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Adverse pregnancy outcomes and long-term cardiovascular disease risk.

Pregnancy provides a unique physiological stress test for the cardiovascular system, during which, adverse pregnancy outcomes (APOs) can unmask latent susceptibility to future disease. Common complications, including hypertensive disorders of pregnancy (HDP), gestational diabetes, and preterm birth (delivery before 37 weeks' gestation), identify women at substantially higher long-term risk of cardiovascular morbidity and mortality compared with women without a history of APOs. These excess risks likely reflect the combined effects of pre-existing cardiometabolic and genetic susceptibility, as well as the haemodynamic and metabolic stressors of pregnancy, heralding accelerated risk factor trajectories, relative impairment in endothelial and microvascular function, and early disease onset. This final Review in the Series extends the focus from cardiovascular disease during pregnancy and HDP to the long-term cardiovascular implications of APOs after delivery. We synthesise epidemiological data quantifying cardiovascular risk across major APO phenotypes and emerging evidence linking maternal APO history with cardiometabolic risk trajectories in offspring. We also delineate putative mechanistic pathways and summarise guidelines and consensus-informed recommendations for short-term and long-term follow-up after APOs. Finally, we propose practical approaches for integrating APO history into cardiovascular disease risk assessment and guideline-directed prevention across the female life course. We highlight key knowledge gaps, including uncertainty about optimal follow-up models, the limitations of current risk-stratification tools, and the absence of APO-specific prevention trials. We also outline priorities for mechanistic and implementation research. Positioning APOs as early, sex-specific indicators of cardiovascular risk offers a key window of opportunity to shift prevention upstream and improve cardiovascular health outcomes for women.

Humans↗

Short-Term Success, Long-Term Failure: Strain Turnover and Virulence Re-Emergence May Drive Relapse in Pouchitis.

BACKGROUND & AIMS: Pouchitis, de-novo small intestinal inflammation is the most common complication developing in patients with ulcerative colitis after total large bowel resection and ileal pouch-anal anastomosis (IPAA) reconstruction. While the first line treatment is antibiotics, the microbial properties underlying flare, remission, and relapse remain vague. We aimed to investigate how antibiotic treatment drives microbial shifts that underlie remission and contribute to relapse. METHODS: Patients after IPAA were prospectively recruited during clinical flare (active pouchitis defined by the pouchitis disease activity index) and received a two-week course of metronidazole with either ciprofloxacin or doxycycline. Longitudinal follow up was conducted during a year. Clinical data were recorded, and fecal samples were obtained during consequent flares, recovery, and relapses. Microbial gene repertoire, strains, and resistance to antibiotics were determined. Metagenomic sequencing was integrated with whole-genome sequencing of Escherichia coli isolates, providing strain-specific virulence and antibiotic resistance profiles. RESULTS: Patients (n=21) recruited provided 130 samples over one-year follow-up. Both antibiotic regimens induced rapid but transient clinical improvement, reflected by a decrease in fecal calprotectin (728 to 265 &#x3bc;g/g, p<.05), and a marked reduction in bacterial exotoxin genes (p<.05), yet both parameters rebounded by 6 weeks post-treatment. Antibiotic resistance gene abundance significantly increased during treatment (p<.05), without expansion of resistance gene diversity, indicating that pre-existing resistant strains increased. CONCLUSIONS: Antibiotic-induced remission in pouchitis likely results from a temporary suppression of exotoxin-producing bacteria, enabling resistant, low-virulence strains to transiently dominate; The fact that harmful strains quickly rebound after treatment cessation highlights the need for targeted approaches to achieve sustained microbial control.

Inflammatory bowel disease↗

[Effect of anesthesia and operation on essential immune functions].

Study of the references listed leaves no doubt that essential specific and unspecific immune functions are more or less strongly influenced by a wide variety of anaesthetics. In clinically employed concentrations these negative effects are rapidly and completely reversible. No clinically relevant adverse actions on the immune system have ever been identified in short-term anaesthesia with any substance, not even with the thiobarbiturates although these are known to be highly inhibitory. However, matters are entirely different in respect of highly dosed long-term sedation. In such cases, it may occur with e.g. thiobarbiturates or diazepam that in the course of days or weeks concentrations are attained in the tissue which may lead us to expect in vivo quite considerable suppression of both unspecific and antigen-specific cellular immune mechanisms. This expectation, which is first of all based on in-vitro results, has been indirectly supported by a clinical study in patients suffering from craniocerebral trauma who received artificial respiration and in whom an association was seen between thiopental administration and the incidence of bacterial pneumonias. Over and above this, however, the preoperative condition of the patient and of course mainly the operation as such with its associated stress reaction will cause direct and indirect changes in the immune system (Fig. 4). Trauma and anaesthesia exert not only a direct action, but act as inhibitors or stimulators of important immune functions chiefly by modulating the stress response. We are still unaware as to whether and to what extent the prognosis of the individual patient is actually adversely affected by the combined action of these factors. Many findings, however, seem to point to an essential role played by both the surgical trauma and the stress response it induces, as well as by the pre-operative immune status of the patient, in the occurrence of subsequent infectious complications (Fig. 4).

Anesthesia, General↗

Curdlan sulfate and HIV-1: II. In vitro long-term treatment of HIV-1 infection with curdlan sulfate.

Short-term (1 h) treatment with a newly synthesized sulfated polysaccharide, curdlan sulfate (CRDS), showed relatively weak blocking effects on the binding of human immunodeficiency virus type 1 (HIV-1) to the surface of H9 cells. To investigate whether long-term treatment with CRDS could strengthen this effect, CRDS in various doses (0.1, 1, 10, and 100 micrograms/ml) was used in 2-week treatment periods in four separate protocols or "Procedures." SF titers and p24 antigen levels were partially suppressed during long-term CRDS treatment but returned to control levels after the treatment was terminated. In addition, no direct cytotoxicity of CRDS to H9 cells or H9/HIV-1 cells was observed in vitro in the course of continuous exposure to 100 micrograms/ml CRDS for 2 weeks. These results demonstrate the effectiveness of long-term treatment of cells infected with HIV-1 in inhibiting virus expression. The most dramatic inhibition results were obtained when the compound was present both at the time of exposure of cells to virus and during a long-term follow-up treatment. These results show that CRDS inhibits both the cell-free and cell-associated transmission of HIV-1 to host cells and interferes with early events in virus infection. In contrast, CRDS exhibits no significant virucidal activity and has little effect on already infected cells.

Antiviral Agents↗

Assessment of autonomic nervous function in human hypertension.

In spite of the popular belief that "nervous tension," "stress," and hypertension are causally related, it has been difficult to prove a role of autonomic dysfunction in the genesis of essential hypertension. There are three major reasons for this: 1) autonomic function cannot be assessed with one simple test, 2) the short-term "phasic" and long-term "tonic" autonomic control of blood pressure are not necessarily interrelated, and 3) hypertension is a dynamic process in the course of which there are changes in autonomic control. Some of the controversies in the field stem from the lack of appreciation of these limitations.

Autonomic Nervous System↗

Treatment of peptic ulcer disease with furazolidone.

Furazolidone (FZ) has been used in China as a treatment of peptic ulcer disease for about 20 years. Clinical and experimental studies suggest that it has good short-term and long-term effects on both human and animal ulcers. The ulcer healing rate is related to the dosage and course of treatment. The healing rate of a high dose, 2 week course is about 70-75% and the relapse rate after 3 years is 9.5%. The adverse reactions to FZ are not severe, and are well tolerated in most patients. However the mutagenic studies of several biological systems indicate that it has a mutagenic effect, but the mutagenic and carcinogenic effects on humans and animals remain questionable, because FZ has been biotransformed into other metabolites. The mechanisms of FZ in the treatment of peptic ulcer disease are not fully understood, perhaps partly due to the monoamine oxidase (MAO) inhibitory reaction and partly to the antibacterial activity to Helicobacter pylori (HP). The long-term effects of FZ are still not clear.

Animals↗

Periodic psychosis of puberty: a review on near-monthly episodes.

Published cases of periodic psychosis of puberty and related papers were reviewed. The clinical picture is near-monthly recurrence of episodes of stupor or excitement lasting about 1 or 2 weeks, which are accompanied by delusion and in some cases also by hallucinations or confusion. This condition was found to occur more commonly in girls than in boys, and in half of the girls reported the episodes tended to start a few days before menses. Adolescents with mental retardation were more commonly affected, and this suggests that organic brain damage may play a role in the etiology in some cases. Short-term prognosis is usually favorable, but at long-term follow-up, nearly half of them were found to be suffering from affective or schizophrenic illness. The clinical importance of recognizing this psychosis early in the course of illness is emphasized.

Adolescent↗

Reduplicative paramnesia.

A striking behavioral abnormality is described in three individuals who had severe head trauma. At a point when general mnestic capabilities had returned to a near normal level, the patients persistently relocated the hospital at another geographical site, even in the face of compelling counter-evidence. The strong parallels in the etiology and course of the three cases justify the positing of a syndrome, here termed reduplicative paramnesia. A neuropsychologic analysis of the disorder stresses the cognitive operations entailed in geographical localization and confabulation. Clinical-pathologic considerations underline the role of right hemisphere and frontal lobe structures in the syndrome.

Adult↗

[The functional outcome of patients with subacute thyroiditis].

Whether with the passage of time subacute thyroiditis leads to hypothyroidism remains to be determined. Therefore, we evaluated the thyroid function including TRH test of 66 patients with a previous history of subacute thyroiditis and age-matched control subjects with special reference to the measurement of inorganic iodide. The patients were divided into 3 groups according to time lapse since the occurrence. Group 1 consisted of 24 cases followed up for 4 to 24 months. Sixteen cases in group 2 had their courses from 2 to 5 years, and group 3 was composed of 26 cases over the past 5 to 30 years. We selected 169 subjects without history of subacute thyroiditis and divided them into three control groups matched for age, each corresponding to the patient groups (group 1a, 2b and 3c, respectively). 41.7% and 29.2% of cases in group 1 had high basal levels of serum TSH (greater than 3.6 microU/ml) and delta TSH (the increment of TSH after TRH, greater than 46.8 microU/ml). In group 2, levels of serum T3 and T4 returned to normal ranges. However, in group 3, significant higher elevations in TSH and delta TSH than those in group 3c were observed, and the T4, FT4, T3 and FT3 levels were lower than those of group 3c (p less than 0.01 and p less than 0.05, respectively). 42.3% of cases in group 3 showed high TSH, and there were 4 cases with clinical hypothyroidism. Among the cases studied, a significant negative correlation (p less than 0.01) between levels of TSH and T4 was observed, while a correlation between TSH and delta TSH was positive (p less than 0.001). High levels of serum inorganic iodide were observed in 6.1% of cases and a correlation between inorganic iodide and TSH was significantly positive (p less than 0.01) not only in patients with subacute thyroiditis, but also in the control subjects. Antithyroid autoantibodies were detected in 42.4% of all the cases with subacute thyroiditis and also in 45.6% of all the controls. In group 3, MCHA was detected in 64.5% of the cases, and the frequency was higher than that of group 3c as well as that of 25% in group 2 (p less than 0.01), respectively. In 15.4% of the cases in group 3, the titers of MCHA were more than 40(2), and the titers of MCHA were significantly higher in patients with a long-term period after the onset of subacute thyroiditis than those with a short-term period.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

[Tetanic fatigue and proximate post-tetanic recuperation in sartorius and flexor carpi radialis muscles of the male frog. Effects of iodoacetic acid (author's transl)].

The time-course of the isometric tension output, at 20 degrees C, during a long tetanus and after a short period of rest, was investigated in two isolated frog muscles : the sartorius and flexor carpi radialis muscles. To prevent aerobie and glycolytic recovery processes, some muscles were poisoned with 0,4 mM iodoacetic acid (IAA) and nitrogen, for 20 or 40 min. 1. For the unpoisoned sartorius muscle, tetanic tension declined quickly, but after a 0,8 sec period of rest, the muscle was able to develop high tension. Poisoning with IAA-N2 increased fatigue without suppressing the property of a proximate post-tetanic recuperation. 2. In the flexor carpi radialis muscle resistance to fatigue was very large before poisoning and diminished after poisoning. Proximate recuperation was very weak. 3. The results show that the recovery processes are not a primary factor of the development of the short-term fatigue ; they enhance the hypothesis that a failure of the electromechanical coupling can explain the rate of the tension fall in tetanized sartorius muscles.

Anaerobiosis↗

[Special pharmacokinetic aspects in newborns and young infants].

The safety of drug therapy in the newborn period and early infancy is endangered for two main reasons: 1. The relative distribution volume of drugs during maturation and in pathological states varies greatly and thus makes conventional dosage in short-term therapy ineffective. 2. During early childhood, the rate of elimination of many drugs is slow hence there is a risk of overdosage in long-term therapy with doses considered safe in older children. The example of two drugs demonstrates, that the course of blood levels is not only dependent on the elimination half life and on the relative distribution volume, but may also be modified to a large extent by the process of invasion. This increases the risk of iron-dextrane but contributes to the safety of Cephalexine. If drug therapy is to be safe and effective in childhood at least the basic elements of a most simple pharmacokinetical model consisting of Invasion, Volume of Distribution and Elimination must be known as can be shown by the mathematical extrapolation of blood level curves gained from single applications for long-therm therapy.

Age Factors↗

Protein bound radioactivity in neuronal and glial fractions following intra-carotid 3H-leucine perfusion.

Brain proteins in one cerebral hemisphere were labeled by means of intracarotid perfusion with 3H-leucine by a 40 s pulse. Recirculating precursor contributed little to the protein bound radioactivity. This radioactivity reached a peak level 30 min after perfusion. Fractions enriched in neuronal perikarya and glial cells showed a similar time course of labeling, but the neuronal fraction demonstrated the highest level of protein bound radioactivity. Subcellular fractions from whole brain were studied by the same system. The highest protein bound radioactivity was observed in the nuclear and microsomal fractions. The brain entry of the precursor by means of a controlled intracarotid pulse of short duration offers particular advantages in short-term experiments since the systemic metabolism of the labeled precursor is largely avoided. The easily achieved high labeling of proteins facilitates assay of the radio-activities in different cellular and subcellular fractions and also allows analyses of relative turnover rates in electrophoretically separated proteins.

Animals↗

[Certain hemodynamic indicators during rest and after intensive physical exercise at high altitude].

For 5 years 364 normal males, aged 19--25, were studied at the altitude of 3800--4200 m, along with local inhabitants of the mountain region; the hemodynamic shifts and arterial blood oxygenation were studied with the base metabolism conditions preserved both at rest, and after intensive physical exercises performed according to the step-test method with the maximum tempo of the work (cardiological motion test, WHO, 1967). The initial reaction of the cardiovascular system to the high altitude conditions manifested itself in an increased stroke volume and cardiac output, of the volume speed of blood ejection, of the cardiac index in a decrease of the total peripheral resistance and oxygen saturation of the arterial blood. This reaction was interpreted as a compensatory one. In the course of acclimatizing, the cardiac output and the pulse amplitude of the arterial pressure gradually decreased, and the total peripheral resistance increased. These hemodynamic changes must be of an adaptative nature. The maximum physical workload caused a distinct intensification of the circulatory reactions, especially in those living for considerable periods of time at high altitude and in local inhabitants. The general state of the examined remained good. Hence, these persons have a considerable reserve of functional capacities of their cardiovascular system, and can perform hard muscle work at high altitude. Individuals staying at high altitude for only short periods of time react to intensive physical workloads by a less distinct intensification of the contractile capacity of the heart and by a sharp decrease of blood oxygenation, considerable acceleration of the heart rate and respiration rate, as well as by a deterioriation of their general state. Such muscular efforts cause overloading of the heart only in persons with a short-term acclimatizing.

Acclimatization↗

Effect of short-term administration of cyproterone acetate on the reproductive tract histology, ovarian and serum cholesterol contents of female monkey (Presbytis entellus entellus).

Short courses of cyproterone acetate, a compound with progestational and antiandrogenic activities were administered to normally cycling female monkeys to investigate into the effects of cyproterone acetate on the reproductive tract. In little earlier follicular stage 20 mg of the drug daily for 30 days increased the cholesterol contents in the gonads. Serum cholesterol contents were slightly increased. When the reproductive tract was examined histologically, the gonads showed reduction in size, along with widespread degeneration of the young follicles as well as other growing follicles. Uterus showed progestational endometrial proliferation and sloughing of the vaginal productive tract.

Animals↗

Marital discord and early child development.

As part of a prospective study on the neuropsychiatric development of children born at varying degrees of organic and psychosocial risk, the effect of marital discord on the cognitive and social-emotional development of 315 first-born children into two parent households was investigated. Both the children and the quality of the parental relationship were evaluated when the children were 3 months and 2 years of age. The findings show that marital discord at 3 months does not affect child performance at 3 months, or at 24 months. Marital discord at 2 years does affect the emotional well-being of the 2 year olds, i.e. it is accompanied by a significant rise in psychopathological symptoms. When the effect of the stability of marital strife from the first assessment to the second was studied, a significant increase of behaviour problems and decrease in cognitive performance was found in the group of children whose parents' marital situation had deteriorated and failed in the meantime but surprisingly not in the group with chronic discordant relationships. Conversely, poor child performance and emotional adjustment improved with a positive change in the parental relationships. Analysis shows that negative marital change goes hand in hand with a decrease in parenting skills which affect children more adversely than their counterparts whose parents had a history of marriage and child-rearing problems. Further study of the course of marital relationships and child development at the next research waves (4.5 and 8 years) will show which results are of long-term versus short-term relevance.

Adolescent↗

[Modification of the body's resistance to acute ionizing radiation by synthetic beta-carotene].

Radiomodifying efficiency of short-term and chronic medicinal and treatment-prophylactic enrichment of rations with artificial beta-carotene, administered at single doses of 0.1-10.0 mg, were studied after acute external gamma-irradiation of adult nonlinear and Wistar rats (0.029 Gy/s) or female SBA mice (0.0037 Gy/s), where the absorbed dose was equal to 8-3 Gy or 9.9-9.5 Gy, respectively. Suspension of beta-carotene paste in olive oil accelerated death of rats irradiated at doses of 8 and 7 Gy (P = 0.04), and shortened their lifespan. At a dose of 6 Gy single and long-term enrichment of rations with beta-carotene decreased the rate of rat death within 30 days from 33.3% to 16.7% (P = 0.14) and 3.3% (P = 0.01), while their life time was increased from 48 days to 67 days (P = 0.05) and 508 days (P = 0.01). beta-Carotene was found to affect favourably the radiation-induced (5 Gy) leukocytopenia, and decreased thymus mass (6 Gy) and body weight (8 Gy). In treatment-prophylactic enrichment with beta-carotene of mice (9.9 Gy) ration their survival was increased from 15% to 30% and lifespan from 14.4 days to 28.9 days (P = 0.05). During medicinal or treatment-prophylactic courses of beta-carotene death of mice (9.7 Gy) was decreased from 75% to 35% (P = 0.01) or 60% and life time was increased from 16.7 days to 22.17 days or 39.9 days (P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Echocardiographic evaluation of left ventricular wall motion before and after heart transplantation.

Forty transplanted hearts were retrospectively investigated before, immediately after, and 15 +/- 12 months after heart transplantation by two-dimensional echocardiography for the presence and course of left ventricular myocardial wall motion abnormalities. Fourteen heart donors who were brain dead because of subarachnoid hemorrhage formed group 1 (mean age, 35 years); 21 heart donors who were brain dead because of head injury formed group 2 (mean age, 29 years), and five heart donors who were brain dead because of head injury with an additional chest trauma formed group 3 (mean age, 28 years). Myocardial wall motion was examined in six different myocardial segments (inferior, septal, anterior, posterior, posterolateral, apical) and was quantitatively assessed by a modified score index system (score index 0 = normal wall motion; score index 1 = diffuse hypokinesia). Overall, 27 of the 40 heart donors showed mild to severe (9 of the 40) wall motion abnormalities, which improved shortly after heart transplantation (score index: 0.36 vs 0.18, p < 0.01), and remained improved 15 months after heart transplantation (score index: 0.15). Among the different study groups, a significant improvement occurred in the myocardial wall motion score index on a short-term and long-term basis in all the groups, except for group 2, regarding the long-term follow-up. This study concluded that brain-dead, potential heart donors often reveal mild-to-severe left ventricular wall motion abnormalities, which are readily detected and semiquantitated by two-dimensional echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Serial testing of antiarrhythmic agents using programmed stimulation in recurrent ventricular tachycardia].

Serial testing of drugs (STL) by means of programmed electric stimulation (PES) was implemented in 41 patients with relapsing monomorphic persisting ventricular tachycardia (S-KT) of varying aetiology and severity. To reduce underrating of the action of antiarrhythmics, milder criteria were used for evaluation of the short-term and long-term effectiveness of therapy. By STL a total of 137 drugs and their combinations were tested. S-KT was not induced by 60 of them (44%) and in 35 patients (85%). In the remaining 6 patients STL could not be completed because of non-adherence of the patients to the method or because of serious proarrhythmic action of therapy. In the course of long-term follow up (mean 21 months) in positive therapy an arrhythmic episode did not occur during the first year in any of the patients, in the course of two years it occurred in 14%, in three years in 29% and in the course of four years in 33% of the patients. Treatment preventing S-KT had to be abandoned because of serious side-effects in four patients. In all of these four patients later an arrhythmic episode developed. Long-term treatment with antiarrhythmics selected by means of STL by programmed stimulation is a rational approach to pharmacotherapy of serious ventricular arrhythmias. In cases leading to combined treatment with amiodarone and antiarrhythmics class I it would be, however, better in view of the high incidence of serious effects of this treatment to use implantation of a defibrillator.

Adult↗