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Using monoclonal antibodies and flow cytometry, we serially monitored lymphocyte subpopulations in renal-allograft recipients treated with either conventional immunosuppression or a monoclonal antibody. In 29 patients given conventional suppression, highly significant correlations between changes in T-cell subsets and rejection were noted. Normal or elevated ratios of OKT4 (helper/inducer) to OKT8 (suppressor/cytotoxic) cells were associated with rejection unless the donor was HLA identical or the total number of T cells was extremely low. In patients with low ratios, rejection seldom occurred. Two patients treated with OKT3 monoclonal antibody for acute rejection had rapid disappearance of OKT3-reactive cells from the peripheral blood and prompt reversal of rejection. The use of monoclonal antibodies allows the precise determination of changes in T-cell subsets and promises the development of therapeutic protocols that can be designed to manipulate selected lymphocyte populations. (N Engl J Med....

Ciprofloxacin is a new quinolone derivative which is particularly well adapted for the treatment of bacterial urinary tract infection. Virtually all uropathogens are susceptible, and the development of resistance is uncommon. Its pharmacokinetic characteristics reveal that effective concentrations of the drug are easily achieved with twice a day oral therapy in the blood, urine, kidneys, and prostate-even in advanced renal failure. The drug is well tolerated, even with prolonged courses of therapy. It will be particularly useful in the treatment of antibiotic-resistant, complicated, and/or prostatic infection.

Anticoagulation during hemodialysis is necessary to prevent clotting of the blood on contact with the dialysis membrane. Heparin is the usual anticoagulant used, but systemic anticoagulation may persist for hours, and hemorrhage is common. We successfully used an infusion of prostacyclin, which has an in vitro half-life of three to five minutes, as the sole anticoagulant in 10 patients on long-term hemodialysis and in one patient undergoing dialysis for acute renal failure (this patient bled severely on three occasions when heparin was used). Prostacyclin was infused intravenously for 10 minutes before dialysis and into the arterial line of the dialyzer during dialysis. We adjusted the rate of infusion into the dialyzer to prevent prostacyclin-induced hypotension. Each patient completed 240 minutes of dialysis and received a total of 423 +/- 91 ng of prostacyclin per kilogram of body weight (mean +/- S.E.M.; range, 56 to 780). Prostacyclin caused no clinically important changes in the intrinsic clotting system, and there were no hemorrhages or clotting of the coil. We conclude that prostacyclin can safely replace heparin as the sole antithrombotic agent during hemodialysis and may be more advantageous if anticoagulation is contraindicated.

The problem of human immunodeficiency virus (HIV) infection and that of the acquired immunodeficiency syndrome (AIDS) are becoming increasingly important in clinical transplantation. The epidemiologic characteristics of this infection are important factors in determining the impact of this infection on transplant patients: in particular, the presence of a transmissible virus in the blood, tissues, and body fluids of even asymptomatic individuals for prolonged periods; the role of lymphocyte activation in accelerating the pace and effects of HIV infection, with the transplant patient having more reasons for lymphocyte activation than other patient categories; and the possible contributions of immunosuppressive therapy to the course of HIV infection. Already, at least 20 cases of primary HIV infection conveyed by infected blood or allografts at the time of transplant have been noted; a similar number of transplants have been carried out in asymptomatic carriers of the virus. The initial impression is that the course of HIV infection in these patients is accelerated, but information is incomplete and an international registry for the study of this problem has been established.

We studied the interrelation among herpes-virus infections, T-lymphocyte subsets, opportunistic infections, and renal histopathology in 28 recipients of renal allografts. All primary or reactivated herpesvirus infections occurring in the first three months after transplantation in recipients of cadaveric grafts accompanied persistent inversions in the ratio of OKT4 (helper/inducer) to OKT8 (cytotoxic/suppressor) lymphocytes. In the less heavily immunosuppressed recipients of organs of living related donors, these inversions were seen only in association with clinically apparent cytomegalovirus infections. Five of seven opportunistic infections occurred in patients with OKT4/OKT8 ratios of less than 1.0. Biopsy specimens from patients with renal dysfunction occurring in association with a low OKT4/OKT8 ratio frequently revealed glomerular damage rather than acute cellular rejection. Monitoring of T-lymphocyte subsets provides early evidence of herpesvirus infections and identifies patients at increased risk for opportunistic infection after renal transplantation.

Thirty-one immunocompromised patients (22 renal allograft recipients, 5 patients receiving chronic corticosteroid therapy, and 4 patients undergoing chemotherapy for acute leukemia) with significant dermatologic infection, excluding typical cellulitis and herpesvirus infections, were retrospectively identified over a 12-year period. Of these 31 patients, 15 (48%) had infection restricted to their skin, 6 (19%) appeared to have primary cutaneous infection that spread hematogenously to other parts of the body, 2 (6%) had infections of adjoining nasal tissue that spread to contiguous skin, and 8 (26%) appeared to have disseminated systemic infection that spread to the skin. In six of the eight patients with apparent secondary skin involvement, the development of the cutaneous lesion was the first clinical indication of disseminated infection. Eleven immunocompromised patients (35%) with bacterial infection of the skin or subcutaneous tissue were identified. These patients could be divided into three categories: leukemic patients with bacteremic gram-negative infection metastasizing to the skin (3 cases), renal transplant recipients with recurrent staphylococcal infection on and around the elbow ("transplant elbow") or streptococcal sepsis from a site of cellulitis (5 cases), and immunocompromised patients with opportunistic bacterial infection due to Nocardia asteroides or atypical mycobacteria (3 cases). Seventeen immunocompromised patients (55%) with fungal infection of the skin or subcutaneous tissue were identified. These included 12 patients with opportunistic fungal infection (Cryptococcus neoformans, 4 cases; Aspergillus species, 3 cases; Paecilomyces, 2 cases; Rhizopus species, 2 cases; and Candida tropicalis, 1 case) and 5 patients with extensive, confluent cutaneous dermatophyte infections. One patient with protothecosis and two patients with extensive papillomavirus infection were identified. Of these latter two cases, one had his immunosuppression discontinued, with clearing of his extensive warts; the other had confluent warts of the face and neck that subsequently underwent malignant degeneration to squamous cell carcinoma while chronic immunosuppressive therapy was continued.(ABSTRACT TRUNCATED AT 400 WORDS)

BK virus (BKV) and JC virus (JCV) infections were evaluated in a serological study of 496 renal transplant recipients and their donors. A seropositive donor increased the rate of primary and reactivation infections with BKV and of primary infections with JCV. BKV infection rates were not influenced by the source of the renal allograft (cadaver versus living related donor); however, primary JCV infections occurred more often in recipients of seropositive cadaveric kidneys. Reactivated JCV infections occurred less frequently in patients treated with antilymphocyte preparation. BKV and JCV infections in renal transplant recipients may be caused either by reactivation of the recipient's latent virus or by virus from the donor kidney. These infections are, however, not associated with adverse outcome (death, high serum creatinine level, or loss of renal function) in the recipient in the early post-transplant period.

When there are changes in gas density within a nebula, various methods of determining the electron density Ne can give different results. Irrespective of differences in ionization structure, there will be deviations in derived values of Ne due to the physics of populating the energy levels. To focus on Ne variations, the electron temperature is held constant. For two cases presented, the values of Ne inferred range over a factor of ten from nine species (line pairs); in order of increasing Ne, they are N+(122/204 ym), 0++(52/88 μm), S+(6716/6731 A), S++(18.7/33.5 μm), 0+(3726/3729 A), Ne++(15/36 μm), Ar+3(4711/4740 A), Ar++(8.99/21.8 ym), and C++(1906/1909 A). This is basically a progression from lower to higher critical densities, Nc, for the lines involved, although other factors are involved. The above order can change somewhat for different mixes of densities.

Over the past three decades the major question dominating the field of urinary tract infection has been, "What is the contribution of such infec­ tions to the development of chronic renal failure?" The question was ini­ tially posed because of the frequent demonstration at autopsy or at the time of transplantation of the pathologic changes of chronic pyelonephritis­ even in patients without a clearcut history of documented urinary tract infection. Because of these pathologic findings, the hypothesis arose that symptomatic or asymptomatic bacteriuria could cause progressive pa­ renchymal damage and loss of renal function. However, in recent years at least three different lines of evidence have developed, demonstrating that in adults infection is essentially never the primary cause of chronic renal failure (1): 1. The pathologic changes of chronic pyelonephritis are caused by a number of different disease processes, ranging from chronic analgesic abuse and other intoxications to long-standing ischemia (Table 1). Therefore, the term now used to describe these pathologic findings is interstitial nephritis, and only in those cases of interstitial nephritis in which clearcut evidence of infection is present is the diagnosis of chronic pyelonephritis made (1, 2). 2. Long-term clinical studies of both adult males (3) and females (1, 4, 5) with chronic or recurrent bacteriuria have not demonstrated progressive renal damage in the absence of significant anatomical defects.

Described herein are three patients over the age of 50 years who had cellulitis of the neck and the upper portion of the chest, associated with Hemophilus influenzae type B bacteremia and respiratory tract infection—particularly that of the upper airway. Only one of the patients with cellulitis had the classic bluish-purple hue commonly seen in children affected with this syndrome. In the other two, the H. influenzae type B cellulitis could not be distinguished clinically from the more common group A streptococcal or staphylococcal cellulitis. Since the antibiotics employed in treating patients with infection due to the latter two organisms differ significantly from those used to treat patients with H. influenzae type B infection, the possibility of disease due to H. influenzae type B must be considered in any adult or child in whom cellulitis of the neck, chest and possibly face is associated with a respiratory tract infection, especially of the upper airway.

OKT3, a monoclonal antibody reactive with a surface glycoprotein present on all postthymic T cells, was used to treat the initial acute episode of rejection in 30 recipients of cadaveric donor renal allografts. The first 16 patients received 1-5 mg daily for a period of 10-21 days during which the azathioprine and prednisone dosages were sharply reduced. Circulating T cells were eliminated within minutes after the first OKT3 infusion. T cells reactive with OKT3 remained depressed throughout the period of treatment, although a significant number of cells reactive with other T cells subset reagents became detectable after several days of OKT3 treatment. In all instances, the established rejection episode was reversed in 2-8 days without the addition of other immunosuppressive measures. Recurrent rejection occurred in 12 of 16 patients, but with further conventional immunosuppression, 50% of the renal allografts remain functional 20-44 months after transplantation. Fever, chills, and, in some instances, dyspnea following the first dose of OKT3 were the only side-effects observed. Most patients developed antiidiotypic or antimouse immunoglobulin antibodies without apparent clinical sequelae. In the subsequent 14 patients, modifications in the protocol included a steroid bolus prior to the first OKT3 infusion, limitation of therapy to 10 days, resumption of maintenance levels of azathioprine and prednisone prior to discontinuing OKT3, and addition of 3 i.v. doses of cyclophosphamide at the termination of treatment. Respiratory symptoms after the first infusion of the reagent have been eliminated. Antibody responses to OKT3 have been reduced, occurring in 38% as compared with 73% of patients treated previously. Recurrent rejection episodes observed in 8 of 14 patients have been reversible in all but one case. Allograft survival is 86% at 6-17 months posttransplantation. In the entire series of 30 OKT3-treated patients, only 4 grafts (13%) have been lost because of recurrent episodes of rejection.

Double-blind placebo-controlled trials in human renal transplant recipients indicate that interferon-α may be a useful agent in the prophylaxis of significant CMV infections.

During the past two decades, remarkable strides have been made in the field of renal transplantation. From a fascinating experiment in human biology, renal transplantation has evolved into a practical therapeutic modality widely applied to the treatment of chronic renal failure. For the first time in history, not only does renal transplantation offer the best chance for rehabilitation of the uremic patient but, in addition, at many centers, it offers at least as good a chance for patient survival as the other widely available treatment modality, chronic hemodialysis. For example, at the Massachusetts General Hospital over the past 3 years, the 1-year patient survival for recipients of kidneys from living related and cadaveric donors has been greater than 95%, with a 1-year graft survival of more than 85%. For patients surviving with a functioning graft at 1 year, the subsequent mortality rate is less than 5% per year. By comparison, the reported patient loss on hemodialysis is 5–10% each year.

Experiences sur souris. Aucun pretraitement du donneur (soit cyclophosphamide a hautes doses soit irradiation) n'est efficace contre la transmission de cytomegalovirus. Le traitement devrait etre oriente sur le receveur

SUMMARYBecause of the ubiquity of cytomegalovirus (CMV) infection among renal transplant patients, the correlation between CMV isolation and clinical events is often difficult. In this prospective study, clinical CMV disease was diagnosed in 26 of 68 patients (38%) that received transplants between

Polymorphonuclear (PMN) and mononuclear (M) leukocyte random migration and chemotaxis were assessed in twenty patients with malignant melanoma, employing a modified Boyden technique and a radiomigration assay, with human kallikrein and C5a as the chemotactic stimuli. M leukocyte chemotaxis in both assays was significantly depressed for patients with Stage III melanoma compared to normal subjects and patients with Stage I and II melanoma. No abnormalities were detected in M leukocyte random migration or ascorbate enhancement of migration, nor in any parameter of PMN leukocyte function. Stage I patients had normal M leukocyte chemotactic responses and remained free of tumor. Of nine Stage II and III patients with residual tumor studied serially, five had or developed a defect in M leukocyte chemotaxis of whom four survived and improved, while four patients who had or developed normal chemotactic responsiveness all died. Monitoring of M leukocyte chemotactic responsiveness in melanoma patients may provide a useful index in evaluating their course and therapy.

Over the past two decades, remarkable progress has been made in dealing with the twin barriers to successful renal transplantation-rejection and infection. Twenty years ago, more than 50% of transplanted patients were dying of infection in the first year post-transplant, and the kidneys in less than half of the remaining patients continued to function. Today, at the best transplant centers, the one-year patient survival rate for recipients of kidneys from living related donors is >95% and for recipients of kidneys from cadaveric donors >90%, with graft survival rates of >85% and >65%, respectively. Advances in the use of immunosuppression, in surgical techniques, and in the prevention and treatment of infection have all contributed to these improved results. It must be emphasized, however, that more than 80% of transplant recipients still develop significant infection, with 26% of them dying as a direct result , and much has yet to be accomplished in terms of preventing and treating such infections (1,2). Our purpose here is ti outline a practical approach for achieving this objective.

A sandwich ELISA assay has been formatted from two commercially available murine monoclonal antibodies, URO-4 and URO-4a, directed against a 120,000 dalton glycoprotein, the adenosine deaminase binding protein (ABP), found on the brush border of the renal proximal tubular epithelial cell. Untimed urine samples from 37 normal individuals and urinary ABP less than 0.1 AU; 37 patients with pure glomerular disease had ABP less than 0.4 AU (with 29, or 76% less than 0.2 AU); 10 patients with pre-renal azotaemia had ABP less than 0.6 (with 8, or 80% less than 0.3 AU). In contrast, 79 patients with post-ischaemic acute tubular necrosis had ABP greater than 0.6 AU. Acute renal failure due to myoglobinuria, contrast dye, and aminoglycoside toxicity were all associated with urinary ABP greater than 1.0 AU. In addition, all six patients with acute bacteraemic pyelonephritis had ABP greater than 0.7 AU, as opposed to ABP less than 0.2 AU in the urines of 12 women with acute cystitis. We conclude that this monoclonal antibody based urinary assay is a sensitive measure of renal proximal tubular injury, reliably distinguishes acute tubular from glomerular disease, and may be helpful in differentiating forms of urinary tract infection.

We have previously demonstrated that six weeks of prophylaxis with interferon-alpha delays cytomegalovirus excretion and decreases viremia in recipients of kidney transplants. In a double-blind trial to evaluate the effects of a longer course of prophylaxis, we gave either 3 X 10(6) units of interferon or placebo intramuscularly to 42 patients before transplant surgery was performed. After surgery, doses were given three times a week for six weeks and then twice a week for eight weeks (total of 102 X 10(6) units). Clinical signs of cytomegalovirus infection were markedly reduced in interferon recipients. These signs developed in 7 of 22 placebo recipients and 1 of 20 interferon recipients (P = 0.03). Opportunistic superinfections (Aspergillus fumigatus and Pneumocystis carinii) occurred only in patients given placebo. Cytomegalovirus-associated glomerulopathy developed in one interferon recipient and three placebo recipients. Survival of patients and grafts was equivalent in both treatment groups, and minimal toxicity was observed with interferon. In seropositive renal-transplant recipients, interferon-alpha affords effective prophylaxis against serious cytomegalovirus infections.

A 65-year-old man infected with Babesia microti failed to respond to therapy with oral chloroquine phosphate. He was then successfully dreated with diminazene aceturate, an experimental anti-protozoal agent. After his recovery from babesiosis, the patient developed acute idiopathic polyneuritis (Landry-Guillain-Barre Syndrome), which was probably related to his diminazene therapy.

A 25-year-old white female returned from West Africa with a two-year history of epidosic swelling, pruritus, and pain in a wrist, associated with peripheral eosinophilia. Serologic and immediate skin tests with Dirofilaria immitis antigen were positive, and blood smears transiently showed microfilariae of Acanthocheilonema perstans after the patient had been treated with diethylcarbamazine. Before treatment, both the serum concentration of IgE and the eosinophil content of arylsulfatase, an enzyme that selectively inactivates slow-reacting substance of anaphylaxis, were elevated; the patient's peripheral leukocytes released histamine and eosinophil chemotactic factor of anaphylaxis when challenged with D. immitis antigen. After one course of diethylcarbamazine, the clinical manifestations and abnormal in vitro immunologic results resolved. Host response to A. perstans infection appears to involve both IgE-mediated hypersensitivity and alterations in an eosinophil enzyme.

Clinical, bacteriologic and therapeutic aspects of 53 patients with hepatic abscess seen from 1961 to 1973 are reviewed. Of these abscesses, 50 were pyogenic and 3 amebic in etiology. The mortality was 63 per cent; the greatest number of cases (38) and the greatest mortality (79 per cent) occurred in patients over 50 years of age. Thirty-five patients had macroscopic abscesses; in the remaining 18 the abscesses were microscopic in size. The most common causes of pyogenic macroscopic abscess were biliary tract infection (11 cases), direct extension from contiguous sites of infection (8 cases) and nonpenetrating trauma (5 cases). The causes of microscopic abscesses were biliary tract infection (9 cases), systemic bacteremia (8 cases) and pylephlebitis (1 case). Although the diagnosis was often obscure with nonspecific clinical and laboratory findings, the hepatic scintiscan and abdominal angiography were positive in all cases in which the abscesses were greater than 1 cm in diameter. Bacteria of bowel origin (particularly Escherichia coli, other Enterobacteriaceae and anaerobes) were the common etiologic agents. Staphylococcus aureus was implicated predominantly in children with bacteremia. Prolonged antibiotic administration and aggressive surgical drainage are the cornerstones of effective therapy.

Une observation. L'infection a provoque des hemorragies necessitant l'ablation du rein greffe; elle n'avait pas ete diagnostiquee malgre des examens approfondis et des cultures des liquides de perfusion

The effect of cytomegalovirus (CMV) infection on T-lymphocyte subpopulations (employing the monoclonal antibody OKT4 to delineate helper cells and OKT8 for suppressor-cytotoxic cells) was studied in 10 normal individuals with CMV mononucleosis and four renal transplant patients with symptomatic primary CMV disease. In both clinical settings, acute CMV infection is associated with a reversal of the normal helper/suppressor-cytotoxic T cell ratio, with both a relative and absolute decrease in T helper cells and an increase in T suppressor-cytotoxic cells observed. With clinical recovery, there is a return of these cell populations toward normal ranges. In two patients, one with chronic CMV infection and one with chronic Epstein-Barr virus infection, the helper/suppressor-cytotoxic cell ratio was found to be reduced four years after the onset of infection. Five patients with febrile illnesses were also studied: two with viral infection and one with a self-limited febrile illness had decreased helper/suppressor-cytotoxic cell ratios, and two with bacterial infection had increased ratios. Thus, delineation of T lymphocyte subpopulations may be of value not only in evaluating the immunologic effects of a particular infectious agent, but also in the clinical evaluation of the febrile patient.

nervous system with certain time-honored epidemiologic, clinical, and laboratory characteristics. Epidemiologically, it exists in 2 forms: urban, propagated chiefly by unimmunized domestic dogs, and sylvatic, propagated in skunks, foxes, wolves, mongooses, other carnivores, and bats [1]. In the United States, infection in domestic animals usually results from a "spillover" of sylvatic reservoirs of infection, and man can be infected by either. Clinically, rabies has been considered to be invariably fatal, and therapy during clinical disease is directed at sedation and symptomatic treatment of seizures [2]. In the laboratory, positive results with any of 3 techniques?^histologic staining for Negri bodies, fluorescent antibody staining for rabies viral antigen, and mouse inoculation tests?confirm the diagnosis; negative results in all 3 together are generally believed to rule out rabies [3]. The case of human rabies presented here con

Mechanical devices which maintain viability during periods of reduced or absent mechanical cardiac function have permitted the utilization of a variety of surgical techniques for the treatment of acquired and congenital cardiac disease. In addition, many advances in cardiac pharmacology have improved the treatment of abnormal mechanical and electrical cardiac function. Despite a variety of therapeutic approaches, survival rate of hospital patients in cardiogenic shock remains between 10% to 20%.1Malach and Rosenberg2reviewed 264 consecutive cases of acute myocardial infarction at this institution and found the frequency of cardiogenic shock to be 9.4%. Those patients in shock were treated with several pharmacologic and volume replacement regimens with no survivors. More recently, Eichna3reported on the treatment of 26 cardiogenic shock cases at this institution using intravenously administered isoproterenol hydrochloride as the major pharmacologic agent. The death rate was 72%. Drugs remain the most frequent means of

Human-derived rabies immune globulin (HRIG) was administered intramuscularly to 24 male volunteers according to two dose schedules: either 20 ml (equivalent to the World Health Organization [WHO] recommendation of 40 internation units/kg for equine-derived antiserum) or one-fourth of the WHO recommendation (10 IU/kg). The 10-IU/kg dose gave barely detectable antirabies antibody titers and is not considered of therapeutic value. The 20-ml dose gave higher, longer lasting titers of antirabies antibody than the comparable doses of equine antiserum currently in use. There were no untoward reactions. Before administration of HRIG, all 24 volunteers had IgG class anti-IgG antibodies (mean titer, 114μg/ml); 22 of 24 had IgA class anti-IgG antibodies (mean titer, 65μg/ml); and none of the 24 had IgM class anti-IgG antibodies. Administration of HRIG caused no significant change in these titers.

Objective : To determine whether preemptive ganciclovir therapy administered daily during antilymphocyte antibody therapy can prevent cytomegalovirus disease in renal transplant recipients who are positive for cytomegalovirus antibody. . Design : Randomized, controlled, multicenter trial. . Setting : 6 university-affiliated transplantation centers. . Patients : 113 renal transplant recipients who were positive for cytomegalovirus antibody. . Intervention : Patients were randomly assigned to receive either 1) ganciclovir, 2.5 mg/kg body weight administered intravenously on every day that antilymphocyte antibody therapy was administered or 2) no anticytomegalovirus therapy. . Measurements : Patients were observed for 6 months after completion of antilymphocyte antibody therapy for development of cytomegalovirus disease and cytomegalovirus viremia. . Results : Cytomegalovirus disease occurred in 14% of patients (9 of 64) who received preemptive ganciclovir therapy and in 33% of controls (16 of 49) (P = 0.018). Cytomegalovirus was isolated from buffy-coat specimens from 17% of patients (11 of 64) receiving preemptive ganciclovir and from 35% of controls (17 of 49) (P = 0.03). Controlling for the reason (induction or treatment of rejection) for using antilymphocyte antibodies in a Cox proportional hazards model, we found that preemptive ganciclovir still protected against cytomegalovirus disease (adjusted relative risk, 0.27 ; 95% Cl, 0.12 to 0.64). No adverse events were attributed to preemptive ganciclovir therapy during or within 6 months of its administration. . Conclusions : Preemptive ganciclovir therapy administered daily during courses of treatment with antilymphocyte antibodies reduced the excessive occurrence of cytomegalovirus disease in renal transplant recipients who were positive for cytomegalovirus antibody. This approach, which links the most potent immunosuppression to intensive antimicrobial therapy, allows preventive therapy to be given to those patients at greatest risk for developing infectious complications. These patients are likely to benefit most from the preventive strategy.

Cytomegalovirus (CMV) produces a latent infection in its host. The actively or latently infected transplanted kidney and heart are sources of debilitating CMV infection in transplant recipients [1], but the organs and cellular sites of viral latency and the mechanisms of CMV activation have not been fully defined. Latent murine cytomegalovirus (MCMV) has been activated in vitro by cocultivating spleen cells or peritoneal macrophages with allogeneic, syngeneic, or both mouse embryo cultures (MECs) [2-5]. MCMV has also been activated from explant cultures of spleens and prostate glands, cultured with or without MECs [6, 7]. Cultures of salivary glands, liver, kidney, and brain from latently infected mice, however, have failed to yield MCMV in vitro [8]. Latently infected, heterotopic cardiac isografts are the source of lethal MCMV infection in the immunosuppressed recipient [9]. Results presented below demonstrate the activation of latent MCMV from cardiac explants and dissociated cardiac cell cultures when cultured alone or with allogeneic MECs. The Smith strain of MCMV was maintained in this laboratory by serial passage of CD-1 Swiss mice (Charles River Breeding Laboratory, Wilmington, Mass) followed by salivary gland harvest as described elsewhere [9]. The stock virus had a titer of 2 x 10' pfu/ml. Noninfected salivary gland homogenates (NSG) were prepared in a similar manner after inoculation of weanling mice with saline. Virus stocks and NSG were stored at 70 C until use. Latent infection was established by ip inoculation of five-weekold female BALB/c mice (Cumberland View Farms, Clinton, Tenn) with 104 pfu of MCMV (0.1 ml of infected salivary gland homogenate). These mice were then maintained in our animal facility for four to six months, at which time their hearts were used for tissue culture. Control animals had been injected with an equal volume of NSG and maintained for four to six months in the same way. These animals showed no evidence of virus by salivary gland culture or by antibody testing at the time of death. Explants of cardiac tissue were prepared by aseptically removing hearts from latently infected or NSG-inoculated mice and placing them in cold, lactated Ringers solution with 507o dextrose. Hearts were transferred into petri dishes containing fresh Ringers solution and cut into 1x 2-mm pieces that were kept on ice. Secondary MECs (prepared as previously described [9] from pathogen-free CD-1 Swiss mice) seeded the previous day in six-well plates (Falcon Plastics, Oxnard, Calif) containing RPMI medium with

• Kidney and pancreaticoduodenal transplantation were simultaneously performed in 12 insulin-dependent diabetic patients. These patients had advanced secondary complications, including blindness, vascular disease, and disabling neuropathy. Average posttransplant hospitalization and charges were 17.7 days and $42 780 compared with 11.2 days and $29 000 for patients who received renal allografts alone. Following transplantation, blood glucose and glycosylated hemoglobin A levels promptly returned to normal in all patients. Two patients subsequently died, one after five months of a cytomegalovirus infection and one after seven months of a ruptured bladder. After a mean of 11.6 months of follow-up, ten patients (83%) remained independent of insulin and dialysis. The success of pancreas transplantation in diabetics with advanced complications now approaches that of other organ allografts. It therefore appears reasonable to recommend transplantation for diabetics with less severe secondary complications, since these candidates are most likely to realize the potential benefits of long-term normoglycemia. (Arch Surg1988;123:621-625)

The evolution of organ transplantation from an interesting experiment in human immunobiology to a highly successful, practical approach for rehabilitating patients with end-stage kidney, heart, liver, and lung disease is one of the great successes of modern medicine. However, the very success of organ transplantation has created in an ever-increasing number of individuals a series of phenomena that have no precedent in medicine or biology: (1) the long-term presence of vascularized organs that differ from the host at a variety of major and minor histocompatibility loci, (2) the lifelong intake of broadly active immunosuppressive agents to permit the continued function of the allograft, and (3) the reactivation, tissue invasion, and continued proliferation of certain infectious agents, particularly the herpes group of viruses, within the individual. The net result of these phenomena are a series of clinical syndromes and effects that are unique to the transplant recipient. Among the most important

In a 12-month prospective study of cytomegalovirus infection on an acute hemodialysis unit, 10 of 80 patients (13%) and none of 26 staff developed active cytomegalovirus infection. Seven infections were coincidental with renal allograft rejection; three occurred 3 to 6 weeks after the transfusion of multiple units of conventional blood into seronegative patients. No person-to-person transmission was documented. In contrast to the effects of transfusing conventional blood, all 21 patients who entered dialysis without detectable cytomegalovirus antibody and received 2 to 10 U of frozen deglycerolyzed erythrocytes (total of 157 U) remained seronegative. Transmission of cytomegalovirus infection with transfusion with conventional blood is probably secondary to passage of leukocyte-borne virus that is lost during the freezing and deglycerolization procedure. Frozen erythrocytes prepared by cytoagglomeration procedures appear to be free of viable leukocytes and appear to carry a minimal risk of transmitting cytomegalovirus infection.

• In 196 cases of subphrenic abscess from 1964 through 1979, 56% were attributable to gastric, hepatic, and colonic disease or surgery. Posttraumatic abscesses in younger patients became more frequent. Synchronous suprahepatic and subhepatic abscesses or bilateral abscesses accounted for 19%. Streptococci, Escherichia coli, Klebsiella , and Bacteroides species were the most frequently isolated organisms. Although the overall mortality rate was 40%, the surgical mortality rate decreased from 33% initially to 17% recently. The mortality rate of transperitoneal drainage decreased from 41% to 16%. From 1980 through early 1983, a success rate of 84%, with no fatalities, was achieved in percutaneous radiologic drainage of 25 unilocular abscesses. At present, radiologically guided drainage should be considered for unilocular abscesses and some bilocular ones. Although extraperitoneal, extrapleural surgical drainage remains an expeditious form of treatment, it may give way to radiologic drainage. Transperitoneal drainage is preferable for multifocal abscesses and for many abscesses secondary to complications of intraabdominal surgery. ( Arch Surg 1984;119:942-945)

Numerical techniques to calculate the thermal and geometric properties of line emission from H II 'blister' regions are presented. It is assumed that the density distributions of the H II regions are a function of two dimensions, with rotational symmetry specifying the shape in three-dimensions. The thermal and ionization equilibrium equations of the problem are solved by spherical modeling, and a spherical sector approximation is used to simplify the three-dimensional treatment of diffuse ionizing radiation. The global properties of H II 'blister' regions near the edges of a molecular cloud are simulated by means of the geometry/density distribution, and the results are compared with observational data. It is shown that there is a monotonic increase of peak surface brightness from the i = 0 deg (pole-on) observational position to the i = 90 deg (edge-on) position. The enhancement of the line peak intensity from the edge-on to the pole-on positions is found to depend on the density, stratification, ionization, and electron temperature weighting. It is found that as i increases, the position of peak line brightness of the lower excitation species is displaced to the high-density side of the high excitation species.

Infections due to BK papovavirus frequently occur in renal transplant recipients [2] and may be involved in a variety of syndromes, including ureteral obstruction, deterioration of graft function, and pancreatic disease. The source of the BK papovavirus in these cases is not clear. Because the renal allograft has been implicated as a source of primary cytomegalovirus infections in renal transplant recipients [3], we investigated the possibility that donor kidneys may also contribute to the transmission of BK papovavirus. A fourfold or greater increase in titers of HAI antibodies to BK papovavirus was observed in 55 (24%) of 230 renal transplant recipients. Seronegative recipients who received kidneys from seropositive donors were 3.5 times more likely to develop an infection due to BK papovavirus than were seronegative recipients of kidneys from seronegative donors. The antibody status of the donor did not affect the likelihood of an increase in titers of antibody to BK papovavirus in seropositive recipients. These results suggest that BK papovavirus may be transmitted with transplanted kidneys and that transplant recipients who are at risk for primary infection by this route are more than twice as likely to have increased titers of antibody to BK papovavirus as those who are at risk for the reactivation of an infection. Further studies should be performed to define the relative role of cadaver vs. living, related kidney donors in the transmission of BK papovavirus and the clinical syndromes that are related to primary and reactivated infections.

Consideration is given to the effects of processes other than electron collisional excitation on the energy level populations of species of C, N, and O. It is found that dielectronic as well as direct-radiative recombination may contribute significantly and in some cases be the major input to populating the low-lying metastable levels. It is concluded that the most pronounced changes occur when there is a large effective recombination coefficient to a level and when T(e) is low. The most dramatic change among the forbidden lines occurs for the O II forbidden lines.

Excerpt For the past two decades the empiric initiation of broad-spectrum antimicrobial therapy at the first sign of possible infection (unexplained fever, rigors, tachypnea, or acidosis) has been ...

Observations of the (O III) 52 and 88 micron lines and the (N III) 57 micron line have been made at 6 positions and the (Ne III) 36 micron line at 4 positions in the Orion Nebula to probe its ionization structure. The measurements, made with a -40" diameter beam, were spaced every 45" in a line south from and including the Trapezium. The wavelength of the (Ne III) line was measured to be 36.013 + or - 0.004 micron. Electron densities and abundance ratios of N(++)/O(++) have been calculated and compared to other radio and optical observations. Detailed one component and two component (bar plus halo) spherical models were calculated for exciting stars with effective temperatures of 37 to 40,000K and log g = 4.0 and 4.5. Both the new infrared observations and the visible line measurements of oxygen and nitrogen require T sub eff approx less than 37,000K. However, the double ionized neon requires a model with T sub eff more than or equal to 39,000K, which is more consistent with that inferred from the radio flux or spectral type. These differences in T sub eff are not due to effects of dust on the stellar radiation field, but are probably due to inaccuracies in the assumed stellar spectrum. The observed N(++)/O(++) ratio is almost twice the N(+)/O(+) ratio. The best fit models give N/H = 8.4 x 10 to the -5 power, O/H = 4.0 x 10 to the -4 power, and Ne/H = 1.3 x 10 to the -4 power. Thus neon and nitrogen are approximately solar, but oxygen is half solar in abundance. From the infrared O(++) lines it is concluded that the ionization bar results from an increase in column depth rather than from a local density enhancement.

Measurements of the 52- and 88-micron forbidden O III line ratios and the 57-micron forbidden N III line ratio for six H II regions have been obtained with the NASA Kuiper Airborne Observatory. The derived N/O ratio for most Galactic regions (of about 0.2-0.3) is greater than that obtained by optical studies, and it exceeds the solar value. Although enhancement of N/O at a galactocentric distance of about 6 kpc may be possible, no evidence is found for an overall linear gradient in N/O with galactocentric distance, suggesting that N-14 is predominantly produced by primary rather than secondary nucleosynthesis.

Two patients developed fever, interstitial pneumonitis, and pancytopenia associated with extremely high titers of antibody to replicative antigens of the Epstein-Barr virus. In contrast to most patients seropositive for Epstein-Barr virus, neither patient had an antibody response to the Epstein-Barr nuclear antigen K polypeptide. In addition, virus isolated from one patient had a deletion of the B95-8 type in the EcoRI C region of the genome. An etiologic relation between Epstein-Barr virus replication and the clinical manifestations of this syndrome is further shown by the response of each patient to acyclovir therapy. These patients have a new Epstein-Barr-virus-associated syndrome and provide additional evidence that acyclovir may play a role in therapy for selected patients with Epstein-Barr virus infection.