Genetic blindness: current concepts in the pathogenesis of human outer retinal dystrophies

The biogenesis of bacterial c-type cytochromes generally involves many gene products--some of which may also have roles in other processes--and their interaction with the disulphide-bond-forming system of the bacterial periplasm. However, in some bacteria a simpler process appears to operate that might be related to the formation of c-type cytochromes in thylakoids of photosynthetic cells. The corresponding process in fungal mitochondria is distinct.     

Cystic fibrosis: current concepts

Cystic fibrosis (CF), a common fatal genetic disease, is a multisystem disorder whose pathogenesis has recently been linked to defects in CFTR, a newly discovered protein. CFTR is a molecular channel which controls chloride concentration in secretions of the sweat glands and the respiratory, GI, and reproductive tracts. Defective forms of CFTR, arising from various mutations in its gene, are responsible for the inadequate hydration of mucus, pancreatic juice, and other exocrine secretions. The result is dysfunction of the lungs, pancreas, and other involved organs. This article describes the diagnosis, clinical features, and approach to management of CF.     

Endodontic cleaning and shaping: current concepts

Temperature-sensitive (ts) mutant E/1/3 of Salmonella enteritidis was selected to evaluate its capacity to induce protective responses after peroral (p.o.) or intragastric (i.g.) inoculation to mice. This ts mutant of coasting phenotype was detected in Peyer's patches until day 4, and in spleen by days 3 and 4 after the mice were inoculated by the p.o. route with 10(10) colony forming units. Peroral immunization induced significant protection from oral challenge with 240 LD50 of the wild-type (wt) strain. Higher protection was achieved when the animals were boosted intraperitoneally after p.o. immunization. Intragastric inoculation with the same dose of the ts mutant increased both the level of protection, and colonization and persistence of the micro-organism in Peyer's patches and spleen. Immunization with a single i.g. inoculation induced 70% protection from p.o. challenge of the animals with the wt S. enteritidis. Two i.g. immunizations with E/1/3 raised the level of protection to 90%. Specific IgG, IgM and IgA antibodies, measured in plasma using a micro-ELISA method, were detected after i.g. immunization with ts mutant E/1/3. In addition, specific antibody-secreting cells were detected by means of an ELISPOT assay in spleen and mesenteric nodes of mice immunized with the ts mutant.     

Airway protective mechanisms: current concepts

There are at least eight mechanisms identified that result either in volume clearance of the pharynx and esophagus (secondary peristalsis and pharyngeal swallow) or prevent entry of the gastric content into the esophagus and pharynx (LES and UES), accentuate these barriers (esophago-UES and pharyngo-UES contractile reflexes), or induce closure of the vocal cords and introitus to the trachea (esophagoglottal and pharyngoglottal reflexes). The sum effect of various combinations of these mechanisms is suggested to help prevent retrograde aspiration. In other words, airway protective mechanisms against retrograde aspiration are multifactorial and involve delicate interaction between upper GI and upper airway tracts. Although the existence of these mechanisms in normal volunteers has been documented, their function in patients with retrograde aspiration and supraesophageal complications of gastroesophageal reflux disease currently awaits investigation.     

Diabetic foot ulcers: current concepts

OBJECTIVE: To determine whether a Maine law lowering the legal blood alcohol limit (BAL) from 0.10% to 0.05% for people convicted of driving while intoxicated (DWI) reduced the involvement of this group in fatal crashes. METHODS: The authors calculated changes in the proportions of fatal crashes involving drivers with prior DWI convictions from the six-year period before enactment of the law to the six-year period following enactment of the law, comparing Maine with the other New England states. RESULTS: In Maine, the proportion of fetal crashes involving drivers with recorded prior DWI convictions declined 25% following passage of the 0.05% DWI law, while the proportion rose in the rest of New England during the same years. The proportion of fatal crashes involving drivers with recorded prior DWI convictions and illegal alcohol levels also declined significantly in Maine, as did the proportion of fatal crashes involving fatally injured drivers with recorded prior DWI convictions and illegal alcohol levels. Most of the latter decline was due to a decline in alcohol-related fatalities of previously convicted drivers with very high BALs, of 0.15% or higher, at the time of the fatal crash. Each of these declines in Maine was significant relative to the rest of New England. CONCLUSION: Other states should consider instituting 0.05% BAL limits for convicted DWI offenders.     

Antiphospholipid antibody syndrome: current concepts

Antiphospholipid antibody syndrome is a well-recognized cause of hypercoagulability and has multiple manifestations. Patients with an unexplained thrombotic event should be evaluated for the disorder, which can be primary or secondary to another autoimmune disease. The mechanisms of thrombosis are still being elucidated, and the optimal therapeutic regimens remain controversial.     

Idiopathic pulmonary fibrosis: current concepts

Idiopathic pulmonary fibrosis (IPF) is generally defined as a progressive, fibrosing inflammatory disease of the lung parenchyma of unknown cause. It is characterized by slowly increasing dyspnea, diffuse interstitial lung infiltrates, restrictive lung dysfunction, and impaired gas exchange. Ultimately, it is fatal in most patients, and treatment options remain unsatisfactory. The advent of high-resolution computed tomography of the chest and modifications in the histopathologic classification of interstitial pneumonias have reshaped the concept of IPF. Although initially thought to be a relatively specific clinicopathologic entity, it seems likely that IPF as previously defined is a heterogeneous disorder consisting of several clinicopathologic entities with differing histopathologic patterns, clinical course, response to therapy, and prognosis. The most common histologic pattern in cases previously defined as IPF is usual interstitial pneumonia, which is associated with a median survival of less than 3 years. For accurate prognosis and optimal management of patients, the clinician should attempt to be as precise as possible in distinguishing various clinicopathologic entities that have been included under the clinical heading of IPF. In the future, we recommend that the use of the term "idiopathic pulmonary fibrosis" be restricted to patients with usual interstitial pneumonia and that clinicians recognize the fact that other idiopathic interstitial pneumonias do not have the same prognostic effect traditionally ascribed to IPF.     

Erbium laser resurfacing: current concepts

Laser skin resurfacing has enjoyed great popularity in recent years with the introduction of computerized, pulsed carbon dioxide lasers. However, the morbidity and side effects of carbon dioxide lasers have stimulated a search for alternative methods of skin remodeling. The erbium:YAG laser can be successfully used for skin resurfacing, with lower morbidity than the carbon dioxide laser. In a series of 625 patients who had erbium:YAG resurfacing, the following conclusions were reached. (1) Long-term (> 6 months) improvement in wrinkles and acne scars required total fluences exceeding 20 J/cm2. Periocular wrinkles required total fluences of between 20 and 40 J/cm2, depending on the depth of the wrinkles and skin thickness. Perioral rhytids required total fluences of between 40 and 80 J/cm2, whereas the cheeks and forehead required total fluences of 30 to 60 J/cm2. (2) Deeper wrinkles were best treated with a combination of erbium and carbon dioxide lasers, which minimized the bleeding that occurs with deeper erbium resurfacing. The simultaneous combined erbium with carbon dioxide laser was particularly advantageous. (3) Complications were relatively uncommon using the scanning erbium laser, and most adverse effects occurred early in the series. Scarring occurred in 5 of the 625 patients (0.8 percent) and mostly resolved with intralesional steroids. Hyperpigmentation occurred in 21 of the 625 patients (3.4 percent) and was temporary in nature. Hypopigmentation, which became evident after 6 months, occurred in 25 of the 625 patients (4.0 percent) but was mild and not a significant cosmetic problem, except in one patient who developed scarring on the neck. Hypopigmentation seemed to be related to the depth of resurfacing. Four of the 625 patients (0.6 percent) developed temporary scleral show, but no patients had permanent ectropion. Eight of the 625 (1.3 percent) developed synechiae under the lower eyelid, which required minor correction.     

Sedation in children: current concepts

Sedation in children poses a great challenge, with the main concern one of safety. The importance of providing adequate sedation to children was realized only in the last decade and a half, and relevant data are severely lacking. Use of potent sedative agents is not without risk. Children are given sedative agents in a wide variety of settings by practitioners with different degrees of experience with the drugs and management of adverse effects. Controversial issues must be addressed in this area, and appropriate tools developed to measure sedation and individualize treatment based on the drugs' pharmacokinetic and pharmacodynamic properties.     

Etiology and pathogenesis of heritable connective tissue diseases

There are many heritable disorders of the connective tissues and many of them produce major musculoskeletal anomalies. The etiology of most of them is unknown, but collagen mutations have been characterized in osteogenesis imperfecta (OI), in some forms of the Ehlers-Danlos syndrome (EDS) and in some of the chondrodysplasias. These diseases, particularly OI, provide a model for investigation of other heritable connective tissue diseases in which the mutant genes have not yet been identified.     

Interdigital athlete's foot: new concepts in pathogenesis

In our view, interdigital athlete's foot usually begins with invasion of the horny layer by dermatophytes. Because of hot weather, sweating, exercise, or tight shoes, enough moisture accumulates to stimulate an overgrowth of bacteria. Large numbers of normally resident aerobic diphtheroids cause the common wet, macerated type of athlete's foot, while an overgrowth of Gram-negative organisms, such as Pseudomonas and Proteus, is responsible for the more serious cases. The dry, scaly type (dermatophytosis simplex) often alternates with the wet, macerated type (dermatophytosis complex). Flare-ups are common in summer and can be experimentally induced by occlusion of fungus-infected feet. Suppression of bacteria is essential in treating symptomatic athlete's foot. This can be accomplished by exposing the feet to air (eg, wearing sandals) to enhance evaporation of water and prevent the accumulation of excess moisture that stimulates bacterial overgrowth. Topical antibiotics are another approach, with the ideal perhaps being an agent with both broad-spectrum antibacterial and antifungal activity. The newer imidazoles are broad-spectrum compounds but have limited activity against Gram-negative organisms. Our agent of choice, aluminum chloride, combines broad-spectrum antimicrobial activity with chemical drying, a two-pronged attack. We view drying as the decisive element. We doubt that any local treatment can permanently eradicate athlete's foot. Potent antifungal agents can virtually exterminate interdigital dermatophytes, but the inevitable presence of infection in the nails or on the soles assures reinfection. In shoe-wearing populations living in temperate climates, interdigital athlete's foot is mainly a seasonal disease. The various therapies discussed provide a variety of approaches to prevent or ameliorate hot-weather exacerbations.     

Vocal fold scarring: current concepts and management

Scarring of the vocal folds can occur as the result of blunt laryngeal trauma or, more commonly, as the result of surgical, iatrogenic injury after excision or removal of vocal fold lesions. The scarring results in replacement of healthy tissue by fibrous tissue and can irrevocably alter vocal fold function and lead to a decreased or absent vocal fold mucosal wave. The assessment and treatment of persistent dysphonia in patients with vocal fold scarring presents both diagnostic and therapeutic challenges to the voice treatment team. The common causes of vocal fold scarring are described, and prevention of vocal fold injury during removal of vocal fold lesions is stressed. The anatomic and histologic basis for the subsequent alterations in voice production and contemporary modalities for clinical and objective assessment will be discussed. Treatment options will be reviewed, including nonsurgical treatment and voice therapy, collagen injection, fat augmentation, endoscopic laryngoplasty, and Silastic medialization.