Changes in the inpatient and outpatient cancer patient population at a teaching institution over a three-year period

Admission and outpatient clinic records of cancer patients seen by members of the University of Nebraska Medical Center Section of Oncology/Hematology in that section's clinic and on that section's hospital service were studied over a three-year period to determine if the tumor types of patients differed importantly from year to year. Cancer patients seen in other clinics or on other clinical services in the medical center were not included in this study. Some striking variations were found. The percentage of cancer patients with lymphoma admitted to the hospital increased significantly, from 23% to 41% (p less than .00001), and the percentage of those patients seen in the outpatient area increased correspondingly. In contrast, the percentage of colorectal cancer patients fell from 11% in 1984 to 4% in 1985 and to 3% in 1986 (p less than .00001). A similar decrease was found in the outpatient clinics as well. In addition, the percentage of breast cancer patients admitted to the hospital fell from 17% in 1984 to 12% in 1985 and to 11% in 1986 (p = .003); there was also a similar decline in the outpatient clinic (p = .00001). Other tumor types were equally represented in all three years in the inpatient and outpatient setting. The patient mix can vary markedly from year to year and should be monitored, so that changes in the teaching program can be made to assure the desired emphasis of all tumor types.     

Role of the estrogen receptor coactivator AIB1 (SRC-3) and HER-2/neu in tamoxifen resistance in breast cancer

BACKGROUND: AIB1 (SRC-3) is an estrogen receptor (ER) coactivator that, when overexpressed in cultured cells, can reduce the antagonist activity of tamoxifen-bound ERs. Signaling through the HER-2 receptor pathway activates AIB1 by phosphorylation. To determine whether high AIB1 expression alone or together with HER-2 reduces the effectiveness of tamoxifen in breast cancer patients, we quantified expression of AIB1 and HER-2 in tumors from breast cancer patients with long-term clinical follow-up who received either no adjuvant therapy or adjuvant tamoxifen therapy after breast cancer surgery. METHODS: AIB1 and HER-2 protein levels in tumors from 316 breast cancer patients were determined using western blot analysis. Molecular variables (e.g., expression of AIB1, ER, progesterone receptor, p53, Bcl-2), tumor characteristics, and patient outcome were assessed using Spearman rank correlation. Disease-free survival (DFS) curves were derived from Kaplan-Meier estimates, and the curves were compared by log-rank tests. The effect of AIB1 on DFS adjusted for other prognostic factors was assessed by multivariable analysis using the Cox proportional hazards model. All statistical tests were two-sided. RESULTS: High AIB1 expression in patients not receiving adjuvant tamoxifen therapy was associated with better prognosis and longer DFS (P =.018, log-rank test). In contrast, for patients who did receive tamoxifen therapy, high AIB1 expression was associated with worse DFS (P =.049, log-rank test), which is indicative of tamoxifen resistance. The test for interaction between AIB1 expression and tamoxifen therapy was statistically significant (P =.004). When expression of AIB1 and HER-2 were considered together, patients whose tumors expressed high levels of both AIB1 and HER-2 had worse outcomes with tamoxifen therapy than all other patients combined (P =.002, log-rank test). CONCLUSIONS: The antitumor activity of tamoxifen in patients with breast cancer may be determined, in part, by tumor levels of AIB1 and HER-2. Thus, AIB1 may be an important diagnostic and therapeutic target.     

MR imaging of laser-tissue interactions

A new application of magnetic resonance (MR) imaging to map the spatial and temporal distribution of the effects of Nd:YAG lasers on tissues was studied. The temperature dependence of MR relaxation mechanisms and the high sensitivity of MR to changes in the mobility and distribution of tissue water make it particularly suitable for the demonstration and control of thermal energy deposition in tissues. In heterogeneous tissues, MR imaging does not follow changing temperatures directly because even in the case of reversible thermal interactions, there is a hysteresis in the dynamic relationship between MR signal intensity and temperature. Appropriate matching of the laser and MR pulse sequences can, however, optimize the detection of relatively small laser energy deposition, and reversible and irreversible tissue changes can be distinguished. There is a potential for the integration of MR imaging and lasers for three-dimensional control and monitoring of laser-tissue interactions.     

Progress of labor and cardiotocographic parameters in mobilization during labor

Report about 156 intrapartum ambulations who failed progress of labor. Internal fetal monitoring was used in all patients. Labor progress with cervical dilatation was stated in 92,1% in first stage and in 68,7% in second stage of labor. An average increase of 10 mmHg in baseline tonus and an increase in amplitude and contraction frequency were found. No significant changes in either FHR baseline, variability or floating line were observed during ambulation. The lack of any demonstrable ill effects with ambulation in labor and the improved tolerance to pain and comfort are remarkable. Intrapartum ambulation with internal fetal monitoring has a great efficacy for progress of labor and is safe for both mother and fetus.     

Three-dimensional reconstruction of the human central sulcus reveals a morphological correlate of the hand area

One way to improve our understanding of cortical anatomy is to visualize the three-dimensional (3D) shape of the cerebral sulci which is normally hidden. Here, we reconstructed the 3D morphology of the central sulcus (CS) in 17 normal subjects, using conventional magnetic resonance images and dedicated software. We found that the 3D morphology was remarkably consistent in all central sulci. Our analyses revealed three different regions (upper, middle and lower), which were easily identifiable by morphological criteria and sharply interconnected in the reconstructed CS. These morphological regions appear to have a strong functional significance, since the middle region corresponded precisely to the 'hand area', as verified by hand vibration positron emission tomography activation studies in eight cases. These data suggest that the 3D anatomy of the cerebral cortex may facilitate sulcal recognition, and sulcal subdivision into smaller morphological elements, bearing remarkable relationships with functional cortical maps.      

Longitudinal measurement of non-specific bronchial hyperresponsiveness in non-allergic children and adolescents

Non-speeifie bronchial hyperresponsiveness (BHR) is intimately associated with the clinical condition recognized as asthma. BHR ean be present, however, in non-asthmatic subjects, most notable in siblings of sthmatic subjects. What is not well understood, however, is whether inereased bronchial responsiveness, once present, persists over time. In this regard we report on our longitudinal study of BHR in non-allergic children and adolescents. The reported subjects are part of a larger on-going study in a selected population of asthma families, normal families, and twins. Initiated in 1972, t he subjects reported here are those who have had at least one follow-up visit through 1990, and did not have asthma or allergic histories at either their initial or follow-up(s). Subjects completed a standardized respiratory questionnaire, had skin tests, a serum IgE level and a determination of non-specific BHR using a methacholine challenge. Subjects were 6 to 21 years at initial visit. Non-allergic subjects trom asthma families (n = 25), twins (n = 37), and normal families (n = 28) were followed longitudinally, and their age at subsequent visits was not restricted. In this study, we found subjects from asthma families and twins had significantly increased BHR when compared to subjects from normal families. This increased BHR persisted over time and was not influenced by the atopic status of the studied subjects.     

Experimental and modeling study of the excitability of carotid sinus baroreceptors

In this study we examined the effects of blockade of a transient K+ current with 4-aminopyridine (4-AP) on the static stimulus-response relation of myelinated carotid sinus baroreceptors (n = 8), using a vascularly isolated sinus preparation in sodium thiopental-anesthetized dogs. In one class of baroreceptors (type I), which did not fire spontaneously below the pressure threshold (Pth), 4-AP (10(-5) to 10(-4) M) decreased Pth in a dose-dependent manner and transformed the stimulus-response relation from a discontinuous, hyperbolic shape to a sigmoidal, continuous curve. After exposure to 10(-4) M of 4-AP, baroreceptors were spontaneously active below Pth. These effects of 4-AP were more pronounced in baroreceptors with a high control Pth and were independent of enhanced neurotransmitter release or changes in carotid sinus distensibility. In contrast, 4-AP had relatively little effect on type II baroreceptors, which under control conditions are characterized by a continuous, sigmoidal stimulus-response curve. We believe that these effects of 4-AP on baroreceptor discharge were mediated by blockade of a transient K+ conductance that was present at the receptor spike-initiation zone. This hypothesis was examined using a mathematical model based on the Hodgkin-Huxley axon, but modified to include the transient K+ conductance. The modeling results showed that the minimum current necessary to elicit action potential firing is an extremely sensitive function of the magnitude of this K+ conductance, supporting our experimental results obtained with 4-AP. Our findings suggest that a transient K+ conductance might play a role in the determination of Pth and that differences between type I and II receptors could be the result of differences in the effectiveness of this conductance in controlling spike-initiation zone excitability.     

Clinical features of renal diseases in South-East Asia

Summary: The renal diseases in South-East Asia are similar to other parts of the world (i.e. glomerulonephritis, diabetes mellitus, HT, obstructive uropathy, adult-onset polycystic kidney disease, nephrolithiasis and tubulointerstitial diseases). IgA nephropathy with haematuria is most common in Singapore, while IgM nephropathy with nephrotic syndrome is common in Thailand. Lupus nephritis is the most common cause of secondary glomerulonephritis and a major cause of rapidly progressive glomerulonephritis. Acute renal failure from specific infection (malaria, leptospirosis, melioidosis), from toxin exposure (snake bite, wasp sting), from exertional heat stroke, and from drugs is frequently found. Nephrolithiasis, distal renal tubular acidosis and hypokalaemia are endemic in NE Thailand. In conclusion, the broad clinical features of renal diseases in South-East Asia are similar to other regions, with additional specific causes from infections, toxic, metabolic and environmental derangements associated with these tropical locations.