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Background: Our objective was to assess the health impact of coronavirus disease 2019 (COVID-19) during 2020-2022 in the Madrid region., Methods: We included all individuals registered in the Madrid Health System Registry as of 31 December 2019, and followed them until 31 December 2022. Using a unique personal identifier, we linked the databases of primary care, hospitals, pharmacies, certified laboratories performing diagnostic tests, vaccines, and mortality., Results: Of 6 833 423 individuals, 21.4% had a confirmed COVID-19 diagnosis, and 1.5% had a COVID-19 hospitalization (primary diagnosis). Thirty-day mortality was 1.6% for confirmed COVID-19 (from 11.4% in first semester 2020 to 0.4% in first semester 2022). Thirty-day mortality was 10.8% for COVID-19 hospitalizations (from 14.0% in first semester 2020 to 6.0% in second semester 2022). There were 24 073 deaths within 30 days of a confirmed COVID-19 diagnosis. Advanced age, male sex, higher socioeconomic deprivation, and comorbidities were associated with higher mortality., Conclusions: By linking administrative and clinical databases, we characterized the burden of the COVID-19 pandemic in Madrid over 3 years. Our analysis proposes a high-level framework for comparisons of the burden of COVID-19 across areas worldwide., Competing Interests: Potential conflicts of interest. J. B. reports grants and personal fees from Gilead, MSD, and ViiV Healthcare; and personal fees from GSK and Janssen, outside the submitted work. J. R. A. reports grants and personal fees from Alexa, Gilead, MSD, Janssen, Serono, Teva, and ViiV Healthcare, outside the submitted work. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: Sphenoid sinuses mucocele (SSM) is an uncommon cause of orbital apex syndrome (OAS). Diagnosis of neurological complications in SSM might be delayed when the expansion of mucocele beyond the sinuses is not evident in conventional sinuses imaging., Methods: We present a case of a 76-years old man with spared-pupil ophthalmoplegia associated with ptosis caused by a unilateral left SSM in which internal carotid artery Doppler ultrasound showed distal sub-occlusion waves pattern., Results: Sinus occupation was noted in the magnetic resonance imaging (MRI) and was further evaluated in computed tomography (CT) scan and MR angiography. Nor CT or MR angiography showed clear evidence of neighboring structures compression. Doppler ultrasound of internal carotid showed high-resistance waveforms and decreased wave velocities helping diagnosis. Structures compression was confirmed intra-operatively and the patient was discharged asymptomatic after sphenoid sinus drainage., Conclusion: In this first report of carotid Doppler ultrasound findings in a patient with a neurological presentation of a sphenoid sinus mucocele, a high-resistance waveform of the internal carotid may help differentiate uncomplicated sinusitis from invasive mucocele.

We describe the synthesis of trihydroxylated cyclohexane β-amino acids from (-)-shikimic acid, in their cis and trans configuration, and the incorporation of the trans isomer into a trans -2-aminocyclohexanecarboxylic acid peptide chain. Subsequently, the hydroxyl groups were partially or totally deprotected. The structural study of the new peptides by FTIR, CD, solution NMR and DFT calculations revealed that they all fold into a 14-helix secondary structure, similarly to the homooligomer of trans -2-aminocyclohexanecarboxylic acid. This means that the high degree of substitution of the cyclohexane ring of the new residue is compatible with the adoption of a stable helical secondary structure and opens opportunities for the design of more elaborate peptidic foldamers with oriented polar substituents at selected positions of the cycloalkane residues.

The modulation of the A 2B adenosine receptor is a promising strategy in cancer (immuno) therapy, with A 2B AR antagonists emerging as immune checkpoint inhibitors. Herein, we report a systematic assessment of the impact of (di- and mono-)halogenation at positions 7 and/or 8 on both A 2B AR affinity and pharmacokinetic properties of a collection of A 2B AR antagonists and its study with structure-based free energy perturbation simulations. Monohalogenation at position 8 produced potent A 2B AR ligands irrespective of the nature of the halogen. In contrast, halogenation at position 7 and dihalogenation produced a halogen-size-dependent decay in affinity. Eight novel A 2B AR ligands exhibited remarkable affinity ( K i < 10 nM), exquisite subtype selectivity, and enantioselective recognition, with some eutomers eliciting sub-nanomolar affinity. The pharmacokinetic profile of representative derivatives showed enhanced solubility and microsomal stability. Finally, two compounds showed the capacity of reversing the antiproliferative effect of adenosine in activated primary human peripheral blood mononuclear cells.

Double nucleophilic displacement of D-xylo-ditriflate by amines, water and alkyl cyanoacetates, respectively, gave a series of bicyclic divergent intermediates for the synthesis of a wide range of highly functionalized targets, including hydroxylated prolines, pyrrolidines, furanoic acids, and cyclopentanes.

We herein document a large collection of 108 2-amino-4,6-disubstituted-pyrimidine derivatives as potent, structurally simple, and highly selective A 1 AR ligands. The most attractive ligands were confirmed as antagonists of the canonical cyclic adenosine monophosphate pathway, and some pharmacokinetic parameters were preliminarilly evaluated. The library, built through a reliable and efficient three-component reaction, comprehensively explored the chemical space allowing the identification of the most prominent features of the structure-activity and structure-selectivity relationships around this scaffold. These included the influence on the selectivity profile of the aromatic residues at positions R 4 and R 6 of the pyrimidine core but most importantly the prominent role to the unprecedented A 1 AR selectivity profile exerted by the methyl group introduced at the exocyclic amino group. The structure-activity relationship trends on both A 1 and A 2A ARs were conveniently interpreted with rigorous free energy perturbation simulations, which started from the receptor-driven docking model that guided the design of these series.

A stereoselective synthesis of polyhydroxylated cyclopentane β-amino acids from hexoses is reported. The reaction sequence comprises, as key steps, ring-closing metathesis of a polysubstituted diene intermediate followed by the stereoselective aza-Michael functionalization of the resulting cyclopent-1-ene-1-carboxylic acid ester. Examples of synthesis of polysubstituted 2-aminocyclopentanecarboxylic acid derivatives starting from protected d-mannose and d-galactose are presented. A general protocol for the incorporation of these highly functionalized alicyclic β-amino acids into peptides is also reported., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

We present the synthesis and structural study of a new peptidomimetic of morphiceptin, which can formally be considered as the result of the replacement of the central proline residue of this natural analgesic drug with a subunit of (1 S ,2 R ,3 S ,4 S ,5 R )-2-amino-3,4,5-trihydroxycyclopentane-1-carboxylic acid, previously obtained from L -idose. An optimized synthesis of this trihydroxylated cispentacin derivative is also reported. Molecular docking calculations on the target receptor support a favorable role of the hydroxy substituents of the non-natural β-amino acid incorporated into the peptidomimetic.

Here, the synthesis and glycosidase inhibition properties of the two first known 3-ethyloctahydro-1 H -indole-4,5,6-triols are reported. This study shows the transformation of d-glucose into polyhydroxylated 1-(2-nitrocyclohexane) acetaldehydes, followed by a protocol involving the formation of the azacyclopentane ring. Results of inhibitory potency assays and docking calculations show that at least one of them could be a lead for optimization in the search for compounds that behave like folding chaperones in lysosomal storage diseases.

New enantiomerically pure C 16 -alkyl diamides derived from trihydroxy cyclohexane-1,2-dicarboxylic acid have been synthesized from (-)-shikimic acid. The hydroxyl groups in these compounds are free or, alternatively, they present full or partial protection. Their gelling abilities towards several solvents have been tested and rationalized by means of the combined use of Hansen solubility parameters, scanning electron microscopy (SEM), and circular dichroism (CD), as well as computational calculations. All the results allowed us to account for the capability of each type of organogelator to interact with different solvents and for the main mode of aggregation. Thus, compounds with fully protected hydroxyl groups are good organogelators for methanol and ethanol. In contrast, a related compound bearing three free hydroxyl groups is insoluble in water and polar solvents including alcohols but it is able to gelate some low-polarity solvents. This last behavior can be justified by strong hydrogen bonding between molecules of organogelator, which competes advantageously with polar solvent interactions. As an intermediate case, an organogelator with two free hydroxyl groups presents an ambivalent ability to gelate both apolar and polar solvents by means of two aggregation patterns. These involve hydrogen bonding interactions of the unprotected hydroxyl groups in apolar solvents and intermolecular interactions between amide groups in polar ones.

Introduction: Laparoscopic splenectomy was reserved for selected cases, however and because of the improvement in surgical technique and laparoscopic instruments, nowadays, there are few contraindications., Method: Retrospective and observational study of patients surgically treated of laparoscopic splenectomy secondary to hematologic diseases in a period span of 6 years. We analyzed demographic, preoperative, transoperative and postoperative variables., Results: We studied eight patients, 62.5% were men with a mean age of 47.5 years. The most frequent hematologic diagnosis was idiopathic thrombocytopenic purpura (50%). The approach was laparoscopic in 100%. Median surgical time was 129.87 min and median transoperative bleeding was 396.25 cc. Median length of resected spleen was 15 cm. Median time for oral feeding was 20.62 h and total hospital stay was 4 days. There was only one reported complication., Conclusion: Laparoscopic splenectomy represents a safe and feasible option with rapid recovery and few complications., (Copyright: © 2019 Permanyer.)

This work shows that hybrid peptides formed by alternating trans-2-aminocyclopentanecarboxylic acid (trans-ACPC) and trans-2-aminocyclohexanecarboxylic acid (trans-ACHC) do not fold in the solvents typically used in the study of their homo-oligomers. Only when the peptides are assayed in SDS micelles are the predicted helical structures obtained. This indicates that the environment could play an equally important role (as the backbone stereochemistry) in determining their fold, possibly by providing a sequestered environment., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The first example of a new protocol for the incorporation of γ-amino acids into peptides is reported. It involved a shikimic acid based stereoselective synthesis polyhydroxylated-2-nitromethylcyclohexanecarboxylic acids, which were directly incorporated into peptides.

Spironucleosides are a type of conformationally restricted nucleoside analogs in which the anomeric carbon belongs simultaneously to the sugar moiety and to the base unit. This locks the nucleic base in a specific orientation around the N -glycosidic bond, imposing restrictions on the flexibility of the sugar moiety. Anomeric spiro-functionalized nucleosides have gained considerable importance with the discovery of hydantocidin, a natural spironucleoside isolated from fermentation broths of Streptomyces hygroscopicus which exhibits potent herbicidal activity. The biological activity of hydantocidin has prompted considerable synthetic interest in this nucleoside and also in a variety of analogues, since important pharmaceutical leads can be found among modified nucleoside analogues. We present here an overview of the most important advances in the synthesis of spironucleosides., Competing Interests: The authors declare no conflict of interest.

Enantiomerically pure C 16 -alkyl amides derived from cis and trans cycloalkane-1,2-dicarboxylic acids, respectively, have been synthesized and their behavior as organogelators has been investigated. These compounds include cis/trans diastereomeric cyclobutane and cyclohexane derivatives with the aim to explore the influence of the ring size as well as the relative configuration in their hierarchical self-assembly to form gels. High resolution 1 H NMR spectroscopy studies allowed the determination of the dynamics of the gelation process in [D 8 ]toluene and the sol-gel transition temperature. The morphology and size of the aggregates have been investigated and results have shown that, in the case of cyclobutane derivatives, the cis/trans stereochemistry is not relevant for the gelation behavior and the properties of the soft-materials obtained, but it is remarkable for cyclohexane diamides, which are better organogelators. The four compounds produce chiral aggregates despite that two of them are meso achiral molecules. We show herein that this fact is an example of stochastic symmetry breaking induced by sonication. The self-assembly of these molecules has been modelled providing information and support about the structure and the chirality of the aggregates., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We present a case of congenital diaphragmatic hernia diagnosed in an adult. It is a kind of exceptional pathology outside the pediatric age with few cases reported in the literature. Its presentation is unusual, especially in the form of mechanical intestinal obstruction, requiring surgical treatment.

A series of new 2-aminonaphthoquinones and related compounds were synthesized and evaluated in vitro as trypanocidal and cytotoxic agents. Some tested compounds inhibited epimastigote growth and trypomastigote viability. Several compounds showed similar or higher activity and selectivity as compared with current trypanocidal drug, nifurtimox. Compound 4l exhibit higher selectivity than nifurtimox against Trypanosoma cruzi in comparison with Vero cells. Some of the synthesized quinones were tested against cancer cells and normal fibroblasts, showing that certain chemical modifications on the naphthoquinone moiety induce and excellent increase the selectivity index of the cytotoxicity (4g and 10). The results presented here show that the anti-T. cruzi activity of 2-aminonaphthoquinones derivatives can be improved by the replacement of the benzene ring by a pyridine moiety. Interestingly, the presence of a chlorine atom at C-3 and a highly lipophilic alkyl group or aromatic ring are newly observed elements that should lead to the discovery of more selective cytotoxic and trypanocidal compounds., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To determine the percentage of new Specialist Healthcare prescriptions received and modified by Primary Healthcare physicians., Design: Descriptive, cross-sectional and multi-centre study with the participation of Primary Healthcare physicians from one Madrid Health Area during 2 months. A method was established for registering the origin of the new prescriptions in the Computerised Medical Record System. In order to register new prescriptions without any change from Specialist Healthcare, the «second level» option was marked when the prescription was issued. A protocol was prepared and was available on the Computerized Medical Record System, so for those cases where there was a new Specialist Healthcare prescription, the Primary Healthcare physician would not issue any prescription or issue a prescription with changes as regards the original one., Results: A total of 69 Primary Healthcare physicians from 15 Primary Healthcare centres registered 46,512 new prescriptions, 3,893 (8.4%) from Specialist Healthcare. From this number, 3,544 prescriptions (91.0% 95% CI: 90.1-91.9) were issued without changes, and 298 prescriptions were modified (7.7% 95% CI: 7.0-8.7). In 46 cases (1.2% 95% CI: 0.8-1.5) no prescription was issued. Some prescriptions were changed by 51% of Primary Healthcare physicians, and the median of prescriptions changed or not issued was 3. The main reason for the modification was replacement with generics., Conclusions: A high percentage of new Specialist Healthcare prescriptions are issued without any changes being made by Primary Healthcare physicians. Modifications are concentrated in half of the participating physicians. Therefore, these data suggest that this practice is not generally adopted by the professionals., (Copyright © 2011 SECA. Published by Elsevier Espana. All rights reserved.)

β-Secretase is one of the aspartic proteases involved in the formation of amyloid plaques in Alzheimer's disease patients. Our previous results using a combination of surface plasmon resonance experiments with molecular modeling calculations suggested that the Asp dyad in β-secretase bound to hydroxylethylene containing inhibitors adopts a neutral charged state. In this work, we show that the Asp dyad diprotonated state reproduced the binding ranking of a set of these inhibitors better than alternative protonation states.

The determination of pleural fluid triglycerides (PF-TRIG) is useful in the diagnosis of chylothorax, but its diagnostic value for other causes of pleural effusions is unknown. The aim of this study was to evaluate the usefulness of PF-TRIG in the diagnosis of other pleural effusions and investigate the origin of their increase in these fluids. We studied 390 pleural effusions (75 tuberculous, 107 neoplastic, 39 parapneumonic, 30 miscellaneous, 42 idiopathic, and 97 transudates). The correlation was analyzed with the PF-TRIG values as the dependent variable and serum triglycerides (S-TRIG) and the pleural fluid/serum protein ratio (PF/S PROT ratio) as independent variables. The PF-TRIG was significantly higher in exudates. The sensitivity of PF-TRIG for identifying exudates was 84.3%, specificity 61.9%. The correlation between PF-TRIG and S-TRIG was significant in the exudates and in the total pleural effusions. There was a significant correlation between PF-TRIG and S-TRIG and capillary permeability, which worsened when looking at the transudates and exudates separately. No correlations were found between the PF-TRIG and the number of red cells and white cells in any of the groups. Except for diagnosing a chylothorax, the determination of triglycerides in pleural fluid does not appear to be justified. The cause of the increase in PF-TRIG in exudates could not be established because the correlations obtained were insufficient to be able to predict PF-TRIG values from their serum values and the measurement of capillary permeability.

Pheochromocytomas, which derive from chromaffin cells, can secrete catecholamines in large amounts. The incidence of these tumors is low at 2 to 8 cases per million population and only 10% of cases occur in children. A thorough understanding of the pathophysiology of these tumors and the consequent effect of drugs will be necessary for treating these patients during the perioperative period. A great deal has been published on drugs that can be used in this setting, but only a small portion of the information is relevant to children. Esmolol, a short-action beta-blocker, figures among the drugs that have been developed in recent years. We report a case in which esmolol was used during surgery in a 10-year-old girl undergoing scheduled removal of a bilateral pheochromocytoma.

Background and Objective: Early alterations in retinal microcirculation are observed in most hypertensive patients seen in daily practice and the European guidelines consider it is necessary an objective method to quantify these alterations. We have previously described a semi-automatic computerized system to evaluate the calibre of retinal blood vessels that has shown high sensitivity and specificity to calculate the arteriovenous ratio (AVR), though with limitations. We describe a method based on the snakes model to calculate the arteriovenous ratio., Patients and Method: We had compared it with the previously reported lineal method, and we have analyzed 173 digital photographs from 96 hypertensive patients, most of them receiving treatment. Photos were made in two hospitals (A Coruña: 66 and Santiago de Compostela: 107), and were analysed by the same people in each Centre, by the lineal and snake method., Results: We have observed that the arithmetic mean and the differences in AVR between both methods were minimal and showed a normal distribution. Cronbach statistics was 0.974 and intraclass correlation coefficient 0.949 (p<0.001), for the images from Santiago and 0.923 with an intraclass correlation coefficient of 0.857 (p<0.001) for the images from A Coruña., Conclusion: This semiautomatic method to calculate the AVR ratio has a high sensitivity and a greater specificity than previous method, and the correlation between the results obtained with both is excellent., (Copyright © 2009 Elsevier España, S.L. All rights reserved.)

Pleural fluid (PF) cholesterol is a useful parameter to differentiate between pleural transudates and exudates, although the pathophysiologic mechanisms for its increase in exudates are not fully understood. We aim to elucidate the cause of this increase by analyzing the levels of cholesterol-high-density lipoproteins (HDLs), low-density lipoproteins (LDLs), apolipoprotein A (ApoA), and apolipoprotein B (ApoB)-in PF and blood as well as the number of leucocytes and red cells in the PF. We studied 259 patients with pleural effusion (57 transudates and 202 exudates). The correlations of the pleural and serum (S) levels of these parameters were analyzed, with the pleural cholesterol fractions as the dependent variables and their levels in blood and the pleural/serum protein ratio (P/S prot ratio) as the independent variables. The pleural fluid cholesterol levels (PFCHOL) correlated with their blood levels and the capillary permeability (r=0.885). No significant differences were found between the percentage of LDL, with regard to total cholesterol in the serum [SCHOL], and the same percentage in the exudates, between the PF/S LDL ratio (0.46) and the PF/S CHOL ratio (0.48), or between the PF/S ApoB ratio and the PF/S LDL ratio. The percentage of PF cholesterol bound to HDL and LDL was significantly higher (91.9%) than in the blood (90%). No significant correlations were found between any of the lipids studied and the number of erythrocytes and leucocytes. In conclusion, the PFCHOL may be predicted from the SCHOL, and the capillary permeability may be reflected by the PF/S prot ratio., (Copyright 2010 Mosby, Inc. All rights reserved.)

Cornelia de Lange syndrome involves multiple malformations with particular phenotypic features (craniofacial abnormalities such as microcephaly or hypertrichosis with synophrys; cutaneous abnormalities such as hirsutism, and limb anomalies) and it is associated with a high percentage of mental retardation and complications such as digestive tract abnormalities, cardiac defects, and endocrine disorders. We report the case of a 2-month-old infant girl who underwent a laparoscopic antireflux procedure, with closure of a diaphragmatic hernia and a gastric stoma. The medical history included repeated episodes of aspiration pneumonia and hypertension. Early in the procedure, 2 episodes of sudden desaturation, hypotension, and bradycardia with a probable diagnosis of air embolism. The complications resolved with specific treatment. Anesthetic management for laparoscopic surgery in these patients is truly complex and must be informed by a thorough understanding of the disease and complications that may develop.

There is an increasing interest in the secondary structure of beta-amino-acid-containing peptides, since these compounds exhibit an intrinsic propensity to form stable folds even for short peptides, a feature that is rarely observed in alpha-amino-acid-containing peptides. In this work, we use a multiple trajectory molecular dynamics approach to study a panel of cyclic beta-amino-acid-containing peptides with a variety of motifs that differ in the ring size, ring substituents, and terminal protecting groups. We find a reasonable agreement between the predicted and the experimentally observed structures, in spite of the simple solvent representation used, indicating that in most cases the folding proceeds energetically downhill and it is driven to a great extent by structural preferences coded in the internal degrees of freedom, a result supported by our energy partition analysis. Our results also show that when the N-terminal end is unprotected, it is likely to be charged in a protic polar solvent. In that case, we find that only a molecular dynamics simulation with an "all atom" solvent representation is capable of reproducing the experimentally observed secondary structure of the peptide. Finally, the time evolution analysis of the hydrogen-bond-induced turns as well as of the root-mean-square deviation from the observed structure indicates that some peptides could have a higher intrinsic flexibility than others, within a given fold, a result that correlates to some degree with our molecular mechanics energy analysis.

The title compound, C(24)H(27)NO(9), is one of the epimers of the Henry reaction of 3-O-benzyl-6-O-benzoyl-2-O-isopropyl-idene-a-d-glucofuran-5-one with nitro-methane. The conformation of the five membered rings is as expected from the precursor compound and the mol-ecule is folded with a dihedral angle of 51.4 (2)° between the aromatic rings. One O-H⋯O hydrogen bond and some intra-molecular and inter-molecular C-H⋯O inter-actions are observed in the structure.

The title compound {systematic name: (2S,3R)-ethyl 3-[(3aS,4R,6S,6aS)-6-tert-butyl-dimethyl-silyl-oxy-2,2-dimethyl-per-hydro-furo[3,4-d][1,3]dioxol-4-yl]-2-nitro-3-[(S)-tetra-hydro-2H-pyran-2-yl-oxy]propanoate}, C(23)H(41)NO(10)Si, is the product of the Henry reaction of 1-O-tert-butyl-dimethyl-silyl-2,3-O-isopropyl-idene-α-d-lyxo-penta-dialdo-1,4-furan-ose with ethyl nitro-acetate and the subsequent protection of its C-5 hydr-oxy group as tetra-hydro-pyranyl, in order to avoid the retro-Henry reaction. The tetra-hydro-pyranyl group adopts a chair conformation. The absolute configuration, assumed from the synthesis, was confirmed from the diffraction data.

Objective: To find out the opinion of Primary Health Care (PHC) professionals on the impact of the Preventive Activities and Health Promotion Program (PAPPS)., Design: Descriptive qualitative-quantitative study. In a first phase the SWOT technique was used. In a second phase a 47 item questionnaire was designed using an ordinal scale., Participants: Professionals of PAPPS health centre, PAPPS managers and PHC management, using the Autonomous Community, and the time of ascribing or knowledge of PAPPS as segmentation criteria. In the qualitative study 62 participants were selected by theoretical sampling. In the quantitative study, 198 professionals took part in the survey., Principal Measurements: The assessment of the results has taken into account the responses to the questions formulated and by performing a crossed analysis between strengths/threats and weaknesses/opportunities. A descriptive statistical analysis of the questions in the questionnaire., Results: There is agreement in that PAPPS has greatly influenced the development of PHC, contributing to improving the quality of care, but it is also fundamental to try revitalise the programme, as the limited involvement by the professionals in the postulated preventive recommendations is its main weakness, due to lack of motivation and professional burn-out.., Conclusions: According to the participants PAPPS has contributed significantly to the development of PHC in our country and has had an influence on professional practice by instilling a prevention culture that hardly existed before.

A novel promising strategy for the transformation of nitrosugars into branched pyrrolidines, based on double Henry reaction with formaldehyde followed by reductive ring closure, allowed the first enantiospecific synthesis of a 4-C-hydroxymethyl branched derivative of the well-known glycosidase inhibitor 1,4-dideoxy-1,4-imino-pentanol. This strategy also afforded a new route to some other interesting derivatives, such as N-hydroxy, N-propyloxy, and imino derivatives, a new kind of compounds with promising biological properties. [reaction: see text].

[reaction: see text] An intramolecular Henry cyclization provides a promising new strategy for the transformation of nitroheptofuranoses into deoxyhydroxymethylinositols. This method has allowed a stereospecific transformation of d-glucose into 1D-3-deoxy-3-hydroxymethyl-myo-inositol.

A promising new strategy for the transformation of nitrohexofuranoses into cyclopentylamines, based on intramolecular cyclization followed by controlled opening of the resulting 2-oxabicyclo[2.2.1]heptane derivatives, allowed the first total synthesis of a carbocyclic beta-amino acid and its incorporation into peptides. This strategy also afforded a new route to cyclopentylamines with well-known glycosidase inhibition properties. [reaction: see text]

Background: To evaluate the possible relation between left ventricular hypertrophy and vascular changes in retine, in patients with mild hypertension., Patients and Methods: We established a group with 51 hypertensives (27 males and 24 females), with essential mild hypertension, which had never been treated. An ambulatory monitoring blood pressure, 24 hours electrocardiographic monitoring, echocardiography and funduscopy were realized to all of them., Results: Fifty-five per cent of the hypertensives had retinopathy grades I-II. We established two subgroups with and without retinopathy. The age, systolic, diastolic and mean blood pressures, so as body mass index higher in the group with retinovascular damage. No significant differences were observed in the ecographic parameters between two subgroups except the interventricular septal thickness (10.5 +/- 2.1 min in the subgroup without vs 11.1 +/- 2.3 mm in the subgroup with retinovascular damage) (p < 0.05). As 24-hour maximum and mean systolic and diastolic blood pressure, daytime mean systolic blood pressure (SBP) and diastolic blood pressure (DBP), daytime and night-time DBP load, as daytime SBP load were higher in the hypertensive patients with retinovascular changes. There was echocardiographic left ventricular hypertrophy in 51% of the hypertensive patients, without differences between both subgroups of hypertensive patients. Body mass index (g/m) correlated significantly (p < 0.01) with the retinovascular damage. In the multivariant analysis, male as well as female, the funduscopy correlated with left ventricular mass index (g/m2). We established a discriminant function to separate hypertensives with and without left ventricular hypertrophy and another to separate hypertensives with and without retinopathy. Both functions included body mass index and maximum SBP, so as daytime SBP load and nighttime mean DBP to the left ventricular hypertrophy function., Conclusions: Left ventricular hypertrophy and retinovascular damage appear early in the course of blood pressure elevation and both changes develop in parallel. Our results indicate that there exists a relation between both cardiac and vascular changes in the hypertension. Body mass index and maximum SBP, appear to be important determinants of structural adaptation in mild hypertension.

Background: To establish if the differences between male and female hypertensives, with similar characteristics, are associated with different cardiovascular damage., Patients and Methods: We compare a group of 27 mild hypertensive males with another one of 24 females with similar characteristics. A 24-hour ambulatory blood pressure monitoring, a 24-hour ECG holter, an echocardiography and eye funduscopy, were done to all the patients., Results: The mean of 24 hour-systolic blood pressure (p < 0.01), the daytime and night-time systolic blood pressure load (p < 0.05), and the mean of systolic blood pressure daytime, were significantly are not higher in male than in female hypertensives. Neither echocardiographic differences nor frequency of arrhythmias were observed between both groups. 66.7% of the women had left ventricular hypertrophy vs 37% of the men, without significant difference. 40.7% of the male had rethynopathy I-II vs 50% of the female. Left ventricular mass index correlated with different parameters of the ambulatory monitoring in the multivariate analysis. Body mass index and daytime systolic blood pressure load classified correctly 89% of the male-group in with or without hypertensive rethynopathy. The body mass index, age and 24-hour maximal systolic blood pressure, classified correctly 87.5% of female hypertensives in with and without hypertensive rethynopathy., Conclusions: The differences in the ambulatory blood pressure monitoring between male and female mild hypertensive patients, were not associated with different cardiovascular damage. We emphasize the importance of the body mass index in the development of hypertensive rethynopathy in both sexes.

Objective: To determine the clinical implications of mild white coat hypertension (WCH)., Subjects and Methods: We studied 102 subjects (54 men, 48 women), 51 of whom were normotensive and 51 slightly hypertensive. None had ever received antihypertensive therapy. An ambulatory blood pressure (ABP) record (Accutracker II), a 24-h electrocardiogram and an echocardiogram were obtained from each, and each was examined by funduscopy. WCH subjects were compared with sustained hypertension (SH) subjects and with normotensives., Results: Fifty-three percent of the hypertensives qualified as WCH. The ultrasonographic characteristics and the ABP variables of the WCH group differed significantly from those of normotensives, but not from those of the SH group. The prevalence of left ventricilar hypertrophy (LVH) in the SH group (62.5%) did not differ significantly from its prevalence in the WCH group (40.7%), but the prevalence among normotensives (17.6%) was significantly lower than in either of the other two groups. The WCH and SH groups did not differ significantly as regards the prevalence of hypertensive retinopathy (33.3% in the former, 58.3% in the latter). For no non-LVH, non-retinopathic subject, whether normotensive or hypertensive, were more than 18% of daytime diastolic ABP measurements > or = 90 mmHg. Ultrasonographic findings were no better correlated with ABP than with in-clinic BP measurements. Fundus findings correlated well with in-clinic BP and with numerous ABP parameters. Retinopathy, with or without LVH, was efficiently predictable among hypertensives on the basis of body mass index and the 24-h maximum of systolic BP., Conclusions: Myocardiac remodelling and vascular retinopathy develop early and in parallel in hypertensives, and both developments appear to involve determinants including body mass index and 24-h maximum systolic BP. WCH subjects, as defined by current ABP-based criteria, have cardiac and retinovascular characteristics different to normotensive subjects. Stricter criteria are needed to discriminate between hypertensives with and without the systemic developments that constitute the immediate source of risk to the hypertensives individual.

Background: The development of arrhythmias in patients with high blood pressure has been related to the presence of left ventricular hypertrophy. The aim of this study was to determine the presence and relationship between left ventricular hypertrophy and arrhythmias in patients with slight arterial hypertension., Methods: One hundred and two individuals (54 males and 48 females), 51 of whom were hypertensive and 51 normotensive, were included in the study. None of the subjects had received antihypertensive treatment. Twenty-four hour electrocardiographic registry, echocardiogram and ambulatory blood pressure monitorization were performed., Results: Fifty one percent of the hypertensive individuals had left ventricular hypertrophy (LVH) versus 18% of the normotensive subjects. Supraventricular and ventricular arrhythmias were equally frequent in the hypertensive and the normotensive subjects as were the episodes of ST depression (7.8% versus 9.8%, respectively). Both types of arrhythmias were correlated with the age of the hypertensive subject. Twenty-seven of the hypertensive subjects had white coat hypertension. The left ventricular mass in these subjects was similar to that of the hypertensive subjects with maintained hypertension and both were greater than the normotensive subjects. In regard to the frequency of LVH in the hypertensive subjects with maintained hypertension, 15 (62.5%) did not differ from either the LVH in white coat hypertensive subjects 11 (40.7%) or in regard to the frequency of supra and ventricular arrhythmias. On multivariate analysis both types of arrhythmias correlated with the index of ventricular mass in the hypertensive patients in both males and females., Conclusions: Left ventricular hypertrophy may develop early in hypertension although it is not related to a greater frequency of arrhythmias in patients with slight arterial hypertension.

A study of 100 patients with chronic urticaria by Giardia lamblia parasitic infection were reviewed. The urticaria had been resistant to antihistamine, corticosteroid and antiparasitic therapy. An urticaria evaluation included CBC, immunoglobulins M, G, A and E determinations, and stool examination, bile drainage and duodenal smear for ova and parasites. A prick test with Giardia's allergen 1, 10 and 100 UNP dilutions were realized. We found a 93% improvement in clinical symptoms using allergy immunotherapy with Giardia's antigen preparation associated to treatment.

A prospective study that included 50 patients with acute anterior uveitis was done. The aim was to describe their immunological behavior. According to the results, patients with an allergic basis are predisposed and have more severe disease. However, immunoallergic tests are positives in patients with acute anterior uveitis where associated pathologies modify the tests, even if allergic etiology may or may not be possible. We recommend further studies in patients with allergic antecedents, in order to pay more attention to them.