Comparative MIC evaluation of a generic ceftriaxone by broth microdilution on clinically relevant isolates from an academic hospital complex in South Africa

We evaluated the in vitro microbiological efficacy of a generic ceftriaxone product against several clinically significant organisms collected from sterile sites. The minimum inhibitory concentration (MIC) of each was determined simultaneously with the reference and the generic ceftriaxone product. Comparative analysis of MICs between the two products for each isolate was performed using both categorical (interpretive) agreement and essential (actual MIC value) agreement. A total of 260 isolates were tested. Overall, there was categorical agreement of 98.9% and essential agreement of 95.8%. The categorical agreement for all isolates (96.7 - 100%) accorded with international standards, as no very major errors were seen and the major error rate was less than 3%. Of the 90 isolates of E. coli (40), Klebsiella spp. (40) and Salmonella spp. (10), 87.6% had an MIC less than or equal to 0.12mg/l. The generic ceftriaxone product showed equivalent efficacy by MIC determination to the reference formulation. Ceftriaxone remains a viable and useful antimicrobial agent against a variety of clinically relevant organisms in our setting.     

Spinal cord injury: effect of thyrocalcitonin on periarticular bone formation in three subjects.

Sodium fluoride 18F scintimetry was performed before and after 1 month of salmon thyrocalcitonin treatment of 3 spinal cord injured patients with periarticular ossification of the hips and knees. Thyrocalcitonin therapy caused a marked diminution of 18F uptake in 1 patient with long-standing periarticular bone of both hips. Clinically, the range of motion in this subject increased by 25 degrees and there was a marked decrease in pain locally. The results were, however, not duplicated in the 2 patients with periarticular bone formation of short duration.     

RAPIDLY FATAL FAMILIAL HISTIOCYTOSIS ASSOCIATED WITH EOSINOPHILIA AND PRIMARY IMMUNOLOGICAL DEFICIENCY

Two new cases are reported of a familial disease clinically characterised by onset within the first month of life of an erythematous, maculopapular skin eruption associated with hepatomegaly, lymphadenopathy, eosinophilia, hypoglobulinæmia, or agammaglobulinæmia, increased susceptibility to infections, diarrhœa, and a rapidly fatal course. Histopathological findings, not previously described, included a profound depletion or absence of lymphocytes in the thymus, lymph-nodes, spleen, and lamina propria of the gut and an absence of Hassall's corpuscles in the thymus. An abnormal myeloid/erythroid ratio in the bone-marrow and blood, with a preponderance of eosinophilic granulocytes and their precursors, and a diffuse proliferation of bizarre histiocytes in the bone-marrow, lymphnodes, and skin were also noted. Possibly these signs and symptoms represent either a variant of the Letterer-Siwe syndrome or a graft-versus-host reaction in infants with severe combined immunological deficiency, but the unusual clinical and pathological findings suggest that this is a distinct disease. If this were correct, the disease might aptly be called familial malignant histiocytosis with eosinophilia.     

Novel oral insulin delivery systems based on complexation polymer hydrogels: Single and multiple administration studies in type 1 and 2 diabetic rats

Insulin-loaded polymer microparticles (ILP) composed of crosslinked poly(methacrylic acid) and poly(ethylene glycol) are multi-functional carriers showing high insulin incorporation efficiency, a rapid insulin release in the intestine based on their pH-dependent complexation properties, enzyme-inhibiting effects and mucoadhesive characteristics. Thus, they are potential carriers for insulin delivery via an oral route. Recent studies suggest that the polymer composition and particle size of ILP strongly influenced insulin bioavailability. Therefore, the present study aimed at finding an optimal formulation and designing carriers for oral insulin delivery using in vivo experiments. Various types of ILPs were prepared and administered orally to healthy and type 1 and 2 diabetic rats. The most promising formulation was subsequently used for in vivo multiple oral administration studies using diabetic rats. The microparticles of diameters of < 53 μm (SS-ILP) composed of a 1 : 1 molar ratio of methacrylic acid / ethylene glycol units showed the most pronounced hypoglycaemic effects following oral administration to healthy rats, achieving a 9.5% pharmacological availability compared to subcutaneous insulin injection. Their usefulness was also confirmed with both type 1 and 2 diabetic rat groups. In a multiple administration study, SS-ILP significantly suppressed the postprandial rise in blood glucose and showed continuous hypoglycaemic effects following 3 times/day oral administration to both diabetic rat groups in the presence of foods. These results indicate that the blood glucose levels of diabetic rats can be effectively controlled by oral SS-ILP administration, and thus SS-ILP would be a promising delivery carrier of insulin via the oral route.     

Evaluation of in vitro release and in vivo efficacy of mPEG-PLA-haloperidol conjugate micelle-like structures

Polymeric prodrugs of mPEG-PLA-haloperidol (methoxy poly(ethylene glycol)-b-poly (lactic acid)), self-assemble into nanoscale micelle-like structures in aqueous solutions. The micelles range in size from 28 to 52 nm in diameter and have been shown to be spherical in shape using cryogenic transmission electron microscopy. In this current work there is evidence shown that suggests these micelle-like structures do not dissociate below their critical micelle concentration (CMC) when the PEG weight percent is at least 68, releasing physically entrapped drug from intact micelles over a 3-day period. However, 55 wt % PEG micelles dissociate below their CMC, and release their physically entrapped drug within 8 h. Conjugate polymer micelles most closely approach a linear release profile over a 5-day period. Conjugate micelles with free drug incorporated, known as combination micelle-like structures, release drug over 4 days. However, these combination micelles have the fastest burst release indicating that free drug was potentially dominating the first 8 h of release, after which hydrolysis of covalently linked drug took over. In vivo behavioral studies can assess haloperidol bioactivity from drug loaded micelle-like structures on ketamine induced hyperlocomotion. Results are consistent with in vitro release data, showing that conjugate and combination micelles continue to release haloperidol 4 days post injection, attenuating the effects of the ketamine induced hyperlocomotion. Furthermore, results indicate that the sedative side effects of haloperidol were reduced with the micelle delivery systems as compared to the acute haloperidol injection.     

Odors from Sewage Sludge and Livestock: Associations with Self-Reported Health

Objectives

Class B treated sewage sludge (TSS) contains microbes and toxicants and is applied to land in areas where livestock wastes may be present. We evaluated relationships of reports of TSS and livestock odors with acute symptoms and excessive flies.

Methods

A total of 158 adults living near liquid TSS application sites, 85 living near cake TSS application sites, and 188 living in comparison areas responded to a household survey regarding odors, health, and demographics. We identified symptom groups using factor analysis. We used generalized estimating equations to fit linear models for associations between factor scores and odors, and Poisson models for associations with specific symptoms.

Results

Most factor scores were similar between exposure groups. Covariate-adjusted z-scores for lower respiratory symptoms were 0.28 (95% confidence interval [CI] –0.10, 0.65) higher among residents who reported moderate to very strong liquid TSS odor than among residents in comparison areas, and 0.28 (95% CI 0.05, 0.50) higher among residents who reported moderate to very strong livestock odor compared with residents reporting no or faint livestock odor. The factor score for dermatologic conditions was higher among residents who reported higher liquid sludge odor (0.27, 95% CI –0.13, 0.68), primarily due to skin rash (prevalence ratio = 2.21, 95% CI 1.13, 4.32). Excessive flies were reported twice as commonly among respondents who reported moderate to very strong TSS odor than among other residents.

Conclusions

Reported odors from TSS and livestock were associated with some acute symptoms. Health departments should monitor land applications of human and animal wastes and conduct surveillance of health problems reported by neighbors.Waste disposal is a universal public health challenge. Industrial and agricultural production and consumption can expose people to toxicants and pathogens. Technological innovation, while advancing methods for waste treatment, has created novel anthropogenic pollutants and contributed to the capacity of humans to create greater volumes of waste in smaller areas, increasing potential health impacts.Recycling waste is an alternative to disposal. Treated sludge from municipal wastewater, which is composed of solid residues from wastewater as well as microbes and chemicals used for treatment, contains nutrients and is used as a soil amendment. In 2004, approximately 2.6 million dry tons of treated sludge were applied to agricultural land in the United States.¹ Land-applying sludge is cheaper than landfilling or incineration, and farmers receive free fertilizer and labor. Most land-applied sludge is designated Class B, which has less stringent pathogen load-reduction requirements than Class A. Treated sludge is called “biosolids” by its producers, appliers, and regulators;² however, the neologism is not well recognized by people uninvolved in its production and disposition. We use the term “treated sewage sludge” (TSS).³TSS is applied to agricultural land as a liquid or dewatered (semisolid) cake using tractors with sprayers, injectors, or manure spreaders. Some people living near sites where TSS is applied to land report offensive odors, excessive flies, mucous membrane irritation, headaches, and symptoms of acute respiratory, dermatological, and gastrointestinal (GI) illness.^4–8 In addition to odorant chemicals, endotoxins, allergens, and pathogens that could cause acute effects, TSS contains numerous persistent organic pollutants and heavy metals.^9–12 Genetic markers of human TSS can be detected in air samples taken downwind from cake TSS application.^13,14Animal wastes receive far less treatment for pathogens and vector control. Airborne pollutants from industrial swine operations have been measured in nearby communities;^15–19 residents report more mucous membrane irritation, acute respiratory symptoms,²⁰ stress and anxiety,²¹ and interference with activities of daily living¹⁹ during periods of acute exposure compared with unexposed periods, and their blood pressure is higher.²² Children living or attending school near industrial swine operations have higher rates of wheezing and doctor-diagnosed asthma.^23–25 TSS and animal manure may be land applied to the same or nearby fields. Therefore, in assessing possible acute effects of TSS, it may be important to evaluate coincident exposure to airborne pollutants from livestock.We report results of a survey conducted in rural North Carolina in which we assessed TSS odor, livestock odor, and acute symptoms in areas where TSS was recently applied and comparison areas where TSS land application is not permitted.     

Self-Help Devices: Crutch Prescriptions: Modifications

In estimating physical impairment, accurate measurement of range of motion is essential, but other factors also must be considered. In the method of calculation described, the percentage of impairment due to limited motion is determined first, and if they are important, estimations of impairment due to pain, weakness, instability, sensory loss, or shortened extremities are added.