Upper gastrointestinal hemorrhage in African-American and Hispanic elderly patients.

OBJECTIVES: To investigate the frequency and etiology of upper gastrointestinal hemorrhage (UGIH) in African-American and Hispanic elderly patients, and to determine the risks and benefits of endoscopic intervention. SETTING: An inner-city county hospital serving predominantly African-American and Hispanic populations. METHODS: Records of 290 patients, 65 to 95 years of age, with diagnosis of UGIH, were reviewed retrospectively, 12 White and 8 Asian patients were excluded. RESULTS: Source of bleeding remained unidentified in 25 of 270 patients and they were also excluded. Endoscopic findings in 245 patients were: 59 gastric ulcers, 52 duodenal ulcers, 49 gastric erosions, 37 gastroesophageal varices, 25 Mallory Weiss tears, 15 angiodysplasias, 13 Dieulafoy's lesions, 12 portal hypertensive gastropathies, 8 esophageal cancers with bleeding, and 7 gastric cancers with bleeding; 32 patients had more than one lesion. Endoscopic therapy was administered to 159 patients, and was helpful in stopping bleeding and/or delaying surgery in 102 patients. Overall, there were 59 deaths, mostly due to underlying multiple system disease. There was no death directly due to endoscopy. CONCLUSIONS: Acute UGIH in African-American and Hispanic elderly patients is a serious condition, associated with significant morbidity and mortality. Benefits of endoscopy should be offered to all such patients, and endoscopy should not be withheld because of age alone.

Safety and efficacy of digital rectal examination in patients with acute myocardial infarction.

OBJECTIVE: Digital rectal examination (DRE) is often ignored or deferred in acute myocardial infarction (AMI). The aim of this study was to determine the safety and efficacy of DRE in patients with AMI. METHODS: This was a prospective, comparative, stratified study in an inner-city teaching hospital. A total of 480 patients from intensive care and telemetry units were stratified into three groups. Group I included 160 patients with AMI in whom a DRE was performed and electrocardiographic (EKG) recordings were obtained. Group II included 155 patients with AMI in whom DRE was not done, but EKG recordings were made. Group III consisted of 165 patients without AMI in whom DRE was performed and EKG recordings were obtained. Sustained arrhythmias and vital signs were measured. RESULTS: None of the patients developed sustained arrhythmias and there was no change in vital signs. DRE resulted in the detection of several clinically significant findings. CONCLUSION: DRE was found to be safe in our stable patients with AMI.

Selective radiosensitization of p53-deficient cells by caffeine-mediated activation of p34cdc2 kinase.

The induction of tumor cell death by anticancer therapy results from a genetic program of autonomous cell death termed apoptosis. Because the p53 tumor suppressor gene is a critical component for induction of apoptosis in response to DNA damage, its inactivation in cancers may be responsible for their resistance to genotoxic anticancer agents. The cellular response to DNA damage involves a cell-cycle arrest at both the G1/S and G2/M transitions; these checkpoints maintain viability by preventing the replication or segregation of damaged DNA. The arrest at the G1 checkpoint is mediated by p53-dependent induction of p21WAF1/CIP1, whereas the G2 arrest involves inactivation of p34cdc2 kinase. Following DNA damage, p53-deficient cells fail to arrest at G1 and accumulate at the G2/M transition. We demonstrate that abrogation of G2 arrest by caffeine-mediated activation of p34cdc2 kinase results in the selective sensitization of p53-deficient primary and tumor cells to irradiation-induced apoptosis. These data suggest that pharmacologic activation of p34cdc2 kinase may be a useful therapeutic strategy for circumventing the resistance of p53-deficient cancers to genotoxic anticancer agents.

The effects of sulindac on colorectal proliferation and apoptosis in familial adenomatous polyposis.

BACKGROUND & AIMS: The mechanism by which sulindac causes regression of adenomas in patients with familial adenomatous polyposis (FAP) is unclear. Conflicting data on the drug's effects on colorectal epithelial proliferation have been reported. An alternative mechanism, and one not previously studied, is via induction of colorectal epithelial cell apoptosis (programmed cell death). This hypothesis was tested by studying the effects of sulindac on colorectal epithelial proliferation and apoptosis in patients with FAP. METHODS: Cell proliferation was studied via immunohistochemistry for cell nuclear antigen in a group of 22 patients randomized to either sulindac (150 mg twice a day) or placebo in a previously published trial. The rectal epithelium from 7 additional patients with FAP treated with sulindac was examined by flow cytometry to assess changes in cell-cycle distribution and apoptosis. RESULTS: Although sulindac caused a significant decrease in polyp size and number, there was no significant change in cytokinetic variables or cell cycle distribution 3 months after treatment. However, the subdiploid apoptotic fraction was increased significantly 3 months after treatment with sulindac (31.3% +/- 4.8% compared with 10% +/- 4.3% at baseline; P = 0.01). CONCLUSIONS: Our findings suggest that sulindac does not affect colorectal epithelial proliferation and that its effects in patients with FAP may instead result from induction of apoptosis.

BCR-ABL-mediated inhibition of apoptosis with delay of G2/M transition after DNA damage: a mechanism of resistance to multiple anticancer agents.

A critical determinant of the efficacy of antineoplastic therapy is the response of malignant cells to DNA damage induced by anticancer agents. The p53 tumor-suppressor gene is a critical component of two distinct cellular responses to DNA damage, the induction of a reversible arrest at the G1/S cell cycle checkpoint, and the activation of apoptosis, a genetic program of autonomous cell death. Expression of the BCR-ABL chimeric gene produced by a balanced translocation in chronic myeloid leukemia, confers resistance to multiple genotoxic anticancer agents. BCR-ABL expression inhibits the apoptotic response to DNA damage without altering either the p53-dependent WAF1/CIP1-mediated G1 arrest or DNA repair. BCR-ABL-mediated inhibition of DNA damage-induced apoptosis is associated with a prolongation of cell cycle arrest at the G2/M restriction point; the delay of G2/M transition may allow time to repair and complete DNA replication and chromosomal segregation, thereby preventing a mitotic catastrophe. The inherent resistance of human cancers to genotoxic agents may result not only by the loss or inactivation of the wild-type p53 gene, but also by genetic alterations such as BCR-ABL that can delay G2/M transition after DNA damage.

Inhibition of apoptosis during development of colorectal cancer.

Colorectal tumorigenesis proceeds through an accumulation of specific genetic alterations. Studies of the mechanism by which these genetic changes effect malignant transformation have focused on the deregulation of cell proliferation. However, colorectal epithelial homeostasis is dependent not only on the rate of cell production but also on apoptosis, a genetically programmed process of autonomous cell death. We investigated whether colorectal tumorigenesis involved an altered susceptibility to apoptosis by examining colorectal epithelium from normal mucosa, adenomas from familial adenomatous polyposis, sporadic adenomas, and carcinomas. The transformation of colorectal epithelium to carcinomas was associated with a progressive inhibition of apoptosis. The inhibition of apoptosis in colorectal cancers may contribute to tumor growth, promote neoplastic progression, and confer resistance to cytotoxic anticancer agents.

Motor function after stroke.

Two hundred and eighty-seven patients who had survived an acute stroke for up to one week after admission to hospital were examined for loss of motor function in the arm and leg. There was a highly significant difference in problem-solving, spatial neglect, communication and postural function between those with significant motor loss and those without. There was no significant difference in memory impairment. Significant loss in motor power had a bad prognosis for functional outcome, length of stay in hospital and survival. If recovery was to occur, it had done so by eight weeks.

Proprioception and spatial neglect after stroke.

Proprioception and neglect were studied in 287 patients surviving up to one week after the onset of their stroke. The presence of proprioceptive loss indicated a more extensive lesion and a larger proportion of these patients had impairment of intellectual function, motor power in the upper and lower limb, and postural function. Proprioceptive loss also had an adverse effect on the level of independence achieved by discharge, final placement, mortality and length of stay in hospital. In 87% of the survivors recovery of proprioception had occurred by eight weeks. Significant neglect was associated with high mortality and poor outcome for functional recovery.

Predicting functional outcome following acute stroke using a standard clinical examination.

In a series of 149 patients admitted to a stroke unit, the outcome of the acute phase of stroke rehabilitation, assessed by the patients' return to independence, was found to be related to the results of standardized weekly clinical examinations of mental, motor, sensory and communication function. The prediction of subsequent independence was estimated just as accurately using the results from three of these tests (upper limb motor function, postural function and proprioception) as when using the entire set of tests. A group of patients with little chance of responding to rehabilitation was identified.

Malalignment of the shoulder after stroke.

One hundred and ten consecutive patients (51 men, 59 women) admitted to a stroke unit were studied for radiographic changes at the shoulder on the affected side. Malalignment was found in 51 (46%) patients, of whom 37 (72.5%) had changes on the initial x-ray film and a further 14 (27.5) developed malalignment over the following 12 months. These findings indicate that malalignment of the shoulder is common in the early stages of a stroke and may be missed unless radiographs are taken with the patient erect and the arm unsupported. Malalignment may lead to delay and limitation in restoration of function. The consequences of malalignment can be prevented by correct handling, positioning, and full passive movement of the shoulder from the onset of the stroke.

Therapy impact on functional outcome in a controlled trial of stroke rehabilitation.

In a randomized controlled trial of management of acute stroke in the elderly, a higher proportion of patients were assessed as independent in self-care in a stroke unit compared with patients with similar levels of neurologic impairment treated in medical units. The use of physical therapy and occupational therapy in the stroke unit and medical units was compared. Patients in the stroke unit received less therapy over a shorter period of time; however, a higher proportion had occupational therapy beginning at a much shorter interval after admission. Early introduction of rehabilitation by therapists may be more important than the amount of duration of treatment.

The use of health and social services in the management of stroke in the community: results from a controlled trial.

The use of hospital and community services during the follow-up of a controlled trial which evaluated the effectiveness of a stroke unit and medical units in the management of acute stroke in the elderly is described. Patients from the stroke unit received more health and social services compared with medical unit patients, particularly in the initial follow-up period. The use of services was not related to the functional outcome of patients at hospital discharge. No overall difference occurred between stroke unit and medical unit patients in hospital bed days used throughout the study.

The triage of stroke rehabilitation.

In this paper we describe the use of triage to select patients for a trial in which a comparison was made of the effectiveness of a stroke unit and medical units in the rehabilitation of acute stroke. Completing the triage for hospital admission of stroke enabled an estimate to be made of the size of a stroke unit per unit of population.

Management of acute stroke in the elderly: follow-up of a controlled trial.

Follow-up of a controlled trial of the management of acute stroke in the elderly showed that the improvement in functional outcome at the time of discharge from hospital that had been achieved through establishing a stroke unit had disappeared by one year. Factors that might have contributed to this included overprotection by the families of patients who had been treated in the stroke unit, who were not permitted to carry out activities of daily living in which they were independent, and the early discharge from medical units of patients whose full rehabilitation potential had not been realised. Prolonging the benefits of short-term gains in functional outcome through the intervention of a stroke unit requires that all the links in the chain of stroke rehabilitation are maintained, including the proper orientation of patients' families before discharge from hospital.

Management of acute stroke in the elderly: preliminary results of a controlled trial.

A randomised controlled trial compared the management of elderly patients with acute stroke in a stroke unit and medical units. A significantly higher proportion of patients discharged from the stroke unit (78 of the 155 admitted) were assessed as independent compared with patients discharged from medical units (49 of the 152 admitted). The intensive use of treatment that might have been implied by creating a stroke unit did not occur, although almost all the patients admitted to the unit received occupational therapy while only 47% of the patients admitted to medical units received occupational therapy. The delay before starting treatment was significantly shorter in the stroke unit. Results of this trial show that the stroke unit improved the natural history of stroke by increasing the proportion of patients who were returned to functional independence.

Observer variation in the clinical assessment of stroke.

Clinical assessments have to be used in epidemiological studies in the absence of more objective means of establishing diagnosis or recording events in the natural history of disease. This requires the standardization of definition, technique and interpretation as a means of reducing observer variability in clinical examination. The methods used to reduce the observer variation in the clinical assessment of stroke patients are described and results are presented which demonstrate the degree to which this was achieved.

Neurological disorders in the elderly at home.

Eight hundred and eight subjects participated in three surveys of random samples of people aged 65 years or more living in their own homes. Neurological history and examination showed the prevalence of completed stroke to be 73 per 1000. Eighty-seven subjects per 1000 gave a history of transient cerebral ischaemic attacks. These prevalence rates were unaffected by age or sex. Senile dementia was diagnosed in 24 subjects per 1000 under 75 years and 109 per 1000 over that age. The prevalence of dementia of all types was 43 per 1000 under, and 140 per 1000, over 75 years of age. Parkinsonism was diagnosed in 16 subjects per 1000, and essential tremor in 17 per 1000. The prevalence of epilepsy was four subject per 1000. Other neurological disorders were diagnosed in 36 subjects, and a similar number had neurological abnormalities to which a definite diagnosis could not be given.