Allergens and irritants transcriptionally upregulate CD80 gene expression in human keratinocytes.

The human CD80 costimulatory molecule is an important signal between professional antigen-presenting cells and T helper cells. The immunobiology of CD80 expression by keratinocytes, especially during allergic and irritant contact dermatitis, however, is less well understood. CD80 cell surface expression and gene transcription by keratinocytes was increased when keratinocytes were exposed to certain allergens (chemicals that induce inflammation via hapten-specific T cells) and irritants (chemicals that are toxic to epidermal cells). Therefore, the human CD80 promoter was cloned and luciferase reporter constructs containing various promoter fragments were engineered. Promoter mapping of these CD80 constructs in transiently transfected keratinocytes showed that a construct containing the proximal 231 bp immediately upstream of the transcription start site of the CD80 promoter was most active in keratinocytes and was inducible to a level ranging from 2- to 10-fold higher in keratinocytes treated with certain allergens and irritants, compared with untreated keratinocytes. This pattern of promoter fragment activity in keratinocytes is identical to that found in professional antigen-presenting cells. This is the first demonstration that the CD80 promoter is active in keratinocytes and that this activity is further increased in keratinocytes treated with certain allergens and irritants. These data suggest that allergens and irritants may, in part, break peripheral tolerance by their direct effects on keratinocyte costimulatory molecule expression, thereby facilitating interactions with epidermotropic T helper cells via the CD80-CD28 or CTLA-4 pathways.

Uveitis in melanomatous swine: lack of evidence for humoral immune melanocyte destruction.

A strain of miniature Sinclair swine that have cutaneous malignant melanomas destroy their tumors via an immunologic process. Destruction of apparently normal melanocytes of the uveal tract occurs concurrently with tumor cell lysis. The authors investigated possible involvement of humoral antibodies in uveal melanocyte lysis. Uveal antigens solubilized by a variety of reagents were tested by immunodiffusion against autologous and homologous sera; no precipitation lines were found. Western blots of electrophoresed uveal proteins when tested against serum from an animal with a great tumor load showed no antigen-antibody reactions. No specific humoral antibodies were detected. Sera tested for immune complexes also were negative. Invasion of the uveal tract by mononuclear cells was quantified in 1-micron-thick sections of tissue taken at various stages of ocular depigmentation. Disappearance of melanocytes was preceded by an increase in mononuclear cells and followed by an increase in melanin-containing macrophages. The ultrastructural features of the invading cells are presented. The authors conclude that cell-mediated uveal melanocyte destruction is the most likely basis for the uveitis and other damaging sequelae.

Association of uveal melanocyte destruction in melanoma-bearing swine with large granular lymphocyte cells.

Sinclair strain miniature swine spontaneously develop and regress malignant melanoma lesions, with uveitis and vitiligo occurring subsequent to tumor regression. Peripheral blood lymphocytes (PBL) of Sinclair swine undergoing tumor regression and melanocyte destruction demonstrated significant lytic activity against K562, porcine semiallogeneic uveal melanocytes, and melanoma cells in 4-h chromium release assays. The ability of porcine PBL to lyse these target cells appears to be an age-associated immune response, as evidenced by the relative inability of PBL of pigs less than 4 weeks old to lyse target cells. In young adult pigs, however, PBL cytotoxic activity significantly increases; piglets 6 weeks old and older demonstrate efficient killing of all three targets. Conjugate formation assays demonstrate that a lymphoid effector cell possessing large granular lymphocyte (LGL) morphology may be involved in melanocyte destruction. These findings suggest that a LGL subpopulation may participate in melanoma and melanocyte destruction which can induce a uveitic syndrome in Sinclair swine with melanoma.

Pathogenesis of corneal damage from pseudomonas exotoxin A.

Pseudomonas aeruginosa exotoxin A was injected into rabbit corneas. Death of epithelial, endothelial, and stromal cells resulted, and necrosis of the cornea followed. Control eyes with exotoxin neutralized by specific antitoxin showed minimal damage. A dose-response pattern was evident. Antitoxin neutralization of pseudomonas exotoxin A in corneal ulcers may have possible therapeutic implications.

Ultrastructure and acid phosphatase activity in hereditary cataracts of deer mice.

Lenses of cataract-webbed (cw) Peromyscus maniculatus were examined by electron microscopy and compared to age-matched normal deer mouse lenses. Precataractous lenses of offspring of cw/cw matings were examined and compared to early cataract development in the opposite eye of the same animal. The earliest ultrastructural change leading to disturbance of lens transparency was cell fusion and formation of fiber cell syncytia in the posterior subcapsular region. Fiber cells lost their regular hexagonal packing. Small osmiophilic densities on the plasma membrane coincided with many of the sites of cell confluency. Larger osmiophilic whorls were usually localized in ball-and-socket interlocking junctions after the opacity spread. Epithelial cells from the nasal ventral equator migrated to the posterior pole. Later when underlying cortical fibers ruptured, the migrated cells phagocytized lens proteins and incorporated them in acid-phosphatase positive lysosomes. Fiber cells 3 to 20 layers deep in the cortex of normal and cataractous lenses had acid phosphatase reaction product coating the plasma membrane; the possible significance of this finding is discussed. We postulate that this hereditary cataract results from a defect in turnover and control of plasma membrane components.

Cataract-webbed trait in Peromyscus. II. Biomicroscopy and histology of eyes.

A longitudinal biomicroscopic study of lenses and fundi of over 2,000 Peromyscus maniculatus (deer mice) which have cataracts as an autosomal recessive trait has been correlated with histologic development of cataracts. By selective breeding, early-onset cataracts (Type I), which are frequently associated with abnormal closure of the fetal fissure and hyaloid vascular abnormalities, have been separated from later-onset (Type II) cataracts, which are more heterogeneous. Type I cataracts occur in syndactylous deer mice, develop rapidly, and histologically may show backward migration of disrupted lens bow cells before lens opacity is apparent biomicroscopically. Posterior subcapsular cataracts then develop and spread centrally and inferonasally to the equatorial area and then to the entire equator. The nucleus opacifies in either a "shell" pattern or as isolated dots. Anterior cortical opacification progresses to mature cataract. Histologically, abnormal migration and proliferation of lens epithelium and enlargement and vacuolar degeneration of the basal (posterior) process of cortical lens fibers are early changes in Type I cataracts. Disruption of the lens bow with failure of differentiation and inward turning of lens epithelium to become lens fibers occurs concurrently. Type II cataracts may follow the developmental pattern of Type I but are rarely associated with severe hyaloid vascular abnormalities and progress more slowly. About 6% of animals develop diabetes, which is not associated with the cataract-webbed trait.

Uveitis caused by cytotoxic immune response to cutaneous malignant melanoma in swine: destruction of uveal melanocytes during tumor regression.

In a substrain of Sinclair miniature black swine, bred for increasing incidence of cutaneous malignant melanomas, tumor regression occurs spontaneously and is accompanied by depigmentation of the skin, hair, and eyes. We conducted a 12-month longitudinal study of the ocular phenomena in 30 swine beginning at 3 weeks of age. The clinically observed sequence of depigmentation of the fundus and iris was correlated with histopathologic changes in selected enucleated eyes. Normal melanocytes of the uveal tract are destroyed between the 4th and 16th week of life. Melanocyte destruction is preceded by an invasion of the uveal tract by mononuclear cells having the ultrastructural features of lymphocytes and monocytes. Melanin and other cellular debris of ruptured melanocytes are ingested by macrophages which then migrate to the walls of blood vessels. Cataracts and band keratopathy develop secondary to the uveitis in some animals. Pilot electroretinograms show diminished electrical activity in photoreceptors of totally depigmented eyes possibly indicating ischemic or toxic damage to the retina. The retinal pigment epithelium remains essentially normal during the acute stages of uveal inflammation; later some damage and reparative hyperplasia may occur. The death of normal uveal melanocytes that occurs during the systemic attack on the cutaneous malignant melanomas appears to be an "innocent bystander" error in the immune recognition mechanism. The antigenic basis of this immunologic cross reaction is under investigation.

Human subretinal fluid. Its cellular and subcellular components.

A light and electron microscopical study of subretinal fluid removed at surgery for rhegmatogenous retinal detachment showed a heterogeneity of cell types originating from the neural retina, pigment epithelium, and wandering cells of the blood. Subcellular organelles sedimenting in the centrifuged pellets could be identified as to cell of origin, health of the parent cell, and time since cell rupture. Acellular specimens were typical of angiomatous detachments or long-standing rhegmatogenous detachments. Because various mechanisms of cellular pathophysiology contribute to the destructive and reparative processes during retina detachment, the cytologic analysis of subretinal fluid becomes a useful tool in understanding the biological processes that affect visual recovery or impairment after successful retinal detachment surgery.

Immunosuppressive therapy for severe chronic uveitis.

Twenty-five patients with severe, progressive, chronic uveitis who were poorly responsive or unresponsive to corticosteroid therapy received low-dose prednisone and cytotoxic immunosuppressive therapy. Azathioprine (2.0 to 2.5 mg/kg) or chlorambucil (6 to 8 mg) was combined with prednisone (10 to 15 mg) daily in a long-term therapeutic program. All 25 patients exhibited a therapeutic response. In 18 of 25 patients, complete quiescence of the inflammatory process was observed. The remaining seven patients showed a substantial decrease of uveitis with persistence of some inflammatory changes. Adverse side effects that resulted from this therapy were infrequent.

Epidemic keratoconjunctivitis due to adenovirus type 19.

A new type of epidemic keratoconjunctivitis, caused by adenovirus type 19, occurred in Oregon in 1974. Although it can be spread by tonometry, in this epidemic finger-to-eye contact appeared to be the cause.

Hereditary cataracts in deer mice (Peromyscus maniculatus).

A new type of hereditary cataract was predicted in the deer mouse (Peromyscus maniculatus) by the presence of syndactyly of the hind feet. Early morphologic changes were found in the equatorial cells that differentiated into new lens fibers. Later swelling at the anterior and posterior poles of these cells produced lens opacities. Anterior and posterior subcapsular cataracts progressed to a hypermature shrunken lens.

Irrigation of the anterior chamber for the treatment of alkali burns.

A 31-year-old man had sodium hydroxide blown into his amblyopic left eye after an explosion caused by placing solid sodium hydroxide cleanser into a plugged drain. The eye was treated with topical and intraocular irrigation, and lactated Ringer's solution and the patient was given topical antibiotics, systemic and topical corticosteroids, and carbonic anhydrase inhibitors. Acetylcysteine drops were administered, and a contact lens was placed. The patient subsequently developed severe pain, hypopyon, and hyphema. The cornea was ulcerated and perforated 27 days after injury, and the eye was enucleated 70 days after injury.

Age-related macular changes in humans over 90 years old.

The macula lutea of 23 donors aged 90 to 101 years were examined by light and electron microscopy and compared to maculas from a 49- to 68-year-old age group. The number of foveal photoreceptors and retinal pigment epithelial cells, the presence of macular pigment, and lipofuscin fluorescence were assessed. Pathologic characteristics typical of age-related macular degeneration occurred in nine of the 90- to 101-year-old group with changes ranging from early neovascularization to fully developed disciform scars, geographic atrophy, and macular holes. Several retinas had pigment epithelial and photoreceptor cell numbers equal to those of the younger group, but most showed cell loss. Thickened, debris-filled Bruch's membrane and choriocapillary atrophy, although common, were not an invariable accompaniment to old age. Clinicians should advise elderly patients that their chances of maintaining macular structure, and hopefully function, are better than 50%.

Topical vancomycin formulation for methicillin-resistant Staphylococcus epidermidis blepharoconjunctivitis.

We successfully treated two patients with severe Staphylococcus epidermidis blepharoconjunctivitis by means of a topical vancomycin hydrochloride solution (50 mg/ml) prepared with sterile water. Aqueous vancomycin preparations, however, cause significant ocular irritation probably because of low pH and osmolality values. Solutions prepared with normal saline (5 mg/ml) and phosphate-buffered artificial tears (5 mg/ml and 50 mg/ml) were significantly less irritating and possessed equivalent in vitro antimicrobial activity. Topical vancomycin should be used only when commercially available antibiotics are inadequate.

Image-guided breast biopsy.

Widespread application of mammography and breast ultrasound has led to improved recognition and delineation of breast lesions. Localization of these lesions with specialized, computerized stereotactic radiographic equipment or ultrasound imaging with subsequent use of this image to guide percutaneous core sampling of the abnormal area is less invasive, less painful, highly accurate, and less expensive than incisional breast biopsy with preoperative needle localization. These image-guided techniques have progressively matured in recent years, are used regularly by more and more surgeons, and are areas of clinical care and technology in which surgeons should be familiarized and educated.

Stereotactic and ultrasound core needle breast biopsy performed by surgeons.

BACKGROUND: The authors evaluated outcomes and treatment costs of stereotactic core needle biopsy (SCNB) and ultrasound core needle biopsy (UCNB), and needle localization biopsy (NLB) in managing patients with mammographic abnormalities presenting to the surgeon. METHODS: Data for all patients with mammographic lesions who underwent SCNB or UCNB since their introduction at this institution were prospectively collected over 17 months. Mean inclusive costs of the three procedures were accumulated and compared. RESULTS: Stereotactic core needle biopsy was performed for 342 lesions in 319 women, for a malignancy rate of 19%; UCNB was performed for 157 lesions in 144 patients, yielding a malignancy rate of 17%. With a mean follow-up of 13.5 months, 1 patient with in situ carcinoma was diagnosed late. Absolute cost savings for the period studied was $721,963. CONCLUSIONS: Minimally invasive breast biopsy procedures can safely and reliably be performed by surgeons in clinical practice with increased patient convenience and decreased costs.

10 years' experience treating pancreatic and periampullary cancer.

The records of 136 patients with periampullary and pancreatic carcinoma were reviewed and the information compared with other reported series. The clinical presentation with jaundice without other manifestations is associated with the greatest number of potentially curable tumors. The majority of patients were treated by palliative bypass or had exploration and biopsy only. A tissue diagnosis is not imperative before radical excision, providing a systematic preoperative and operative evaluation indicates tumor. Ligation of the pancreatic duct with external drainage results in low morbidity and mortality and good functional results. Radical pancreaticoduodenectomy done in 21 per cent of our patients offers the best palliation and the only hope for cure.

Autotransfusion utilization in abdominal trauma.

The purpose of this review is to investigate the utility of autotransfusion in trauma patients in the past 3 years. A retrospective review was conducted of the charts for whom the Haemonetics Cell Saver autotransfusion device (Haemonetics Corp., Natick, MA) was utilized between January 1, 1993, and December 31, 1995. The estimated blood loss and quantity of blood transfused were noted for abdominal trauma patients. Costs of autotransfusion were then compared to estimated blood bank costs for this group. The Haemonetics Cell Saver autotransfusion device was requested for 592 cases from January 1, 1993, to December 31, 1995. Nonorthopedic trauma cases comprised 25 per cent of all autotransfusion cases. One hundred twenty-six patients had isolated abdominal trauma and had a mean estimated blood loss of 4864 +/- 6070 cc. The average volume of intraoperatively salvaged autologous blood transfused (autotransfusion) per patient was 1547 +/- 2359 cc, or a bank blood equivalent of 6.9 units of packed red blood cells. The total cost of autotransfusion in these patients was $63,252.00. Had bank blood been used instead of salvaged autologous blood, the cost would have been $114,523.00; thus, autotransfusion resulted in a savings of $51,271.00. The use of salvaged autologous blood comprised 45 per cent of total blood transfused. On a case-by-case basis, 75 per cent of cases were cost-effective compared to blood bank costs for an equivalent transfusion. Transfusion of intraoperatively salvaged autologous blood (autotransfusion) is a cost-effective, efficient way to provide blood products to operative trauma patients.

Temporary closure of open abdominal wounds: the vacuum pack.

Temporary closure of abdominal surgical wounds is occasionally required when conditions of the abdominal wall or peritoneal cavity prevent closure or when early re-exploration is planned. The optimal temporary closure should contain and protect the contents of the peritoneal cavity from external contamination and injury; preserve the integrity of the abdominal wall; be simple to perform and maintain; provide ease of reentry; and have minimal adverse physiologic effects. Based on these criteria, a method of temporary abdominal wound closure (termed the vacuum pack) has been designed and evaluated. The operative technique includes 1) placement of a fenestrated polyethylene sheet between the abdominal viscera and anterior parietal peritoneum; 2) placement of a moist, sterile laparotomy towel over the polyethylene sheet; 3) placement of two closed suction drains over the towel; 4) placement of an adhesive backed drape over the entire wound, including a wide margin of surrounding skin; and 5) suction applied to the drains, creating a vacuum and rigid compression of the layers of closure material. This creates a tight, external seal of the adhesive backed drape and facilitates drainage of the peritoneal cavity. From April 1992-December 1993, this temporary abdominal wound closure was performed 56 times in 28 patients, ages 6-78 years, for periods of 1-11 days. The procedure was used in 17 trauma patients and 11 non-trauma patients. Indications for use included increased intra-abdominal pressure in nine, mandatory re-exploration in 10, and a combination of these indications in nine patients. Pre- and postprocedural airway and systemic blood pressures were unaffected by this closure.(ABSTRACT TRUNCATED AT 250 WORDS)

Traumatic fracture of the hyoid bone: three case presentations of cardiorespiratory compromise secondary to missed diagnosis.

Hyoid bone fractures secondary to blunt trauma other than strangulation are rare (ML Bagnoli et al., J Oral Maxillofac Surg 1988; 46: 326-8), accounting for only 0.002 per cent of all fractures. The world literature reports only 21 cases. Surgical intervention involves airway management, treatment of associated pharyngeal perforations, and management of painful symptomatology. The importance of hyoid fracture, however, rests not with the rarity of it, but with the lethal potential of missed diagnosis. We submit three cases with varying presentations and management strategies. All three of our cases incurred injury by blunt trauma to the anterior neck. Two patients required emergent surgical airway after unsuccessful attempts at endotracheal intubation. One patient presented without respiratory distress and was managed conservatively. After fracture, the occult compressive forces of hematoma formation and soft tissue swelling may compromise airway patency. It is our clinical observation that hypoxia develops rapidly and without warning, leading to cardiorespiratory collapse. With endotracheal intubation prohibited by obstruction, a surgical airway must be established and maintained. Recognition of subtle clinical and physical findings are critical to the diagnosis of laryngotracheal complex injuries and may be life-saving in many instances. To ensure a positive outcome, a strong degree of suspicion based on mechanism of injury is mandated.