Pertussis toxin does not affect the adenosine-induced inhibition of the efferent function of cardiac capsaicin-sensitive nerves

Summary The negative inotropic effect of adenosine (1–100 M) was abolished in isolated guinea-pig atria obtained from pertussis toxin-pretreated guinea pigs electrically driven at 4 Hz. However, the inhibitory effect of the same concentrations of adenosine on the cardiac response to stimulation of non-adrenergic non-cholinergic (NANC), capsaicin-sensitive sensory nerves, was not modified by the toxin.These results suggest that, while pertussis toxin-sensitive G proteins are involved in the negative inotropic effect of adenosine, they do not mediate the inhibitory effect of adenosine on cardiac NANC neurotransmission.     

Laparoscopic treatment of pediatric varicocele: a multicenter study of the italian society of video surgery in infancy

PURPOSE: We report preliminary results of a multicenter study of the Italian Society of Video Surgery in Infancy on the laparoscopic treatment of pediatric varicocele. MATERIALS AND METHODS: A total of 161 children 6 to 16 years old (median age 12.5) underwent laparoscopic treatment of varicocele at 6 pediatric surgery divisions. Varicocele was on the left side in 159 cases (98.7%) and bilateral in 2 (1.3%). Two boys had recurrent left varicocele. All children were treated with laparoscopy, including ligation of the spermatic veins only in 28 (17.3%), and ligation of the testicular veins and artery in 133 (82.7%). In 10 boys (6.2%) an additional procedure was done simultaneously, including closure of an apparently patent peritoneal vaginal duct on the right side in 7 and resection of epiploic adhesions between the intestinal loops and abdominal wall from previous appendectomy in the remaining 3. RESULTS: Average operative time was 30 minutes and hospitalization was about 24 hours. At followup there were 13 minor complications (8%), including left hydrocele in 9 children who underwent the Palomo technique, minor scrotal emphysema in 2 and umbilical granuloma in 2. In our series varicocele recurred in 1 boy (3.5%) who underwent ligation of the spermatic veins only and in 3 (2.2%) treated with the Palomo technique. CONCLUSIONS: Our preliminary experience shows that the results of the laparoscopic approach are comparable to those of the open approach. However, the important advantages of laparoscopy over the open approach are its minimal invasiveness and precision of intervention. Moreover, laparoscopy allows treatment of other intra-abdominal pathological conditions using the same anesthesia, as in 10 patients in our series. We believe that ligating the testicular veins and artery is preferable to ligating the testicular veins only, even if the incidence of hydrocele is not negligible after the Palomo procedure.     

Gingival recessions caused by Herpes Simplex Virus in a patient with COVID‐19 infection

Herpes Simplex Virus type 1 (HSV‐1) is a very common infection often localized in the mucocutaneous junction of the lip. Rarely, it could be detected also in periodontal tissues, associated with an elevated risk of periodontal disease progression and gingival recessions. Recently, HSV‐1 and numerous co‐infections have been reported in literature associated with the Coronavirus and subsequent COVID‐19 disease. This report illustrates a case of HSV‐1 in a patient with Covid‐19 infection, showing the presence of ulcers and vesicles on the gingival margin of maxillary teeth associated with soreness and pain. The histology highlighted the presence of intraepithelial cell ballooning, confirming the diagnosis of HSV‐1 infection.     

A Low-Cost Wireless Bite Force Measurement Device

Assessing maximum voluntary bite force is important to characterize the functional state of the masticatory system. Due to several factors affecting the estimation of the maximum bite force, a unique solution combining desirable features such as reliability, accuracy, precision, usability, and comfort is not available. The aim of the present study was to develop a low-cost bite force measurement device allowing for subject-specific customization, comfortable bite force expression, and reliable force estimation over time. The device was realized using an inexpensive load cell, two 3D printed ergonomic forks hosting reusable subject-specific silicone molds, a read-out system based on a low-cost microcontroller, and a wireless link to a personal computer. A simple model was used to estimate bite force taking into account individual morphology and device placement in the mouth. Measurement reliability, accuracy, and precision were assessed on a calibration dataset. A validation procedure on healthy participants was performed to assess the repeatability of the measurements over multiple repetitions and sessions. A 2% precision and 2% accuracy were achieved on measurements of forces in the physiological range of adult bite forces. Multiple recordings on healthy participants demonstrated good repeatability (coefficient of variation 11%) with no significant effect of repetition and session. The novel device provides an affordable and reliable solution for assessing maximum bite force that can be easily used to perform clinical evaluations in single sessions or in longitudinal studies.     

Recombinant CD4-Pseudomonas exotoxin hybrid protein displays HIV-specific cytotoxicity without affecting MHC class II-dependent functions

The present study describes several in vitro activities of CD4(178)-PE40, a recombinant protein containing a portion of human CD4 linked to active regions of Pseudomonas aeruginosa exotoxin A. Using assays for cell viability, we demonstrate that the hybrid toxin displays highly selective cytotoxicity for HIV-infected T lymphocytes. In a latently infected human T-cell line which is inducible for HIV expression, toxin sensitivity is observed only upon virus induction. At concentrations which readily kill HIV-infected T cells, CD4(178)-PE40 has no observable cytotoxic effects on uninfected human cell lines expressing surface major histocompatibility complex (MHC) Class II molecules, and does not interfere with cellular responses known to be dependent on functional association between CD4 and MHC Class II molecules.     

Immunoregulatory T-lymphocyte subset deficiency in newly diagnosed Type 1 (insulin-dependent) diabetes mellitus

Summary Humoral and cell-mediated disorders in Type 1 (insulin-dependent) diabetes suggest that an imbalance of immunoregulatory T-cell subsets exists. In 23 newly diagnosed (onset < 3 months) and 21 long-standing Type 1 diabetic patients, T lymphocyte subsets were analyzed using monoclonal antibodies (OKT3, OKT4, OKT8, OKM1). The newly diagnosed patients showed a reduction with a significant difference from healthy controls in total T cells (OKT3⁺: 58.1 ±8.5% versus 70.7±8.0%), helper/inducer cells (OKT4⁺: 33.8 ±7.0% versus 47.1 ±8.3%), suppressor/cytotoxic cells (OKT8⁺: 18.5±7.3% versus 32 ± 6.8%) and monocytes (OKM1⁺: 11.5±3.8% versus 19.9±5.2%) (p< 0.001). The long-standing diabetic patients also revealed a low number of immunoregulatory T cells compared with control subjects, although to a lesser extent (p< 0.01–0.05). The helper/suppressor ratio (OKT4⁺/OKT8⁺) was higher in newly diagnosed patients than in control subjects (2.2±1.3 versus 1.5±0.3; p< 0.02). When compared with 95% tolerance limits in the control subjects, the reduction of OKT8⁺ cells in the newly diagnosed diabetic patients appeared more marked: the mean (18.5%) coincided with the lower limit of normal subjects (18.3%). Ten of the newly diagnosed Type 1 diabetic patients had a value below the normal lower limit. Our data point to the occurrence of different immunoregulatory abnormalities in newly diagnosed Type 1 diabetic patients, especially in OKT8⁺ and OKT4⁺ cells. The imbalance in T lymphocyte subsets is further proof of the role of cellular autoimmunity in the pathogenesis of the early phases of Type 1 diabetes.     

Clinical features of infection caused by non-tuberculous mycobacteria: 7 years’ experience

Introduction

Non-tuberculous mycobacteria (NTM) are ubiquitous organisms associated with various infections. The aim of the study was to determine the most relevant clinical characteristics of NTM during the 7-year period.

Methodology

A retrospective study of NTM infections was conducted between January 2009 and December 2016. The American Thoracic Society/Infectious Disease Society of America criteria were used to define cases of pulmonary or an extrapulmonary site.

Results

A total of 85 patients were included in the study. Pulmonary cases predominated 83/85 (98%), while extrapulmonary NTM were present in 2/95 (2%) patients. Overall, ten different NTM species were isolated. The most common organisms were slow-growing mycobacteria (SGM) presented in 70/85 (82.35%) patients. Isolated SGM strains were Mycobacterium avium complex (MAC) in 25/85 (29.41%) patients, M. xenopi in 20/85 (23.53%) patients, M. kansasii in 15/85 (17.65%) patients and M. peregrinum and M. gordonae in 5/85 (5.88%) patients each. Isolated rapid-growing mycobacteria (RGM) strains were M. abscessus in 8/85 (9.41%) patients, M. fortuitum in 4/85 (4.71%) patients and M. chelonae in 3/85 (3.53%) patients. Almost all patients (98%; 83/85) had comorbidities. Among 75 (88.24%) patients who completed follow-up, 59 (69.41%), 10 (11.76%) and 6 (7%), were cured, experienced relapse and died, respectively.

Conclusion

In the present study, pulmonary NTM infections were more frequent compared to extrapulmonary disease forms. SGM were most common isolates with MAC pulmonary disease the most frequently found. Comorbidities have an important role in NTM occurrence. Further investigation should focus on an NTM drug susceptibility testing.

     

Is Migraine Primarily a Metaboloendocrine Disorder?

Purpose of the Review

The goals of this review are to evaluate recent studies regarding comorbidity between migraine and different metabolic and endocrine disorders and to discuss the role of insulin resistance as a common pathogenetic mechanism of these diseases.

Recent Findings

Recently, several studies showed that migraine is associated with insulin resistance, a condition in which a normal amount of insulin induces a suboptimal physiological response. All the clinical studies that used the oral glucose tolerance test to examine insulin sensitivity found that, after glucose load, there is in migraine patients a significant increase of both plasmatic insulin and glucose concentrations in comparison with controls. On the contrary, no association was found between migraine and type 2 diabetes, while type 1 diabetes seems to have a protective effect in the disease. Obesity and hypertension were shown to be risk factors for both episodic and chronic migraine. Metabolic syndrome has been recently associated mainly with migraine with aura and is now considered a risk factor also for medication overuse headache. Finally, a bidirectional association between migraine and hypothyroidism has been recently demonstrated, suggesting that common genetic or autoimmune mechanisms underlie both diseases.

Summary

Recent studies showed that insulin receptor signaling and the related physiological responses are altered in migraine and may have a relevant pathogenic role in the disease. Further studies are warranted in order to better elucidate mechanisms underlying insulin resistance in migraine in order to develop new therapeutic strategies for this debilitating disease.

     

Haemodynamic effects of metoprolol and intravenous nitroglycerin versus metoprolol alone in patients with acute myocardial infarction

Among the various treatments adopted to protect the acutely ischaemic myocardium, favourable results have been reported for beta-blockers. Nitrates can also reasonably be expected to exert favourable effects in acute myocardial infarction considering their haemodynamic action. In this study we compared the haemodynamic effect of metoprolol alone with the effect of metoprolol plus nitroglycerin. Fourteen patients, admitted within 12 hours from the clinical onset of acute myocardial infarction, were initially given intravenous metoprolol (5 + 5 + 5 mg) followed 15 minutes later by an additional 50 mg oral dose. Thereafter, they were randomly allocated to a treatment with metoprolol alone (Group 1) or metoprolol plus intravenous nitroglycerin (Group 2). The two groups were comparable with regard to age, sex, time to admission, time to therapy, site of necrosis, Killip class, and infarct size. Acute beta-blockade induced a marked decrease of cardiac output, systolic blood pressure and heart rate along with a small increase of pulmonary wedge pressure and a marked systemic vasoconstriction. In Group 1 patients these haemodynamic changes persisted up to twelve hours after randomization; in Group 2 patients the addition of nitroglycerin induced a prompt decrease of pulmonary wedge pressure and peripheral vascular resistance whereas the double product was unchanged. In conclusion, intravenous nitroglycerin induces a beneficial haemodynamic effect after early beta-blockade with metoprolol.