Surgical treatment of gastroesophageal reflux with esophageal stricture in infancy and childhood

During the past 5 years, 26 infants and children with gastroesophageal reflux were operated on. The results have been highly satisfactory and unattended by serious complications or mortality. Barium fluoroscopy was the most reliable diagnostic method. The indications for operation were persistent vomiting with failure to thrive, recurrent aspiration pneumonia, gastrointestinal bleeding and peptic stricture of the esophagus, not relieved by medical treatment. The high incidence of peptic stricture of the esophagus (50 percent) may reflect delay in diagnosis and medical treatment, which is successful in 60 to 87 percent of the infants with gastroesophageal reflux. Surgical treatment consisted of Nissen fundoplication combined with gastrostomy in cases of esophageal stenosis where dilatations were indicated. Complications related to the operation were minimal. In a follow-up period of 9 months to 5 years, all patients had obtained relief of symptoms of reflux and had excellent nutritional status and normal growth.     

Simultaneous activation of gamma and theta network oscillations in rat hippocampal slice cultures

Hippocampal activity in vivo is characterized by concurrent oscillations at theta (4–15 Hz) and gamma (20–80 Hz) frequencies. Here we show that cholinergic receptor activation (methacholine 10–20 nm) in hippocampal slice cultures induces an oscillatory mode of activity, in which the intrinsic network oscillator (located in the CA3 area) expresses simultaneous theta and gamma network oscillations. Pyramidal cells display synaptic theta oscillations, characterized by cycles consisting of population EPSP-IPSP sequences that are dominated by population IPSPs. These rhythmic IPSPs most probably result from theta-modulated spiking activity of several interneurons. At the same time, the majority of interneurons consistently display synaptic gamma oscillations. These oscillatory cycles consist of fast depolarizing rhythmic events that are likely to reflect excitatory input from CA3 pyramidal cells. Interneurons comprising this functional group were identified morphologically. They include four known types of interneurons (basket, O-LM, bistratified and str. lucidum-specific cells) and one new type of CA3 interneuron (multi-subfield cell). The oscillatory activity of these interneurons is only weakly correlated between neighbouring cells, and in about half of these (44 %) is modulated by depolarizing theta rhythmicity. The overall characteristics of acetylcholine-induced oscillations in slice cultures closely resemble the rhythmicity observed in hippocampal field and single cell recordings in vivo . Both rhythmicities depend on intrinsic synaptic interactions, and are expressed by different cell types. The fact that these oscillations persist in a network lacking extra-hippocampal connections emphasizes the importance of intrinsic mechanisms in determining this form of hippocampal activity.     

Role of ultrasound in the diagnosis of abdominal hydatid disease

Experience with the use of ultrasound for investigating hydatid disease of the abdomen is reported. The presence of daughter cysts within the parent cyst gives a pathognomonic sonographic picture, whether the cyst is single or multiple. The presence of single cysts without daughter cysts is still a diagnostic problem, unless calcification is seen. Associated secondary infection changes the picture to one of a nonspecific abscess, and only the presence of additional cysts can give a clue about the etiology.     

Post-exposure treatment of VX poisoned guinea pigs with the engineered phosphotriesterase mutant C23: A proof-of-concept study

The highly toxic organophosphorus (OP) nerve agent VX is characterized by a remarkable biological persistence which limits the effectiveness of standard treatment with atropine and oximes. Existing OP hydrolyzing enzymes show low activity against VX and hydrolyze preferentially the less toxic P(+)-VX enantiomer. Recently, a phosphotriesterase (PTE) mutant, C23, was engineered towards the hydrolysis of the toxic P(−) isomers of VX and other V-type agents with relatively high in vitro catalytic efficiency (k_cat/K_M = 5 × 10⁶ M⁻¹ min⁻¹). To investigate the suitability of the PTE mutant C23 as a catalytic scavenger, an in vivo guinea pig model was established to determine the efficacy of post-exposure treatment with C23 alone against VX intoxication. Injection of C23 (5 mg kg⁻¹ i.v.) 5 min after s.c. challenge with VX (∼2LD₅₀) prevented systemic toxicity. A lower C23 dose (2 mg kg⁻¹) reduced systemic toxicity and prevented mortality. Delayed treatment (i.e., 15 min post VX) with 5 mg kg⁻¹ C23 resulted in survival of all animals and only in moderate systemic toxicity. Although C23 did not prevent inhibition of erythrocyte acetylcholinesterase (AChE) activity, it partially preserved brain AChE activity. C23 therapy resulted in a rapid decrease of racemic VX blood concentration which was mainly due to the rate of degradation of the toxic P(−)-VX enantiomer that correlates with the C23 blood levels and its k_cat/K_M value. Although performed under anesthesia, this proof-of-concept study demonstrated for the first time the ability of a catalytic bioscavenger to prevent systemic VX toxicity when given alone as a single post-exposure treatment, and enables an initial assessment of a time window for this approach. In conclusion, the PTE mutant C23 may be considered as a promising starting point for the development of highly effective catalytic bioscavengers for post-exposure treatment of V-agents intoxication.     

Renal impairment according to acute kidney injury network criteria among ST elevation myocardial infarction patients undergoing primary percutaneous intervention: a retrospective observational study

Objective

Conflicting data exists regarding the frequency and significance of acute kidney injury (AKI) in ST segment elevation MI (STEMI) patients. The acute kidney injury network (AKIN) classification has been shown to predict mortality in various critically ill patients; however, limited information is available regarding its use and its clinical relevance among STEMI patients.

Study design and methods

We retrospectively studied 1,033 STEMI patients undergoing primary percutaneous intervention (PCI). AKI was identified on the basis of the changes in serum creatinine during hospitalization according to the AKIN criteria. Patients were assessed for in-hospital adverse outcomes as well as all-cause mortality up to 5 years.

Results

Overall, 100 patients (9.6 %) developed AKI: 79 patients (79 %) had stage 1, 14 patients (14 %) developed stage 2, and 7 patients (7 %) developed stage 3 AKI. Patients with AKI had more complications during hospitalization, with higher 30 days (11 vs 1 %; p < 0.001) and 5-year all-cause mortality (29 vs 6 %; p < 0.001) compared to those without AKI. The adjusted risk of death increased proportionally to AKI severity. Compared to patients with no AKI, the adjusted hazard ratio for all-cause mortality was 6.68 (95 % confidence interval: 2.1–21.6, p = 0.002) in patients with AKI. Age, hypertension, chronic kidney injury and low left ventricular ejection fraction were independent predictors of developing AKI.

Conclusion

In STEMI patients undergoing primary PCI, AKI assessed by AKIN criteria is a frequent complication, associated with an increased risk of both short- and long-term mortality.     

Impact of Metabolically Healthy Obesity in Patients with Andrological Problems

BackgroundAlthough the pathogenic role of metabolically complicated obesity (MCO) in erectile dysfunction (ED), major adverse cardiovascular events (MACE), and male infertility has been widely studied, that of metabolically healthy obesity (MHO) has been poorly investigated.AimTo assess the role of MHO in the pathogenesis of ED, prediction of MACE, and male reproductive health.MethodsA consecutive series of 4,945 men (mean age, 50.5 ± 13.5 years) with sexual dysfunction (SD) (cohort 1) and 231 male partners of infertile couples (mean age, 37.9 ± 9.1 years; cohort 2) were studied. A subset of men with SD (n = 1,687) was longitudinally investigated to evaluate MACE. All patients underwent clinical, biochemical, erectile function, and flaccid penile color Doppler ultrasound (PCDU) assessment. Infertile men also underwent scrotal and transrectal ultrasound; semen analysis, including interleukin (IL-) 8; and prostatitis-like symptom assessment. MHO was defined as body mass index >30 kg/m² with high-density lipoprotein cholesterol level >40 mg/dL and absence of diabetes or hypertension. The rest of the obesity sample was defined as MCO. MHO or MCO were compared with the rest of the sample, defined as normal weight (NW) individuals.OutcomesClinical, biochemical, erectile, and PCDU assessment in MHO, MCO and NW men in both cohorts; longitudinal MACE incidence assessment in cohort 1.ResultsIn cohort 1, 816 men (16.5%) were obese, 181 (3.7%) were MHO, and 635 (12.8%) were MCO. In cohort 2, 68 men (28.4%) were obese, 19 (8.2%) were MHO, and 49 (21.2%) were MCO. After adjusting for confounders, in both samples, the men with MHO and MCO had lower total testosterone levels and worse PCDU parameters compared with the NW men. However, only MCO men had worse erectile function compared with NW men. In the longitudinal study, both MHO and MCO men independently had a higher incidence of MACE compared with NW men (P < .05 for both). In cohort 2, MHO and MCO men had a larger prostate volume, and MCO men also had higher ultrasound and biochemical (IL-8) features of prostatic inflammation compared with NW men, but no differences in prostatitis-like symptoms or seminal parameters.Clinical implicationsMHO men should be considered at high cardiovascular risk like MCO men and followed-up for erectile dysfunction and prostate abnormalities overtime.Strengths & LimitationsThe study simultaneously examined several endpoints with validated instruments within 2 different male populations, 1 with SD and 1 with infertility. As for limitations, there is no consensus in the scientific community regarding the definition of MHO, and the results are derived from patients with SD or infertility, which could have different characteristics than the general male population.ConclusionMHO is associated with subclinical ED, increased cardiovascular risk, and prostate enlargement.Lotti F, Rastrelli G, Maseroli E, et al. Impact of Metabolically Healthy Obesity in Patients with Andrological Problems. J Sex Med 2019:16;821–832.     

Laser treatment of leg veins: Physical mechanisms and theoretical considerations

BACKGROUND AND OBJECTIVES: A discussion of laser treatment of leg veins is based on a review of the literature, theoretical analysis, and the clinical experiences of the authors. Theoretical computations are discussed within the context of clinical observations. STUDY DESIGN/MATERIALS AND METHODS: A Monte Carlo model is used to examine volumetric heat production, fluence rate, and temperature profiles in blood vessels at 1,064 and 532 nm wavelengths with various beam diameters, vessel diameters, and pulse durations. RESULTS: Clinical observations, Monte Carlo results, and a review of the literature suggest that longer wavelengths and longer pulses durations favor vessel contraction over intraluminal thrombosis. Monte Carlo simulations show that longer wavelengths are more likely to uniformly heat the vessel compared to highly absorbing wavelengths. Methemoglobin production causes deeply penetrating wavelengths to generate more volumetric heat for the same input radiant exposure. CONCLUSIONS: Clinical observations and models support the role of long wavelengths and long pulses in optimal clearance of most leg telangiectasias.     

New strategies for immune-mediated anti-viral drug and vaccine development

Substantial progress in the development of new anti-viral drugs has taken place in recent years. Most of these new drugs belong to three groups of compounds, nucleoside analogs, thymidine kinase-dependent nucleotide analogs and specific viral enzyme inhibitors. Although these drugs revolutionized the treatment of several viral diseases, the involvement of the immune system is crucial for complete recovery and prevention of re-infection. New advances in the understanding of immune regulation mechanisms, mainly the role of cytokines, led to the development of several new immunologically-based anti-viral drugs and treatments. The most studied group of immunomodulators is the cytokines, some of which were shown to act as potent stimulators of immune responses. Other, non-cytokine immune modulators have also been successfully employed in both humans and experimental animals as anti-viral drugs of which several are currently in clinical trials. Advances in genetic engineering and transgenic mouse technologies facilitated the production of humanized as well as authentic human anti-viral monoclonal antibodies. Some of these antibodies proved to be clinically efficacious and are commercially produced as anti-viral drugs. As is often the case in anti-viral treatments, a combination of conventional and an immune-mediated anti-viral drugs or a combination therapy involving immunomodulators, therapeutic vaccines, immune intervention and even gene therapy might prove most efficacious as a treatment for a particular virus. Most of the advances made in anti-viral treatments have also been applied to the development of new vaccines. Some of the classical attenuated viruses are being replaced by recombinant attenuated viruses. Recombinant viral vaccines containing genes encoding other viral antigens and/or cytokines are being tested as new vaccines. Several chimeric viral vaccines have proven efficacious in experimental animals and are now in different phases of clinical trials. This review will encompass the major new developments in this field, including some that have not yet been subjected to human trials.