Effectiveness of monitored anesthesia care in cataract surgery.

OBJECTIVE: To determine the need for monitored anesthesia care in cataract surgery by evaluating the incidence of intervention by anesthesia personnel and by looking for associated risk factors. DESIGN: Nonrandomized, prospective case series with analysis of consecutive cataract surgery cases. PARTICIPANTS: A total of 1006 consecutive cataract surgery patients at an ambulatory surgery center over a 6-month period. METHODS: Routine cataract surgery was performed with the patient under local anesthesia. A detailed questionnaire was completed by the anesthesia personnel at the conclusion of each phase (before, during, and after) of cataract surgery. MAIN OUTCOME MEASURES: Age, medical history, and preoperative electrocardiogram (EKG) were analyzed as predictors for intervention by anesthesia personnel. The nature of the patient's problem and the type of intervention by anesthesia personnel were recorded. RESULTS: In 1006 consecutive cataract surgery cases, intervention by anesthesia personnel was required in 376 (37.4%) cases. No preoperative identifying characteristics were found to be reliable predictors of the need for intervention. There were no statistically significant differences in preoperative EKG and some medical conditions such as heart disease, diabetes, and thyroid disease between patients who received intervention and those who did not. Certain subgroups of patients did show a statistically significantly greater incidence of intervention, including systemic hypertensives (41.4%) versus nonhypertensives (34.5%) (P = 0.030), patients with pulmonary disease (49.3%) versus no pulmonary disease (36.5%) (P = 0.043), patients with renal disease (68.8%) versus no renal disease (36.9%) (P = 0.019), and patients with cancer (61.9%) versus no cancer (36.3%) (P = 0.001). Intervention was also required in 61.1 % of patients younger than 60 years of age compared to 36.5% of those patients 60 years of age and older (P = 0.005). CONCLUSIONS: Because intervention is required in more than one third of cataract surgery cases and the authors cannot reliably predict those patients at risk, monitored anesthesia care seems justified in cataract surgery with the patient under local anesthesia.

Practice parameters for the diagnosis and management of immunodeficiency. The Clinical and Laboratory Immunology Committee of the American Academy of Allergy, Asthma, and Immunology (CLIC-AAAAI)

In this brief review, only the most useful immunologic tests available for defining host defects that lead to susceptibility to infection have been emphasized. It should be pointed out that those evaluations and tests ordered by the physician will rule out the vast majority of the currently recognized defects. Finally, it is important that any patients identified as abnormal by these screening tests be characterized as fully as possible in centers specializing in these diseases before therapy is initiated, since what may appear to be a simple diagnosis on the surface may be an indicator of more complex underlying problems.

Inherited human complement C5 deficiency. Nonsense mutations in exons 1 (Gln1 to Stop) and 36 (Arg1458 to Stop) and compound heterozygosity in three African-American families.

Hereditary C5 deficiency has been reported in several families of different ethnic backgrounds and from different geographic regions, but the molecular genetic defect causing C5 deficiency has not been delineated in any of them. To examine the molecular basis of C5 deficiency in the African-American population, the exons and intron/exon boundaries of the C5 structural genes from three C5-deficient (C5D) African-American families were sequenced, revealing two nonsense mutations. The nonsense mutations are located in exon 1 (C84AG to TAG) in two of the C5D families (Rhode Island and North Carolina) and in exon 36 (C4521GA to TGA) in the third C5D family (New York). The exon 1 and 36 mutations are contained in codons that encode the first amino acid of the C5 beta-chain (Gln1 to Stop) and residue 1458 in the alpha-chain (Arg1458 to Stop), respectively. Allele-specific PCR and sequence analyses demonstrated that the exon 1 mutation is present in only one of the C5 null genes in both the Rhode Island and North Carolina families, and the exon 36 mutation is contained in only one C5 null gene in the New York family. Neither of the nonsense mutations was found in the European or Caucasian-American C5D individuals examined. Collectively, these data indicate that: 1) C5 deficiency is caused by several different molecular genetic defects, 2) C5 deficiency in the African-American population can be explained in part by two distinct nonsense mutations in exons 1 and 36, and 3) compound heterozygosity exists in all of the reported African-American C5D families.

Erythrocyte membrane proteins reactive with IgG (warm-reacting) anti-red blood cell autoantibodies: II. Antibodies coprecipitating band 3 and glycophorin A.

In our initial immunochemical study of the red blood cell (RBC) membrane proteins targeted in 20 cases of warm-antibody autoimmune hemolytic anemia (AHA), RBC eluates of 6 patients mediated immunoprecipitation (IP) of both band 3 and glycophorin A (GPA). This dual IP pattern had previously been observed with murine monoclonal antibodies (MoAbs) against the high frequency blood group antigen, Wrb (Wright), suggesting that the Wrb epitope may depend on a band 3-GPA interaction. Earlier, anti-Wrb had been identified serologically as a prominent non-Rh specificity of AHA autoantibodies. In the present study, 6 autoantibody eluates immunoprecipitating band 3 and GPA from common Wr(b+) RBCs were retested, in parallel with murine anti-Wrb MoAbs, against very rare Wr(a+b-)En(a+)RBCs. One patient's autoantibodies were unreactive with the Wr(b-) RBCs by either IP or indirect antiglobulin test (IAT) and were judged to have "pure" anti-Wrb specificity. Two other patients' autoantibodies displayed both IP and serologic evidence for anti-Wrb as a major component in combination with one or more additional specificities. However, among 3 other patients whose autoantibodies coprecipitated band 3 and GPA, there was no reduction in IP or IAT reactivity with Wr(b-) RBCs in 2 and only slight reduction in the third. We conclude (1) that human anti-Wrb autoantibodies, like their murine monoclonal counterparts, coprecipitate band 3 and GPA from human RBCs; but (2) that not all antibodies with this IP behavior have anti-Wrb serologic specificity, as defined by this donor's Wr(b-) RBCs. The possibility of an additional (non-Wrb) RBC epitope dependent on a band 3-GPA interaction is raised.

Persistent Torulopsis magnoliae endophthalmitis following cataract extraction.

Postoperative fungal endophthalmitis typically manifests as an indolent uveitis, weeks to months after surgery. In our patient, Torulopsis magnoliae endophthalmitis appeared as an acute, purulent postoperative endophthalmitis on the third day following extracapsular cataract extraction with implantation of a posterior chamber intraocular lens (IOL). The patient required three separate vitrectomy operations with instillation of intravitreal Amphotericin B; the last operation also included complete removal of the posterior capsule and IOL. This case, which is to our knowledge the first reported case of T. magnoliae endophthalmitis, is unusual in that it manifested as an acute, fulminant infection in the early postoperative period and was recalcitrant to standard endophthalmitis therapy.

Cytokine production by mite-specific T cells from donors with mild atopic disease.

This study was designed to determine whether allergen-specific T cells from patients with mild atopic disease were similar to TH2 cells. Tetanus-specific and house mite-specific T-cell clones were derived from peripheral blood of donors with strong immediate epicutaneous skin tests to Dermatophagoides farinae but with mild allergic disease. Overall, the tetanus- and mite-specific clones produced similar amounts of interleukin-4 (IL-4) and gamma interferon (INF-gamma). However, when donors were divided into those with high and low serum levels of mite-specific IgE as determined by RAST, mite-specific clones from donors with high specific IgE produced significantly more IL-4 and less IFN-gamma than mite-specific clones from donors with low levels of specific IgE. These results suggest that circulating allergen-specific T cells from patients who do not have severe allergic disease may nonetheless be skewed toward a TH2 profile. We also examined IL-4 and IFN-gamma production during primary culture of antigen-stimulated peripheral blood mononuclear cells. Detectable amounts of IL-4 were not produced. Stimulation with tetanus antigen induced two to three times as much IFN-gamma as did stimulation with mite antigen. However, the amount of IFN-gamma produced during primary culture did not correlate with the cytokine production of the T-cell clones subsequently generated.

Position dependent livedo reticularis in cholesterol emboli syndrome.

We describe a case of a 64-year-old Filipino man who presented with cholesterol emboli syndrome manifesting as worsening hypertension, renal failure and livedo reticularis involving the upper legs and lower abdomen. The livedo reticularis became very prominent with the patient standing, but completely vanished after several minutes of lying supine. Deep cutaneous biopsy of an area of skin that was found to be consistently involved with livedo reticularis demonstrated cholesterol clefts in several vessels, thus establishing the diagnosis in this patient, and avoiding the more problematic option of biopsying an involved visceral organ.

Erythrocyte membrane proteins reactive with human (warm-reacting) anti-red cell autoantibodies.

Immunoglobulin G (IgG) autoantibodies of 20 patients with autoimmune hemolytic anemia (AHA) were used in immunoaffinity assays with surface-radioiodinated human red blood cells (RBCs), and detergent-solubilized products were analyzed by SDS-PAGE/autoradiography. Four membrane proteins were identified as candidate autoantigens: a nonglycosylated polypeptide with an apparent molecular mass of 34 kD (p34) that was expressed in all available RBC phenotypes except Rhnull but differed consistently in apparent molecular mass from the 32-kD Rh(D) polypeptide co-isolated by IgG allo-anti-D; a heterogenous 37-55-kD glycoprotein, also deficient in Rhnull RBCs, which disappeared after deglycosylation by N-glycanase, with the appearance of a sharp, new approximately 31-kD band distinct from p34 and from Rh(D) polypeptide; a approximately 100-kD major membrane glycoprotein identified by immunoblotting as the band 3 anion transporter; and glycophorin A (GPA), also confirmed by immunoblotting. GP37-55 was not seen in the absence of p34, and both proteins are likely to be members of the Rh family. Indeed, a 34-kD polypeptide band and 37-55-kD poly-disperse "smear," isolated concurrently from the same labeled RBCs by IgG allo-anti-e, were indistinguishable from their autoantibody-isolated counterparts and may well be the same protein identified at different epitopes by the auto- and allo-antibodies. Individual AHA patients' autoantibodies isolated p34 and gp37-55, alone or in combination with band 3 (nine cases); strong band 3 alone (five cases); and combinations of band 3 with GPA (six cases). The autoantibodies of three additional patients whose AHA had been induced by alpha-methyldopa also isolated p34 and gp37-55.

Penicillin resensitization among hospitalized patients.

The purpose of this study was to determine the frequency of resensitization to penicillin after oral or intravenous treatment with beta-lactam antibiotics in hospitalized patients with histories of penicillin allergy. Seventeen adults (aged 24 to 76 years) and one child (aged 10 years) were treated intravenously and/or orally with beta-lactam antibiotics after negative skin tests were obtained with benzylpenicilloyl polylysine, potassium penicillin G, and alkaline hydrolysis products of penicillin G as minor determinant mixture. Repeat skin testing was performed 1 to 12 months after the therapy. Three patients (16%) became skin test positive after the treatment. Two patients reacted to potassium penicillin G alone, and the other patient reacted to benzylpenicilloyl polylysine and minor determinant mixture. These three patients were among the 15 patients who were treated with intravenous antibiotics. This study reveals a high percentage of skin test conversion after intravenously administered penicillin therapy and confirms the present practice of advising patients with a history of penicillin allergy who have successfully completed penicillin treatment to have a repeat skin test before future exposure to beta-lactam antibiotics.

Granular epithelial keratopathy as an unusual manifestation of Pseudomonas keratitis associated with extended-wear soft contact lenses.

We describe four patients who, using extended-wear soft contact lenses for myopia, abruptly developed ocular irritation and injection associated with elevated granular opacities initially confined to the central corneal epithelium. Cultures of the granular epithelial lesions were positive for Pseudomonas aeruginosa in all patients. Cultures of the contact lenses and lens case solutions grew Pseudomonas species and other gram-negative organisms. All patients responded to discontinuation of lens wear and frequent topical antibiotics. All recovered baseline visual acuity, and three have successfully resumed contact lens wear. These cases document that Pseudomonas keratitis may be manifested as a granular epithelial keratopathy.

Sarcoidosis of the female genital tract: a case presentation and survey of the world literature.

Sarcoidosis of the female genital tract is a rare clinical entity with only 20 cases reported in the world literature to date. An additional case is presented with a review of the previously reported cases. The diagnostic and histologic aspects of the disease are also discussed. The presence of granulomatous diseases in the female genital tract should initiate a thorough investigation for potential etiologies by both the pathologist and clinician. Etiologies of granuloma fraction must include coccidiomycosis, foreign body reactions, lymphogranuloma inguinale, and tuberculosis. Bacteriologic proof is essential to differentiate these from sarcoidosis.

Secretion of the terminal complement proteins, C5-C9, by human platelets.

The terminal complement components, C8 and C9, and to a lesser extent C5, C6, and C7, but minimal amounts of C3, were shown to be associated with washed human platelets. In unactivated platelets, the complement components were detected in the platelet pellet by hemolytic assays after centrifugation and disruption of the platelets by freeze-thawing. However, after platelets had been activated by collagen, thrombin, or aggregated IgG to induce aggregation, the complement components were released into the supernatant. The rank order of hemolytic activity of C9, C8, C7, C6, and C5 detected in the supernatants of activated platelets was quite different from that found in serum from the same donors, in the same assays. In particular, the serum C7 hemolytic titer was more than twice the serum C9 hemolytic titer, whereas the activity of C9 detected from platelets was more than twice that of C7. This argues against a purely nonspecific uptake of these proteins by platelets from plasma. The functional role of terminal complement components released from platelets during activation is unknown, but it is tempting to speculate that these proteins may have a role in platelet-dependent immunological tissue injury. Because the C5b-9 membrane attack complex activates platelets, it is possible that release of terminal complement proteins serves to amplify platelet activation and may also play a role in diseases in which complement membrane attack complexes have been implicated.

Structural polymorphism of the human platelet Fc gamma receptor.

A variable T lymphocyte proliferative response to murine IgG1 anti-T3 monoclonal antibodies, in which most North American Caucasians respond whereas a minority do not, is well established. This is most likely the result of a genetic polymorphism manifested by 1) the inability of the monocyte 40-kDa IgG FcR of some individuals to bind murine IgG1, and 2) a distinctive trimorphic pattern on IEF of the monocyte 40-kDa FcR, one form being seen in all individuals who do not respond and another form (or a combination of both forms) being seen in those who do respond. We have evaluated the IEF patterns of the platelet 40-kDa FcR and find that in every individual tested the pattern for platelet FcR correlates with that seen for the monocyte 40-kDa FcR pattern. Furthermore, the platelets of those individuals whose "nonresponder" monocyte 40-kDa FcR did not mediate a murine IgG1 anti-T3 response did not respond with an aggregation reaction to murine IgG1 immune complexes (opsonized E). In contrast, platelets from donors possessing "responder" monocytes displayed positive "aggregation" responses to E coated with murine IgG1 antibody. However, the platelet FcR structural polymorphism described earlier did not correlate with the donor-specific variability in capacity of platelets to respond functionally to aggregated human IgG described in an earlier paper. Rather, the variation in capacity of platelets from individual donors to respond functionally to aggregated human IgG was related to the quantitative expression of platelet FcR. These data indicate that the molecular mechanisms responsible for the platelet 40-kDa FcR structural polymorphism are quite different from the mechanisms governing the variation in quantitative expression of the receptor.

Recurrent abdominal pain as the sole manifestation of hereditary angioedema in multiple family members.

This paper describes a previously unreported finding of abdominal pain as the only lifelong manifestation of hereditary angioedema in multiple family members. This diagnosis was obscured by the absence of cutaneous, oropharyngeal, and respiratory involvement. Barium studies performed during painful attacks showed transient intestinal wall edema which, along with abnormalities in the C4 level and C1 esterase inhibitor activity, confirmed the diagnosis. It is important that hereditary angioedema be recognized in its various forms so that invasive procedures can be avoided and prophylactic therapy can be administered.

Aberrant immunoglobulin and c-myc gene rearrangements in patients with nonmalignant monoclonal cryoglobulinemia.

The status of the immunoglobulin (Ig) genes was investigated in patients with idiopathic nonmalignant monoclonal IgG cryoglobulinemia (NCG). In NCG, monoclonal antibodies are synthesized at an accelerated rate by nonmalignant B lymphocytes. In order to determine whether this high production rate is related to a clonal B cell expansion, the rearrangement of the Ig genes was investigated by Southern blot analysis of genomic DNA extracted from the peripheral blood lymphocytes of four NCG patients. In three of four (VI, BR, and CH) clonal expansion of B cells was detected using probes specific for the c kappa, JH, c gamma 4 genes (in accordance with detecting IgG kappa cryoproteins in these patients). BamHI digestion of DNA from VI and BR produced three rearranged fragments which cohybridized with JH and c mu probes. This finding suggested the presence of additional nonsecretory B cell clones and/or disruption of the gene segments spanned by and detected with the probes. In VI the idiotype of the IgG cryoglobulin was also detected in association with IgM in the supernatant of Epstein-Barr virus-stimulated B lymphocytes using a murine monoclonal anti-idiotypic antibody. In addition, the possibility of aberrant gene rearrangements was supported by noting the alteration of the c-myc gene locus in genomic DNA from peripheral blood leukocytes of VI and CH. Northern blot analysis of RNA isolated from peripheral blood B cells of VI and CH demonstrated aberrant transcripts of the c-myc gene, showing an active role of the altered c-myc locus. Detection of c-myc rearrangement in NCG patients clearly shows that this event may not be a final step in malignant B cell transformation; however, it may be related to the clonal expansion and high rate of cryoglobulin synthesis of nonmalignant B lymphocytes.

Human Fc gamma receptors: stable inter-donor variation in quantitative expression on platelets correlates with functional responses.

Evidence has recently been presented that a 40,000 dalton membrane sialoglycoprotein (p40) shared by monocytes and granulocytes serves as the human platelet receptor for aggregated IgG. We now report that the platelets of normal donors exhibit stable quantitative differences in the expression of this receptor molecule, as determined by flow cytometry using fluorescent staining with murine monoclonal antibody to p40 (mab IV.3). These inter-donor differences were reproducible on repeated testing over at least 4 mo. In concurrent assays, the binding of mab IV.3 to each donor's platelets was highly correlated with the binding of heat-aggregated human IgG, also assayed by flow cytometry. The biological relevance of this quantitative variation in IV.3 binding is suggested by its reproducible correlation with platelet responsiveness to aggregated IgG measured by aggregometry. Such stable quantitative variation in platelet Fc receptor expression among individual humans could contribute to differences in severity of certain pathologic processes initiated by IgG-containing immune complexes.