Serum thyroglobulin levels predict total body iodine scan findings in patients with treated well-differentiated thyroid carcinoma

Forty-eight consecutive patients with treated thyroid carcinoma were studied with 131-I total body scans and serum thyroglobulin (hTg) levels. Serum hTg levels during thyroxine treatment accurately predicted scan results (chi square = 18.6, p < 0.001). All patients with negative scans (24 patients) had serum hTg levels (< 7 ng/ml whereas in patients with metastatic thyroid cancer (eight patients) they ranged from 11 to 690 ng/ml. In patients with iodine uptake confined to the thyroid bed (16 patients) serum hTg values ranged from 2 to 17 ng/ml. Serum hTg levels rose in patients with negative scans during hypothyroidism or after exogenous TSH suggesting that hTg levels are more sensitive than iodine scans in detecting residual thyroid tissue. Serum hTg levels could replace total body iodine scans in many patients with treated thyroid carcinoma.     

Serologic analysis of first-episode nonprimary genital herpes simplex virus infection: Presence of type 2 antibody in acute serum samples

Acute serum samples from patients with nonprimary first-episode genital herpes were evaluated for the presence of type-specific antibody to herpes simplex virus type 1 and type 2. A standard microneutralization assay and western blot analysis, which Identified the response to individual polypeptides of type 1 and type 2 herpes, were performed in both unadsorbed serum samples and serum samples adsorbed with either type 1 or type 2 antigens to remove cross-reacting antibodies. Of 24 serum samples examined, seven were found to contain only type 1 antibodies, 11 had type 2 antibodies alone, and six serum samples had both type 1 and type 2 antibodies. It is believed that a majority of the 17 patients whose acute serum samples already contained type 2 antibody were experiencing their first clinically apparent recurrence of a previous asymptomatic type 2 infection. Physicians should, therefore, acknowledge that patients with first-episode nonprimary herpes 2 infection may not have had a recent sexual contact with a herpes simplex virus-infected partner.     

Sites of airway dilatation in asthma following inhaled versus subcutaneous terbutaline: Comparison of physiologic tests with radionuclide lung images

In 12 asthmatic subjects with mild to severe airways obstruction, we compared the relative magnitude and sites of airway dilatation of a beta-adrenergic stimulant administered by different routes. Specific airway conductance (SG_aw), peak expiratory flow, the sum of the absolute volume of isoflow and residual volume as a percentage of total lung capacity (capacity of isoflow) and the ratio of maximal expiratory flow at 50 per cent of vital capacity breathing 80 per cent helium-20 per cent oxygen to that breathing air (ratio V?max₅) were determined before and after the administration of aerosolized terbutaline (0.5 mg), subcutaneous terbutaline (0.5 mg) or placebo. Increases in SG_aw and peak expiratory flow of ≥ 25 per cent were considered to indicate significant dilatation of central airways; increases in ratio Vmax₅₀ of ≥ 0.10 and decreases in capacity of isoflow of ≥10 per cent were assumed to reflect dilatation of peripheral airways. In addition, radioaerosol and radioxenon lung imaging was performed to determine the relationship between changes in lung imaging patterns and changes in physiologic indices in response to bronchodilator therapy. Placebo caused little change in lung function or lung imaging. After inhaled terbutaline, SG_aw and peak expiratory flow increased ≥25 per cent in seven subjects, ratio Vmax₅₀ increased ≥0.10 in only three subjects, capacity of isoflow decreased ≥10 per cent in only one subject, radioaerosol images showed less central deposition in nine subjects and radioxenon images showed improved distribution and/or washout of xenon in five subjects. After the administration of subcutaneous terbutaline, SG_aw and peak expiratory flow increased ≥25 per cent in 10 subjects, ratio Vmax₅₀ increased ≥0.10 in 10 subjects, capacity of isoflow decreased ≥10 per cent in 11 subjects, and radioaerosol and xenon images showed improvement in 11 and eight subjects, respectively. These findings are consistent with the action of inhaled terbutaline mainly on large airways and of subcutaneous terbutaline on both large and small airways. Although reduced central radioaerosol deposition correlated well with physiologic evidence of large airway dilatation, improvement in xenon distribution and washout could be attributed to dilatation of either large and/or small airways.     

Prevalence and clinical correlates of pulmonary arterial hypertension in progressive systemic sclerosis

Forty-nine patients with progressive systemic sclerosis who had undergone extensive studies including pulmonary artery catheterization as part of an ongoing prospective study of the natural course of progressive systemic sclerosis were evaluated. The overall prevalence of pulmonary arterial hypertension in this population of patients with progressive systemic sclerosis was 33 percent, and among 10 subjects with the CREST syndrome the prevalence of pulmonary hypertension was 50 percent. The relation between pulmonary arterial hypertension documented at catheterization and abnormal results of noninvasive studies suggesting pulmonary hypertension, including physical examination, chest x-ray, electrocardiography, echocardiography, single-breath diffusing capacity, and vital capacity, was studied. Diffusing capacity was significantly lower in those patients with definite pulmonary hypertension (mean pulmonary artery pressure of 22 mg Hg or more) compared with those with a normal mean pulmonary artery pressure, and a diffusing capacity below 43 percent of predicted showed the greatest sensitivity (67 percent) of any single diagnostic test in detecting definite pulmonary hypertension. Chest x-ray suggesting pulmonary hypertension was the least sensitive of the tests evaluated, but showed the greatest specificity (100 percent) in identifying patients with pulmonary hypertension. A classification matrix based on discriminant function analysis utilizing the combination of diffusing capacity below 43 percent of predicted and chest x-ray and electrocardiographic findings correctly identified 75 percent of patients with definite pulmonary hypertension and 97 percent of patients with a normal pulmonary artery pressure, but failed to identify correctly patients with mild pulmonary hypertension (mean pulmonary artery pressure of 20 mm Hg). These findings indicate that specific noninvasive studies are helpful in assessing the likelihood of normal or definitely elevated pulmonary artery pressures in patients with progressive systemic sclerosis, but patients with mild pulmonary hypertension are not likely to be identified by these noninvasive studies.     

Serum prolactin levels in untreated primary hypothyroidism

The serum prolactin level was found to be elevated (>14.0 ng/ml) in 39 per cent of patients with untreated primary hypothyroidism, none of whom were receiving drugs known to affect serum prolactin levels. The mean serum thyroid-stimulating hormone (TSH) (± SEM), thyroxine (T₄) and triiodothyronine (T₃) levels prior to therapy were, respectively, 106.0 μU/ml ± 19.3, 0.9 μg/dl ± 0.2, 50.6 ng/dl ± 5.8. The mean serum prolactin level in the hypothyroid group (14.3 ng/ml ± 1.1; range: 4.7 to 42.0 ng/ml; 49 subjects) was significantly higher (P < 0.01) than in the euthyroid controls (8.2 ng/ml ± 0.5; range 5.1 to 14.0 ng/ml; 24 subjects). The mean serum prolactin level in the hypothyroid women (15.4 ng/ml ± 1.3; range 4.7 to 42.0 ng/ml; 39 subjects) was significantly higher (P < 0.002) than in the euthyroid female controls (8.1 ng/ml ± 0.7; range 5.1 to 14.0 ng/ml; 15 subjects). The mean serum prolactin level in the hypothyroid men (10.3 ng/ml ± 1.4; range 5.1 to 18 ng/ml; 10 subjects) was not significantly different from that in the male controls (8.3 ng/ml ± 0.7; range 5.3 to 13 ng/ml; nine subjects). A significant correlation was found between log serum prolactin and log serum TSH (r = 0.34, P < 0.05), suggesting that the elevated serum prolactin level in primary hypothyroidism may be mediated by a common factor, such as TRH. Despite the increased frequency of elevated serum prolactin levels, galactorrhea is an uncommon accompaniment of primary hypothyroidism.     

Small airways in progressive systemic sclerosis (PSS).

Obstructive disease involving peripheral airways has been noted in diffuse interstitial pulmonary disease, including sarcoidosis and cryptogenic fibrosing alveolitis. The possibility of obstruction of small airways in progressive systemic sclerosis (PSS) has been suggested by widespread bronchiolectasis and peribronchial fibrosis noted at necropsy. We performed pulmonary function studies in 39 subjects (22 nonsmokers and 17 smokers) with PSS, most of whom had functional evidence of interstitial pulmonary involvement (increased static recoil pressure and reduced diffusing capacity). The 1 second forced expiratory volume to forced vital capacity ratio (FEV1:FVC) was normal in all subjects. Although the severity of the restrictive process was greater in nonsmokers compared with that in smokers, the maximal mid-expiratory flow rate, closing volume, closing capacity, volume of isoflow, change in maximal expiratory flow at 50 per cent of vital capacity during 80 per cent helium--20 per cent oxygen breathing compared with air breathing (delta Vmax50), ratio of dynamic to static lung compliance at different breathing frequencies and upstream airway conductance at static recoil pressures of 5 and 10 cm H2O were nearly always normal in the nonsmokers but were frequently abnormal in the smokers with PSS. These findings suggest that diffuse interstitial pulmonary disease due to PSS generally does not lead to functional evidence of obstruction in peripheral airways and that when the latter is found it can likely be attributed to the effects of concomitant cigarette smoking.     

"Hairy cell" leukemia: a heterogeneous chronic lymphoproliferative disorder.

Thirteen patients with “hairy cell” leukemia and circulating tartrate-resistant acid phosphatase (TRAP)-positive mononuclear cells were studied. A high percentage of peripheral mononuclear cells from 12 patients were positive for surface membrane immunoglobulin (Smlg). Unlike studies in chronic lymphocytic leukemia, in most of these patients with “hairy cell” leukemia it was not possible to establish “clonality” on the basis of λ/κ or immunoglobulin-class cell surface markers because of frequent weak reactions with more than one antiserum in each group. Complement (C₃) receptor-bearing cells accounted for 69 per cent of the peripheral mononuclear cells in one patient. In another patient, 80 per cent of the peripheral mononuclear cells were positive for Fc receptors. Both patients also had high levels of Smlg-positive cells. In a third patient, peripheral mononuclear cells were of T-cell type as determined by over 80 per cent E rosetting and only 2 per cent Smlg-bearing cells. Phytohemagglutinin (PHA) stimulation on peripheral mononuclear cells from five patients revealed weak responses at three days. However, when this response was followed further, it reached normal intensity by five days of incubation, in contrast to cells from patients with chronic lymphocytic leukemia which gave a peak PHA response at eight to nine days. Cells from all patients, except cells from patients with T-cell type “hairy cell” leukemia, showed positive cytotoxic reactions with antiserums designating various B-cell (Merrit; la-like) alloantigenic groups. “Hairy-cell leukemia” appears to be a heterogeneous group of chronic lymphoproliferative disorders.     

Cyclic cushing's syndrome

Cyclic Cushing's syndrome is a rare but increasingly recognized disorder of periodic fluctuations of adrenal steroid production. A case of cyclic Cushing's syndrome due to a pituitary adenoma is described. The patient demonstrated a prolonged cycle length of approximately six months, during which a spontaneous remission occurred both clinically and biochemically. Previously documented cases of cyclic Cushing's syndrome are reviewed, and the pitfalls in interpretation of results of dexamethasone suppression testing in the presence of spontaneous fluctuations in cortisol production are discussed.     

Moxalactam plus piperacillin versus moxalactam plus amikacin in febrile granulocytopenic patients

In a prospective randomized trial, febrile granulocytopenic patients received either moxalactam plus piperacillin or moxalactam plus amikacin as initial empiric antimicrobial therapy. Most patients were also given prophylactic vitamin K. The overall response rates for the two regimens were similar (105 of 136, or 77 percent, for moxalactam plus piperacillin versus 107 of 136, or 79 percent, for moxalactam plus amikacin). For Pseudomonas aeruginosa infections, the response rate was better in patients receiving moxalactam plus amikacin (seven of nine versus one of five, p = 0.06); two patients treated with moxalactam plus piperacillin experienced relapse of P. aeruginosa bacteremia in association with the emergence of beta-lactam-resistant P. aeruginosa isolates. On the other hand, bacteremic enterococcal superinfections occurred in seven patients receiving moxalactam plus amikacin but in none given moxalactam plus piperacillin (p = 0.02). Serious side-effects were minimal with both regimens, and nephrotoxicity was less common in patients receiving moxalactam plus piperacillin (two of 136 versus six of 136, p = 0.28). There was no antibiotic-related hemorrhage. These results suggest that the overall efficacy and toxicity of moxalactam plus piperacillin and moxalactam plus amikacin are similar. Moxalactam/piperacillin therapy may be limited in certain patients by the emergence of beta-lactam-resistant P. aeruginosa, whereas enterococcal superinfections may complicate moxalactam/amikacin therapy.     

Adenovirus infection in the immunocompromised patient

Illness associated adenovirus infection is described in 15 immunocompromised patients. Patients were immunocompromised by severe underlying disease, immunosuppressive or corticosteroid therapy or by age (prematurity). Evidence of adenovirus infection was obtained by either viral isolation or, in two cases, characteristic adenovirus inclusion bodies at postmortem study.All clinical illness was associated with high fever (temperature >39 °C). Eighty per cent of the patients had severe systemic complaints including malaise, lethargy, fatigue and night sweats; a similar number of gastrointestinal symptoms. Pulmonary complaints were described in 11 of 15 cases and included cough (67 per cent) and tachypnea (53 per cent). Roentgenologic evidence of pneumonia was demonstrated in 12 of 15 patients (80 per cent). Elevation of serum hepatic enzyme levels (serum glutamic pyruvic transaminase (SGPT)) occurred in eight of 11 patients (73 per cent) and was moderate to severe (serum glutamic pyruvic transaminase >450 IU/liter) in five of 11 (45 per cent). Nine patients died; seven after a rapid downhill course and two after a prolonged illness. Evidence of adenovirus infection microscopically by autopsy in the lung, liver or both is demonstrated in four patients with fulminant systemic illness. Adenovirus infection should be considered in the etiology of severe overwhelming illness in the immunocompromised host.     

Serum inhibitors of hematopoiesis in a patient with aplastic anemia and systemic lupus erythematosus. Recovery after exchange plasmapheresis.

A 36 year old black woman with serologic evidence of systemic lupus erythematosus had aplastic anemia that failed to respond to corticosteroid or androgen therapy. Bone marrow culture studies were performed to determine if the marrow aplasia was immunologically mediated. A potent serum inhibitor of in vitro myeloid and erythroid colony formation was demonstrated. Incubation of normal bone marrow cells with the patient's serum and a source of complement caused a 95 per cent reduction in myeloid colony formation. Under these conditions, bone marrow from 35 normal volunteer subjects formed a mean of 5 ± 1 colonies per 2 × 10⁵ marrow cells plated (control = 95 ± 8 colonies). The addition of the patient's serum plus complement to normal marrow cultured in methylcellulose also caused a 98 per cent reduction in erythroid colony numbers. Assay of serum immunoglobulin fractions obtained by gel filtration demonstrated that the inhibitory activity was contained in the immunoglobulin G (IgG) fraction. In association with a series of plasma exchanges, the titer of inhibitor fell, and marrow cellularity and peripheral blood counts returned to normal. Additional studies indicated that the inhibitor of allogeneic marrow was not directed against HLA or “B-cell” antigens. Incubation of the patient's recovery marrow with stored preplasmapheresis serum and complement did not produce a reduction in myeloid colony formation. It seems most likely that the inhibitor represents alloantibody directed against heretofore unrecognized antigens widely distributed on normal human hematopoietic progenitor cells.     

Quantitative changes in T helper or T suppressor/cytotoxic lymphocyte subsets that distinguish acquired immune deficiency syndrome from other immune subset disorders

Quantitative measurements of the immune cell subgroups, T helper (Leu 3+/OKT4+) cells and T suppressor/cytotoxic (Leu 2+/OKT8+) cells, were made in patients having acquired immune deficiency syndrome (AIDS) with Kaposi's sarcoma and in patients with AIDS and opportunistic infection, as well as in three other relevant populations. These included patients with lymphadenopathy syndrome, e.g., homosexually active males with lymphadenopathy who sought medical care for additional symptoms, and healthy male homosexuals, as well as a control population. Decrease in the number of T helper cells is characteristic of AIDS with Kaposi's sarcoma or opportunistic infection. Augmentation of the T suppressor/cytotoxic cell population is rare in AIDS with Kaposi's sarcoma but is more frequent in AIDS with opportunistic infection. Augmentation of the T suppressor/cytotoxic cell population, however, may occur in a variety of circumstances, including cytomegalovirus and other viral infections, in healthy, homosexually active males, and in otherwise healthy hemophiliac subjects receiving factor VIII treatment. Reduced T helper:T suppressor/cytotoxic cell ratio can be caused by either decrease in the number of T helper cells or augmentation of the T suppressor/cytotoxic cell population. Lowered T helper:T suppressor/cytotoxic cell ratio does not, by itself, help to distinguish between AIDS and other causes of reduced ratios. Quantitative measurements are needed to define the T subset changes. AIDS is characterized by decrease in the number of T helper cells and reduced T helper:T suppressor/cytotoxic cell ratio. The T helper (Leu 3+) and T suppressor/cytotoxic (Leu 2+) cell subpopulations can change independently. Identification of decrease in the number of T helper cells as an alteration that occurs independently of numerical change in other lymphoid subpopulations, such as T suppressor/cytotoxic cells and B cells, and the close association of the decrease in the number of T helper cells with AIDS are consistent with a distinct pathogenesis (and cause) for AIDS.     

Accuracy of the echocardiographic diagnosis of aortic regurgitation

Anterior mitral leaflet diastolic flutter and flutter of contiguous cardiac structures are accepted M-mode echocardiographic signs of aortic regurgitation. Ninety-four subjects (47 normal and 47 with aortic regurgitation on angiography) had echocardiograms evaluated (double-blind) by two observers for the presence of anterior mitral leaflet diastolic flutter or ventricular septal diastolic flutter. For the entire study population, sensitivity was 66 percent for anterior mitral leaflet diastolic flutter, 36 percent for ventricular septal diastolic flutter and 72 percent for diastolic flutter over-all (i.e., present on either or both). Severe chronic aortic regurgitation always revealed anterior mitral leaflet diastolic flutter. Mild to moderate aortic regurgitation without mitral stenosis had an 81 percent sensitivity for over-all diastolic flutter; with mitral stenosis, over-all sensitivity of diastolic flutter was 44 percent. Specificity of anterior mitral leaflet diastolic flutter was 83 percent, of ventricular septal diastolic flutter 98 percent, of diastolic flutter over-all 83 percent. There was no observer discordance over diastolic flutter in severe aortic regurgitation, but 19 percent discordance over diastolic flutter in mild to moderate aortic regurgitation without mitral stenosis, and 31 percent discordance in mild to moderate aortic regurgitation with mitral stenosis. There was 26 percent disagreement over the absence of diastolic flutter in normal subjects, predominantly regarding anterior mitral leaflet diastolic flutter. Predictive value of diastolic flutter was 81 percent when present and 75 percent when absent. We conclude the following: (1) In severe aortic regurgitation, interobserver agreement is good for anterior mitral leaflet diastolic flutter, which is a highly sensitive sign; (2) interobserver agreement is good for ventricular septal diastolic flutter, which is highly specific but insensitive; (3) disagreement was greatest over anterior mitral leaflet diastolic flutter in normal subjects; and, (4) with coexisting mitral stenosis, diastolic flutter is not a sensitive sign.     

Primary mediastinal lymphoma in adults

The incidence of primary mediastinal lymphoma in adults was investigated in 184 patients with non-Hodgkin's lymphoma. This entity was defined as disease within the mediastinum in patients who presented with symptoms due to an enlarging mediastinal mass. Of 184 patients, 17 presented with primary mediastinal lymphoma. All had a diffuse histologic pattern. The most common pathologic type was poorly differentiated lymphocytic lymphoma, diffuse (PDL-D), (11 cases). In nine of these 11 cases the patients had tumors of convoluted lymphocytes. The presentation was rapid in onset, with heart failure, pericarditis, dyspnea and superior vena caval syndrome predominating. Eleven of the 17 were clinical stage I or II, but eight of these had widespread disease on pathologic staging or rapid dissemination soon after diagnosis. In conclusion (1) primary mediastinal lymphoma is always diffuse in histology. (2) The most frequent pathologic type is PDL-D, with convoluted morphology. (3) Compression of vital intra-thoracic structures is common. (4) Although seemingly localized at presentation, this entity usually implies disseminated disease.     

Immune suppression of hematopoiesis.

Recent evidence suggests that immune mechanisms can injure proliferating hematopoietic precursor cells in the bone marrow. These may involve either humoral antibody or cell-mediated cytotoxic mechanisms. Immune injury can result in a variety of bone marrow failure syndromes. Immunologically induced abnormalities or blood cell production may be restricted to a single series, such as erythrocyte or granulocyte precursors, or may involve several hematopoietic lines; clinical manifestations reflect the cell line or lines that are injured. Immune suppression of hematopoiesis has now been described in pure red cell aplasia, immune panleukopenia, systemic lupus erythematosus, atypical cases of aplastic anemia and miscellaneous other hematologic diseases.     

The first 24 hours of acute pancreatitis. Changes in biochemical and endocrine homeostasis in patients with pancreatitis compared with those in control subjects undergoing stress for reasons other than pancreatitis

As a group, 20 patients with acute pancreatitis showed alterations in biochemical and endocrine homeostasis that differed from the metabolic reactions observed in 13 control patients undergoing stress for reasons other than pancreatitis. In patients with acute pancreatitis, hyperglycemia was associated with inappropriately low serum insulin levels (p < 0.005). Plasma glucagon concentrations were markedly increased in the patients with acute pancreatitis and exceeded control values (p < 0.0001) throughout the 24-hour study period. The lipolytic effect of the inadequate serum insulin concentrations, elevated blood cortisol levels and hyperglucagonemia produced in a rise in nonesterified fatty acid levels. Serum gastin and growth hormone measurements remained within the normal range. Plasma parathyroid hormone (PTH) and calcitonin concentrations were increased in both patient populations, although calcitonin levels in patients with pancreatitis were significantly lower than those in the control group (p < 0.001). In patients experiencing a recurrent attack of pancreatitis, plasma glucagon levels were low (p < 0.005) compared with levels in patients experiencing their first episode of acute pancreatitis. Appreciation of the metabolic derangements in acute pancreatitis that are independent of the normal metabolic changes which occur in response to stress will help to rationalize exogenous endocrine therapy and possibly the prognostic accuracy in this disease.     

Myeloblastic leukemic cells causing suppression of granulopoiesis and excessive binding of colony-stimulating activity. The effect of antithymocyte globulin.

The three and a half year course of an adult woman (65 years) with myeloblastic leukemia, the leukemic clone being trisomic for chromosome #8, was characterized by suppressed granulopoiesis despite a small mass of leukemic tissue relative to cytogenetically normal marrow precursors. The leukemic tissue was shown to be productive of mature neutrophilic granulocytes with hypersegmented nuclei and increased alkaline phosphatase content. These granulocytes showed active phagocytosis but diminished fungicidal capacity. The leukemic tissue inhibited granulocyte-monocyte colony formation in soft agar with colony-stimulating activity from human and murine sources when co-cultured with normal, chronic myelocytic leukemia, Philadelphia chromosome positive (CML Ph¹⁽⁺⁾) human and C57 black (BL) murine marrow. This inhibition was associated with binding of colony-stimulating activity at sites on the leukemic cells which failed to elicit colony formation by leukemia colony-forming units, culture (CFUc). Pretreatment of the leukemic tissue with antithymocyte globulin (ATG) before co-culture removed the inhibitory effect of the leukemic tissue and promoted colony formation by leukemic CFUc. This effect of ATG involved competitive binding of colony-stimulating activity and ATG by leukemic cells since the consumption of colony-stimulating activity by leukemic cells was blocked by prior treatment of leukemic cells with ATG. Infusion of autochthonous cytogenetically normal marrow after two years of cryopreservation was ineffective in altering the neutropenic state. Bacteremia (Klebsiella pneumoniae) at a time when the marrow contained mostly leukemic precursors was associated with transient neutrophilic granulocytosis involving mature leukemic progeny. ATG given to the patient in a preterminal state was associated with a simitar leukocytosis as well as colony formation in vitro by the leukemic marrow tissue.     

Prophylactic granulocyte transfusions during human bone marrow transplantation

Thirty-eight uninfected patients undergoing bone marrow transplantation were assigned at random to receive prophylactic granulocyte transfusions and oral nonabsorbable antibiotics (group 1) or oral nonabsorbable antibiotics alone (group 2) when their neutrophil count fell below 0.5 x 10(9)/liter. The two groups were comparable in terms of age, sex, underlying disease, immunosuppressive therapy and days of neutropenia. There were three cases of septicemia (all due to gram-positive organisms) in group 2 and none in group 1 (p = 0.23). There was no difference in the incidence of other documented infections, and survival between the two groups was comparable. Recipients of prophylactic granulocyte transfusions had a significantly higher incidence of cytomegalovirus (CMV) infections (13 of 18 versus six of 17, p = 0.043). These data suggest that prophylactic granulocyte transfusions may prevent septicemia, have no effect on other infections or survival in patients undergoing bone marrow transplantation, and are associated with a higher incidence of CMV infection. Oral nonabsorbable antibiotics alone are equally effective in preventing serious infections in bone marrow transplant recipients.     

Symposium on infectious complications of neoplastic disease (Part II). Immunoprophylaxis and serotherapy of bacterial infections

Immunologic approaches to the prevention and treatment of bacterial infections date back to the antecedent century. Recent interest and controversy has centered about the efficacy of gram-negative bacillary vaccines, antiserum against endotoxin, and pneumococcal vaccines. Immunization of cancer patients with Pseudomonas lipopolysaccharide vaccines has yielded inconsistent results. Factors limiting the further application of this approach are the poor immune responses in neutropenic patients and the marked pyrogenicity and pain associated with vaccine administration. Similarly, patients being treated for neoplasms of the hematopoietic system are not likely to show good antibody responses to pneumococcal antigens, even though they are not toxic. Pneumococcal immunization appears to be effective, at least as measured in terms of antibody titers, in those patients with lymphoma who have not undergone splenectomy and are not receiving chemotherapy at the time of immunization. The most reliable approach towards immunoprophylaxis may be the passive one, with antibody being produced in normal donors. The antibodies are short-lived, and this type of prophylaxis still needs to be evaluated in controlled trials. In a recently completed controlled therapeutic trial, the therapeutic application of an antiserum against core endotoxin antigens resulted in a significant reduction in deaths and increased recovery from shock complicating gram-negative sepsis. However, antiserum failed to protect cancer patients or neutropenic subjects.     

Chronic graft versus host disease: a syndrome of disordered immunity.

A chronic, debilitating syndrome related to graft-versus-host disease (GVHD) has been recognized in long-term survivors following allogeneic bone marrow transplantation. In six of 20 marrow graft recipients who survived for more than one year after receiving a transplant, this complication developed; they were studied to better define the syndrome. There was no association between the sex of either donor or recipient, HLA type, blood group, conditioning regimen or marrow cell dose and subsequent development of chronic GVHD. All six patients had mild to moderate manifestations of acute GVHD following prompt engraftment. Chronic GVHD was characterized in each patient by progression to scleroderma-like skin involvement with hyperkeratosis, reticular hyperpigmentation, atrophy with ulceration and fibrosis with limitation of joint movement. A sicca syndrome was prominent in five patients. Four patients had idiopathic interstitial pneumonitis. Infectious complications were frequent, and DNA viral infections were prominent. Autoimmune hemolytic anemia was present in three patients, and one patient had antinuclear antibody (ANA). A spectrum of immune abnormalities was observed including hypergammaglobulinemia, immunoglobulin M (IgM) paraprotein, elevated circulating immune complexes, plasma cell hyperplasia, lymphocytotoxic antibodies and autoantibodies to autologous or donor lymphocytes. Despite clinical similarity to collagen vascular diseases, none of these patients had anti-DNA antibodies or antibodies to smooth muscle, thyroid or extractable nuclear antigens. In one patient, a skin graft from the marrow donor remained healthy despite progressive involvement in recipient skin, whereas unrelated skin grafts were rejected. Immunosuppressive therapy and plasmapheresis have not been effective. Four patients have died (median survival 458 days from transplantation). Chronic GVHD appears to be a syndrome of disordered immune regulation features of immunodeficiency and autoimmunity.