Late pulmonary sequelae after childhood bone marrow transplantation

BACKGROUND: Respiratory function in transplanted children is important because of the long life expectancy of bone marrow transplant recipients, particularly children. Attention is now being focused on the late sequelae of treatment on organ system function. A few papers have been published but available data are somewhat conflicting. METHODS: A cross sectional study aimed at evaluating the late effects of transplantation on lung function was performed in a group of 52 young patients who were given autologous or allogeneic bone marrow transplants during childhood for haematological malignancies. RESULTS: No patients reported chronic respiratory symptoms. The distribution of respiratory function patterns showed that only 62% of patients had respiratory function within the normal limits; 23% had a restrictive pattern and 15% had isolated transfer factor impairment. The percentage of patients with lung function abnormalities was higher in those who (1) received a bone marrow transplant after two or three complete remissions compared with those who were transplanted immediately after the first remission (54% vs 21%; p < 0.02), (2) underwent allogeneic bone marrow transplantation rather than an autologous transplantation (45% vs 26%; p = 0.06), and (3) had a pulmonary infection compared with those without (56% vs 26%; p = 0.07). CONCLUSIONS: In spite of the absence of chronic respiratory symptoms there is a high prevalence of children with late pulmonary sequelae after bone marrow transplantation. Regular testing is recommended after transplantation, in particular in subjects at higher risk of lung injuries, such as those receiving transplants after more than one remission, those receiving allogeneic transplants, and those having suffered from pulmonary infections. When lung function abnormalities become apparent, long term follow up is necessary to see whether they become clinically relevant. All patients should remain non-smokers after transplantation and should have active early and aggressive treatment for respiratory illnesses.     

Lung function in survivors of childhood acute lymphoblastic leukemia

STUDY OBJECTIVES: To evaluate lung function in patients cured from childhood acute lymphoblastic leukemia (ALL) with chemotherapy alone or plus bone marrow transplantation (BMT). Pulmonary toxicity is a well-recognized side effect of many ALL treatments. DESIGN: Cross-sectional study conducted at least 3 years after cessation of therapy. SETTING: Outpatient pneumology department of the University Hospital. PATIENTS: Forty-four subjects (age range at observation, 6 to 23 years): 21 treated only with intensive Berlin-Frankfurt-Munster (BFM)-type chemotherapy for newly diagnosed ALL (group A), and 23 treated with chemotherapy plus BMT (group B). MEASUREMENTS: A detailed history of smoking habit, respiratory symptoms, and diseases was recorded directly from the patients with the aid of their parents. A complete physical examination and lung function testing (lung volumes and diffusion capacity for carbon monoxide [DLCO]) were performed in all subjects. RESULTS: No patient reported acute or chronic respiratory symptoms or diseases. In group A patients, lung function was in the normal range, except for three subjects in whom there was an isolated impairment of DLCO. In group B patients, lung function was markedly impaired, with more than half the patients having an abnormal DLCO. A statistically significant difference was found between the two groups for FVC (p = 0.022) and DLCO (p = 0.004). CONCLUSIONS: Intensive, BFM-type frontline chemotherapy is not associated with late pulmonary dysfunction; however, retreatment including BMT can frequently injure the lung. Thus, in patients who undergo BMT and whose life expectancy is long, careful monitoring of lung function and counseling about avoiding additional lung risk factors is recommended.     

Erectile Dysfunction in Young Men: Testosterone,Androgenic Polymorphisms,and Comorbidity With Premature Ejaculation Symptoms

BackgroundThe association between erectile dysfunction (ED), free testosterone (T), and androgenic genetic polymorphisms is still unclear. As most studies in the field have focused on older (>40 y.o.) men, data from young men is scarce. In addition, the clinically observed comorbidity between ED and premature ejaculation (PE) has not been explained.AimThe aim of the present study was 3-fold: to assess in a sample of young men (1) the association between ED and T; (2) the role of androgenic genetic polymorphisms in the aforementioned association; and (3) comorbidity between ED and PE symptoms.MethodsStatistical analyses were performed on a population-based sample of 2,302 Finnish men, (M_age = 26.8 years). Hormone samples were available from 317 men, and genotype information was available from a minimum of 1,144 men depending on genetic locus. For twin analyses, the sample contained 533 male individuals from opposite-sex fraternal twin pairs, 491 identical male individuals (110 complete pairs), 493 male individuals from male fraternal twin pairs (92 complete pairs), and 658 siblings of twins.OutcomesThe main outcome measure includes association between levels of salivary T and ED, main effects of the androgen-related genetic polymorphisms on ED scores. Bivariate twin models of PE and ED were fitted to elucidate possible shared etiology.ResultsWe found no significant association between T levels and ED and no significant main effects of the androgenic genetic polymorphisms on ED. We found no evidence suggesting that any of the genetic polymorphisms would moderate the association between T and ED symptoms. We found shared unique environmental influences between PE and ED (r_E = .28).Clinical TranslationObtained data suggest that ED has T-independent causes and that any comorbidity between PE and ED is not explained by a set of genes affecting both phenotypes.Strengths & LimitationsFirst, the sample size for both parts of the study was relatively small, which may make some statistical analyses underpowered. Furthermore, as the sample was a population-based sample of relatively young men, the number of clinically relevant ED cases was low. Second, some concerns about T derived from saliva exist because saliva sampling comes with increased risks of error particularly because saliva samples are more vulnerable to contamination.ConclusionWe found no significant association between free T levels, androgenic genetic polymorphisms, and ED in the younger age cohort. Twin analysis suggested a common nonshared environmental component in PE and ED.Zhuravleva1 ZD, Johansson A, Jern P. Erectile Dysfunction in Young Men: Testosterone, Androgenic Polymorphisms, and Comorbidity With Premature Ejaculation Symptoms. J Sex Med 2021;18:265–274.     

The contribution of the interosseous muscles to the hypothenar compound muscle action potential

The contributions of the various ulnar‐innervated muscles of the hand to the hypothenar compound muscle action potential (CMAP) were estimated by directly stimulating individual muscles and by analyzing CMAP shape changes resulting from manipulations that changed individual muscle lengths. The results show that the first peak of the negative phase of the hypothenar CMAP comes from the hypothenar muscles, but that the second peak is due to a large volume‐conducted potential from the interosseous muscles. The interosseous contribution affects both the amplitude and the area of the CMAP, and makes these parameters sensitive to changes in the configuration of the fingers and the temperature gradient in the hand. To reduce the interosseous contribution, a “balanced reference” consisting of two reference electrodes, one over each tendon, is proposed. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 6–15, 1999     

Shedding Lights on Crude Venom from Solitary Foraging Predatory Ant Ectatomma opaciventre: Initial Toxinological Investigation

Some species of primitive predatory ants, despite living in a colony, exercise their hunting collection strategy individually; their venom is painful, paralyzing, digestive, and lethal for their prey, yet the toxins responsible for these effects are poorly known. Ectatomma opaciventre is a previously unrecorded solitary hunting ant from the Brazilian Cerrado. To overcome this hindrance, the present study performed the in vitro enzymatic, biochemical, and biological activities of E. opaciventre to better understand the properties of this venom. Its venom showed several proteins with masses ranging from 1–116 kDa, highlighting the complexity of this venom. Compounds with high enzymatic activity were described, elucidating different enzyme classes present in the venom, with the presence of the first L-amino acid oxidase in Hymenoptera venoms being reported. Its crude venom contributes to a state of blood incoagulability, acting on primary hemostasis, inhibiting collagen-induced platelet aggregation, and operating on the fibrinolysis of loose red clots. Furthermore, the E. opaciventre venom preferentially induced cytotoxic effects on lung cancer cell lines and three different species of Leishmania. These data shed a comprehensive portrait of enzymatic components, biochemical and biological effects in vitro, opening perspectives for bio-pharmacological application of E. opaciventre venom molecules.     

Triceps Brachii in Incomplete Tetraplegia: EMG and Dynamometer Evaluation of Residual Motor Resources and Capacity for Strengthening

Background:

Candidates for activity-based therapy after spinal cord injury (SCI) are often selected on the basis of manual muscle test scores and the classification of the injury as complete or incomplete. However, these scores may not adequately predict which individuals have sufficient residual motor resources for the therapy to be beneficial.

Objective:

We performed a preliminary study to see whether dynamometry and quantitative electromyography (EMG) can provide a more detailed assessment of residual motor resources.

Methods:

We measured elbow extension strength using a hand-held dynamometer and recorded fine-wire EMG from the triceps brachii muscles of 4 individuals with C5, C6, or C7 level SCI and 2 able-bodied controls. We used EMG decomposition to measure motor unit action potential (MUAP) amplitudes and motor unit (MU) recruitment and firing-rate profiles during constant and ramp contractions.

Results:

All 4 subjects with cervical SCI (cSCI) had increased MUAP amplitudes indicative of denervation. Two of the subjects with cSCI had very weak elbow extension strength (<4 kg), dramatically reduced recruitment, and excessive firing rates (>40 pps), suggesting profound loss of motoneurons. The other 2 subjects with cSCI had stronger elbow extension (>6 kg), more normal recruitment, and more normal firing rates, suggesting a substantial remaining motoneuron population.

Conclusions:

Dynamometry and quantitative EMG may provide information about the extent of gray matter loss in cSCI to help guide rehabilitation strategies.Key words: dynamometry, electromyography, motor units, spinal cord injury, triceps brachiiRestoring upper limb function is a high priority for individuals with tetraplegia due to cervical spinal cord injury (cSCI).¹ Triceps brachii muscle function is critical to upper limb performance. The inability to produce adequate elbow extension force reduces the available workspace in which it is possible to position and stabilize the hand, hindering the ability to perform activities of daily living. Triceps brachii strength is also helpful for pressure relief activities and transfers into and out of a wheelchair. Weakness of the triceps brachii can also lead to elbow flexion contractures, which limit the ability to use compensatory strategies.² Unfortunately, it is common for individuals with cSCI to have weak or absent elbow extension strength as a result of their injury.There is increasing interest in the use of activity-based therapy involving intensive exercise schedules coupled with somatosensory augmentation to improve upper limb function in persons with incomplete tetraplegia.³ This type of exercise has been shown to increase both cortical^4–6 and spinal excitability⁷ and to improve upper limb function.^4–7 However, it is not clear that all individuals with incomplete tetraplegia are necessarily good candidates for these types of programs. If the motoneuron pool of a particular muscle remains largely intact, then an activity-based therapy program that targets the re-establishment of neural connections to activate those motoneurons may increase strength and contribute to improved function. On the other hand, if there has been a major loss of lower motoneurons (gray matter), then the remaining ones may not be able to support an intense schedule of exercise. For these individuals, activity-based therapy might result in overuse weakness and fatigue, as it does in post-polio syndrome.^8,9 The conventional clinical measures for assessing motor impairment after cSCI may not be adequate for distinguishing the level of gray matter damage. Overall motor impairment is classified according to the American Spinal Injury Association (ASIA) Standard Neurological Classification of SCI (ASIA classification),¹⁰ which identifies a single level at and above which motor function is normal and classifies the injury as either complete or incomplete. This classification by itself does not thoroughly characterize the motor resources in the zone of injury. The strength of key muscle groups is assessed by manual muscle testing, which has been shown to be a poor predictor of voluntary strength.^11–13 Moreover, although the triceps brachii is associated in manual muscle testing as the key muscle group of the 7th cervical motor nerve (C7), the muscle actually has 3 heads with multiple innervation levels (C6-8), each of which contributes to elbow extension. Thus more precise knowledge about the deficits and capabilities of particular muscles is needed for making choices about rehabilitation strategies.In this article, we consider 2 more precise modalities for assessing available motor resources: dynamometry and quantitative EMG. Dynamometry presents a quantitative measure of muscle strength during voluntary actions. The intramuscular EMG signal represents the final output of the motoneuron pool and so provides a direct view of neural function at the spinal level.^14–16 In particular, EMG signals from muscles affected by SCI can show reduced numbers of active motor units (MUs) and increased motor unit action potential (MUAP) amplitudes, which are signs of motoneuron loss and subsequent collateral reinnervation, and irregular recruitment and firing patterns, which can indicate impairment of the descending or peripheral drive to the motoneuron pool. We studied 4 individuals with C5, C6, or C7 level SCI to explore the use dynamometry and quantitative EMG for characterizing motor resources in their triceps brachii muscles.     

Comparative study of artificial chromosome centromeres in human and murine cells

Human artificial chromosomes (HAC) are a valuable tool in the analysis of complex chromatin structures such as the human centromere because of their small size and relative simplicity compared with normal human chromosomes. This report includes a comprehensive study of the centromere and chromatin composition of HAC, expressing human genes, generated in human cells and transferred to murine cells. The analysis involved chromatin immuno-precipitation and immuno-FISH on metaphase chromosomes and chromatin fibres. In both the cell types, the HAC consisted of alphoid and non-alphoid DNA and were mainly euchromatic in composition, although a pericentromeric heterochromatic region was present on all the HAC. Fibre-FISH and chromatin immuno-precipitation data indicated that the position of the centromere differed between HAC in human cells and in murine cells. Our work highlights the importance and utilisation of HAC for understanding the epigenetic aspects of chromosome biology.     

Nutritional,Gastrointestinal and Endo-Metabolic Challenges in the Management of Children with Spinal Muscular Atrophy Type 1

The management of patients with spinal muscular atrophy type 1 (SMA1) is constantly evolving. In just a few decades, the medical approach has switched from an exclusively palliative therapy to a targeted therapy, transforming the natural history of the disease, improving survival time and quality of life and creating new challenges and goals. Many nutritional problems, gastrointestinal disorders and metabolic and endocrine alterations are commonly identified in patients affected by SMA1 during childhood and adolescence. For this reason, a proper pediatric multidisciplinary approach is then required in the clinical care of these patients, with a specific focus on the prevention of most common complications. The purpose of this narrative review is to provide the clinician with a practical and usable tool about SMA1 patients care, through a comprehensive insight into the nutritional, gastroenterological, metabolic and endocrine management of SMA1. Considering the possible horizons opened thanks to new therapeutic frontiers, a nutritional and endo-metabolic surveillance is a crucial element to be considered for a proper clinical care of these patients.