Safety assessment of Streptococcus salivarius M18 a probiotic for oral health.

The development of probiotics targeting non-intestinal body sites continues to generate interest amongst researchers, biotech companies and consumers alike. A key consideration for any bacterial strain to be developed into a probiotic is a robust assessment of its safety profile. Streptococcus salivarius strain M18 was originally isolated from a healthy adult and evaluated for its probiotic capabilities targeted to dental and oral health applications. This publication presents the safety characterisation of strain M18. Application of a diverse range of techniques showed that strain M18 can be specifically distinguished from other S. salivarius using a variety of molecular and phenotypic methodologies and that it lacks any relevant antibiotic resistance or virulence determinants. Direct comparison of the strain M18 safety profile with that of the prototype S. salivarius probiotic, S. salivarius strain K12, supports the proposition that strain M18 is indeed safe for probiotic application in humans.

A comprehensive review of oral glucosamine use and effects on glucose metabolism in normal and diabetic individuals.

Glucosamine (GlcN) is a widely utilized dietary supplement that is used to promote joint health. Reports that oral GlcN supplementation at usual doses adversely affects glucose metabolism in subjects with impaired glucose tolerance have raised concerns that GlcN should be contraindicated in individuals with diabetes and those at risk for developing it. This review addresses its potential, when used at typical doses, to affect glucose metabolism and insulin sensitivity in healthy individuals and those with diabetes or 'pre-diabetes'. Publicly available scientific information and data on GlcN were systematically compiled using the electronic search tool, Dialog , and reviewed with special emphasis on human studies. In long-term clinical trials, including those containing subjects with type 2 diabetes or 'pre-diabetes', GlcN produced a non-significant lowering of fasting blood glucose concentrations in all groups of subjects treated for periods of up to 3 years. Owing to limitations in study design, conclusions based on studies that report adverse affects of GlcN on insulin sensitivity and glucose tolerance in pre-diabetic subjects are suspect. However, no definitive long-term studies of GlcN use for individuals with pre-diabetes are available. Nevertheless, based on available evidence, we conclude that GlcN has no effect on fasting blood glucose levels, glucose metabolism, or insulin sensitivity at any oral dose level in healthy subjects, individuals with diabetes, or those with impaired glucose tolerance.

Genotoxicity and subchronic toxicity evaluation of Active Hexose Correlated Compound (AHCC).

Active Hexose Correlated Compound (AHCC), a mushroom extract rich in α-1,4 linked glucans, is associated with immunostimulatory effects. AHCC is used in Japan as a dietary supplement to boost immune function and it also is purported to improve the symptoms of cancer and liver disease patients. A series of toxicological studies were conducted on a freeze dried preparation of AHCC (AHCC-FD) to further develop the body of evidence supporting the safety of this ingredient. AHCC-FD was not mutagenic to Salmonella typhimurium and did not exhibit clastogenicity in a mouse micronucleus assay. In a 90-day study, Sprague-Dawley rats were administered 1000, 3000, or 6000 mg/kg body weight/day by gavage. No changes attributable to AHCC-FD treatment were observed in overall condition, body weight, food consumption, ophthalmology findings, hematology and clinical chemistry parameters, and absolute and relative organ weights. Changes in urinary pH values observed in high-dose animals and mid-dose females were considered physiological rather than adverse effects given the acidic nature of AHCC-FD. Urinary protein also was increased in the same dose groups. As this finding was associated with decreased urinary pH and no evidence of kidney dysfunction was observed, it was considered of no toxicological significance. Histopathological changes related to AHCC-FD administration were observed in the limiting ridge of the stomach and in the liver of the high-dose group. The NOAEL was considered to be 3000 mg/kg body weight/day.

Toxicological assessment of a particulate yeast (1,3/1,6)-beta-D-glucan in rats.

This study investigates the toxicity of WGP 3-6, a yeast-derived beta-glucan ingredient, during single-dose acute and sub-chronic toxicity studies in rats. For the acute study, Fisher-344 rats were administered WGP 3-6 via gavage at a dose of 2000 mg/kg body weight, and any evidence of toxicity was monitored over a 14-day period. WGP 3-6 was well tolerated, indicating that the LD(50) value is greater than 2000 mg/kg body weight. For the sub-chronic study, Fisher-344 rats (10/sex/group) were randomly allocated to receive daily gavage treatment with WGP 3-6 at doses of 0, 2, 33.3, or 100 mg/kg body weight. Control and high-dose satellite recovery groups of each sex also were included. Full toxicological monitoring and endpoint investigations were performed throughout and upon completion of the study. No negative effects on animal weights or food consumption attributable to WGP 3-6 were evident at any dose. In addition, no mortality, clinical pathology, functional/behavioral, microscopic, or gross observations indicating toxicity were observed. Sporadic changes in some biochemical and hematological parameters were observed; however, since the effects were within the physiological ranges in historical controls, were not dose-responsive, or were not observed in both sexes, they were determined to be of no toxicological significance. In conclusion, no adverse or toxic effects were observed after subchronic oral administration of 2, 33.3, or 100mg/kg body weight/day of WGP 3-6 in Fisher-344 rats, and therefore, a no observed adverse effect level (NOAEL) of 100 mg/kg body weight/day, the highest dose tested, was determined.

Position and diaphoresis in acute asthma.

Presence of pulsus paradoxus, PCO2, sternocleidomastoid retraction, and flow rates have been used at the bedside to assess the severity of acute asthma. In our study of 49 adult patients, pulse rate, respiratory rate and pulsus paradoxus were shown to be significantly higher in patients assuming the upright position on admission to the emergency center; arterial pH, PO2, and peak expiratory flow rate were significantly lower in the upright patients. All upright patients had sternocleidomastoid retraction. Peak expiratory flow rate was 73.3 +/- 5 liters per minute in diaphoretic patients, 134 +/- 21 liters per minute in non-diaphoretic, upright patients, and 225 +/- 7.5 liters per minute in recumbent patients (p less than 0.02). No recumbent patient had a peak expiratory flow rate of less than 150 liters per minute or a PCO2 of greater than 44 mm Hg. The index of Fischl, signifying a need for admission to the hospital if greater than 4, was 4 or higher in 70 percent of upright patients and in 88 percent of diaphoretic patients. Only 7 percent of recumbent patients had Fischi indexes of greater than 4.

Management of salicylate intoxication.

Salicylate intoxication is common. It results in impaired generation of adenosine triphosphate and produces a primary respiratory alkalosis. In adults the clinical manifestations may closely simulate a cerebrovascular event or alcoholic ketoacidosis. Central nervous system dysfunction, fever, glycosuria, ketonuria, respiratory alkalosis with an elevated anion gap, tinnitus, dehydration, hypokalaemia and haemostatic defects are common. The diagnosis may be made rapidly by the ferric chloride test or Phenistix test. Standard therapy includes gastric emptying, activated charcoal and alkalinisation of the urine. Osmotic diuresis is a controversial measure. Haemodialysis is indicated for patients with serum salicylate levels more than 100 mg/100ml, severe acid-base disturbance, or deterioration despite optimum therapy.

Emergency tracheotomy in patients with massive neck swelling.

Immediate control of the airway in a patient with massive neck swelling caused by cervical or maxillofacial trauma is often difficult. A modified new technique, discussed in this article, has been developed based on anatomic principles for the performance of a modified tracheotomy in these patients.

Metacarpal and phalangeal fractures.

Metacarpal and phalangeal fractures are common presenting injuries in many emergency departments. The emergency physician should become skilled at properly evaluating and initiating appropriate management and follow-up for these injuries when they occur. Failure to properly do so may result in permanent disability.

The specialty of emergency medicine.

We have focused on those features of emergency medicine that distinguish it as a separate and independent specialty. We have emphasized rapidity and efficiency in approach to emergency patients with chief complaint, set of vital signs, and general appearance, mandating an appropriate history, physical examination, and generic differential diagnosis. The most serious illness (not the most probable) is considered first and the patient protected against the morbid complications of the most serious disease(s). We have pointed out that the development of a rapid rapport with patients, prioritization of care between patients and even between organ systems in a single patient, and a breadth and depth of expertise and technical skills in dealing with the initial presentation of a variety of common acute illnesses are intrinsic to emergency medicine. It is true that emergency physicians and other physicians overlap at times with regard to each of these characteristics. However, as a whole, these facets define a constellation of special expertise. The key to the specialty of emergency medicine is the ability to successfully manage the acute deterioration and pathophysiology of any life or limb threat. There are many technical skills pertinent to this management which are often shared with other disciplines, but the judgment required to manage this acute deterioration, in fact, defines the specialty of emergency medicine.

Safety assessment of the post-harvest treatment of button mushrooms (Agaricus bisporus) using ultraviolet light.

Wild mushrooms are an excellent source of vitamin D. The presence of vitamin D in mushrooms is attributed to sunlight exposure, which catalyzes the conversion of fungal ergosterol to vitamin D2 via a series of photochemical/thermal reactions. Mushroom growers now incorporate UV light treatments during processing to produce mushrooms with levels of vitamin D that compare to those in wild mushrooms. Presented herein is a comprehensive review of information relevant to the safety of introducing vitamin D mushrooms, produced using UV light technologies, to the food supply. Historical reference to the use of UV light for production of vitamin D is discussed, and studies evaluating the nutritional value and safety of vitamin D mushrooms are reviewed. Traditional safety evaluation practices for food additives are not applicable to whole foods; therefore, the application of substantial equivalence and history-of-safe-use is presented. It was demonstrated that vitamin D in mushrooms, produced using UV light technologies, are equivalent to vitamin D in mushrooms exposed to sunlight, and that UV light has a long-history of safe use for production of vitamin D in food. Vitamin D mushrooms produced using UV light technologies were therefore considered safe and suitable for introduction to the marketplace.

Subchronic toxicity evaluation of potato protein isolates.

The protein content of potatoes has a high nutritional value on par with eggs and soybeans. As a result, processed potato protein isolates may have commercial value for addition to other food products to increase protein content. A manufacturing process has been developed to produce total potato (TP), as well as low (LMW) and high molecular (HMW) weight, protein isolates as food ingredients. To assess the safety of these isolates, groups of 10 Wistar rats/sex were administered dietary admixtures containing 15% HMW, 7.5% LMW or 15% TP protein isolates for a period of 90days. There was no effect of treatment on clinical signs, mortality, body weight and body weight gain. No biologically significant changes occurred in hematological and clinical chemistry parameters. No statistically significant changes in organ weights were recorded. Histopathological analyses revealed no clear, treatment-related changes. A slight increase in the incidence, but not severity, of vacuolation of the zona fasciculate of the adrenal gland was noted in males of the 15% HMW and 7.5% LMW groups. The finding was not considered adverse or ascribed any toxicological significance. Overall, HMW, LMW, and TP protein isolates were well-tolerated and without adverse effect. These data support the safety of potato protein isolates.

Evaluation of safety and human tolerance of the oral probiotic Streptococcus salivarius K12: a randomized, placebo-controlled, double-blind study.

Streptococcus salivarius is naturally a predominant member of the human oropharynx and the commercial probiotic strain K12 has been consumed for more than a decade. The present study examines the health responses of human volunteers to oral ingestion of high doses of S. salivarius K12. A randomized group of 53 subjects received a dose of 1 × 10(10)cfu S. salivarius K12 (N=25) or placebo (N=28) for 28 days, followed by a 28-day wash out period. Blood, urine and saliva samples were collected at baseline and following treatment and analyzed, while the oral and gastrointestinal tolerance of the subjects to the dosing regimen was determined by use of questionnaires. Adverse events (AE)s were recorded for both groups. No statistically significant differences between the probiotic and placebo treated groups were detected in either the blood clinical chemistry or hematology results (P>0.05). The questionnaire responses of the subjects indicated that both treatments were well tolerated. The frequency and intensity of AEs was similar in the two groups. This data demonstrates that the daily ingestion of S. salivarius K12 over a 28-day period does not adversely affect the human host and supports the safety of its oral delivery in a food-based carrier.

A new technique for subclavian puncture.

A new technique for performing and teaching subclavian punctures based on the finding of a new landmark--a small tubercle on the medial aspect of the deltopectoral groove, is presented. This tubercle has been found to be easily palpable on 92% of individuals examined. With this new landmark and the technique described the novice can quickly master this procedure with very little difficulty. The author found that both clinicians inexperienced in subclavian puncture and nursing personnel performed the procedure successfully after the first or second trial.

Subungual hematoma: association with occult laceration requiring repair.

Subungual hematomas are one of the most common injuries involving the hand. On conducting a literature search, we were unable to find any studies that investigated the association between subungual hematomas, fractures, and the presence of an occult laceration of the nail bed requiring repair. Forty-seven consecutive patients who presented to the emergency department with subungual hematoma involving more than one fourth of the nail bed were included in this study. In these cases, radiographs were taken, and the nail was lifted to look for a laceration. In the subgroup of patients who had subungual hematoma associated with a fracture, all of them had a laceration requiring repair. Patients with a subungual hematoma greater than one half of the size of the nail bed had a 60% incidence of a laceration requiring repair. The authors believe that patients presenting with a subungual hematoma involving greater than one half of the nail surface and a fracture of the distal phalanx should have the nail lifted and the nail bed explored and repaired.

Emergency cricothyroidotomy in the patient with massive neck swelling: Part 1: Anatomical aspects.

A method for localizing the hyoid bone in normal adult and children subjects is presented. The reliability of this calculated value in permitting localization of the hyoid was examined in 200 adult subjects in relationship to age, sex, neck size, and ethnic origin. The same method was utilized in 198 children with similar results. It was found to be a constant and remarkably predictable dimension which was unaffected by any of these variables. Because the hyoid serves as a frame from which the respiratory passage is suspended, it can be easily located and used to stabilize and retract superiorly and anteriorly the larynx and trachea, allowing easier access to these structures by a tracheotomy or cricothyroidotomy in the patient with massive neck swelling where emergency tracheotomy or cricothyroidotomy are difficult.

Moisture-vapour-permeable film as an outpatient burn dressing.

This study compares a moisture-vapour-permeable film (MVPF) with silver sulphadiazine in a randomized prospective manner for the treatment of outpatient burns. The two treatment groups were closely matched in age, sex, per cent of BSA burned, and in burn severity and locations. The MVPF group demonstrated a 39.0 per cent greater reduction in pain after application of the dressing over the silver sulphadiazine group. Patients in the MVPF film group also reported significantly less difficulty in wound care and in dressing interference with their daily functions. The clinical infection rate and time to healing were similar in both groups. In the management of outpatient burns, MVPF was found to be superior to silver sulphadiazine.

Cephalic vein cutdown at the wrist: comparison to the standard saphenous vein ankle cutdown.

We first developed a technique for cutdown of the cephalic vein at the wrist. We then conducted a prospective cross-over cadaver study comparing the ability of medical students to perform this technique with that of the standard saphenous vein cutdown at the ankle. All students had a previous course in anatomy but had never performed a cutdown. Before testing, the students were given written material and a ten-minute lecture describing both approaches. Seventeen students performed 34 cutdowns; nine students attempted the cephalic cutdown followed by the saphenous cutdown; the remaining eight used the reverse order. The mean time (+/- SD) to isolation of the cephalic vein was 85 +/- 70 seconds; for the saphenous vein, mean time was 70 +/- 89 seconds (P = NS). There was one failure (inability to isolate the vein within five minutes) in 17 attempts at the cephalic vein and two failures in 17 attempts at the saphenous (P = NS). There were no complications (nerve, artery, or tendon injury) with either technique. The mean external vein diameter (+/- SD) of the cephalic vein and the saphenous vein were 3.2 +/- 1.0 mm and 3.6 +/- 0.7 mm, respectively (P = NS). We conclude that relatively inexperienced providers can learn to perform the cephalic vein cutdown at the wrist on fresh cadavers with similar speed and success as that for the saphenous vein cutdown at the ankle. Cutdown at this site may provide a useful alternative to the saphenous cutdown in certain clinical situations.

Radiographic comparison of plain films in second- and third-degree ankle sprains.

A literature search failed to demonstrate any investigations of the plain films of the ankle to determine whether there were any measurable differences in the ankle mortise, which would differentiate between a second and a third degree ankle sprain, thus obviating the need for stress views. In this study, the authors independently measured the distances between the talus and tibia at eight predetermined sites on the lateral and mortise views. This was done blindly so that neither author knew which cases were second- or third-degree ankle sprains. Only definite third-degree ankle sprains, as defined by a positive anterior drawer sign and/or a positive inversion stress test result on clinical evaluation, were included. The authors found there was severe interobserver variability. The authors thus feel that there is no clinically significant measurement on plain films of the ankle that can be used to differentiate accurately between second and third degree ankle sprains, and current reliance on clinical findings and subsequent stress x-ray films is appropriate and must remain the non-operative standard for evaluation of this problem.

Modified new approaches for rapid intravenous access.

We studied the venous system at the groin, ankle, and antecubital area in relationship to easily palpable or visible surface landmarks, and developed new approaches or modifications of existing approaches to localize the saphenous vein at the groin, ankle, and the basilic vein in the antecubital area. A prospective crossover study comparing these new cutdown techniques with the most commonly described traditional techniques was performed, using inexperienced medical personnel. They were divided into two groups, and the average time to successful venous isolation with each method at each of the three sites was studied. Both groups were similar in that all participants were medical personnel (interns, flight nurses, an equal number in each group) who had not previously performed venous cutdowns. In each group, at all sites, the new cutdown techniques resulted in a more rapid isolation of the vein. This was true in each case regardless of which technique was learned and attempted first.

Logistics of medical care in rural Afghanistan.

The logistics of maintaining and supplying underground clinics located in war-torn rural Afghanistan are presented. Medical supplies are transported by pack animals over mountainous terrain, and must be specially packaged for the rigorous journey. Twenty percent of supplies are lost en route due to attacks or accidents. Medical and surgical equipment, some of which had to be specially designed, must be lightweight and durable. The system of monitoring clinic efficacy is also discussed.