Patients with Lemierre syndrome have a high risk of new thromboembolic complications, clinical sequelae and death: an analysis of 712 cases.

BACKGROUND: Lemierre syndrome is characterized by head/neck vein thrombosis and septic embolism usually complicating an acute oropharyngeal bacterial infection in adolescents and young adults. We described the course of Lemierre syndrome in the contemporary era. METHODS: In our individual-level analysis of 712 patients (2000-2017), we included cases described as Lemierre syndrome if these criteria were met: (i) primary site of bacterial infection in the head/neck; (ii) objectively confirmed local thrombotic complications or septic embolism. The study outcomes were new or recurrent venous thromboembolism or peripheral septic lesions, major bleeding, all-cause death and clinical sequelae. RESULTS: The median age was 21 (Q1-Q3: 17-33) years, and 295 (41%) were female. At diagnosis, acute thrombosis of head/neck veins was detected in 597 (84%) patients, septic embolism in 582 (82%) and both in 468 (80%). After diagnosis and during in-hospital follow-up, new venous thromboembolism occurred in 34 (5.2%, 95% CI 3.8-7.2%) patients, new peripheral septic lesions became evident in 76 (11.7%; 9.4-14.3%). The rate of either was lower in patients who received anticoagulation (OR: 0.59; 0.36-0.94), higher in those with initial intracranial involvement (OR: 2.35; 1.45-3.80). Major bleeding occurred in 19 patients (2.9%; 1.9-4.5%), and 26 died (4.0%; 2.7-5.8%). Clinical sequelae were reported in 65 (10.4%, 8.2-13.0%) individuals, often consisting of cranial nerve palsy (n = 24) and orthopaedic limitations (n = 19). CONCLUSIONS: Patients with Lemierre syndrome were characterized by a substantial risk of new thromboembolic complications and death. This risk was higher in the presence of initial intracranial involvement. One-tenth of survivors suffered major clinical sequelae.

Parent-Infant Interaction during the First Year of Life in Infants at High Risk for Cerebral Palsy: A Systematic Review of the Literature.

Introduction: Perinatal adverse events put neonates at high risk for short and long-term disabilities, including cerebral palsy (CP). The most recent guidelines about early intervention in infants with brain damage have emphasized the importance of family involvement from the very first phases of development. Early parent-infant interactions are pivotal in promoting infant cognitive and social developmental trajectories. However, little is known about the extent to which severe adverse perinatal events can affect the quality of early parent-infant interactions. Patients and Methods: We systematically searched five databases (PubMed, PsycINFO, EMBASE, CINAHL, and Cochrane Library) for the publications assessing parent-infant interactions in infants at high neurological risk within 1 year of age. Articles were selected if they involved direct comparison between high-risk populations and healthy controls or low-risk populations, and if quantitative or semiquantitative tools were used to assess the parent-infant interaction. Measures of parent-infant interaction included infant interactive behaviors, parental interactive behaviors, and dyadic interactive patterns. Results: The search yielded 18 publications that met the inclusion criteria. The articles represent a high level of heterogeneity in terms of infant neurological risk, infant age, and tools assessing interactive behaviors. Both infant and maternal behaviors within the investigated interactive exchanges were reported to be compromised, leading to subsequent overall impairment of the dyadic patterns. Conclusion: While the studies reviewed here provide general and important information, the review did not yield a clear picture of early dyadic interactions in high-risk infant populations. Further observational studies are warranted in order to provide a more accurate knowledge of the early dyadic exchanges between infants at high neurological risk and their parents, as they might provide a critical opportunity for early family centered habilitative interventions.

1-Halobenzyl-1H-indazole-3-carboxylic acids. A new class of antispermatogenic agents.

The synthesis of a series of halogenated 1-benzylindazole-3-carboxylic acids and related derivatives is described. These compounds were studied for their effect on testicular weight and on the inhibition of spermatogenesis. Many of the derivatives, but in particular 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid (11), 1-(2,4-dibromobenzyl)-1H-indazole-3-carboxylic acid (13), 1-(4-chloro-2-methylbenzyl)-1H-indazole-3-carboxylic acid (27), and their glycerol esters, showed potent antispermatogenic activity.

PIP: The synthesis of 1-halobenzyl-1H-indazole-3-carboxylic acids is described and the effects of these compounds on testicular weight and inhibition of spermatogenesis are reported. Histologically, the antispermatogenic activity of all the active derivatives was similar. Rat testis showed disorganization of the seminiferous tubules consisting mainly of lesion and loss of spermatocytes and spermatids while the spermatogonia and interstitial tissue appeared normal. 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid, 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid, 1-(4-chloro-2-methylbenzyl)-1H-indazole-3-carboxylic acid and their glycerol esters showed the most potent antispermatogenic activity.

Synthesis and pharmacological evaluation of a new class of 2-(2-aminothiazol-4-yl)-2-hydrazonoacetamido cephalosporins.

A series of 2-(2-aminothiazol-4-yl)-2-hydrazonoacetamido cephalosporins 1a-h was prepared. Whenever possible, E and Z isomers were isolated, and their relative stabilities and their interconversions were tested. The antibacterial activity was tested against Gram-positive and Gram-negative bacteria. For compound 1c, whose Z and E forms do not interconvert rapidly, the Z form was the more active one. Among the other compounds, for which the E form is the only stable one for practical purposes, compound 1a was the most active. When compared with cefuroxime and cefotaxime, compound 1a showed slightly lower antibacterial activity but good serum level and half-life values.

No evidence of chromosomal instability in nevoid basal-cell carcinoma syndrome.

The nevoid basal-cell carcinoma syndrome (NBCCS) is a rare multisystem disorder characterized by several alterations of the skin, skeletal, nervous, endocrine system. These patients are more susceptible to cancer and suggestions have been made about an association with the chromosomal breakage syndromes. We studied the induction of chromosomal aberrations by mitomycin C (MMC) and bleomycin and that of sister-chromatid exchanges by MMC and 4-nitroquinoline N-oxide in lymphocytes of 4 NBCCS patients. The frequencies of both spontaneous and induced cytogenetic effects were within normal ranges, suggesting that there is no chromosomal instability in NBCCS patients.

Chemical modifications in the tetracycline series.

New tetracycline analogs modified at position 5, 6 and 2 were synthetized. The 5-deoxy-5-oxo-derivatives, 2a and 3a, were obtained by DMSO/acetic anhydride oxidation of doxycycline (2) and methacycline (3), respectively; the 6-demethyl-6-hydroxymethyl-6-alpha-hydroxyoxytetracycline (3b) by methacycline oxidation with the KCIO3/OsO4 system and the 6-hydroxyanhydrooxytetracycline (4) treating 3b with periodic acid. The 2-ethoxycarbonyl-2-decarboxamidodoxycycline (2b), was synthesized by treating doxycycline nitrile (2c) with EtOH and anhydrous HCl, 2-thiocarboxamide-2-decarboxamidodoxycycline (2d) by reaction of doxycycline with P2S5 in dioxane and 2-aminomethyl-2-decarboxamidodoxycycline (2e) by RANEY-Nickel reduction of 2d. All the synthetized compounds proved to be almost inactive on agar plates both on Gram-positive and Gram-negative bacteria.

Biological monitoring of workers with past lead exposure. Biochemical findings.

In 56 subjects with lead exposure that had terminated at least 3 a previously and in a reference group of nonexposed subjects, the behavior of several biochemical indicators of dose and effect were studied. The mean values for blood lead (PbB) (1.4 +/- 0.4 mumol/l), chelatable lead (PbUEDTA) (3.4 +/- 1.5 mumol/24 h) and free erythrocyte protoporphyrin (FEP) (62 +/- 25.2 micrograms/100 ml red blood cells) were found to be significantly higher in the subjects with past lead exposure than in the referents. The cut-off levels (mean + 2 SD calculated for the reference group) of PbB, PbUEDTA and FEP were exceeded in 35.7, 67.9, and 28.6% of the exposed subjects, respectively. A normalization of lead doses and indicators of effect was reached only when the exposure had not exceeded 2 a. The time elapsed after termination of exposure did not significantly reduce the PbB level and PbUEDTA excretion, whereas these parameters correlated significantly with the length of exposure. A close correlation was found between the PbB and the PbUEDTA. Due to poor sensitivity at PbUEDTA values of less than 5.3 mumol/24 h (91% of the cases), PbB and FEP were not useful for subjects whose exposure had terminated more than 3 a earlier. In these cases, only PbUEDTA was capable of revealing elevated active lead deposits.

Risk factors for varicose disease before and during pregnancy.

Risk factors for varicose disease before and during pregnancy have been analyzed by use of data from a survey on venous disease in pregnancy conducted in 611 women (mean age thirty years, range fifteen to forty-seven) who consecutively delivered at the Obstetric-Gynecologic Clinic "L. Mangiagalli" of Milan between January and April, 1989. In total, 137 women (22%) reported varicose disease before the index pregnancy. The relative risk (RR) of varicose disease before the index pregnancy increased with age, being, as compared with women aged twenty-nine years or less, 1.6 in those aged thirty to thirty-four and 4.1 in those aged thirty-five years or more (chi 2(1) trend 25.28, p < 0.001). Compared with nulliparae, women reporting a full-term pregnancy before the index pregnancy had an RR of venous disease of 1.2, and the risk increased to 3.8 in women reporting two or more births (chi 2(1) trend 25.28, p < 0.001). A family history of varicose disease was associated with an RR of venous disease of 6.2 (95% confidence interval, CI, from 4.1 to 9.6). No relationship emerged between varicose disease and overweight. Of the 474 women who did not report venous disease before the index pregnancy, 132 (28%) developed venous disease during the index pregnancy. The risk of developing venous disease in pregnancy increased with age, being, as compared with women aged twenty-four years or less, 4.0 in those aged thirty-five years or more, and the trend in risk was statistically significant (chi 2(1) trend 16.25, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Synthesis and pharmacological evaluation of 2,3-dialkylindoles, "in vitro" inhibitors of thrombin-induced platelet aggregation.

A series of 2,3-dialkylindoles (1-5) have been prepared and tested as antithrombotic agents. The whole class showed in vitro interesting activity in the inhibition of thrombin-induced aggregation. Among these compounds some ones showed activity comparable to standards also in the inhibition of collagen-induced aggregation. Owing to a very fast metabolic degradation through a beta-oxidative mechanism, a drastic decrease of activity in several tests ex vivo or in vivo was observed.

[Our experience concerning scrotal traumatology]. / La nostra esperienza sulla traumatologia scrotale.

The Authors present their experience on 24 blunt scrotal traumas observed since January 1991. They underline the importance of an ecographic scanning that enables a precise evaluation of the traumatic event. Patients that present positive ultrasonic findings are promptly operated thus permitting bleeding and infection control. In this way gonadic function is restored and hospital care reduced. The diagnostic approach is presented, cases reported and results discussed. After a review of the literature on the topic they stress the role of Eco-Color-Doppler examination in scrotal blunt trauma for the intrinsic characteristics of precision, rapidity and non invasivity. This permits a nosologic evaluation of all types of blunt trauma and selects, for surgery, only those patients with a well definied diagnosis.

[Epidemiological study of mortality in a cohort of rayon industry employees]. / Studio epidemiologico di mortalità in una coorte di addetti alla produzione del rayon viscosa.

A cohort of 166 employees in the SNIA viscosa rayon production plant in Padua was followed up for mortality up to 1989. The study detected a statistically significant increase in total mortality mainly due to an excess of deaths from ischaemic heart diseases (ICD 410-414). Workers affected by occupational disease in the age group 50-64 years had the highest risk with a threefold increase in mortality compared to the general population. An increasing pattern of lung cancer mortality with time since first exposure was observed. The SMR for lung cancer was 192 for smokers with occupational disease.

[A new inclusion complex of silibinin and beta-cyclodextrins: in vitro dissolution kinetics and in vivo absorption in comparison with traditional formulations]. / Nuovo complesso di inclusione tra la silibina e la beta-ciclodestrina: velocità di dissoluzione in vitro e assorbimento in vivo in confronto a formulazioni tradizionali.

The very low bioavailability of silybinin, the main constituent of silymarin, so far prevented the development of an oral pharmaceutical specialty based on this active ingredient. To overcome this difficulty, an inclusion complex between Silybinin and beta-Cyclodextrin was prepared. The new complex was compared in vitro tests (dissolution rate) and in a in vivo test (rat bile elimination) with silybinin, silymarin and one traditional formulation based on silybinin. The results show a dramatic increase in the dissolution rate of the complex (> 90% within 5 min) respect to the silybinin that confirm to be practically insoluble (< 5%). The in vivo results agree with the dissolution rates; after administration of the silybinin complex p.o., the silybinin concentration in the rat bile was near 20 times more than after administration of silybinin as is or in a traditional formulation. In the last two cases, the silybinin concentration was even 6 times less than after administration of the same amount of silymarin. These data show that the beta-CD complex solved the problem of the bioavailability of silybinin which, in the traditional formulation utilised as reference, proved to be not bioavailable.