Cyclotron production and radiochemical separation of 55Co and 58mCo from 54Fe, 58Ni and 57Fe targets.

This work presents the production with a cyclotron of the positron emitter 55Co via the 54Fe(d,n) and 58Ni(p,α) reactions and the Auger electron emitter 58mCo via the 57Fe(d,n) reaction after high current (40µA p and 60µA d) irradiation on electroplated targets. High specific activity radionuclides (up to 55.6 GBq/µmol 55Co and 31.8GBq/µmol 58mCo) with high radionuclidic purity (99.995% 55Co from 54Fe, 98.8% 55Co from 58Ni, and 98.7% 58mCo from 57Fe at end of bombardment, EoB), in high activity concentration (final separated radionuclide in < 0.6mL) and with almost quantitative overall activity separation yield (> 92%) were obtained after processing of the irradiated targets with novel radiochemical separation methods based on HCl dissolution and the resin N,N,N',N'-tetrakis-2-ethylhexyldiglycolamide (DGA, branched). One hour long irradiations using 38-65, 110-214 and 59-78mg of enriched 54Fe (99.93%), 58Ni (99.48%) and 57Fe (95.06%), respectively, electroplated over a 1.0cm2 surface, yielded 582 ± 66MBq 55Co, 372 ± 14MBq 55Co and 810 ± 186MBq 58mCo, respectively, decay corrected to EoB. The separation methods allow for the recovery of the costly enriched target materials, which were reconstituted into metallic targets after novel electroplating methods, with an overall recycling efficiency of 93 ± 4% for iron. The produced radionuclides were used to radiolabel the angiogenesis marker antibody TRC105 conjugated to the chelator NOTA as a demonstration of their quality.

Endoglin targeting inhibits tumor angiogenesis and metastatic spread in breast cancer.

Endoglin, a transforming growth factor-ß co-receptor, is highly expressed on angiogenic endothelial cells in solid tumors. Therefore, targeting endoglin is currently being explored in clinical trials for anti-angiogenic therapy. In this project, the redundancy between endoglin and vascular endothelial growth factor (VEGF) signaling in angiogenesis and the effects of targeting both pathways on breast cancer metastasis were explored. In patient samples, increased endoglin signaling after VEGF inhibition was observed. In vitro TRC105, an endoglin-neutralizing antibody, increased VEGF signaling in endothelial cells. Moreover, combined targeting of the endoglin and VEGF pathway, with the VEGF receptor kinase inhibitor SU5416, increased antiangiogenic effects in vitro and in a zebrafish angiogenesis model. Next, in a mouse model for invasive lobular breast cancer, the effects of TRC105 and SU5416 on tumor growth and metastasis were explored. Although TRC105 and SU5416 decreased tumor vascular density, tumor volume was unaffected. Strikingly, in mice treated with TRC105, or TRC105 and SU5416 combined, a strong inhibition in the number of metastases was seen. Moreover, upon resection of the primary tumor, strong inhibition of metastatic spread by TRC105 was observed in an adjuvant setting. To confirm these data, we assessed the effects of endoglin-Fc (an endoglin ligand trap) on metastasis formation. Similar to treatment with TRC105 in the resection model, endoglin-Fc-expressing tumors showed strong inhibition of distant metastases. These results show, for the first time, that targeting endoglin, either with neutralizing antibodies or a ligand trap, strongly inhibits metastatic spread of breast cancer in vivo.

The role of oral contrast administration immediately prior to the computed tomographic evaluation of the blunt trauma victim.

BACKGROUND: It is unclear whether the administration of oral contrast followed by immediate computerised tomographic (CT) scanning presents a significant risk of aspiration and whether it is useful in the diagnosis of hollow viscus injury. OBJECTIVE: Determine the number of intestinal perforations diagnosed by oral contrast enhanced CT scans for blunt trauma and identify those who developed aspiration pneumonitis causally related to oral contrast administration. METHODS: We analysed a database of consecutive blunt trauma admissions over a 2-year period. The majority received oral contrast immediately prior to CT scanning. We determined the number of intestinal perforations identified by abdominal CT confirmed at laparatomy and the number of cases of aspiration pneumonia. RESULTS: Nine (1%) of the 1173 CT scans identified enteric perforations. Oral contrast enhanced CT scans demonstrated pneumoperitoneum (3), extraluminal contrast extravasation (2), and the presence of free fluid with small bowel wall thickening (8). In this same cohort, eight (0.7%) cases of aspiration pneumonia were diagnosed within 48 h of admission in patients with a mean GCS of 4.25; only one (0.1%) was temporally related to oral contrast administration. In a prospective study, none of the 65 consecutive patients who received oral contrast had witnessed aspiration. CONCLUSIONS: Oral contrast administration given immediately prior to CT scanning does not increase the risk of clinically significant aspiration and assists in the detection of enteric perforation.

Racial and ethnic colorectal cancer patterns affect the cost-effectiveness of colorectal cancer screening in the United States.

BACKGROUND & AIMS: Colorectal cancer screening beginning at age 50 is recommended for all Americans considered at "average" risk for the development of colorectal cancer. METHODS: We used 1988-1995 California Cancer Registry data to compare the cost-effectiveness of two 35-year colorectal cancer screening interventions among Asians, blacks, Latinos, and Whites. RESULTS: Average annual age-specific colorectal cancer incidence rates were highest in blacks and lowest in Latinos. Screening beginning at age 50 was most cost-effective in blacks and least cost-effective in Latinos (measured as dollars spent per year of life saved), using annual fecal occult blood testing (FOBT) combined with flexible sigmoidoscopy every 5 years and using colonoscopy every 10 years. A 35-year screening program beginning in blacks at age 42, whites at age 44, or Asians at age 46 was more cost-effective than screening Latinos beginning at age 50. CONCLUSIONS: Colorectal cancer screening programs beginning at age 50, using either FOBT and flexible sigmoidoscopy or colonoscopy in each racial or ethnic group, are within the $40,000-$60,000 per year of life saved upper cost limit considered acceptable for preventive strategies. Screening is most cost-effective in blacks because of high age-specific colorectal cancer incidence rates.

The topography of colorectal cancer varies by race/ethnicity and affects the utility of flexible sigmoidoscopy.

Colorectal cancer screening beginning at age 50 is recommended for all Americans considered at "average" risk for the development of colorectal cancer either with flexible sigmoidoscopy and fecal occult blood testing (FOBT) or with colonoscopy. Patients who elect flexible sigmoidoscopy and FOBT undergo full colonoscopy only if left-sided neoplasia is detected or if the FOBT is positive. Unfortunately in blacks and whites most right-sided colorectal lesions are unaccompanied by left-sided sentinel lesions, which leads some to prefer colonoscopic screening in these patients. The topography of colorectal cancer in Asians and Latinos is unavailable. We used 1988-1995 California Cancer Registry data to determine the topography of 105,906 consecutive colorectal cancers among Asian, black, Latino, and white patients. We found that the proportion of colorectal cancer distal to the splenic flexure and therefore detectable by flexible sigmoidoscopy varied by ethnicity: Asian (71%) > Latino (63%) > white (57%) > black (55%); P < 0.001. These differences were significant after adjusting for age and sex. The risk of distal disease relative to whites was 1.61 in Asians, 1.15 in Latinos, and 0.82 in blacks (P < 0.001). Flexible sigmoidoscopy detects a higher proportion of colorectal cancers in Asians and Latinos than in whites or blacks. Further study is needed to assess whether the topography of benign colorectal neoplasia parallels that of malignant disease. Colorectal screening recommendations may need to incorporate racial and ethnic differences in colorectal neoplasia topography.

Asian patients with gastric carcinoma in the United States exhibit unique clinical features and superior overall and cancer specific survival rates.

BACKGROUND: The 5-year survival rate from gastric carcinoma, stratified by stage, is markedly greater in the Far East than in the United States. This survival rate advantage may reflect differences in diagnostic criteria, more complete staging, more radical surgery, or less aggressive tumor biology. METHODS: A historic cohort of consecutive cases of gastric carcinoma reported to the population-based California Cancer Registries of Orange, San Diego and Imperial Counties from 1984 to 1996 was studied. Factors associated with Asian race were profiled using logistic regression. Multivariate survival analyses were performed using a Cox proportional hazard model. RESULTS: Two thousand four hundred sixteen patients (64%) were non-Latino white; 690 (18%) were Latino; 94 (2.5%) were black; 541 (14%) were of Asian descent: Korean (22%), Vietnamese (20%), Japanese (20%), Chinese (14%), and Filipino (12%). Asian patients were more likely to have localized (lymph node negative) disease (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.23-2.10), less likely to have tumors of the gastroesophageal junction (OR, 0.22; 95% CI, 0.15-0.31,), and less likely to be older than 50 years (OR, 0.58; 95% CI, 0.43-0.77). Asian patients with gastric carcinoma were twice as likely as non-Latino whites to be alive at 5 years (20.9% vs. 10.2%; P < 0.0001). Multivariate analyses indicated that whites had an increased risk of dying from all causes (relative risk [RR], 1.34; 95% CI, 1.16-1.55; P < 0.01) and of dying from cancer in comparison to Asian patients (RR, 1.26; 95% CI, 1.07-1.48; P < 0.05). CONCLUSIONS: Asians who received a diagnosis of gastric carcinoma in the United States have less advanced disease than non-Asians. The increased proportion of localized disease and improved survival rates of patients of Asian descent in the United States is consistent with less aggressive tumor biology.

Asian gastric cancer patients at a southern California comprehensive cancer center are diagnosed with less advanced disease and have superior stage-stratified survival.

The 5-year overall survival after curative gastrectomy for gastric cancer is markedly different in the West from that in the Far East. Japanese surgeons feel that extended lymphadenectomy contributes to this superior survival, although survival differences may reflect improved staging or less aggressive tumor biology. We analyzed consecutive cases of gastric adenocarcinoma diagnosed and treated at the University of California, Irvine Medical Center from 1989 through 1998 to determine whether patients of Asian descent diagnosed with gastric cancer in Southern California have improved outcome. Fifty-two cases (36%) occurred in patients of Asian descent (39% Vietnamese, 31% Chinese, 13% Korean, 6% Filipino, and 2% Japanese). Only one Asian patient was born in the United States. Non-Asian patients (67% white, 30% Latino, and 3% black) were younger (59 years vs 64 years; P < 0.05) and more likely to have tumors of the gastroesophageal junction (33% vs 4%; P < 0.001). Asian patients were less likely to have distant metastases (24% vs 39%; P = 0.08), were more likely to undergo formal gastrectomy (71% vs 45%; P < 0.01), and were more likely to undergo a curative resection (40% vs 18%; P < 0.01). The overall survival of Asian patients at 3 years was significantly higher than the overall survival of non-Asians (39.4% vs 19.6%, P < 0.05). Asians with regional (node-positive) disease had superior survival (40.2% vs 14.8%, P < 0.05), which can be largely attributed to greater rates of resectability. We conclude that the clinical behavior of gastric cancer in Asians in Southern California differs from that in non-Asians. The increased proportion of resectable disease and improved survival of patients of Asian descent likely reflects less aggressive tumor biology.

Signet ring cell histology is associated with unique clinical features but does not affect gastric cancer survival.

Signet ring cell histology is found in 3 to 39 per cent of gastric cancer cases and has been reported to be a feature of poor prognosis, although this issue has not been rigorously examined. The objective of this study was to determine those demographic and clinical variables associated with signet ring cell histology and to determine the effect of signet ring cell histology on survival using multivariate analyses. We studied a historical cohort of consecutive cases of gastric cancer reported to the population-based California Cancer Registries of Orange, San Diego, and Imperial Counties from 1984 through 1994. Factors associated with signet ring cell histology were assessed using chi2 and logistic regression. Life tables were constructed to assess unadjusted survival and survival differences in patient subgroups. Multivariate survival was determined using a Cox proportional hazards model. Of 3020 patients, 464 (15%) had signet ring cell histology. Patients with signet ring cell histology were more likely to be younger than 50 years (odds ratio (OR) = 2.4; 95% confidence interval (CI) = 1.6-3.5), less likely to be male (OR = 0.49; 95% CI = 0.37-0.66), and more likely to have tumors of the distal stomach (OR = 2.0; 95% CI = 1.4-3.0). Signet ring cell histology did not adversely affect unadjusted overall survival, race-stratified survival, or stage-stratified survival. Multivariate analysis indicated that patients with signet ring cell histology had an insignificant increased risk of dying (relative risk = 1.027; P>0.10) in comparison with patients without signet ring cell histology. Patients with signet ring cell histology were more likely to be young women and to have tumors of the distal stomach. Signet ring cell histology did not impact survival in our group of largely advanced gastric cancer cases.

Unique features of gastric carcinoma in the young: a population-based analysis.

BACKGROUND: It is suspected that young patients with adenocarcinoma have a more aggressive form of disease and therefore a poorer prognosis than older patients. METHODS: A retrospective cohort study used the population-based tumor registries of Orange, San Diego, and Imperial Counties. Cases (patients age < or =40 years with gastric carcinoma) were compared with controls (patients age >40 years with gastric carcinoma). RESULTS: The overall, age-adjusted incidence rate of gastric carcinoma was 10.2/100,000. Approximately 5.5% of 3,020 cases occurred in patients age <41 years. Young patients (especially whites and Latinos) were more likely to have distant metastases [45% versus 34%; odds ratio (OR)=2.6; 95% confidence interval (CI), 1.4-4.8; P < 0.001]. The histology of young patients (especially Latinos and Asians) was more likely to be signet ring cell (28% versus 15%; OR=2.3; 95% CI, 1.6-3.3; P < 0.001), and the grade of young patients (especially whites and Latinos) was more likely to be Grade 3 or 4 (according to the World Health Organization International Classification of Diseases for Oncology; 68% versus 56%; OR=2.1; 95% CI, 1.4-3.3; P < 0.001). The tumors of young patients (especially Asians) were less likely to be of the gastroesophageal junction (16% versus 27%; OR=0.47; 95% CI, 0.31-0.72; P < 0.001) and of the antrum (17% versus 22%; OR=0.62; 95% CI, 0.41-0.95; P=0.03) than the gastric body. Younger patients were more likely to receive chemotherapy (50% versus 28%; OR=2.7; 95% CI, 1.9-3.7; P < 0.001). Only patients age >70 years had an independent increased risk of dying from all causes in comparison with young patients (relative risk 1.46; P=0.01). CONCLUSIONS: Young gastric carcinoma patients have adverse clinical and pathologic features in comparison with older patients. In this study, young age was not found to be an independent predictor of overall survival.

Gastric adenocarcinoma in patients 40 years of age or younger.

BACKGROUND: Gastric adenocarcinoma is considered a disease of the middle aged and elderly and has been infrequently reported in patients under 40 years of age. The purpose of this study was to determine the proportion of young patients diagnosed with gastric adenocarcinoma and to compare the demographic, clinical and pathologic features of younger and older patients with gastric adenocarcinoma. METHODS: A retrospective cohort study using tumor registry records of all patients with gastric adenocarcinoma diagnosed from 1982 through 1996 at a public teaching hospital. Demographic, clinical, and pathologic comparisons were made between patients younger than 41 years of age and race- and sex-matched older patients with gastric adenocarcinoma. RESULTS: Thirty of 203 (15%) cases of gastric adenocarcinoma were diagnosed in patients less than 41 years (range 23 to 40). Male to female ratio was 1:1. Young patients were more likely to be black (33% versus 17%, P = 0.04) Both younger and older patients presented with advanced disease, with nearly half of each group having metastases. Twelve of 29 (41%) younger patients were operated on without a histologic diagnosis of gastric adenocarcinoma in contrast to only 1 older patient (P < 0.001). One of 30 (3%) young patients is alive 39 months following gastrectomy. Twenty patients died and the remaining 9 were lost to follow-up, all with known residual or recurrent disease. Six-month survival of young patients (23%) was less than older patients (42%) (P = 0.14). Young patients were more likely to have diffuse histology (80% versus 55%, P = 0.12). Overt infection with Helicobacter pylori was uncommon in both groups. CONCLUSIONS: Young patients accounted for an unusually high proportion of patients with gastric adenocarcinoma diagnosed at our public teaching hospital. Young patients were significantly more likely to be black and less likely to have an accurate preoperative histologic diagnosis. Both young and older patients presented with advanced disease and had poor survival. Young patients were more likely to have diffuse histology and had poorer 6-month survival, suggesting a more aggressive variety of the disease in this group.

Immunotoxins and recombinant toxins in the treatment of solid carcinomas.

Cancer remains the second most common cause of death in our society, and advanced disease is often refractory to surgical, chemotherapeutic, and radiologic interventions. One novel approach to cancer treatment involves targeting a cytotoxic agent to a cancer cell. Immunotoxins have been developed that contain a potent toxin (either Pseudomonas exotoxin, ricin toxin, or diphtheria toxin) coupled to a targeting moiety that directs the molecule to cells expressing a certain antigen. Chemically coupled immunotoxins have been developed over the past 12 years. These bind to and kill cells expressing many tumor-associated antigens. Initial clinical results were disappointing, but recent results have been more promising. Furthermore, newer immunotoxins have been developed that will soon be in clinical trials. Some of these are recombinant toxins that have been developed using techniques of genetic engineering. Transforming growth factor-alpha, acidic fibroblast growth factor, insulin-like growth factor-1, interleukin-2, interleukin-4, interleukin-6, the binding portions of monoclonal antibodies, and CD4 have been used to direct toxins to cancer cells or cells infected with the human immunodeficiency virus type 1. Efforts are under way to circumvent problems such as immunogenicity that may limit the clinical usefulness of immunotoxins.

The N-terminal region of the 37-kDa translocated fragment of Pseudomonas exotoxin A aborts translocation by promoting its own export after microsomal membrane insertion.

The 37-kDa C-terminal fragment of Pseudomonas exotoxin A (PE; termed PE37 and composed of aa 280-613 of PE) translocates to the cell cytosol to cause cell death. PE37 requires a C-terminal endoplasmic reticulum retention sequence to be cytotoxic, indicating that the toxin may translocate to the cytosol from the endoplasmic reticulum. We show here that the N-terminal region of nascent PE37 can be inserted into the membrane of canine pancreatic microsomes by the preprocecropin signal sequence but then is exported or released from microsomes. The 34 N-terminal amino acids of the toxin fragment are sufficient to arrest translocation and prevent the microsomal accumulation of nascent chains that otherwise are sequestered into microsomes. These data support a role for the N-terminal region of PE37 in the translocation of the toxin from the endoplasmic reticulum to the cytosol in mammalian cells.

A recombinant form of Pseudomonas exotoxin A containing transforming growth factor alpha near its carboxyl terminus for the treatment of bladder cancer.

The epidermal growth factor receptor (EGFR) is overexpressed on the superficial layers of malignant urothelium and is suspected of playing a role in tumor progression. TP40 is a chimeric protein composed of transforming growth factor-alpha (TGF alpha) fused to a modified form of Pseudomonas exotoxin A (PE) that is selectively cytotoxic to EGFR-bearing cells and is currently undergoing clinical study for the intravesical therapy of bladder cancer. We constructed a recombinant toxin PE35/TGF alpha-KDEL as an improved agent for the local therapy of EGFR-bearing bladder cancer. PE35/TGF alpha-KDEL does not require intracellular proteolysis to generate a carboxyl-terminal fragment capable of reaching the target cell cytosol and contains a modified carboxyl-terminal sequence KDEL, that increases toxin activity. These features make PE35/TGF alpha-KDEL from 10- to 700-fold more potent than TP40 on four human bladder cancer cell lines. PE35/TGF alpha-KDEL may be a useful agent for treatment of EGFR-bearing cancers.

Immunotoxins made with a recombinant form of Pseudomonas exotoxin A that do not require proteolysis for activity.

We used recombinant DNA technology to construct a mutant form of Pseudomonas exotoxin A (PE) called cysPE35 that contains amino acids 280-364 and 381-613 of PE. cysPE35 begins at the native PE proteolytic cleavage site and contains a single cysteine residue at position 287 that can be used to conjugate the toxin to monoclonal antibodies (MAbs). Unlike immunotoxins containing larger mutant forms of PE, such as PE40 or PE38, immunotoxins containing cysPE35 linked through a disulfide bond do not require proteolysis to generate a toxin fragment able to translocate to the cytosol. cysPE35 was conjugated to several MAbs and their activities were studied in vitro and in vivo. The concentration of toxin that inhibited protein synthesis as measured by a decrease in [3H]leucine incorporation of 50% of cysPE35 conjugated through a disulfide bond to the MAb HB21, which targets the human transferrin receptor, was 1 ng/ml on A431 cells. The MAb HB21 conjugated through a thioether bond to cysPE35 was much less active (concentration of toxin that inhibited protein synthesis as measured by a decrease in [3H]leucine incorporation of 50%, 200 ng/ml). An immunotoxin containing PE38 conjugated through either a disulfide or thioether bond to the MAb HB21 had a concentration of toxin that inhibited protein synthesis as measured by a decrease in [3H]leucine incorporation of 50% of 5 ng/ml, indicating that proteolysis of PE38 may be rate limiting in the action of these immunotoxins. Two other MAbs, LL2 and B3, were also conjugated through a disulfide bond to cysPE35. Both immunotoxins were also more active against cultured cells than conjugates using PE38 or PE40, and caused complete regression of human tumor xenografts growing in nude mice. In conclusion, we have constructed a mutant form of PE which must be coupled to MAbs through a disulfide bond to produce fully active immunotoxins that do not require proteolysis to generate a toxin fragment able to reach the cell cytosol.

A recombinant form of Pseudomonas exotoxin directed at the epidermal growth factor receptor that is cytotoxic without requiring proteolytic processing.

Pseudomonas exotoxin A is composed of three structural domains that mediate cell recognition (I), membrane translocation (II), and ADP-ribosylation (III). Within the cell, the toxin is cleaved within domain II to produce a 37-kDa carboxyl-terminal fragment, containing amino acids 280-613, which is translocated to the cytosol and causes cell death. In this study, we constructed a mutant protein (PE37), composed of amino acids 280-613 of Pseudomonas exotoxin A, which does not require proteolysis to translocate. PE37 was targeted specifically to cells with epidermal growth factor receptors by inserting transforming growth factor-alpha (TGF-alpha) after amino acid 607 near the carboxyl terminus of Pseudomonas exotoxin A. PE37/TGF-alpha was very cytotoxic to cells with epidermal growth factor receptors. It was severalfold more cytotoxic than a derivative of full-length Pseudomonas exotoxin A containing TGF-alpha in the same position, probably because the latter requires intracellular proteolytic processing to exhibit its cytotoxicity, and proteolytic processing is not 100% efficient. Deletion of 2, 4, or 7 amino acids from the amino terminus of PE37/TGF-alpha greatly diminished cytotoxic activity, indicating the need for a proper amino-terminal sequence. In addition, a mutant containing an internal deletion of amino acids 314-380 was minimally active, indicating that other regions of domain II are also required for the cytotoxic activity of Pseudomonas exotoxin A.

Are blood cultures effective in the evaluation of fever in perioperative patients?

Blood cultures are routinely performed as part of the evaluation of fever in the perioperative period. Results of 364 blood culture vials representing 108 consecutive febrile events (temperature greater than or equal to 101.5 degrees F) in 72 patients on adult surgical services without evidence of sepsis in a metropolitan hospital were prospectively studied. Eighty-nine percent of patients had undergone an operation prior to the febrile episode. Microorganisms were isolated in blood culture vials from 9 of 108 patient febrile events. Of these blood cultures, five were positive (contained pathogens), and four represented contaminants. Two of five positive blood cultures occurred in patients with an identifiable source of bacteremia. The cost of processing all blood culture vials was $13,992, which amounted to $2,798 spent to identify each of the five patients with positive blood cultures. Blood culture vials were more likely to be positive if blood was drawn during postoperative days 4 through 10, as opposed to days 1 through 3, or if it was drawn from patients with factors depressing immune function or who had indwelling devices. Neither the magnitude of the absolute leukocyte count nor the maximum temperature at the time of phlebotomy predicted a positive blood culture. The use of resin vials produced sterile cultures in the 10 vials submitted. In no case did a positive blood culture have a measurable effect on reducing patient morbidity or mortality.

Human immunodeficiency virus infection in tuberculosis patients.

Human immunodeficiency virus (HIV) serology was performed in non-Asian-born patients 18-65 years old with newly diagnosed tuberculosis at a county tuberculosis clinic, and demographic and clinical features of HIV-seropositive and HIV-seronegative patients were compared. Sixty of 128 eligible patients agreed to participate, of whom 17 (28%) were seropositive. Risk of HIV was associated with homosexual contact, intravenous drug use, or both; however, 4 (24%) of the 17 seropositives denied risk behaviors. Significantly more blacks (48%) than whites (10%) or Latinos (20%) were HIV-seropositive (P less than .01). Site of disease, tuberculin reactivity, response to therapy, drug toxicity, and relapse did not differ significantly between groups. HIV-seropositive patients had significantly lower median CD4+ cell counts (326/mm3, range 23-742/mm3, vs. 929/mm3, range 145-2962/mm3, P less than .0005) and median CD4+:CD8+ ratios (0.50, range 0.14-1.07 vs. 1.54, range 0.35-4.36, P less than .0001). HIV infection is associated with clinically typical tuberculosis and HIV screening of tuberculosis patients is recommended in areas where HIV is endemic.