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Biomedical subjects

M Shapiro

Publications and source records attributed to M Shapiro.

At least 127 records · Page 7Linked to original sources

Multicenter trial of transscleral diode laser retinopexy in retinal detachment surgery.

PURPOSE: To evaluate the safety and efficacy of transscleral diode laser for retinopexy in rhegmatogenous retinal detachment surgery in a multicenter trial. DESIGN: 67 patients with primary rhegmatogenous retinal detachment underwent scleral buckling surgery, using transscleral diode laser for retinopexy, at five study centers. STUDY PARTICIPANTS: 72 patients with primary rhegmatogenous retinal detachments were enrolled. No patient with chronic detachment, a retinal break greater than 90 degrees, history of uveitis or infectious retinopathy, or proliferative vitreoretinopathy was enrolled. Five eyes were excluded because they required additional nonprotocol treatment at the time of surgery (vitrectomy or supplementary cryotherapy due to probe malfunction). MAIN OUTCOME MEASURES: Retinal reattachment at six months after one operation. Secondary measures: visual acuity and complications, including choroidal, retinal, and vitreous hemorrhage, inflammation, and scleral damage. RESULTS: Six months or greater follow-up information was available on 65 eyes. Retinas were attached at 6 months with a single operation in 58 (89%) of these eyes. Complications included apparent pinpoint breaks in Bruch is membrane in 15 eyes, scleral thermal effect in 14 eyes, and limited hemorrhage, which was intraretinal in 10 eyes, and extended into the vitreous in 3 eyes. In one case, hemorrhage was judged to have contributed possibly to initial surgical failure. The other complications had no known adverse effects. Complications were significantly associated with the physicians experience with transscleral laser retinopexy. CONCLUSION: In this multicenter series, transscleral diode laser retinopexy served as a safe and effective means of creating chorioretinal adhesion during retinal reattachment surgery. Minor complications were minimized by increasing experience with the technique.

Adolescent↗

Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum against the hypervariable region 1 of the envelope 2 protein.

The identification of the neutralization domains of hepatitis C virus (HCV) is essential for the development of an effective vaccine. Here, we show that the hypervariable region 1 (HVR1) of the envelope 2 (E2) protein is a critical neutralization domain of HCV. Neutralization of HCV in vitro was attempted with a rabbit hyperimmune serum raised against a homologous synthetic peptide derived from the HVR1 of the E2 protein, and the residual infectivity was evaluated by inoculation of HCV-seronegative chimpanzees. The source of HCV was plasma obtained from a patient (H) during the acute phase of posttransfusion non-A, non-B hepatitis, which had been titered for infectivity in chimpanzees. The anti-HVR1 antiserum induced protection against homologous HCV infection in chimpanzees, but not against the emergence of neutralization escape mutants that were found to be already present in the complex viral quasispecies of the inoculum. The finding that HVR1 can elicit protective immunity opens new perspectives for the development of effective preventive strategies. However, the identification of the most variable region of HCV as a critical neutralization domain poses a major challenge for the development of a broadly reactive vaccine against HCV.

Amino Acid Sequence↗

Intragraft IL-15 transcripts are increased in human renal allograft rejection.

IL-15, a novel growth factor made by a variety of cells, stimulates T cell proliferation in a fashion similar to IL-2. IL-2 transcripts are not routinely found in rejecting human renal allografts at the time of clinically evident rejection. However, T cell proliferation continues as the rejection progresses. We postulated that IL-15 may be actively transcribed during clinical rejection and account, at least in part, for the ongoing T cell expansion. RNA was extracted from renal biopsies and reverse transcribed to cDNA which was used as template for competitive PCR. IL-2 mRNA was detected in just 3 of the 45 biopsy samples. IL-15 transcripts were detected in all renal biopsy specimens and was significantly increased in specimens obtained from rejecting as compared with nonrejecting renal allografts. IL-15 transcription correlates with rejection and may play an important role in T cell mediated rejection.

Acute Disease↗

Varicella in Chimpanzees.

Two chimpanzees were inoculated subcutaneously with the wild-type Oka strain of varicellazoster virus (VZV). Viral DNA was detected in peripheral blood mononuclear cells of both animals using the polymerase chain reaction (PCR) shortly after inoculation. Ten days after inoculation both animals developed an erythematous, papular rash near the site of inoculation that extended into the adjacent dermatome. Viral DNA was found by PCR in a skin biopsy from one of the animals at the time of the rash. While only two animals were studied, the development of a mild form of varicella in chimpanzees indicates that these animals might be useful for molecular studies of viral genes involved in virulence or attenuation of VZV.

Animals↗

Efficacy of iontophoresis in the rat cornea.

BACKGROUND: Iontophoresis can enhance penetration of drugs into tissues. We examined the extent of penetration of gentamicin into the cornea of rats during iontophoresis and the effect of varying the concentrations of gentamicin, the duration of iontophoresis and the current densities during iontophoresis. METHODS: Eight groups of rats underwent corneal iontophoresis using gentamicin dissolved in agar. Low and high concentrations of gentamicin were used, as well as low and high current densities and long and short durations of iontophoresis. Control groups received topical or subconjunctival gentamicin, topical saline solution and mock iontophoresis with the agar-gentamicin mixture. The Mann-Whitney test was used for statistical evaluation. RESULTS: Highly bactericidal concentrations of gentamicin were obtained in all the iontophoresis-treated corneas. The high concentration compared to the low concentration of gentamicin in agar significantly increased the concentration of gentamicin in the corneas, as did the longer duration of iontophoresis. However, higher current intensity did not significantly enhance the drug concentration in the cornea. CONCLUSION: Iontophoresis with a concentrated gentamicin-agar mixture may provide a rapid increase of gentamicin levels in the cornea.

Absorption↗

Outcome and utility of scoring systems in the management of the mangled extremity.

BACKGROUND: The role of scoring systems as predictors of amputation and functional outcome in severe blunt extremity trauma was examined. METHODS: All severe extremity injuries treated over a 10-year period were scored retrospectively using four scoring systems: Mangled Extremity Syndrome Index (MESI), Mangled Extremity Severity Score (MESS), Predictive Salvage Index (PSI), and Limb Salvage Index (LSI). RESULTS: Twenty-three upper (UE) and 51 lower extremity (LE) injuries were evaluated. Sensitivity and specificity, respectively, were MESI 100% and 50%, MESS 79% and 83%, PSI 96% and 50%, and LSI 83% and 83%. For each system, there were no differences between patients with good and poor functional outcomes. CONCLUSION: All of the scoring systems were able to identify the majority of patients who required amputation. However, prediction in individual patients was problematic. None of the scoring systems were able to predict functional outcome.

Adult↗

A simian strain of hepatitis A virus, AGM-27, functions as an attenuated vaccine for chimpanzees.

The AGM-27 strain OF hepatitis A virus (HAV) was originally isolated from an African green monkey with hepatitis and appears to represent a true simian strain. The virus caused acute hepatitis after intravenous inoculation into African green monkeys, rhesus monkeys, and marmosets. Cynomolgus monkeys inoculated with the virus did not develop hepatitis, probably because of prior exposure to HAV. Chimpanzees inoculated with a high dose of the virus did not develop signs of hepatitis, although the virus replicated and the animals seroconverted. Marmosets and chimpanzees convalescent from infection with the AGM-27 strain of HAV were rechallenged with the virulent HM-175 strain of human HAV. They were partially or totally protected from disease.

Animals↗

Limitations of paperless on-line reporting of diagnostic bacteriology culture results.

AIMS: To estimate the extent to which microbiology laboratory results made available on a computerised reporting system do not reach their intended destination. METHODS: Prospective observational study of 180 urine cultures submitted from patients seen at the accident and emergency department of a 250 bed university affiliated general hospital. Observations were made of: telephone requests for results; whether results were noted in patients' charts; and antibiotic administration to patients sent home. RESULTS: Results were requested/recorded for 73% of 37 patients admitted to hospital and for only 23% of 143 patients sent home (p < 1 x 10(-7)). Overall, results were more frequently recorded for patients with positive cultures (p = 0.04). When determined separately for admitted and discharged groups, this association was not shown. Three of 14 culture positive patients sent home and for whom results were not recorded received inappropriate therapy; 19 culture negative patients were given antibiotics. CONCLUSIONS: In view of the results, measures were instituted to ensure delivery of printed reports to the health care providers of patients not admitted from the accident and emergency department. Organisations operating computerised reporting systems in evolving health care settings must ensure that system design guarantees delivery of reports to all end-users. This will minimise therapeutic problems, reduce wastage of laboratory resources, and limit risks of litigation.

Bacteriology↗

The intragraft gene activation of markers reflecting T-cell-activation and -cytotoxicity analyzed by quantitative RT-PCR in renal transplantation.

T-cell activation is the key event in the development of acute allograft rejection and precedes clinically apparent organ damage. We have performed competitive RT-PCR to quantify the intragraft gene expression for T-cell associated cytokines (IL-2, IL-4, IL-7, IL-15), CTLA4 and cytotoxic lymphocyte specific molecules to test their potential as rejection markers and to further elucidate mechanisms involved in graft rejection. RNA was isolated from snap-frozen portions of core biopsies obtained for the evaluation of graft dysfunction in 34 adults and 8 children. Reverse transcription derived cDNA was coamplified with a known amount of a competitor (a mutated target gene fragment) and normalized for the house keeping gene GAPDH. IL-2, the principal T-cell growth factor and IL-4 were not detectable in any biopsy at the time of histologically apparent rejection. Transcripts of the novel cytokine IL-15 were found in all dysfunctioning grafts and in two donor kidneys prior to reperfusion. CTLA-4, expressed in activated T-cells after costimulation by CD28 was uniformly present post transplantation, but not in the two donor kidneys. Transcripts for IL-7 (p < 0.001), IL-15 (p < 0.0005), CTLA4 (p = 0.04), granzyme B (p < 0.00015) and perforin (p < 0.0003) showed a significant correlation to acute rejection episodes. Heightened gene expression declined rapidly after initiation of rejection treatment. Fas-ligand mRNA gene expression was upregulated in both acute and chronic rejections. While this study shows that competitive RT-PCR is a reliable diagnostic tool to detect acute rejection in renal core biopsies, a future challenge will be to identify molecular markers of evolving rejections utilizing RT-PCR in sequential samples of fine needle aspirations, urine and blood.

Adult↗

HIV infection and AIDS in Jerusalem: a microcosm of illness in Israel.

During the decade 1985-94, 158 individuals (124 males, 34 females) with HIV/AIDS were seen at the AIDS clinic of Hadassah University Hospital. They comprised 10% of the total reported number of HIV-infected Israelis and included 6% of all reported HIV-infected Ethiopians and all HIV-infected West Bank Palestinians. Most individuals (82%) were self-referred; 12% were detected through the local HIV screening clinic. Risk groups for AIDS were homo/bisexuality (39%), heterosexual relations (30%), intravenous drug abuse (15%), contaminated blood transfusions (9%), born to HIV+ mothers (1%), and hemophilia (< 1%). In 5% (all males) no risk factor was given. Of the 158 individuals 29 were Ethiopian immigrants, 25 West Bank Palestinians, and the rest were local Israelis and tourists. Of the 34 females seen, 21 acquired HIV heterosexually, 6 were intravenous drug abusers, 5 were recipients of contaminated transfusions, and 2 were infants. An initial clinical presentation with full-blown AIDS was observed in 30% of the individuals. The range of clinical presentations was similar to that seen in western countries, with Pneumocystis carinii pneumonia, cytomegalovirus retinitis, mycobacterial infections and Kaposi's sarcoma seen most frequently. One case of disseminated cutaneous leishmaniasis was observed. The mortality rate during the follow-up was 55%. In 35% of individuals the immediate cause of death was severe bacterial infections. The Palestinian subpopulation presented at an advanced stage of the disease with a high incidence of transfusion recipients, while most HIV-infected Ethiopians presented with asymptomatic disease transmitted heterosexually. HIV/AIDS as seen at Hadassah University Hospital during 1985-94 exhibited the mixed form of Euro-American AIDS with additional facets of recently introduced African infection.

Adult↗

Attenuation of morphine tolerance and dependence with the highly selective delta-opioid receptor antagonist TIPP[psi].

We examined the effects of i.c.v. treatment with naltrindole, and the two highly selective peptide delta-opioid receptor antagonists H-Tyr-Tic-Phe-Phe-OH (TIPP) and H-Tyr-Tic psi [CH2-NH]-Phe-Phe- OH (TIPP[psi]), on the development of morphine tolerance and dependence. Each treatment significantly decreased naloxone-precipitated withdrawal, with TIPP[psi] reducing the most symptoms. TIPP[psi], but neither naltrindole nor TIPP, attenuated the development of analgesic tolerance in the tail-flick test. These results suggest that delta-opioid receptors are critically involved in the development of morphine tolerance and dependence.

Animals↗

Bacterial pneumonia in recipients of bone marrow transplantation. A five-year prospective study.

Bacterial pneumonia as an important complication of bone marrow transplantation (BMT) has not been subjected to comprehensive analysis. Two hundred fifty-five consecutive allogeneic and autologous BMT recipients, ranging in age from 1 month to 53 years, were prospectively followed for 3 days to 3 years (median, 108 days) for development of bacterial pneumonia. Etiology, place acquired, chest radiography, and outcome were recorded and the association between bacterial pneumonia and demographic and clinical variables was analyzed. Thirty-seven (15%) patients experienced 52 episodes of bacterial pneumonia: onset of 13 episodes occurred within 30 days after transplantation, 10 episodes occurred on days +31 to +100, and 29 episodes occurred thereafter. Bacterial pneumonia was the terminal event or contributed to fatal outcome in 8 patients (22% of bacterial pneumonia cases, 3% total study population). Mortality due to hospital-acquired pneumonia (6/21) was significantly higher than (P = 0.03). Bacterial pathogens were identified in 27 (52%) episodes. During the first 100 days after BMT, hospital-acquired Gram-negative bacteria predominated, caused mainly by Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter lwoffi, and Enterobacter cloacae. After day +100, community-acquired, Gram-positive bacteria predominated, particularly Streptococcus pneumoniae. Haemophilus influenzae occurred periodically. Considering all episodes, significant association was found between bacterial pneumonia and veno-occlusive disease (VOD) (P < 0.01) and chronic graft-versus-host disease (GVHD) (P < 0.02). For culture-positive episodes, the association between bacterial pneumonia and VOD was significant (P < 0.001) and borderline for acute GVHD (P = 0.07). It is concluded that VOD and GVHD are positively associated with post-BMT bacterial pneumonia. Its incidence, etiology, risk factors, and outcome are important considerations in its prevention and treatment.

Adolescent↗