Dose Reduction While Preserving Diagnostic Quality in Head CT: Advancing the Application of Iterative Reconstruction Using a Live Animal Model.

BACKGROUND AND PURPOSE: Iterative reconstruction has promise in lowering the radiation dose without compromising image quality, but its full potential has not yet been realized. While phantom studies cannot fully approximate the subjective effects on image quality, live animal models afford this assessment. We characterize dose reduction in head CT by applying advanced modeled iterative reconstruction (ADMIRE) in a live ovine model while evaluating preservation of gray-white matter detectability and image texture compared with filtered back-projection. MATERIALS AND METHODS: A live sheep was scanned on a Force CT scanner (Siemens) at 12 dose levels (82-982 effective mAs). Images were reconstructed with filtered back-projection and ADMIRE (strengths, 1-5). A total of 72 combinations (12 doses × 6 reconstructions) were evaluated qualitatively for resemblance to the reference image (highest dose with filtered back-projection) using 2 metrics: detectability of gray-white matter differentiation and noise-versus-smoothness in image texture. Quantitative analysis for noise, SNR, and contrast-to-noise was also performed across all dose-strength combinations. RESULTS: Both qualitative and quantitative results confirm that gray-white matter differentiation suffers at a lower dose but recovers when complemented by higher iterative reconstruction strength, and image texture acquires excessive smoothness with a higher iterative reconstruction strength but recovers when complemented by dose reduction. Image quality equivalent to the reference image is achieved by a 58% dose reduction with ADMIRE-5. CONCLUSIONS: An approximately 60% dose reduction may be possible while preserving diagnostic quality with the appropriate dose-strength combination. This in vivo study can serve as a useful guide for translating the full implementation of iterative reconstruction in clinical practice.

Effect of zidovudine on serum human immunodeficiency virus core antigen levels. Results from a placebo-controlled trial.

We assessed the effect of antiviral therapy on serum human immunodeficiency virus core antigen (HIV-Ag) levels in patients enrolled in the phase II trial on zidovudine for acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. Human immunodeficiency virus core antigen was detected in 45% of subjects at entry (59% with AIDS and 37% of patients with AIDS-related complex). Median HIV-Ag levels in zidovudine-treated subjects fell from 111 pg/mL at entry to 46 pg/mL at four weeks, while levels in placebo recipients did not change significantly. Decline in HIV-Ag in zidovudine recipients was sustained through 16 weeks of treatment and was significantly different from the placebo group. Anti-p24 antibody levels did not change in either group. We conclude that in patients with HIV-antigenemia changes in HIV-Ag level are an important marker of anti-retroviral activity.

Oral candidiasis in HIV infection: pseudomembranous and erythematous candidiasis show similar rates of progression to AIDS.

Candidiasis is the most common oral fungal infection seen in association with HIV infection. It may present in a number of clinical forms, including pseudomembranous and erythematous candidiasis. To determine whether erythematous candidiasis, like the pseudomembranous form, is predictive of the development of AIDS, we reviewed the records of 169 HIV-seropositive patients seen at clinic of the Oral AIDS Center, University of California, San Francisco who were diagnosed with pseudomembranous or erythematous (or both) forms of oral candidiasis at their first examination. Kaplan-Meier analysis showed a rapid rate of progression to AIDS (median, 25 months) and to death (median, 43.8 months) in all three groups. We conclude that erythematous candidiasis is as serious a prognostic indicator as pseudomembranous candidiasis. Because the erythematous form is more difficult to recognize and hence is underdiagnosed, efforts should be made to teach non-dental clinicians who care for HIV-infected patients to diagnose and treat this lesion.

The prevalence of oral lesions in HIV-infected homosexual and bisexual men: three San Francisco epidemiological cohorts.

To establish the prevalence of HIV-related oral lesions, we performed oral examinations of members of three San Francisco epidemiological cohorts of homosexual and bisexual men over a 3-year period. Hairy leukoplakia, pseudomembranous and erythematous candidiasis, angular cheilitis, Kaposi's sarcoma, and oral ulcers were more common in HIV-infected subjects than in HIV-negative subjects. Among HIV-infected individuals, hairy leukoplakia was the most common lesion [20.4%, 95% confidence interval (CI) 17.5-23.3%] and pseudomembranous candidiasis was the next most common (5.8%, 95% CI 4.1-7.5%). Hairy leukoplakia, pseudomembranous candidiasis, angular cheilitis and Kaposi's sarcoma were significantly more common in patients with lower CD4 lymphocyte counts (P less than 0.05). The prevalence of erythematous candidiasis and Kaposi's sarcoma increased during the 3-year period. Careful oral examinations may identify infected patients and provide suggestive information concerning their immune status.

Risk factors for rapid progression from hairy leukoplakia to AIDS: a nested case-control study.

To determine risk factors for early progression from oral hairy leukoplakia to AIDS, this case-control study compared 27 patients who had not progressed to AIDS within 1,000 days of diagnosis of hairy leukoplakia with 28 patients who progressed rapidly. The risk factors that proved most predictive fell into two categories: (a) those reflecting sexual practices that correlated with how early in the epidemic patients were likely to have been infected, and (b) those reflecting immune competence. Hepatitis B was associated with a fourfold risk for early progression and syphilis with a nearly threefold risk. Skin test anergy for Candida species was strikingly predictive: all of 17 tested in the early progression group were anergic, compared with only two of 12 tested in the late progression group. Although skin testing has been largely supplanted by assessment of T-cell subsets, Candida species skin testing may be of particular prognostic value in otherwise apparently healthy HIV-infected persons.

Estrogen replacement therapy and the risk of venous thrombosis.

PURPOSE: Estrogen replacement therapy is believed by many physicians to cause thrombophlebitis and to be contraindicated in women at risk for this disease. However, clinical data supporting this assumption are scant, and further investigation is required. PATIENTS AND METHODS: We tested the estrogen-thrombophlebitis association in a case-control study. Charts of all consecutive women aged 45 years or older with a primary or secondary discharge diagnosis of thrombophlebitis, venous thrombosis, or pulmonary embolism were reviewed; 121 cases and 236 controls matched for age, year of admission, admitting service, and socioeconomic status were obtained. Hormone use and nonuse were validated in a subset of randomly selected women. RESULTS: Cases and controls, whose average age was 65 years, did not differ significantly on matching variables or on current use of exogenous estrogen (5.1% of cases versus 6.3% of controls). Other analyses that variously excluded women with a past history of thrombosis, women less than 50 years of age, women with thrombosis occurring after admission, and women whose estrogen use was indeterminate also did not support an increased risk of thrombotic disease. Adjustment for the presence of independent thrombotic risk factors did not alter the odds ratio for estrogen use. CONCLUSION: This case-control study of older women, unselected for other thrombotic risk factors, does not support the commonly held assumption that replacement estrogen increases the risk of venous thrombosis.

Giant cell arteritis associated with mononeuritis multiplex and complement-activating 19S IgM rheumatoid factor.

Giant cell arteritis is a necrotizing granulomatous arteritis of large arteries, especially the aorta and its branches. Mononeuritis multiplex is a peripheral sensorimotor neuropathy usually producing foot or wrist drop, commonly associated with necrotizing arteritis of small and medium-sized arteries. Rheumatoid vasculitis is an example of the latter type of arteritis associated with high-titer 19S IgM rheumatoid factor typically occurring in patients with long-standing erosive rheumatoid arthritis. This report describes a 71-year-old man with biopsy-proved giant cell arteritis, mononeuritis (foot drop) multiplex, and high-titer complement-activating rheumatoid factor without rheumatoid arthritis. Possible pathogenic relationships are discussed.

Use of diuretics in treatment of hypertension in the elderly.

Men and women with isolated systolic hypertension who were at least 60 years of age were treated for 1 year with chlorthalidone (25-50 mg daily) or matching placebo as the step I drug. Most patients reached goal blood pressure without requiring a step II drug. The blood pressure response was similar in all age, sex and race subgroups, with an overall difference between the randomised groups of 17 mm Hg for systolic blood pressure (p less than 0.001) and 6mm Hg for diastolic blood pressure (p less than 0.001). The only common adverse effects were asymptomatic changes in the serum concentrations of potassium (0.5 mmol/L lower in the chlorthalidone group, p less than 0.001), uric acid (0.9 mg/dl higher, p less than 0.001), and creatinine (0.08 mg/dl higher, p = 0.02). Compliance was good, and more than 80% of participants were still taking the study medications at the end of the year.

Starting an academic career. A survey of junior academic pulmonary physicians.

OBJECTIVE: To learn about the status of junior faculty in the specialty of pulmonary diseases and about their attitudes concerning their future in academic medicine. DESIGN: Mailed survey. PARTICIPANTS: A total of 209 junior pulmonary faculty were reported by the directors of the 106 US pulmonary training institutions with at least 3 fellow training positions; 157 (75 percent) responded to our questionnaire. RESULTS: Most respondents described themselves as happy and productive, and almost all planned to stay in academic medicine. However, some problems were evident that could interfere with their plans to remain: a lack of protected time for research (only 15 percent of assistant professors and instructors spent 75 percent or more of their time in research), a lack of understanding about the rules and procedures of promotion (only 31 percent said they understood), failure of communication with the Chiefs of the Division and of Medicine (less than half had had a meeting about promotion with the Chief of the Division, 16 percent with the Chairman of Medicine), and a concern about their financial security (73 percent were concerned). Although women, who represented only 13 percent of the respondents, reported similar work hours and publication rates, they were less optimistic about promotion than the men (40 percent of women considered their chance for promotion good to excellent vs 64 percent of men). The junior faculty reported that the greatest obstacles to their academic success were insufficient protected time for their research, maintaining research productivity, and inadequate and uncertain funding. CONCLUSIONS: The success of junior faculty is important to the success of academic medicine. More attention should be paid to ensuring protected continuous time for research, educating about promotion, and improving funding opportunities.

Length of stay and survival after intensive care for severe Pneumocystis carinii pneumonia. A prospective study. California Collaborative Treatment Group.

Survival rates for persons receiving intensive care for Pneumocystis carinii pneumonia have improved. However, the utility of prolonged intensive care for patients who do not show initial improvement remains unclear. We assessed survival in a nested cohort study of patients receiving intensive care while participating in a randomized trial of early adjunctive corticosteroids for Pneumocystis pneumonia. Twenty-eight of 251 (11 percent) participants were admitted to an intensive care unit. Fourteen (50 percent) of these were discharged alive from the intensive care unit and 11 (39 percent) were discharged alive from the hospital. Survivors and nonsurvivors were similar demographically and with respect to treatment received but differed in the mean days of intensive care received (4.5 vs 8.6 [p = 0.02]). The conditional probability surviving to hospital discharge after intensive care dropped steadily from 39 percent at intensive care unit admission to 17 percent after one week and to 0 percent after two weeks.

A method for evaluating patient care and auditing skills of family practice residents.

A system of chart review is presented which develops both auditing skills and patient care skills. The model suggested is a flexible one, applicable at various levels of training in both inpatient and outpatient settings. Its application to family practice resident training is shown by comparing the performances of residents at the beginning and end of a demonstration period.

FDA explores new antiretroviral trial designs: interview with David Feigal, M.D. Interview by John S. James.

AIDS: At its public meeting, July 14 and 15, the Food and Drug Administration's (FDA) Antiviral Drugs Advisory Committee will explore ways to design clinical drug trials so that they are completed faster and more safely. The FDA is considering changing the clinical endpoints requirement for antiretroviral confirmatory trials. Rather than waiting for a major disease event to occur, the new kind of trial would record effective viral suppression over a period of time. Dr. David Feigal of the FDA's Division of Antiviral Drug Products discusses the problems that the proposed changes should solve, the protocol designs, and how interested people can contact the Committee.^ieng

Protease inhibitors and beyond: interview with David Feigal, M.D. Interview by John S James.

AIDS: Dr. David Feigal, M.D., Director of the Division of Antiviral Drug Products of the U.S. Food and Drug Administration (FDA), agrees that protease inhibitors are the most promising single approach to HIV treatment today. There are, however, several obstacles to the development of these experimental drugs. The compounds are difficult to produce, often requiring multi-step synthesis processes, and there are additional problems with trying to scale-up to large quantities. The supply problem makes it difficult to decide how to provide the product to people who cannot participate in clinical trials. The lottery method, used with Betaseron for multiple sclerosis, was unpopular. Dr. Feigal suggests a partnership between the community and the companies to devise a distribution strategy. In addition, there are other treatment options showing preliminary data results in the same general magnitude as the protease inhibitors. Dr. Feigal also mentions that a workshop on AIDS clinical trials will be organized for late spring or early summer.^ieng

Hypernatremia in elderly patients. A heterogeneous, morbid, and iatrogenic entity.

The causes, therapy for, and consequences of hypernatremia in elderly patients are not well understood. We found that in 15,187 consecutive hospital admissions, 162 (1.1%) patients who were at least 60 years of age had serum sodium levels that measured greater than 148 meq/L. Of that 162, 57% had become hypernatremic in the hospital; the remaining 43% were hypernatremic at hospitalization. The mean peak serum sodium level was 154 meq/L (range, 149 to 182), and mean water deficit, 9% of total body water (range, 6% to 30%). The most frequent primary causes were complications of surgery (21%), febrile illness (20%), infirmity (11%), and diabetes mellitus (11%), with more than 40 causal factors identified. Depression of sensorium correlated with severity of hypernatremia (p less than 0.001). The mortality rate (42%) was seven times that of age-matched hospitalized patients, but was not predicted by severity of hypernatremia. Mortality increased with increasing rates of fluid replacement (p less than 0.008). Hypernatremia in elderly patients is usually iatrogenic and often a marker for severe associated systemic illness.

Relationship of serum IgG rheumatoid factor to IgM rheumatoid factor and disease activity in rheumatoid arthritis.

Rheumatoid factors (RF) constitute the major autoantibodies in rheumatoid arthritis (RA). RF are directed against IgG Fc, are polyclonal, and are predominantly of the IgG and IgM classes. RF may participate in both synovial and extraarticular inflammation in RA, although the precise roles of serum IgG and IgM RF are unclear. The purpose of our study was to correlate serum IgG RF with serum IgM RF levels measured by radioimmunoassay and with clinical disease activity in 42 prospectively evaluated seropositive RA patients. IgM RF correlated with IgG RF levels and articular disease activity. IgG RF correlated with IgM RF but not with articular disease activity when adjusted for IgM RF.

Recurrent aphthous ulcers in association with HIV infection. Description of ulcer types and analysis of T-lymphocyte subsets.

This study was conducted to characterize the recurrent aphthous ulcers (RAU) found in association with human immunodeficiency virus (HIV) infection, to examine evidence for increased severity of the ulcers with HIV disease, and to determine whether increased severity is associated with abnormalities of peripheral blood lymphocyte subsets. Seventy-five HIV-seropositive patients with RAU were followed for up to 2 years, and lymphocyte subsets were analyzed in 42. Minor, herpetiform, and major ulcer types were seen, but unexpectedly, 66% of the patients had the usually uncommon herpetiform and major types. These types were temporally associated with symptomatic HIV disease. Patients with major RAU were significantly more immunosuppressed than those with minor or herpetiform RAU in that they had fewer CD4 and CD8 lymphocytes (p less than 0.05). The lesion of RAU is considered to represent a local breakdown in immunoregulation. The systemic immune imbalance seen with HIV disease may amplify the local defect and lead to more severe ulcers.