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Biomedical subjects

J J Kelly

Publications and source records attributed to J J Kelly.

At least 19 recordsLinked to original sources
PubMed1996

Phosphodiesterase 4 in macrophages: relationship between cAMP accumulation, suppression of cAMP hydrolysis and inhibition of [3H]R-(-)-rolipram binding by selective inhibitors.

A perplexing phenomenon identified in several tissues is the lack of correlation between inhibition of phosphodiesterase 4 (PDE4) and certain functional responses such as smooth muscle relaxation, gastric acid secretion and cAMP accumulation. Interpretation of these data is complicated further by the finding that function correlates with the ability of PDE4 inhibitors to displace [3H]rolipram [4-(3-cyclopentenyloxy-4-methoxyphenyl)-2-pyrrolidone] from a high-affinity site in rat brain that is apparently distinct from the catalytic centre of the enzyme. We have investigated this discrepancy by using guinea pig macrophages as a source of PDE4 and have confirmed that the ability of a limited range of structurally dissimilar PDE inhibitors (Org 20241, nitraquazone and the enantiomers of rolipram and benafentrine) to increase cAMP content did not correlate with their potency as inhibitors of partly purified PDE4, whereas a significant linear and rank order correlation was found when cAMP accumulation was related to the displacement of [3H]R-(-)-rolipram from a specific site identified in macrophage lysates. An explanation for these data emerged from the finding that the IC50 values and rank order of potency of these compounds for inhibition of partly purified PDE4 and the native (membrane-bound) form of the same enzyme were distinct. Similarly, no correlation was found when membrane-bound PDE4 was compared with the same enzyme that had been solubilized with Triton X-100. These unexpected results were attributable to a selective decrease in the potency of those inhibitors [nitraquazone, R-(-)- and S-(+)-rolipram] that interacted preferentially with the rolipram binding site. Indeed, if membrane-bound PDE4 was used as the enzyme preparation, excellent linear and rank order correlations between inhibition of cAMP hydrolysis, displacement of [3H]R-(-)-rolipram and cAMP accumulation were found, which improved further in the presence of the vanadyl (Vo)/2. GSH complex. Moreover, using Vo/2.GSH-treated membranes, the IC50 values of nitraquazone and the enantiomers of rolipram for the inhibition of PDE4 approached their affinity for the rolipram binding site. Collectively, these data suggest that the rolipram binding site and the catalytic domain on CPPDE4 might represent part of the same entity. In addition, these results support the concept that PDE4 can exist in different conformational states [Barnett, Manning, Cieslinski, Burman, Christensen and Torphy (1995) J. Pharmcol. Exp. Ther. 273, 674-679] and provide evidence that the cAMP content in macrophages is regulated primarily by a conformer of PDE4 for which rolipram has nanomolar affinity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Binding site size limit of the 2:1 pyrrole-imidazole polyamide-DNA motif.

Polyamides containing N-methylimidazole (Im) and N-methylpyrrole (Py) amino acids can be combined in antiparallel side-by-side dimeric complexes for sequence-specific recognition in the minor groove of DNA. Six polyamides containing three to eight rings bind DNA sites 5-10 bp in length, respectively. Quantitative DNase I footprint titration experiments demonstrate that affinity maximizes and is similar at ring sizes of five, six, and seven. Sequence specificity decreases as the length of the polyamides increases beyond five rings. These results provide useful guidelines for the design of new polyamides that bind longer DNA sites with enhanced affinity and specificity.

Amides↗
PubMed1996

Sex steroid regulation of growth hormone secretion and action.

Evidence that oestrogen is involved in the regulation of the somatotrophic axis in adult humans is provided by the observations that mean growth hormone (GH) levels are higher in women than men, that the fall in GH and insulin-like growth factor-1 (IGF-1) with aging are correlated to oestradiol levels and that oestrogen increases the GH responses to provocative stimuli. To investigate whether oestrogen modulates GH secretion and action in adult life, we studied the impact of oestrogen replacement on circulating GH and IGF-1 levels in postmenopausal women. Since the liver is the major source of circulating IGF-1 and the oral route of oestrogen delivery causes nonphysiologic effects on hepatic proteins, we compared the effects of oral and transdermal routes of delivery. Oral ethinyl oestradiol administration resulted in a significant fall in mean IGF-1 levels and a threefold increase in mean 24-hour GH. Transdermal administration of 17 beta-oestradiol resulted in a slight increase in serum IGF-1 but no change in mean 24-hour GH levels. To determine whether differences in oestrogen type rather than in the route of delivery caused the different effects on the GH/IGF-1 axis, we compared the effects of three oral oestrogen formulations. Ethinyl oestradiol, conjugated equine oestrogen and oestradiol valerate each induced a fall in IGF-1 and a rise in mean 24-hour GH levels in postmenopausal women. To determine the significance of oestrogen-induced changes on IGF-1, we studied effects on markers of connective and bone tissue activity. We found that propeptide concentrations of type III and type I collagen, and osteocalcin rose and fell in parallel with IGF-1 during oral or transdermal oestrogen therapy. Oestrogen causes distinct, route-dependent effects on the somatotrophic axis. The dissociation of the GH/IGF-1 axis by the oral route is likely to arise from impaired hepatic IGF-1 production which causes increased GH secretion through reduced feedback inhibition. Oestrogen treatment may have longer-term metabolic effects on hypogonadal women exerted through effects on the somatotrophic axis.

Adult↗
PubMed1996

Alaska Native cancer update: incidence rates 1989-1993.

Five-year average annual age-adjusted cancer incidence rates for Alaska Natives (Eskimos, Indians, and Aleuts) for the most recent period (1989-1993) are compared to rates of 20 years earlier. Rates for all cancers combined increased 28 and 25% in men and women, respectively, during the 25-year interval. Increases were seen in men in cancers of the lung, prostate, and colon and in women for cancers of the lung, breast, and corpus uteri. Rates are also compared to data from the the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program for United States whites. Rates for all cancers combined in Alaska Native women are now similar to those of United States whites, whereas rates in Alaska Native men are lower than the United States, but only 10% lower. Significant site-specific differences previously reported between Alaska Natives and United States whites persist.

Alaska↗
PubMed1995

Requesting consent for an invasive procedure in newly deceased adults.

OBJECTIVE: Ethical concerns exist over the performance of medical procedures, such as endotracheal intubation, on newly deceased patients without family consent. This study examined the process of obtaining consent for the purpose of performing an invasive procedure in newly deceased adults. DESIGN: A prospective case series. PARTICIPANTS: The families of patients who died during a 5-month period were requested to provide consent to perform wire-guided retrograde tracheal intubation. MAIN OUTCOME MEASURES: Differences between success and failure in obtaining consent including information on the decreased, family reasons for their decision, and the experience of those requesting consent. RESULTS: Consent was requested from 44 families and 26 (59%) agreed to the procedure. This success rate was achieved despite the lack of a prior relationship with the family by the persons requesting consent. Consent was obtained more frequently in unexpected than expected deaths (77% vs 41%, P = .03). There were no differences in success rates for consent for age, race, sex, or do-not-resuscitate status of the deceased. Spouses consented more frequently than children (77% vs 50%, P = .25). The two physicians reported greater comfort in requesting consent than the nurse anesthetist investigator. In one instance, the consent process may have increased the emotional distress of the family. CONCLUSION: Consent can frequently be obtained from families for an invasive procedure in newly deceased adults. Physicians should reconsider the practice of performing postmortem procedures without obtaining family consent.

Adult↗
PubMed1995

Mechanisms of cortisol-induced hypertension in humans.

There is emerging evidence that cortisol plays a significantly greater role in human hypertension than previously thought. Apart from the well recognized role of cortisol in the hypertension of Cushing's syndrome, local cortisol excess has been recognized as responsible for rare forms of hypertension such as apparent mineralocorticoid excess and licorice abuse and more recently implicated in the hypertension of chronic renal failure, hypertension related to low birth weight and essential hypertension. Although cortisol-induced hypertension is characterized by sodium retention and volume expansion, studies with synthetic glucocorticoids or sodium restriction suggest that the hypertension is, to a substantial degree, independent of sodium and volume. Increase in cardiac output is not essential for cortisol-induced blood pressure rise but the precise role of increases in total or regional peripheral resistance as a primary mechanism has nto been determined. Increased pressor responsiveness, particularly to catechols, is a prominent feature but whether these changes are sufficient to account for the hypertension remains unclear. There is no evidence for increased sympathetic nervous activity as judged by measurements of plasma catcholamines, neuropeptide-Y, or resting noradrenaline spillover rate. Responses to mental stress or maximal hand-grip are unchanged and baroreflex sensitivity is increased. Octreotide profoundly reduced the elevated plasma insulin concentrations seen with cortisol administration but had no effect on the rise in blood pressure.

Hemodynamics↗
PubMed1995

Prognostic value of assessing contact system activation and factor V in systemic inflammatory response syndrome.

OBJECTIVE: To test if serially sampled determinations of the contact system proteins and factor V have prognostic value for death in patients who develop the systemic inflammatory response syndrome. DESIGN: Prospective, observational study with sequential measurements in an inception cohort. SETTING: Medical intensive care unit (ICU) in a community hospital. PATIENTS: Over a 1-yr period, a population base sample of 23 patients was selected from all ICU admissions who met established criteria for the systemic inflammatory response syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Components of the contact system, factor XII, prekallikrein, high-molecular-weight kininogen, factor XI, alpha 2-macroglobulin-kallikrein complexes and factor V values were measured in plasma samples collected serially (day of admission, and at 2, 12, 24, 48 and/or 72 hrs or at discharge). Data were analyzed to determine if admission values or serially obtained values within 48 hrs were useful in predicting outcome. Fourteen patients survived and nine died. At admission, in all patients, assay values indicated that prekallikrein, high-molecular-weight kininogen, and factor V were significantly lower than normal (as observed in a range of 20 to 23 healthy adults), alpha 2-macroglobulin-kallikrein complexes were higher than normal, while concentrations of factor XII and factor XI were in the normal range. No differences were detected in the admission values between survivors and nonsurvivors, nor between patients with positive or negative blood cultures. However, subsequent values demonstrated a difference in values between survivors and nonsurvivors. Survivors showed improvement in high molecular weight kininogen values and higher than normal factor V values, as compared with nonsurvivors. CONCLUSIONS: Low or persistently low serial factor XII, high-molecular-weight kininogen and factor V values are associated with a poor prognosis, whereas high or increasing values of factor XII, high-molecular-weight kininogen, prekallikrein, and factor V all correlate with a favorable outcome.

Aged↗
PubMed1995

Oestrogen effects on calcitriol levels in post-menopausal women: a comparison of oral versus transdermal administration.

BACKGROUND AND OBJECTIVES: In some studies oral oestrogen therapy in post-menopausal women has been shown to increase both total and free 1,25-dihydroxyvitamin D (calcitriol) levels, suggesting that oestrogen therapy may prevent post-menopausal bone loss, in part, by increasing calcium absorption as a result of raised calcitriol levels. Transdermal oestrogen, however, has not been shown to increase calcitriol levels although it prevents bone loss. These two routes of administration have not previously been directly compared in the same subjects at bioequivalent doses as assessed by FSH and LH suppression. DESIGN AND PATIENTS: In a randomized cross-over study, 15 women at least 12 months post-menopausal (mean age 56 years (range 50-66)) were randomized to either oral conjugated equine oestrogen (1.25 mg daily) or transdermal 17 beta-oestradiol (100 micrograms daily) for 12 weeks after which each subject changed over to the alternative medication. For the last 12 days of each medication, 10 mg medroxyprogesterone acetate (MPA) was added to the treatment protocol. A fasting blood sample was taken at baseline and at the end of each treatment period prior to administration of the MPA. MEASUREMENTS: Serum calcium, phosphorus, albumin, bicarbonate, intact parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (calcitriol), 25-hydroxyvitamin D (25OHD), vitamin D-binding protein (DBP) were measured. The free calcitriol index was calculated as the molar ratio of calcitriol to DBP. Free calcitriol was measured by centrifugal ultrafiltration. RESULTS: The degree of suppression of FSH and LH was similar with the two routes of oestrogen administration. Total calcitriol was significantly higher with oral oestrogen treatment compared to transdermal oestrogen and compared to baseline (mean +/- SEM, baseline 80 +/- 5; oral oestrogen 102 +/- 8; transdermal oestrogen 82 +/- 4) as was DBP (mean +/- SEM, baseline 5.2 +/- 0.2; oral oestrogen 6.9 +/- 0.4; transdermal oestrogen 5.8 +/- 0.2) which accounted for the rise in calcitriol. Free calcitriol measured by equilibrium dialysis showed no rise with either oestrogen preparation. Phosphorus was not different between treatment groups and fell with both oestrogen treatments (baseline 1.32 +/- 0.15, oral oestrogen 1.23 +/- 0.10, transdermal oestrogen 1.17 +/- 0.16) and PTH rose with both treatments (baseline 1.33 +/- 0.21, oral oestrogen 1.52 +/- 0.27, transdermal oestrogen, 1.99 +/- 0.32). Calcium was not different between treatment groups and was not different from baseline. CONCLUSIONS: These results show that in this study the total calcitriol rose after oral but not transdermal oestrogen due to a rise in vitamin D-binding protein. Free calcitriol was not affected by oral or transdermal oestrogen treatment despite a fall in plasma phosphorus and a rise in PTH, both of which are considered agonists for calcitriol production. We may therefore conclude that neither oral nor transdermal oestrogen replacement routinely stimulates free calcitriol levels. In the studies where a rise in free calcitriol was noted, the degree of suppression of bone resorption by oestrogen may have been greater, thus producing a larger demand for calcium due to filling of a larger bone remodelling space with consequent stimulation of calcitriol levels.

Administration, Cutaneous↗
PubMed1995

Energy metabolism and substrate oxidation in acromegaly.

Short term GH administration increases lipid breakdown and oxidation (lipidox) and reduces glucose uptake and carbohydrate oxidation (CHOox). It is not clear whether similar shifts in substrate oxidation occur in acromegaly, and our aim was to investigate this. Using indirect calorimetry, we compared energy expenditure, CHOox, and lipidox in 20 acromegalic patients and 20 normal subjects pair-matched for sex, age, height, and weight. Investigations were performed in the basal state (12-h fast) and during a 75-g oral glucose tolerance test (OGTT). Acromegalic patients had significantly higher fasting glucose levels and greater glucose and insulin responses during an OGTT than normal subjects. Fasting nonesterified free fatty acid and insulin-like growth factor (IGF)-binding protein-1 levels were similar in the two groups, and both were acutely suppressed by oral glucose to the same degree. Basal energy expenditure was significantly greater in the acromegalic patients (1682 +/- 49 vs. 1540 +/- 45 Cal/24 h; P < 0.05), who showed a trend toward higher basal CHOox. Oral glucose resulted in a significantly higher rise in energy expenditure in the normal compared to the acromegalic subjects. During the OGTT, CHOox significantly increased in both groups, but rose to a higher level in the acromegalic patients (177 +/- 10 vs. 138 +/- 9 mg/min; P = 0.004). Oral glucose significantly reduced lipidox in both groups, but lipidox was reduced to a significantly lower level in the acromegalic patients (32 +/- 4 vs. 46 +/- 3 mg/min; P = 0.004). In acromegaly, basal CHOox (r = 0.56; P = 0.01) and postglucose CHOox (r = 0.79; P = 0.0001) were both positively correlated to IGF-I, but not to insulin and/or glucose. In normal subjects, postglucose CHOox was positively correlated to IGF-I. In summary, hyperinsulinemia in acromegaly was associated with higher glucose levels and a blunted thermogenic response to glucose, and displayed no relationship to the pattern of substrate oxidation. CHOox was increased, and lipidox was reduced in acromegaly, and the extent of IGF-I elevation was related to CHOox in the basal and postglucose states. We conclude that 1) the chronic effects of GH excess on substrate oxidation differ from the short term effects of GH administration; 2) impaired insulin action in acromegaly extends to effects on energy expenditure; and 3) IGF-I may be an important regulator of substrate oxidation in acromegaly.

Acromegaly↗
PubMed1995

Experimental studies on cortisol-induced hypertension in humans.

Studies in humans have shown that cortisol administration (200 mg/day) increases cardiac output, renal vascular resistance, glomerular filtration rate, plasma volume, extracellular fluid volume, exchangeable sodium, plasma glucose, insulin, renin substrate and atrial natriuretic peptide concentrations as well as urinary kallikrein excretion. Cortisol treatment decreases renin and angiotensin II concentrations while catecholamines and vasopressin are decreased or unchanged. We have clear evidence from a number of studies that cortisol-induced hypertension is modulated by, but not dependent on, exogenous sodium. The increase in cardiac output normally seen with cortisol administration is not essential for the blood pressure rise. The role of the increase in renal vascular resistance in the genesis of the hypertension is unclear. Studies using measurements of noradrenaline spillover and assessment of reflex function have not shown any increase in sympathetic nervous system activity but changes in vascular responsiveness, particularly to phenylnephrine and noradrenaline are marked. Cortisol is known to have a variety of effects on brain, heart, kidneys, blood vessels and body fluid volumes. To what extent the observed changes are epiphenomena, amplifiers or modulators, or are causal is unclear. Cortisol hypertension may reflect a complex interplay of these factors varying with the steroid concentrations achieved, underlying genetic factors and the particular experimental circumstances.

Extracellular Space↗
PubMed1995

Characterization of ORG 20241, a combined phosphodiesterase IV/III cyclic nucleotide phosphodiesterase inhibitor for asthma.

The pharmacological profile of a novel cyclic nucleotide phosphodiesterase (PDE) inhibitor, Org 20241, has been characterized. The compound selectively inhibits PDE IV (pIC50, 5.2-6.1) and PDE III (pIC50, 4.4-4.6) from animal and human tissues. Org 20241 relaxed preparations of bovine trachea (pD2, 5.9 and 5.4), guinea pig trachea (pD2, 6.2 and 4.9) and human bronchi (pD2, 5.3 and 4.7) for histamine and methacholine-induced contractions, respectively. Rolipram and Org 20241 inhibited leukotriene B4-induced thromboxaneB2 (IC50, 0.3 and 1.4 microM, respectively) and H2O2 (IC50, 2.1 and 0.4 microM, respectively) production in guinea pig eosinophils. In phenylephrine (0.3 microM) precontracted rabbit aorta preparations, the PDE III inhibitor Org 9935 (pD2, 6.3 and 6.1 in the presence and absence of endothelium, respectively) was the most effective relaxant, whereas Org 20241 (pD2, 5.3 and 5.4 in the presence and absence of endothelium, respectively) was more effective than rolipram (pD2, 4.6 and 4.1 in the presence and absence of endothelium, respectively). Org 20241 relaxed rabbit aorta preparations and airway preparations at similar concentrations. In electrically stimulated rabbit cardiac papillary muscles, Org 20241 had little effect on contractility at concentrations up to 30 microM. Lower concentrations (10 microM) potentiated the inotropic effect of Org 9935. Whereas the PDE III inhibitor milrinone (1-100 microM) enhanced the rate of repolarization of guinea pig papillary muscles and shortened the effective refractory period, Org 20241 and rolipram (1-100 microM) did not reduce the action potential duration. In the presence of Org 20241 or rolipram, isoproterenol did not produce a greater increase in the rate of repolarization or reduction in the effective refractory period than in the absence of these PDE inhibitors. Org 20241 is a dual PDE IV/III inhibitor with some PDE IV selectively. This compound relaxes airways smooth muscle and inhibits eosinophil activation. The data indicate that such PDE IV/III inhibitors may be effective for the long-term therapy of asthma.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1994

Absent F-waves early in a case of transverse myelitis.

A 29-year-old female presented with acute onset of interscapular pain, followed by weakness of both legs and both hands, and a thoracic sensory level. F-waves in her legs and arms were absent initially, but other conduction studies were normal. An initial spine MRI was normal but a second study 10 days later revealed an enlarged spinal cord with areas of enhancement. Repeat neurophysiologic studies showed return of F-waves in the legs and absent compound muscle action potential (CMAP) in the hands with early denervation on needle examination. An acute intraxial lesion needs to be included in the differential diagnosis of absent F-waves.

Adult↗
PubMed1994

Nerve conduction and biopsy correlation in over 100 consecutive patients with suspected polyneuropathy.

Neuropathy was classified physiologically and histologically as normal, axonal, demyelinative, or indeterminate using specific motor nerve conduction (NC) and sural sensory nerve biopsy (NB) criteria. Physiological and histological diagnoses were concordant in 63%, and minimally discordant in 14% of patients. The most important discordant patients were 6 with demyelinative neuropathy, 4 by NC, of which 2 were pure motor syndromes, and 2 by NB, both predominantly sensory syndromes. In the 55 patients with predominant axonal degeneration on biopsy, the extent of NC slowing was determined. As compound motor and sensory nerve action potential (CMAP and SNAP) amplitude declined, distal motor latency increased, whereas motor and sensory conduction velocity (CV) did not. Minimum F response latency increased as motor CV decreased, more in lower than upper extremity nerves. We conclude that: (1) except for sensory neuropathy, routine motor NC studies generally suffice in identifying demyelinative neuropathy; (2) NC slowing in axonal neuropathy is usually slight but may result in significantly prolonged distal motor latencies when CMAP amplitude is very low, and prolonged F wave latency when motor CV is slightly low; and (3) The physiologic criteria employed in this study rarely misclassifies neuropathy as demyelinative in patients with predominant axon loss on biopsy.

Action Potentials↗
PubMed1994

Body composition and energy expenditure in acromegaly.

To investigate whether GH is a regulator of body composition and energy metabolism in adult life, we have compared body composition and resting energy expenditure (REE) in a cross-sectional study in 20 acromegalic and 20 normal subjects, pair-matched for sex, age, height, and weight. In a longitudinal study, 8 acromegalic patients were also studied before and after 12 weeks of treatment [n = 6 during octreotide (100 micrograms, 3 times/day); n = 2 after pituitary surgery], and 7 patients were studied 12 weeks after withdrawal of octreotide. REE was measured by indirect calorimetry and fat mass and fat-free soft tissue mass (FFSTM) by dual energy x-ray absorptiometry. A subgroup of 12 matched pairs of subjects and 7 treated patients had measurement of extracellular water (ECW) by 24Na dilution, which when subtracted from FFSTM provided an estimate of body cell mass (BCM). Fat mass was significantly reduced (25.4 +/- 2.2 vs. 29.7 +/- 2.7 kg; P = 0.007) and FFSTM increased (53.3 +/- 2.2 vs. 49.2 +/- 2.3 kg; P = 0.003) in acromegaly with ECW (25.6 +/- 1.6 vs. 21.1 +/- 0.9 L; P = 0.0003), but not BCM, significantly elevated. Treatment of acromegaly increased fat mass and reduced FFSTM [change (delta), -1.3 +/- 0.4 kg; P = 0.004]; the latter reflected a significant fall in ECW (delta, -2.2 +/- 0.4 L; P = 0.002), but not BCM. The opposite effect on body composition occurred after treatment withdrawal. REE was increased in acromegaly (1682 +/- 49 vs. 1540 +/- 45 Cal/24 h; P = 0.02) and significantly related to insulin-like growth factor-I (P = 0.02). REE was significantly reduced (delta, -154 +/- 17 Cal/24 h; P = 0.0001) with treatment and increased after treatment withdrawal (P = 0.003). In acromegaly, there is a reversible 1) reduction in fat mass; 2) increase in FFSTM, accounted for by an increase in ECW, but not BCM; and 3) increase in REE, which is dependent on disease activity. We conclude from these observations in acromegaly that GH is a regulator of energy metabolism and body composition.

Absorptiometry, Photon↗
PubMed1994

Racial differences in the use of total knee arthroplasty for osteoarthritis among older Americans.

The purpose of this study was to determine differences in the use of total knee arthroplasty for osteoarthritis among black and white older Americans and to determine whether clinical and economic factors contribute to these differences. Data on black and white Americans aged 65 years and older were gleaned from national Medicare hospitalization records for 1980 through 1988 and the Medicare enrollment file for 1987, the First National Health and Nutrition Examination Survey of 1971 through 1975, the National Hospital Discharge Survey of 1979 through 1988, the 1980 through 1988 US census counts and estimates, and 1980 census economic data. Information gathered includes prevalence of osteoarthritis of the knee among blacks and whites; rate of total knee arthroplasty use in the United States by race, sex, and age of subjects at the time of operations; use of competing procedures; and economic factors. Results showed that blacks were less often treated with total knee arthroplasty than were whites (white-to-black rate ratios = 3.0 to 5.1 for men and 1.5 to 2.0 for women) but had nonsignificantly higher rates of clinical osteoarthritis of the knee (white-to-black rate ratios = 0.39 for men and 0.78 for women). This racial difference in total knee arthroplasty rates was consistent across income levels and was unexplained by black patients' having operations at earlier ages or using competing procedures. Furthermore, the discrepancy occurred even among Medicaid-eligible Medicare recipients, who had no direct economic disincentive for surgery. These findings suggest that even though elderly blacks have higher rates of knee osteoarthritis, they do not receive total knee arthroplasty as often as do elderly whites. This discrepancy does not appear to have an economic explanation. Even if a comprehensive care system were in place to remove economic barriers, inequality in the use of this procedure would likely persist. Future studies should assess the nonclinical and noneconomic causes of these differences.

Black or African American↗
PubMed1993

Effects of different oral oestrogen formulations on insulin-like growth factor-I, growth hormone and growth hormone binding protein in post-menopausal women.

OBJECTIVE: Insulin like growth factor-I (IGF-I) levels in post-menopausal women are reduced by oral administration of the synthetic oestrogen ethinyl oestradiol but increased by transdermal delivery of 17 beta-oestradiol. Since these oestrogen types are different, the aim of this study was to clarify whether reduction in IGF-I is a specific effect of ethinyl oestradiol or common to other oral oestrogen formulations. DESIGN: Randomized cross-over study comparing one month of treatment with ethinyl oestradiol (20 micrograms), conjugated equine oestrogen (1.25 mg Premarin) and oestradiol valerate (2 mg). SUBJECTS: Six healthy post-menopausal women, age 60.3 +/- 5.6 years. MEASUREMENTS: Mean 24 hour GH (from hourly sampling), IGF-I, GH binding protein (GHBP), pituitary (LH, FSH) and hepatic function (SHBG and angiotensinogen) were measured. RESULTS: All three oestrogen formulations resulted in a significant reduction in IGF-I levels compared to baseline and significant elevations of GH and GHBP (P < 0.05). The percentage increase in GH during oestrogen treatment was significantly related to the percentage decrease in IGF-I levels (P = 0.04). All three oestrogen formulations resulted in significant suppression of LH and FSH and induction of the hepatic proteins, SHBG and angiotensinogen (P < 0.05). GHBP increased in parallel with other hepatic proteins. CONCLUSIONS: Reduction in IGF-I levels is an intrinsic effect of oral oestrogen therapy and increased GH levels may occur as a result of reduced feedback inhibition by IGF-I. Since GHBP activity is not changed by transdermal oestrogen, we conclude that the liver is a major source of circulating GHBP and that GHBP is an oestrogen sensitive protein.

Aged↗
PubMed1993

Polyneuropathy associated with monoclonal gammopathy of undetermined significance: further evidence that IgM-MGUS neuropathies are different than IgG-MGUS.

We evaluated the clinical characteristics and electromyographic features of 39 patients with monoclonal gammopathy of undetermined significance (MGUS) and neuropathy. Twenty-three patients had a monoclonal IgM protein, 13 had an IgG, and three had an IgA. In 15 patients of the IgM group, the M protein reacted with myelin-associated glycoprotein (MAG). Comparing IgM-MGUS and IgG-MGUS neuropathies, we found the following differences: (1) There was a statistically significant higher frequency of sensory loss in the IgM group. (2) Nine attributes of nerve conduction abnormality were statistically worse in the IgM group, with slowing of conduction velocities and prolonged distal latencies. (3) The frequency of monoclonal IgM was overrepresented in the MGUS neuropathy group. In general, the clinical and electrophysiologic features of the IgM-MGUS MAG-reactive group were not significantly different than the MAG-nonreactive group. Our cases are similar to those previously reported and suggest that monoclonal IgM-MGUS should be separated conceptually from monoclonal IgG neuropathies.

Adult↗