High titer anti-HIV antibody reactivity associated with a paraprotein spike in a homosexual male with AIDS related complex

We observed a human immunodeficiency virus (HIV)-infected homosexual male with AIDS related complex (ARC) who had a serum globulin level of 80 g/L. Serum protein electrophoresis revealed a gamma globulin fraction of 40 g/L, of which 50% (20 g/L) was contained within a paraprotein spike, comprised predominantly of IgG kappa. This patient also had high titer anti-HIV antibodies in his serum, which were Western blot reactive at a final dilution of 1:500,000, and recognized gp120env, p66pol, p55gag, p53pol, p41gag, and p24gag. Because paraproteins in the past have been shown to be directed against specific antigens, we purified this patient's paraprotein using a modified high performance liquid chromatography (HPLC)-hydroxylapatite procedure and tested the purified paraprotein for anti-HIV antibody activity. The purified paraprotein retained anti-HIV antibody activity to a final dilution of 1:100,000, and recognized p66pol, p55gag, p53pol, p41gag, and p24gag. The recognition of both "gag" and "pol" gene products suggested that the purified paraprotein might not be monoclonal in origin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that the purified paraprotein contained at least two immunoglobulin light chain species (Mol wt 30 to 33 Kd). Affinity chromatography of the purified paraprotein using a p24- Sepharose 4B matrix separated the "gag" and "pol" antibody activities. Immunoglobulin gene rearrangement analysis of a bone marrow aspirate (which contained 15% plasma cells) failed to reveal a clonal population of immunoglobulin producing cells. We conclude that this patient's paraprotein accounted for most of the anti-HIV activity present in whole serum, and that this paraprotein was not monoclonal in origin.     

The Influence of Long-Term Care Insurance on the Likelihood of Nursing Home Admission

OBJECTIVES: To determine the effect of long-term care (LTC) insurance on nursing home use.
DESIGN: Longitudinal analysis, 1998 to 2006 waves of the Health Retirement Study.
SETTING: Community-dwelling nationally representative sample.
PARTICIPANTS: Nineteen thousand one hundred seventy adults aged 50 and older, 1998 wave.
METHODS: Two groups of respondents were created at baseline: those with and without an LTC insurance policy. Respondents admitted to the nursing home from 1998 to 2006 were identified. Propensity scores were used to control for known predictors of LTC insurance possession. A Cox proportional hazards model was used to compare the probability of nursing home admission over 8 years of follow-up for respondents possessing LTC insurance and those without a policy.
RESULTS: Of the 19,170 respondents aged 50 and older in 1998, 1,767 (9.2%) possessed LTC insurance. A total of 1,778 (8.5%) were admitted to a nursing home during the 8-year period: 149 (8.7%) of those with LTC insurance and 1,629 (8.4%) of those without LTC insurance. The hazard ratio, adjusted for propensity score, for those with LTC insurance entering a nursing home compared with those without was 1.07 (95% confidence interval=0.83–1.38). Likelihood of nursing home admission was relatively low because the low-risk population included in the study, limiting the power to detect small differences in risk of nursing home utilization between groups.
CONCLUSION: There was no difference in nursing home utilization between low-risk older adults who did and did not possess an LTC insurance policy.     

“Below average” self-assessed school performance and Alzheimer's disease in the Aging,Demographics, and Memory Study

BackgroundA low level of formal education is becoming accepted as a risk factor for Alzheimer's disease (AD). Although increasing attention has been paid to differences in educational quality, no previous studies addressed participants' own characterizations of their overall performance in school. We examined whether self-assessed school performance is associated with AD beyond the effects of educational level alone.MethodsParticipants were drawn from the population-representative Aging, Demographics, and Memory Study (ADAMS, 2000-2002). The ADAMS participants were asked about their performance in school. Possible response options included “above average,” “average,” or “below average.” The ADAMS participants also underwent a full neuropsychological battery, and received a research diagnosis of possible or probable AD.ResultsThe 725 participants (mean age, 81.8 years; 59% female; 16% African-American) varied in self-assessed educational performance: 29% reported “above average,” 64% reported “average,” and 7% reported “below average” school performance. Participants with a lower self-assessed school performance had higher proportions of AD: 11% of participants with “above average” self-assessed performance had AD, as opposed to 12% of participants with “average” performance and 26% of participants with “below average” performance (P < 0.001). After controlling for subjects' years in school, a literacy test score (Wide-Range Achievement Test), age, sex, race/ethnicity, apolipoprotein E-?4 status, socioeconomic status, and self-reported comorbidities, respondents with “below average” self-assessed school performance were four times more likely to have AD compared with those of “average” performance (odds ratio, 4.0; 95% confidence interval, 1.2–14). “Above average” and “average” self-assessed school performance did not increase or decrease the odds of having AD (odds ratio, 0.9; 95% confidence interval, 0.5–1.7).ConclusionsWe suggest an association between “below average” self-assessed school performance and AD beyond the known association with formal education. Efforts to increase cognitive reserve through better school performance, in addition to increasing the number of years of formal education in early life, may be important in reducing vulnerability throughout the life course.     

Correlation of P-glycoprotein expression and function in childhood acute leukemia: a children's cancer group study

Clinical drug resistance may be attributed to the simultaneous selection and expression of genes modulating the uptake and metabolism of chemotherapeutic agents. P-glycoprotein (P-gp) functions as a membrane-associated drug efflux pump whose increased expression results in resistance to anthracyclines, epipodophyllotoxins, vinca alkaloids, and some alkylating agents. This type of resistance occurs as both de novo and acquired resistance to therapy for leukemia. We have studied P- gp expression and function in childhood acute leukemias by developing a series of doxorubicin- and vincristine-selected CEM, T-cell lymphoblastoid cell lines that recapitulate the low levels of expression and resistance seen clinically. These cell lines have been used to develop flow cytometric assays for the semiquantitative measurements of P-gp expression with the MRK16 monoclonal antibody and P-gp function using the enhanced retention of rhodamine 123 in the presence of verapamil, a resistance modulator. Kolmogorov-Smirnov statistics, represented by the D measurement, are used to determine the difference in level of P-gp expression by comparing MRK16 staining to an IgG2a isotype control. When D is > 0.09, there is an excellent correlation (R = 0.82) between P-gp expression and function. The evaluation of 107 bone marrow specimens from 84 children with lymphoblastic or myelogenous leukemia showed a statistically significant (P = .004) increase in P-gp function at relapse. P-gp expression at relapse, however, approached but did not reach a significant level (P = .097). Using this methodology, we can identify patients with levels of P-gp expression and function that we can define clinically, as well as children with discordant multidrug resistance phenotypes. This study supports the role of P-gp-mediated drug resistance in childhood leukemia and confirms that P-gp expression and function are measurable in their leukemic blasts. These assays provide the means for the in vitro testing of resistance modulators and the monitoring of in vivo response to treatment with these agents.     

Hospitalization,depression and dementia in community-dwelling older Americans: findings from the National Health and Aging Trends Study

Objective

The objective was to estimate the prevalence of both dementia and depression among community-dwelling older Americans and to determine if hospitalization is independently associated with dementia or depression in this population.

Method

This cross-sectional study utilized data from a nationally representative, population-based sample of 7197 community-dwelling adults ≥ 65 years old interviewed in 2011 as part of the National Health and Aging Trends Study. Information on hospitalizations was obtained from self- or proxy-report. Possible and probable dementia was assessed according to a validated algorithm. Depressive symptoms were assessed with the Patient Health Questionnaire-2.

Results

An estimated 3.1 million community-dwelling older Americans may have dementia, and approximately 5.3 million may have substantial depressive symptoms. After adjusting for demographic and social characteristics, medical diagnoses, smoking history, serious falls and pain symptoms, being hospitalized in the previous year was independently associated with greater odds of probable dementia (odds ratio [OR]: 1.42, 95% confidence interval [95% CI]: 1.16–1.73) and substantial depressive symptoms (OR: 1.60, 95% CI: 1.29–1.99).

Conclusions

Dementia and depression are common in community-dwelling older Americans, and hospitalization is associated with these conditions. Additional research increasing understanding of the bidirectional relationship between hospitalizations, dementia and depression, along with targeted interventions to reduce hospitalizations, is needed.     

Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression

Fifty-two of 175 (30%) survivors of allogeneic marrow transplantation developed chronic graft-versus-hose diseases (GVHD). Five with limited chronic GVHD had an indolent clinical course with involvement of only the skin and liver. Forty-seven with extensive chronic GVHD had an unfavorable multiorgan disorder that resembled several autoimmune diseases. Thirteen patients with extensive disease (group I) were not treated and only 2 survive with Karnofsky scores >- 70%. Mortality resulted from infections and morbidity from sica syndrome, pulmonary and hepatic insufficiency, scleroderma-like skin disease, and contractures. Another 13 (group II) received a median of 8 mo prednisone and/or a brief course of antithymocyte globulin, and 3 survive without disability. The other 21 (group III) were treated with a combination of prednisone (1.0 mg/kg/q.o.d.) and either cyclophosphamide, procarbazine, or azathioprine (all 1.5 mg/kg/day) for a median of 13 mo. Combination therapy was well tolerated with only modest myelotoxicity. Fifteen in group III had a good and 4 a fair response to treatment while 2 with no response died. Azathioprine and prednisone was the most effective regimen. All therapy has been discontinued in 12 group III patients: GVHD returned in 5 (including 2 who died in spite of retreatment) while 7 remain free of GVHD for a median of 11 (range 6-30) mo observation. Only I group III survivor is disabled and 16 of the original 21 are alive 2-4 yr after transplant with Karnofsky scores of 70%-100%. Thus, combination immmunosuppression appears to favorably affect and, in some cases, premanently arrest the adverse natural course of extensive chronic GVHD.     

Feasibility of using interpolated contours of targets and organs at risk in intensity‐modulated radiation therapy treatment planning for advanced‐stage nasopharyngeal carcinoma

To assess the dosimetric effect of using interpolated contours in planning intensity‐modulated radiation therapy (IMRT) for advanced T‐stage nasopharyngeal carcinoma. The present study focused on T3–T4 tumours where the proximity of targets to neurological organs poses a stringent test on the feasibility of such an approach. Contours of targets and organs were delineated on CT images of 2.5‐mm interval and a reference IMRT plan was generated. An investigative (INV) IMRT plan was then generated with the same planning protocol, but based on interpolated contours that replaced deleted contours on alternate slices. The reference and INV plans were compared. Regarding target coverage, all targets in the INV plans met the acceptance criteria except for the PTV in one case. Regarding organs, the mean dose to 1% volume of the brainstem and spinal cord in the INV plans were kept below their dose limits. No significant differences in the mean doses to others organs were found. Satisfactory target coverage and protection of critical organs to a degree similar to full‐scale contouring could be achieved with use of interpolated contours. The saving in manpower time for contouring is expected to significantly improve the throughput of the IMRT planning process.     

Computed tomography fluoroscopy‐guided chemical lumbar sympathectomy: Simple,safe and effective

Demographic, clinical and laboratory data were retrospectively collected from records of 146 cases of CT fluoroscopy‐guided chemical lumbar sympathectomy for the palliation of inoperable peripheral vascular disease (PVD) between January 1997 and August 1999. Of these, 16% had claudication, 39% had rest pain and 44% had ischaemic ulcers or gangrene. Seventy‐three percent of elective cases were outpatients. At 3 months, 27 cases were lost to follow up, leaving 119 cases. Within 3 months, improvement, defined as doubling of the walking distance, cessation of rest pain or healing of ulcers, occurred in 30.3% of cases. No change was observed in 45.4% of cases and 24.3% of cases deteriorated. Patients with ulcers or gangrene had significantly poorer results than those without any ischaemic lesions, as only 19% versus 39% of patients improved (P < 0.05). The presence of hypertension, diabetes mellitus, hyperlipidaemia and smoking had no value in predicting clinical outcome (P > 0.05). There were no major complications noted. CT fluoroscopy‐guided chemical lumbar sympathectomy is safe and effective, with a complication rate of less than 1%, and efficacy of at least 30% measured within 3 months. It is a simple and minimally invasive procedure, easily performed on an outpatient basis. CT fluoroscopy‐guided chemical lumbar sympathectomy should be considered for all patients in the early stages of inoperable PVD.     

Steroids for intubated croup masking airway haemangioma

Recently, the beneficial role of steroids for acute laryngotracheobronchitis has been more clearly defined for both intubated and unintubated patients. However, corticosteroids also improve the clinical signs of airway haemangiomata. Two patients are described who illustrate how this can be a source of diagnostic confusion.