Differential pathogenicity and lethality of bubonic plague (1720-1945) by sex, age and place.

COVID-19 brought back to the attention of the scientific community that males are more susceptible to infectious diseases. What is clear for other infections-that sex and gender differences influence both risk of infection and mortality-is not yet fully elucidated for plague, particularly bubonic plague, although this knowledge can help find specific defences against a disease for which a vaccine is not yet available. To address this question, we analysed data on plague from hospitals in different parts of the world since the early eighteenth century, which provide demographic information on individual patients, diagnosis and course of the disease in the pre-antibiotic era. Assuming that the two sexes were equally represented, we observe a worldwide prevalence of male cases hospitalized at any age, a result which seems better explained by gender-biased (thus cultural) behaviours than biological sex-related factors. Conversely, case fatality rates differ among countries and geographic macro-areas, while globally, lethality appears slightly prevalent in young females and older adults (regardless of sex). Logistic regression models confirm that the main risk factor for bubonic plague death was the geographical location of the cases and being older than 50 years, whereas sex only showcased a slight trend.

A critical review of anthropological studies on skeletons from European plague pits of different epochs.

In historical times, plague epidemics intermittently ravaged Europe for more than 1,400 years, and still represent a threat in many countries all over the world. A debate is ongoing about the past plague, if it killed randomly in a population or discriminated among persons on the basis of their biological features. To address questions of plague lethality, we reviewed a large number of anthropological studies published in the last twenty years on victims of the past pestilences in Europe. In particular, we focused on data concerning demography (age at death and sex determination), and health status (skeletal biomarkers). We applied to these data a model system based on Multiple Linear Regression, which aimed to discern among possible predictors of sex-selective plague lethality in entire populations, in different periods and regions. Based on available data, we lack evidence for general trends of association between biological features. Differences in sex ratio are more likely due to the original population compositions or to distinct cultural behaviours of the two genders. We concluded that generalizations on biological evidence are not feasible for ancient plagues if we exclude that the infection possibly killed primarily persons between 5-10 and 20-35 years of age.

Correlation of 99mTc-sestamibi SPECT myocardial perfusion imaging with absolute coronary flow reserve by a new noninvasive Doppler method in patients with stenoses of the left anterior descending coronary artery. A preliminary report.

BACKGROUND: Myocardial perfusion assessed by a pharmacological scintigraphic test is a time-honored method to assess the functional significance of a coronary stenosis. There is no study that has compared coronary flow reserve assessed by adenosine/base contrast-enhanced transthoracic echo Doppler in harmonic mode with myocardial perfusion by adenosine/base 99mTc-sestamibi SPECT. The aim of this study was to compare the absolute coronary flow reserve measured in the left anterior descending coronary artery using a new noninvasive method (transthoracic harmonic Doppler) with adenosine/base 99mTc-sestamibi SPECT. METHODS: Twenty-two patients scheduled for coronary angiography underwent evaluation of basal and hyperemic flow in the left anterior descending coronary artery using transthoracic harmonic Doppler. Simultaneously (during the same adenosine infusion) the patients were injected with 99mTc-sestamibi (10 mCi). Baseline scintigraphic study was obtained 4 hours later (99mTc-sestamibi, 30 mCi). RESULTS: Angiography showed in the left anterior descending coronary artery no or not significant stenosis (< 40% lumen narrowing) in 14 patients (Group I) and a severe stenosis (> 75%) in the remaining 8 patients (Group II). Coronary flow reserve dichotomized as normal (> or = 2.0) or abnormal (< 2.0) gave concordant results with SPECT. Overall, in fact, 18 studies (81%) were in agreement (k = 0.48, p = 0.02). In addition, coronary flow reserve proved to be a useful complementary tool to SPECT in patients with severe multivessel disease (and global hypoperfusion; 2 cases) and left bundle branch block (1 case). CONCLUSIONS: Coronary flow reserve assessed by transthoracic harmonic Doppler gives concordant results with SPECT perfusion scintigraphy. The diagnostic potential of SPECT may be increased by the noninvasive assessment of coronary flow reserve in the left anterior descending coronary artery.

Validation of a new noninvasive method (contrast-enhanced transthoracic second harmonic echo Doppler) for the evaluation of coronary flow reserve: comparison with intracoronary Doppler flow wire.

OBJECTIVES: We tested the hypothesis that coronary flow reserve (CFR) in the left anterior descending coronary artery (LAD) as assessed by a new noninvasive method (contrast-enhanced transthoracic second harmonic echo Doppler) is in agreement with CFR measurements assessed by intracoronary Doppler flow wire. BACKGROUND: Contrast-enhanced transthoracic second harmonic echo Doppler is a novel noninvasive method to detect blood flow velocity and reserve in the LAD. However, it has not yet been validated versus a gold-standard method. METHODS: Twenty-five patients undergoing CFR assessment in the LAD by Doppler flow wire were also evaluated by contrast-enhanced transthoracic Doppler to record blood flow in the distal LAD at rest and during hyperemia obtained by adenosine i.v. infusion. In five patients CFR was evaluated twice (before and after angioplasty). RESULTS: As a result of the combined use of i.v. contrast and second harmonic Doppler technology, feasibility in assessing coronary flow reserve equaled 100%. The agreement between the two methods was high. In fact, in all but five patients the maximum difference between the two CFR measurements was 0.38. Overall, the prediction (95%) interval of individual differences was -0.69 to +0.72. Reproducibility of CFR measurements was also high. The limits of the agreement (95%) between the two measurements were -0.32 to +0.32. CONCLUSIONS: Coronary flow reserve in the LAD as assessed by contrast-enhanced transthoracic echo Doppler along with harmonic mode concurs very closely with Doppler flow wire CFR measurements. This new noninvasive method allows feasible, reliable and reproducible assessment of CFR in the LAD.

Contrast-enhanced transthoracic second harmonic echo Doppler with adenosine: a noninvasive, rapid and effective method for coronary flow reserve assessment.

OBJECTIVES: The purpose of this study is to evaluate the feasibility in detecting blood flow in the left anterior descending coronary artery (LAD) using transthoracic color Doppler (CD) imaging (in both second harmonic and fundamental mode) along with contrast enhancement and to verify if this new noninvasive method along with adenosine is safe, rapid and effective in assessing coronary flow reserve (CFR). BACKGROUND: Feasibility of contrast-enhanced transthoracic Doppler recording (in both second harmonic and fundamental mode) of blood flow velocity in the LAD has not been assessed. Adenosine has a greater vasodilator potency and more favorable kinetics than dipyridamole and thus it can be more suitable for assessing CFR in conjunction with this method. METHODS: Sixty-one patients with angiographically patent LAD underwent CD (both in fundamental and harmonic mode) as well as color-guided pulsed wave (PW) Doppler recording of blood flow velocity in the distal LAD before and after intravenous contrast injection. A second group of patients (n = 77), undergoing coronary angiography, was submitted to transthoracic contrast-enhanced PW Doppler recording of blood flow velocity in the LAD using harmonic CD as a guide, at rest and during adenosine-induced hyperemia. RESULTS: Harmonic CD along with echo contrast consistently improved blood flow detection in the LAD; the success rate in detecting flow of optimal quality was 88% with this approach, whereas it was 11% and 16% with CD in fundamental mode, respectively, before and after contrast. Pulsed wave Doppler results paralleled those of harmonic CD (p < 0.001 contrast harmonic vs. fundamental). In the second group of patients coronary angiography revealed 0% to <40% stenosis in 24 patients (group I), > or =40% to < or =75% in 17 patients (group II) and >75% stenosis in 34 patients (group III). There was a significant difference in CFR among the three groups of patients; CFR for peak diastolic velocity was (mean +/- SD): 2.88+/-0.7 (group I), 2.09+/-0.5 (group II) and 1.51+/-0.5 cm/s (group II) (p < 0.05 group I vs. both group II and group III; p < 0.05 group II vs. group III). The whole examination took less than 10 min. CONCLUSIONS: Contrast-enhanced second harmonic Doppler recording of blood velocity in the LAD is highly feasible and in combination with adenosine it is a rapid, safe and effective method for assessing CFR ratio.

New noninvasive method for coronary flow reserve assessment: contrast-enhanced transthoracic second harmonic echo Doppler.

BACKGROUND: We tested the hypothesis that blood flow velocity could be recorded in the left anterior descending coronary artery (LAD) during transthoracic echocardiography by use of second harmonic echo Doppler modality along with contrast enhancement (intravenous Levovist) at rest and after pharmacologically induced maximal vasodilation to assess coronary flow reserve (CFR) with a totally noninvasive approach. METHODS AND RESULTS: Fifty-six consecutive patients undergoing coronary angiography underwent transthoracic contrast-enhanced pulsed-wave Doppler recording of blood flow velocity in the LAD by use of harmonic color Doppler as a guide at rest and after maximal vasodilation by dipyridamole infusion. Contrast enhancement with the harmonic mode greatly improved the success rate of recording adequate pulsed-wave Doppler signal in the LAD. CFR was (mean+/-SD) 1.54+/-0.7 in patients with (group 1) and 2. 79+/-0.9 in patients without (group 2) significant LAD stenosis (lumen narrowing >70%) (P<0.001); sensitivity and specificity in detecting significant LAD stenosis were 86% and 90%, respectively. There was close agreement between CFRs determined by this new method and intracoronary Doppler flow wire. CONCLUSIONS: Contrast-enhanced transthoracic echo Doppler with the harmonic mode is a feasible and promising technique for assessing CFR in a totally noninvasive way.

[Does a genetic predisposition for infarction expansion exist? Evaluation of genetic polymorphisms of the renin-angiotensin system]. / Esiste una predisposizione genetica per l'espansione infartuale? Valutazione dei polimorfismi genetici del sistema renina-angiotensina.

Aim of this study is to carry out a genetic analysis of polymorphisms of the renin-angiotensin system in a genetically homogeneous population, in patients with and without myocardial infarction (AMI) expansion and to evaluate the influence of non genetic, mechanical factors. The study was conducted on 299 patients with first AMI. Ecocardiography studies were performed on all patients on day 1 and 3 from the onset of AMI and before discharge. Eighty-four patients were excluded because of inadequate quality of echocardiograms and 215 (163 males, 52 females) were admitted. Of these, 157 had no evidence of AMI expansion (EXP-) while 58 had expansion (EXP+). DNA was extracted by standard methods from blood samples. Age and gender had no influence on AMI expansion. Anterior infarction (p < 0.000001) and Q-wave infarction (p < 0.00002) were found more frequently in EXP+. Peak of creatine phosphokinase was higher in EXP+ than in EXP- (p < 0.00001). The percent of patients treated with thrombolysis or with hypertension and/or left ventricular hypertrophy was not significantly different in the two groups. AGT MT235 polymorphism of angiotensinogen gene, I/D polymorphism of ACE gene and AT1 A1166C of AT1 receptor of angiotensin II were not significantly different in two groups. Stratified analysis showed that in patients with anterior AMI (n = 87), with a higher risk of AMI expansion, there is a significant difference (p < 0.02) in ACE genotype between EXP- and EXP+. Odds ratio assuming the dominant effect of I allele (II+ ID < DD) was 3.35 (confidence interval 1.41-7.56) with increased risk of expansion. More extension studies are need to verify if these results can contribute to early identification of patients at higher risk and to optimize therapeutic approach.

[Hemodynamic assessment at rest and during dynamic physical exercise in young subjects with and without hypertensive parents]. / Comportamento dei parametri emocardiodinamici a riposo e durante escercizio fisico dinamico in giovani soggetti con e senza familiarità ipertensiva.

The aim of this research was to identify any early cardiovascular changes that may be predictive of future hypertension in young subjects with family history of hypertension. The study was conducted on 25 offspring of hypertensive parents, mean age 17 years (22 with hypertension only in 1 parent and 3 with both hypertensive parents) and 20 offspring of both normotensive parents, matched by age. Subjects were divided into children (7-13 years) and young adults (19 years on). All subjects underwent three office blood pressure measurements with a mercury sphygmomanometer. On the third control, BoMed thoracic electrical bioimpedance at rest and during upright bicycle exercise was performed. Physical characteristics were similar in subjects matched by age in the two groups. Systolic blood pressure was similar in offspring of normotensives and hypertensives, both at rest and during exercise; diastolic blood pressure was greater in offspring of hypertensive parents at rest (73.1 +/- 10.5 vs 63.5 +/- 7.1 mmHg, p < 0.05), during the first minutes of exercise and during the recovery phase (p < 0.05). Moreover, at the third blood pressure measurement at rest, diastolic blood pressure decreased, with respect to the first measurement, only in children and young adult offspring of normotensive parents, while systolic blood pressure decreased in the two groups of child subjects. No differences in heart rate were observed, both at rest and during physical exercise, between offspring of normotensives and hypertensives. Left ventricular end-diastolic volume, stroke volume, ejection fraction, cardiac output and systemic vascular resistance at rest and their response to decubitus changes and exercise were normal and similar in offspring of normotensive and hypertensive parents both in children and young adults. In conclusion, a different behavior of diastolic blood pressure was found in offspring of hypertensive parents compared to that of normotensive parents, both in children and, to a higher degree, in young adults. This may be an expression of early vascular change in subjects with a genetic predisposition to hypertension.

[The effect of antihypertensive therapy on the seasonal variations in arterial pressure in hypertensive patients]. / Influenza della terapia antipertensiva sulle variazioni stagionali della pressione arteriosa in pazienti ipertesi.

To evaluate the influence of antihypertensive therapy (AHT) on blood pressure (BP) seasonal variations, we have analyzed the systolic and diastolic BP values in 145 hypertensives, 112 males and 33 females, aged 23-65 years, in the 10-year period 1981-1990. All patients received medical treatment and were examined for at least 5-7 consecutive years. The year was divided in 2 (cold and warm months) and 4 periods in relation to mean monthly environmental temperature (10 degrees C, 13 degrees C, 18 degrees C and 23 degrees C). Systolic and diastolic BP was higher in cold months (142/93 vs 137/88 mmHg, p less than 0.05). In cold periods AHT was increased in 11% of patients and decreased in 8%. In the warm periods AHT was decreased in 11% of patients and increased in 6%. The AHT reduction in the warm months was not significantly different in comparison to that of cold months. Vice versa, the AHT increase in cold months was greater than that of warm periods (p less than 0.001). In the 10-year period considered, 18% of patients reduced AHT in the warm period and increased it in the cold period. It was also found a small correlation between diastolic blood pressure and wind, which is, in our country, mostly the mistral. Betablockers, calcium-antagonists and the association betablocker-diuretics showed a seasonal BP variation, while patients treated by diuretic had the same BP both in winter and in summer. A small negative correlation was observed between systolic and diastolic BP and temperature in patients treated by all antihypertensive drugs except the diuretics.(ABSTRACT TRUNCATED AT 250 WORDS)

[Arterial blood pressure behavior during progressive muscular exercise in subjects with stable arterial hypertension]. / Comportamento della pressione arteriosa durante esercizio muscolare progressivo in soggetti affetti da ipertensione arteriosa stabile.

To assess the behaviour of blood pressure (BP) during exercise in hypertensive patients (H), 103 males aged 21 to 59 years (mean 43 years) with essential hypertension WHO class I-II were studied. All H, without antihypertensive therapy for at least 15 days, underwent sitting bicycle exercise (10 W/min). BP was measured on the left arm by a standard mercury sphygmomanometer. The fifth Korotkoff phase was taken as the diastolic pressure. Heart rate was measured by electrocardiogram. Subjects were studied at rest in sitting position, during exercise every 3 min and during recovery at 1, 3 and 5 min. As controls we took 100 normotensive (N) males aged 20 to 59 years (mean 39 years). The results were analyzed also by decades. Systolic (S) and diastolic (D) blood pressure were higher in H in comparison with N at rest, in sitting position, (N 119 +/- 10/79 +/- 7 mmHg; H 162 +/- 21/112 +/- 11 mmHg; p less than 0.01), during exercise and recovery. SBP and, to a lesser extent DBP, progressively increased during exercise both in N and in H patients (at peak exercise: N 192 +/- 20/85 +/- 13 mmHg; H 239 +/- 25/121 +/- 13 mmHg, p less than 0.01). The mean increase of SBP during exercise was 77 mmHg in H and 73 mmHg in N (NS). DBP increment was about 6 mmHg in N and 9 mmHg in H (NS). Within the age decades, SBP during exercise was higher in the age group of 50 to 59 in comparison with 20 to 29 in N and H (p less than 0.05) and DBP in the age group of 40 to 49 and 50 to 59 in comparison with 20 to 29 and 30 to 39 (p less than 0.01). The fall of SBP and DBP was greater at 1 min of recovery both in H and N and became progressively smaller thereafter. At a same workload (90 and 120 W) 60% of H had SBP and 85% had DBP higher than BP in N (above 200/104 mmHg--mean + 2 SD--at 90 W and 215/106 mmHg at 120 W). No difference was observed in heart rate at rest and during exercise between N and H. In conclusion, H had SBP and DBP higher at rest, during exercise and recovery in comparison with N. However, a parallel increase of BP was found in the 2 groups during exercise. Ergometric test showed that 60-85% of H had also excessive increase of systolic and diastolic blood pressure during exercise.