Biomarkers in 5q-associated spinal muscular atrophy-a narrative review.

5q-associated spinal muscular atrophy (SMA) is a rare genetic disease caused by mutations in the SMN1 gene, resulting in a loss of functional SMN protein and consecutive degeneration of motor neurons in the ventral horn. The disease is clinically characterized by proximal paralysis and secondary skeletal muscle atrophy. New disease-modifying drugs driving SMN gene expression have been developed in the past decade and have revolutionized SMA treatment. The rise of treatment options led to a concomitant need of biomarkers for therapeutic guidance and an improved disease monitoring. Intensive efforts have been undertaken to develop suitable markers, and numerous candidate biomarkers for diagnostic, prognostic, and predictive values have been identified. The most promising markers include appliance-based measures such as electrophysiological and imaging-based indices as well as molecular markers including SMN-related proteins and markers of neurodegeneration and skeletal muscle integrity. However, none of the proposed biomarkers have been validated for the clinical routine yet. In this narrative review, we discuss the most promising candidate biomarkers for SMA and expand the discussion by addressing the largely unfolded potential of muscle integrity markers, especially in the context of upcoming muscle-targeting therapies. While the discussed candidate biomarkers hold potential as either diagnostic (e.g., SMN-related biomarkers), prognostic (e.g., markers of neurodegeneration, imaging-based markers), predictive (e.g., electrophysiological markers) or response markers (e.g., muscle integrity markers), no single measure seems to be suitable to cover all biomarker categories. Hence, a combination of different biomarkers and clinical assessments appears to be the most expedient solution at the time.

[New treatments for spinal muscular atrophy]. / Neue Therapien der spinalen Muskelatrophie.

5­q-associated spinal muscular atrophy (SMA) has so far been a causally untreatable disease, which leads to severe, progressive physical restrictions due to the loss of spinal motor neurons. However, the monogenetic cause of the relatively short coding "survival motor neuron" (SMN) 1 gene sequence and the presence of almost identical gene copies, the SMN2 genes, offer favorable conditions for the development of new therapeutic approaches. While previously only supportive and palliative therapies could be used, new disease-modifying drugs are now available for the first time. Nusinersen, an antisense oligonucleotide (ASO), is the first drug that has received approval in Germany to treat SMA. Further therapeutic approaches such as the so-called "small molecules" or the gene replacement therapy are currently still being tested in clinical studies or are already waiting for approval by the European Medicines Agency (EMA). In this article, the most important disease-modifying drugs of SMA, the associated studies and their challenges are presented.

Comparison of secondary ion mass spectrometry and micromilling/continuous flow isotope ratio mass spectrometry techniques used to acquire intra-otolith delta18O values of wild Atlantic salmon (Salmo salar).

The chemical signals in the sequential layers of fish otoliths have the potential to provide fisheries biologists with temporal and spatial details of migration which are difficult to obtain without expensive tracking methods. Signal resolution depends, however, on the extraction technique used. We compared the use of mechanical micromilling and continuous flow isotope ratio mass spectrometry (CF-IRMS) methods with secondary ion mass spectrometry (SIMS) to obtain delta(18)O profiles from otoliths of wild Atlantic salmon (Salmo salar) and used these to corroborate the time of freshwater emigration of the juvenile with macroscopic patterns within the otolith. Both techniques showed the transition occurring at the same visible feature on the otolith, allowing future analyses to easily identify the juvenile (freshwater) versus adult (marine) life-stages. However, SIMS showed a rapid and abrupt transition whereas micromilling provided a less distinct signal. The number of samples that could be obtained per unit area sampled using SIMS was 2 to 3 times greater than that when using micromilling/CF-IRMS although the delta(18)O values and analytical precisions (approximately 0.2 per thousand) of the two methods were comparable. In addition, SIMS delta(18)O results were used to compare otolith aragonite values with predicted values calculated using various isotope fractionation equations.

The use of nutritional supplements among master athletes.

We assessed the use of nutritional supplements among master athletes focusing on their source of information and source of supply of nutritional supplements. 1560 standardized, anonymous questionnaires were distributed among participants of the World Masters Athletics Championships Indoors 2004. These questions were related to biometric parameters, social indicators, training parameters, illicit drugs, and nutritional supplements. Chi2-tests were computed to reveal meaningful associations between basic information (age, gender, family status, children, education, country of origin, disciplines, training years, smoking, and the use of alcohol, illicit drugs, and doping) and the intake of nutritional supplements. Descriptive information on the history of their use of nutritional supplements was also provided. 60.5 % of all participants reported the actual use of nutritional supplements. We found no significant differences between nutritional supplement users and non-users with regard to basic information. The substances predominantly used were vitamins (35.4 %) and minerals (29.9 %). In contrast to elite athletes who use nutritional supplements to increase their athletic performance, master athletes use these substances predominantly for health reasons and, thus, have a closer contact to the health care system. Physicians are their preferred source of information about nutritional supplements. More than half of the interviewed athletes obtain their nutritional supplements from pharmacies or physicians. The results of this study indicate that nutritional supplement users in master athletics show no specific user profile. Since it is not rare for nutritional supplements to contain trace contaminations of anabolic androgenic steroids or pro-hormones, physicians should also inform master competitive athletes of the dangers of testing positive for doping substances due to their intake of nutritional supplements and advise them accordingly.

Bioeffects of diagnostic ultrasound in vitro.

Biological effects induced by ultrasound were frequently reported for continuous wave (cw) mode. Thresholds for the onset of bioeffects of pulsed ultrasound, starting from diagnostic conditions, have not yet been defined by standardized in vitro models. We therefore investigated the effects of pulsed ultrasound on cultured cells using diagnostic ultrasound devices, a selfmade transducer and a sonochemical laboratory reactor tunable from pulsed diagnostic conditions to cw ultrasound. Additionally, we determined physical parameters of the ultrasonic field by different types of hydrophones. Sonochemical reactions and the effects induced by the ultrasonic fields in cultured cells indicated a threshold for bioeffects.

A quantitative test method for the examination of antimycobacterial disinfection procedures.

Various aspects of the test methods currently established in western industrial countries for the qualitative and to a certain extent quantitative measurement of the antimycobacterial efficacy of disinfection procedures have recently been increasingly criticized in the international literature. For this reason, a quantitative test method for suspension trials and carrier trials, which includes the test strain Mycobacterium terrae ATCC 15755, has been developed. Experience with the new methods has proved them easy to learn and to reproduce. Before the methods, presented here in detail, can be recommended to the German Society for Hygiene and Microbiology (Deutsche Gesellschaft für Hygiene und Mikrobiologie, DGHM) as official testing procedures, their acceptability should be tested in a multicenter study. Taking the results thus obtained into consideration, recommendations for the reduction factors required for the declaration of a safe antimycobacterial disinfection procedure should be made.

Laser lingual tonsillectomy.

Diseases of the lingual tonsils are generally overlooked in both clinical practice and medical literature. Infections of the lingual tonsils are usually treated medically, although in patients with symptomatic chronic inflammation or hyperplasia of the lingual tonsils, surgical intervention may be indicated. Eighty-two patients with benign inflammatory problems of the lingual tonsils, who were not improved by medical management, underwent laser lingual tonsillectomy at four different medical centers, between 1984 and 1987. The procedure was tolerated well by all of the patients, with no significant operative complications. Short- and long-term results were satisfactory. Laser surgery is an effective method for the treatment of benign hyperplastic and inflammatory diseases of the lingual tonsils.

Expenditures and revenues of state mental health agencies, 1981-1985.

Data compiled by the National Association of State Mental Health Program Directors were used to compare expenditures and revenues of state mental health agencies in fiscal years 1981, 1983, and 1985. The agencies had direct control of funds totaling $8.3 billion in 1985, compared with $7.1 billion in 1983 and $6.1 billion in 1981, but spending in the three years varied by less than 1 percent in inflation-adjusted dollars. Spending for state mental hospitals declined by 5 percent, while spending for community-based programs grew by 10 percent. The great majority of the agencies' funds, 78 percent in 1985, were provided by state governments. Information about the budgets of state mental health agencies can help fill the financial information gap that confronts policymakers in the federal, state, and local mental health service delivery systems.

Mediastinitis occurring as a complication of odontogenic infections.

Mediastinitis occurring from a descending odontogenic infection occurs rarely. The diagnosis is sometimes difficult to make and is often delayed until the patient is in extremis. The physical examination is often nondiagnostic, but may include brawny edema of the neck and chest. CT scanning provides the most accurate diagnostic information. The treatment is always surgical, in combination with appropriate antibiotics. Five patients with mediastinitis secondary to odontogenic infections are presented, and the technique of transcervical drainage of the anterior and posterior mediastinum is reviewed.

Chin reconstruction with pectoralis myocutaneous flap.

Chin reconstruction after radical surgery for carcinoma of the oral cavity is a complex and controversial problem. We have developed a simple, single-stage, primary procedure for chin reconstruction. It is easily mastered and is based on a simple modification of the pectoralis major myocutaneous flap. Our experience includes seven cases, including two with total chin reconstructions. The number and type of complication is low and consistent with the magnitude of the surgical procedure. This operation provides acceptable aesthetic and functional results to patients undergoing partial or total resection of the chin.

Hypoparathyroidism following total laryngopharyngectomy and gastric pull-up.

We have used the gastric pull-up technique for closure of large pharyngoesophageal defects after radical oncological surgery since 1979. The management of severe hypocalcemia and hypovitaminosis D seemed more difficult in patients undergoing pull-up reconstruction than in patients undergoing the same extirpative surgery, but reconstructed with more traditional methods. To determine if hypocalcemia and hypovitaminosis D were more common in gastric pull-up patients, and if postoperative management of these conditions is more problematic in this group, we retrospectively compared three groups of head and neck surgery patients. Group 1 consisted of 17 patients undergoing total laryngectomy with thyroid complex preservation. Group 2 consisted of 7 patients undergoing mediastinal dissection with total laryngectomy-thyroidectomy previously or concurrently. Group 3 consisted of 30 patients undergoing total laryngopharyngoesophagectomy-thyroidectomy and gastric pull-up reconstruction. The incidences of hypocalcemia requiring therapy were 12%, 50%, and 73%, respectively, with an overall incidence of 51%. The average amounts of supplemental calcium and vitamin D in the three groups were compared. A significant between the three groups was noted. Finally, the dietary calcium and vitamin D requirements for one problematic patient were prospectively recorded and summarized graphically. We conclude that any patient should be carefully monitored for the signs and symptoms of hypocalcemia after major head and neck surgery. In the special instance of the gastric pull-up patient, calcium requirements and the range of serum calcium fluctuation are greatly increased compared to patients undergoing more traditional methods of reconstruction.

Reconstructive techniques after ablative head and neck surgery.

This article describes the reconstructive alternatives available to the head and neck surgeon today. Myocutaneous flaps, osteomyocutaneous flaps, and free flaps for reconstruction in the head and neck are detailed. Complications attendant to the use of these flaps are reported and cataloged.

Management of recurrent head and neck cancer.

The management of recurrent head and neck malignancy can be one of the most frustrating experiences faced by the head and neck surgeon. A recent study indicates that twice the number of patients succumb to distant metastasis from primary tumors than did 20 years ago. This article discusses the operative management of these patients and the role of radiotherapy and chemotherapy in their treatment.

Combined functional oral rehabilitation after radical cancer surgery.

Formerly, patients requiring extensive reconstruction of the oral cavity and oropharynx after radical, ablative oncologic surgery faced the unhappy prospect of lengthy, multistaged repair to enjoy acceptable cosmesis and a functional oral cavity. The advent of the pectoralis major myocutaneous flap has made soft-tissue, single-stage closure of large oral cavity and oropharyngeal defects a reality. Unfortunately and frequently, restoration of mucocutaneous continuity of the mouth does not result in acceptable function. Advances in the materials and design of prostheses suggested the combination of myocutaneous flap reconstruction and functional, prosthetic restoration as a method of returning the patient with head and neck cancer to a state of acceptable function and appearance soon after major resection.