Disparities in Obesity, Physical Activity Rates, and Breast Cancer Survival.

The significantly higher breast cancer (BCa) mortality rates of African-American (AA) women compared to non-Hispanic (NHW) white women constitute a major US health disparity. Investigations have primarily focused on biological differences in tumors to explain more aggressive forms of BCa in AA women. The biology of tumors cannot be modified, yet lifestyle changes can mitigate their progression and recurrence. AA communities have higher percentages of obesity than NHWs and exhibit inefficient access to care, low socioeconomic status, and reduced education levels. Such factors are associated with limited healthy food options and sedentary activity. AA women have the highest prevalence of obesity than any other racial/ethnic/gender group in the United States. The social ecological model (SEM) is a conceptual framework on which interventions could be developed to reduce obesity. The SEM includes intrapersonal factors, interpersonal factors, organizational relationships, and community/institutional policies that are more effective in behavior modification than isolation from the participants' environmental context. Implementation of SEM-based interventions in AA communities could positively modify lifestyle behaviors, which could also serve as a powerful tool in reducing risk of BCa, BCa progression, and BCa recurrence in populations of AA women.

Identification of global data and partitioning scheme for modeling biological data within the electronic medical record.

Using "Black Box" theory we analyzed human physiology. The major physiological means of communication are the vascular and nervous systems. The fundamental partitions of physiology are the vascular capillary fields and efferent and afferent fields of the nervous system. These fields are generally associated with organs and organ systems. Such analysis leads to the conclusion that the global biological data are information carried within the vascular and nervous systems. Data elements and processes within organs are important to other organs only through their effects on these global elements. Incorporation of these concepts into medical databases would allow the partitioning of the software around physiological systems. As a result of partitioning the utility of the electronic medical record, software could be greatly expanded.

The relationship of the subarachnoid injection of blood and blood fractions with cardiac rate change and arrhythmias.

The relationship of subarachnoid hemorrhage and cardiac arrhythmias was studied utilizing a Sprague-Dawley rat model. A total of 30 male animals were divided into five groups and given subarachnoid injections of either blood, blood fractions, or control substances. Blood pressure, intracranial pressure, serum electrolytes, arterial blood gases, hypothalamic multiple unit activity and an electrocardiogram were concurrently monitored. Cardiac arrhythmias were graded on a 0 to 4 + objective scale. Control parameter values were similar for all animals. Arrhythmias, hypotension, and decreased hypothalamic multiple unit activity were seen with infusion of whole blood and packed red blood cells. Packed red blood cells were statistically demonstrated to have the most potent arrhythmogenic effect. Cardiac histopathology revealed myocardial contraction band lesions most predominant in the packed red blood cell group. In addition, significant QT interval prolongation was observed after subarachnoid injection of either whole blood or packed red blood cells. These findings indicate that packed red blood cells, or a component thereof, may play an important role in the etiology of immediate (i.e. acute) post subarachnoid hemorrhage induced cardiac arrhythmias.

Epileptologist's assistant: a cost effective expert system.

Epileptologist's Assistant is an expert system designed to cost effectively handle routine care in an epilepsy follow up clinic. The system guides nurses in gathering patient histories and then generates progress notes and a patient information sheet. The progress note, organized in the SOAP format, is reviewed by the physician with the patient. For difficult cases the physician may modify the Assessment or Plan sections; the Subjective and Objective sections rarely need modifications. The assertion of cost-effectiveness is based on time/motion data. Without the system a physician in our epilepsy clinic spends about 21 minutes seeing a patient. With the system the nurse spends about 14 minutes with the patient and the physician spends about 7 minutes. Two nurses and a physician handle the work load of 3 physicians. Physician time is cut by about 66%. Using the average salaries for physicians and nurses at the Department of Veterans Affairs, the cost of a clinic visit is reduced 39% by using the expert system and nurses. In addition, the progress note is more legible, it contains more information, Q/A procedures are implemented at the point of patient contact, and the data is entered into a computer system in a data field format.

A cost effective expert system to assist physicians: epileptologists' assistant.

While medical expert systems helped demonstrate that artificial intelligence was possible, few medical systems have been heralded as practical successes. We believe that expert systems will be practical successes if they cost effectively handle most of a physician's workload (i.e., routine care). To accomplish this goal, technology must appear invisible to the user; the system must be intuitive and anticipate users' needs. "Epileptologists' Assistant" is an example of our approach of combining a graphical user interface with an expert system and data base in a system to help in a routine specialty clinic. The goal is for two nurses and a physician to handle the workload of three physicians while increasing the quality of care. The current system reduces physician time by 66%. Our ultimate goal is to create a unified family of systems for medical specialties.

Plasma 5-S-cysteinyldopa differentiates patients with primary and metastatic melanoma from patients with dysplastic nevus syndrome and normal subjects.

To determine whether plasma 5-S-cysteinyldopa levels are useful in following up patients at risk for melanoma, we measured plasma 5-S-cysteinyldopa in patients with dysplastic nevus syndrome and/or malignant melanoma and in control subjects. In patients with dysplastic nevus syndrome, plasma 5-S-cysteinyldopa levels did not differ from those in control subjects. Conversely, patients with malignant melanomas had significantly higher plasma 5-S-cysteinyldopa levels than did controls. Those with localized cutaneous malignant melanoma and no distant metastases (Stage I and II disease) had 5-S-cysteinyldopa levels twofold greater than those of control subjects, whereas the levels of those with regional lymph node involvement (Stage III disease) were fourfold greater than those of control subjects. Levels of those with extraregional metastases (Stage IV disease) were 7- to 450-fold higher than those of control subjects. Moreover, plasma 5-S-cysteinyldopa levels correlated with the spread of disease and were useful in distinguishing primary melanoma and Stages III and IV melanoma. We conclude that plasma 5-S-cysteinyldopa may be an important tool for identifying melanoma at an earlier, more curable stage and for following up patients at risk for the development of melanoma, for example, those with dysplastic nervus syndrome.

Variable region framework differences result in decreased or increased affinity of variant anti-digoxin antibodies.

Rare spontaneous variants of the anti-digoxin antibody-producing hybridoma 40-150 (Ko = 5.4 x 10(9) M-1) were selected for altered antigen binding by two-color fluorescence-activated cell sorting. The parent antibody binds digoxin 890-fold greater than digitoxin. The variant 40-150 A2.4 has reduced affinity for digoxin (Ko = 9.2 x 10(6) M-1) and binds digoxin 33-fold greater than digitoxin. A second-order variant, derived from 40-150 A2.4 (designated 40-150 A2.4 P.10), demonstrated partial regain of digoxin binding (Ko = 4.4 x 10(8) M-1). The altered binding of the variant 40-150 A2.4 was accounted for by a point mutation resulting in substitution of arginine for serine at position 94 in the heavy chain variable region. Antibody 40-150 A2.4 P.10 also contains this arginine but owes its enhanced antigen binding to deletion of two amino acids from the heavy chain amino terminus. This unusual sequence alteration in an immunoglobulin framework region confers increased affinity for antigen.

Plasma 5-S-cysteinyldopa correlates with tumor size in melanoma-bearing mice.

A sensitive assay method employing high performance liquid chromatography with electrochemical detection (HPLC-ED) was used to compare 5-S-cysteinyldopa (CD) levels in plasma to tumor size in a murine melanoma model system. Plasma CD levels correlated with the sizes of primary tumor masses in mice, and the presence of metastatic tumors did not significantly affect the relationship. Elevated plasma CD levels appear to be directly related to tumor pigmentation: mice who had nonpigmented tumors induced by injections of amelanotic melanoma cells (NP) did not have elevated plasma CD levels. These studies indicate that plasma CD levels may serve as a marker for pigmented malignant melanomas and may be useful in following patients who are at high risk for these tumors.

Serotonin type-2 receptor mediated regulation of substance P release in the ventral spinal cord and the effects of chronic antidepressant treatment.

Regulation of the release of substance P (SP) by the coexisting neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) in the ventral spinal cord and the effects of chronic antidepressant treatment mediated changes in serotonin metabolism on the regulation, were examined. The K+ (40 mmol/l) evoked release of (SP) from slices of the ventral spinal cord of the rat was potentiated by (5-HT) applied to 100 mumol/l concentration. This effect was blocked by the serotoninergic antagonists methysergide (10 mumol/l), methiotepin (10 mumol/l) and fully blocked by ketanserin (10 mumol/l). Thus the 5-HT receptor which regulates the release of SP appears to belong to the type-2 5-HT receptors. Chronic treatment with the selective serotonin uptake inhibitor zimelidine (14 days, 2 X 10 mumol/kg/day, p.o.) lowered the tissue levels of the 5-HT metabolite: 5-hydroxyindol acetic acid (5-HIAA) and elevated the tissue levels of SP in both the ventral and dorsal spinal cord as compared to that in the vehicle treated group (14 days, 2 X 5 ml saline/kg/day, p.o.). The decrease in the 5-HIAA levels after chronic zimelidine treatment was quantitatively similar in the dorsal (33%, p less than 0.01) and ventral (31%, p less than 0.05) spinal cord. The increase in SP levels after chronic zimelidine treatment was more pronounced in the ventral cord (80%, p less than 0.01) where the majority of the SP containing nerve endings also contain 5-HT, than in the dorsal spinal cord (22% increase in SP, p less than 0.05), where only a minor fraction of the SP-containing nerve endings shows a 5-HT/SP coexistence.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticholinergic potency of psychoactive drugs in human and rat cerebral cortex and striatum.

The affinity of selected antipsychotic and antidepressant drugs for the muscarinic receptor was studied in membranes from both human and rat striatum and cerebral cortex. While there are regional differences in the anticholinergic potency of the drugs, there is good agreement between the obtained inhibition constants from the corresponding human and rat striatum (r: 0.98) and from human and rat cerebral cortex (r: 0.96). There is also good agreement between the obtained Ki values within one species: human cerebral cortex versus human striatum (r: 0.99) and for rat cerebral cortex and rat striatum (r: 0.87). Thus, the previously published quantitative estimates of the antimuscarinic activity of psychoactive drugs which were derived from studies on membranes from rat brain give an accurate estimate of the antimuscarinic activity in human brain. The drugs tested in this study include chlorpromazine acetophenazine, haloperidol, sulpiride, remoxipride (FLA-731 (-), a substituted benzamide), amitriptyline and two serotonin uptake blockers: norzimelidine and alaproclate.

In vivo and in vitro studies on the potentiation of muscarinic receptor stimulation by alaproclate, a selective 5-HT uptake blocker.

Alaproclate (10-60 mg/kg) injected i.p. into male mice potentiated and prolonged the oxotremorine and physostigmine-induced tremor in a dose-dependent manner. Atropine completely blocked the tremor caused by oxotremorine or physostigmine both in the presence and absence of alaproclate. Pretreatment with the 5-HT receptor antagonist metitepine completely blocked the enhancement of oxotremorine-induced tremor caused by alaproclate. Biochemical studies indicated that the above effects cannot be explained by assuming that alaproclate a) acts as a cholinergic agonist, b) inhibits the acetylcholine esterase, c) interferes with choline uptake or acetylcholine synthesis, or d) directly potentiates the release of acetylcholine. In ligand binding studies alaproclate was found to be a weak competitive inhibitor of muscarinic antagonist binding to membranes from the rat cerebral cortex, rat striatum, human cerebral cortex and human striatum. (Ki approximately 28-40 microM in all four tissues). The present results suggest that alaproclate may potentiate muscarinic responses by a mechanism involving serotonergic receptor mechanisms rather than by a direct interaction with the muscarinic cholinergic receptors.

Uncoupler-accelerated efflux of 5-hydroxytryptamine from platelets of healthy subjects and patients with unipolar and bipolar depression.

The efflux of 14C-5-hydroxytryptamine (5HT) from platelets of 25 depressed patients (16 unipolar and 9 bipolar) and 22 control subjects was studied in the presence of carbamyl cyanide m-chlorophenylhydrazone (FCCP), which dissipates H+ gradients. FCCP (0.31 microM), at 10 minutes' incubation time, enhanced the efflux of 14C-5HT to a significantly higher extent from platelets of patients with bipolar depression than from platelets of control subjects. An analysis of variance revealed a significant interaction between the diagnostic categories (unipolar, bipolar, and control) and sex in accounting for variation of the FCCP-evoked efflux. The diagnostic category X sex effect was also significant. The results reported indicate that the FCCP-evoked efflux of 5HT is an easily measured biochemical parameter of possible diagnostic interest.

Glucagonoma syndrome: in vitro evidence that glucagon increases epidermal arachidonic acid.

A 63-year-old white woman with perioral dermatitis, a sore tongue, and an erythematous dermatosis in the inframammary and perineal regions underwent surgical removal of a pancreatic glucagonoma. The patient's plasma and pooled normal human plasma containing Sigma glucagon were fed to human keratinocyte cultures and increased arachidonic acid levels by 300% and 200%, respectively, when compared to pooled normal human plasma with no added commercial glucagon. These experiments suggest that glucagon may increase inflammatory mediators such as arachidonic acid and its metabolites in the epidermis, causing the skin lesions seen in the glucagonoma syndrome.

Isolation and purification of a pemphigus vulgaris antigen from human epidermis.

Pemphigus vulgaris is an autoimmune disease associated with an autoantibody directed against a keratinocyte membrane antigen. The purpose of this study was to purify the human pemphigus vulgaris antigen, to produce an antibody to this antigen, and to use the antibody to induce pemphigus in newborn mice. Various techniques to extract the membrane-rich pellet from human epidermal homogenate were compared; 1% sodium dodecyl sulfate (SDS) and 1% dimethylsulfoxide proved to be superior to extract the pemphigus vulgaris antigen. This antigen was identified by transfer blotting to nitrocellulose paper, incubated with pemphigus vulgaris serum, or 20 control sera, and detected with fluorescein labeled antisera to human IgG. Since concanavalin A inhibits the binding of pemphigus vulgaris antibody to tissue sections, we studied the binding of the extracted proteins to concanavalin A covalently coupled to Sepharose. Pemphigus vulgaris antigen bound to the concanavalin A column and was released by 0.02 M methyl alpha-D-mannopyranoside. The proteins thus recovered were subjected to AcA 54 gel permeation chromatography, and the pemphigus antigen was detected by the transfer blot assay. The antigen corresponded to a discrete peak at 66,000 D by gel permeation and gave one homogeneous band at 33,000 D in urea-SDS-polyacrylamide gel electrophoresis. Monospecific antibody to the antigen raised in rabbits stained human epidermis in the same manner as the pemphigus vulgaris autoantibody and induced pemphigus vulgaris in newborn mice when injected intraperitoneally. A pemphigus vulgaris antigen has been purified from adult human epidermis. It is a 66,000-D membrane glycoprotein that is composed of two apparently identical subunits of 33,000 D each.

Hydralazine-induced systemic lupus erythematosus presenting as pyoderma gangrenosum-like ulcers.

A 48-year-old white woman who for 3 years had been taking hydralazine, 100 mg three times a day, propranolol, 160 mg twice a day, and chlorothiazide, 500 mg/day, for hypertension suddenly developed rapidly expanding ulcers that looked like pyoderma gangrenosum. Arthralgias, fevers, and occasional shortness of breath were also noted. A pericardial effusion was diagnosed by echocardiography. The antinuclear antibody (ANA) titer on routine mouse liver substrate was initially negative, but the ANA titer was positive (1:1,920) on human epithelioid cell substrate. Antibodies to histones and single-stranded DNA were also elevated. After discontinuing hydralazine, all signs and symptoms cleared over a 4-week period. At the time of discharge the ANA titer had decreased to 1:480.

Lentiginosis associated with a left atrial myxoma.

A 14-year-old white male patient with lentiginosis was in congestive heart failure. He was noted to be redheaded, and the lentigines were especially concentrated on the face, including the lips. A two-dimensional echocardiogram revealed an orange-sized mobile mass in the left atrium. Cardiac surgery for removal of the left atrial myxoma was successful, and a complete recovery was made. This is the second report of lentiginosis associated with a left atrial myxoma and the first in which the immediate family did not have similar pigmentary changes. Lentiginosis and associated cardiac manifestations are briefly reviewed.