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Consensus conference. Adjuvant chemotherapy for breast cancer.

In 1985, breast cancer will be diagnosed in approximately 120,000 women; in 90% of these women, the disease will apparently be limited to the breast and axillary lymph nodes. Despite advances in early diagnosis and primary treatment with surgery, radiation therapy, or both, more than a third of these patients will develop systemic disease and ultimately die. In the broadest sense, all of these patients are potential candidates for some form of systemic adjuvant therapy. Adjuvant therapy of breast cancer involves the use of cytotoxic drugs or endocrine therapy after definitive primary therapy. The rationale is to eradicate occult metastatic disease that otherwise would be fatal. The goal of adjuvant therapy is to significantly prolong survival, while maintaining an acceptable quality of life. Three measures are important in evaluating whether this goal is met by specific treatments: 1. The effect of therapy on overall survival: the length of time a woman survives following a diagnosis of breast cancer. 2. The effect of therapy on disease-free survival: the length of time a woman remains free of any recurrence of disease. Prolonged periods of disease-free survival may be advantageous in their own right, since quality of life is likely to be better before than after relapse. There is also some evidence that longer periods of disease-free survival may translate into better overall survival rates. 3. The effect of therapy on quality of life: in choosing an adjuvant therapy program, potential benefits must be balanced against both short-term and long-term side effects. Also important are the substantial psychological, social, and economic problems women may experience as a result of treatment. An increasing number of important prognostic variables have been identified that define the natural history of breast cancer. These include well-established factors such as histological status of axillary lymph nodes, primary tumor size, steroid hormone receptors, menopausal status or age, and histopathology. Assessment of cell differentiation and proliferation, which can be determined by newer techniques, may also be significant. The pathological status of the axillary lymph nodes remains the single most important prognostic variable, and four lymph node categories have been defined (negative, one to three positive nodes, four to nine positive nodes, and ten or more positive nodes). Since definitions of menopausal status vary widely among clinical trials, age (less than 50 vs greater than or equal to 50 years) can be substituted as a prognostic variable.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Agents↗

A case of mild Alzheimer's disease accompanied by periodic synchronous discharges.

Periodic synchronous discharges (PSD) on the electroencephalogram can be observed in diseases such as Creutzfeldt-Jakob disease, hypoxic encephalopathy and Alzheimer's disease (AD). However, in previously reported cases of AD with PSD, PSD have only been found many years after the diagnosis of AD. We recently encountered a patient with mild AD accompanied by transient PSD. To our knowledge, this is the first case report to suggest that PSD can occur in mild AD.

Aged↗

Monthly variation of hospital admission and mortality of peptic ulcer disease: a reappraisal of ulcer periodicity.

The occurrence of peptic ulcer is characterized by a seasonal variation, the meaning of which is poorly understood. The present study examined the periodicity of hospital admissions and mortality resulting from gastric and duodenal ulcer to determine its etiologic relevance. Ulcer periodicity was studied in the nationwide data sets of the Department of Veterans Affairs, the Health Care Financing Administration, and the Vital Statistics. Both ulcer types were characterized by similar patterns of periodicity. Hospital admissions peaked during the first 3 months of the year, followed by a marked decline during summer and a second smaller peak around October. This pattern occurred independently of age, sex, race, and place of residence. It also pertained to ulcers complicated by hemorrhage or perforation. Although total admissions peaked earlier during the year and showed a less consistent peak in October, there was a close resemblance between the periodicity of all diseases and that of peptic ulcer. Mortality was highest in January and lowest in July for all disease and ulcer diseases alike. The similarity between the periodicity of peptic ulcer and other diseases suggests that the major factors responsible for the cyclic behavior of gastric and duodenal ulcer are not particular to these diseases but affect other unrelated diseases alike.

Hospitalization↗

[Cardiac involvement in neuromuscular diseases].

Many neuromuscular disorders involve the heart, occasionally with overt clinical disease. Muscular dystrophies (dystrophinopathies, limb girdle muscular dystrophy, Emery-Dreifuss muscular dystrophy, Steinert's myotonic dystrophy), congenital myopathies, inflammatory myopathies and metabolic diseases (glycogenosis, periodic paralysis, mitochondrial diseases) may produce dilated or hypertrophic cardiomyopathy and heart rhythm or conduction disturbances. Furthermore the heart is commonly involved in some hereditary and degenerative diseases (Friedreich's ataxia and Kugelberg-Welander syndrome) and acquired (Guillain-Barré syndrome) or inherited (Refsum's disease and Charcot-Marie-Tooth syndrome) polyneuropathies. A cardiologist's high clinical suspicion and a simple but systematic skeletal muscle and peripheral nerve investigation, including muscle enzymes quantification, neurophysiological study and muscle biopsy, are necessary for an accurate diagnosis. In selected patients, more sophisticated biochemical and genetic analysis will be necessary. In most cases, endomyocardial biopsy is not essential for the diagnosis.

Adolescent↗

[Changes in the protein metabolic indices in the early postshock period of traumatic disease].

The article analyzes changes in the protein metabolism of the organism of patients with associated trauma followed by shock. It was found that during shock and postshock period (as long as 14 days after trauma) of the traumatic disease hypoproteinemia was developing with the degree proportional to the severity of shock. To normalize protein metabolism it is necessary, in addition to a wide use of transfusions of blood and protein hydrolysates, to use protein mixtures (food concentrates) for oral feeding of critical patients in the complex of simultaneous measures directed to valuable correction of systemic and organic hemodynamics during this period.

Alanine Transaminase↗

Malaria control and long-term periodicity of the disease in Pakistan.

The classic investigations of the malaria epidemics in the Punjab led to the conclusion that in this most populous and most malarious province of the present-day Pakistan, epidemics occurred regularly at intervals of approximately eight years. Against this background, the results of a Malaria Control Programme launched in 1975 are examined. The Programme, supported by USAID and WHO, represents in economic terms the greatest effort made against malaria in the country. Malathion, the main attack weapon of the Programme, was used on an unprecedented scale. This created logistic and--unexpectedly--toxicity problems among the spraying workers. Despite these difficulties, an over-all reduction of 76% in the slide positivity rate was observed in the first two years of operations of the Programme. The authors warn against measures which may curtail the activities of the Programme when, according to the cyclical periodicity of malaria in the Punjab, an epidemic wave can be expected in 1980-81, with inevitable repercussions all over the country.

Disease Outbreaks↗

[The pathogenetic correction of disorders of blood oxygen transport in the postshock period of traumatic disease].

The state of the gas exchange system was analyzed in 79 patients with a severe combined trauma (SCT) at the postshock period. It allowed detection of specific features of disturbances of the oxygen transport by blood in different kinds of injuries. The SCT with a critical injury of the brain is more often accompanied by hyperdynamia of circulation within the first two days after trauma, while the 3rd-4th days are characterized by a sharp drop of the heart index to (2,17 +/- 0,21) l/min.m2, oxygen transport to (261,9 +/- 37,2) ml/min.m2, oxygen consumption to (99,9 +/- 8,3) ml/min.m2. If the SCT was accompanied by a contusion of the heart the changes of central hemodynamics were especially pronounced and prolonged having a hypocirculatory character with a decreased cardiac and stroke index from the first hours of stay at the hospital (20,4 +/- 1,5) ml/m2 and (2,10 +/- 0,14) ml/min.m2 correspondingly. It led to a substantial decrease of indicators of the transport and consumption of oxygen correspondingly: (266,5 +/- 25,1) ml/min.m2 and (112,6 +/- 8,2) ml/min.m2. For the pathogenetically substantiated therapy of disturbances of the oxygen transport by blood the following measures are considered: isovolemic hemodilution, moderate sympathetic blockade, the use of membrane stabilizers, glucocorticoids, adrenolytics, solcoseryl. The state of the organism system of respiration and subsystem of the oxygen transport must be taken into consideration when choosing the optimum time for performing the postponed operative interventions at the postshock period.

Acute Disease↗

Hydroxyurea and periodicity in myeloproliferative disease.

Three patients, one with polycythaemia vera (PV) and two with chronic myeloid leukaemia (CML), are described who had cycling of blood counts which became apparent whilst receiving hydroxyurea therapy. Significant periodicity was confirmed with the use of the Lomb periodogram. This is Fourier power spectral analysis tailored for unevenly sampled data. The patient with PV had marked oscillations of platelet counts with a periodicity of 29 d and an amplitude of (202-588)x10(9)/L. Smaller oscillations of neutrophil, monocyte and lymphocyte numbers and Hb levels occurred with a similar periodicity. Anticipatory changes in hydroxyurea dosage or the maintenance of a constant dose did not abolish periodicity, but a change in therapy to the non-cycle-specific drug anagrelide dampened and abolished the cycling. One of the patients with CML had tremendous and clear oscillations in white cell, platelet and Hb levels, with a mean periodicity of 74 d. The other had erratic counts which were confirmed to be significantly periodic (64 d), on spectral analysis. A change in therapy to busulphan in both these patients again dampened and abolished the cycling. Hydroxyurea, which is a cell-cycle-specific agent, probably exacerbates the periodicity which may be present in some patients with myeloproliferative disease. A change in therapy to non-cycle-acting compounds such as busulphan or anagrelide results in much more stable counts in such patients.

Adult↗

Identification of a prodromal period in Crohn's disease but not ulcerative colitis.

OBJECTIVES: Irritable bowel syndrome, a common gastrointestinal diagnosis, has not been clearly studied in inflammatory bowel disease. Some of the residual symptoms in subjects treated with Crohn's disease and ulcerative colitis are thought to be related to irritable bowel syndrome. The aims of this study were 1) to describe the duration and nature of complaints before the diagnosis of Crohn's disease and ulcerative colitis (prodromal period), and 2) to determine the role of IBS in this prodromal period. METHODS: A total of 66 patients with confirmed inflammatory bowel disease were enrolled in the study. The subjects received a questionnaire to ascertain the nature and duration of symptoms preceding the diagnosis of Crohn's disease or ulcerative colitis, including features described under the Rome criteria for irritable bowel syndrome. RESULTS: Of the 66 subjects analyzed, 45 had Crohn's disease and 21 had ulcerative colitis. The prodromal period was 7.7 +/- 10.7 yr for Crohn's disease and 1.2 +/- 1.8 yr for ulcerative colitis (p < 0.05). Once patients meeting the Rome criteria for irritable bowel syndrome during the prodrome were excluded, the duration of the prodromal period (non-IBS) for ulcerative colitis dropped to 0.8 +/- 1.3 yr compared to 6.9 +/- 9.8 yr in the Crohn's disease group (p < 0.05). The symptoms of the non-IBS prodrome in subjects with Crohn's disease were bloating, diarrhea, stomach pain, heartburn, fever, weight loss, and fatigue. Further analysis demonstrated that subjects whose Crohn's disease initially began as colonic disease had a longer prodrome than with small bowel. In the non-IBS Crohn's group, there was also a correlation between the age at the time of diagnosis and the duration of prodrome (r = 0.67, p < 0.0001). CONCLUSIONS: There is a significant prodromal period before the time of diagnosis of Crohn's disease that is not found in ulcerative colitis even after exclusion of subjects with IBS.

Adult↗

Seasonality of infectious diseases.

Seasonality, a periodic surge in disease incidence corresponding to seasons or other calendar periods, characterizes many infectious diseases of public health importance. The recognition of seasonal patterns in infectious disease occurrence dates back at least as far as the Hippocratic era, but mechanisms underlying seasonality of person-to-person transmitted diseases are not well understood. Improved understanding will enhance understanding of host-pathogen interactions and will improve the accuracy of public health surveillance and forecasting systems. Insight into seasonal disease patterns may be gained through the use of autocorrelation methods or construction of periodograms, while seasonal oscillation of infectious diseases can be easily simulated using simple transmission models. Models demonstrate that small seasonal changes in host or pathogen factors may be sufficient to create large seasonal surges in disease incidence, which may be important particularly in the context of global climate change. Seasonality represents a rich area for future research.

Communicable Diseases↗