PubMed Health⌕ Search

Biomedical subjects

K Hoffman

Publications and source records attributed to K Hoffman.

At least 19 recordsLinked to original sources
PubMed1997

Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer.

BACKGROUND: The extent to which chemotherapy may relieve tumour-related symptoms, improve quality of life and prolong survival in patients with gastric cancer is not known in spite of the extensive use of this treatment modality. The aim of this study was to estimate any gain in the quantity and quality of life produced by chemotherapy in these patients. PATIENTS AND METHODS: Between January 1991 and February 1995, 61 patients with gastric cancer were randomized to either chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not lead to palliation. Chemotherapy was the ELF-regimen consisting of 5-fluorouracil, leucovorin and etoposide, or, in elderly patients with poor performance, a 5-fluorouracil/leucovorin regimen (FLv). Quality of life was evaluated with the EORTC-QLQ-C30 instrument. RESULTS: More patients in the chemotherapy group (45%, 14/31) had an improved or prolonged high quality of life for a minimum period of 4 months compared to those in the best supportive care group (20%, 6/30, P < 0.05). A similar difference was seen in the treating physician's evaluation of whether the patient was subjectively improved or continued to do well for at least 4 months (17/31, 55% versus 6/30, 20%, P < 0.01). Overall survival was longer in the chemotherapy group (median 8 vs. 5 months) although the difference was not statistically significant (P = 0.12). After corrections for imbalances in pretreatment characteristics, chemotherapy treatment was, however, associated with a survival benefit (P = 0.003). Also, the quality-adjusted survival time and time to disease progression were longer for patients randomized to chemotherapy (median 5 vs. 2 months, P = 0.03). CONCLUSIONS: The results show that chemotherapy can add to both quantity and quality of life in advanced gastric cancer. The number of patients who benefit from treatment is, however, still rather limited.

Adenocarcinoma↗
PubMed1996

Phase I-II study: triciribine (tricyclic nucleoside phosphate) for metastatic breast cancer.

Triciribine is a purine analogue which inhibits DNA and protein synthesis. We performed two studies to define its activity against metastatic breast cancer. The first study was a phase II study in 14 patients with metastatic breast cancer who had received two or fewer chemotherapy treatments. The treatment schedule was tricirbine 20 mg/m2 per day by 24-h infusion (CI) daily for 5 days every 6 weeks as recommended by a previous open phase I trial. When neither response nor toxicity was seen in the phase II trial, we assumed the starting dose was too low for this group of patients with good performance status and repeated the phase I trial in patients with metastatic breast cancer with good performance status. The starting dose was 35 mg/m2 per day using the same 5-day CI schedule, and starting doses were increased in subsequent cohorts of three patients in increments of 5 mg/m2 until toxicity occurred. In the initial (phase II) study, one patient had stable disease for 18 weeks (three courses), the remainder progressed. There were no significant toxic effects. In the subsequent phase I study, ten patients were treated until the study was closed. The maximum dose was 40 mg/m2. Two patients died, one each at the 35 and 40 mg/m2 levels, respectively, 3 months and 6 weeks after their last course, one without intervening disease progression. Both had severe hypertriglyceridemia (18- and 21-fold elevation) and severe fatigue. At postmortem examination, one had congestive cardiomyopathy, and the other had severe pancreatitis and hypothyroidism. One patient had severe exacerbation of psoriasis which made her bedridden for more than 30 days. Four patients had hyperglycemia. Plasma pharmacology studies showed erratic drug levels, presumably related to enterohepatic circulation. Postmortem pharmacology studies showed residual drug present as long as 12 weeks after the last dose. We conclude that triciribine is ineffective at all doses tested and at doses of > or = 35 mg/m2 has unacceptable toxic effects.

Adult↗
PubMed1996

Three complementary liquid chromatographic methods for determination of the peptoid cholecystokinin-B antagonist, CI-988, in rat plasma.

Three different liquid chromatographic methods (two quantitative methods which employ fluorescence detection and one qualitative method which employs selected ion-monitoring detection) were developed and validated to provide complementary specificity for determination of CI-988, a cholecystokinin-B antagonist, in rat plasma. The first quantitative method involves isocratic separation of "non-ionized" CI-988 and internal standard on a C-18 column, whereas the alternative quantitative method involves isocratic separation of the "anionic" analytes. These two quantitative HPLC methods rely on the intrinsic fluorescence of CI-988 and internal standard for detection, and both methods are equally sensitive (linear range of 2.0-1000 ng ml-1), accurate (+/- 15% relative error), and precise (< or = 15% relative standard deviation). Plasma CI-988 concentrations for samples (N = 69) assayed with the "non-ionized" separation are linearly correlated with concentrations for the same samples assayed with the "anionic" separation (y = 1.08 chi - 0.57, R = 0.999). In addition, a third qualitative method, HPLC-thermospray mass spectrometry, was developed to provide complementary evaluation of assay specificity through the use of selected CI-988 fragment ion monitoring. When investigating an anomalous chromatographic result that calls into question the specificity of a method, the availability and use of alternative validated chromatographic separations and orthogonal detection schemes are beneficial.

Animals↗
PubMed1996

Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer.

BACKGROUND: In certain patients with pancreatic and biliary cancer, chemotherapy may relieve tumour-related symptoms, improve quality of life and possibly prolong survival. The extent of these improvements is not completely known in spite of the extensive use of this treatment modality. The aim of this study was to estimate any gain in the quantity and quality of life produced by chemotherapy in patients with pancreatic and biliary cancer. PATIENTS AND METHODS: Between January 1991 and February 1995, 90 eligible patients with pancreatic or biliary cancer were randomized to either chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not lead to palliation. Chemotherapy was either sequential 5-fluorouracil/leucovorin combined with etoposide (FELv) or, in elderly and poor performance patients, the same regimen without etoposide (FLv). Quality of life was evaluated with the EORTC-QLQ-C30 instrument. RESULTS: Mean scale scores in the QLQ-C30 improved more often/deteriorated less frequently in the chemotherapy group than in the best supportive care group. More patients in the chemotherapy group (36%, 17/49) had an improved or prolonged high quality of life for a minimum period of 4 months compared to those in the best supportive care group (10%, 4/41, P < 0.01). Overall survival was significantly longer in the chemotherapy group (median 6 vs. 2.5 months, P < 0.01). Also, the quality-adjusted survival time was longer for patients randomized to chemotherapy (median 4 vs. 1 months, P < 0.01). The effects were seen both in pancreatic and biliary cancer. CONCLUSIONS: The results show that chemotherapy can add to both quantity and quality of life in advanced pancreatic and biliary cancer. The number of patients who benefit from treatment is, however, still limited; for this reason careful selection before, and close monitoring during, treatment are necessary.

Adult↗
PubMed1996

Monitoring palliative chemotherapy in advanced gastrointestinal cancer using serial tissue polypeptide specific antigen (TPS) measurements.

Tissue polypeptide antigen specific (TPS) was analysed in serum taken prior to chemotherapy in 90 patients with advanced gastrointestinal cancer and prior to every treatment course in 68 of these patients in order to explore whether serial tumour marker measurements can be of importance in monitoring patients treated with palliative chemotherapy. Elevated TPS levels were seen in 83/90 (92%) patients (48/52 colorectal, 9/9 pancreatic, 9/11 biliary, 17/18 gastric). Baseline TPS level correlated with performance status, tumour response and survival. Based upon the change in TPS levels after the first two courses in relation to baseline, a decrease by >50% had a high sensitivity for a favourable treatment outcome (partial remission and prolonged stationary disease (90%) or a subjective response (100%)), whereas the specificity was lower (72% and 73% respectively). A similar result was seen when the TPS levels were analysed at the time of the response evaluation after 2 months (sensitivity 91 and 95%, specificity 74 and 75% for an objective or subjective response respectively). In 7 out of 15 patients with an initially favourable outcome, an increase in TPS levels of >50% at two occasions was seen 8-20 weeks prior to clinical disease progression. In advanced gastrointestinal cancer serial TPS measurements can with high accuracy early identify patients who will not benefit from the treatment. On the other hand, a response must be confirmed using other methods in the presence of a decrease, since this was also seen in non-responding patients.

Adult↗
PubMed1995

Endometrial carcinoma in elderly women.

Endometrial carcinoma remains the most common invasive gynecologic malignancy. Increased longevity is associated with an increased incidence of endometrial carcinoma (EC) in elderly women. While recent studies have looked at aging and its relation to ovarian, breast, and cervical cancer, few have focused on EC in the growing elderly population. This study analyzed 35 histologic specimens of EC in women 75-92 years of age. Findings revealed that only 23% of the tumors were Stage I, G1. The majority (77%) were deeply invasive or of advanced stage (IC-IV). These were G2, G3, or "virulent" types of nonendometrioid EC (undifferentiated, clear cell, uterine serous papillary, and squamous cell carcinoma). Fifty-seven percent of tumors were endometrioid, of which 9% were mixed, including a rare case of nongestational choriocarcinoma. The nonendometrioid tumors, compared to the endometrioid types, were more often high-stage tumors with vascular invasion. They were also more often associated with atrophic (vs hyperplastic) uninvolved endometrium. Clinical risk factors (nulliparity, obesity, estrogen replacement therapy) were assessed and correlated with the histologic findings. It was shown that tumors in the elderly were less likely to be estrogen-related. It was concluded that EC in this age group is more aggressive, histologically less differentiated, and often nonendometrioid compared with EC in the general population. The increased virulence of EC in the elderly may be related to the tumor's independence from hormonal factors, to the poorly understood but well-known diminished immunologic defense against cancer in general in elderly patients, and/or to the belated diagnosis of the disease in this population.

Aged↗
PubMed1995

The ultrasonic localization of abdominal wall adhesions.

Laparoscopic candidates with abdominal scars may have adhesions that result in visceral injury during trocar insertion. The purpose of this study was to evaluate the use of preoperative ultrasound mapping of abdominal wall adhesions, to provide safe initial laparoscopic access, and to guide the placement of subsequent trocars, facilitating adhesolysis when necessary. Thirty consecutive patients with previous abdominal surgery who were scheduled for laparoscopy underwent a preoperative ultrasonic examination of the abdominal wall using a 7-MHz linear ultrasound probe. Spontaneous viscera slide was measured during longitudinal scanning (normal = 2-5 cm) and induced viscera slide was evaluated during longitudinal and transverse scanning (normal = 1 cm or more) over the existing abdominal scar, the peri-umbilical region, and the remaining abdominal quadrants. Sixteen (53%) of 30 patients had adhesions under their scar and only four patients (25%) had umbilical adhesions. The 12 patients without umbilical adhesions all had successful closed cannulation while open cannulation at alternate sites was successful in the four individuals with umbilical adhesions. Blind umbilical needle cannulation was successfully done in all of the remaining 14 patients (47%) without visceral injury, including three patients (21%) with upper abdominal scars who were adhesion-free elsewhere. No adhesions were encountered that had not been preoperatively predicted by ultrasound. We conclude that examination of the abdominal wall with spontaneous and induced viscera slide, using ultrasound scanning, can reliably detect intraabdominal adhesions. The examination is best done on a highly selective basis by the operating surgeon to guide the location for initial trocar insertion and determine the type of abdominal wall cannulation in those individuals with previous abdominal scars.

Abdominal Muscles↗
PubMed1995

Information to and communication with cancer patients: improvements and psychosocial correlates in a comprehensive care program for patients and their relatives.

Between 1987 and 1989, 177 cancer patients who were to receive intensive chemotherapy with curative intention, participated in a comprehensive care project with the aim of improving their total situation, and that of their relatives (n = 120). A number of steps were taken to improve, among other things, the information to, and communication with, patients and their relatives. Compared with a pre-project evaluation in 54 patients and 24 relatives, significantly lower problem scores were seen in most aspects relating to interaction with medical staff. Strong associations were seen between, on the one hand, various aspects of patient- and relative-staff interaction and, on the other, psychosocial problems, although they were weaker for problems relating to information, than for communication and control problems.

Communication↗
PubMed1995

Effects of dairy products on bone and body composition in pubertal girls.

OBJECTIVE: To study the effect of calcium supplementation with dairy products on the bone and body composition of pubertal girls. DESIGN: Randomized control study with 12-month follow-up. SETTING: General community. SUBJECTS: Forty-eight white girls whose mean age was 11 years and sexual development at Tanner stage 2. INTERVENTION: One group's diet was supplemented with dairy products to the recommended dietary allowance of 1200 mg calcium daily. The other group ate their usual diet. MAIN OUTCOME MEASURES: Bone mineral content and density were measured at the radius, femoral neck, lumbar spine, and total body bone mineral by single-photon and dual-energy x-ray absorptiometry at the start of the study and after 3, 6, 9, and 12 months. Body composition (lean body mass and body fat) was measured by dual-energy x-ray absorptiometry at the same intervals. Serum calcium, phosphate, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, alkaline phosphatase, magnesium, and albumin concentrations were determined at the start and end of the study. The urinary calcium/creatinine ratio and hydroxyproline concentration were also determined. RESULTS: The dairy group had higher intakes of calcium, phosphate, vitamin D, and protein than control subjects. The dairy group had significantly greater increases during the 1-year study in bone mineral density at the lumbar spine bones (22.8% +/- 6.9% vs 12.9% +/- 8.3%) and in total body bone mineral (14.2% +/- 7.0% vs 7.6% +/- 6.0%) than control subjects. Dietary calcium, phosphate, vitamin D, and protein intakes were associated with the lumbar bone density and total body bone calcium. There were no differences in serum or urinary biochemical values between the two groups at the start or end of the study. CONCLUSIONS: Young girls whose dietary calcium intake was provided primarily by dairy products at or above the recommended dietary allowances had an increased rate of bone mineralization. Increased intake of dairy foods did not increase overall total or saturated fat intake and was not associated with excessive weight gain or increased body fat.

Body Composition↗
PubMed1995

Cost-effectiveness of palliative chemotherapy in advanced gastrointestinal cancer.

BACKGROUND: Chemotherapy may relieve tumor-related symptoms, may improve quality of life and prolong survival in advanced gastrointestinal cancer. The extent of such improvements is unclear despite the extensive use of this treatment modality, and there are no studies concerning the economic cost of any gain achieved in the quantity and quality of life by chemotherapy. PATIENTS AND METHODS: Between January 1991 and May 1992, 61 patients with inoperable cancer (18 gastric, 22 pancreatic or biliary, and 21 colorectal) were randomized to either primary chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not achieve palliation. All economic costs for medical care were prospectively recorded, and marginal cost-effectiveness analyses were performed. RESULTS: More patients in the primary chemotherapy group (19/33, 58%) had improved/prolonged high quality of life (QoL-patient, minimum duration 4 months) than in the best supportive care group (8/28, 29%, p < 0.05). Overall survival and quality-adjusted survival were significantly longer in the primary chemotherapy group (median 9 vs. 4 months, p < 0.05), and median 7 vs. 2 months, p < 0.05, respectively). When analysed by cancer site, survival was significantly prolonged in gastric cancer patients (median 10 vs. 4 months, p < 0.02), but not in colorectal (median 12 vs. 6 months, p = 0.1) and pancreatic-biliary cancer patients (median 8 vs. 5 months, p = 0.8). The average cost for all medical care was approximately 50% higher in the primary chemotherapy group, but the average cost per day was the same in the two groups. Hospitalization accounted for most of the costs in both groups. The incremental costs per gained year of life was SEK 166,400 ($21,300), per gained quality-adjusted year of life SEK 157,200 ($20,200), and per QoL-patient SEK 160,300 ($20,600). These costs were lower for gastric and colorectal cancer patients, and much higher for pancreatic-biliary cancer patients. CONCLUSIONS: The results of this study suggest that palliative chemotherapy is cost-effective in patients with advanced gastric and colorectal cancer. Knowledge about survival and quality of life benefits is still limited in patients suffering from gastric and pancreatic-biliary cancer.

Adult↗
PubMed1994

Quality of life during chemotherapy in patients with symptomatic advanced colorectal cancer. The Nordic Gastrointestinal Tumor Adjuvant Therapy Group.

BACKGROUND: To increase the knowledge about the palliative effects of chemotherapy in patients with symptomatic advanced colorectal cancer, physician- and patient-rated "quality of life" was studied in a randomized multicenter trial comparing a regimen of methotrexate/5-fluorouracil (5-FU) followed by leucovorin rescue (MFL) with a regimen of 5-FU/leucovorin (FLV). METHODS: Between January 1989 and December 1990, 70 patients completed a quality of life questionnaire at randomization and after every fourth treatment course. At one of the hospitals, the evaluation was done as an interview (interview group, n = 24), whereas a questionnaire was used at the other hospitals (questionnaire group, n = 46). RESULTS: Objective responses (complete response plus partial response) were obtained in 15 (21%) patients, subjective responses in 29 (41%) patients, and an overall improved quality of life in 25 (36%) patients. In addition, 16 (23%) patients had unchanged quality of life during at least 4 months. There was a correlation between objective responses, subjective responses, and improvements in quality of life, although discrepancies were noticed, particularly in patients with only slight symptoms. Response rates were higher in the interview group than in the questionnaire group (P < 0.01). This difference could be related to a more favorable outcome when 5-FU was given as a bolus injection, rather than as a short-term infusion (more than 5 minutes). CONCLUSIONS: Improvements or prolonged stabilization of disease in quality of life can be achieved in at least half of the patients with tumor-related symptoms. However, factors related to the administration of chemotherapy may influence this proportion.

Adult↗
PubMed1994

A pilot experience with competency-based clinical skills assessment in a surgical clerkship.

This investigation examines a competency-based clinical skills assessment program for surgical clerks using checklists and rating forms for precise measurement of physical exam (PE) skills, physician-patient interaction (PPI) skills, and patient write-up (PW) skills. Analysis of variance demonstrated improvement in PW skills across the academic year when measured by the rating instrument, but this improvement was not detected on traditional subjective rating forms (SRF). PPI skills improved between first rotations across 2 academic years with the addition of orientation to expectations (mean, 79% versus 92%, P = 0.000). Poor correlation was noted between the National Board of Medical Examiners Surgery Subtest scores and PE skills (r = .19), PW skills (r = .20), and PPI skills (r = .15). While the overall ratings given by faculty on SRF correlated with the SRF ratings of PE skills (r = .77) and PPI skills (r = .58), these same faculty ratings correlated poorly with these skills as assessed by checklist (r = .16 and r = .14, respectively). This pilot experience demonstrates that PE skills, PW skills, and PPI skills (1) improve only with orientation to expectations and feedback, (2) correlate poorly with fund of knowledge assessment, and (3) are best assessed with precise measurement (eg, checklist, direct observation), which avoids the halo effect of overall evaluation that occurs with subjective rating forms.

Clinical Clerkship↗
PubMed1994

Prevention of venous thromboembolism in North America: results of a survey among general surgeons.

PURPOSE: The purpose of this study was to analyze current attitudes toward the prevention of postoperative venous thromboembolism among North American general surgeons. METHODS: A survey regarding awareness of the problem of venous thromboembolism and preferred modalities of prophylaxis was sent to 3500 randomly selected Fellows of the American College of Surgeons. RESULTS: A total of 1018 (29.1%) surveys was returned. Most of the responding surgeons consider venous thromboembolism a serious health problem. Ninety percent of the surgeons use prophylaxis against venous thromboembolism routinely. The most frequently used modalities are intermittent pneumatic compression, low-dose heparin, and elastic stocking. A combination of physical and pharmacologic methods is used by one fourth of respondents, and only 50% start pharmacologic prophylaxis before the surgical procedure. The thrombosis risk factors that are most frequently considered by surgeons when deciding about using prophylaxis are history of venous thromboembolism, immobility, and length of operation. CONCLUSIONS: North American surgeons who responded to this survey are well aware of the problem of venous thromboembolism and their approach to prevention has been significantly modified in the last 10 years. Compared with similar European surveys this survey reveals a higher implementations of physical methods such as intermittent pneumatic compression and elastic stockings. Because of the limited response rate and possibility of sampling bias, these findings should be interpreted with caution.

Adult↗
PubMed1994

In healthy primates, circulating autoreactive T cells mediate autoimmune disease.

A T cell response against myelin basic protein (MBP) is thought to contribute to the central nervous system (CNS) inflammation that occurs in the human demyelinating disease multiple sclerosis. To test whether MBP-reactive T cells that are normally retrieved from the circulation are capable of inducing CNS disease, MBP-reactive T cell clones were isolated from the peripheral blood of healthy, unimmunized Callithrix jacchus (C. jacchus) marmosets. This primate species is characterized by a natural chimerism of bone marrow elements between siblings that should make possible adoptive transfer of MBP-reactive T cells. We report that MBP-reactive T cell clones efficiently and reproducibly transfer CNS inflammatory disease between members of C. jacchus chimeric sets. The demyelination that is characteristic of experimental allergic encephalomyelitis induced in C. jacchus by immunization against human white matter did not occur after adoptive transfer of the MBP-reactive clones. It was noteworthy that encephalitogenic T cell clones were diverse in terms of their recognition of different epitopes of MBP, distinguishing the response in C. jacchus from that in some inbred rodents in which restricted recognition of MBP occurs. These findings are the first direct evidence that natural populations of circulating T cells directed against a CNS antigen can mediate an inflammatory autoimmune disease.

Animals↗
PubMed1993

Stability of babyfaceness and attractiveness across the life span.

Differential, structural, and absolute stability of babyfaceness and attractiveness at 5 ages were investigated. Attractiveness had differential stability across the life span. Babyfaceness had differential stability from childhood through the 30s for males and through adolescence for females. Consistent with sexual dimorphisms in facial maturation, males had less differential stability in babyfaceness from childhood to puberty than females. Structural stability of facial appearance, as reflected in the relationship between babyfaceness and attractiveness across the life span, was low, with these qualities positively related for females in childhood and for both sexes in their 30s and 50s but unrelated in puberty and adolescence. Absolute stability of babyfaceness and attractiveness was also low, with mean levels decreasing across the life span. Contrary to cultural stereotypes, age-related decreases in attractiveness were equal for male and female Ss.

Adolescent↗