Linkage of Rieger syndrome to the region of the epidermal growth factor gene on chromosome 4.

Rieger syndrome is an autosomal dominant disorder of morphogenesis in which previous cytogenetic arrangements have suggested chromosome 4 as a candidate chromosome. Using a group of highly polymorphic short tandem repeat polymorphisms (STRP), including a new tetranucleotide repeat for epidermal growth factor (EGF), significant linkage of Rieger syndrome to 4q markers has been identified. Tight linkage to EGF supports its role as a candidate gene, although a recombinant in an unaffected individual has been identified. This study demonstrates the utility of using polymorphic STRP markers when only a limited number of small families are available for study.

Induction of a CD8+ cytotoxic T lymphocyte response by cross-priming requires cognate CD4+ T cell help.

Class I-restricted presentation is usually associated with cytoplasmic degradation of cellular proteins and is often considered inaccessible to exogenous antigens. Nonetheless, certain exogenous elements can gain entry into this so-called endogenous pathway by a mechanism termed cross-presentation. This is known to be effective for class I-restricted cytotoxic T lymphocyte (CTL) cross-priming directed against a variety of exogenous tumor, viral, and minor transplantation antigens. The related effect of cross-tolerance can also effectively eliminate responses to selected self components. In both cases, this presentation appears to require the active involvement of a bone marrow-derived antigen presenting cell (APC). Here, we show that CTL induction by cross-priming with cell-associated ovalbumin requires the active involvement of CD4+ helper T cells. Importantly, this CD4+ population is only effective when both the helper and CTL determinants are recognized on the same APC. Moreover, we would argue that the cognitive nature of this event suggests that the CD4+ T cell actively modifies the APC, converting it into an effective stimulator for the successful priming of the CTL precursor.

B cells directly tolerize CD8(+) T cells.

This report investigates the response of CD8(+) T cells to antigens presented by B cells. When C57BL/6 mice were injected with syngeneic B cells coated with the Kb-restricted ovalbumin (OVA) determinant OVA257-264, OVA-specific cytotoxic T lymphocyte (CTL) tolerance was observed. To investigate the mechanism of tolerance induction, in vitro-activated CD8(+) T cells from the Kb-restricted, OVA-specific T cell receptor transgenic line OT-I (OT-I cells) were cultured for 15 h with antigen-bearing B cells, and their survival was determined. Antigen recognition led to the killing of the B cells and, surprisingly, to the death of a large proportion of the OT-I CTLs. T cell death involved Fas (CD95), since OT-I cells deficient in CD95 molecules showed preferential survival after recognition of antigen on B cells. To investigate the tolerance mechanism in vivo, naive OT-I T cells were adoptively transferred into normal mice, and these mice were coinjected with antigen-bearing B cells. In this case, OT-I cells proliferated transiently and were then lost from the secondary lymphoid compartment. These data provide the first demonstration that B cells can directly tolerize CD8(+) T cells, and suggest that this occurs via CD95-mediated, activation-induced deletion.

Angiotensin in cardiac surgery: efficacy in patients on angiotensin converting enzyme inhibitors.

BACKGROUND: Patients presenting for cardiac surgery are often treated with angiotensin converting enzyme inhibitors (ACEIs), either for heart failure or hypertension. Control of systemic vascular resistance (SVR) during surgery can be difficult in such patients. Angiotensin II has been available as an unlicensed vasoconstrictor, but there is concern about renal damage and its use. AIM: This study compared a standard vasoconstrictor with angiotensin II and examined the effect on renal function after cardiac surgery. METHOD: Twenty consecutive, consenting patients scheduled for cardiac surgery that had been taking ACEIs for at least 6 months, were randomly assigned to receive either phenylephrine or angiotensin II for the control of SVR during and for 24 h after cardiac surgery. A pulmonary artery catheter was used to guide therapy. Creatinine clearance was measured before, 24 and 48 h after surgery. RESULTS: Low SVR and blood pressure requiring intervention was seen in all patients, particularly during cardiopulmonary bypass. One patient in the control group failed to respond to P, but responded normally to angiotensin II. Neither drug caused renal impairment. CONCLUSION: Angiotensin II is a safe alternative to phenylephrine in patients on ACEIs and should be considered in patients who fail to respond to conventional vasoconstrictors.

Transpupillary thermotherapy as primary treatment for small choroidal melanomas.

OBJECTIVE: To report the short-term follow-up results of eyes containing small choroidal melanomas that were treated with transpupillary thermotherapy. METHODS: Twenty eyes with suspected small choroidal melanomas were treated with transpupillary thermotherapy using infrared light delivered from the diode laser. RESULTS: The age of the patients ranged from 26 to 82 years. In 14 patients, there was documented growth of the melanoma before transpupillary thermotherapy. The tumor thickness ranged from less than 1.0 to 3.2 mm. Seven tumors were treated more than once. Follow-up ranged from 6 months to more than 3 years. Following treatment, the tumor thickness decreased in all cases, usually within 2 months. Progressive atrophy of tumor mass and loss of pigmentation within the tumor continued beyond 1 year of follow-up in some eyes. Complications included field defects, vascular changes, and macular abnormalities. CONCLUSIONS: Transpupillary thermotherapy of small choroidal melanomas is usually followed by early tumor shrinkage but is complicated by dense scotomas, nerve fiber bundle defects, and, occasionally, macular abnormalities. The short-term follow-up results suggest that transpupillary thermotherapy may arrest the growth of selected small melanomas.

Death due to splenic rupture in suppressor cell mycosis fungoides: a case report.

A case of mycosis fungoides in which pathologic rupture of the spleen led to intraperitoneal hemorrhage and death is described. To our knowledge, splenic rupture has not been reported previously as a cause of death in mycosis fungoides. Immunologic studies demonstrated that the neoplastic cell was a suppressor/cytotoxic T-cell. In most cases of mycosis fungoides or the Sézary syndrome, the neoplastic cell has been a helper/inducer T-cell. This case was very aggressive clinically with prominent visceral involvement and suggests that mycosis fungoides may be clinically diverse as well as immunologically heterogeneous.

An autosomal dominant form of low-tension glaucoma.

A condition causing glaucomatous optic atrophy and visual field loss at normal or borderline intraocular pressure affected eight members of a family of consecutive generations. The disease was detectable in early adulthood and progressed slowly throughout life. The pattern of inheritance is autosomal dominant. One affected individual died of a myocardial infarction, and his eyes were obtained post mortem. Light and electron microscopic examination demonstrated glaucomatous optic atrophy with loss of ganglion cells. The trabecular meshwork, choroidal and optic nerve vasculature, retinal pigment epithelium, and photoreceptors were normal in appearance. We believe this family has an autosomal dominant genetic condition that is a distinct type of low-tension glaucoma.

Factors prognostic of visual outcome in patients with subretinal hemorrhage.

We reviewed the charts of 29 patients with large subretinal hemorrhages involving the center of the fovea to evaluate factors that might be prognostic of visual outcome. The average final visual acuity was 20/480 with a mean follow-up of three years. Patients with thick hemorrhages (causing an obvious elevation of the fovea) had worse final visual acuity than patients with thin hemorrhages (P = .02). The diameter of the hemorrhage was not a significant predictor of outcome. Patients with aging macular degeneration had poorer final visual acuity (mean, 20/1,700, P = .002), and patients with choroidal ruptures had better final visual acuity, (mean 20/35, P less than .001) than the remainder of the patients. We found that the presence of aging macular degeneration was a more important predictor of the outcome of legal blindness than the thickness of the hemorrhage (P = .03). Although the prognosis in patients with subfoveal blood is generally poor, some patients have excellent return of vision.

Myopia induced by vitreous hemorrhage.

Six of 11 children developed myopia in one eye after vitreous hemorrhage. None had retinopathy of prematurity, glaucoma, aphakia, or scleral buckling. In seven children developing vitreous hemorrhage before 1 year of age, six exhibited a myopic anisometropia in the affected eye of 1.37 to 12.00 diopters (mean, -4.7 diopters; S.D., 4.0). The degree of myopia correlated with the age of onset and duration of media opacification. In the child without myopia, the hemorrhage did not obscure the posterior pole. None of the four children whose hemorrhage occurred after 2 1/2 years of age showed myopic anisometropia (mean, +0.16 diopters; S.D., 0.24). We conclude that vitreous hemorrhage occurring in infancy is strongly associated with the development of myopia in the affected eye.

Surgical management of posteriorly dislocated silicone plate haptic intraocular lenses.

PURPOSE: To report a large series of delayed posterior dislocation of silicone plate haptic intraocular lenses after Nd:YAG laser capsulotomy and discuss the surgical management of this complication. METHODS: We reviewed the records of 11 consecutive patients (11 eyes) with delayed onset of posterior dislocation of a plate haptic silicone intraocular lens. The cause of the posterior capsular defect, time to dislocation, surgical management techniques, complications, and visual outcome were recorded. RESULTS: In eight of the 11 eyes, the silicone plate haptic intraocular lens dislocated an average of 1.8 months (range, 0 to 6.5 months) after Nd:YAG posterior capsulotomy. The other three eyes had surgical complications at the time of cataract extraction that compromised posterior capsular or zonular integrity and led to silicone plate haptic intraocular lens dislocation from 9 weeks to 6 months (mean, 3.6 months) postoperatively. Surgical management consisted of pars plana vitrectomy with intraocular lens repositioning (six eyes) or exchange (five eyes). The average follow-up period after intraocular lens repositioning or exchange was 6.5 months (range, 1 to 14 months). Best-corrected visual acuity at the last follow-up examination measured 20/40 or better in all but one eye that had preexisting macular disease. CONCLUSIONS: Cataract surgeons and patients should be aware of the potential for plate haptic silicone intraocular lenses to undergo delayed posterior dislocation through capsular defects. This complication can be managed effectively with vitrectomy and either repositioning or exchange of the implant. Postoperative visual acuity is generally excellent, and complications are minimal.

The risk of cytomegalovirus transmission by penetrating keratoplasty.

To investigate the risk of cytomegalovirus transmission by corneal transplantation, we quantitated anticytomegalovirus IgG levels of donor, preoperative, and postoperative serum samples. Of 118 patients, 79 (67%) were seropositive preoperatively. Twenty-five patients who were seronegative preoperatively received a graft from a positive donor and two (8%) seroconverted. Eleven patients who were seronegative preoperatively received a graft from a negative donor and one (9%) seroconverted. None of the patients who seroconverted had a febrile illness and all three grafts were clear.

Reversible loss of light perception after vitreoretinal surgery.

PURPOSE: We studied reversible loss of light perception after vitreoretinal surgery to show that functional vision can return in some patients. METHODS: We reviewed the medical records of seven patients who had postoperative reversible loss of light perception in the eye that underwent vitreoretinal surgery. Differences in the postoperative courses and interventions were studied. RESULTS: Five of the seven patients had diabetes mellitus but none had hypertension. The indications for vitreoretinal surgery were severe proliferative diabetic retinopathy in five patients and retinal detachment with advanced proliferative vitreoretinopathy in two patients. Seven patients had reversible loss of light perception within the first three postoperative days. Six of the seven patients had an intraocular pressure greater than 26 mm Hg at the time the eye had no light perception. Decreasing the intraocular pressure was associated with return of light perception in five of seven patients. Return of useful vision was gradual. Four of seven patients had a visual acuity of 20/400 or better one month after surgery, and all seven had a visual acuity of 20/400 or better three months after surgery. Visual acuity in four eyes improved further to 20/70 or better at six months or more after surgery. CONCLUSION: Reversible loss of light perception after vitreoretinal surgery does occur in some patients. Monitoring vision and intraocular pressure is important because prompt treatment may assist in the recovery of functional vision.

Neuro-ophthalmologic emergencies.

This article is designed to provide the emergency physician with the knowledge necessary for the diagnosis and management of the more common neuro-ophthalmologic emergencies. Emphasis is placed on the recognition and initial evaluation of neuro-ophthalmologic disease.

Hemorrhage associated with localization of melanoma margins during radioactive plaque placement.

Accurate placement of a radioactive plaque is essential in brachytherapy of choroidal melanoma. Various localization techniques, including transillumination of anteriorly located tumours and scleral indentation to mark the anterior margin of posteriorly located tumours, have been used in initially placing a plaque over the base of the tumour. Of 40 consecutive patients treated for choroidal melanoma between 1986 and 1990, 8 had posteriorly located tumours, all localized by means of scleral indentation; subretinal hemorrhage occurred in 3 of the 8 during marking of the tumour margins. No hemorrhages occurred in the 32 patients with tumours localized by means of transillumination (p less than 0.01). It is not clear whether the method of marking or the location of the tumour itself contributed to the development of the hemorrhage. Hemorrhage around the base of a tumour may mask the tumour margins, making assessment of the response to therapy difficult. Caution should be used when marking posteriorly located tumours.

Favourable outcome of traumatic endophthalmitis with associated retinal breaks or detachment.

Traumatic endophthalmitis in association with retinal breaks or detachments is reported to have uniformly poor visual and anatomic outcomes. We describe two cases of culture-positive traumatic endophthalmitis with retinal breaks or detachment in which the final visual result was 20/70 in one case and 20/40 in the other. Factors that may improve the prognosis in such cases include attention to the possibility of infection, selective use of broad-spectrum antibiotics, prompt surgical intervention and improvement in vitreous surgical techniques. Modification of intravitreal antibiotic regimens may be indicated in eyes in which the vitreous cavity is partially filled with air or gas.

Perioperative autologous blood transfusion in elective total hip prosthesis operations.

The aim of this study was to determine if acute perioperative normovolaemic haemodilution with retransfusion of the autologous blood at the end of operation would reduce or eliminate the need for homologous (banked) blood. Forty patients scheduled for total hip prosthesis replacement (THPR) were randomly divided into two groups: Group A, 20 patients from whom 900 ml of blood was taken 20 min preoperatively, the volume being replaced with 1000 ml of gelatin solution (Haemaccel). Group B, 20 patients who were undergoing the same operation but from whom no blood was taken. Both groups were allowed a fall in haematocrit (Hct) to 0.25 before transfusion was started. A standard formula to calculate allowable blood loss plus intraoperative Hct measurements were used to achieve the haemodilution. There was no significant difference in blood loss between the two groups. Transfusion requirement was the same in the two groups. In this study, autotransfusion by the withdrawal of 900 ml of blood is inadequate to reduce the transfusion requirement further than that which can be achieved by haemodilution alone.

Transpupillary thermotherapy as primary treatment for small choroidal melanomas.

PURPOSE: To report short-term follow-up of eyes containing small choroidal melanomas that were treated with transpupillary thermotherapy (TTT). METHODS: Twenty eyes with suspected small choroidal melanomas were treated with TTT using infrared light delivered from the diode laser. RESULTS: The age of patients ranged from 26 to 82 years. In 14, there was documented growth of the melanoma prior to TTT. Tumor thicknesses ranged from less than 1 to 3.2 mm. Seven tumors were treated more than once. Follow-up ranged from 6 months to more than 3 years. Following treatment, tumor thicknesses decreased in all cases, usually within 2 months. Progressive atrophy of tumor mass and loss of pigmentation within the tumor continued beyond 1 year of follow-up in some eyes. Complications included field defects, vascular changes, and macular abnormalities. CONCLUSIONS: Transpupillary thermotherapy of small choroidal melanomas is usually followed by early tumor shrinkage but is complicated by dense scotomas, nerve fiber bundle defects, and occasionally macular abnormalities. Short-term follow-up suggests that TTT may arrest growth of selected small melanomas.

Collection of blood-engorged black flies (Diptera: Simuliidae) and identification of their source of blood.

Blood-engorged black flies were captured by 2 methods: early morning application of a quick knock down insecticide (resmethrin) into tree canopies, and late afternoon to early evening truck trapping. More engorged flies were captured per man-hour with the tree spraying method than with the truck trap. The percentages of females captured by the spraying and truck trap methods that were engorged were 18 and 1.3, respectively. The most commonly engorged species captured were Prosimulium magnum and P. mixtum/fuscum, and Simulium jenningsi and S. venustum (70% of total). Blood sources of 12 black fly species were identified. Mammals comprised 95% of the blood sources identified. The most common hosts were equines (31%), bovines (25%) and raccoons (19%). Seven percent of all meals identified were from mixed sources, of which 43% involved both mammals and birds.