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Biomedical subjects

P Cox

Publications and source records attributed to P Cox.

At least 73 records · Page 4Linked to original sources
PubMed1995

Renal replacement therapy after repair of congenital heart disease in children. A comparison of hemofiltration and peritoneal dialysis.

The development of renal failure necessitating peritoneal dialysis after cardiac operations is associated with a reported mortality greater than 50%. Improved fluid removal and nutritional support have been reported with the use of continuous arteriovenous hemofiltration and continuous venovenous hemofiltration techniques. We have compared our experience with all three techniques in managing children who required renal replacement therapy after cardiac operations in terms of efficacy (fluid removal, calorie intake, and clearance of urea and creatinine), complications, and outcome. Over a 5-year period renal replacement therapy was initiated in 42 children, and in 34 of them it was successfully established for more than a 24-hour period: 17 were managed with peritoneal dialysis, 8 with continuous arteriovenous hemofiltration, and 9 with continuous venovenous hemofiltration. A net negative fluid balance was achieved in only 6 (35%) patients treated with peritoneal dialysis compared with 50% of those treated with continuous venovenous hemofiltration and 89% of those treated with continuous venovenous hemofiltration. In terms of nutritional support, calorie intake increased by 43% after peritoneal dialysis was started compared with 515% and 409% in the arteriovenous and venovenous hemofiltration groups, respectively, (p < 0.005). The serum urea levels fell by 36% (p = 0.02) and 39% (p = 0.005) compared with pre-therapy levels with arteriovenous and venovenous hemofiltration, respectively, and the creatinine content was reduced by 19% and 33% (p = 0.003). Neither parameter was reduced in the peritoneal dialysis group. We conclude that the use of hemofiltration as a renal replacement therapy after surgical correction of congenital heart disease offers significant advantages over the more traditional approach of peritoneal dialysis. In addition, we suggest that a more aggressive approach to the management of fluid overload and nutritional depletion with hemofiltration may result in a decrease in the very high mortality seen in renal failure after cardiac operations.

Acute Kidney Injury↗
PubMed1995

Sunscreens and T4N5 liposomes differ in their ability to protect against ultraviolet-induced sunburn cell formation, alterations of dendritic epidermal cells, and local suppression of contact hypersensitivity.

Exposure of skin to ultraviolet (UV) radiation can lead to diverse biologic effects, including inflammation, sunburn cell formation, alterations of cutaneous immune cells, and impaired induction of contact hypersensitivity responses. The molecular mechanisms of these UV-induced effects are not completely understood. We investigated the ability of sunscreens and liposomes containing the DNA excision repair enzyme T4 endonuclease V to prevent these effects of UV radiation. The use of T4N5 liposomes, which increase the repair of cyclobutyl pyrimidine dimers, provides an approach for assessing the role of DNA damage in the effects of UV radiation on the skin. Exposing C3H mice to 500 mJ/cm2 UVB radiation from FS40 sunlamps resulted in skin edema, sunburn cell formation, and morphologic alterations and decreased numbers of Langerhans cells and Thy-1+ dendritic epidermal T cells. In addition, the induction of contact hypersensitivity after application of 2,4-dinitrofluorobenzene on UV-irradiated skin was diminished by 80%. Applying sunscreens containing octyl-N-dimethyl-p-aminobenzoate, 2-ethylhexyl-p-methoxycinnamate, or benzophenone-3 before this dose of UV irradiation gave nearly complete protection against all of these effects of UV irradiation. In contrast, topical application of T4N5 liposomes after UV irradiation had no effect on UV-induced skin edema and only partially protected against sunburn cell formation and local suppression of contact hypersensitivity, although its ability to protect against alterations in dendritic immune cells was comparable to that of the sunscreens. These results suggest that DNA damage is involved in only some of the local effects of UV radiation on the skin. In addition, T4N5 liposomes may be a useful adjunct to sunscreens because they can reduce some of the deleterious effects of UV radiation on skin even after a sunburn has been initiated.

Animals↗
PubMed1994

Localization of liposomes containing a DNA repair enzyme in murine skin.

T4N5 liposomes, which contain the DNA repair enzyme T4 endonuclease V, were applied to mouse skin in vivo and added to cultured murine keratinocytes in vitro. The fate of the liposome membrane was followed using a fluorescent, lipophilic dye, and the fate of the enzyme was traced by immunogold labeling, followed by brightfield, fluorescence, or transmission electron microscopy. In vivo, T4N5 liposomes penetrated the stratum corneum, localized in epidermis and appendages of the skin, and were found inside basal keratinocytes. The enzyme was found inside keratinocytes treated in vitro and in the epidermis, hair follicles, and sebaceous glands of topically treated skin. Ultrastructural studies demonstrated the presence of liposomes in the cytoplasm of cells in the epidermis often concentrated in a perinuclear location. The enzyme was present in both nucleus and cytoplasm of keratinocytes and Langerhans cells. Liposomes were found in cells of the lymph nodes draining the site of contact sensitization, in association with topically applied antigen. The results demonstrate that liposomes can deliver encapsulated proteins into cells of the skin in vivo and provide insight into how liposome-enhanced DNA repair reduces UV-induced skin cancer and systemic immunosuppression in mice.

Animals↗
PubMed1994

A simple method for monitoring the concentration of inhaled nitric oxide.

Nitric oxide is a potent endogenous vasodilator involved in the homeostatic control of systemic blood pressure. It has also recently been demonstrated that when inhaled in low concentrations it acts as a specific pulmonary vasodilator. The concept of inhaled nitric oxide as a form of therapy is almost an anathema to anaesthetists. However, nitric oxide is being used increasingly for the treatment of persistent pulmonary hypertension of the neonate and in the adult respiratory distress syndrome. One major limitation to its frequent and widespread use is the problem of measuring the concentration of nitric oxide delivered. Currently, the gold standard technique used is chemiluminesence. However, the equipment required is costly and can be difficult to use. If the use of inhaled nitric oxide increases and it develops a therapeutic role then its applications may be limited only to centres which can afford such equipment. Others may be prevented from using a potentially valuable therapy due to lack of a controlled delivery system for nitric oxide. An inexpensive, simple alternative technique to chemiluminesence is described, which will allow most intensive care units the freedom to use inhaled nitric oxide if necessary.

Administration, Inhalation↗
PubMed1994

Nucleotide sequence of the equine interferon gamma cDNA.

Interferon gamma, a cytokine produced by T-lymphocytes and natural killer cells, plays a central role in the modulation of the immune response, and its antiviral and antitumourigenic properties have made it a potential candidate for use in immunoprophylactic and therapeutic regimes. We have cloned the equine IFN gamma cDNA to facilitate production of this cytokine for clinical evaluation in the horse. The predicted equine IFN gamma amino acid sequence is 67% identical to that of the human equivalent and 78% to the bovine equivalent.

Amino Acid Sequence↗
PubMed1993

Reproductive axis suppression in acute illness is related to disease severity.

Changes in the adrenal and thyroid axes in critically ill patients are accentuated by increasing disease severity. However, the relationship of gonadal axis suppression to severity of illness is not well defined. We evaluated serial serum levels of LH, FSH, and testosterone (T) in 59 men and 42 postmenopausal women admitted to critical care units with a spectrum of disease severity. Patients were grouped according to severity of illness by the Acute Physiologic and Chronic Health Evaluation II (APACHE II) scores and by survival. Patients with surgery, renal or hepatic failure, alcohol abuse, endocrine disease, or head trauma were excluded to avoid these confounding factors. In men, mean admission serum T levels in all groups were lower than in healthy controls (P < 0.005). In addition, T levels in men with severe illness (APACHE > 15) were lower than in men with relatively mild (APACHE < 10; P < 0.01) or moderate illness (APACHE 10-15; P < 0.05). These differences were accentuated as hospitalization progressed. In postmenopausal women and men, nadir serum FSH but not LH levels during hospitalization were lower in patients with APACHE greater than 15 than in patients with APACHE scores of 10-15 or less than 15 (P < 0.05). Grouping patients by survival yielded similar results. Analysis of drug effects, age, and PRL did not explain these relationships. We conclude that the degree of both central and peripheral suppression of the reproductive axis in acute illness is related to disease severity. This suppression could not be attributed to other factors known to alter the reproductive axis independently from critical illness (e.g. age, drugs, head trauma, hepatic failure, etc.). These findings further document a general endocrine response to acute illness involving several axes which is graded according to disease severity.

Acute Disease↗
PubMed1992

Both hyper- and hypogonadotropic hypogonadism occur transiently in acute illness: bio- and immunoactive gonadotropins.

Previous reports of hypogonadotropic hypogonadism in critically ill men may not reflect the complexity of changes in the hypothalamic-pituitary-gonadal (HPG) axis during acute illness. We sampled blood throughout hospitalization in 55 men admitted to acute care units to delineate the spectrum of changes in circulating gonadotropin and sex steroid levels at the onset and during recovery from acute illness. Bioactive LH and FSH were measured in a subset of patients. Percent free testosterone was measured to assess changes in binding to sex hormone binding globulin. Medications and serum estrogen and prolactin levels were monitored as potential causes of hypogonadotropism. Sustained suppression of serum testosterone levels below the normal range occurred in 62% of men with varying diagnoses and disease severity. Percent free testosterone remained constant. Hypogonadotropism was observed in most men (60%) and occurred independently from head injury, surgery, medications, or hyperprolactinemia. In a subset of men (n = 16), LH and/or FSH rose transiently above the normal range. Bioactivity of both LH and FSH remained constant while serum testosterone levels decreased. In contrast to serum testosterone levels, mean serum levels of E1, E2 and androstenedione were not less than control values. We conclude that both primary and secondary hypogonadism occur transiently in acutely ill men and cannot be explained solely by medications, hyperprolactinemia, or hyperestrogenemia. Neither biopotency of gonadotropins nor binding of testosterone to SHBG change across the course of acute illness. The hypogonadism, often severe and prolonged, may contribute to the persistent catabolic state observed in many critically ill patients.

Acute Disease↗
PubMed1991

Differential expression of GABAA receptor alpha-subunits in rat brain during development.

Unique cytoplasmic loop regions of the alpha 1, alpha 2, alpha 3, and alpha 5 subunits of the GABAA receptor have been expressed in E. coli and used to generate polyclonal antisera specific for these subunits. The antibodies identify proteins by SDS-polyacrylamide gel electrophoresis and western blotting of molecular size 51 kDa, 53 kDa, 59 kDa and 55 kDa, respectively, which show differential patterns of expression during development. Whereas the alpha 2 and alpha 3 subunits are present at early stages, the expression of alpha 1 and alpha 3 subunits is low at birth and increases with age. This differential expression could be correlated with previous studies examining the developmental expression of BZ1 and BZ2 benzodiazepine binding sites.

Animals↗
PubMed1991

Prevention of IUD-related pelvic infection: the efficacy of prophylactic doxycycline at IUD insertion.

It is believed that much of the small increased risk for developing pelvic inflammatory disease (PID) associated with the use of an intrauterine device (IUD) appears to be caused by bacterial contamination of the endometrial cavity at the time of insertion. Previous research suggests that use of prophylactic antibiotics immediately prior to IUD insertion may reduce the risk of developing PID. This paper presents results from a randomized clinical trial of 1485 women in Ibadan, Nigeria evaluating the effectiveness of 200 mg of doxycycline (versus placebo) given orally at the time of IUD insertion in reducing the incidence of PID during the first three months of IUD use. Rate of PID infection in the doxycycline-treated group was not significantly lower than that in the placebo-treated group. The rate of unscheduled IUD-related visits to the clinic also was not significantly lower among the doxycycline-treated group. However, the incidence of PID was low (21 cases) for both study groups. Aseptic conditions during IUD insertion, follow-up visits with short intervals to monitor health, and treatment of opportunistic infections may have reduced the potential of PID within this population.

Administration, Oral↗
PubMed1991

Thin-layer chromatographic analyses of lipids in different layers of porcine epidermis and oral epithelium.

Frozen cryosections were cut parallel to the surface of porcine skin and palatal, buccal and floor-of-mouth mucosa so as to provide separate samples representing various epithelial layers. The samples were dried, extracted with chloroform:methanol, and the lipids were chromatographed on silica gel plates in various solvent systems. After charring, lipids were quantified with a scanning densitometer. Overall, greater differences in proportions and distributions of lipid components were evident between keratinized and non-keratinized epithelia than between epidermis and keratinized oral epithelium. For epidermis and palate there was an increase in neutral lipids, including ceramides, from the deeper layers to the surface; ceramides were most abundant in surface layers. In buccal epithelium there was a distinct increase in glycosylceramides toward the surface, and in both non-keratinized regions ceramides were present in only very small amounts. The results suggest that although neutral lipids may be associated with a superficial barrier layer in skin and oral mucosa, there are differences in the composition of this barrier between keratinized and non-keratinized epithelia.

Animals↗
PubMed1991

Lipid content and water permeability of skin and oral mucosa.

It has been claimed that total lipid content may be the critical factor determining the water permeability of skin. The present study examined this relationship in various oral epithelia and epidermis. Epithelia was heat separated from specimens of porcine skin, gingiva, buccal mucosa, palate, and floor of mouth. Lipids were solvent extracted and separated by thin layer chromatography with appropriate standards. The plates were sprayed with sulfuric acid and charred, and the concentration of lipids was determined by densitometry as mg lipid/gm tissue dry weight. Permeability constants were determined for each tissue by using tritiated water in perfusion chambers. When these values were compared over all regions, total lipid did not appear to be related to the permeability of these tissues. However, in the keratinized regions (epidermis, gingiva, and palate) a lower water permeability was related to a greater content of total lipid, nonpolar lipid, ceramide, and glucosylceramide. In non-keratinized tissues, a lower permeability corresponded to increased amounts of an unidentified glycosylceramide. The role of lipid in the permeability barrier of these tissues was further demonstrated by extracting specimens of skin and oral mucosa with chloroform/methanol and then determining Kp values; in both tissue regions, there was a significant increase in water permeability. Thus, although lipid is a component of the water permeability barrier in both skin and oral mucosa, different lipid components subserve this function in keratinized and non-keratinized tissues.

Animals↗
PubMed1990

Radioimmunodetection in rhabdo- and leiomyosarcoma with 111In-anti-myosin monoclonal antibody complex.

In patients with rhabdo- and leiomyosarcoma a radioimmunodiagnostic study was performed with 111In labeled F(ab) fragments of a monoclonal antibody against myosin. Eight patients with rhabdomyosarcoma and 18 patients with leiomyosarcoma were studied. Scanning was performed at 4, 24, and 48 h after administration of 74 MBeq of the antibody complex. A high uptake with a tumor:background ratio of 10:1 was observed in several patients with rhabdomyosarcoma but the results were less accurate in leiomyosarcoma.

Adolescent↗
PubMed1989

Interleukin-2 protects neonatal mice from lethal herpes simplex virus infection: a macrophage-mediated, gamma interferon-induced mechanism.

Administration of human recombinant interleukin-2 (IL-2) protected neonatal mice from a lethal herpes simplex virus (HSV) infection. Protection was not associated with viral antibody production, enhanced natural killer cell cytotoxicity, or intrinsic resistance of macrophages to viral infection. Protection was associated with increased macrophage-mediated antiviral antibody-dependent cellular cytotoxicity (ADCC). Spleen cells from IL-2-treated neonatal mice and from neonatal mice that were treated in vitro with IL-2 transferred protection to neonatal mice. These cells, by adherence, silica, and asialo GM 1 antibody treatment, were shown to be macrophages. IL-2 treatment in vitro enhanced the neonatal macrophages' ADCC function and superoxide release. Similar protection was induced by gamma interferon (IFN-gamma)-treated spleen cells. Antibody to IFN-gamma ablated both IFN-gamma- and IL-2-induced protection by adherent spleen cells. Thus, IL-2-mediated protection against murine neonatal HSV infection was affected by stimulated macrophage activity, via helper T cell-produced IFN-gamma.

Animals↗
PubMed1989

Intravenous regional analgesia--a new modification.

A modification of the standard intravenous regional analgesia technique is described whereby excess local anaesthetic solution is removed from the veins of the isolated arm once analgesia has been established. This simple procedure was shown to reduce the incidence of oozing at the site of operation without affecting the quality of analgesia. Measurement of the quantity of local anaesthetic agent removed from the isolated arm 15 min after injection revealed that the amounts removed were small, indicating rapid uptake and binding in the tissues. This would imply that removal of excess local anaesthetic agent from the isolated arm after 15 min does not confer added safety as regards reducing the risk of leakage of agent into the general circulation in the event of cuff failure.

Adult↗
PubMed1988

Pressure infusor devices. Do they generate the pressures indicated?

Three currently available pressure infusor devices, based on three different principles, were tested to see if the pressure reading on the infusor manometer corresponds to the pressure generated in the infusion system. Each device was tested in two ways. First, the pressure generated in the infusion system was measured when the infusor bag pressure was maintained at 300 mmHg while the infusion bag was emptied in aliquots of 50 ml. Second, the pressures in the infusor bag required to maintain a pressure of 300 mmHg were measured as the infusion bag was emptied stepwise. The results reveal surprisingly large discrepancies between the pressure registered on the infusor manometer and the actual pressure generated in the fluid, which are not due to manometer inaccuracy. The degree of discrepancy depends on the amount of fluid that remains in the infusion bag and, when the infusor manometer shows a pressure of 300 mmHg, pressure in the fluid can be as much as 170 mmHg above or 200 mmHg below this value. Furthermore, it was impossible to maintain a pressure of 300 mmHg in the infusion system using one of the devices despite the fact that 100 ml fluid remained. The clinical significance of these findings is discussed.

Infusions, Parenteral↗