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Biomedical subjects

B J Grube

Publications and source records attributed to B J Grube.

At least 19 recordsLinked to original sources
PubMed2001

Surgical management of breast cancer in the elderly patient.

BACKGROUND: Breast cancer in the older woman is a major health issue and therapeutic challenge. This study asked if presentation, surgical treatment, and outcome of breast cancer are different in elderly women compared with their younger counterparts. METHODS: There were 816 women < 70 years (younger) and 190 > or = 70 years (older) treated surgically for breast carcinoma between January 1992 and April 2000. Data for younger and older patients was analyzed from our prospective database. RESULTS: More older women had mammographic lesions (P < 0.006). Breast conservation was the treatment of choice for both groups. Stage, tumor size, histology and disease-specific survival were similar for both. There was no evidence of disease in 93% of cases in the < 70 years group at median follow-up of 38.4 months and 91% for the > or = 70 years group at 44.5 months. CONCLUSIONS: In our population the presentation, surgical treatment, and survival from breast cancer is similar in older and younger women.

Adult↗
PubMed2001

White button mushroom phytochemicals inhibit aromatase activity and breast cancer cell proliferation.

Estrogen is a major factor in the development of breast cancer. In situ estrogen production by aromatase/estrogen synthetase in breast cancer plays a dominant role in tumor proliferation. Because natural compounds such as flavones and isoflavones have been shown to be inhibitors of aromatase, it is thought that vegetables that contain these phytochemicals can inhibit aromatase activity and suppress breast cancer cell proliferation. Heat-stable extracts were prepared from vegetables and screened for their ability to inhibit aromatase activity in a human placental microsome assay. The white button mushroom (species Agaricus bisporus) suppressed aromatase activity dose dependently. Enzyme kinetics demonstrated mixed inhibition, suggesting the presence of multiple inhibitors or more than one inhibitory mechanism. "In cell" aromatase activity and cell proliferation were measured using MCF-7aro, an aromatase-transfected breast cancer cell line. Phytochemicals in the mushroom aqueous extract inhibited aromatase activity and proliferation of MCF-7aro cells. These results suggest that diets high in mushrooms may modulate the aromatase activity and function in chemoprevention in postmenopausal women by reducing the in situ production of estrogen.

Agaricus↗
PubMed1994

Identification of a regulatory domain of the interleukin-6 receptor.

IL-6 signal transduction occurs when the liganded interleukin-6 receptor (IL-6R) interacts with glycoprotein (gp) 130. We hypothesized that synthetic peptides modeled from the extramembranous domain of the IL-6R may interfere with the IL-6-induced reaction between IL-6R and gp130 and may serve to elucidate the initial steps in IL-6 signal transduction. The capacity of such peptides to modulate two different IL-6 functions was evaluated: 1) IL-6-dependent B9 cell mitogenesis, and 2) IL-6-induced acute phase protein synthesis in HepG2 cells. A synthetic peptide, 249Y16T264, corresponding to residues 249-264, inhibited IL-6-dependent B9 proliferation and IL-6-induced acute phase protein up-regulation in HepG2 cells. Other peptides modeled from different regions of the IL-6R were not inhibitory. 249Y16T264 did not inhibit IL-6-independent HepG2 cell proliferation or total cellular protein synthesis. The inhibitory effect was reversible, indicating that the peptide was not cytotoxic. 249Y16T264 did not inhibit 125I-IL-6 binding in U266 cells. Delineation of this domain identified 249Y10R258 as the minimum effective sequence capable of inhibiting fibrinogen synthesis. Amino acid substitutions in 249Y10R258 obliterated the inhibitory effect on fibrinogen synthesis. In conclusion, a region of the extramembranous domain of the IL-6R has been identified that is involved in the regulation of IL-6 signal transmission. A synthetic peptide representing this region inhibits IL-6-dependent B9 cell mitogenesis and IL-6-stimulated acute phase response in HepG2 cells without affecting ligand binding.

Acute-Phase Proteins↗
PubMed1994

Lipopolysaccharide binding protein expression in primary human hepatocytes and HepG2 hepatoma cells.

Lipopolysaccharide (LPS)-binding protein (LBP) is a normal plasma protein and an acute phase reactant important for host responses to Gram-negative bacteria and LPS. LBP forms high affinity complexes with LPS which bind to CD14, a monocyte surface protein, to initiate the release of inflammatory mediators. We found that human primary hepatocytes synthesize LBP and that the synthesis is up-regulated by interleukin (IL)-6. To examine this phenomenon in more detail, we evaluated the capacity of IL-6, IL-1, and tumor necrosis factor to induce LBP synthesis in HepG2 cells in the presence or absence of dexamethasone. IL-6 induced LBP synthesis. Dexamethasone, IL-1, and tumor necrosis factor had a synergistic effect when combined with IL-6, but demonstrated minimal effect independently. LBP biosynthesis was evaluated by immunoprecipitation of 35S-labeled LBP from HepG2 supernatants, measurement of steady-state LBP mRNA levels, and analysis of LBP-dependent LPS binding to CD14 positive cells. An 35S-labeled, 60-kDa protein was immunoprecipitated with anti-LBP antibody from IL-6-stimulated HepG2 cell supernatants. Northern blot analysis of cellular RNA revealed an increase in LBP mRNA in IL-6-stimulated cells. CD14 expressing cells bound fluoresceinated LPS in the presence of supernatants from HepG2 cells treated with IL-6. These data provide the first information about specific cytokine and dexamethasone regulation of LBP expression in HepG2 cells. LBP behaves like a Type 1 acute phase protein.

Acute-Phase Proteins↗
PubMed1992

Early ambulation and discharge in 100 patients with burns of the foot treated by grafts.

Traditional treatment after grafting of foot, ankle, and lower leg burns is bedrest, limb elevation, and gradual ambulation only after 5 to 10 days. In 1982 we suggested that aggressive surgical treatment and early ambulation could shorten hospital stay and decrease morbidity. Our treatment of these burns is excision and grafting, application of an Unna (dome paste) boot immediately in the operating room or the next morning, with normal ambulation 4 hours later and discharge of the patient if there are no other reasons for continued hospitalization. This paper reports the continuation of this plan in 100 patients treated since 1982 with a mean age of 28.8 +/- 16.9 (SD) years and burn size of 3.7% +/- 4.4%. Sheet grafts were applied to 64% with a 96% take and narrowly meshed grafts to 36% with a 97% take. Results were excellent in 85 patients, satisfactory in ten, and poor in three who required another graft. Return to work was in 4.7 +/- 3 weeks. Unna boot application permits immediate ambulation, avoids frequent dressing changes, permits a brief or no hospital stay, and provides excellent graft take with prompt return to work.

Administration, Topical↗
PubMed1990

Treatment of the concrete scalp donor site.

The scalp has become a popular donor site for split-thickness skin, and few complications have been reported. However, we have been troubled by 5 patients in whom the donor site did not epithelialize but rather turned into dried granulation tissue with embedded growing hairs, a situation rather like concrete with steel reinforcing rods. The pathophysiology is not clear but seems to be related to thick grafts from hair-bearing areas. We treated the lesions by removing the granulation tissue, shaving the hair, and treating the wound as a new donor site. Four lesions healed with total or near total regrowth of hair, and one required a small skin graft.

Adolescent↗
PubMed1990

Outcome and treatment of electrical injury with immediate median and ulnar nerve palsy at the wrist: a retrospective review and a survey of members of the American Burn Association.

Electrical injury to the upper extremity with immediate median and ulnar nerve palsy at the wrist is uncommon but devastating. When it does occur, the immediate clinical questions are (1) will the nerves recover, and (2) should the carpal tunnel and Guyon's canal be released? Our review of the literature did not answer these two questions. Therefore, we reviewed our experience with such patients and surveyed approximately 10% of the physician members of the American Burn Association. We reviewed approximately 80 patients with electrical injuries treated between January 1983 and September 1988, and found 5 patients (8 extremities) who did not require amputation and who manifested immediate palsy of the median and ulnar nerves at the wrist. The questionnaire was returned by 83% of those contacted. We concluded that such nerve palsies can recover to a significant degree and that a majority of surgeons would release the carpal tunnel and Guyon's canal, expecting improved recovery. Although it is still not proven whether decompression is beneficial, we will continue to decompress the carpal tunnel and Guyon's canal in such circumstances.

Adult↗
PubMed1990

Neurologic consequences of electrical burns.

Permanent neurologic damage following major electric injury is a dreaded and often discussed complication. The incidence, severity, and sequelae are not clear from the literature. Therefore we reviewed the charts of 90 consecutive patients admitted to the University of Washington Burn Center between 1980 and 1986 looking at neurologic consequences. Electric injuries accounted for 4% of 2,305 admissions. The mean age was 31 +/- 13 years, total body surface area involved (TBSA), 6 +/- 11%, and length of stay, 13 +/- 20 days. There were 82 males and eight females. There were four deaths, for a mortality rate of 4%. Fourteen patients had 18 amputations. Twenty-two patients sustained low-voltage injury; 50% had immediate neurologic symptoms which resolved in nine of 11 patients. Eleven patients (50%) were asymptomatic. Sixty-four patients sustained high-voltage injury and 33% were asymptomatic. Forty-three patients (67%) had immediate central and/or peripheral neurologic symptoms. Loss of consciousness accounted for the largest fraction of CNS sequelae in the high-voltage group (45%). Twenty-three patients (79%) recovered consciousness before arrival at the hospital. Six patients remained comatose, three died, and three awoke but had neurologic sequelae. Twenty-two patients in the high-voltage group had one or more acute peripheral neuropathies. Sixty-four per cent of these neuropathies resolved or improved. Five patients had transient initial paralysis, but there were no delayed spinal cord symptoms. Eleven patients developed one or more delayed peripheral neuropathies. Half of these delayed neuropathies resolved or improved.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1988

Candida. A decreasing problem for the burned patient?

Multiple recent reports have suggested that Candida wound infection and sepsis are major complications of severe burn injury. Our current burn treatment plans include aggressive early burn excision and grafting, avoidance of invasive monitoring and central hyperalimentation lines, enteral nystatin, and judicious use of antibiotics. A retrospective review of 168 severely burned patients admitted to the Intensive Care Unit of the University of Washington Burn Center, Seattle, during the 18-month period from June 1984 through December 1985 was undertaken. Thirteen percent of these patients had one or more cultures positive for Candida from any site. Three patients (1.8%) developed Candida sepsis, which was diagnosed on the basis of clinical signs of sepsis, a positive blood culture for Candida, and at least two additional culture sites positive for Candida. All three patients were treated with amphotericin B. One of these patients died of Candida sepsis, for an overall mortality of 0.6%. Therefore, Candida septicemia was not a major cause of morbidity or mortality in our burn patients in the Intensive Care Unit during this 18-month period under the current management regimen.

Adult↗
PubMed1988

Nutritional modulation of tumor growth.

The relationship between tumor and host tissue proliferation as a function of protein calorie deficiency followed by balanced nutritional repletion was examined in a series of C3H female mice with MA16/C tumors. Tumor and host tissue DNA synthesis was determined in animals with subcutaneously implanted tumors who were randomized to either regular diet (RD) or a totally protein-free diet (PFD) for 5 days followed by refeeding for 4, 8, 12, 24, 36, 48, or 72 hr. Animals maintained on a protein-free diet demonstrated a decrease in DNA synthetic activity in both tumor and host tissues. Following refeeding of a regular diet to animals fed the protein-free diet, resumption of DNA synthesis in tumor preceded that of liver and was greatest by four hours of refeeding. In the liver, return of DNA synthetic activity was delayed but exceeded control levels by 36 hr. Compared to our previous studies examining the effects of starvation, we found that an isocaloric protein-free diet caused a smaller decrease in tumor DNA synthetic activity and an earlier resumption in tumor proliferation with the reinstitution of a normal protein diet. These studies suggest a nutrient-specific response for tumor and host tissues with nutritional deprivation and refeeding.

Animal Nutritional Physiological Phenomena↗
PubMed1987

Toxic epidermal necrolysis. A step forward in treatment.

Toxic epidermal necrolysis is an uncommon but severe form of epidermal sloughing with associated mucositis. Treated in a general hospital, it carries a high mortality (25% to 70%) and substantial long-term morbidity. If the patient is referred early to a burn center, where it can be treated with biologic dressings and intensive support care, the mortality can be reduced below 20% and there may be negligible long-term morbidity. We describe 19 patients so treated, with three deaths and no long-term complications.

Adolescent↗
PubMed1987

Clostridium difficile diarrhea in critically ill burned patients.

We followed up 112 patients in the University of Washington Burn Center, Seattle, for the development of Clostridium difficile diarrhea. Diarrhea developed in 20 patients with a mean burn size of 42%, mean age of 38 years, and 49 mean total antibiotic days, for an incidence of 17%. Eleven patients had 16 episodes of nonspecific diarrhea. Nine patients had 11 episodes of C difficile-positive diarrhea and 15 episodes of nonspecific diarrhea for an incidence of 45% of all patients with diarrhea. There were no differences in patient age, burn size, or length of stay between the groups. When the 31 episodes of nonspecific diarrhea were compared with the 11 episodes of C difficile diarrhea, there were no differences between the groups in temperature, albumin levels, or total number of antibiotic days preceding the episodes of diarrhea. The only significant finding that differed between the two types of diarrhea was the white blood cell count on the day of diagnosis. The nonspecific diarrhea was self-limited, requiring antimotility agents in 45% of the episodes. The C difficile diarrhea responded promptly to vancomycin hydrochloride, with resolution of symptoms in an average of 3.3 days. There were two recurrences, and both responded to a second course of vancomycin.

Adolescent↗
PubMed1985

Refeeding differentially affects tumor and host cell proliferation.

Tumor and host tissue DNA synthesis in C3H female mice with MA16/C tumors were examined for the effects of starvation and refeeding. Animals with subcutaneously implanted tumors were randomized to either regular diet or starvation for 48 hr followed by refeeding for 6, 12, 24, 48, or 72 hr. With starvation, both tumor and host tissues demonstrated a decrease in DNA synthetic activity. After refeeding, resumption in DNA tumor synthesis preceded that of host tissues and was greatest within the first 6-12 hr. Host tissue DNA synthetic activity resumed at different times in the various tissues examined with bone marrow being earlier than spleen or liver. The differential time course between induction of tumor and host DNA synthesis could allow a more precise modeling in studies dealing with the interaction of nutritional repletion and antitumor therapy.

Animals↗
PubMedDate not supplied

Observation of the breast cancer patient with a tumor-positive sentinel node: implications of the ACOSOG Z0011 trial.

Axillary lymph node status has been the most important prognostic factor for breast cancer throughout the past century. During the past decade, intraoperative lymphatic mapping with sentinel lymph node dissection (SLND) has been investigated as an alternative staging modality. This technique may be as accurate as ALND, and certainly is less invasive. Adjuvant treatment recommendations, which historically were made on the basis of lymph node status alone, now take into account primary tumor features, molecular markers, and patient characteristics. This evolution of current treatment patterns is driven in part by the diminishing size of tumors, the simultaneous decrease in the presence of axillary metastases, and a better understanding of tumor-specific risk factors. How do these trends affect the interpretation of a tumor-positive sentinel node (SN)? Can an axilla with a positive SN be observed? Should it be observed? This review examines the implications of a positive SN in the context of smaller tumor size, decreased nodal disease, and increased reliance on alternative prognostic factors for treatment decisions. The historical data comparing ALND to no ALND in clinically node-negative patients is reviewed and discussed in the context of observation for a positive SN. These are the issues underlying the ACOSOG Z0010 and Z0011 trials.

Axilla↗
PubMedDate not supplied

Molten metal burns to the lower extremity.

In this study of ten consecutive patients sustaining molten metal injuries to the lower extremity who were treated with excision and grafting, treatment with compression Unna paste boot was compared with that with conventional dressing. Hospital stay was decreased from 12.2 days in the conventional dressing group (five patients) to 6.4 days in the Unna group (five patients). Ambulation was initiated on postoperative day (POD) 2.2 in the Unna group, compared with POD 8.0 in the conventional dressing group. Return to work was on POD 44.8 in the Unna group versus POD 86.3 in the conventional dressing group. Treatment of molten metal injuries to the lower extremity with Unna paste compression dressing resulted in shorter hospital stay, earlier ambulation, and more rapid return to work.

Accidents, Occupational↗