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Biomedical subjects

C Hardy

Publications and source records attributed to C Hardy.

At least 55 records · Page 3Linked to original sources

[Carotid surgery under locoregional anesthesia].

Eight-five carotid endarterectomies were performed in 77 patients, under regional anaesthesia using 2 different techniques: cervical epidural anaesthesia (35 cases) and cervical plexus block (50 cases). The patients' mean age was 71 years; 80 per cent had arterial hypertension and 41 per cent coronary disease. Transoperative cerebral ischaemia was detected by a 5-minute carotid clamping test, the occurrence of a neurological event indicating that shunting was required. In 62 patients this test was combined with measurement of carotid back pressure. None of the patients needed general anaesthesia. Intraoperative neurological events occurred more frequently (P less than 0.01) when the carotid back pressure was 25 mmHg or less, and 12 temporary shunts were installed for that reason (14.1 per cent). Three neurological events occurred at the end of endarterectomy: no shunt was installed and complete recovery was observed immediately after declamping. No complications ascribable to the anesthetic techniques were recorded. Mortality was nil, and the only neurological morbidity was a brachio-facial deficit which left few sequelae. The frequency of intra- or postoperative arterial hypertension was similar in both groups. Intraoperative hypotension, frequent under epidural anaesthesia, was observed in only one patient who had brachial plexus block (P less than 0.01). The analgesia obtained was equally good with both anaesthetic techniques, but cervical plexus block anaesthesia is easier to perform, had less haemodynamic repercussions and therefore tends to be preferred to cervical epidural anaesthesia. The lack of mortality, low morbidity and absence of systemic complications in this series despite the high number of patients at risk are in favour of this type of anaesthesia, notably for such patients. Moreover, because vigilance is preserved attention can be paid to the quality rather than the rapidity of endarterectomy, which is the best way of preventing embolism.

Adult↗

Erythropoiesis in murine long term marrow cultures.

We utilized a system of long-term bone marrow cultures that favored erythropoiesis and allowed the production of CFU-E for four weeks. Certain conditions of culture were crucial for erythropoiesis to occur. These conditions have been discussed. This system should allow further in vitro study of the regulation of erythropoiesis.

Animals↗

Internal banding for palliation of truncus arteriosus in the neonate.

A method for surgically limiting pulmonary blood flow in the critically ill neonate with truncus arteriosus is described. Two recent cases utilizing this technique are presented. Comparisons are made between this and other palliative surgical procedures used in truncus arteriosus.

Constriction↗

Prostate cancer: a model of cancer in the elderly.

Prostate cancer is the most common malignancy in men over 70. Chronic course of the disease and multiple therapeutic options allow a customized management of the patient's individual problems. Prognostic factors are stage, size of primary tumors, serum acid phosphatase levels, number of metastases, ureteral obstruction and patient's age. In localized disease, surgery and radiation therapy are equally effective for patients with a life expectancy less than or equal to 10 years. Surgery may be superior to radiation if longer survival is expected. In locally advanced disease radiation therapy is preferred to surgery, due to a lower rate of complications. Management of metastatic disease requires offsetting androgen effects by castration or by antiandrogens. Orchiectomy, the safest way to produce castration, is unacceptable to 50% of patients. LHRH analogs are safer than estrogens, but more expensive; the risk of tumor flare up controindicates these compounds in life-threatening situations. The use of ketoconazole is limited by long-term toxicity, but may be life-saving in life-threatening situations, due to a rapid onset of action. Antiandrogens are as effective as castration, but are not commercially available in the USA. Alternative treatments include Estracyt, intermittent estrogentherapy, progesterone derivative and aminogluthetimide. Radical prostatectomy and radiation therapy to the prostate cause erectile impotence with persistence of orgasmic sensations. These patients are ideal candidates for erection-restoring interventions, such as intrapenile injections or penile implants.

Aged↗

Transient synthesis of K6 and K16 keratins in regenerating rabbit corneal epithelium: keratin markers for an alternative pathway of keratinocyte differentiation.

Cultured rabbit corneal epithelial cells undergo three distinct stages of growth and differentiation characterized by the sequential appearance of K5/K14 keratin markers for basal keratinocytes, K6/K16 keratin markers for "hyperproliferative" keratinocytes, and K3/K12 keratin markers for corneal-type differentiation. Analyses of [35S]methionine-labeled, newly synthesized keratins revealed that K6/K16 are synthesized only briefly when the cells undergo exponential growth, and their synthesis is suppressed when the cells reach confluence and switch to synthesizing K3/K12. Transient synthesis of K6/K16 was also observed in vivo during corneal epithelial regeneration. Although K6/K16 expression in general correlates well with cellular growth, drug-induced inhibition of corneal epithelial growth and related data on human epidermal keratinocytes indicate that these two events are dissociable. These results establish clearly for the first time a reciprocal relationship, on a protein level, between the synthesis of K6/K16 and a differentiation-related keratin pair, K3/K12. Such a relationship strongly suggests a competitive mechanism controlling the synthesis of these two major classes of keratins in the suprabasal compartment. Our results also indicate that although hyperproliferation is usually accompanied by K6/K16 expression, the reverse is not always true. Taken together, the data suggest that K6/K16 are synthesized, perhaps by default, as an alternative suprabasal keratin pair under conditions that are nonpermissive for keratinocytes to express their normal, differentiation-related keratin pairs.

Animals↗

Characterization of membrane homing receptors in two cloned murine hemopoietic progenitor cell lines.

To characterize homing receptors that are responsible for the recognition and specific binding of hemopoietic progenitor cells to the stroma, we synthesized and 125I-labeled a number of neoglycoproteins. We used these neoglycoproteins as ligand to detect receptors on the membrane of two cloned murine hemopoietic progenitor cell lines, B6SUT and FDCP-1. Both cell lines demonstrated membrane receptors with galactosyl and mannosyl, but not fucosyl, specificities. B6SUT galactosyl receptors showed a single receptor population with a Kd of about 2.3 X 10(-7) M and 10(6) receptors per cell. Mannosyl receptors demonstrated two components with high and low affinities respectively with Kd of about 2.5 X 10(-8) M and 1.0 X 10(-7) M, and respectively about 7.4 X 10(5) and 3.7 X 10(5) receptors per cell. Comparable data were also obtained for FDCP-1. Displacement experiments indicated that radioactive ligands bound to receptors could be increasingly displaced by homologous cold ligand giving typical sigmoid-shaped curves. Cold mannosyl probe could also displace radioactive galactosyl probe in a similar manner, but cold galactosyl probe displaced radioactive mannosyl ligand with a curve demonstrating two phases, further suggesting two receptor components for the mannosyl ligand. Mature murine neutrophils and red cells as well as human neutrophils, monocytes, and red cells showed no receptors. The functional significance of these receptors in binding to stromal cells was demonstrated by quantitation of the binding of 51Cr-labeled progenitor cells to the cloned stromal cell line, D2X, before and after enzymatic removal of various carbohydrate residues of membrane glycoconjugates. Enzymatic removal of galactosyl and mannosyl, but not fucosyl, residues almost totally eliminated the binding. The findings strongly suggest that these homing receptors are present on the surface of early hemopoietic progenitor cells. With maturation the cells lose their receptors, so that mature cells can be released into the blood stream.

Animals↗

[Surgical treatment of perforated diverticular sigmoiditis. A retrospective study apropos of 45 cases].

The authors report their experience with 45 cases of perforated diverticular sigmoiditis (10 cases of mesocolic abscesses, 13 cases of localised peritonitis and 22 cases of generalised peritonitis). The mean age of the patients was 69 years and a previous history of diverticulosis was found in 26.6% of patients. 18% were taking steroids or anti-inflammatories. The often atypical symptomatology only suggested sigmoid perforation in 50% of cases. Surgical procedures consisted of 33 immediate resections (group 1) and 12 conservative procedures (group 2). Overall mortality was 17.8%, and was 13% at the abscess and localised peritonitis stage, and 22.7% at the generalised peritonitis stage (difference not significant). 12% of patients died after resection in comparison with 33.3% after conservative surgery (difference not significant). Mortality was significantly higher when there was evidence of shock, pre-operative leucopenia and pyostercoral peritonitis. In group 1, the surgical morbidity was 24% with 9% reinterventions, while in group 2, there was a 50% complication rate and 25% reintervention rate. Intestinal continuity was reestablished in 67.5% of surviving patients with zero mortality. In view of the results obtained and after review of the literature, immediate resection would appear to give better results than conservative treatment.

Adult↗

Extramammary Paget's disease: an annotated review.

The incidence, clinical features, histogenesis, and treatment of extramammary Paget's disease (EMPD) are reviewed. This unusual skin lesion is associated with an underlying adnexal neoplasm in about 50% of cases. Also, the incidence of distant organ malignancies of EMPD is higher than expected by chance. Even in the absence of a recognizable underlying cancer, EMPD may occasionally produce distant metastases, indicating the malignant potential of this condition. Histochemical, immunohistological, and lectin binding studies demonstrate that the cell of origin of EMPD is the exocrine cell of sweat glands. Although EMPD may arise from eccrine cells, derivation from apocrine cells appears more common. The treatment of the primary lesion, by wide margin excision, is fraught by a high recurrence rate. Chemosurgery may reduce local relapse of EMPD. The value of adjuvant radiation therapy is unestablished. Chemotherapy has induced remission in 2 cases of advanced EMPD and needs testing in clinical trials.

Diagnosis, Differential↗

An electron microscopic study of hemopoietic tissues in the course of Lewis lung carcinoma.

Lewis lung carcinoma of C57Bl/6 mice causes a progressive anemia with reticulocytosis and splenomegaly, metastasizes to lungs, liver, and kidneys but does not invade hemopoietic tissues. The cause of this anemia is uncertain. We studied the structure of spleen and bone marrow in these tumor hosts by light and electron microscopy. Splenic congestion of the red pulp with numerous erythropoietic islands and marrow hyperplasia characterized the hemopoietic tissues of these mice, which, when coupled with other hematological parameters suggested a hemolytic condition. However, the erythropoietic response appeared to be in part ineffective as evidenced by phagocytosis of immature as well as mature red blood cells within the spleen and marrow. Thus, the condition of anemia in Lewis lung carcinoma may result from a multifactorial response of hemolysis and ineffective erythropoiesis and hemolysis.

Anemia↗

Cytoskeletal organization of a cloned hemopoietic stromal cell line during attachment and spreading.

The cell membrane of a cloned murine bone marrow stromal cell line D2XRII was extracted in situ using Triton X-100 detergent and the cytoskeletal structure studied during the process of adherence and spreading. During this process, three zones can be identified in the cytoplasm: the perinuclear zone, which was the fixed part of the cell; the peripheral mixed filamentous zone, which formed the core of long cytoplasmic projections; and an outer zone, which formed the boundary of cytoplasmic projections and contained only intermediate filaments. The process of spreading appeared to originate from very long strips of microfilaments emanating from the second zone, crossing the width of the outer zone, and extending beyond for a long distance. The second and third zones then appeared to "stream out" around the axis of this strip, and in this fashion the cytoplasm spreads over the substratum.

Animals↗

Cancer chemotherapy in the elderly.

Although age may reduce the physiologic reserve of many systems, elderly patients with good performance status may receive chemotherapy without undue toxicity. Both survival and quality of life may be improved by treatment of responsive neoplasms, such as acute leukemia, multiple myeloma, small cell cancer of the lung, lymphomas and breast cancer. Age-related decrements in glomerular filtration rate and cardiac reserve suggest that doses of renally excreted drugs and cardiotoxic anthracyclines should be reduced in the elderly.

Aged↗

Ouabain sensitivity is linked to ras -transformation in human HOS cells.

Mouse cells transformed by the retroviral oncogene v-Ki- ras are significantly more sensitive to the toxic effects of 1mM ouabain than are their nontransformed counterparts. We have extended these findings to a human cell line (HOS). HOS cells (ATCC CRL 1543) are relatively resistant to treatment with 1 microM ouabain while KHOS cells (transformed by Kirsten murine sarcoma virus) are extremely sensitive. Two flat revertant cell lines isolated from the KHOS line and lacking the v- ras gene sequences are resistant to ouabain. This effect may be observed morphologically and can also be demonstrated by dye exclusion and plating efficiency tests. In addition, the toxic effects of ouabain may be rapidly and efficiently quantitated in a 51Cr-release assay. This differential lethality may be used to enrich the proportion of non-transformed revertants in populations of mutagen-treated transformed cells.

Animals↗

Acidic and basic hair/nail ("hard") keratins: their colocalization in upper cortical and cuticle cells of the human hair follicle and their relationship to "soft" keratins.

Although numerous hair proteins have been studied biochemically and many have been sequenced, relatively little is known about their in situ distribution and differential expression in the hair follicle. To study this problem, we have prepared several mouse monoclonal antibodies that recognize different classes of human hair proteins. Our AE14 antibody recognizes a group of 10-25K hair proteins which most likely corresponds to the high sulfur proteins, our AE12 and AE13 antibodies define a doublet of 44K/46K proteins which are relatively acidic and correspond to the type I low sulfur keratins, and our previously described AE3 antibody recognizes a triplet of 56K/59K/60K proteins which are relatively basic and correspond to the type II low sulfur keratins. Using these and other immunological probes, we demonstrate the following. The acidic 44K/46K and basic 56-60K hair keratins appear coordinately in upper corticle and cuticle cells. The 10-25K, AE14-reactive antigens are expressed only later in more matured corticle cells that are in the upper elongation zone, but these antigens are absent from cuticle cells. The 10-nm filaments of the inner root sheath cells fail to react with any of our monoclonal antibodies and are therefore immunologically distinguishable from the cortex and cuticle filaments. Nail plate contains 10-20% soft keratins in addition to large amounts of hair keratins; these soft keratins have been identified as the 50K/58K and 48K/56K keratin pairs. Taken together, these results suggest that the precursor cells of hair cortex and nail plate share a major pathway of epithelial differentiation, and that the acidic 44K/46K and basic 56-60K hard keratins represent a co-expressed keratin pair which can serve as a marker for hair/nail-type epithelial differentiation.

Antibodies, Monoclonal↗

Nutrition, cancer, and aging: an annotated review. II. Cancer cachexia and aging.

The interactions of cancer and malnutrition are discussed with the focus on aging. To establish whether the elderly are more likely to develop cancer cachexia and its complications, this review encompasses the pathogenesis of malnutrition in cancer; the age-related alterations of appetite, gastrointestinal function, energy expenditure, and protein turnover; the diagnosis of malnutrition; and the effectiveness of nutritional support in the elderly. Although metabolic and physiologic changes induced by cancer and age appear synergistic in causing cachexia, more frequent complications of malnutrition have not been observed in the geriatric cancer patients. This may be due to only a small proportion of the elderly with cancer being enrolled in clinical studies or to a reduced cachexia-inducing ability of tumors in these patients. A limited number of studies indicate nutritional replenishment is obtainable in malnourished elderly by hyperalimentation. As restoration of the lean body mass may be slower in older patients, early institution of nutritional support is recommended in malnourished elderly or elderly at risk for malnutrition during neoplastic treatment.

Aged↗

Nutrition, cancer, and aging: an annotated review. I. Diet, carcinogenesis, and aging.

The interrelationships of diet and carcinogenesis are discussed with the focus on aging. To establish whether the elderly are more susceptible to dietary carcinogens and whether dietary prevention of cancer is a reasonable goal for this population, the mechanisms of chemical carcinogenesis, the age-related metabolic and physiologic changes, and the current cancer preventive dietary strategies are reviewed. Vulnerability to dietary carcinogens results from a combination of factors that may increase or decrease the occurrence of cancer in the elderly, and it is, therefore, a very individualized feature, unpredictable when based solely on a subject's age. Dietary prevention of cancer may be effective in advanced age, and the dietary guidelines of the National Academy of Sciences should be implemented in this population.

Aflatoxins↗