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Biomedical subjects

P Kelly

Publications and source records attributed to P Kelly.

At least 19 recordsLinked to original sources

Assessment of spinal and femoral bone density by dual X-ray absorptiometry: comparison of lunar and hologic instruments.

Clinical application of techniques for assessing bone mineral density (BMD) requires accurate and precise measurements that can be related to clearly defined normal ranges. In this study we investigated the clinical interpretation of BMD values in a group of individuals measured on the same day with two different dual-energy x-ray densitometers (Lunar DPX and Hologic QDR 1000). The BMD results were analyzed as absolute values in g/cm2 and with respect to young and age-specific normals as defined by each manufacturer. Absolute BMD values measured by the two instruments were highly correlated (lumbar spine r = 0.98, femoral neck r = 0.95; p less than 0.0001). In the lumbar spine, the two instruments assigned almost identical values when expressed as a percentage of age-matched values and as a percentage of young normals, despite a small but systematic difference between the values assigned for the latter index. In the femoral neck, however, there were significant differences in assignments between instruments, expressed both as a percentage of young normal (mean difference 6.2%) and with respect to age-matched values (mean difference 3.3%). In particular, in premenopausal subjects femoral neck values with the Hologic instrument were assigned significantly lower values. This study shows effective comparability between these two instruments for absolute and relative values for the lumbar spine, as well as for absolute values at the femoral neck, but important differences for normality assignments at the femoral neck. These latter differences may produce bias in the "diagnosis" of femoral neck osteoporosis and may have important implications for clinical decision making.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon

Papanicolaou smear abnormalities in ambulatory care sites for women infected with the human immunodeficiency virus.

OBJECTIVE: We attempted to determine the prevalence of cervical dysplasia in human immunodeficiency virus-infected women in ambulatory care settings and to correlate Papanicolaou smears with demographic and clinical variables. STUDY DESIGN: Papanicolaou smears of 135 women attending three ambulatory care clinics were reviewed. Chart review identified demographic and clinical variables, including CD4 count. Prevalence of abnormal smears was compared with baseline community rates. Demographic and clinical variables were correlated with Papanicolaou results with the chi 2 test. RESULTS: Fivefold to eightfold increased rates of abnormal smears in human immunodeficiency virus-infected women were observed. Prevalence of abnormal smears increased from 21% in women with CD4 counts greater than 600/mm3 to 45% in women with CD4 counts less than 400/mm3. Age, ethnicity, or mode of human immunodeficiency virus transmission was not significantly correlated with Papanicolaou smear findings. CONCLUSION: Increased rates of abnormal Papanicolaou smears and significant correlation with CD4 counts were observed in human immunodeficiency virus-infected women at ambulatory care sites. We recommend comprehensive gynecologic care, including semiannual Papanicolaou smears, for all human immunodeficiency virus-infected women.

Acquired Immunodeficiency Syndrome

Skin anergy and tuberculosis.

In our experience tuberculin skin anergy (negative response to 10 TU Mantoux) occurs in 8% of patients with tuberculosis. In this study we compare 81 patients with skin anergy and proven tuberculosis with a background reactive population of patients with tuberculosis. Patients with skin anergy and tuberculosis were older and had fewer symptoms--less cough, less sputum production, less haemoptysis, less malaise, less chest pain--than patients with skin reactivity. There was no difference with respect to male/female ratio, marital status, smoking habits, coexistent major illness, prescribed medications at diagnosis, nor the proportion of patients with extrapulmonary tuberculosis, previous history of BCG vaccination or past history of tuberculosis. Comparison of chest radiographs showed more advanced, more bilateral and more miliary disease in the anergic patients. Pyrexia and elevated ESR at diagnosis were also more common in this group. Fewer of the anergic group of patients were consistently culture negative after 1 month's treatment compared to the background population. Mortality was higher in the anergic group, but this excess mortality occurred from causes other than tuberculosis. Repeat Mantoux testing was performed in 20 of the 81 anergic patients, after a minimum of 3 months of antituberculous chemotherapy, and 14 had become tuberculin positive, suggesting that tuberculin skin anergy may be a temporary phenomenon.

Adult

AIDS, i.v. drug use and mycobacterial disease: the Dublin experience.

In the period 1980-1985, we treated 1641 patients for tuberculosis of whom two were known to be intravenous drug users (IVDU) and none had HIV infection. Of the next 1000 patients treated for tuberculosis (January 1986-December 1989), six were HIV-negative intravenous drug users (IVDU), 18 patients were HIV-positive (12 IVDU; six homosexual/bisexual). Statistical analysis (chi 2) showed a numerically small but statistically significant (P < 0.00001, d.f. = 1, chi 2 = 20.38) increase in intravenous drug users with a diagnosis of tuberculosis. The HIV-positive patients who completed treatment responded well to anti-tuberculous drugs. The importance of tuberculosis in the context of HIV infection is that it is preventable, treatable and is the only bacterial infection to which HIV subjects are prone which can be readily transmitted to a non-HIV infected subject.

Acquired Immunodeficiency Syndrome

Stimulation of human breast cancers by dietary L-arginine.

1. The amino acid L-arginine has been shown to enhance immune mechanisms and inhibit tumour growth in experimental animals, but although many of the immunological effects of arginine have been reproduced in man there have been few studies of its effects on human tumours. In this study the effects of arginine on human breast cancers were determined by measuring tumour protein synthesis and comparing this with immunohistochemical assessments of cell proliferation. 2. Patients with breast cancer were randomized to receive either a standard diet or arginine supplementation. At the time of surgery, the rate of tumour protein synthesis was measured by the incorporation of the stable isotope [1-13C]leucine into tumour protein. Tumours were also assessed histologically and by staining for the presence of the activation antigen Ki67. 3. The median rate of tumour protein synthesis was 10%/day (range 5.5-15.8%/day) in the control patients and 25.6%/day (range 9-37%/day) in the patients receiving arginine supplements (P less than 0.005, Wilcoxon rank sum test). The rates of protein synthesis correlated with Ki67 expression within these tumours (r = 0.78, P less than 0.001). A double-staining technique confirmed that tumour cells, rather than tumour-infiltrating lymphoreticular cells, expressed Ki67. 4. This study demonstrates that, in contrast to animal studies, L-arginine stimulates human tumours in vivo. This represents the first direct evidence that a single amino acid can modulate the behaviour of a human cancer.

Administration, Oral

An evaluation of buffered aspirin and aspirin tablets in postoperative pain after third molar surgery.

1. Single doses (500 and 1000 mg) of both buffered aspirin and aspirin tablets were compared with placebo in a randomised double-blind trial of parallel design in patients with postoperative pain after third molar surgery. 2. Only buffered aspirin 500 mg provided significant pain relief (P = 0.016) during the 5 h investigation period. 3. A significant correlation (P = 0.004) was observed between overall pain scores after the various aspirin treatments and aspirin esterase activity. 4. Buffered aspirin preparations afforded a slight advantage over aspirin tablets in the control of postoperative pain after third molar surgery. However, the duration of analgesia was short (approximately 2 h). 5. Aspirin esterase activity appears to be an important determinant of the drug's efficacy in postoperative dental pain.

Adult

Generalized elastosis perforans serpiginosa in Down's syndrome.

Elastosis perforans serpiginosa is a rare disorder of epidermal perforation characterized by the extrusion of dermal elastic tissue through the epidermis. Its aetiology is unknown, but there is histological and biochemical evidence of an abnormality of elastic tissue. Three forms of elastosis perforans serpiginosa exist. It may be either idiopathic, iatrogenic, or, in approximately one quarter of cases, associated with certain genetically determined disorders of connective tissue. Cutaneous lesions appear between the ages of 6 and 20 years, and persist for 6 months to 5 years. They may be confined to one anatomic area, or less frequently are disseminated. We review the case of a 28-year-old woman with recent onset of unusually extensive elastosis perforans serpiginosa with co-existing Down's syndrome and (secondary) sclerosing cholangitis.

Adult

Isolation of Kingella kingae from a corneal ulcer.

Kingella kingae was isolated from a corneal ulcer in an 11-month-old male. This organism has been previously reported from normally sterile sites, including sites of endophthalmitis, but this is the first time isolation from the cornea has been reported.

Bacterial Typing Techniques

Impact of insulin deficiency on glucose fluxes and muscle glucose metabolism during exercise.

Exercise in the insulin-deficient diabetic state is characterized by a further increase in elevated circulating glucose and NEFA levels and by excessive counterregulatory hormone levels. The aim of this study was to distinguish the direct glucoregulatory effects of insulinopenia during exercise from the indirect effects that result from the metabolic and hormonal environment that accompanies insulin deficiency. For this purpose, dogs underwent 90 min of treadmill exercise during SRIF infusion with (SRIF + INS, n = 8) or without (SRIF - INS, n = 6) intraportal insulin replacement. Glucagon was not replaced, thus allowing assessment of the direct effect of insulinopenia at the liver independent of the potentiation of glucagon action. Glucose was infused to maintain euglycemia. Hepatic glucose production (Ra); glucose utilization (Rd); and LGlcU, LGlcE, and LGlcO were assessed with tracers ([3H]glucose, [14C]glucose) and arteriovenous differences. With exercise, insulin fell from 66 +/- 6 to 42 +/- 6 pM in the SRIF + INS group, and was undetectable in the SRIF - INS group. Plasma glucose was 6.33 +/- 0.38 and 6.26 +/- 0.30 mM at rest in the SRIF + INS and SRIF - INS groups, respectively, and was unchanged with exercise. Ra rose from 7.5 +/- 2.3 to 16.5 +/- 2.2 mumol.kg-1.min-1 and 9.1 +/- 2.0 to 31.4 +/- 3.9 mumol.kg-1.min-1 with exercise in the SRIF + INS and SRIF - INS groups, whereas Rd rose from 19.5 +/- 2.0 to 46.8 +/- 3.9 mumol.kg-1.min-1 and 15.1 +/- 1.8 to 29.9 +/- 3.3 mumol.kg-1.min-1. LGlcU rose from 36 +/- 9 to 112 +/- 25 mumol/min and 15 +/- 4 to 59 +/- 13 mumol/min and LGlcO rose from 5 +/- 2 to 61 +/- 12 mumol/min and 5 +/- 3 to 32 +/- 9 mumol/min with exercise in the SRIF+INS and SRIF-INS groups, respectively. Arterial levels and limb balances of NEFAs and glycerol were similar in the two groups. In summary, during exercise: 1) marked insulinopenia attenuates the increases in muscle glucose uptake and oxidation by approximately 50%, independent of changes in circulating metabolic substrate levels; 2) substantial increases in muscle glucose uptake and oxidation are, however, still present even in the absence of detectable insulin levels; and 3) insulinopenia facilitates the increase in Ra, independent of the potentiation of basal glucagon action. In conclusion, marked insulinopenia contributes directly to the exacerbation of glucoregulation during exercise in the diabetic state by limiting the rises in glucose uptake and metabolism and by enhancing hepatic glucose production.

Analysis of Variance

Continuous intravenous infusion and simultaneous pharmacokinetic monitoring in ambulatory rabbits with a programmable micropump and dual subcutaneous Silastic central venous catheters.

We describe a newly developed method of continuous intravenous infusion and simultaneous monitoring of plasma levels of investigational compounds in ambulatory untethered rabbits. Continuous infusion was administered by means of a portable programmable external micropump which permitted adjustable dosing. Simultaneous plasma pharmacokinetic monitoring during infusion was accomplished by dual silastic central venous catheters. The potential applications of the micropump infusion system as an alternative to current methods of continuous infusion in other species and in other studies are further discussed. This method provided a safe, reliable, and well-tolerated method of adjustable continuous intravenous infusion and simultaneous sampling of central venous blood in rabbits.

Animals

Postmenopausal bone loss in rheumatoid arthritis: effect of estrogens and androgens.

Osteoporosis is a frequent complication of rheumatoid arthritis (RA), especially in postmenopausal women, and may involve both juxtaarticular and generalized bone loss. To examine the effect of exogenous estrogens and endogenous androgens on bone loss in RA we determined rates of bone loss by serial bone density measurement for up to 4 years in 38 postmenopausal women with RA. Serum dehydroepiandosterone sulfate concentrations correlated significantly with the change in femoral neck bone but not in lumbar spine bone. Estrogen therapy prevented lumbar spine bone loss, but did not affect bone loss from the hip. These data suggest adrenal androgen status may influence bone loss in RA and that, although estrogen therapy can prevent bone loss from the spine, it may not prevent bone loss at sites near involved joints.

Androgens

Update on osteoporosis.

Osteoporosis is an increasing and major public health problem as our population ages. Advances in our understanding of osteoporosis have been facilitated by the advent of accurate and precise methods of bone density measurement. Developments in therapy include transdermal oestrogens, nasal calcitonin and bisphosphonates. The most important principles of management involve maximising bone mass in early adult years and preventing postmenopausal bone loss by oestrogen therapy.

Absorptiometry, Photon

Comparison of cAMP receptor protein (CRP) and a cAMP-independent form of CRP by Raman spectroscopy and DNA binding.

The secondary structures of the cAMP receptor protein (CRP), a complex of CRP and cAMP, and a cAMP-independent receptor protein mutant (CRP*141 gln) were examined by using Raman spectroscopy. Spectra were obtained from CRP and CRP*141 gln dissolved in 0.3 M NaCl and 30 mM sodium phosphate at protein concentrations of 30-40 mg/mL. CRP and CRP.cAMP1 were compared at lower protein concentrations (10-12 mg/mL) in a solvent of 0.35 M NaCl and 20 mM sodium phosphate. Raman analysis indicates that CRP structural changes induced by one bound cAMP or by the Gly to Gln mutation at residue 141 are small. Spectra of the three CRP samples are essentially identical from 400 to 1900 cm-1. This result differs from the Raman spectroscopy study of CRP and CRP.cAMP2 cocrystals [DeGrazia et al. (1990) Biochemistry 29, 3557]. The latter work showed spectral differences between CRP and CRP.cAMP2 consistent with alterations in the protein conformation. These studies indicate that CRP and CRP.cAMP1 in solution are similar in structure and differ from CRP.cAMP2 cocrystals. Protease digestion and a DNA binding assay were also employed to characterize the wild-type and mutant proteins. CRP*141 gln exhibited the same conformational characteristics of previously reported cAMP-independent mutant proteins. It was sensitive to proteolytic attack in the absence of cAMP, or upon addition of cGMP. In the absence of cAMP, both wild-type and mutant CRPs bound noncooperatively to a 62 bp lac promoter DNA. The equilibrium constants were approximately 10(6) M-1 in 0.1 M Na+. CRP*141 gln had a 2-4-fold higher affinity for the 62 bp DNA than CRP.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclic AMP

Tin oxide coating of aluminous porcelain by reactive ion plating.

Alumina reinforced dental porcelain has been coated directly with tin oxide by reactive ion plating. Samples were prepared at different distances from the tin source in the ion plating rig. Tensile bond strengths of treated and untreated porcelain discs to a commercially available phosphate-methacrylate based dental cement were determined. Bond strengths of certain coated samples were found to be in excess of the cohesive strength of the porcelain substrates (greater than 7.8 MPa), whereas untreated porcelain achieved an average bond strength of only 3.4 MPa. The microstructures of coatings produced under conditions similar to those which yielded the maximum bond strength were examined in a scanning electron microscope and were found to be approximately 0.5 microns thick. It is believed that ion plating has great potential for rendering inert ceramic surfaces capable of direct bonding to dental cements.

Adhesives