Functional bracing for the treatment of fractures of the humeral diaphysis

BACKGROUND: Nonoperatively treated fractures of the humeral diaphysis have a high rate of union with good functional results. However, there are clinical situations in which operative treatment is more appropriate, and, though interest in plate osteosynthesis has decreased, intramedullary nailing has gained popularity in recent years. We report the results of treating fractures of the humeral diaphysis with a prefabricated brace that permits full motion of all joints and progressive use of the injured extremity. METHODS: Between 1978 and 1990, 922 patients who had a fracture of the humeral diaphysis were treated with a prefabricated brace that permitted motion of adjacent joints. The injured extremities were initially stabilized in an above-the-elbow cast or a coaptation splint for an average of nine days (range, zero to thirty-five days) prior to the application of the prefabricated brace. Orthopaedic residents, supervised by teaching staff, provided follow-up care in a special outpatient clinic. Radiographs were made at each follow-up visit until the fracture healed. RESULTS: We were able to follow 620 (67 percent) of the 922 patients. Four hundred and sixty-five (75 percent) of the fractures were closed, and 155 (25 percent) were open. Nine patients (6 percent) who had an open fracture and seven (less than 2 percent) who had a closed fracture had a nonunion after bracing. In 87 percent of the 565 patients for whom anteroposterior radiographs were available, the fracture healed in less than 16 degrees of varus angulation, and in 81 percent of the 546 for whom lateral radiographs were available, it healed in less than 16 degrees of anterior angulation. At the time of brace removal, 98 percent of the patients had limitation of shoulder motion of 25 degrees or less. We were unable to follow most of the patients long-term, as they did not return to the clinic once the fracture had united and use of the brace had been discontinued. CONCLUSIONS: Functional bracing for the treatment of fractures of the humeral diaphysis is associated with a high rate of union, particularly when used for closed fractures. The residual angular deformities are usually functionally and aesthetically acceptable. The present study illustrates the difficulties encountered in carrying out long-term follow-up of indigent patients treated in charity hospitals that are affiliated with teaching institutions. These difficulties are also becoming common with patients insured under managed-care organizations and are frequent in our peripatetic population.     

Ectodermal dysplasia–skin fragility syndrome: a novel mutation in the PKP1 gene

Ectodermal dysplasia–skin fragility syndrome (EDSFS) is an autosomal recessive genodermatosis characterized by skin fragility, palmoplantar hyperkeratosis, onichodystrophy, perioral fissuring and noncicatricial alopecia. It is caused by plakophilin‐1 (PKP1) deficiency, which results in desmosomal abnormality and poor intercellular cohesion between the epidermal cells. We report a case with a novel PKP1 mutation in intron 6.     

Physiological concentrations of melatonin inhibit the nitridergic pathway in the Syrian hamster retina

In the present work, the effect of melatonin on the hamster retinal nitridergic pathway was examined. When the retinas were incubated in the presence of low concentrations (1 pM-10 nM) of melatonin for 15 min, a significant decrease of nitric oxide synthase (NOS) activity was observed. However, when crude retinal homogenates were preincubated with melatonin for 15 min, no changes in NOS activity were detected, despite the fact that under the same conditions trifluoperazine, a calmodulin inhibitor, significantly decreased enzymatic activity. Kinetic analysis showed that melatonin decreased the V(max) of retinal NOS without changes in the K(m). On the other hand, low concentrations (100 pM) of melatonin significantly reduced retinal L-arginine influx. A decrease in the V(max) of L-arginine uptake was observed in the presence of melatonin, whereas the K(m) remained unchanged. Melatonin significantly inhibited the accumulation of cyclic guanosine monophosphate (cGMP) levels induced by both L-arginine and sodium nitroprusside (SNP). In summary, the present results indicate that melatonin could be a potent inhibitor of the retinal nitridergic pathway.     

Comparison of sodium nitroprusside and adenosine for fractional flow reserve assessment: a systematic review and meta-analysis

Background: Fractional flow reserve (FFR) has become a useful tool in the assessment of physiological significance of coronary artery stenosis (CAS), and Adenosine (ADE) is associated with a high incidence of transient side effects. Sodium nitroprusside (NPS) has been proposed as an alternative vasodilator agent. A meta-analysis of studies comparing ADE and NPS for FFR assessment in the same coronary lesions was performed.

Methods: Authors searched for articles comparing NPS and ADE for FFR assessment in intermediate coronary lesions published through January 2018. The following keywords were used: ‘fractional flow reserve’ AND ‘nitroprusside’. Data were summarized using weighted mean differences for paired data.

Results: Seven studies were identified comprising 342 patients and 401 lesions. Four studies evaluated intravenous ADE and 3 studies intracoronary ADE administration. Weighted means FFR values obtained with ADE and NPS were 0.8411 and 0.8445, respectively (weighted mean difference: 0.00, 95% confidence interval (CI) ?0.01 to 0.01, p = 0,548). Adverse events were significantly reduced with IC NPS (RR = 0.08, 95%CI 0.02–0.30, P < 0.0001).

Conclusions: NPS produces similar FFR measurements compared to ADE with a significant reduction in adverse effects. These results may support its use as a suitable alternative to ADE for FFR assessment.     

CorrespondenceLack of Association of Latent Autoimmune Diabetes in Adults (LADA) with Enterovirus Infection

In myasthenia gravis (MG) and experimental autoimmune MG (EAMG), many pathologically significant autoantibodies are directed at the main immunogenic region (MIR), a conformation-dependent region at the extracellular tip of α1 subunits of muscle nicotinic acetylcholine receptors (AChRs). Human muscle AChR α1 MIR sequences were integrated into Aplysia ACh-binding protein (AChBP). The chimera was potent in inducing both acute and chronic EAMG, though less potent than Torpedo electric organ AChR. Wild-type AChBP also induced EAMG but was less potent, and weakness developed slowly without an acute phase. AChBP is more closely related in sequence to neuronal α7 AChRs that are also homomeric; however, autoimmune responses were induced to muscle AChR, but not to neuronal AChR subtypes. The greater accessibility of muscle AChRs to antibodies, compared to neuronal AChRs, may allow muscle AChRs to induce self-sustaining autoimmune responses. The human α1 subunit MIR is a potent immunogen for producing pathologically significant autoantibodies. Additional epitopes in this region or other parts of the AChR extracellular domain contribute significantly to myasthenogenicity. We show that an AChR-related protein can induce EAMG. Thus, in principle, an AChR-related protein could induce MG. AChBP is a water-soluble protein resembling the extracellular domain of AChRs, yet rats that developed EAMG had autoantibodies to AChR cytoplasmic domains. We propose that an initial autoimmune response, directed at the MIR on the extracellular surface of muscle AChRs, leads to an autoimmune response sustained by muscle AChRs. Autoimmune stimulation sustained by endogenous muscle AChR may be a target for specific immunosuppression.     

Evaluation of the humoral immune response and cross reactivity against <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> of mice immunized with liposomes containing glycolipids of <Emphasis Type="Italic">Mycobacterium smegmatis</Emphasis>

Mycobacterium smegmati s (Ms) is a nonpathogenic mycobacteria of rapid growth, which shares many characteristics with Mycobacterium tuberculosis (MTB), the major causative agent of tuberculosis. MTB has several cell wall glycolipids in common with Ms, which play an important role in the pathogenesis of tuberculosis and the induction of a protective immune response against MTB infection in some animal models. In this study, the humoral immune response and cross reactivity against MTB, of liposomes containing a mixture of cell wall glycolipids of Ms and commercial lipids was evaluated, in order to study its possible use as a component of a vaccine candidate against tuberculosis. Liposomes containing total lipids extracted from Ms, distearoyl phosphatidyl choline and cholesterol were prepared by the dehydration-rehydration technique. Balb/c mice were immunized with the liposomes obtained and the antibody response and cross reactivity against MTB were tested by ELISA. Total lipids extract from Ms showed the presence of several polar glycolipids in common with MTB, such as phosphatidylinositol mannosides. Liposomes that contained glycolipids of Ms were capable of inducing a specific IgG antibody response that allowed the recognition of surface antigens of MTB. The results of this study demonstrated the presence of immunogenic glycolipids in Ms, which could be included to enhance the protective effects of subunit vaccine formulations against tuberculosis.     

Evaluation of specific humoral immune response and cross reactivity against <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> antigens induced in mice immunized with liposomes composed of total lipids extracted from <Emphasis Type="Italic">Mycobacterium smegmatis</Emphasis>

The development of a new tuberculosis (TB) vaccine has become one of the main objectives of the scientific community. Protein antigens have been widely explored as subunit TB vaccines, however lipid antigens could be equally important to be used or included in such a vaccine. The aim of this study was to demonstrate the potential of a liposome formulation composed of an extract of lipids from Mycobacterium smegmatis (Ms) as a TB vaccine candidate. We evaluated the immunogenicity of this formulation as well as the cross reactive response against antigens from Mycobacterium tuberculosis (MTb) in BALB/c mice. We determined the anti-liposome IgG response in sera from TB patients and from healthy subjects who displayed a positive (PPD+) or negative (PPD-) tuberculin skin test. A significant increase in anti-liposome IgG (p<0.05) was detected in animals immunized with Bacille Calmette-Guérin (BCG) compared with all groups, and in the group immunized with liposomes from Ms (LMs) compared to animals immunized with either LMs adjuvanted with aluminium (LMs-A) or the negative control group (phosphate buffered saline, PBS) respectively. With respect to the cross reactive response against a cocktail of cell wall antigens (CWA) from MTb, significantly higher IgG levels were observed in animals immunized with BCG and LMs compared to negative controls and either, aluminium-adjuvanted liposomes (LMs-A) or montanide (LMs-M) (p<0.05). Furthermore, the anti-liposome IgG response was significantly superior in sera from pulmonary TB patients compared to PPD+ and PPD- healthy subjects (p<0.001) suggesting the expression of these antigens in vivo during active MTb infection. The results obtained provide some evidence for the potential use of liposomes containing total lipid extracts of Ms as a TB vaccine candidate.