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The application of radioimmune imaging techniques to the evaluation of non-neoplastic disease is largely based on the same principles as tumor imaging; specificity and high affinity of antibodies. Currently the most common non-tumor applications of antibody imaging are the detection of clots (peripheral and pulmonary emboli), myocardial necrosis (myocardial infarction, myocarditis and cardiac transplant rejection) and focal sites of infection/inflammation. In the area of injection imaging, both antigen-specific and non-specific properties of antibodies have been successfully exploited in imaging studies. While the number of non-tumor applications of antibodies are far fewer than the number of tumor studies, in many cases, they appear to be more reliable. The basis for the reliability of antibodies for detecting non-neoplastic lesions is probably related to the availability of abundant antigen, lack of antigen modulation and enhanced permeability at the lesion site. These observations suggest that there will be rapid proliferation of work in this area.

Cytomegalovirus (CMV) infection is the most important single infectious complication of organ transplantation, affecting more than 70% of transplant recipients. Its emergence as a major pathogen has coincided with the use of cytotoxic therapy. Manifestations of serious CMV disease include: pneumonia, hepatitis, gastrointestinal disease, leukopenia and chorioretinitis. CMV is associated with superinfection with opportinistic organisms, graft failure and increased mortality. Serious infection most frequently occurs with primary CMV infection in which latently infected cells from CMV-positive donors are given to seronegative recipients. Pediatric patients who have a lower pre-transplant rate of CMV seropositivity are at particularly high risk of developing serious CMV disease. Preventative efforts range from the ideal but impractical use of only CMV-negative donors (organ and blood products), to the use of CMV hyperimmune globulin and antiviral chemotherapy. Data support the use of prophylactic hyperimmune globulin and preliminary information supports the use of prophylactic high-dose acyclovir in renal transplant patients. Prophylactic gancyclovir alone or with hyperimmune globulin and pre-transplant vaccination with live-attenuated Towne strain CMV vaccine remain investigational.

Cytomegalovirus (CMV) is the single most important infectious agent affecting recipients of organ transplants, with at least two-thirds of these patients having CMV infection 1-4 months after transplantation. Latently infected allografts are the major exogenous source of CMV infection in transplant recipients, although leukocyte-containing blood products can also transmit the virus. Three patterns of CMV infection are recognized: primary infection, reactivation infection, and superinfection. Primary infection has the greatest clinical impact. The clinical effects of CMV infection include infectious disease syndromes such as pneumonia and chorioretinitis; an immunosuppressed state that predisposes to potentially lethal opportunistic infection; and the initiation of a process that can result in allograft injury. Progress has been made in controlling CMV infection; hyperimmune anti-CMV globulin and certain antiviral drugs appear promising for prophylaxis, and the combination of hyperimmunoglobulin and ganciclovir appears promising for therapy.

Treatment of cytomegalovirus (CMV) infections has assumed increasing importance in the care of immunocompromised patients, particularly allograft recipients and patients with symptomatic infection with the human immunodeficiency virus. The crucial role of T cells in the host defense against CMV may be inferred by the expression of life-threatening CMV disease in these restricted patient subpopulations. However, detailed understanding of the pathogenesis of CMV disease in the compromised host is lacking, and the mechanisms by which T cells confer protection are unknown. Insight into the pathogenesis of CMV in these patients is crucial for the development of rational therapeutic strategies. A considerable body of data has been generated to explore the role of T cell-mediated immunity in a number of model viral infections as well as in experimental CMV infections in both normal and immunocompromised mice. This experience will be critically reviewed to clarify the often conflicting observations regarding a protective or, conversely, a pathogenic role for T cells in producing CMV disease.

OVER THE PAST 30 YEARS, ORGAN TRANSPLANTAtion has evolved from an interesting experiment in human immunobiology to the most practical means of rehabilitating patients with end-stage dysfunction. At the same time, the requirement for chronic antirejection therapy, the presence of chronic or relapsing viral infection, and environmental exposures to a variety of opportunistic pathogens, have created a pathophysiological state and set of vulnerabilities rarely seen before. It has been estimated that 75% or more of organ transplant patients will have evidence of microbial replication and invasion in the first year posttransplant. Several principles have emerged from this experience. First, allograft rejection and invasive infection are closely linked, creating the need for a “therapeutic prescription” that has 2 components: an immunosuppressive program to prevent and treat rejection, and an antimicrobial strategy to make this safe. Changes in the immunosuppressive regimen should result in appropriate changes to the antimicrobial program. Second, bidirectional linkages between different processes are the rule, not the exception. Thus, hepatitis C virus (HCV) replication will increase the level of replication of cytomegalovirus (CMV) and vice versa, whereas CMV infection increases the incidence of Epstein-Barr virus–associated lymphoproliferative disease by a factor of 7 to 10. Third, perhaps the most important linkage is that in which viruses and allograft injury interact. The observation by Gasink and colleagues reported in this issue of JAMA that receipt of heart allografts from HCV-seropositive donors is associated with a poorer posttransplant survival is both expected and important. Expected because other viruses, such as CMV, appear to have this effect. Important because the chronic shortage of donors has resulted in attempts to expand the guidelines for accepting allografts, and there has been the hope that organs from HCV-positive donors could be used, particularly for critically ill organ recipients. The results of this study suggest that with current immunosuppressive therapy and antiviral prescription, the use of HCV-positive heart donors is not without hazard, even for HCV-positive recipients; that is, superinfection with HCV occurs, is clinically important, and cannot be generally recommended with current regimens of therapy. The question that emerges is whether special regimens can be developed that would allow the use of such organs with greater safety. In the meantime, the use of hearts from HCVpositive donors should be restricted to the critically ill who would not survive without an immediate transplant; whether such an approach is appropriate for other organs remains to be seen. The traditional view of the pathogenesis of allograft injury is that the triggering of a given pathway results in a unique histopathology. If a different pathway is involved, then the end result is a different histopathology that is recognizable. This so-called silo hypothesis was thought to provide insight into the pathogenesis of different clinical states. Compelling evidence now suggests that this view of pathogenesis is incorrect; rather than separate silos for each process, multiple paths exist that provide entrance into a final common pathway. Thus, such widely disparate processes as ischemia-reperfusion injury, immunologic injury, and certain infections (including HCV, CMV, and presumably other viruses such as human herpesvirus 6 and Epstein-Barr virus) can produce comparable histopathologic findings. The pattern of cytokine, chemokine, and growth factor release associated with each of these processes appears to be quite similar, thus explaining the final common pathway hypothesis. Similarly, the possibility of additive or synergistic effects due to multiple processes occurring simultaneously does not appear unreasonable. In addition, identification and control of these concomitant processes could improve the outcome in certain patients at risk for HCV-mediated processes. The clinical effect of HCV for patients undergoing organ transplantation can be divided into 2 general categories: the direct causation of acute and chronic liver injury, and the

Summary Background Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. It has been suggested that cardiovascular disease has not had a prominent place in the public health agenda in Latin America and the Caribbean. Recently there has been momentum toward formation of partnerships between public and private sectors to develop an improved capacity for CVD research. Notwithstanding these efforts, cardiovascular clinical research output in Latin America and the Caribbean has not kept pace with the need to overcome the burden of CVD. Methods Bibliometric data for clinical medicine publications and cardiovascular specialties in the region were assessed from 2000 to 2005. Data were compared with previous bibliometric studies. Results Scientific output from Latin America and the Caribbean has not increased. In addition, our findings also suggest that Latin American and Caribbean investigators continue to prefer to publish in local and regional journals in languages other than English. Conclusion To overcome the expected economic impact of CVD and to diminish the burden of disease in the region it is necessary to raise the priority for funding of CVD research. With support from ethical research foundations, improved quality and quantity of clinical study data with allow for expedited transformation of the productivity of CVD research within Latin America and the Caribbean.

Emission-line observations made with the Spitzer Space Telescope are used to test the predicted ionizing spectral energy distributions of various stellar atmosphere models.

The management of the patient with cancer who has chemotherapy-induced neutropenia and fever has changed markedly over the past four decades. Empirical antimicrobial therapy is now the standard of ...

Far-infrared lines of (N III) (57 microns), (O III) (52, 88 microns), (Ne III) (36 microns), and (S III) (19, 33 microns) have been measured in the H II regions G1.13 - 0.11, W31B, G23.95 + 0.15, G25.38 - 0.18, G29.96 - 0.02, W43, W51e, S156, S158, NGC 3576, NGC 3603, and G298.22-0.34. These observations were made with the facility Cryogenic Grating Spectrometer on the Kuiper Airborne Observatory to examine variations in abundances throughout the Galaxy. Previously published observations of G0.095 + 0.012, G333.60 - 0.21, G45.13 + 0.14A, K3-50, and M17 are also discussed. The giant H II region 30 Doradus in the Large Magellanic Cloud (LMC) was observed for comparison. Fluxes for (Ne II) (12.8 microns), (S IV) (10.5 microns), and the radio free-free continuum were collected from the literature for those sources. Electron densities were estimated from FIR line-pair ratios, and ionic abundances were estimated from the FIR line and radio fluxes. The excitation was estimated from the O(2+)/S(2+) ratio. Corrections for unseen ionization stages were calculated with the use of constnat-density H II region models. The validity and range of applicability of such semiempirical ionization correction schemes are discussed. The abundances with respect to hydrogen exhibit gradients with R(sub G) comparable to those previously measured for our Galaxy and for other galaxies. The overall gradients are d (log N/H)/dR = -0.10 +/- 0.02 dex/kpc, d(log Ne/H)/dR = -0.08 +/- 0.02 dex/kpc and d(log S/H)/dR = 0.07 +/- 0.02 dex/kpc. Compared to the Orion Nebula, the intermediate R(sub G) H II regions with 6 is less than R(sub G) is less than 11 kpc have similar or lower S/H and N/O ratios. The N/O ratios in the inner Galaxy are more than twice those observed in the Orion Nebula and intermediate R(sub G) H II regions. In fact, all the abundance ratios are as well or better fitted by a step fit with two levels than by a linear gradient. As has been noted in previous studies, the N/O ratio estimated from infrared observations of the doubly ionized N and O lines in H II regions is larger than the ratio estimated from optical observations of the singly ionized N and O lines. The Ne(2+)/O(2+) ratio is observed to be essentially constant over a wide range of excitation. This contradicts predictions of model H II regions calculated with the use of Local Thermodynamic Equilibrium (LTE) model stellar atmospheres. We conclude that these stellar atmospheres significantly underestimate the actual emergent fluxes for energies greater than 41 eV.

Background: Three studies were undertaken to determine the minimum effective dosing regimen of ciprofloxacin for the treatment of acute, symptomatic, uncomplicated lower urinary tract infection. Methods: All studies were multicenter, prospective, randomized, double-blind trials. A total of 970 evaluable patients with a diagnosis of urinary tract infection received oral ciprofloxacin (200 mg to 500 mg daily in one or two divided doses for 1, 3, 5, or 7 days) or norfloxacin (400 mg twice daily [BID] for 7 days). The primary measure of efficacy was bacteriologic eradication at the end of therapy. Results: In study 1, bacteriologic eradication was reported in 95 (89%) and 101 (98%) of patients in the groups who received ciprofloxacin, 500-mg single dose and 250 mg BID for 7 days, respectively. Clinical success occurred in 101 patients (94%) who received a 500-mg single dose and in 103 patients (100%) who were administered 250 mg BID for 7 days. In study 2, eradication rates in the groups who received ciprofloxacin, 100 mg BID for 3 days, 250 mg BID for 3 days, and 250 mg BID for 7 days, were 98 (93%), 95 (90%), and 98 (93%), respectively. Clinical success was reported in 102 (97%), 105 (100%), and 104 (98%) of the patients, respectively. In study 3, the eradication rates in the groups who received ciprofloxacin in dosages of 500 mg once daily for 3 days and 500 mg once daily for 5 days and norfloxacin in a dosage of 400 mg BID for 7 days were 137 (92%), 134 (90%), and 133 (94%) of the women, respectively. Clinical success was the same (97%) in all three groups. Overall, short-course (either 3- or 5-day) therapy with ciprofloxacin was statistically equivalent to conventional (7-day) therapy with either ciprofloxacin or norfloxacin. Single-dose ciprofloxacin therapy was statistically less effective than conventional treatment. Conclusions: Ciprofloxacin at a dosage of 100 mg BID for 3 days was the minimum effective dose for the treatment of uncomplicated urinary tract infection in women. (Arch Intern Med. 1995;155:485-494)

Theoretical O I density-sensitive emission-line ratios R = I(2s(sup 2))(2p(sup 4))((sup 3)P(sub 0))-((2s(sup 2))(2p(sup 4))((sup 3)P(sub 1)))/I((2s(sup 2))(2p(sup 4))((sup 3)P(sub 1))-(2s(sup 2))(2p(sup 4))((sup 3)P(sub 2))) = I(146 micrometers)/I(63 micrometers) are presented for a range of temperatures (T = 100-10,000 K), neutral hydrogen densities (N(sub H) = 10(exp -2) to 10(exp 7)/cu cm) and radiation fields (G(sub 0) = 1-10(exp 6)) applicable to both photodissociation regions (PDRs) and H II regions and the diffuse ionized medium (DIM). The observed values of R for several PDRs, measured from far-infrared spectra obtained with the Kuiper Airborne Observatory (KAO), imply hydrogen densities which are in good agreement with those determined using other methods. This provides observational support for the validity of the theoretical O I line ratios, and hence the atomic data used in their derivation.

The H II regions near K3-50 (G70.3 + 1.6) have been imaged at high angular resolution (approximately 1 sec .3) in the continuum and the recombination lines H76(sub alpha and He76(sub alpha) using the Very Large Array (VLA). The helium line is detected in only the brightest component K3-50A while the hydrogen line is detected in three components (K3-50A, B and C1). K3-50A shows a pronounced velocity gradient of approximately 150 km/sec/pc along its major axis (P.A. = 160 deg); in addition a wide range of line widths are observed, from 20 to 65 km/sec. Kinematics from the line data and the morphology of the continuum emission suggest that the ionized material associated with K3-50A is undergoing a high-velocity bipolar outflow.

Detection of the 205 micrometer fine structure line of N II in the nearby starburst galaxy M82 is reported. The intensity wihin a 54 sec Full width at Half Maximum (FWHM) beam is (7.1 +/- 1.2) x 10(exp -19) W cm(exp -2). The ratio of the intensity of the recently detected 122 micrometer line to that of the 2.5 micrometer lines is = (4.2) (sup =1.6) (sub -1.2), significantly larger than the corresponding Galactic value of 1.6 +/- 0.3, reflecting higher electron densities within the central 850 pc of M82 in comparison to the Cosmic Background Explorer (COBE) Galactic average. The 2.5 micrometer line profile is consistent with other far-infrared fine-structure line profiles observed in M82. The observations are interpreted in the context of a two-component model of the ionized medium in M82. We find that a component of density as low as approximately 50 cm(exp -3) can comprise up to 70% of the total mass of warm ionized gas within the beam. The balance of the ionized mass is comprised of a component of density approximately greater than 100 cm(exp -3). A model is explored in which the dneser ionized medium constitute the boundaries of neutral surfaces which border the expanding hot plasma from the nuclear region.

We discuss observations of the (C II) 158 micrometers, (O I) 63 micrometers, (Si II) 35 micrometers, (O III) 52,88 micrometers, and (S III) 33 micrometers fine-structure transitions toward the central 45 seconds of the starburst galaxies NGC 253 and NGC 3256. The (C II) and (O I) emission probably originates in photodissociated gas at the surfaces of molecular clouds, although a small (less than or approximately 30%) contribution to the (C II) flux from H II regions cannot be ruled out. The (O III) and (S III) lines originate in H II regions and the (Si II) flux is best explained as originating in H II regions with some contribution from photodissociation regions (PDRs). The gas phase silicon abundance is nearly solar in NGC 253, which we interpret as evidence for grain destruction in the starburst region. We find that the photodissociated atomic gas has densities approximately 10(exp 4)/cu cm and temperature 200-300 K. About 2% of the gas is in this phase. The thermal gas pressure in the PDRs, P(PDR)/k approximately 1-3 x 10(exp 6) K/cu cm, might represent the 'typical' interstellar gas pressure in starburst systems. The Far Ultraviolet (FUV) radiation fields illuminating the clouds are 10(exp 3)-10(exp 4) stronger than the local Galactic FUV field and come from the contribution of many closely packed O and B stars. For the central 250 pc of NGC 253, we find that the H II gas has an average density n(sub e) is approximately 400/cu cm. This corresponds to a thermal pressure P(H II)/k approximately 7 x 10(exp 6) K/cu cm which is approximately P(PDR)/k, suggesting that the ionized gas is in pressure equilibrium with the photodissociated gas at the surfaces of molecular clouds. The H II gas fills a significant fraction, approximately 0.01-0.3, of the volume between the clouds. The effective temperature of the ionizing stars in NGC 253 is greater than or approximately 34,500 K; 2 x 10(exp 5) O7.5 stars would produce the observed Lyman countinuum photon luminosity. The average separation between the stars is approximately 3 pc. Applying the simple model for the interstellar medium in galactic nuclei of Wolfire, Tielens, & Hollenbach (1990), we find the molecular gas in the central regions of NGC 253 and NGC 3256 to be distributed in a large number (5 x 10(exp 3) to 5 x 10(exp 5)) of small (0.5-2 pc), dense (approximately 10(exp 4)/cu cm) clouds (or alternatively 'thin-flattened' structures) with volume filling factors 10(exp -3) to 10(exp -2), very different from the local Interstellar Medium (ISM) of the Galaxy. We suggest a self-consistent scenario for the ISM in NGC 253 in which clouds and H II gas are in pressure balance with a supernova-shocked, hot 1-3 x 10(exp 6) K, low-density (approximately 10(exp 4)/cu cm), all pervasive medium. A feedback mechanism may be indicated in which the pressure generated by the supernovae compresses the molecular clouds and triggers further massive star formation. The similarity of ISM parameters deduced for NGC 253, NGC 3256, and M82 (Lord et al. 1993) suggests that the ISM properties are independent of the luminosity of the starburst or the triggering mechanism, but are rather endemic to starburst systems. The starburst in NGC 3256 appears to be a scaled-up version of the NGC 253 and M82 starbursts.

We describe a semiempirical methodology-based on measurements of far-infrared (FIR) lines-that yields information on electron densities in regions where various ionic species exist, effective temperatures (T(sub eff)) for stars ionizing H II regions, and gas-phase heavy element abundances. Although this capability has long been available via optical data, the special features of FIR lines-relative insensitivity to extinction and electron temperature variations-extend the analysis ability. Several line ratios serve as diagnostics of electron density, N(sub e), probing different ionization conditions and different density regimes. The more N(sub e)-diagnostic observations made, the more reliable will be the deciphering of the actual variation in density throughout a nebula. A method to estimate T(sub eff) from the FIR (N III)/(N II) line ratio requires that the nebula be ionization bounded and that substantially all of the flux from the revevant lines be observed. However, to estimate T(sub eff) by a second method that uses the ratio of FIR (S III)/(O III) lines, an ionization-bounded nebula is a sufficient, but not necessary, condition. These restrictions are unnecessary for estimating densities and heavy element abundances. We show that a fairly general determination of metallicity, via the S/H ratio, may be made for H II regions with observations of just two lines-(S III) 19 micron and a hydrogen recombination line (or appropriate substitute). These techniques are applied to recent FIR data for the G333.6-0.2 H II region, including application to the recently measured (N II) 122 and 205 micron lines.

We assess the gas-phase abundances of Si and C from our recent measurements of Si(2+), C(2+), and C(+) in the Orion Nebula by expanding on our earlier 'blister' models. The C and Si abundances are derived from new IUE high-dispersion spectra of the C(2+) 1907, 1909 A and Si(2+) 1883, 1892 A lines and archival IUE data. Gas-phase Si/C = 0.016 in the Orion ionized volume and is particularly insensitive to uncertainties in extinction and temperature structure. The solar value is 0.098. Gas-phase C/H = 2.8 x 10 exp -4 and Si/H = 4.5 x 10 exp -6. Compared to solar, Si is depleted by a factor of about 8 in the ionized region, while C is much less depleted (factor of 1.3), if depleted at all. This suggests that most Si resides in dust grains even in the ionized volume. Thus, most of the observed forbidden Si II 34.8-micron emission in Orion does not arise in the H II region.

Measurements of the G333.6-0.2 H II region which include the first detection of the N II 122 micron forbidden line in an astronomical force and the first measurement of the N II 205 micron forbidden line in a discrete source are presented. Also considered are fine structure lines of forbidden S III, forbidden Fe III, forbidden Si II, forbidden Ne III, forbidden O III, forbidden N III, forbidden O I, and forbidden C II from 19 to 206 microns. It is concluded that the N II 122 and 205 microns forbidden line pair in a discrete astronomical source was detected for the first time. The emission in transitions is produced largely by low-ioninzation, low-density material not easily probed by other lines. Other FIR line pairs generally originate in higher density regions closer to the exciting force.

As the number of immunocompromised patients increases due to the spread of the AIDS epidemic and the successes being achieved with transplantation, cancer chemotherapy and immunosuppressive therapy, increased attention is being turned to the prevention and treatment of the infections that afflict these individuals. The risk of infection in these patients is determined by the interaction between the epidemiologic exposures that the patient experiences and the net state of immunosuppression (the greater the exposure, the greater the chances of infection even in an immunologically competent individual; the greater the net state of immunosuppression, the greater the chances of infection even with minimal exposures). The bacterial and fungal infections that affect these patients are reviewed and strategies of antimicrobial management defined, recognizing that there are three modes of use of antimicrobial agents in these patients: therapeutic administration to treat clinical infection, and prophylactic and pre-emptive administration to prevent or abort clinical infection. These last two are of particular importance in this patient population because the prime aim of the infectious disease clinician in dealing with these problems is the prevention of clinical disease.

Measurements of far-infrared lines and continuum from GO.095 + 0.012 and the E2 thermal 'arched' radio filament near the Galactic center are well explained by numerous embedded stars with T(sub eff) approximately 35,000 K. The structure of the filament and the apparent absence of hotter stars are qualitatively difficult to reconcile with this idea.

Properties of two compact H II regions, K3-50 A and G45.13 + 0.14 A, were investigated by measuring FIR fluxes from forbidden O III 51.8 and 88.4 micron lines, forbidden N III 57.3 micron line, forbidden S III 33.5 micron line, and forbidden Ne III 36.0 micron line of these regions, using a cooled grating spectrometer on NASA's Kuiper Airborne Observatory. For both H II regions, the ratio of the two FIR O(2+) lines indicates an electron density of about 1000/cu cm, which for K3-50 A is a factor of 10 to 100 lower than the density determined from optical line observations of the lower excitation species S(+) and N(+) and than the peak rms density deduced from radio continuum measurements by Turner and Matthews (1984). Detailed spherically symmetric models of the two sources were constructed using all available measurements.

Abundances of neon and sulfur for 95 H II regions whose spectra were measured by the IRAS Low Resolution Spectrometer (LRS) are determined; and theoretical implications of the neon ionization level and the sulfur-to-neon abundance ratio are discussed. The abundances show a distinct gradient of Ne/H with respect to Galactocentric radius RG, and a smaller gradient for S/H. The neon ionization is high only for sources with both low neon abundance and high luminosity. It is concluded that, due to the fact that the luminosities observed are so high compared to those predicted for the zero-age main sequence star, the most luminous H II regions are probably excited by several stars or a cluster of stars. The observed ionization of neon shows that the effective temperatures of the exciting stars cannot be more than 40,000 K, with an alternative explanation that 04 and 03 stars have Lyman continuum spectra cooler than the 45,000 - 50,000 K effective temperatures that are found for their visible and UV spectra.

Peripheral blood T-lymphocyte populations were monitored sequentially in diabetic recipients of renal allografts. Unfractionated buffy coat preparations were reacted with the murine monoclonal antibodies, OKT3 (all circulating T-cells), OKT4 (helper/inducer/regulatory T-cells), and OKT8 (cytotoxic/suppressor cells). Levels of peripheral blood lymphocyte subpopulations of diabetic patients monitored prior to transplantation revealed no significant abnormalities. Following transplantation, but prior to any therapy for acute rejection, the mean percentage of OKT3, 4, and 8 reactive cells in diabetic recipients closely resembled those observed in nondiabetic recipients. After treatment for acute rejection, a marked decrease in the mean OKT4/OKT8 ratio from normal (1.90 ± 0.7) was observed in both diabetic (1.04 ± 0.5), and nondiabetic (1.35 ± 0.5) allograft recipients. Eleven of thirteen diabetic recipients with long-term functioning allografts were found to have a depressed OKT4/OKT8 ratio (mean 1.03 ± 0.6). T-cell subset monitoring of diabetics with end-stage renal failure failed to reveal any significant differences from nondiabetic, uremic patients. The high incidence (75%) of allograft rejection noted in these diabetic allograft recipients similarly suggests normal immunocompetence. Following successful completion of rejection therapy, however, reduction in the ratio of OKT4 to OKT8 reactive cells suggests that an alteration in immune responsiveness has occurred. Immunological monitoring of these long-term diabetic recipients with functioning allografts suggests that the observation of a consistently depressed OKT4/OKT8 ratio may (1) be useful in predicting continued allograft function and (2) prompt the more rapid reduction of steroid medication to maintenance dosage since this pattern may be indicative of subclinical viral infection.

A double-blind, placebo-controlled trial of interferon prophylaxis against viral infections was conducted in renal-transplant recipients receiving standard immunosuprressive therapy with or without antithymocyte globulin. Interferon was administered for six weeks, beginning on the day of transplantation. Cytomegalovirus excretion began earlier and viremia was more frequent in placebo-treated than in interferon-treated patients. Cytomegalovirus viremia correlated with clinical syndromes was more frequent in recipients of antithymocyte globulin. In contrast, neither interferon nor antithymocyte globulin altered excretion of herpes simplex virus. Reversible leukopenia and thrombocytopenia occurred in seven interferon recipients. Patient and graft survival were comparable in interferon and placebo groups. There preliminary results suggest that a six-week course of prophylactic interferon delays shedding of cytomegalovirus and decreases the incidence of viremia after transplantation. In contrast, antithymocyte globulin appears to increase the severity of infection from cytomegalovirus among these patients.

Presentation of Case A 34-year-old business executive was admitted to the hospital because of pulmonary infiltrates. He was well until 14 months previously, when fever, sore throat and chest pain d...

We performed radionuclide scanning after the intravenous injection of human IgG labeled with indium-111 in 128 patients with suspected focal sites of inflammation. Localization of 111In-labeled IgG correlated with clinical findings in 51 infected patients (21 with abdominal or pelvic infections, 11 with intravascular infections, 7 with pulmonary infections, and 12 with skeletal infections). Infecting organisms included gram-positive bacteria, gram-negative bacteria, Pneumocystis carinii, Mycoplasma pneumoniae, and Candida albicans. No focal localization of 111In-labeled IgG was observed in 63 patients without infection. There were five false negative results, and nine results were unusable. Serial scans were carried out in eight patients: continued localization correctly predicted relapse in six, and the absence of localization indicated resolution in two. To determine whether 111In-labeled IgG localization was specific for inflammation, we studied 16 patients with cancer. Focal localization occurred in 13 of these patients (5 with melanomas, 5 with gynecologic cancers, and 1 each with lymphoma, prostate cancer, and malignant fibrous histiocytoma). No localization was seen in patients with renal or colon cancer or metastatic medullary carcinoma of the thyroid. We conclude that 111In-labeled IgG imaging is effective for the detection of focal infection and that serial scans may be useful in assessing therapeutic efficacy. This technique may also be helpful in the evaluation of certain cancers.

The detection of focal sites of inflammation is an integral part of the clinical evaluation of the febrile patient. When anatomically distinct abscesses are present, lesion detection can be accomplished by standard radiographic techniques, particularly in patients with normal anatomy. At the phlegmon stage, however, and in patients who have undergone surgery, these techniques are considerably less effective. While radionculide methods, such as Gallium-67 ( 87 Ga)-citrate and Indium-111 ( 111 In)-labeled WBCs have been relatively successful for the detection of early inflammation, neither approach is ideal. In the course of studies addressing the use of specific organism-directed antibodies for imaging experimental infections in animals, we observed that non-specific polyclonal immunoglobulin G (IgG) localized as well as specific antibodies. Preliminary experiments suggested that the Fc portion of IgG is necessary for effective inflammation localization. Since polyclonal IgG in gram quantities has been safely used for therapy in patients with immune deficiency states, we decided to test whether milligram quantities of radiolabeled IgG could image focal sites of inflammation in humans. Thus far, we have studied a series of 84 patients with suspected lesions in the abdomen, pelvis, vascular grafts, lungs, or bones/joints. In 48 of 52 patients with focal lesions detected by surgery, computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound (US), the IgG scan correctly localized the site, while 31 patients without focal inflammation had no abnormal focal localization of the radiopharmaceutical. Four patients had false negative scans and one patient had a false positive scan. For this small series, the overall sensitivity and specificity were 92% and 95%, respectively. In this report, we review our experience with this exciting new agent.

The combination of amoxicillin and potassium clavulanate will soon be marketed in 2:1 and 4:1 fixed ratio dosage forms. In vitro and in vivo evidence suggests that clavulanic acid, a potent inhibitor of many bacterial beta-lactamase enzymes, will increase the spectrum of amoxicillin to include, at achievable serum concentrations, Haemophilus influenzae, H. ducreyi, Neisseria gonorrhoeae, Staphylococcus aureus and Branhamella catarralis and, at achievable urine levels, many beta-lactamase-producing strains of E. coli, Klebsiella, Proteus and Citrobacter. Both amoxicillin and clavulanic are well absorbed after oral administration, reach peak serum levels in 40-120 min and have similar half-lives of 45 to 90 min. This combination will be suitable for the treatment of complicated urinary tract infections, otitis media, sinusitis and respiratory tract infections. However, precise recommendations for its use will need to await further clinical trials that compare amoxicillin/clavulanate to alternative therapies.