Two different proteoheparan sulfate species are synthesized by bovine corneal endothelial cells

Cultured bovine corneal endothelial cells were labeled with either [35S]sulfate or a combination of [3H]glucosamine and [35S]methionine. The medium proteoheparan sulfate (HS-PG) and cell-associated HS-PG were isolated and identified as heparan sulfate-containing proteoglycans by the susceptibility of their glycosaminoglycan component to specific enzymatic and chemical degradation. The native medium HS-PG has an apparent Mr of about 300,000 and an Mr of its protein core of 64,000, while the native cell-associated HS-PG had a lower molecular weight (approx. 100,000) and an Mr of its protein core of 33,000. The protein core of both HS-PG types consisted of a single polypeptide chain. After beta-elimination reaction of the native HS-PGs the resulting heparan sulfate side chains of medium HS-PG had an Mr of about 60,000, and those of cell-associated HS-PG an Mr of about 30,000. The different molecular parameters of medium HS-PG and cell-associated HS-PG refer to different functional roles. The medium HS-PG secreted by the endothelial cells is regarded as a metabolic precursor of the Descemet's membrane, while the cell-associated HS-PG might represent a cell membrane-integrated proteoglycan.     

Polyglactin 910 implants in muscle revision surgery for the reconstruction of physiologic limits in Tenon's capsule

Iatrogenic damage to the orbital fascial system during strabismus surgery may lead to adherences with resulting problems of motility. To prevent new adherences in revisional surgery, several materials were tried, with varying degrees of success. The authors tested Polyglactin 910, popular as a suture material in strabismus surgery, in the form of a net. The material is hydrolytically soluble. Since the tissue response is finished before dissolution of the implant, it seemed that Polyglactin would be a suitable barrier to the formation of adhesions in Tenon's capsule. The implant was applied in 11 patients, some of whom had already undergone several strabismus operations and had adhesions at the surgical site. In one case the implant was used in a primary procedure. In one patient revisional surgery was needed four weeks after surgery because of overeffect, and this provided an opportunity to investigate the implanted area histologically.     

Safety pharmacology of the respiratory system: Techniques and study design

The known effects of drugs from a variety of pharmacologic/therapeutic classes on the respiratory system and worldwide regulatory requirements support the need for conducting respiratory evaluations in safety pharmacology. The objective of these studies is to evaluate the potential for drugs to cause secondary pharmacologic or toxicologic effects that influence respiratory function. Changes in respiratory function can result either from alterations in the pumping apparatus that controls the pattern of pulmonary ventilation or from changes in the mechanical properties of the lung that determine the transpulmonary pressures (work) required for lung inflation and deflation. Defects in the pumping apparatus are classified as hypo- or hyperventilation syndromes and are evaluated by examining ventilatory parameters in a conscious animal model. The ventilatory parameters include respiratory rate, tidal volume, minute volume, peak (or mean) inspiratory flow, peak (or mean) expiratory flow, and fractional inspiratory time. Defects in mechanical properties of the lung are classified as obstructive or restrictive disorders and can be evaluated in animal models by performing flow-volume and pressure-volume maneuvers, respectively. The parameters used to detect airway obstruction include peak expiratory flow, forced expiratory flow at 25 and 75% of forced vital capacity, and a timed forced expiratory volume, while the parameters used to detect lung restriction include total lung capacity, inspiratory capacity, functional residual capacity, and compliance. Measurement of dynamic lung resistance and compliance, obtained continuously during tidal breathing, is an alternative method for evaluating obstructive and restrictive disorders, respectively, and is used when the response to drug treatment is expected to be immediate (within minutes post-dose). The species used in the safety pharmacology studies conducted in our laboratory are the same as those used in toxicology studies since pharmacokinetic and toxicologic/pathologic data are available in these species. These data can be used to help select test measurement intervals and doses and to aid in the interpretation of functional change. The techniques and procedures for measuring respiratory function parameters are well established in guinea pigs, rats, and dogs.     

Evaluation of Tissue-Engineered Skin (Human Skin Substitute) and Secondary Intention Healing in the Treatment of Full Thickness Wounds after Mohs Micrographic or Excisional Surgery

BACKGROUND: Human Skin Substitute (Apligraf, Organogenesis, Inc., Canton, MA) is a bi-layered tissue-engineered living biological dressing developed from neonatal foreskin. It consists of a bovine collagen matrix containing human fibroblasts with an overlying sheet of stratified human epithelium containing living human keratinocytes. Human Skin Substitute (HSS) appears to be immunologically inert, and has shown usefulness in the treatment of chronic and acute wounds. OBJECTIVE: Primary objectives were to evaluate the safety and efficacy of HSS in the treatment of full-thickness wounds in a prospective case series. Secondary objectives were to determine the rate of complete wound reepithelialization, incidence of complete wound healing, pain at wound site, overall cosmetic outcome, and patient satisfaction. METHODS: Fourteen patients were enrolled in the study, of which 12 were evaluable. HSS was applied in a blinded fashion to 6 of the patients immediately following Mohs or excisional surgery for skin cancer. The remaining 6 patients were allowed to heal by secondary intention. Both groups were evaluated at weekly appointments until complete reepithelialization occurred. During each evaluation, wound quality was assessed through the Vancouver Burn Scar Assessment Scale by the investigator and an independent blinded dermatologist. The investigator, blinded observer, and patient further evaluated the cosmetic outcome of the wound through the use of a Visual Analog Scale over a 6-month period. RESULTS: HSS patients and secondary intention patients were equivalent in comorbid factors such as pain, erythema, edema, exudate, infection, or hematoma between the groups. The incidence of complete wound healing at 6 months was 100% for both groups. Both groups also appeared to heal at similar rates, as defined by the complete reepithelialization of the wound. HSS patients ultimately resulted in more pliable and less vascular wounds as defined by the Vancouver Burn Scar Assessment Scale. Patient satisfaction with cosmetic outcome in both groups was positive at 6 months. CONCLUSIONS: HSS appears to be a safe, well-tolerated biological dressing with equivalent comorbid factors to secondary intention healing. HSS, however, seems to produce a more pliable and less vascular scar than those developed through healing by secondary intention. HSS also appears to produce more satisfactory cosmetic results when compared to secondary intention healing.     

Diagnostic accuracy of progressive supranuclear palsy in the Society for Progressive Supranuclear Palsy brain bank.

Diagnostic accuracy has been addressed previously for Parkinson's disease in a brain bank collection, but accuracy of progressive supranuclear palsy (PSP) has not been addressed in a similar setting. Clinical and genetic features of pathologically confirmed cases of PSP were compared with misdiagnosed cases to determine ways to improve diagnostic accuracy. Medical records were reviewed for 180 cases sent to the Society of Progressive Supranuclear Palsy Brain Bank that had standardized neuropathologic evaluations as well as determination of apolipoprotein E and tau genotypes. Of the 180 cases studied, 137 had PSP and 43 had other pathologic diagnoses. Corticobasal degeneration (CBD), multiple system atrophy (MSA), and diffuse Lewy body disease (DLBD) accounted for 70% of the misdiagnosed cases. History of tremor, psychosis, dementia, and asymmetric findings were more frequent in misdiagnosed cases. The frequency of H1 tau haplotype (93 vs. 80%) and H1H1 genotype (86 vs. 66%) were significantly greater and APOE epsilon4 carrier state was significantly less (17 vs. 41 %) in PSP compared with misdiagnosed cases. Pathologic evaluation of clinically diagnosed PSP remains important for definitive diagnosis, and CBD, MSA, and DLBD are the disorders most likely to be misdiagnosed as PSP. Tremor, psychosis, early dementia, asymmetric findings, absence of H1 haplotype, and presence of APOE epsilon4 should raise questions about a diagnosis of PSP.     

Neuroprostheses in the management of incontinence in myelomeningocele patients

A 16-year-old boy and a 17-year-old girl underwent successful closure of the meningomyelocele defect in childhood but they continued to suffer incontinence of stool and urine. After a 5-day trial with percutaneous electrostimulation of the pudendal nerve both patients received permanent neuroprosthetic implants. They became completely continent of stool and exhibited greater than 90% improvement in urinary control. These patients demonstrate that there is a small subset of meningomyelocele patients who, despite absence of spontaneous reflex tonus in the urinary and bowel sphincters, nevertheless have preserved motor capabilities.     

The Stafford outbreak of Legionnaires' disease

A large outbreak of Legionnaires' disease was associated with Stafford District General Hospital. A total of 68 confirmed cases was treated in hospital and 22 of these patients died. A further 35 patients, 14 of whom were treated at home, were suspected cases of Legionnaires' disease. All these patients had visited the hospital during April 1985. Epidemiological investigations demonstrated that there had been a high risk of acquiring the disease in the out patient department (OPD), but no risk in other parts of the hospital. The epidemic strain of Legionella pneumophila, serogroup 1, subgroup Pontiac 1a was isolated from the cooling water system of one of the air conditioning plants. This plant served several departments of the hospital including the OPD. The water in the cooling tower and a chiller unit which cooled the air entering the OPD were contaminated with legionellae. Bacteriological and engineering investigations showed how the chiller unit could have been contaminated and how an aerosol containing legionellae could have been generated in the U-trap below the chiller unit. These results, together with the epidemiological evidence, suggest that the chiller unit was most likely to have been the major source of the outbreak. Nearly one third of hospital staff had legionella antibodies. These staff were likely to have worked in areas of the hospital ventilated by the contaminated air conditioning plant, but not necessarily the OPD. There was evidence that a small proportion of these staff had a mild legionellosis and that these 'influenza-like' illnesses had been spread over a 5-month period. A possible explanation of this finding is that small amounts of aerosol from cooling tower sources could have entered the air-intake and been distributed throughout the areas of the hospital served by this ventilation system. Legionellae, subsequently found to be of the epidemic strain, had been found in the cooling tower pond in November 1984 and thus it is possible that staff were exposed to low doses of contaminated aerosol over several months. Control measures are described, but it was later apparent that the outbreak had ended before these interventions were introduced. The investigations revealed faults in the design of the ventilation system.     

Stenting of the left carotid artery to relieve anginal symptoms.

Stenting of the carotid artery is usually performed either to prevent an acute neurologic event or to treat episodes of recurrent transient ischemic attacks. Occasionally, it may be performed for other indications. We describe the case of a patient with prior coronary artery bypass grafting using a left internal mammary arterial graft, in addition to left carotid artery to left subclavian artery bypass for symptomatic left subclavian stenosis, who subsequently underwent left common carotid artery stenting to relieve anginal symptoms.