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S Starr

Publications and source records attributed to S Starr.

At least 37 records · Page 2Linked to original sources

Delayed type hypersensitivity to human cytomegalovirus.

A skin test for immunity to human cytomegalovirus (HCMV) is described in which skin induration is measured after intradermal injection of antigen derived from heat-inactivated Towne strain HCMV or of envelope prepared from the virus. Randomly selected healthy young adult males and females were prescreened for evidence of past infection with HCMV using serologic tests. Each individual was inoculated with heat inactivated whole virion HCMV antigen prepared from serum-free supernatants of HCMV-infected MRC-5 cells, non-infected MRC-5 cell lysates, and Candida extract. HCMV seropositive individuals developed positive skin reactions to both the Candida extract and the HCMV test antigen. No response was observed at the MRC-5 cell lysate inoculation site. The envelope antigen also elicited a response in seropositive individuals. Seronegative individuals who were negative to the HCMV intradermal antigen at the start of the study developed a positive response 1 week after subcutaneous immunization with live attenuated Towne strain HCMV. This response also correlated with the onset of in vitro proliferation responses to HCMV antigens by peripheral blood lymphocytes obtained from the immunized individuals. Furthermore, skin test and lymphocyte proliferation responses remained positive when tested up to 93 days post-immunization. In guinea pig experiments with HCMV, those animals immunized with purified HCMV or a virus envelope preparation developed strong skin reactions to intradermal injection of each of those antigens. In contrast, no reaction was observed in immune animals, either to viral capsid antigen or uninfected cell-lysate antigen, and no reactions were observed to any HCMV antigen in non-immune animals.

Animals↗

Linear single-dose pharmacokinetics of ganciclovir in newborns with congenital cytomegalovirus infections. NIAID Collaborative Antiviral Study Group.

The pharmacokinetic characteristics of ganciclovir were determined in neonates (age range, 2 to 49 days) after an 1-hour intravenous infusion of a single dose of either 4 mg/kg (n = 14) or 6 mg/kg (n = 13). Twenty-seven newborns with symptomatic cytomegalovirus inclusion disease were enrolled in this open phase I-II pharmacokinetics, safety, and tolerance trial of ganciclovir at one of two doses. Ganciclovir disposition was best described by a one-compartment open model with zero-order input and first-order elimination. The mean elimination half-life (t1/2) for both dose groups was 2.4 hours. The mean apparent volume of distribution (Vd) was 669 +/- 70 ml/kg for the 4 mg/kg group and 749 +/- 59 ml/kg for the 6 mg/kg group. The mean total body clearance (CL) for the 4 mg/kg and 6 mg/kg groups was 189 +/- 28 ml/hr/kg and 213 +/- 21 ml/hr/kg, respectively. No significant differences were observed in Vd or CL between the two groups. The Vd, expressed in milliliters, increased with increasing patient weight (r = 0.689; p = 0.0001). The CL, expressed in milliliters per hour per kilogram, increased with increasing age (r = 0.413; p = 0.032). No significant differences were observed between the two dose groups for the area under the curve normalized for dose (AUC/Dose) or the maximum plasma concentration normalized for dose (Cmax/Dose), indicating that ganciclovir exhibited linear pharmacokinetics in these neonates.

Creatinine↗

The effect of decreasing amounts of live virus, while antigen content remains constant, on immunogenicity of Oka/Merck varicella vaccine.

The purpose of the study was to establish the minimum immunizing dose of stored Oka/Merck varicella vaccine and mimic effects of prolonged storage of vaccine at freezer temperatures. Ninety children were randomized to one of three groups: group A (1770 pfu/dose), group B (400-500 pfu/dose), or group C (80-160 pfu/dose). Seroconversion rates for groups A-C were 97%, 96%, and 92%, respectively. Group A and B vaccinees had higher antibody titers at 1 year than did group C subjects (P = .01). The difference between groups B and C approached significance (P = .058). At 1 year after immunization, 73%, 83%, and 80% in groups A-C, respectively, demonstrated cell-mediated responses. Since freshly reconstituted vaccine contains 1770 pfu/dose, vaccine failure from loss of potency is unlikely if vaccine is stored properly and administered promptly after reconstitution.

Antibodies, Viral↗

A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. Infectious Diseases Collaborative Antiviral Study Group.

BACKGROUND: Despite the use of vidarabine, herpes simplex virus (HSV) infection in neonates continues to be a disease of high morbidity and mortality. We undertook a controlled trial comparing vidarabine with acyclovir for the treatment of neonatal HSV infection. METHODS: Babies less than one month of age with virologically confirmed HSV infection were randomly and blindly assigned to receive either intravenous vidarabine (30 mg per kilogram of body weight per day; n = 95) or acyclovir (30 mg per kilogram per day; n = 107) for 10 days. Actuarial rates of mortality and morbidity among the survivors after one year were compared overall and according to the extent of the disease at entry into the study (infection confined to the skin, eyes, or mouth; encephalitis; or disseminated disease). RESULTS: After adjustment for differences between groups in the extent of disease, there was no difference between vidarabine and acyclovir in either morbidity (P = 0.83) or mortality (P = 0.27). None of the 85 babies with disease confined to the skin, eyes, or mouth died. Of the 31 babies in this group who were treated with vidarabine and followed for a year, 88 percent (22 of 25) were judged to be developing normally after one year, as compared with 98 percent (45 of 46) of the 54 treated with acyclovir (95 percent confidence interval for the difference, -4 to 24). For the 71 babies with encephalitis, mortality was 14 percent with vidarabine (5 of 36) and with acyclovir (5 of 35); of the survivors, 43 percent (13 of 30) and 29 percent (8 of 28), respectively, were developing normally after one year (95 percent confidence interval for the difference, -11 to 39). For the 46 babies with disseminated disease, mortality was 50 percent (14 of 28) with vidarabine and 61 percent (11 of 18) with acyclovir (95 percent confidence interval for the difference, -20 to 40); of the survivors, 58 percent (7 of 12) and 60 percent (3 of 5), respectively, were judged to be developing normally after one year (95 percent confidence interval for the difference, -40 to 50). Both medications were without serious toxic effects. CONCLUSIONS: In this multicenter, randomized, blinded study there were no differences in outcome between vidarabine and acyclovir in the treatment of neonatal HSV infection. The study lacked statistical power to determine whether there were sizable differences within the subgroups of those with localized HSV, encephalitis, or disseminated disease.

Acyclovir↗

Predictors of morbidity and mortality in neonates with herpes simplex virus infections. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.

BACKGROUND: In a controlled trial comparing acyclovir with vidarabine in the treatment of neonatal herpes simplex virus (HSV) infection, we found no significant difference between the treatments in adjusted mortality and morbidity. Hence, we sought to define for the entire cohort (n = 202) the clinical characteristics that best predicted the eventual outcome in these neonates. METHODS: Data were gathered prospectively at 27 centers between 1981 and 1988 in infants less than one month of age who had virologically confirmed HSV infection. We examined the outcomes by multivariate analyses of 24 variables. Disease was classified in one of three categories based on the extent of the involvement at entry into the trial: infection confined to skin, eyes, or mouth; encephalitis; or disseminated infection. RESULTS AND CONCLUSIONS: There were no deaths among the 85 infants with localized HSV infection. The mortality rate was significantly higher in the 46 neonates with disseminated infection (57 percent) than in the 71 with encephalitis (15 percent). In addition, the risk of death was increased in neonates who were in or near coma at entry (relative risk, 5.2), had disseminated intravascular coagulopathy (relative risk, 3.8), or were premature (relative risk, 3.7). In babies with disseminated disease, HSV pneumonitis was also associated with greater mortality (relative risk, 3.6). In the survivors, morbidity was most frequent in infants with encephalitis (relative risk, 4.4), disseminated infection (relative risk, 2.1), seizures (relative risk, 3.0), or infection with HSV type 2 (relative risk, 4.9). With HSV infection limited to the skin, eyes, or mouth, the presence of three or more recurrences of vesicles was associated with an increased risk of neurologic impairment as compared with two or fewer recurrences.

Consciousness↗

Isolated gA/gB glycoprotein complex of human cytomegalovirus envelope induces humoral and cellular immune-responses in human volunteers.

Three human cytomegalovirus (HCMV) seronegative individuals were immunized with a single dose of HCMV envelope; two individuals developed neutralizing antibodies. Two naturally HCMV seropositive and three HCMV seronegative human volunteers were immunized with a major glycoprotein complex, gA/gB, of HCMV that had been purified by immunoadsorbent column chromatography. After a single injection of the gA/gB preparation, the naturally seropositive individuals developed higher titres of neutralizing antibodies and temporarily higher HCMV-specific lymphocyte proliferation (HCMV-LP) responses in vitro. The seronegative individuals developed neutralizing antibodies after the third injection of gA/gB, which were present only transiently, but showed a rapid reappearance and increase in titre after the fourth injection. At 1 year after the first injection, the neutralizing antibody titres were still comparable with those of the naturally seropositive individuals. HCMV-LP responses to HCMV in the initially seronegative individuals developed after the second or third injection with the gA/gB preparation and remained positive during the 1-year observation period. These results show that the gA/gB protein induces both humoral and cellular immune responses in humans, and might serve as the basis of a subunit vaccine.

Animals↗

Significance of epididymal and ductal anomalies associated with testicular maldescent.

Epididymal abnormalities have long been found in conjunction with cryptorchid testicles. The aim of this study was to document the different types of epididymal and ductal anomalies in relation to the position of the cryptorchid testis and to determine their clinical significance. Exploration was performed on 187 cryptorchid testes in 174 boys. The position of the testis and the epididymal and ductal anomalies were documented at operation. A biopsy was taken from the testis or atretic spermatic cord structures for light microscopy. Epididymal, ductal and/or testicular anomalies were detected in 43 per cent of the 187 testes, including anomalies of ductal fusion, anomalies of ductal suspension and anomalies associated with absent or vanishing testes. Biopsy of the testes with severe anomalies of ductal fusion showed preservation of germ cells in 69 per cent and diminished germ cells in 31 per cent. The higher the arrest of testicular descent, the more grossly abnormal was the associated ductal system. Early successful orchiopexy alone may not ensure subsequent fertility despite the presence of normal germ cells.

Biopsy↗

A comparative study of herpes simplex infections in renal transplant and leukemic patients.

Herpes simplex virus (HSV) reactivation and lesion formation were studied in 68 renal transplant recipients and 30 leukemic patients. Antibody titers to HSV were determined, and seropositive patients were examined three times weekly for up to one month. Surveillance cultures were taken for oral HSV, and HSV culture and cytology were done for all oral lesions found. In a smaller number of patients, immune responses were determined. HSV reactivation was similar in the transplant and leukemic groups (46.8% vs. 50%), but a significant difference in the incidence of HSV lesion formation was noted between the two groups. Of the transplant patients in whom HSV reactivated, 31.8% developed HSV lesions; of leukemic patients in whom HSV reactivated, 100% developed HSV lesions. Differences in the incidence of formation of HSV lesions in these groups of immunosuppressed patients suggest that reactivation of HSV and formation of HSV lesions may involve different mechanisms. Low levels of antibody-dependent cellular cytotoxicity were noted in leukemic patients and may contribute to increased formation of HSV lesions in this group.

Adolescent↗

Immune responses to isolated human cytomegalovirus envelope proteins.

A group of envelope proteins of human cytomegalovirus, gA protein (L. Pereira, M. Hoffman, M. Tatsuno, and D. Dondero, Virology 139:73-86, 1984; L. Pereira, p. 383-404, in B. Roizman, ed., The herpesviruses, vol. 3, 1985), and two protein mixtures (58,000-molecular-weight [58K]-66K and 130K-66K), separated by serial columns prepared with anti-gA immunoglobulin G from sera of immunized guinea pigs, induced neutralizing antibodies and a cellular immune response in the animals. The gA is a disulfide-linked protein complex consisting of high-molecular-weight (greater than 200K), 130K-150K, and 55K-58K proteins.

Animals↗

Human leukocytes kill varicella-zoster virus-infected fibroblasts in the presence of murine monoclonal antibodies to virus-specific glycoproteins.

Seven murine monoclonal antibodies reacting with major glycoproteins of varicella-zoster virus were tested for functional activity in assays for antibody-dependent cellular cytotoxicity (ADCC) and antibody-plus-complement-mediated lysis. Human peripheral blood mononuclear cells killed varicella-zoster virus-infected fibroblasts in the presence of three of four monoclonal antibodies directed against gp98/62 and a single monoclonal antibody directed against gp118. Neither of two monoclonal antibodies directed against gp66 was able to mediate ADCC. In 18-h assays, adherent effector cells were more active than nonadherent effector cells in mediating ADCC. Adherent cells treated with anti-Leu-11b and complement retained their cytotoxic activity, suggesting that monocytes are responsible for most of the adherent-cell-mediated cytotoxicity. Both immunoglobulin G1 and G2a murine monoclonal antibodies were able to participate in ADCC. Of the two immunoglobulin G2a monoclonal antibodies tested, both of which reacted with gp98/62, only one mediated lysis in the presence of complement. These results indicate that some murine monoclonal antibodies against major glycoproteins of varicella-zoster virus have functional activity in cytotoxicity assays.

Antibodies, Monoclonal↗

A team approach to pharmacologic treatment of chronic schizophrenia.

The authors describe a therapeutic approach to the pharmacologic treatment of the schizophrenic patient. This team approach relies on interaction between the patient, the patient's family, and the clinician, and helps to eliminate blaming behavior that often demoralizes all parties involved. The authors maintain that neuroleptic therapy can control the positive symptoms of schizophrenia. However, they point out that neuroleptics may cause side effects and may interfere with improvement in negative symptoms and interpersonal relationships. The authors suggest that reduced-dosage strategies may prove the most effective way to prevent relapse, while minimizing the side effects of neuroleptics.

Antipsychotic Agents↗

HCMV envelope antigens induce both humoral and cellular immunity in guinea pigs.

Antibody and cellular immunity were measured in guinea pigs immunized with whole virion, with nucleocapsids of human cytomegalovirus or with solubilized antigens containing virus envelope proteins. All the three types of immunogens induced the production of humoral antibody as well as cytomegalovirus (CMV)-specific cellular immunity. In immunization experiments envelope antigen was as effective as immunization with whole virion.

Animals↗

Human natural killer cells analyzed by B73.1, a monoclonal antibody blocking Fc receptor functions. I. Characterization of the lymphocyte subset reactive with B73.1.

We describe the production of the monoclonal antibody B73.1, reacting with a subset of human lymphocytes and, in about one-half of the donors, with neutrophilic polymorphonuclear leukocytes. In the peripheral blood from normal adult donors, 14.6 +/- 8.5% of the lymphocytes react with B73.1 antibody. The B73.1(+) lymphocyte subset does not bear markers of typical T or B cells and corresponds to the lymphocyte subset containing antibody-dependent killer (K) and natural killer (NK) cells. We demonstrate that: a) virtually all lymphocytes with K/NK cytotoxic activity are found in the lymphocyte subpopulation bearing the B73.1-defined antigen; b) the B73.1(+) lymphocyte subset bears the combination of antigens known to be present on K/NK cells; and c) there is a positive correlation between the level of cytotoxicity and the actual number of B73.1(+) lymphocytes in individual donors. We also report the distribution of B73.1(+) lymphocytes according to donor age and tissue types. The use of the B73.1 antibody in quantitating the actual number of K/NK cells and in performing functional studies on spontaneous cytotoxicity is discussed.

Adolescent↗

A non-x-linked syndrome with susceptibility to severe Epstein-Barr virus infections.

Three siblings developed severe (two) or fatal (one) infectious mononucleosis. This family differed from previously described kindreds with a susceptibility to overwhelming Epstein-Barr virus infections in that: (1) both males and females were affected; (2) they had a history of the recurrent bacterial infections; (3) they produced the full spectrum of antibodies to EBV in the expected range of titers; and (4) survivors recovered completely. Two of these youths, but not their parents or an unaffected sibling with mild IM, had a deficiency of natural killer activity that did not respond to preincubation of their peripheral blood mononuclear cells with interferon. NK activity may have an important role in controlling infections with EBV.

Adolescent↗

The bacteriologically battered baby: another case of Munchausen by proxy.

We present a case in which a mother who had had self-inflicted infections as a teenager also caused life-threatening infections in her year-old child. After testing for and treating various immunologic deficiencies without success, it was apparent that the infection was caused by contamination of intravenous sites. Strict isolation of the patient, with restricted and observed visitations by the mother, was the critical step in stopping the infections. Because the woman took her child to several emergency departments, this case is presented to alert emergency personnel to this entity and to explain some of the dynamics and the social issues that cause the problem.

Adult↗