Search

Ileal pouch-anal anastomosis (IPAA) surgery is the reference standard surgical procedure for treatment of ulcerative colitis and most patients with familial adenomatous polyposis. This procedure allows preservation of fecal continence and gastrointestinal continuity. However, it is associated with a wide variety of complications, which often have nonspecific and overlapping clinical presentations, making imaging an important part of workup for pouch dysfunction. The purpose of this article is to propose structured reporting templates for MRI and water-soluble contrast enema (WSCE), based on our referral pouch center's experience, in patients who have undergone IPAA surgery. We review salient surgical technique, pouch anatomy, and imaging protocols, with an emphasis on a systematic search pattern for evaluation of ileal pouch complications using proposed structured reporting templates for MRI and WSCE.

Surgery has been associated with proangiogenic plasma protein changes that may promote tumor growth. Angiopoietin-like protein 4 (ANGPTL4) is expressed by endothelial cells and other tissues in response to hypoxia. Both intact ANGPTL4 and its partly degraded C-terminal fragment may promote tumor angiogenesis. This study had two purposes: to measure and compare preoperative plasma ANGPTL4 levels in patients with colorectal cancer (CRC) and benign colorectal disease (BCD) and to determine plasma levels after minimally invasive colorectal resection (MICR) for CRC. Plasma was obtained from an IRB-approved plasma/data bank. Preoperative plasma ANGPTL4 levels were measured for CRC and BCD patients, but postoperative levels were determined only for CRC patients for whom a preoperative, a postoperative day (POD) 3, and at least one late postoperative sample (POD 7–55) were available. Late samples were bundled into four time blocks and considered as single time points. ANGPTL4 levels (mean ± SD) were measured via ELISA and compared (significance, p

Angiogenesis is central to wound healing and tumor growth. Postoperative (postop) plasma from weeks 2 and 3 after minimally invasive colorectal resection (MICR) stimulates endothelial cell (EC) migration (MIG), invasion (INV), and proliferation (all vital to angiogenesis) compared with preoperative (preop) plasma results and may promote postop tumor growth. The purpose of this study was to determine whether plasma from open colorectal resection (OCR) patients has similar proangiogenic EC effects in vitro.OCR cancer patient plasma from institutional review board-approved banks was used; patients with preop and one postop sample from postoperative days (POD) 7-33 were eligible. Samples were bundled into 7- to 13-day periods and considered as single time points. In vitro cultures of human umbilical venous ECs were used for the EC proliferation (BPF, Branch Point Formation), INV, and MIG assays performed with preop, POD 7-13, POD 14-20, and POD 21-33 plasma. Data were analyzed by paired t test and were reported as mean ± standard deviation (significance, P0.05).Plasma from 53 cancer patients (25 rectal and 28 colon) was used. Because of limited postop samples, the number for each time point varies: POD 7-13, n = 30; POD 14-20, n = 26; and POD 21-33, n = 17. In vitro EC BPF was significantly greater at the POD 7-13 (P0.0001) and POD 14-20 (P0.0001) time points versus preop results. Significantly greater EC INV and MIG were noted on POD 7-13 and POD 14-20 versus the preop plasma results (P0.0001). In regards to POD 21-33, a significantly greater result was noted only for the INV assay versus preop.Plasma from weeks 2 and 3 after OCR stimulates in vitro EC BPF, INV, and MIG. A significant difference from preop baseline was noted only for the INV assay in week 4. The OCR and previous MICR results were largely similar. Tumor angiogenesis may be stimulated after OCR and MICR for 3 weeks. Further studies are warranted.

Purpose There’s no consensus about what defines a conversion for laparoscopic-assisted colorectal resection (LACR). This study’s goal was to assess the utility of a strict incision length (IL) definition of conversion (incision > 7 cm) and compare it with results obtained when the surgeon determined (SD) if a LACR had been successfully completed. Methods. The demographic and perioperative data for 580 elective LACRs were reviewed. The short-term outcomes for each conversion definition were determined and compared. Results. Conversion rates were 22% using the IL definition and 16% via the SD method. Both methods detected significant differences between completed and converted groups regarding the following: incision size, hospital stay, time to flatus, bowel movement, and regular diet as well as rate of wound infection and ileus. The IL method alone detected significant differences in the rate of pulmonary complications and BMI between the completed and converted groups. Conclusions . The 2 methods yielded similar results for most parameters. The IL method better separated the patients in regard to 2 parameters. This method is objective and easy to apply; however, it may discriminate against obese patients whose extraction incisions are often longer. A conversion definition that considers BMI and IL is needed.

Background Soluble CD23 is the proteolytic cleavage product of the low affinity receptor (FcERII). Functions of CD23 and its soluble products may include upregulation of IgE production and stimulation of B lymphocyte growth. Methods Soluble CD23 was quantitated in supernatants of lymphocytes from nine ragweed-sensitive and eight nonatopic subjects stimulated in vitro by antigen E (amb A1), crude ragweed extract, and pokeweed mitogen (PWM). Results Although PWM stimulation produced no significant difference between groups, sCD23 release was significantly elevated in the cells of nontoxic patients stimulated with antigen E and crude ragweed extract. ( P Conclusions This finding supports the concept of separate pathways of activation by antigen and mitogen for sCD23 release and suggests ragweed-sensitive and nonatopic patients have fundamental differences in the response of sCD23 release to ragweed antigen stimulation.

Endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR), and partial circumference resection are used for large benign polyps to avoid an "Oncologic" Colorectal Resection (OCR); polyps with invasive cancer require OCR. This review of polyp patients who had OCR was done to stratify polyps into risk groups to guide treatment.Colonoscopy, operative, and pathology reports of patients with adenoma (+/- dysplasia) who had OCR were reviewed. Polyp size, location, and pathology were assessed.Three hundred eighty-six polyp patients who had OCR were studied. Polyp locations were: right, 263 (68.1%); transverse, 33 (8.6%); sigmoid, 38 (9.8%); rectum, 23 (6.0%); and multiple sites, 13 (3.4%). The preoperative diagnosis was adenoma for 288 (74.6%) and dysplastic adenoma for 98 patients (25.4%). Final pathology revealed 62 invasive cancers (16.1%); 35% (34 out of 98) with dysplasia preoperatively had cancer versus 9.7% (28 out of 288) with adenoma alone (p 0.0001). The mean lymph node count was 16.0 ± 10.2. Cancer stage breakdown was: stage 1, 74%; stage 2, 8.1%; stage 3, 16%; and stage 4, 1.6%. The mean benign polyp size was 3.0 ± 1.9 versus 3.9 ± 2.4 cm for malignant polyps (p = 0.0008).Over one out of three of dysplastic polyps and 10% of adenomas were invasive cancers. OCR is advised for dysplastic polyps; ESD, EMR, and wedge resection are appropriate for non-dysplastic adenomas.

Soluble CD54 levels in sera were quantitated in asymptomatic intravenous drug users, homosexuals, and patients with lymphadenopathy, AIDS-related complex, or acquired immunodeficiency syndrome. Soluble CD54 levels were elevated in human immunodeficiency virus (HIV)-seronegative asymptomatic intravenous drug users, reflecting infections like cytomegalovirus, Epstein-Barr virus, and hepatitis B virus. The sera of human immunodeficiency virus-seropositive groups of patients also had elevated levels of soluble CD54, reflecting infections like cytomegalovirus and human immunodeficiency virus infection. © 1993 Wiley-Liss, Inc.

Background. Intravenous amphotericin B, with or without flucytosine, is usually standard therapy for cryptococcal meningitis in patients with the acquired immunodeficiency syndrome (AIDS). Fluconazole, an oral triazole agent, represents a promising new approach to the treatment of cryptococcal disease. Methods. In a randomized multicenter trial, we compared intravenous amphotericin B with oral fluconazole as primary therapy for AIDS-associated acute cryptococcal meningitis. Eligible patients, in all of whom the diagnosis had been confirmed by culture, were randomly assigned in a 2:1 ratio to receive either fluconazole (200 mg per day) or amphotericin B. Treatment was considered successful if the patient had had two consecutive negative cerebrospinal fluid cultures by the end of the 10-week treatment period. Results. Of the 194 eligible patients, 131 received fluconazole and 63 received amphotericin B (mean daily dose, 0.4 mg per kilogram of body weight in patients with successful treatment and 0....

Circulating human immunodeficiency virus (HIV) p24 antigen levels were measured by a highly sensitive HIV p24 antigen-capture enzyme-linked immunosorbent assay (ELISA) in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) otherwise negative for HIV p24 antigenmeasured by a commercial antigen-capture ELISA. The assays were performed at baseline and at several intervals during treatment with either zidovudine (ZDV) or dideoxyinosine (ddl). To further enhance the rate of antigen detection, serum was pretreated with hydrochloric acid to denature antibody in immune complexes. Utilizing this assay system, we monitored these patients for drug efficacy. HIV p24 antigen levels obtained by using this sensitive assay decreased in 3 of 8 patients receiving ZDV during 8 weeks of ZDV treatment. Similarly, ddl administration was associated with a decrease of HIV p24 antigen levels in 3 of 5 patients. Thus, the use of the highly sensitive HIV p24 antigen assay permitted the monitoring of surrogate HIV p24 antigen as a measure of efficacy of anti-retroviral therapy in all of these patients who were otherwise HIV p24 antigen-negative at the onset of anti-retroviral therapy. © 1992 Wiley-Liss, Inc.

Circulating immune complexes were quantitated in asymptomatic intravenous drug abusers (IVDA), male homosexuals, and patients with lymphadenopathy or acquired immunodeficiency syndrome (AIDS) by two different methods. Circulating immune complexes were elevated in HIV-seronegative IVDAs and male homosexuals, probably reflecting viral infections such as cytomegalovirus (CMV). Circulating immune complexes were also elevated in HIV-seropositive IVDAs and male homosexuals and in patients with lymphadenopathy or AIDS, reflecting infections such as CMV and HIV.

Background sCD23 is the designation given to the low affinity IgE receptor. The soluble fragment of this receptor (sCD23) participates in the regulation of IgE synthesis. Objective The purpose of this study is to examine the effect of a venom immunotherapy regimen on sCD23 levels. Methods We measured sCD23 levels by ELISA in Hymenoptera venom-allergic patients (positive skin tests and a history of systemic reactions to Hymenoptera sting) in serial sera collected over a course of venom immunotherapy with a mean duration of 54 months. Mean pre-sCD23 and post-sCD23 levels were compared using a Student's two-tailed t test. Results sCD23 levels were found to be unchanged over the course of venom immunotherapy. Conclusions This is the first longitudinal study that has been done. It suggests that while both immunotherapy and sCD23 are known to be involved in the regulations of IgE synthesis in the atopic patient, the immunomodulation seen in venom immunotherapy is not mediated through sCD23 in any simple regulatory manner.

Circulating soluble CD4 (sCD4) levels were measured in 20 patients (11 with the acquired immunodeficiency syndrome [AIDS] and 9 with AIDS-related complex [ARC]) treated with azidothymidine (AZT) and in 12 patients (nine with AIDS and three with ARC) who were in the placebo group. The mean CD4 level in the AZT treatment group at baseline was 41 +/- 12 (SEM) U/ml. After 4 wk of treatment, the mean level decreased to 23 +/- 5; it was 29 +/- 10, 31 +/- 14, and 21 +/- 5 at 8, 12, and 16 wk of therapy, respectively. No significant changes were observed in the placebo group. These results suggest that AZT administration may be associated with reduced sCD4 levels in these patients.

Several members of the seven-transmembrane chemokine receptor family have been shown to serve, with CD4, as coreceptors for entry by human immunodeficiency virus type 1 (HIV-1). While coreceptor usage by HIV-1 primary isolates has been studied by several groups, there is only limited information available concerning coreceptor usage by primary HIV-2 isolates. In this study, we have analyzed coreceptor usage of 15 primary HIV-2 isolates, using lymphocytes from a donor with nonfunctional CCR5 (CCR5 −/−; homozygous 32-bp deletion). Based on the infections of PBMCs, seven of these primary isolates had an absolute requirement for CCR5 expression, whereas the remaining eight exhibited a broader coreceptor usage. All CCR5-requiring isolates were non-syncytium inducing, whereas isolates utilizing multiple coreceptors were syncytium inducing. Blocking experiments using known ligands for chemokine receptors provided indirect evidence for additional coreceptor utilization by primary HIV-2 isolates. Analysis of GHOST4 cell lines expressing various chemokine receptors (CCR1, CCR2b, CCR3, CCR4, CCR5, CXCR4, BONZO, and BOB) further defined specific coreceptor usage of primary HIV-2 isolates. The receptors used included CXCR4, CCR1-5, and the recently described receptors BONZO and BOB. However, the efficiency at which the coreceptors were utilized varied greatly among the various isolates. Analysis of V3 envelope sequences revealed no specific motif that correlated with coreceptor usage. Our data demonstrate that primary HIV-2 isolates are capable of using a broad range of coreceptors for productive infection in vitro. Additionally, our data suggest that expanded coreceptor usage by HIV-2 may correlate with disease progression.

Bronchial asthma is characterized by episodic airway obstruction and associated with wheezing, a bronchodilator response, an elevation in total serum IgE, and atopy. To determine whether asthma is more common in subjects with severe alpha 1-antitrypsin deficiency (alpha 1-ATD) and airway obstruction, we compared 38 patients who had this condition (Group 1) with 22 control patients with chronic obstructive pulmonary disease (COPD) (Group 2) and with five subjects with alpha 1-ATD and normal spirometry (Group 3). Subjects were evaluated with a symptom questionnaire, pulmonary function testing, intradermal allergen testing, and serum IgE measurement. Self-reported wheezing was a common symptom in all patient groups, but attacks of wheezing with dyspnea were significantly more common in Group 1. Of those patients with airway obstruction, more than 50% showed a bronchodilator response whether suffering from alpha 1-ATD or not. Atopy was more common in Group 1 than in Group 2 (48% versus 27%). Mean serum IgE for all groups was similar but significantly greater in patients with atopy. We estimated the prevalence of asthma in the study groups on the basis of the criteria of attacks of wheezing, reversible airway obstruction, atopy, and that increased IgE. The proportion of patients with asthma in Group 1 was significantly greater than that in Group 2 (22% versus 5%, p0.05). Our study shows that with control for the degree of airway obstruction, asthma, as defined, is more common in patients with alpha 1-ATD than in those without it. We suggest that a lack of alpha 1-AT in airways increases the propensity to develop asthma.

Objective:To evaluate the efficacy of Centers for Disease Control and Prevention (CDC)-recommended infection control measures implemented in response to an outbreak of multidrug-resistant (MDR) tuberculosis (TB).Design:Retrospective cohort studies of acquired immunodeficiency syndrome (AIDS) patients and healthcare workers. The study period (January 1989 through September 1992) was divided into period I, before changes in infection control; period II, after aggressive use of administrative controls (eg, rapid placement of TB patients or suspected TB patients in single-patient rooms); and period III, while engineering changes were made (eg, improving ventilation in TB isolation rooms).Setting:A New York City hospital that was the site of one of the first reported outbreaks of MDR-TB among AIDS patients in the United States.Participants:All AIDS patients admitted during periods I and II. Healthcare workers on nine inpatient units with TB patients and six without TB patients.Results:The epidemic (38 patients) waned during period II and only one MDR-TB patient presented during period III. The MDR-TB attack rate among AIDS patients hospitalized on the same ward on the same days as an infectious MDR-TB patient was 8.8% (19 of 216) during period I, decreasing to 2.6% (5 of 193; P= 0.01) during period II. In a small group of healthcare workers with tuberculin skin test data, conversions during periods II through III were higher on wards with than without TB patients (5 of 29 versus 0 of 15; P= 0.15), although the difference was not statistically significant.Conclusions:Transmission of MDR-TB among AIDS patients decreased markedly after enforcement of readily implementable administrative measures, ending the outbreak. However, tuberculin skin-test conversions among healthcare workers may not have been prevented by these measures. CDC guidelines for prevention of nosocomial transmission of TB should be implemented fully at all US hospitals.

Since 1990 several clusters of multidrug-resistant tuberculosis have been identified among hospitalized patients with the acquired immunodeficiency syndrome (AIDS). We investigated one such cluster in a voluntary hospital in New York.We compared exposures among 18 patients with AIDS in whom tuberculosis resistant to isoniazid and streptomycin was diagnosed from January 1989 through April 1990 (the case patients) with exposures among 30 control patients who had AIDS and tuberculosis susceptible to isoniazid, streptomycin, or both. We also compared exposures among the 14 case patients hospitalized during the six months before the diagnosis of tuberculosis (the exposure period) with those among 44 control patients with AIDS matched for duration of hospitalization. Mycobacterium tuberculosis isolates were typed with analysis of restriction-fragment-length polymorphism (RFLP).Case patients with drug-resistant tuberculosis were significantly more likely than controls with drug-susceptible tuberculosis to have been hospitalized during their exposure periods (14 of 18 vs. 10 of 30) (odds ratio, 7.0; 95 percent confidence interval, 1.6 to 36; P = 0.006). Case patients hospitalized during their exposure periods were significantly more likely to have been hospitalized on the same ward as a patient with infectious drug-resistant tuberculosis than were either controls with drug-susceptible tuberculosis hospitalized during their exposure periods or controls matched for duration of hospitalization (13 of 14 vs. 2 of 10 and 23 of 44) (odds ratio, 52; 95 percent confidence interval, 3.1 to 2474; P less than 0.001; and odds ratio, infinity; 95 percent confidence interval, 2.4 to infinity; P = 0.005, respectively). Among those hospitalized on the same ward, the rooms of case patients were closer to that of the nearest patient with infectious tuberculosis than were the rooms of controls matched for duration of hospitalization. M. tuberculosis isolates from 15 of 16 case patients had identical patterns on RFLP analysis. Of 16 patients' rooms tested with air-flow studies, only 1 had the recommended negative-pressure ventilation.Multidrug-resistant tuberculosis is readily transmitted among hospitalized patients with AIDS. Physicians must be alert to this danger and must enforce adherence to the measures recommended to prevent nosocomial transmission of tuberculosis.

Nocardiosis has been increasingly recognized as a serious infection among persons who otherwise appear healthy and among those with underlying chronic disease, neoplasms, and immunosuppression. Nocardial infection as a complication of AIDS has been reported infrequently. Six patients with AIDS and nocardiosis were identified at one New York City hospital from January 1980 through March 1989. Sites of nocardial infection in these patients included the lungs, brain, esophagus, and suprarenal and paraspinal masses. Mycobacteria, fungi, viruses, and bacteria other than Nocardia species caused concomitant infections in three patients. Three patients died of nocardiosis. Because of such factors as the growth properties of Nocardia species, the presence of other organisms, the common use of sulfonamides for treatment of patients with AIDS, and a low index of suspicion among physicians, the incidence of nocardiosis as a complication of AIDS may possibly be underreported. Early recognition of nocardial infection may lead to an improved prognosis.

To determine changes in subsets of CD4 and CD8 in relation to HIV infection and progression to AIDS, we quantitated peripheral blood lymphocytes obtained from 17 heterosexual controls, 22 asymptomatic HIV-seronegative and 18 HIV-seropositive intravenous drug users. 50 patients with AIDS-related complex (ARC), and 9 patients with AIDS using an EPICS "C" flow cytometer by two-color analysis. Both T helper inducer (CD4+ CD45RA-) and suppressor inducer (CD4+ CD45RA+) lymphocytes were decreased significantly in patients with ARC or AIDS. In contrast, T cytotoxic (CD8+ CD11b-) cells were significantly increased and accompanied by a significant decrease in the T suppressor (CD8+ CD11b+) subset in patients with ARC or AIDS. These results suggest that both T helper inducer and T suppressor inducer subsets of the CD4+ population and the T suppressor subset of CD8+ are depleted after HIV infection, while the T cytotoxic subset of CD8+ was increased after HIV infection.

CD4 antigen levels in sera from asymptomatic intravenous drug users and homosexuals and patients with lymphadenopathy, acquired immunodeficiency syndrome-related complex, or acquired immunodeficiency syndrome were quantitated. Like soluble CD8, CD4 antigen levels were elevated in human immunodeficiency virus-seronegative asymptomatic intravenous drug users and homosexuals, probably reflecting infections such as cytomegalovirus, Epstein-Barr virus, and hepatitis B virus infections. The sera from human immunodeficiency virus-seropositive groups of patients with human immunodeficiency virus infection also had elevated levels of CD4 antigen, presumably reflecting infections like cytomegalovirus and human immunodeficiency virus infections.

Circulating HIV P24 antigen, beta 2-microglobulin, neopterin, soluble CD8, soluble interleukin-2 receptor and TNF alpha levels were measured in 20 patients (9 with ARC and 11 with AIDS) treated with azidothymidine (AZT) and in 12 patients (3 with ARC and 9 with AIDS) who were in a placebo group. Mean levels of HIV P24 antigen, beta 2-microglobulin, neopterin and SCD8 decreased significantly (P less than 0.05) after 12 to 16 weeks of AZT administration. SIL-2R and TNF alpha serum levels did not appear to change in association with AZT therapy. No changes were observed in the placebo group except that TNF alpha levels appeared to increase after 12 to 16 weeks. These results suggest that AZT administration may have led to reduced HIV P24 antigen, beta 2-microglobulin, neopterin and SCD8 mean levels in these patients.

Background: We conducted a trial to compare treatment with zidovudine or didanosine in patients with advanced human immunodeficiency virus type 1 (HIV-1) infection who had received little or no previous therapy with zidovudine. Methods: Six hundred seventeen patients with acquired immunodeficiency syndrome (AIDS), advanced AIDS-related complex (CD4 cell count, ≤0.30× 10 9 /L [300/μL]), or asymptomatic HIV (CD4 cell count, ≤0.20× 10 9 /L) received zidovudine, 500 mg/d of didanosine, or 750 mg/d of didanosine in a randomized, double-blind allocation, with cross-over to alternative medication after development of an end point or serious toxic effect. To be eligible, patients must have received either no or up to 16 weeks of zidovudine therapy before entry into the study. Primary end points were development of a new AIDS-defining event or death. Secondary clinical end points were new or recurrent AIDS-defining events, or death, and survival. Results: In the study as a whole, there were no differences in the relative risks (RRs) of the development of end points between treatment groups. However, there was a strong interaction between the relative efficacies of zidovudine and didanosine and previous experience with zidovudine. Among 380 patients with no previous zidovudine therapy, zidovudine was more effective than 750 mg/d of didanosine (RR, 1.43; 90% confidence interval [CI], 1.02 to 2.00), with a similar trend for zidovudine compared with 500 mg/d of didanosine (RR, 1.21; 90% CI, 0.86 to 1.71). However, among 118 patients with more than 8 weeks but no more than 16 weeks of previous zidovudine therapy, 500 mg/d of didanosine was more effective than zidovudine (RR, 0.48; 90% CI, 0.27 to 0.86); there was a similar trend for increased effectiveness of 750 mg/d of didanosine compared with zidovudine (RR, 0.61; 90% CI, 0.36 to 1.03). Among 119 patients who had some but no more than 8 weeks of previous zidovudine therapy, there were no significant differences among the treatment arms. Similar findings were noted in the analysis of the two secondary clinical end points. No significant differences were found in efficacy between the groups receiving 500 and 750 mg/d of didanosine. The major toxic effect associated with zidovudine was hematopoietic (granulocytopenia) and that associated with didanosine was pancreatitis (dosage, 750 mg/d). Conclusions: In patients with advanced HIV disease, zidovudine appears to be more effective than didanosine as initial therapy; however, some patients with advanced HIV disease may benefit from a change to didanosine therapy after as little as 8 to 16 weeks of therapy with zidovudine. (Arch Intern Med. 1995;155:961-974)

The Primary Infection Committee Phase l/II Studies Working Group of the AIDS Clinical Trials Group has authored a working document entitled “Recommended Guidelines for the Phase I/II Study of Drug X in HIV Infected Patients.” The guidelines represent the evolving consensus on optimal Phase I Clinical Trial design for agents directed against Human lmmunodeficiency Virus-l (HIV-l) in adult patients. Three sequential Phase I stages should efficiently yield data necessary to guide subsequent decisions on drug development. Phase I-A studies are single administration, dose ranging studies to determine preliminary safety and pharmacokinetic parameters in human subjects. Phase I-B studies are multiple administration, dose escalation trials of at least 8 weeks per cohort designed to bracket a range of tolerated as well as biologically active dose regimens. Phase I-C/IIA trials entail randomization to 2 2 tolerated and active dosages from a Phase I-B study in order to choose a dose regimen with the best therapeutic index for further comparative efficacy evaluation. Randomization at this phase is recommended to overcome disparities seen between group characteristics in sequential Phase I enrollment. Sample sizes for Phase I-B trials are based on demonstration of anti-HIV activity (e.g. reduction in HIV-l p24 antigen) in a sufficient proportion per group so as to significantly exceed the background level of variability seen in untreated controls from other ACTG studies. Thus, of 8 to 10 patients per dose groups, z 6 would be required to be p24 Ag positive at entry. Sample sizes in Phase I-B are sufficient for enumerating the most serious toxicities which would define the maximally tolerated dose. In Phase I-B and I-C trials, extended dosing of the tolerated and antivirally active arms would be offered to patients in order to gain valuable information on long-term toxicity and duration of activity early in a given agents development. The consensus guidelines will be periodically modified as new anti-HIV agents and biological assays enter clinical trials.

T cell subpopulations as defined by E rosette formation and Fc receptors for immunoglobulins were determined, using ox red blood cells coated with the IgG or IgM fraction of rabbit anti-ox red blood cells antibody to form rosettes with the peripheral blood lymphocytes of 18 pregnant females and 12 healthy non-pregnant females. It was shown that the TG cell population in the pregnant females is significantly increased as compared to those in the nonpregnant controls (mean ± SEM %TG cells: 18 ± 1.2 vs. 9.6 ± 0.7; p < 0.001). By using peripheral blood from normal nonpregnant subjects it was also shown that To cells suppressed one-way mixed lymphocyte reactions (mean ± SEM suppression: 23 ± 7.2; p < 0.01). These findings suggest that the TG cell population may exert a suppressor function on the immune response to alloantigens and act in concert with other humoral factors to protect the fetus from rejection.

The purpose of this study was to determine if clinically effective serum levels of theophylline have an inhibitory effect on intradermal tests for allergic hypersensitivity. Intradermal testing using the threshold-dilution technique was performed in 9 patients, 7 of whom were sensitive to 2 antigens. Testing was performed over a 6-hour period after theophylline administration and compared with the control results. Inhibition of the end-point was demonstrated with 12 of 16 antigens tested associated with serum theophylline levels ranging from 7 to 20 μg/ml. Marked inhibition of the intradermal tests, that might have clinical significance, only occurred with 4 antigens.

We examined the long-term safety and efficacy of zidovudine therapy in 229 subjects with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex who previously participated in a placebo-controlled study of zidovudine. One hundred two placebo recipients (delayed treatment group) and 127 zidovudine recipients (original treatment group) were followed up while receiving zidovudine therapy for a mean of 21 months. Survival rates for the original treatment group were 84.5% and 57.6% at 12 and 21 months, respectively; for the delayed treatment group, 78.8% and 64.6% at 12 and 21 months, respectively, and 78.8% and 47.5% at 12 and 21 months, respectively, for 77 subjects with AIDS and 93.0% and 71.8%, respectively, for 50 subjects with AIDS-related complex in the original treatment group. Adverse reactions decreased over time and newly observed toxic reactions were unusual. The clinical course of these subjects suggests continued survival benefits with long-term zidovudine therapy.

For a period of over two years 99 volunteer healthy homosexual men were examined periodically for the presence of interferon (IFN) in their serum. Thirty-nine subjects had either undetectable IFN levels in serum or IFN was detected only once in three to five samples tested. In another 45 subjects low IFN levels were detected throughout the study period. None of these subjects had or developed any disease symptoms. In the remaining 15 subjects high serum IFN levels were detected at their enrollment or during the study period. All these subjects started to manifest clinical symptoms compatible with AIDS. In six subjects the mean time elapsed between the first detection of serum IFN and disease symptoms was 6.5 months. In all subjects but one, the IFN was of type alpha. The acid-stability of serum IFN alpha decreased with time, and when its decrease was abrupt it was associated with a more rapid evolution of AIDS. Sera containing acid-labile IFN alpha can induce IFN alpha synthesis in normal lymphocyte cultures (LC), but do not influence IFN gamma synthesis in LC stimulated with phytohemagglutinin. LC stimulated with viral antigens in the presence of serum with acid-labile IFN alpha synthesized IFN with an increased sensitivity for acid treatment. The results confirm the prognostic value of serum IFN alpha in the development of AIDS, and suggest that the transition to acid-lability may be a gradual process.

A monoclonal antibody (anti-Tac) that appears to bind the receptor for interleukin-2 (IL-2) was used to quantitate lymphocytes that express IL-2 receptors (IL-2R) in response to phytohemagglutinin (PHA) stimulation. 62 +/- 4% of the cells expressed IL-2R in response to PHA in twelve normal subjects compared to 22 +/- 4% in fourteen patients with acquired immune deficiency syndrome (AIDS) (P less than 0.001) and 50 +/- 6% in six patients with AIDS-related complex (P less than 0.1). There was no effect on IL-2R expression, when lymphocytes from seven controls were incubated with IL-2 (20 mu/ml) or thymosin fraction V (10 mu/ml) for 72 h. However, when the lymphocytes from seven patients with AIDS were incubated with IL-2, the IL-2R rose from 18 +/- 3% to 31 +/- 3% (P less than 0.005) and with a fraction V to 29 +/- 3% (P less than 0.001). In addition, IL-2 augmented the PHA-induced proliferative responses in patients with AIDS-related complex and AIDS and normal controls, whereas thymosin fraction V had no significant effect. Thymosin fraction V also enhanced the IL-2 production of PHA-stimulated mononuclear cells obtained from six patients with AIDS and six normal controls. These results suggest that both IL-2 and thymosin fraction V can modulate in vitro T-cell function in patients with AIDS.

Corticosteroids, known to enhance susceptibility to infection, are used therapeutically for their anti-inflammatory properties in a variety of infectious diseases. The paradox is more apparent than real.

A 44 yr-old woman with non-A, non-B hepatitis developed agranulocytosis and absence of marrow granulocyte precursor cells with only mild involvement of other blood elements. The agranulocytosis was complicated by gram-negative septicemia, successfully treated with antibiotic therapy. Marrow recovery followed 2 wk of supportive therapy. Before reversal of the agranulocytosis, a future bone marrow transplant was a consideration, making the use of therapeutic granulocyte transfusions, with their ability to sensitize the recipient, potentially harmful. Experience in this case indicates that agranulocytosis associated with non-A, non-B hepatitis may be reversible, and supports the use of supportive care including appropriate antibiotics, and if necessary, granulocyte transfusions, pending marrow recovery.

The effect of indomethacin on mitogen-induced lymphocyte proliferative responses was studied in six normal heterosexual subjects and nine patients with the acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC). Indomethacin enhanced only Con A-induced lymphocyte responses in six heterosexual men. In contrast, study of the cells from AIDS and ARC revealed that indomethacin enhanced PHA-induced lymphocyte proliferative responses from 52,600 counts/min to 70,900 counts/min (P less than 0.005) and 81,400 counts/min (P less than 0.001) at 0.1 and 1 microgram/ml. respectively and increased Con A-induced lymphoproliferation from 30,800 counts/min to 52,000 counts/min (P less than 0.01) at 0.1 microgram/mg and 51,1000 counts/min (P less than 0.005) at 1 microgram/ml. These results suggest that indomethacin enhanced mitogen-induced lymphoproliferative responses in vitro with cells from patients with AIDS and AIDS-related complex and may have therapeutic potential in some patients with AIDS.

In a double-blind, randomized study, 93 corticosteriod-independent patients with chronic bronchial asthma were treated with either beclomethasone dipropionate aerosol at 400 μg per day or its vehicle for 4 wk to determine and compare the effectiveness and safety of the preparations. Evaluations made before, at weekly intervals during, and 1 wk after treatment indicated that beclomethasone dipropionate aerosol was superior to its vehicle in improving FVC, FEV 1 , FEF 25%–75% , and clinical signs and symptoms, and in the overall evaluations by both the investigators and the patients. Plasma cortisol levels measured at the end of the second and fourth weeks were not substantially different from those before treatment in either group. No significant side effects or abnormalities in laboratory results were noted.

Peripheral blood lymphocytes from six healthy control subjects were incubated in vitro with fetuin and enumerated for sheep erythrocyte rosette forming T cells. Significant enhancement of rosette-forming T lymphocytes was observed in a dose-related manner. The physical presence of fetuin is not required for this effect. Incubation of lymphocytes with human AB serum has no significant effect on the rosette formation. This enhancing effect of fetuin appears to be secondary to alteration in T lymphocyte surface receptors for sheep erythrocytes.

Rosettes formed by circulating T and B lymphocytes obtained from 23 healthy, chronic marihuana smokers were compared with those in 23 normal control subjects who denied marihuana use. The mean percentage of T cells forming rosettes was lower in the marihuana smokers (p < 0.005). Nine of 23, or 39 per cent, had T-cell rosette formation lower than 2 standard deviations below the mean for control subjects. The percentages of B-cell rosettes were similar in both marihuana smokers and the controls. This study suggests suppression of a T-lymphocyte subpopulation in chronic marihuana smokers. (N Engl J Med 291:874–877, 1974)