Ti n+1C n MXenes with fully saturated and thermally stable Cl terminations.

MXenes are a rapidly growing family of 2D materials that exhibit a highly versatile structure and composition, allowing for significant tuning of the materials properties. These properties are, however, ultimately limited by the surface terminations, which are typically a mixture of species, including F and O that are inherent to the MXene processing. Other and robust terminations are lacking. Here, we apply high-resolution scanning transmission electron microscopy (STEM), corresponding image simulations and first-principles calculations to investigate the surface terminations on MXenes synthesized from MAX phases through Lewis acidic melts. The results show that atomic Cl terminates the synthesized MXenes, with mere residual presence of other termination species. Furthermore, in situ STEM-electron energy loss spectroscopy (EELS) heating experiments show that the Cl terminations are stable up to 750 °C. Thus, we present an attractive new termination that widely expands the MXenes' functionalization space and enables new applications.

Late symptoms in long-term gynaecological cancer survivors after radiation therapy: a population-based cohort study.

BACKGROUND: We surveyed the occurrence of physical symptoms among long-term gynaecological cancer survivors after pelvic radiation therapy, and compared with population-based control women. METHODS: We identified a cohort of 789 eligible gynaecological cancer survivors treated with pelvic radiation therapy alone or combined with surgery in Stockholm or Gothenburg, Sweden. A control group of 478 women was randomly sampled from the Swedish Population Registry. Data were collected through a study-specific validated postal questionnaire with 351 questions concerning gastrointestinal and urinary tract function, lymph oedema, pelvic bones and sexuality. Clinical characteristics and treatment details were retrieved from medical records. RESULTS: Participation rate was 78% for gynaecological cancer survivors and 72% for control women. Median follow-up time after treatment was 74 months. Cancer survivors reported a higher occurrence of symptoms from all organs studied. The highest age-adjusted relative risk (RR) was found for emptying of all stools into clothing without forewarning (RR 12.7), defaecation urgency (RR 5.7), difficulty feeling the need to empty the bladder (RR 2.8), protracted genital pain (RR 5.0), pubic pain when walking indoors (RR 4.9) and erysipelas on abdomen or legs at least once during the past 6 months (RR 3.6). Survivors treated with radiation therapy alone showed in general higher rates of symptoms. CONCLUSION: Gynaecological cancer survivors previously treated with pelvic radiation report a higher occurrence of symptoms from the urinary and gastrointestinal tract as well as lymph oedema, sexual dysfunction and pelvic pain compared with non-irradiated control women. Health-care providers need to actively ask patients about specific symptoms in order to provide proper diagnostic investigations and management.

Enhanced vasodilator responses to calcitonin gene-related peptide (CGRP) in subcutaneous arteries in human hypertension.

Isolated segments (1-2 mm) of small subcutaneous arteries (diameter 0.1-0.9 mm) and veins (0.1-1.0 mm) from patients with hypertension (essential n = 13, renovascular n = 6) and controls (n = 17) were examined. The relaxant responses to the sensory transmitters calcitonin gene-related peptide (CGRP) and substance P, and the contractile responses to potassium and noradrenaline were studied. Enhanced dilatory responses (E(max)) but no change in sensitivity (pEC50) were demonstrated in the arteries but not in the veins to CGRP in hypertensives (P < 0.01) as compared with normotensives, and in the hypertensive subgroups (essential hypertension, P < 0.05; renovascular hypertension, P< 0.05). The relaxant responses to substance P were not altered either in arteries or in veins of hypertensives. Furthermore, there were no differences in the contractile responses to 60 mM potassium or to 10 microM noradrenaline between the groups. The results suggest that the enhanced vasodilator response to CGRP in hypertension is an adaptive reaction. The elevated blood pressure may be augmented by vasodilatory activity since different subgroups of hypertensives showed the same results. However, other common characteristics of hypertension (eg, medication, metabolic disturbances) may have also influenced the results.

Vasodilation in human subcutaneous arteries induced by neuropeptide Y is mediated by neuropeptide Y Y1 receptors and is nitric oxide dependent.

Neuropeptide Y (NPY) is known as a potent vasoconstrictor of peripheral blood vessels both in vivo and in vitro. There have been reports suggesting that NPY also has a dilatory effect. The aim of the present study was to elucidate whether NPY dilates small human subcutaneous arteries. Subcutaneous arteries, obtained from patients undergoing abdominal surgery, were mounted in in vitro tissue baths, and the vascular responses to NPY were investigated. The presence of mRNA encoding the human NPY Y1 receptor in endothelial cells from human umbilical veins was studied by the use of reverse transcriptase - polymerase chain reaction (RT-PCR). In arteries precontracted with the prostaglandin analogue U46619, NPY induced a concentration-dependent vasodilation (Emax 30 +/- 10% of the U46619-induced contraction), which was significantly inhibited by the NPY Y1 receptor antagonist BIBP3226 (1 microM), causing a rightward shift of the concentration-response curve, pEC50 7.1 +/- 0.3 vs. 7.7 +/- 0.3 for NPY alone. After pretreatment with the nitric oxide synthetase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) (10 microM), the dilation was abolished (Emax 6 +/- 5% of the U46619-induced contraction). mRNA encoding the human NPY Y1 receptor was detected in endothelial cells from human umbilical veins. It was concluded that NPY induces vasodilation in human subcutaneous arteries. The dilation is mediated via the NPY Y1 receptor and is dependent on nitric oxide.

Selective increase of the contractile response to endothelin-1 in subcutaneous arteries from patients with essential hypertension.

Endothelin-1 has been shown to contribute to basal vascular tone in man. Since endothelin-1 is a potent vasoconstrictor putatively involved in hypertension, we have compared the contractile responses of endothelin-1 and noradrenaline in relation to potassium chloride in subcutaneous resistance arteries from subjects with established essential hypertension with matched controls. Furthermore, with RT-PCR, the occurrence of mRNA for the ETA and ET(B) receptors was shown in the tunica media layer of subcutaneous arteries in controls and hypertensives. The maximum contractile response to endothelin-1 was significantly higher in the subcutaneous arteries of the hypertensives (by 88% with no change in potency) as compared to controls. The responses to noradrenaline, acetylcholine and potassium chloride did not differ between the groups. This selective increase in the contractile response to endothelin-1 might contribute to the development of essential hypertension.

Attenuation of contractile responses to sympathetic co-transmitters in veins from subjects with essential hypertension.

Neuropeptide Y (NPY), noradrenaline (NA) and ATP are cotransmitters of the sympathetic nervous system and exert vasocontractile effects. The aim of this study was to determine the role of these sympathetic co-transmitters in human hypertension. Subcutaneous vessels from 12 patients with essential hypertension and 12 matched controls were studied in vitro. Vascular contractile responses to NPY, NA, alpha,beta-methylene ATP (alpha,beta-mATP) and potassium were studied in isolated arteries and veins (diameter 0.1-1.1 mm) with intact endothelium. The dilatory effect of acetylcholine was used to test the endothelial function. There was no difference in potency (pD2) or contractile response to NPY, NA or alpha,beta-mATP between hypertensive and control arteries. In veins, however, the contractile response to NPY was significantly reduced in hypertensives and the responses to NA were unchanged. Furthermore, the sensitivity (pD2) to alpha,beta-mATP was significantly reduced in veins from hypertensives. There was no difference in the dilatory response to acetylcholine between the hypertensives and the controls, neither in the arteries nor in the veins, indicating that the observed changes in vascular reactivity to NPY, NA and alpha,beta-mATP were not endothelium-dependent. In conclusion, the postjunctional contractile effect of NPY and sensitivity (pD2) to alpha,beta-mATP, co-transmitters of the peripheral sympathetic nervous system, are attenuated in veins in essential hypertension.

Lisinopril reduces postexercise albuminuria more effectively than atenolol in primary hypertension.

Physical exercise causes transient albuminuria. The mechanisms of postexercise albuminuria are not fully clarified but stimulation of the reninangiotensin system (RAS) probably plays a major role through intrarenal haemodynamic changes causing an elevated filtration pressure. In a randomised, double-blind, crossover study we compared the effects on urinary albumin excretion (UAE) of lisinopril (L) and atenolol (A) therapy, i.e. we aimed to investigate whether inhibition of the RAS or inhibition of beta1-adrenoceptor-mediated effects of the sympathetic nervous system differed with regard to changes in UAE. Sixteen patients with uncomplicated primary hypertension were studied. Four standardised bicycle ergometer exercise tests were performed, before and after each active treatment period. UAE 30 min postexercise, determined by radioimmunoassay, was significantly lowered by both treatments: -278 mu g center dot min-1 (L) and -199 mu g center dot min-1 (A). The reduction of postexercise UAE achieved by treatment with the angiotensin-converting enzyme (ACE) inhibitor (L) was significantly greater than that achieved by the beta1-selective adrenoceptor blocker treatment. Blood pressure (BP) at rest and during exercise were equally reduced by both drugs. In conclusion, this study showed that antihypertensive treatment with an ACE inhibitor was more effective in reducing exercise-induced albuminuria than a beta1-selective adrenoceptor-blocking agent with a similar degree of BP reduction in patients with uncomplicated primary hypertension. This suggests that the RAS plays a major role in postexercise albuminuria in hypertensive subjects. The clinical significance of this finding, however, remains to be clarified.

Different levels of sensory neuropeptides (calcitonin gene-related peptide and substance P) during and after exercise in man.

The aim of this study was to investigate the regulation of two sensory peptides calcitonin gene-related peptide (CGRP) and substance P, reflected as circulating levels during provocation of the sympathetic nervous system. Levels in hypertensives, diabetics (NIDDM) and controls were assayed before, during and after an exercise test (average work load carried out was 76 +/- 10 kJ). CGRP levels increased progressively during exercise (P < 0.001), with maximum level at maximum exercise. This was significant in all three groups; hypertensives P < 0.001, diabetics P < 0.01 and controls P < 0.001. No differences in circulating revels of CGRP between the three groups were found. Substance P levels were fairly constant during exercise but increased 30 min after exercise (P < 0.01) in the total group. We hypothesize that CGRP might provide a counter-regulatory mechanism to the sympathetic vasoconstrictor transmitters noradrenaline (NA) and neuropeptide Y (NPY) during sympathetic activation. Substance P did not increase during exercise. This suggests differential regulation and function of the two vasodilatory peptides.

Selective attenuation of neuropeptide-Y-mediated contractile responses in blood vessels from patients with diabetes mellitus.

Vascular smooth muscle contractile responses to neuropeptide Y, alpha,beta-methyleneATP and noradrenaline were studied in circular segments of isolated vessels with intact endothelium in vitro from 12 patients with diabetes mellitus type 2 (NIDDM) and 12 control subjects. The dilatory effect of acetylcholine was used to test the function of the endothelium. Subcutaneous arteries and veins (diameter 0.1-1.1 mm) were obtained during surgery. There was no difference in contractile responses to noradrenaline or alpha,beta-methyleneATP between diabetic and control vessels. The contractile response to neuropeptide Y, however, was markedly reduced in the diabetic group. The maximal contractile effect (46.0 +/- 14.0%, p < 0.05) but not the sensitivity to neuropeptide Y was significantly less in diabetic veins compared to control (107.5 +/- 19.6%). Thus, the attenuation of neuropeptide Y responses was present in humans as previously observed in alloxan-induced diabetes mellitus in rabbits. There was no difference in the dilator effect of acetylcholine between the diabetic and the control group in any of the vessel types, indicating that the difference in vascular reactivity to neuropeptide Y was not endothelium-dependent. In conclusion, the present study has shown that the postjunctional effects of neuropeptide Y, a co-transmitter of the peripheral sympathetic nervous system, is selectively attenuated in diabetes mellitus.

The effects of alpha-trinositol on haemodynamic variables and neuropeptide Y levels in a pilot study of hypertensives and healthy volunteers.

AIMS: The aim of this study was to examine the effects of D-myo-inositol-1,2,6-trisphosphate (alpha-trinositol) on haemodynamic variables and neuropeptide Y (NPY) levels in hypertensives and healthy volunteers. METHODS: Hypertensives (n = 13) and normotensives (n = 11) were recruited after a screening of cardiovascular risk factors of all men aged 40 living in a well defined area. The hypertensives were previously unmedicated. The effect of alpha-trinositol was studied after intravenous infusion at rest, and during and after a maximal exercise test in a double-blind crossover manner with placebo. RESULTS: Haemodynamic variables and NPY levels were recorded. NPY levels did not differ between normotensives and mild hypertensives at the start of the study. However, a significant increase was seen in hypertensives after they had risen to the sitting position. During exercise, the NPY levels increased significantly both in normotensives and hypertensives. After the exercise test, the NPY levels were significantly higher in hypertensives than in normotensives; alpha-trinositol did not modify these responses. In normotensives no significant difference in systolic blood pressure was seen during or after the exercise test whether they were on alpha-trinositol or placebo. In the hypertensives on active drug, however, the blood pressure tended to be approximately 5 mmHg lower during the exercise test as compared with the placebo group. In the hypertensives on active drug, the heart rate increased significantly more during exercise as compared with the placebo groups. In normotensives, the same tendency was seen, but it did not reach statistical significance. CONCLUSIONS: The NPY antagonist, alpha-trinositol, tends to reduce the increase in systolic blood pressure induced by maximal exercise and increases the heart rate in hypertensives but not in normotensives.

Non-obese men with high lipoprotein(a) values--a cardiovascular risk group different from those with the metabolic syndrome?

We have investigated the prevalence of cardiovascular risk factors including insulin and lipoprotein(a) in 40-year old men from the island of Oland (n = 314, 84% of those invited) in order to assess to what extent insulin and lipoprotein(a)--two of the currently discussed risk factors--correlated with each other, as well as with some of the more established risk factors. An inverse correlation was found in bivariate analyses between lipoprotein(a) and some of the risk factors for cardiovascular disease included in the 'metabolic syndrome' (triglycerides; r = -0.15, BMI; r = -0.18, and insulin/glucose ratio; r = -0.18) (p < 0.001). In multivariate analysis only the inverse correlation with triglycerides remained. Since lipoprotein(a) has been shown to be an independent risk factor for myocardial infarction, there may exist two subgroups of cardiovascular risk patients: one more obese, hyperinsulinaemic and with several metabolic derangements; and another comprising non-obese subjects with higher lipoprotein(a) values.

The effect of prophylactic heparin treatment on enhanced thrombin generation in pregnancy.

OBJECTIVE: To assess the activation status of blood coagulation in thrombosis-prone pregnant women receiving a reduced dosage of heparin. METHODS: Forty-three women were given subcutaneous heparin treatment during pregnancy; the dosage was monitored so that the heparin (anti-Xa) level was within the stipulated range of 0.08-0.15 anti-Xa units 3 hours after injection. Several coagulation variables were investigated and some routine analyses were performed. The results were compared with those of a control group of 26 healthy pregnant women. RESULTS: Compared with the control values, hemoglobin (P < .01), fibrinogen (P < .05), and total protein S (P < .01) were increased already before heparin treatment was started and continued to be increased significantly throughout pregnancy. During heparin treatment, protein C levels (P < .01) and the factors measured by prothrombin time (P < .001) were increased compared with the controls. Antithrombin decreased, though not as much as when patients are given therapeutic dosages. The fibrinolytic inhibitors behaved as in normal pregnancy. Three variables measuring thrombin formation or coagulation activation (ie, thrombin-antithrombin complexes, D-dimers, and soluble fibrin) were increased in a high proportion before heparin treatment was started; they normalized somewhat during treatment. CONCLUSIONS: In early pregnancy, women with previous thrombotic episodes have high plasma levels of coagulation variables and of markers of coagulation activation compared with controls. Such changes may be used to predict the need for treatment and, in the future, to control treatment.

Tick-borne Borrelia-meningitis in children. An outbreak in the Kalmar area during the summer of 1984.

Nine children, aged 5 to 11 years, with subacute or chronic meningitis were studied. Symptoms started during the summer season in all patients and in eight of the patients the disease began with a localized erythematous lesion (ECM), mostly in the face. In one patient only there was a history of an insect bite at the site of the erythema. The neurological abnormalities included aseptic meningitis, peripheral facial nerve palsy (5/9) and oculomotor nerve palsy (1/9). Most children complained of headache, fatigue, loss of appetite and had a low grade fever. High antibody titers to Borrelia spirochetes in serum and/or cerebrospinal fluid (CSF) were demonstrated by ELISA in eight of the nine patients and by indirect immunofluorescence assay (IFA) in three patients. All patients had a dramatic improvement in their general condition and became afebrile within three days of institution of i.v. penicillin G treatment (i.v. cefuroxime in one patient).

Extraskeletal Ewing's sarcoma arising in the broad ligament.

The necessity for ultrastructural and immunohistochemical examination in establishing the diagnosis of extraskeletal Ewing's sarcoma is reemphasized by the unusual presentation of such a tumor in the broad ligament of a 41-year-old woman. Implications for therapy are discussed.

Carcinoembryonic antigen staining in choriocarcinoma.

Choriocarcinoma of the colon presented as life-threatening lower gastrointestinal bleeding and a pathologic femoral fracture in a 42-year-old man. Elevated serum carcinoembryonic antigen (CEA) levels and immunohistochemical positivity for CEA in neoplastic syncytiotrophoblasts were noted, as well as the expected positivity for the beta subunit of human chorionic gonadotropin (beta HCG). Additional cases, including one of two gestational choriocarcinomas and one of four testicular choriocarcinomas studied immunocytochemically for CEA also demonstrated positivity. Although CEA staining is commonly associated with tumors derived from the surface epithelium of the gastrointestinal tract and other organs, its presence in choriocarcinomas should not be interpreted as conclusive evidence of primary origin from these sites.

Thirst following water deprivation in humans.

The effect of 24-h water deprivation and subsequent drinking on systemic fluid balance and subjective sensations has been determined in human beings. The deprivation caused significant intracellular and extracellular depletions, thirst, and a dry unpleasant tasting mouth. During rehydration, subjects drank 65% of their total intake within 2.5 min. The marked decrease in drinking rate thereafter, and the alleviation of thirst, occurred before plasma dilution had become significant. This attenuation of drinking was subjectively attributed to stomach fullness. Presystemic factors may therefore be important for drinking termination in humans. Within 20 min systemic deficits were removed, but intermittent drinking continued at a low rate, reportedly to alleviate unpleasant oral sensations, Following rehydration, the concentrated urine of hydropenia had disappeared. However, the excretion of solute-free water varied between subjects. Plasma renin activity was significantly elevated by water deprivation, while after rehydration this activity had decreased to levels not significantly different from predeprivation values.

Fluorocarbon perfusion medium applied to the isolated rat brain.

In order to overcome the disadvantages of erythrocytes and albumin, a totally synthetic medium for the perfusion of the isolated rat brain was developed. the perfusion medium was based upon Krebs-Henseleit solution and contained in addition a fluorocarbon (FC 43) for oxygen transport and a polyol (Pluronic F 68) to furnish emulsifying and oncotic properties. The physico-chemical properties of this fluorocarbon perfusion medium allowed perfusion of an isolated rat brain to continue for more than 7 hr, while the medium could be stored as a stock emulsion for several months. The appropriate function of the isolated perfused rat brain is demonstrated by the EEG and by various substrates of the energy metabolism. The suitability of the fluorocarbon medium for perfusion of an isolated rat brain preparation is discussed.