Specific cell-mediated immunity and infections with herpes viruses in cardiac transplant recipients.

Immune responses and infections with herpes viruses were studied prospectively in 36 cardiac transplant recipients. Specific lymphocyte transformation and interferon production in response to viral antigens, viral culture results, antibody levels, responses to phytohemagglutinin, and T-cell numbers were determined. Responses to phytohemagglutinin and T-cell numbers were depressed for six to 12 weeks. Cytomegalovirus infection occurred in 100 percent of seropositive patients and in 62 percent of seronegative patients. Primary infection was more frequently symptomatic. Heart implantation from a seropositive patient wwas significantly correlated with subsequent infection in seronegative patients. Depression of transformation in response to cytomegalovirus correlated with prolonged shedding. Herpes simplex infection occurred in 95 percent of seropositive patients but decreased after 12 weeks. Asymptomatic shedding was rare, and primary infection did not occur. Return of transformation in response to herpes simplex was associated with decreased infection. Herpes zoster occurred in 22 percent during the first year, and transformation responses to varicella-zoster returned thereafter. Depression of interferon production in response to viruses did not correlate with infection as well as did lymphocyte transformation.

Demonstration of Ga-67 localization in human placenta.

Gallium-67 uptake was noted in the mid-pelvic uterine area of a 19-week-pregnant female. Lateral and oblique Ga-67 scans revealed an anterior location of radioactivity that correlated with the position of the placenta as determined by ultrasonic technique.

Ultrasonography of the brain and vertebral canal in dogs and cats: 15 cases (1988-1993).

Medical records of 3 cats and 12 dogs with lesions of the brain (3 cats, 2 dogs) or vertebral canal (10 dogs) that underwent intraoperative ultrasonography were reviewed. Ultrasonography was performed after craniotomy, a ventral slot procedure, or laminectomy, using a real-time sector scanner with a 7.5- or 10-MHz transducer. In the 3 cats and 2 dogs with brain lesions, cerebral masses were hyperechoic, compared with normal brain, and were easily located. In the 2 dogs, ultrasonography was necessary to localize deep-seated cerebral lesions that could not be seen following craniotomy. In 7 dogs that underwent a ventral slot procedure because of prolapse of an intervertebral disk, ultrasonography was successfully used to assess completeness of disk removal. The remaining 3 dogs underwent dorsal laminectomy because intradural enlargement of the spinal cord (1 dog) or an intradural mass (2 dogs) could be seen myelographically. In the 2 dogs with intradural masses, intraoperative ultrasonography helped to delineate the extent of the tumor. In the third dog, spinal cord swelling was seen ultrasonographically; the histologic diagnosis was spinal cord edema.

Prognosis after surgical excision of cerebral meningiomas in cats: 17 cases (1986-1992).

Long-term follow-up information was obtained for 17 cats with cerebral meningiomas treated by surgical excision. Three cats died or were euthanatized in the immediate postoperative period: 2 cats, because of brain herniation and 1 cat, because of acute renal failure. In the remaining 14 cats, most clinical signs resolved within 1 week of surgery. Three cats (21.4%) had confirmed or presumed local tumor recurrence. Two of these cats developed recurrent neurologic signs, and died or were euthanatized at 3 and 9 months, respectively, after surgery. One cat was euthanatized for an unrelated problem 72 months after surgery, and on postmortem examination, had a recurrent meningioma at the surgery site. The remaining 11 cats (78.6%) did not develop evidence of local tumor recurrence within follow-up periods ranging from 18 to 47 months (median, 27 months).

Synchronous Hodgkin's disease and non-Hodgkin's lymphoma in an adult with acquired immunodeficiency syndrome (AIDS).

A 26-year-old male seropositive for human immunodeficiency virus (HIV) infection presented with atypical Hodgkin's disease. Subsequently, synchronous, aggressive non-Hodgkin's lymphoma was identified in this patient. Atypical Hodgkin's disease appears to be an opportunistic neoplasm in patients seropositive for HIV infections and should be considered as an indicator disease for the definition of acquired immunodeficiency syndrome (AIDS).

Prolonged herpes-zoster infection associated with immunosuppressive therapy.

Unusually prolonged zoster was observed in four patients, two with cardiac transplants, one with acute lymphocytic leukemia, and one with diffuse histiocytic lymphoma. Lesions increased in number and persisted for 5 to 24 weeks before beginning to resolve. Specific cellular-immune responsiveness to varicella-zoster virus was markedly depressed during these infections. Absolute numbers of T lymphocytes were also very low. Reducing immunosuppressive therapy to increase immune responses appeared to initiate resolution of zoster lesions and halt dissemination. In one patient treatment with adenine arabinoside was also needed for resolution of disseminated zoster. This syndrome appears to be counterpart of the prolonged mucocutaneous herpes-simplex infection previously reported in immunosuppressed cardiac and renal transplant patients.

Adenovirus susceptibility to human interferon during one-step replication.

Susceptibility of adenovirus types 2, 7, and 12 to human interferon was measured in three human diploid cell strains during a single-cycle infection. Although the relative susceptibility of adenovirus to interferon varied in these cell strains, the final yield of each type in each cell strain decreased as the interferon dose increased. On the other hand, wide difference in interferon susceptibility of adenoviruses and vesicular stomatitis virus (VSV) was noted, as interferon doses above 100 units profoundly inhibited VSV but not the adenoviruses.

Sudden hemiparesis as the presenting sign in cryptococcal meningoencephalitis.

A previously healthy young man presented with an acute stroke syndrome and was found to have cryptococcal organisms in the CSF. Though an initial CSF examination for an infectious etiology was negative, a second lumbar puncture was performed because of hypoglycorrhachia, which established the diagnosis. An uneventful recovery followed the administration of Amphotericin B and 5-Flucytosine. A literature search revealed only one previously reported case of cryptococcal meningoencephalitis presenting as a stroke. The need for performing a CSF examination on young patients presenting with a cerebrovascular event, and the aggressive investigation of unexplained hypoglycorrhachia are emphasized.

Controlled clinical trial of intravenous acyclovir in heart-transplant patients with mucocutaneous herpes simplex infections.

Viral cultures of mucocutaneous herpes simplex lesions became negative in 5 heart-transplant patients given a 7-day course of intravenous acyclovir. Relief of pain and healing of lesions paralleled the virological response. Similar clinical and virological responses were not seen in the 5 placebo-treated patients in this double-blind placebo-controlled trial. No adverse reactions attributable to acyclovir were noted. Shedding of herpes simplex viruses recurred in 3 patients after acyclovir therapy.

Legionnaires' disease in patients with cancer.

A 4-year experience with Legionella pneumophila (LD) diagnosed in 36 patients with cancer was reviewed. Cancer patients represented 24% of the total population of patients acquiring LD during that time. Hematologic neoplasms (42%) and lung cancer (22%) accounted for the majority of afflicted patients. Nosocomial infections occurred in 42% of the patients evaluated. Several risk factors were assessed, and only neutropenia, and previous steroid therapy played a causal role (p less than .05) when assessed in a retrospective case control fashion. Overall mortality in oncology patients with LD (53%) was high and underscores the need rapidly to diagnose and treat this entity. This mortality decreased after 1977 when an effective antibiotic was utilized. Mixed infections also played a major role in outcome and occurred in 31% of the 36 patients studied. The mortality in these cancer patients was 73%, and this emphasizes the need to exclude and treat concomitant bacterial or fungal infections.

Female partners' estimations of male veterans' combat-related PTSD severity.

This study investigated concordance between male Vietnam veterans' and their female partners' reports of veterans' posttraumatic stress disorder (PTSD) symptoms. Fifty male Vietnam combat veterans and their partners rated the severity of their own PTSD symptoms. Also, partners rated the severity of veterans' symptoms. Results indicated modest levels of agreement in reports of symptom presence/absence. Partner ratings of veterans' PTSD severity were positively correlated with veteran reports and partners' own self-reported PTSD symptoms. After controlling for veterans' self-reported symptoms, partners' symptoms significantly predicted their estimates of veterans' avoidance symptoms, but not veterans' reexperiencing or hyperarousal symptoms. Theoretical and practical implications of these findings are discussed.

Physical properties of the dimyristoylphosphatidylcholine vesicle and of complexes formed by its interaction with apolipoprotein C-III.

The structure of a single bilayer vesicle of dimyristoylphosphatidylcholine has been characterized by sedimentation, densimetry, and light-scattering measurements. The molecular weight, partial specific volume, Stokes radius, and degree by hydration were found to be 2.68 X 10(6), 0.972 cm3/g, 125 A, and 0.86 g/g, respectively. From these quantities, a spherically symmetrical model has been derived that features a phospholipid bilayer 35.5 A thick and a hydration shell 9.3 A thick. This particle was shown to bind apolipoprotein C-III (apoC-III) up to 0.08 g/g without loss of its original vesicular structure. At protein-lipid ratios in excess of 0.08 g/g, sedimentation, gel chromatography, and light-scattering measurement indicated a dramatic decrease in Stokes radius and molecular weight. The sedimentation data showed these parameters to become constant at protein-lipid ratios in excess of 0.25 g/g. In this region, the Stokes radius and molecular weight were found to be approximately 80 A and 442 000, respectively. Within the constraints of these values and other data, several models for this complex are discussed.

Investigation of the aggregation and activation of prothrombin using quasi-elastic light scattering.

The technique of quasi-elastic light scattering was used to measure the translational diffusion coefficient, D, of purified human prothrombin in buffered aqueous solutions and to monitor for the first time the fragmentation of this protein as it is converted to thrombin. The values of D20,w, measured at two different concentrations, are 4.72 X 10(-7) CM2/S at 2MG/CM3 and 4.51 X 10(-7) CM2/S at 5MG/CM3; the corresponding molecular weights (Mw of 92 000 and 120 000), obtained by combining sedimentation velocity measurements with the diffusion data, confirm the presence of molecular aggregates of prothrombin in these solutions. These results, as well as analysis of the intensity-intensity autocorrelation functions from two-component systems with various dimer conformations, indicated the presence of end-to-end dimers in these prothrombin solutions. The values obtained for D indicate a dimer weight fraction of 0.4 to 0.5 in the 2 mg/cm3 solution and 0.6 or greater in the 5 mg/cm3 solution. The fragmentation of prothrombin was monitored in a nonphysiologic activation system, containing taipan snake venom, dihexanoylphosphatidylcholine, and CaCl2. At a temperature of 15 degrees C, conversion to thrombin proceeded very slowly and was still incomplete after 90 h. A method for determing the percentage of converted prothrombin is an activated system containing aggregates from the average value of D and light scattering data is discussed.

Cytomegalovirus retinitis in immunosuppressed hosts. I. Natural history and effects of treatment with adenine arabinoside.

Cytomegalovirus (CMV) retinitis presents with typical ophthalmologic appearance in patients with underlying immunosuppressive conditions. Fourteen patients with this disorder were diagnosed by culture of cytomegalovirus from urine or throat specimens, elevated complement fixation titers to cytomegalovirus, and characteristic funduscopic appearance. Ten of 11 had decreased CMV-specific cell-mediated immune responses. Three of seven who received no specific therapy improved after decreasing dosages of immunosuppressive drugs. Seven patients with progressive disease despite minimal immunosuppressive therapy were treated with adenine arabinoside at doses from 1 to 20 mg/kg of body weight per day. Daily dosages of 20 mg/kg . d in five patients were associated with decreased inflammatory activity and improvement of retinal lesions and quantitative decreases in urinary virus excretion. Adenine arabinoside administration was associated with significant gastrointestinal, hematologic, and neurologic side effects. Adenine arabinoside may have some beneficial effect on selected patients with progressive CMV retinitis.

Cytomegalovirus retinitis in immunosuppressed hosts. II. Ocular manifestations.

We observed the course of cytomegalovirus (CMV) retinitis in 21 eyes of 14 immunosuppressed patients. In two patients, other organisms, specifically Toxoplasma and Candida, also appeared to be causing retinal disease simultaneously. Post-mortem examination was done on 10 eyes from seven patients. At initial presentation, the retinitis was often asymptomatic and diagnosed during routine examination. The ophthalmoscopic picture was characteristic of cytomegalovirus; the early lesion was a small opaque, white granular area of retinal necrosis that spread in a centrifugal, brush-fire-like manner over 1 to 8 months. Vessel sheating and hemorrhages appeared as the disease progressed. In two patients new foci of retinitis developed remote from the original lesion. Four weeks to 4 months (average, 10 weeks) elapsed from the most extensive disease to total resolution. Resolution of active disease left a subtle retinal scar, and final visual acuity was reduced in one half the eyes. Repeated ophthalmoscopic examinations can aid in early diagnosis of CMV retinitis and in ascertaining which persons are most at risk for visual loss.

Short-course human leukocyte interferon in treatment of herpes zoster in patients with cancer.

Because of encouraging results when human leukocyte interferon was given for 5 to 7 days to treat early localized herpes zoster in patients with cancer, a small placebo-controlled, randomized, double-blind trial was set up involving only 48 h of therapy. In this trial, there was no effect on acute pain or disease progression in the primary dermatome. However, a modest but significant effect was noted in that distal cutaneous spread was diminished in the treated patients compared with the controls and the treated patients had diminished severity and duration of postherpetic neuralgia. No evidence of impairment in varicella-zoster-specific lymphocyte transformation was observed in interferon-treated patients.

Double-blind crossover trial of droperidol, metoclopramide, and prochlorperazine as antiemetics in cisplatin therapy.

Droperidol, metoclopramide, and prochlorperazine were compared in a double-blind crossover trial to determine their relative effectiveness in preventing and controlling the nausea and vomiting caused by cisplatin-containing chemotherapy. Twenty-five patients receiving cisplatin-containing chemotherapy for various malignancies were entered into this trial with 14 patients completing the three-drug randomization sequence. This was the patient's first exposure to cisplatin. Each antiemetic was administered in a diluted 50 ml i.v. injection over 15 minutes beginning 0.5 hour before cisplatin and 1.5, 3.5, 5.5, and 8.5 hours after cisplatin. Dosages of antiemetics for doses of cisplatin greater than or equal to 100 mg/sq m were droperidol 2.5 mg, metoclopramide 2 mg/kg, or prochlorperazine 5 mg in each infusion. For doses of cisplatin less than 100 mg/sq m, the dosages were droperidol 2.5 mg for the first two doses and 1.25 mg for subsequent doses, metoclopramide 1 mg/kg, or prochlorperazine 5 mg for each dose. The median number of emetic episodes for the first 24 hours were as follows: droperidol 3.2; metoclopramide 1.8; prochlorperazine 3.7. There was a significant difference in number of emetic episodes demonstrating antiemetic superiority of metoclopramide over both droperidol and prochlorperazine. For these 14 patients completing the trial, eight preferred metoclopramide, two preferred prochlorperazine, one preferred droperidol, and three had no preference. At the doses used in this study, the antiemetic efficacy of metoclopramide was superior to either droperidol or prochlorperazine.

Follow-up observations on the effect of human leukocyte interferon in non-Hodgkin's lymphoma.

Follow-up data for 11 patients with non-Hodgkin's lymphoma treated with partially purified human leukocyte interferon is presented. The interferon preparation used was 0.1% pure and treatment consisted of 5 x 10(6) U given intramuscularly twice daily for 60 injections. One complete, three partial, and three minimal responses were observed in five of seven evaluable patients with nodular non-Hodgkin's lymphoma. Duration of response appears to be from 6 to 12 mo. One patient achieved a second partial response on retreatment with interferon in spite of having received chemotherapy in the interval between interferon treatments. No responses were seen in three patients with rapidly progressive diffuse histiocytic lymphoma. Dose-limiting toxicity is leukopenia, which necessitated modification or cessation of treatment in three patients. Nonhematologic toxicities consisted of fever, malaise, arthralgia, and loss of appetite. In conclusion, interferon has activity against non-Hodgkin's lymphoma, and prior treatment with chemotherapy does not preclude a response to interferon.

Phase II trials of 5-fluorouracil and leucovorin in patients with metastatic gastric or pancreatic carcinoma.

BACKGROUND: Previous trials in patients with colorectal carcinoma have indicated that enhancement of 5-fluorouracil (5-FU) by leucovorin (LV) can result in an improved response rate and increased survival. METHODS: Phase II trials were performed with patients who had either gastric or papcreatic adenocarcinoma with inetastases. Forty-one gastric carcinoma patients and 31 pancreatic carcinoma patients with measurable disease were treated with 5-FU, 425 mg/m2 intraveneosly (i.v.) on Days 1-5 plus LV, 20 mg/m2 i.v., on Days 1-5, reported at 4 and 8 weeks, and then every 5 weeks thereafter. RESULTS: The patients with metastatic gastric carcinoma had a median survival of 4.8 months. There was a 22% objective response rate, including a 4.9% complete response rate and a 17.1% partial response rate. Among the 31 patients with pancreatic carcinoma, there was a median survival of 5.7 months. No patients in this group showed a response. CONCLUSIONS: The response rate for patients with metastatic gastric adenocarcinoma was modest and this regimen may provide temporary palliation for some patients. However, 5-FU and LV treatment is ineffective against metastatic pancreatic carcinoma.