Patient Characteristics Independently Associated With Knee Osteoarthritis Symptom Severity at Initial Orthopedic Consultation.

BACKGROUND/OBJECTIVE: The objective of this study was to identify patient and disease characteristics associated with the symptomatic severity of knee osteoarthritis (OA) at the time of initial knee OA diagnosis by an orthopedist. METHODS: This medical records review included patients initially diagnosed with knee OA during 2016 to 2017 by a single orthopedic surgeon in a university-based tertiary care setting. All variables were assessed at first OA diagnosis. Main outcomes were subscales of the Knee Injury and Osteoarthritis Outcome Score-Pain, other Symptoms, knee-related quality of life, and function in daily living. Multivariable regression analyses examined the following predictors of main outcomes: sex, race, age, insurance type, body mass index, Charlson comorbidity index, and radiographic OA severity (Kellgren-Lawrence grade). RESULTS: Of the 559 patients included in the study, most were African American (52.1%), female (71.7%), and had severe radiographic OA (Kellgren-Lawrence grade, 4; 68.7%). Female sex, African American racial/ethnic group, Medicaid insurance, younger age, and severe radiographic OA were independently statistically significantly associated with worse symptoms, pain, and function (p < 0.05 for all). Body mass index and Charlson comorbidity index were not statistically significant predictors of any outcome. CONCLUSIONS: This study identified disparities in the perception of knee OA problems at initial orthopedist diagnosis based on sex, age, race, insurance, and radiographic OA severity. Because most of these variables are also associated with more rapid progression of OA, identifying their biopsychosocial underpinnings may help determine which interventions are most likely to redress these disparities and delay progression to end-stage knee OA.

Ovarian hyperstimulation without elevated serum estradiol associated with pure follicle-stimulating hormone-secreting pituitary adenoma.

We report a unique case of a 28-yr-old woman with a gonadotroph adenoma secreting FSH, presented with ovarian hyperstimulation, without elevation of serum estradiol. She presented with abdominal pain and large ovaries (both 10 cm in diameter) with multiple follicular cysts shortly after discontinuing oral contraceptive pills. She had a supranormal PRL level of 71 microg/liter (normal, <20), FSH of 8.4-9.2 IU/liter (normal for follicular phase, 2.4-10), LH of 0.01 IU/liter (normal, 1.6-9.3), estradiol of 108 pmol/liter (normal for follicular phase, 80-790), and free alpha-subunit level of 0.11 microg/liter (normal, <1.8). A nuclear magnetic resonance study revealed invasive pituitary macroadenoma, 30 mm in diameter. Dopamine agonist (cabergoline) treatment normalized serum PRL but had no affect on FSH levels. A transsphenoidal surgery was performed, and most of the adenoma was resected. One month after surgery the patient resumed menstruation, and the hormonal profile included serum FSH of 6.3 IU/liter, LH of 2.1 IU/liter, estradiol of 156 pmol/liter, and PRL of 10 microg/liter. The excised adenoma tissue exhibited intense immunostaining for FSH and secreted this hormone to culture medium. Stimulation with TRH (both in vivo preoperatively and in vitro study of the excised tumor) had no effect on FSH secretion from the adenoma. Estradiol did not suppress FSH release from cultured adenoma cells. Patient serum samples showed significant FSH bioactivity when tested in a human granulosa cell line. This case is remarkable because the ovarian hyperstimulation related to the FSH-secreting adenoma was not associated with high levels of serum estradiol, probably due to insufficient LH production by the normal pituitary. Thus, it supports the two-cell, two-gonadotropin theory, that both FSH and LH are necessary for normal ovarian estrogen production.

Treatment of calcinosis in juvenile dermatomyositis with probenecid: the role of phosphorus metabolism in the development of calcifications.

OBJECTIVE: To report the efficacy of probenecid for calcinosis of juvenile dermatomyositis (JDM) and assess the changes in phosphorus metabolism during treatment. METHODS: Biochemical studies of calcium and phosphorus metabolism were performed in a 9-year-old girl with JDM and extensive calcifications before and during probenecid treatment. RESULTS: The calcifications resolved over 18 months of treatment. Probenecid was found to be effective in reducing calcifications by increasing renal phosphate clearance. CONCLUSIONS: The tendency for calcifications in some patients with JDM might be related to an increase in renal phosphate reclamation, and therefore, probenecid treatment may be effective in these patients.

Geographic variation in groundwater iodine and iodine deficiency in Israel, The West Bank and Gaza.

BACKGROUND: Iodine deficiency during pregnancy and infancy is the world's most common preventable cause of mental retardation. Previous studies have shown a high incidence of goiter and low groundwater iodine concentrations in northern Israel. OBJECTIVE: We examined the relationship between low groundwater iodine and iodine deficiency in pregnant women and schoolchildren. SUBJECTS AND METHODS: We measured the urinary iodine excretion of school-children in the West Bank and Gaza and rural and urban pregnant women in Western Galilee (an area known to have low groundwater iodine concentrations). We also measured iodine concentrations in groundwater in various locations in the West Bank and Gaza. RESULTS: Lower urinary iodine excretion was found among pregnant Arab women living in rural Western Galilee (101+/-7 microg iodine/g creatinine). 20% of them excreted <50 microg I/g creatinine. This is relatively less than found among pregnant Jewish women living in cities in the same area (154+/-13 microg I/g creatinine). Low iodine concentrations (<5 microg/l) were found in groundwater in the Nablus, Ramallah, Bethlehem highlands, as compared to normal concentrations in the lowland districts of the West Bank and Gaza. In a cohort of 728 schoolchildren aged 8-10, 10% (range 8-13%) of children from areas of low groundwater iodine had low levels of urinary iodine excretion, as compared to only <5% of those from districts with groundwater iodine concentrations >10 microg/l. CONCLUSIONS: Lower concentrations of groundwater iodine are related to low urinary iodine excretion in Israel, the West Bank and Gaza.

Control of non-Markovian decay and decoherence by measurements and interference.

Novel methods are discussed for the state control of atoms coupled to multi-mode reservoirs with non-Markovian spectra: 1) Excitation decay control : we point out that the quantum Zeno effect, i.e., inhibition of spontaneous decay by frequent measurements, is observable in open cavities and waveguides using a sequence of evolution- interrupting pulses or randomly-modulated CW fields. 2) Location-dependent interference of decay channels - nonadiabatic (resonant) control : We show that the control of populations and coherences of two metastable states is feasible via resonant single-photon absorption to an intermediate state, by controlled spontaneous emission in a cavity. 3) Decoherence control by conditionally interfering parallel evolutions: We demonstrate that an arbitrary internal atomic state can be completely protected from decoherence by interference of its interactions with the reservoir over many different time interals in parallel . Such interference is conditional upon the detection of appropriate atomic-momentum observables. Realization in cavities is suggested. The rich arsenal of control methods described above can improve the performance of single-atom devices. It can also advance the state-of-the-art of quantum information encoding and processing.

Chemosensitivity testing of human tumors using a microplate adenosine triphosphate luminescence assay: clinical correlation for cisplatin resistance of ovarian carcinoma.

An ATP luminescence assay (TCA 100) was used to measure chemotherapeutic drug sensitivity and resistance of dissociated tumor cells cultured for 6 days in serum-free medium and 96-well polypropylene microplates. Studies were performed with surgical, needle biopsy, pleural, or ascitic fluid specimens using 10,000-20,000 cells/well. ATP measurements were used to determine tumor growth inhibition. Single agent and drug combinations were evaluated using the area under the curve and 50% inhibitory concentration (IC50) results for a series of test drug concentrations. The ATP luminometry method had high sensitivity, linearity, and precision for measuring the activity of single agents and drug combinations. Assay reproducibility was high with intraassay and interassay coefficients of variation of 10-15% for percentage of tumor growth inhibition, 5-10% for area under curve, and 15-20% for IC50 results. Good correlation (r = 0.93) between the area under the curve, and IC50 results was observed. Cytological studies with 124 specimens demonstrated selective growth of malignant cells in the serum-free culture system. Studies with malignant and benign specimens also showed selective growth of malignant cells in the serum-free medium used for assay. The assay had a success rate of 87% based on criteria for specimen histopathology, magnitude of cell growth, and dose-response drug activity. Cisplatin results for ovarian carcinoma are presented for 81 specimens from 70 untreated patients and 33 specimens from 30 refractory patients. A model for interpretation of these results based on the correlation of clinical response with the area under the curve and IC50 results indicates that the assay has > 90% accuracy for cisplatin resistance of ovarian carcinoma. Additional studies are in progress to evaluate the clinical efficacy of this assay.

Prolonged effects of tumor necrosis factor-alpha on anterior pituitary hormone release.

We examined the chronic (72 h) effects of 30 ng/ml recombinant murine tumor necrosis factor (TNF)-alpha on release of immunoreactive growth hormone (GH), prolactin (PRL), thyrotropin (TSH), and TSH glycosylation, as assessed by lectin binding, in cultured rat anterior pituitary cells. In cultured cells from adult female rats, TNF-alpha significantly suppressed basal and GH-releasing hormone (GRH)-stimulated GH release. TNF-alpha also suppressed basal PRL release and completely abolished the PRL response to TRH (0.1-10 nM). Whereas TNF-alpha reduced basal TSH release, it significantly enhanced the maximal TSH response to TRH. TNF-alpha did not affect the concanavalin A and lentil lectin binding of TSH accumulated in the medium during the 4-day culture, but significantly decreased the lentil lectin binding of TSH released in response to acute TRH stimulation. TNF-alpha significantly enhanced the inhibitory effect of somatostatin on stimulated PRL release, but not on GH or TSH release. Compared to cell cultures from adult female rats, in anterior pituitary cell cultures from 12-day-old rats the effects of prolonged exposure to TNF-alpha on hormone release were diminished or absent. Pituitary hormone release was unaffected by acute (3 h) exposure to TNF-alpha. These results demonstrate a direct effect of TNF-alpha on anterior pituitary hormone release, which is cell-type specific and age dependent.

Low-molecular-weight iodoproteins in the congenital goiters of cog/cog mice.

Previously we described sedimentation and immunologic abnormalities of thyroglobulin (Tg) in a strain of mice with inherited congenital goiter and hypothyroidism (cog/cog). The goals of the present study were to determine the extent to which thyroid gland stimulation by TSH accounts for the abnormal properties of cog/cog Tg and to characterize further the abnormally small iodoproteins found in cog/cog mice. Cog/cog and control +/cog and BALB/c mice were fed with either normal or thyroid-hormone-containing diets and were injected with Na125I. Sucrose density gradient centrifugation of labeled thyroid extracts from cog/cog mice on normal diet showed that 82% of the iodine was in iodoproteins smaller than Tg, with sedimentation rates of 3-8S. No 12S and 19S peaks, characteristic of normal Tg, were present, but distinct and stable 12S and 19S peaks emerged after recentrifugation of the 12S and 19S areas. In contrast, in cog/cog mice treated with T4, a smaller (55%) amount of 3-8S iodoproteins and distinct 12S and 19S peaks were present. In both groups of mice, the labeled 3-8S iodoproteins were composed of three fractions: 15% precipitated by antirat Tg serum, 38% precipitated by antimouse albumin serum, and 47% not precipitated by either serum. The 3-8S iodoproteins contained labeled MIT and DIT and no T4. On sodium dodecyl sulfate polyacrylamide gel electrophoresis the 3-8S iodoprotein fraction that reacted with anti-Tg serum contained a distinct electrophoretic band at 49K. The 3-8S nonreactive iodoproteins resolved into several bands of lower molecular weight. We conclude that the 3-8S iodoproteins in cog/cog mice are heterogeneous and that TSH stimulation contributes to the production of these low-molecular-weight iodoproteins.

EO-199, a specific antagonist of antiarrhythmic drugs: assessment by binding experiments and in vivo studies.

EO-199, a demethylated analog of the novel class I antiarrhythmic drug EO-122 was found to antagonize the antiarrhythmic activity of EO-122 and that of procainamide (Class IA). EO-199 did not block significantly the activity of a class IB antiarrhythmic agent, lidocaine. EO-199 also displaced the specific binding of [3H]EO-122 to rat heart membranes similarly to procainamide whereas lidocaine did not. The correlation between binding experiments and pharmacological effects points to a possible subclassification of these drugs; the two chemical analogs EO-199 and EO-122, as well as procainamide (IA) but not lidocaine (IB), compete at the same site or the same state of the sodium channel. The availability of a specific antagonist might be useful for studying the mechanism of action of antiarrhythmic drugs as well as an antidote in cases of antiarrhythmics overdose intoxication.

Distributions of total cholesterol, triglycerides, and high-density lipoprotein cholesterol in Israeli Jewish children of different geographic-ethnic origins, ages 9-17 years.

To determine age and ethnic patterns of blood lipid levels in childhood and adolescence and to extend previous adult and late adolescent Israeli data to prepubertal ages, the levels of plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were determined among 1,153 schoolchildren in the area of Petah-Tikva. Half of the children were born to immigrants from Yemen. Among boys, TC levels progressively decreased as age increased from 10-11 to 14-15 years (159 to 142 mg/dl). The age-specific TC and HDL-C means among boys are compatible with an initial swift fall with age, followed by a rise restricted to TC during puberty. Among girls, progressively lower means through ages 12-13 and increasingly higher ones for older age groups are also compatible with puberty-determined changes, previously observed in American cohorts. The differences in TC were only partly accounted for by lower HDL-C means at higher ages (52 mg/dl in the youngest and 45 mg/dl in the oldest age group, respectively, among boys, compared with 53 mg/dl for girls at both ages 9 and 16-17). TG levels in boys, but not in girls, showed age differences paralleling those found for HDL-C, but in an inverse direction. TC means were lower as age increased only among female offspring of European-born Jews (159 to 148 mg/dl, ages 9-12 compared with ages 13-17), a phenomenon that requires further study. Overall, TC and HDL-C were clearly higher among girls than boys beginning at ages 12-13, with little or no sex differences in TG. The sex differences in TC, contrary to previous studies, were not fully accounted for by HDL-C sex differences. The ethnic variability paralleled previous findings in Israeli adults and adolescents, showing low TC levels among male offspring of Yemenite and other Asian-born fathers. The ethnic differences among girls were small. No specific pattern of age-related lipid changes was found in the group of Yemenite origin, who represented offspring of parents with notoriously low levels of coronary heart disease incidence.

Hypercalcemia associated with transitional cell carcinoma without bone metastases: description of two cases.

Two cases of hypercalcemia associated with transitional cell carcinoma and negative bone scan are described. In both cases hypercalcemia appeared while there was evidence of tumor spread. Although hypercalcemia was controlled, both patients died shortly thereafter. Hypercalcemia rarely occurs in transitional cell carcinoma and its appearance may suggest spreading of the tumor and poor prognosis.