Medication-related dizziness in the older adult

With increased medication use among the older adult population, adverse drug events and polypharmacy can be significant causes of dizziness in the elderly. The evidence evaluated in this review is helpful in clinical practice but requires an additional detailed investigation into the agents discussed to understand the risk/benefit ratio associated with medications. Examples of medications highly associated with dizziness in older adults and discussed in this review include cardiovascular and central nervous system agents. Several other medication classes associated with dizziness are among the medications most commonly used by older patients.     

Integration of conservative surgery, radiotherapy, and chemotherapy for the treatment of early-stage, node-positive breast cancer: sequencing, timing, and outcome

The optimal means of combining breast-conserving surgery, radiation therapy, and chemotherapy for the treatment of patients with early-stage, node-positive breast cancer is not known. We reviewed the results in 295 patients treated at the Joint Center for Radiation Therapy and affiliated institutions from 1976 to 1985. All patients had positive axillary nodes on dissection, had no gross residual disease in the breast or axilla after surgery, and received breast irradiation (with or without nodal irradiation) and three or more cycles of a cyclophosphamide, methotrexate, and fluorouracil (CMF)-based or doxorubicin-containing regimen. Median follow-up in patients without any failure was 78 months. Breast failure rates were assessed in relation to the sequencing of radiotherapy and chemotherapy. The different sequences were not randomly assigned, and the characteristics of the sequence groups differed. The actuarial 5-year breast failure rate was 4% in 99 patients receiving radiotherapy before chemotherapy; 8% in 54 patients sequentially receiving some chemotherapy, then radiotherapy without concurrent chemotherapy, then further chemotherapy; and 6% in 116 patients receiving concurrent chemotherapy and radiotherapy. However, the failure rate was 41% in 26 patients who received all chemotherapy before radiotherapy. The crude incidences of local failure within 4 years of treatment in these groups were 3%, 2%, 4%, and 15%, respectively (P = .065 for all four groups not being the same). The actuarial 5-year local failure rate was 5% for 252 patients irradiated within 16 weeks after surgery compared with 35% for 34 patients irradiated more than 16 weeks after surgery. The 4-year crude incidences were 4% and 12% for the two groups, respectively (P = .06). These results suggest that delaying the initiation of radiotherapy may result in an increased likelihood of local failure. Formal randomized controlled trials will be needed to confirm these results and to improve the integration of these treatment modalities.     

Fusion or Confusion on Holter Recording

Holter recording of a patient with an implanted dual chamber rate responsive pacemaker revealed an electrocardiogram, where ventricular depolarization seemed to be initiated by the atrial stimulus. In a second patient with a VVI pacemaker, Holter recording showed delay of the pacemaker impulse that was registered after the onset of ventricular depolarization. Misalignment in one of the recorder heads of the display system was responsible for this phenomenon, which in case of dual chamber pacing could have been easily misinterpreted as pacemaker malfunction.     

Enhancement of t lymphocyte functions by Fc fragments of immunoglobulins. I. Augmentation of allogeneic mixed lymphocyte culture reactions requires I-A- or I-B-subregion differences between effector and stimulator cell populations

Fc fragments derived from human Ig were found to be capable of enhancing T cell-mediated, antigen-induced proliferative and mixed lymphocyte culture responses. Maximum enhancement occurred when suboptimal amounts of antigen or suboptimal numbers of stimulator cells were employed. Augmentation of the allogeneic mixed lymphocyte culture reaction requires an I-A and/or I-B subregion difference between effector and stimulator cell populations. Although a significant proliferative response was observed with K- or D- region differences, Fc fragments were unable to enhance the response. The T cell population acted upon by Fc fragments in the potentiation of these responses bears the Lyt-1(+)23(-) phenotype.     

Clinical and local biological effects of an intratumoral injection of mda-7 (IL24; INGN 241) in patients with advanced carcinoma: a phase I study.

The melanoma differentiation-associated gene-7 (mda-7; approved gene symbol IL24) is a tumor suppressor gene whose expression induces selective apoptosis in tumor cells. To characterize the safety and biologic activity of mda-7 gene transfer, we conducted a phase I trial using intratumoral injections of an adenovirus containing the mda-7 construct (Ad-mda7; INGN 241; 2 x 10(10) to 2 x 10(12) vp) in 28 patients with resectable solid tumors. One hundred percent of injected lesions demonstrated INGN 241 vector transduction, transgenic mRNA, elevated MDA-7 protein, and apoptosis induction, with the highest levels near the injection site. Apoptosis of cells in injected tumors was consistently observed even in heavily pretreated patients. INGN 241 vector DNA and mRNA were detected more than 1 cm from the injection site, whereas MDA-7 protein and bioactivity were more widely distributed. Toxicity attributable to the injections was self-limiting and generally mild; however, one patient experienced a grade 3 SAE possibly related to the study drug. Evidence of clinical activity was found in 44% of lesions with the repeat injection schedule, including complete and partial responses in two melanoma patients. Thus intratumoral administration of INGN 241 is well tolerated, induces apoptosis in a large percentage of tumor cells, and demonstrates evidence of clinically significant activity.     

CELLULAR IMMUNITY TO HERPES SIMPLEX VIRUS MEDIATED BY INTERFERON

Rabbit kidney cell monolayers infected with herpes simplex virus (HSV) were incubated with leukocytes from rabbits immunized with complete Freund's adjuvant. When the leukocytes were exposed to tuberculin purified protein derivative (PPD), viral replication and plaque formation were markedly inhibited. Similarly, when leukocytes from animals immunized with HSV were exposed to UV-inactivated HSV, viral replication was markedly inhibited. Exposure of leukocytes from unimmunized animals or animals immunized with incomplete Freund's adjuvant to UV-inactivated virus or PPD produced relatively little inhibition of viral replication. Examination of supernatant fluids from stimulated cultures revealed a soluble mediator that had the properties of interferon. Interferon production was detected within several hours after exposure of sensitized leukocytes to antigen. Supernatant fluids from as few as one sensitized leukocyte per 200 rabbit kidney cells inhibited HSV replication by over 90%. These findings support the concept that the cellular immune response to HSV consists of two phases: an immunologically specific antigen recognition phase, and a nonspecific effector phase that stops HSV spread by generating interferon.     

Seroprevalence of human T-lymphotropic virus, hepatitis C virus, and human immunodeficiency virus in Asian American potential bone marrow donors

BACKGROUND: Asian Americans are generally underrepresented both as volunteer blood and bone marrow donors. STUDY DESIGN AND METHODS: To investigate the risk of transfusion transmission of viruses that is associated with increasing participation by Asian American donors, antibodies to human T-lymphotropic virus (HTLV), hepatitis C, and human immunodeficiency virus in Asian American volunteers recruited as potential bone marrow donors were measured. A total of 1354 Asian Americans were enrolled in the study, of whom 54 percent were Chinese, 26 percent Japanese, 9 percent Filipino, 4 percent Korean, 3 percent Indian, and 5 percent of other Asian or mixed Asian and other ethnicity. The majority of the study population was aged 20 through 49 and of high socioeconomic status, as indicated by education and income. Viral antibodies were measured with both screening enzyme-linked immunosorbent assays and supplemental testing, and polymerase chain reaction was used to resolve discrepant HTLV results. RESULTS: Confirmed seroprevalence rates for HTLV were 0.15 percent with one manufacturer's Western blot and 0.3 percent with the other; however, no sample was positive for HTLV types I or II in polymerase chain reaction. Confirmed seroprevalence to hepatitis C virus was 0.5 percent. No subject was seropositive for human immunodeficiency virus. CONCLUSION: On the basis of the moderate size and high education level of this study population, it is concluded that Asian American volunteer bone marrow donors do not pose a greater risk for transmission of HTLV type I or II, human immunodeficiency virus, or hepatitis C virus than does the average American blood donor.     

Changes in Morphology of the Paced QRS Complex Related to Pacemaker Output

The influence of pacemaker output on the morphology of the paced QRS complex was studied from standard lead electrocardiograms in 69 patients with bipolar pacemakers. In 40 of the 69 patients (58%), there was a significant (P less than 0.001) change in electrical axis, from -75 degrees at the low output setting (2.7 V, 0.15 msec) to -67 degrees at the high output setting (8.1 V, 2.29 msec). In 30 patients, these changes were also associated with changes in the QRS morphology and in the T-wave. This phenomenon may be explained by additional stimulation from the proximal electrode at high output, thus altering the pattern of depolarization.