TNF, soluble IL-2R and soluble CD-8 in Behçet's disease.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R Lawrence.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A randomized prospective clinical trial was carried out to assess the usefulness of the addition of mitomycin C to radiation therapy used alone or in combination with surgery for the treatment of squamous cell carcinoma of the head and neck region. One hundred and twenty patients with biopsy proven tumor of the oral cavity, oropharynx, larynx, hypopharynx, and nasopharynx were randomly assigned to receive or not receive mitomycin C; all other aspects were similar in the two treatment groups. One hundred and seventeen patients were evaluable with a median follow-up time of greater than 5 years. Acute and chronic normal tissue radiation reactions were equivalent in the two treatment groups. Hematologic and pulmonary toxicity were observed in the drug treated patients. Actuarial disease-free survival at 5 years was 49% in the radiation therapy group and 75% in the radiation therapy plus mitomycin C group, p less than 0.07. Local recurrence-free survival was 66% in the radiation therapy group and 87% in the radiation therapy plus mitomycin C group, p less than 0.02. The findings demonstrate that mitomycin C can be administered safely as an adjunct to radiation therapy in the treatment of head and neck cancer. The drug improves local tumor control without enhancing normal tissue radiation reactions.
Human immunodeficiency virus type 1 (HIV-1) core antigen was assayed in the plasma of children at risk for infection with HIV to determine its usefulness in the diagnosis of infection and to correlate it with the clinical stage of disease. Antigen was detected in the plasma of all children less than 15 months of age with acquired immunodeficiency syndrome (AIDS). Two thirds of children with AIDS-related illnesses and half of children with asymptomatic infection had antigen. Although 53% of plasma specimens originating from HIV-infected children younger than 6 months of age contained antigen, only 25% of plasma specimens from children younger than 6 months who had no symptoms and none of the 10 specimens from HIV-infected newborn infants contained antigen. Half of the specimens containing core antigen also contained anticore antibody. Quantitative mean antigen levels were more likely to be elevated in children with AIDS (516 pg/ml) than in children with AIDS-related illnesses (295 pg/ml) or in those who had no symptoms (70 pg/ml). Antigen levels tended to increase over time in children with advancing clinical illness, but they tended to decrease over time after a diagnosis of AIDS was made. Antigen was detected in the plasma of 4 of 14 children without symptoms who subsequently reverted to an HIV seronegative state. We conclude that the detection of core antigen occurs with high frequency in children, even young infants, with symptomatic HIV infection. Plasma core antigen was less frequent in children without symptoms and was not detected in 10 infected children when they were tested at birth.
Systemic sclerosis is frequently complicated by fibrosing alveolitis although clinical and radiological abnormalities are not usually apparent until the lung disease is well established. The aim of this study was to investigate pulmonary involvement in systemic sclerosis by thin section CT scan, bronchoalveolar lavage (BAL) and 99mTc-DTPA clearance studies, and assess the value of these tests in defining pulmonary abnormalities in patients with a normal chest radiograph. Patients were divided into those with an abnormal chest radiograph (Group I, n = 14) and those with a normal chest radiograph (Group II, n = 16). CT scans were abnormal in all patients in Group I and 7 of 16 (44%) in Group II. BAL inflammatory cell counts were raised in all 12 (100%) patients studied in Group I and 11 of 15 (73%) in Group II. There was no difference in the type of inflammatory cells observed between the two groups. 99mTc-DTPA clearance was faster than normal controls in ten of 14 patients (71%) in Group I and seven of 15 (47%) in Group II and correlated with carbon monoxide transfer factor (P less than 0.05). Lung biopsies were performed on nine patients in Group I and three in Group II all of whom had abnormal CT scans. Fibrosing alveolitis was confirmed in every case. Group II biopsies could not be distinguished from Group I biopsies; both showed fibrosis as well as inflammation suggesting that pulmonary fibrosis is an early abnormality in systemic sclerosis. Our results indicate that CT scans, BAL and 99mTc-DTPA are frequently abnormal in asymptomatic patients with systemic sclerosis who have normal chest radiographs. When the CT scan is normal abnormalities of BAL and/or 99mTc-DTPA (99mTechnetium diethylenetriamine pentacetate) clearance may indicate lung disease at a still earlier stage. This observation requires further investigation.
There is histopathological evidence that, in certain inflammatory disorders involving the smaller airways, extension of the inflammatory process may occur distally into the respiratory bronchioles, alveolar ducts and alveoli (1,2). The objective of this study was to perform a non-invasive evaluation of the possible involvement of gas exchanging regions of the lung in obliterative bronchiolitis presenting with severe airways obstruction. We measured the clearance of technetium 99m-labelled diethylene triamine penta-acetate (99m Tc-DTPA) with time from the lungs to the blood, in 11 normal, non-smoking subjects (mean age 30 years), ten non-smoking patients with cryptogenic fibrosing alveolitis (CFA, mean age 57 years) and ten patients who were non-smokers with obliterative bronchiolitis (mean age 51 years). There was a substantial increase in clearance in patients with CFA, (mean T1/2 19.9 min), compared with either patients with obliterative bronchiolitis (mean T1/2 52.2 min; mean difference 32.3; 95% confidence intervals (CI) 18.40; P less than 0.001) or normal controls (mean T1/2 84.3; mean difference 64.4; 95% CI 55, 74; P less than 0.001). Clearance was also significantly faster in patients with obliterative bronchiolitis than in normal controls (mean difference 32.1; 95% CI 18.48; P less than 0.001). Peripheral deposition of 99m Tc-DTPA was uniform in normal subjects and patients with CFA, but patchy in patients with obliterative bronchiolitis, possibly resulting from altered patterns of ventilation associated with patchy distribution of bronchiolitis within affected lungs. Increased clearance of 99m Tc-DTPA from the lungs in these patients suggests that subtle derangement of the alveolar-capillary membrane occurs in adult obliterative bronchiolitis.
Neutrophils have been implicated as central mediators in myocardial and skeletal muscle ischemia-reperfusion injury. This study tests whether these cellular elements and the chemoattractant leukotriene (LTB4) play a role in postischemic renal failure. Anesthetized rats underwent 45 min of left renal pedicle clamping. Five minutes after reperfusion, LTB4 levels were elevated to 1.42 ng/ml (P less than 0.05); thromboxane (Tx)B2 was 2,840 pg/ml, higher than 503 pg/ml in sham controls (P less than 0.05); renal artery blood flow was 67% of preclamping values at 1 min of reperfusion compared with 111% in sham (P less than 0.05). At 24 h, creatinine levels were 4.6 mg/dl (P less than 0.05). At 24 h, creatinine levels were 4.6 mg/dl (P less than 0.05); histology showed acute tubular necrosis (ATN). Neutrophil depletion by rabbit antiserum (n = 8) led during reperfusion to reduced LTB4 and TxB2 levels, 1.04 ng/ml and 1.043 pg/ml (P less than 0.05); increased renal blood flow of 174% (P less than 0.05); reduced creatinine levels of 1.8 mg/dl (P less than 0.05); and limited ATN. Pretreatment with diethycarbamazine prevented the increases in LTB4 and TxB2 (P less than 0.05), increased renal blood flow (P less than 0.05), minimized creatinine increase to 1.7 mg/dl (P less than 0.05), and reduced ATN. These data indicate that neutrophils and LTB4 play a role in ischemia-induced Tx synthesis and mediate postischemic renal injury.
Explore the source record for details and available documents.
We examined the incidence of zoster in 346 children with underlying acute lymphoblastic leukemia who were immunized with live attenuated varicella vaccine while in remission. We also compared a subset of 84 of these children with a matched group of 84 children with leukemia who had had natural infection with varicella. Of the 346 vaccinated children, 5 (1.45 percent) became infected with zoster after 10,878 months of observation, for an incidence of 0.552 case per 100 person-years. Among the matched pairs of subjects, zoster occurred in 3 (3.6 percent) of the 84 vaccinated subjects during 2936 months of observation--an incidence of 1.23 cases per 100 person-years--and in 11 (13.1 percent) of the subjects with natural infection during 4245 months--an incidence of 3.11 cases of zoster per 100 person-years. Although the incidence of zoster was more than twice as high in the control children as in the vaccinated children (3.11 vs. 1.23 cases per 100 person-years), a Kaplan-Meier product-limit analysis revealed no significant differences in incidence between the two groups. Children from both groups in whom leukemia recurred were more likely to contract zoster than those who did not have a recurrence (7 of 35 vs. 7 of 133, P less than 0.025). Zoster was not a marker for impending relapse. No case of zoster was severe or disseminated. We conclude that the incidence of zoster following immunization with live attenuated varicella vaccine is no greater than that following natural varicella infection.
The survival of 213 postmenopausal patients with primary endometrial cancer was analyzed as a function of clinicopathologic features and cytosol steroid receptor levels. Estrogen receptor (ER) levels (P = 0.008) and progestin receptor (PR) levels (P = 0.0001) were negatively correlated with grade. ER and PR levels were positively correlated with each other (P = 0.0001), but neither was correlated with age. In 187 patients with stages I and II, ER positivity (greater than or equal to 20 fmole/mg cytosol protein (cp] was statistically associated with grade (P = 0.007); and PR (greater than or equal to 7 fmole/mg cp) was statistically associated with grade (P = 0.001). Univariant analysis revealed that survival for the early endometrial cancer patients was significantly dependent upon ER status (P = 0.0003), PR status (P = 0.0016), and grade (P = 0.0002). Multivariant analysis of ER status, PR status, age, and grade showed that the ER status was a significant prognostic factor for survival (P = 0.0168), even if the positivity of the PR status was defined at greater than or equal to 50 fmole/mg cp. If ER status was divided at 0-19, 20-100, and greater than 100 fmole/mg cp, survival was significantly different between the low range group and the other two groups. If PR status was divided at 0-6, 7-50, and greater than 50 fmole/mg cp survival was significantly different between the first two groups and the high range group. Thus, survival in these endometrial cancer patients was better predicted by ER status than grade.
A retrospective review of 71 children infected with human immunodeficiency virus cared for over a 3.5-year period revealed that 44 of 71 (63%) required a bacterial culture and 27 of 71 (37%) had bacteriologically documented infection. There were 125 episodes in 27 patients. Pneumonia (24 of 125 (19%)), upper respiratory tract syndromes (23 of 125 (19%)), urinary tract infection (24 of 125 (19%)) and wound infection (12 of 125 (10%)) were the most common syndromes identified. Bacteremic infections occurred in 35 of 125 (28%), and in 17 of 125 (14%) no other primary source could be identified. Pneumococci (11 of 35 (31%)) and Salmonella (4 of 35 (11%)) were the most common blood isolates; however, a wide spectrum of Gram-positive and Gram-negative pathogens were recovered. Bacterial pneumonia directly contributed to the death of 4 patients, in whom pneumonia caused by Pneumocystis carinii (2), cytomegalovirus (1) or varicella-zoster virus (1) also coexisted, respectively. Absolute T4 counts less than 400 and depressed lymphocyte-proliferative responses to diphtheria and tetanus toxoids, Candida antigen and pokeweed mitogen correlated with the occurrence of bacterial infection in human immunodeficiency virus-infected children. Although bacterial infections are a frequent cause of morbidity in human immunodeficiency virus-infected children, they are usually treatable.
Cryptogenic fibrosing alveolitis (CFA) is characterized by interstitial fibrosis and parenchymal inflammation. Eleven patients with CFA (10 proved by lung biopsy) were followed over 2 yr using clinical symptoms, radiographic change, and pulmonary function tests to adjust their treatment. Lung lavage, positron camera (PET) measurements of regional extravascular lung density (Dev), pulmonary blood volume (Vb), and the metabolic rate for 18F-deoxyglucose (MRglc), clearance of 99mTc-diethylenetriaminepentacetate (99mTc-DTPA) aerosol, and lung uptake of 67Ga were measured initially and at the end of the first year to give a profile of the inflammatory response. Compared with normal subjects, there was an increased percentage of neutrophils and eosinophils in the lung lavage, increased Dev (p less than 0.002) with no significant difference in Vb, increased MRglc (p less than 0.02), 99mTc-DTPA clearance (p less than 0.002), and 67Ga uptake (p less than 0.02). The smallest increases in Dev were seen in the two patients with most destruction shown by lung biopsy. There were inverse correlations between Dev and both FVC and TLC, but a direct correlation between Vb and transfer factor. 99mTc-DTPA clearance changed concordantly with clinical status and radiographic and respiratory function changes during the first year. If glucose utilization (MRglc) remained in the normal range between the initial and first yearly assessment, the patient improved or remained stable during the second year as shown by clinical status and radiographic and respiratory function measurements. If it rose or remained high, the patient's condition deteriorated.(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
A survey of all admissions of patients under the age of 65 years during the first 6 years of a General Hospital Psychiatric Department identified 16 'long-stay' patients (a year or more of continuous inpatient care) and 8 'medium-stay' patients (at least 6 months inpatient care in any period of a year). The most common diagnoses were organic brain disorders among long-stay patients, and affective disorders among medium-stay patients. There was no consistent accumulation of long-stay patients: those with functional disorders were usually discharged to hostel accommodation, while those with organic brain disorders died or were transferred to inpatient care in other hospitals.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The role of second-look surgery in the management of patients with ovarian cancer has come under question. One hundred one patients have undergone the operation at Yale University over the last decade. Of 67 who had epithelial ovarian cancer, 43% had positive and 57% had negative second-look surgery. Multivariate analysis revealed that stage was a significant prognostic factor with regard to second-look surgery findings, as well as absolute and disease-free survival. We found initial tumor size and results of cytology at second-look surgery to be prognostic factors with regard to survival after a positive second-look surgery. Survival after negative second-look surgery was significantly greater than that after a positive operation. However, no improvement in survival accrued to the group of advanced-stage, platinum-treated patients who underwent second-look surgery, compared with a similar group of patients who were eligible but did not undergo the procedure. We conclude that second-look surgery in epithelial ovarian cancer patients should be limited to experimental protocol situations in which precise measurement of tumor size may be important. In ovarian germ cell malignancies, second-look surgery, in the absence of tumor markers, can be justified.
Both estrogen and progestin receptor concentrations vary in a predictive temporal pattern for breast cancer; in epithelial ovarian cancer a temporal rhythmic pattern is suggested for estrogen receptor concentration only. No pattern for either receptor is seen for endometrial cancer.