success in selected patients with cardiac allograft vasculopathy. The restenosis rate appears to be low despite the aggressive nature of the disease. A multicenter study with a larger number of patients is required to assess its efficacy in reducing restenosis and improving allograft survival.

Energy metabolism in rat pituitary tumors during stimulation of prolactin by vasoactive intestinal polypeptide and thyrotropin-releasing hormone: a study with nuclear magnetic resonance spectroscopy.

The effect of the peptides TRH and vasoactive intestinal polypeptide (VIP) on phosphate-bound energy of GH3 tumor cells in vivo was investigated using the noninvasive technique of topical 31P-nuclear magnetic resonance spectroscopy. VIP (4.0 micrograms/100 g BW) caused a reduction in the high energy metabolite phosphocreatine and an increase in inorganic phosphate. In the same experiments (n = 9), VIP stimulated PRL secretion to a value of 146% +/- 13 of basal concentrations. The change in the inorganic phosphate-phosphocreatinine ratio had a positive correlation with the increase in PRL secretion (P less than 0.001), indicating a VIP-induced energy consumption for a process related to PRL secretion. In separate experiments, in vitro, it was confirmed that VIP increased energy consumption by demonstrating an increase in glycogenolysis by the pituitary tumor cells. TRH also increased PRL secretion to 145% +/- 23 of basal values but, in contrast, did not induce changes in energy metabolites detectable by nuclear magnetic resonance. It is concluded that VIP and TRH promote PRL release through different stages in the secretion process.

Neurohypophysial hormones in the adrenal medulla.

Immunoreactive oxytocin and arginine vasopressin (AVP) were measured in the adrenal medulla of both rat and man as well as in tissue from two pheochromocytomas using highly specific RIAs. In all instances, oxytocin predominated over AVP. The concentrations of oxytocin ranged from 19.9-162.7 pg/g tissue, whereas those for AVP were 9.8-102 pg/g. These values are far greater than those found in plasma. The oxytocin- and AVP-related neurophysins were also present in large quantities in human adrenal medulla and pheochromocytoma. Identity of the peptides was confirmed by demonstrating parallel immunoreactivity with standard compounds and by the high performance liquid chromatographic profiles. In experiments carried out in rats, the source of the adrenal medullary AVP and oxytocin did not appear to be the paraventricular nucleus. It is postulated that the neurohypophysial peptides may have a regulatory function in the secretion of catecholamines.

Vasopressin in human cerebrospinal fluid.

Arginine vasopressin was measured by RIA in samples of plasma and cerebrospinal fluid (CSF) taken synchronously from 62 patients with proven or suspected disorders of the central nervous system in order to determine the relationship between the secretion of vasopressin into the systemic circulation and that into the CSF. In 12 patients without endocrine or brain disease, mean plasma values (+/- SD) were 2.8 +/- 0.7 pg/ml and CSF values were 2.4 +/- 0.7 pg/ml. Thirty-six patients with various intracranial disorders had plasma and CSF values which were both within the range of 1-4 pg/ml. Eight patients had raised plasma concentrations, but their CSF levels were within the normal range. One patient with posttraumatic diabetes insipidus and 2 patients with subarachnoid hemorrhage had concentrations of CSF vasopressin which were greater than plasma levels. These results indicate that a blood CSF barrier to vasopressin exists in man and that under certain pathological conditions excessive amounts of the hormone can be secreted into the CSF independently of that which is released into the blood, a finding which could have clinical significance in disorders of brain function.

Hypothalamic-pituitary function in patients with craniopharyngiomas.

Hypothalamic-pituitary function was investigated in 20 patients with craniopharyngioma, and all showed some degree of hypopituitarism. Pituitary-adrenal dysfunction was present in 50% of the patients whereas all but one had deficiencies of growth hormone and gonadotropin. Serum thyroxine was low in 13 patients, and in a further six there was an abnormal response of thyrotropin (TSH) to thyrotropin-releasing hormone (TRH). Prolactin levels were normal in over half the patients tested and only moderately elevated in the remainder. Gonadotropins failed to increase adequately after gonadotropin-releasing hormone (LRH) in all but one patient, and the response gave no indication of the predominantly hypothalamic site of the tumors.

The evaluation of sodium valproate in the treatment of Nelson's syndrome.

It has previously been reported that sodium valproate (Epilim) lowers plasma ACTH levels in Nelson's syndrome. This report describes further experience with its use. Ten patients with Nelson's syndrome were treated with sodium valproate (600-1200 mg/day) for 5-32 weeks. Plasma ACTH was measured by cytochemical methods and RIA. Initial treatment for 5-12 weeks significantly (P less than 0.005) lowered plasma ACTH from a pretreatment mean of 2460 +/- 1870 ng/liter to 480 +/- 330 ng/liter, and the ACTH circadian rhythm was restored in two patients. On discontinuing treatment, plasma ACTH levels remained suppressed for 3 weeks and rose to pretreatment values in 5-12 weeks. Two patients' plasma ACTH levels failed to show a second response to treatment, while a third patient had a favorable second response to treatment over 32 weeks. In six patients, skin pigmentation lightened with treatment, and in one patient, a reduction in size of a pituitary microadenoma, demonstrated radiographically, occurred with treatment. gamma-Aminobutyric acid and sodium valproate were shown to be ineffective in inhibiting ACTH secretion from cultured pituitary tumor cells from a patient with Nelson's syndrome. The results show that sodium valproate is effective in some cases of Nelson's syndrome. We suggest that it reduces the hypersecretion of ACTH by enhancing gamma-aminobutyric acid function in the hypothalamus, thereby inhibiting the release of corticotropin-releasing factor.

VIP enhances TRH-stimulated prolactin secretion of pituitary tumours. Studies with 31P NMR.

Intravenous thyrotrophin releasing hormone (TRH) caused a 6.5-fold increase in plasma prolactin (PRL) in rats carrying implanted pituitary tumours. Vasoactive intestinal polypeptide (VIP) had no effect, but TRH given after VIP raised TRH stimulated secretion 13-fold above basal. 31P NMR spectroscopy showed that VIP caused a decrease in high energy metabolites (depleted phosphocreatine, elevated inorganic phosphate and lowered intracellular pH). TRH alone caused a similar but smaller effect; given after VIP, it caused no detectable depletion. We suggest that the changes in high energy metabolite concentrations reflect increased cellular energy consumption consistent with a priming process (stage 1) in PRL secretion, followed by hormone release (stage 2). VIP induces stage 1 whereas RTH induced both stages.

Effects of arginine vasopressin (AVP) infusions on circulating concentrations of platelet AVP, factor VIII: C and von Willebrand factor.

To study the possible role of arginine vasopressin (AVP) in the control of haemostasis AVP infusions at 3 doses (0.1, 0.2 and 0.3 mU/kg/min) were performed in 6 male volunteers. Both plasma and platelet AVP concentrations rose in a dose-related manner. At doses of 0.2 and 0.3 mU/kg/min there was an increase in the plasma concentrations of both plasma Factor VIII and von Willebrand factor. The data support the hypothesis that AVP, by interacting with platelets and stimulating factor VIII and von Willebrand factor release, plays a role in the control of haemostasis.

Effects of renal artery stent implantation in patients with renovascular hypertension presenting with unstable angina or congestive heart failure.

This study evaluates the effect of renal artery stent implantation in patients with renovascular hypertension presenting with unstable angina (n = 20) or congestive heart failure (n = 28). There was a significant improvement in the Canadian Cardiovascular Society angina class and the New York Heart Association functional class, and at 8.4 +/- 6.4 month follow-up.

Causes of higher in-hospital mortality in women than in men after acute myocardial infarction.

Clinical, laboratory and cardiac catheterization parameters were reviewed in 355 men and 155 women hospitalized at a tertiary care referral center between February 1987 and December 1991 to analyze why women have a higher in-hospital mortality rate than do men after acute myocardial infarction. Hospital mortality was 21.4% in women and 12.1% in men (p = 0.007). In comparison with men, women were older (63.3 +/- 11.9 vs 60.5 +/- 12.6 years; p = 0.023), had more systemic hypertension (46.5 vs 34.4%; p = 0.001) and higher serum total cholesterol levels (211 +/- 51 vs 197 +/- 49 mg/dl; p = 0.0015), sought medical care later (8.9 vs 5.3 hours; p = 0.026), were referred later (47.7 vs 43.7 hours; p = 0.063) and had more shock (34.8 vs 24.2%; p = 0.013). Logistic regression analysis revealed 5 variables predictive of hospital mortality; age > 65 years, diabetes, shock, non-Q-wave infarction, and not undergoing cardiac catheterization. Gender was of borderline significance in predicting hospital mortality. Cardiac catheterization, performed in 88% of women and 87% of men, showed similar rates of 1-, 2- and 3-vessel disease, and similar characteristics of the infarction-related artery. The differences in hospital mortality between men and women are due to a combination of pre- and in-hospitalization factors in women. The excess mortality is not due to differences in disease severity as evaluated by cardiac catheterization information.

Blood-cerebrospinal fluid barrier to arginine-vasopressin, desmopressin and desglycinamide arginine-vasopressin in the dog.

The passage of 125I-labelled arginine-vasopressin (AVP) and its analogues desmopressin (DDAVP) and desglycinamide arginine-vasopressin (DGAVP) into cerebrospinal fluid (CSF) has been studied in the dog. After intravenous injection or infusion of these peptides radioactive substances were found in the CSF in amounts ranging from 0.5 to 1.4% of the total plasma radioactivity. However, only DDAVP could be identified in the CSF as the unmetabolized peptide. This observation may be related to the long plasma half-life of DDAVP which was found to be 50 min, compared with a half-life of 13 min for AVP and 8 min for DGAVP. After the intranasal administration of either [3H]AVP or 125I-labelled AVP similar results were obtained. Radioactivity was again present in the CSF but no AVP could be identified. These observations showed that the intranasal route of administration provides no increased access to the CSF. The existence of a blood-CSF barrier to AVP is confirmed and indicates that the concentrations of the hormone normally found in CSF arise from sources other than the blood.

Pituitary hormone response to brain stimulation in man.

Plasma cortisol, GH and LH responses to electrical stimulation of the orbital part of the frontal lobe and the cingulate area of the brain were studied in patients undergoing limbic leucotomy. In six out of 15 patients the plasma cortisol levels increased by 5-7--18-0 mug/100 ml after orbito-frontal stimulation whereas plasma GH values did not rise during this period. Plasma LH levels remained unchanged. No definite hormone responses could be attributed to stimulation of the cingulate area. It appears that the orbito-frontal area of the brain is concerned with augmenting the release of ACTH but not that of GH or LH.

Metabolism of [14C]testosterone by human foetal and adult brain tissue.

The metabolism of [14C]testosterone in vitro by various areas of the human foetal brain has been studied and compared with that of adult brain. The predominant metabolites were 5alpha-dihydrotestosterone and 5alpha-androstane-3alpha, 17beta-diol, and also androstenedione, and all areas of the foetal brain showed similar activity. In the foetal pituitary gland, the activity of 5alpha-reductase was less prominent than that of 17beta-hydroxysteroid-dehydrogenase. Small quantities of oestradiol-17beta were produced from testosterone by the hypothalamus, temporal lobe and amygdala only, and no aromatization could be detected in the pituitary gland. 5alpha-Reductase activity was much lower in adult brain tissues and no oestradiol was identified in adult temporal lobe tissue.

Effect of bromocriptine on DNA synthesis, growth and hormone secretion of spontaneous pituitary tumours in the rat.

The 'spontaneous' development of pituitary tumours has been studied in the Wistar-Furth strain of rat. In females aged 64--135 weeks the incidence was as high as 69% whereas in males aged 72--116 weeks only 6% developed tumours. Hyperprolactinaemia was invariably associated with these spontaneous pituitary tumours but excessive secretion of growth hormone (GH) was found in one animal only. Bromocriptine inhibited secretion of prolactin and DNA synthesis of the tumours. In a mixed GH- and prolactin-secreting tumour transplanted to a peripheral site, bromocriptine reduced the size of the tumour as well as the secretion of both hormones. Oestradiol reversed the inhibitory action of bromocriptine on prolactin secretion and tumour growth but failed to influence the reduction in GH secretion caused by the drug.