Validation of an algorithm to identify incident interstitial lung disease in patients with rheumatoid arthritis.

BACKGROUND/PURPOSE: Interstitial lung disease (ILD) is an important problem for patients with rheumatoid arthritis (RA). However, current approaches to ILD case finding in real-world data have been evaluated only in limited settings and identify only prevalent ILD and not new-onset disease. Our objective was to develop, refine, and validate a claims-based algorithm to identify both prevalent and incident ILD in RA patients compared to the gold standard of medical record review. METHODS: We used administrative claims data 2006-2015 from Medicare to derive a cohort of RA patients. We then identified suspected ILD using variations of ILD algorithms to classify both prevalent and incident ILD based on features of the data that included hospitalization vs. outpatient setting, physician specialty, pulmonary-related diagnosis codes, and exclusions for potentially mimicking pulmonary conditions. Positive predictive values (PPV) of several ILD algorithm variants for both prevalent and incident ILD were evaluated. RESULTS: We identified 234 linkable RA patients with sufficient data to evaluate for ILD. Overall, 108 (46.2%) of suspected cases were confirmed as ILD. Most cases (64%) were diagnosed in the outpatient setting. The best performing algorithm for prevalent ILD had a PPV of 77% (95% CI 67-84%) and for incident ILD was 96% (95% CI 85-100%). CONCLUSION: Case finding in administrative data for both prevalent and incident interstitial lung disease in RA patients is feasible and has reasonable accuracy to support population-based research and real-world evidence generation.

Post-traumatic stress disorder and serum cytokine and chemokine concentrations in patients with rheumatoid arthritis✰.

OBJECTIVE: Although post-traumatic stress disorder (PTSD) is identified as a risk factor in the development of rheumatoid arthritis (RA), associations of PTSD with disease progression are less clear. To explore whether PTSD might influence disease-related measures of systemic inflammation in RA, we compared serum cytokine/chemokine (cytokine) concentrations in RA patients with and without PTSD. METHODS: Participants were U.S. Veterans with RA and were categorized as having PTSD, other forms of depression/anxiety, or neither based on administrative diagnostic codes. Multiplex cytokines were measured using banked serum. Associations of PTSD with cytokine parameters (including a weighted cytokine score) were assessed using multivariable regression, stratified by anti-CCP status and adjusted for age, sex, race, and smoking status. RESULTS: Among 1,460 RA subjects with mean (SD) age of 64 (11) years and disease duration of 11 (11) years, 91% were male, 77% anti-CCP positive, and 80% ever smokers. Of these, 11.6% had PTSD, 23.7% other depression/anxiety, and 64.7% had neither. PTSD, but not depression/anxiety, was associated with a higher cytokine score and number of high-concentration analytes in adjusted models, though this was limited to anti-CCP positive subjects. PTSD was associated with heightened expression of several individual cytokines including IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12, IL-17, IFN-γ, GM-CSF, MCP-1, and TNF-α. CONCLUSION: Anti-CCP positive RA patients with PTSD have higher serum cytokine concentrations than those without PTSD, demonstrating that systemic inflammation characteristic of RA is heightened in the context of this relatively common psychiatric comorbidity.

Student outbreak response teams: lessons learned from a decade of collaboration.

OBJECTIVES: Student response teams within colleges of public health effectively address important concerns for two stakeholders. For universities, students learn the fundamentals of field epidemiology and provide popular training and networking opportunities. For health departments, students serve as surge capacity as trained workforce available during outbreak investigations and potentially for routine tasks. STUDY DESIGN: This paper describes the interaction between a student response team and several health departments utilizing specific examples to demonstrate the various roles and activities students can fulfill. Lessons learned from both University team leaders and the various health departments are also included. METHODS: The program evolved over time, beginning with a needs assessment of local health departments and a determination of student training needs, collection, and confidential transmission of data, and interviewing techniques. Over the last decade students have worked on outbreak investigations, case-control studies, program evaluations, and in-field responses. RESULTS: Since 2005, over 200 public health graduate students have contributed more than 1800 h investigating 62 separate disease outbreaks in Arizona. In addition, over the past four years students also worked an additional 2500 h to assist county health departments in routine enteric investigations, specifically for Campylobacter and Salmonella. Best practices and lessons learned found that communication, preplanning and a willingness to collaborate increased the learning opportunities for students and ability for health departments to increase their capacity both during an emergency and for routine work. CONCLUSIONS: Establishment of a student response team (1) trains students in field experiences; (2) creates trained surge capacity for health departments; (3) increases collaboration between schools of public health and state/local health departments; (4) establishes a way to share funding with a local health department; and (5) increases the number of students being placed in health departments for projects, internships, and jobs following graduation.

Reticence to prescribe: utilization of expedited partner therapy among obstetrics providers in Arizona.

Expedited partner therapy (EPT) is the practice of providing an extra dose or prescription of antibiotic to patients diagnosed with chlamydia or gonorrhoea to deliver to their sexual partner(s). Obstetrical providers who delivered more than 20 infants in Maricopa County, Arizona, USA, during the year 2008 were surveyed by telephone regarding their use of EPT. A total of 142 eligible respondents completed the survey, representing 34% (142/421) of the delivering providers, 67 (47%) of whom reported the use of EPT in their clinics. Having received information about EPT was significantly associated with its use (67% versus 41%) (P = 0.008). The most common reasons for not using EPT included the inability to obtain allergy history in partners (24%) and concern for liability (11%). Additional education regarding the use of EPT may increase the use of this personal and public health tool among some obstetrics providers in Maricopa County; however, concerns for liability may limit broad utilization.

Intraoperative parathyroid hormone monitoring fails to detect double parathyroid adenomas: a 2-institution experience.

BACKGROUND: We hypothesized that intraoperative parathyroid hormone monitoring (IOPTH) reliably would detect double parathyroid adenomas. METHODS: This was a retrospective study of 20 patients undergoing conventional parathyroidectomy with resection of exactly 2 abnormal glands. Full exploration was performed regardless of IOPTH values, which were measured after anesthetic induction and 5 and 10 minutes following removal of the first abnormal parathyroid gland. Failure to fall below 50% of baseline value by 10 minutes following resection of the first gland indicated the presence of multiglandular disease. RESULTS: All patients were cured. All excised glands were hypercellular on histology. Mean IOPTH values in 9 of the 20 patients with true negative results (noncurative decrease, another gland present) were 66% +/- 7% at 5 minutes and 83% +/- 15% at 10 minutes. The IOPTH values in 11 of the 20 patients with false positive results (curative decrease, another gland present) were 28% +/- 4% at 5 minutes and 18% +/- 2% at 10 minutes. The false positive rate of IOPTH was 55%. CONCLUSIONS: We found that IOPTH failed to reliably detect the presence of double parathyroid adenomas. These data suggest that caution should be exercised when terminating limited parathyroid exploration based on a curative fall in IOPTH values.

The role of child care in a community-wide outbreak of hepatitis A.

OBJECTIVE: To evaluate the role of child care centers in a community-wide hepatitis A epidemic. METHODS: We analyzed surveillance data during an epidemic in Maricopa County, Arizona, from January to October 1997 and conducted a case-control study using a sample of cases reported from June to November. Cases were physician-diagnosed and laboratory confirmed; control subjects were frequency matched by age and neighborhood. Information regarding hepatitis A risk factors, including child care-related exposures, was collected. Characteristics of all licensed child care centers in the county were obtained through review of computerized lists from the Arizona Office of Child Day Care Licensing. Surveillance data were linked to the child care list to determine which centers had reported hepatitis A cases. We conducted univariate and multivariate conditional logistic analyses and calculated population attributable risks (PAR). RESULTS: In total, 1242 cases (50/100 000 population) were reported. The highest rates occurred among people aged 0 to 4 (76/100 000), 5 to 14 (95/100 000), and 15 to 29 (79/100 000) years. The most frequently reported risk factor was contact with a hepatitis A patient (45%). However, nearly 80% of these contacts were with individuals who attended or worked in a child care center. Overall, child care center-related contact could have been the source of infection for 34% of case-patients. In the case-control study, case-patients (n = 116) and control subjects (n = 116) did not differ with respect to demographic characteristics. A total of 51% of case-patients compared with 18% of control subjects reported attending or working in a child care setting (direct contact; adjusted odds ratio [OR]: 6.0; 95% confidence interval [CI]: 2.1-23.0) or being a household contact of such a person (indirect contact; OR: 3.0; 95% CI: 1.3-8.0). In age-stratified analyses, the association between hepatitis A and direct or indirect contact with child care settings was strongest for children <6 years old and adults aged 18 to 34 years. Household contact with a person with hepatitis A also was associated with hepatitis A (OR: 9.2; 95% CI: 2.6-58.2). The presence of a child <5 years old in the household was not associated with hepatitis A. The estimated PAR for direct child care contact was 23% (95% CI: 16-34), for indirect child care contact was 21% (95% CI: 13-35), and for any child care contact was 40% (95% CI: 30-53). Information on 1243 licensed child care centers was obtained, with capacity ranging from 5 to 479 slots (mean: 87). Thirty-four (2.7%) centers reported hepatitis A cases. Centers that had a mean capacity of >50 children were more than twice as likely to have had a reported case of hepatitis A (OR: 2.6; 95% CI: 1.1-6.7). Among the 747 centers that accepted >50 children, having infant (OR: 3.7; 95% CI: 1.6-8.3), toddler (OR: 6.3; 95% CI: 2.2-20.0), or full-day service (OR; undefined; 95% CI: 1.7- ~) was associated with having a reported case of hepatitis A. CONCLUSIONS: In Maricopa County, people associated with child care settings are at increased risk of hepatitis A, and child care attendees may be an appropriate target group for hepatitis A vaccination. Considering the estimated proportion of children who attended child care and were old enough to receive hepatitis A vaccine (>/=2 years of age) and the calculated PAR, approximately 40% of cases might have been prevented if child care center attendees and staff had been vaccinated. However, epidemiologic studies indicate that the proportion of cases that are attributable to child care center exposure varies considerably among counties, suggesting that this exposure may be associated with an increased risk of hepatitis A in some communities but not in others. To prevent and control hepatitis A epidemics in communities, the Advisory Committee on Immunization Practices and the American Academy of Pediatrics have adopted a long-term strategy of routine vaccination of children who live in areas with consistently elevated hepatitis A rates. After demonstrating cost-effectiveness, a rule was implemented in January 1999 to require hepatitis A vaccination of all children who are aged 2 to 5 years and enrolled in a licensed child care facility in Maricopa County. Other communities with similar epidemiologic features might consider routine vaccination of child care center attendees as a long-term hepatitis A prevention strategy. Consistent with current recommendations, in communities with persistently elevated hepatitis A rates where child care center attendance does not play an important role in hepatitis A virus transmission in the community, child care centers may nonetheless provide a convenient access point for delivering hepatitis A as well as other routine childhood vaccinations.

Modified peptide antagonists of interleukin 5 exhibit extended in vivo persistence but restricted species specificity.

AF18748 is disulphide-linked homodimeric peptide with 19 amino acids in each chain that antagonises the action of the eosinophil-specific cytokine, interleukin 5 (IL-5). We have generated a set of N-terminally truncated peptides derived from AF18748 and demonstrated that the first five amino acids of the peptide do not contribute to receptor binding activity. The shortened peptide blocked IL-5-dependent adhesion of eosinophils with an IC(50)of 350 pM, and had no effect on stimulation by IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF)-alpha or fMet-Leu-Phe. The peptides were rapidly broken down in mouse plasma through cleavage of a single chain of the dimer. However, this breakdown did not correlate with loss of biological activity, indicating that the asymmetric peptide fragment retains full receptor binding capacity. The activity of AF18748 disappeared rapidly from the blood following intravenous injection into mice. Coupling of polyethylene glycol to the N-terminus of AF18748 resulted in a moderate loss in biological potency (IC(50)30 nM), but the resulting conjugate persisted in the circulation for more than 8 h after injection. Despite its high potency at the human IL-5 receptor, AF18748 was unable to antagonise the activity of IL-5 on murine B13 cells, or on canine eosinophils, indicating that the peptide is highly specific for the human IL-5 receptor.

Morphometric analysis of the adrenal compartments exposed to sustained delivery of androgens.

The role of reproductive and adrenal steroid hormones on the structural and functional capacity of adrenal tissue has not been well investigated. The objective of this investigation was to morphometrically evaluate the effect of testosterone (T), dihydrotestosterone (DHT), and androstenedione (AED) given in a sustained manner, by tricalcium phosphate lysine (TCPL) ceramic capsules, on the adrenals of adult male rats. Sixteen adult male rats were randomly divided into four equal groups. Groups II, III, and I were implanted with TCPL capsules loaded with AED, T, and DHT, respectively. Group IV animals were not implanted, and thus served as the control group. At the end of ninety days post-implantation, the animals were euthanized using standard aseptic surgical techniques. The adrenal glands were harvested and stored in 10% formalin. The tissues were processed, embedded, sectioned and stained with H & E using standard laboratory procedure. Random sections of control and experimental tissues were utilized for morphometric analysis by using Image Pro digital analysis techniques. Data collected were analyzed by means of ANOVA (p < 0.05). Results of this study revealed. (1) There was an increase in the total areas of T treated animals in comparison to the control and other experimental groups, (2) the total lengths of each hormonally treated tissue showed an increase in size of DHT treated tissue verses control, but differences of T and AED compared with control remained insignificant, (3) upon analysis of the zona glomerulosa (Z1) and zona fasciculata (Z2) the data demonstrated a significant increase in animals treated with DHT and AED in comparison to control and T treated animals, (4) finally, statistical analysis performed on measurements of the zona reticularies (Z3) indicated notable increases only in the AED exposed animals. The changes in size of the various tissues may be warranted due to reactions of the steroid hormones with different surface receptors in different layers. However, further investigations are needed, especially longer duration of treatment, to fully hypothesize the exact mechanisms of these hormones on the adrenal glands.

Biocompatibility of steroid-HA delivery system using adult castrated rams as a model.

The objective of this study was to analyze the fibrous tissue surrounding dihydrotestosterone (DHT loaded HA devices implanted subcutaneously (S/C) in adult castrated rams. The microcrystals of HA were prepared by following standard laboratory procedure. Housing, surgical implantation and bleeding procedure of all rams used in this study was conducted according to the NIH guideline and approval of UCUCA. A total of 11 rams were castrated by elastrator rings within a week after birth. At 7 months of age the animals were randomly divided into three groups. Group 1 rams (n = 4) were not treated and served as the control group. Rams in group 2 (n = 3) were implanted s.c. with two HA capsules (80 mg DHT/capsule). Each ram (n = 3) in group 3 was implanted with two empty HA capsules and served as a sham group. All animals were housed together throughout this study and water, high quality hay and grain were given ad libitum. The sterilized ceramics were inserted S/C through a single incision using standard aseptic surgical techniques. Gross, radiographic and histological examinations of the site of implantation did not show any untoward reactions during the entire investigation. Histopathological evaluation have revealed that all HA implants were encapsulated with hyaline fibrous tissue at the end of two weeks, and the degree of encapsulation increased with time. Results collected from this investigation showed that the passage of DHT through HA capsules started within 3 days after implantation. Furthermore, sustained delivery of DHT by means of HA devices at levels ranging between 1.4-3.3 ng/ml imposed continuous negative feedback on post-castration rise in serum LH and FSH secretion. Representative retrieved implants showed slight degradation of the implant (27% +/- 38) and increased erosion at the sharp edges with time was observed. Light and electron microscopic evaluation demonstrated that at the end of four weeks postimplantation, a well developed granulation tissue is seen surrounding the implants. The thin developing fibrous capsule infiltrated with macrophages and numerous small and large capillaries were observed. A well-developed fibrous capsule formed at 6 months postimplantation. Four different layers were observed: (i) the HA tissue layer contains macrophages, some mononuclear leukocytes, and fibroblasts indicative of the chronic inflammatory responses, (ii) the fibrous capsule layer is composed of longitudinally oriented fibroblasts and mature collagen fibers, (iii) the vascularization layer contains numerous large and small capillaries, and (iii) the outer side of the fibrous capsule predominately composed of adipose tissue. Data obtained from this study suggest that lack of vascularization at the immediate HA tissue layer and the fibrous capsule layer may function to retard the rapid release of DHT from the HA implants. This retardation of DHT release from HA implants by the formation of fibrous capsule is needed to compensate for the macropores formed during the biodegradation of the implants.

TCPL drug delivery system: the effects of synthetic DHEA and Diosgenin using an ovariectomized rat model.

Dehydroepiandrosterone (DHEA) has been shown in numerous studies to exhibit a host of benefits at the vital and reproductive organ levels. However, the use of naturally occurring DHEA is hindered by its inability to survive the first-pass metabolic process of the liver. One possible alternative means that deserves consideration is the administration of DHEA's precursor, namely, Diosgenin (DG). The specific objectives of this investigation were: 1) to deliver DHEA and DG at sustained levels by Tri-Calcium Phosphate Lysine (TCPL) drug delivery systems using ovariectomized (OVX) adult rats as a model, and 2) to evaluate the biochemical and histopathological changes associated with the sustained delivery of DHEA and DG. A total of 30 adult female rats were used in this investigation. The animals were further divided into 8 groups. Groups 1 and 2 animals served as intact control groups while each rat in groups 3-8 was ovariectomized (sham (33), n = 3 [group 3], sham (47), n = 4 [group 4]). Groups 5 and 6 were implanted with DHEA (group 5) and DG (group 6) loaded TCPL capsules immediately following the OVX procedure. Groups 7 and 8 were implanted with DHEA (group 7) and DG (group 8) loaded capsules 14 days following OVX. Surgical aseptic technique was employed according to standard laboratory protocols. Maliondialdehyde (MDA) and hormonal levels were measured from serum, collected semi-weekly, during the entire investigation (for 47 days) and X-rays were performed weekly. Pap smears were collected daily for 47 days to assess endometrial changes associated with DHEA and DG treatment. Following sacrifice (at day 33 for groups 1, 3, 5, and 6 and at day 47 for groups 2, 4, 7, and 8), routine H and E staining was conducted for histopathological evaluation of the reproductive and vital organs. Results of this investigation demonstrated: 1) OVX resulted in an increase in total body weight, and the use of DHEA and DG returned the body weight to near normal levels as compared to the intact control groups, 2) TCPL capsules delivered DHEA and DG at a sustained level during the 47 day study, 3) serum levels of MDA are as follows: DG > DHEA = OVX > control for the 33 day phase and OVX > DG > DHEA > control for the 47 day phase, 4) no significant changes were observed in total wet weights, as well as the morphology of the spleen, kidney, adrenal, heart, liver, and lung tissues, 5) OVX resulted in an atrophy and non-keratinization trend in the reproductive tissues, and sustained delivery of DHEA and DG showed no remarkable change in these tissues, 6) the use of sustained delivery of DHEA and DG resulted in higher weights of uteri compared to the OVX group. In conclusion, this study provided more information regarding the interrelationship between DHEA and DG, and the physiological responses encountered when they are administered continuously using the adult OVX rat as a model.

Assessment of endometrial function during sustained delivery of estradiol and estradiol plus progesterone in ovariectomized rats.

Previous studies conducted in our laboratories have documented that tricalcium phosphate lysine (TCPL) delivery system can be utilized to deliver estrogen (E) and combination of estrogen with progesterone (E + P) at sustained levels for long duration in intact rats. The specific aim of this investigation was to attempt to reverse the endometrial changes resulted from post-ovariectomy by exogenously delivering sustained levels of E and E + P. A total of 27 adult female rats were used in this study. The animals were randomly divided into seven different groups: groups 1 animals served as intact control group, groups 2 and 6 animals were ovariectomized, 3 and 7 were ovariectomized (OVX) and implanted with TCPL loaded with E (20 mg loaded TCPL), and group 4 was OVX and implanted with E (TCPL, 20 mg) + P (TCPL, 40 mg.) treatment. Group 5 animals served, as intact control group. Blood samples were collected biweekly for 47 days. Vaginal smears were taken and screened daily during the entire investigation. Histopathological evaluations were conducted on reproductive as well as vital organs (H & E). Data obtained from this investigation suggest the following: (I) OVX resulted in an increase in total body weight, however E and E + P maintained the body weights at prior ovariectomy level, (II) sustained delivery of E resulted in maturation of vaginal epithelium and the smears exhibited the estrus at the end of 72 hours post implantation and continued this trend for the duration of the study, (III) E + P treatment induced no estrus and the epithelial changes resembled the OVX group, and (IV) E and E + P treatment resulted in a significant different (P < 0.05) in MDA levels compared to OVX and intact control groups. Results of this investigation conclude that sustained delivery of E and E + P by TCPL can be utilized to maintain the normal function of the reproductive organs and could serve as an efficient and safe therapy in estrogen deficient patients.

A potent dimeric peptide antagonist of interleukin-5 that binds two interleukin-5 receptor alpha chains.

Two series of peptides that specifically bind to the extracellular domain of the alpha chain of the human interleukin-5 receptor (IL-5Ralpha), but share no primary sequence homology to IL-5, were identified from libraries of random recombinant peptides. Affinity maturation procedures generated a 19-aa peptide that binds to the IL-5 receptor alpha/beta heterodimer complex with an affinity equal to that of IL-5 and is a potent and specific antagonist of IL-5 activity in a human eosinophil adhesion assay. The active form of the peptide is a disulfide-crosslinked dimer that forms spontaneously in solution. Gel filtration analysis, receptor-binding studies, and analytical ultracentrifugation reveal that the dimeric peptide binds simultaneously to two receptor alpha chains in solution. Furthermore, the dimer peptide, but not IL-5, can activate a chimeric receptor consisting of the IL-5Ralpha extracellular domain fused to the intracellular domain of the epidermal growth factor receptor, thus demonstrating that the peptide also promotes receptor dimerization in a cellular context. The functional antagonism produced by the bivalent interaction of the dimeric peptide with two IL-5R alpha chains represents a distinctive mechanism for the antagonism of cytokines that use heteromeric receptors.

Coccidioidomycosis in human immunodeficiency virus-infected persons in Arizona, 1994-1997: incidence, risk factors, and prevention.

From 1 January 1995 through 31 June 1997, 153 cases of coccidioidomycosis in human immunodeficiency virus (HIV)-infected persons were identified in Arizona (incidence, 41/1000 persons living with AIDS). A case-control study was conducted to evaluate risk factors for coccidioidomycosis in HIV-infected persons. A case was defined as laboratory-confirmed, incident coccidioidomycosis in a person infected with HIV for > or =3 months, and each case patient had 3 control patients matched by county, age group, sex, HIV/AIDS status, and CD4 lymphocyte count. Multivariable analysis identified black race and a history of oropharyngeal or esophageal candidiasis to be associated with increased risk of coccidioidomycosis; protease inhibitor therapy was associated with a reduced risk. In persons with previous history of oropharyngeal or esophageal candidiasis, having received an azole drug was associated with a reduced risk (odds ratio, 0.4; 95% confidence interval, 0.2-0.9; P=.04). Physicians may need to consider azole chemoprophylaxis for HIV-infected persons who live in areas of endemicity, have CD4 cell counts <200/microL, are black, or have a history of thrush.

Risk factors for acute symptomatic coccidioidomycosis among elderly persons in Arizona, 1996-1997.

Because of the increase in incidence of coccidioidomycosis among the elderly in Arizona between 1990 and 1996, a case-control study was conducted to look at risk factors for disease among these persons. Cases (n=89) were persons aged > or =60 years with laboratory-confirmed coccidioidomycosis; 2 control groups were selected, the first by use of random-digit dialing (geographic controls, n=91) and the second by use of lists of persons with negative serologic coccidioidomycosis tests (laboratory-negative controls, n=58). Elderly persons with coccidioidomycosis had spent significantly less time in Arizona than did persons in either control group and were more likely than geographic controls to have congestive heart failure or cancer, to have smoked, or to have taken corticosteroids. Elderly persons who recently have moved to Arizona or who have chronic illnesses and their physicians need to be aware of their higher risk for coccidioidomycosis in order to improve their chances of early diagnosis and treatment. These persons may benefit from vaccination, once an effective vaccine for coccidioidomycosis is developed.

Serum thyroglobulin levels after thyroxine withdrawal in patients with low risk papillary thyroid carcinoma.

We hypothesized that elevated levels of serum thyroglobulin (Tg) are frequently found as the only index of residual neoplasm in patients with low-risk papillary thyroid carcinoma. The records of patients operated on for papillary thyroid carcinoma over a 2-year period were reviewed, and the patients were allocated to risk groups by a validated staging method that does not include Tg levels. Of the 35 patients who manifested a low-risk carcinoma, 9 (26%) exhibited elevated Tg concentrations (11-53 ng/mL) during thyroxine withdrawal after therapies, while clinical, scintigraphic, and radiographic studies at least 1 year later showed no evidence of tumor. Prior scintigraphic imaging of therapeutic doses of 131I in 8 of 9 patients demonstrated no distant metastases, further confirming the low-risk status of this group. The staging method predicts that only 0.9% of patients with low-risk papillary carcinoma will have a cause specific death in 20 years. Elevated Tg concentrations have not been shown to forecast independently the survival of patients with low-risk papillary carcinoma. Thus, although frequently encountered, elevated Tg concentrations are unlikely to predict shortened survival in patients with papillary carcinoma for whom low risk has been determined from other data.

Abscesses due to mycobacterium abscessus linked to injection of unapproved alternative medication.

An unlicensed injectable medicine sold as adrenal cortex extract (ACE*) and distributed in the alternative medicine community led to the largest outbreak of Mycobacterium abscessus infections reported in the United States. Records from the implicated distributor from January 1, 1995, to August 18, 1996, were used to identify purchasers; purchasers and public health alerts were used to identify patients. Purchasers and patients were interviewed, and available medical records were reviewed. Vials of ACE* were tested for mycobacterial contamination, and the product was recalled by the U.S. Food and Drug Administration. ACE* had been distributed to 148 purchasers in 30 states; 87 persons with postinjection abscesses attributable to the product were identified. Patient and vial cultures contained M. abscessus identical by enzymatic and molecular typing methods. Unusual infectious agents and alternative health practices should be considered in the diagnosis of infections that do not respond to routine treatment.

Is pregnancy in diabetic women associated with folate deficiency?

OBJECTIVE: To determine whether folate metabolism in pregnant diabetic women is significantly different from that in pregnant nondiabetic women, thus predisposing them to having offspring with major congenital anomalies. RESEARCH DESIGN AND METHODS: A total of 31 pregnant diabetic women and 54 pregnant nondiabetic control subjects were studied at their first prenatal visits. Dietary folate intake, serum folate, red blood cell folate, urinary folate, and homocysteine were measured and compared after controlling for folate supplementation. Among diabetic women the relationships among parameters of folate metabolism and glycemic control were also assessed. RESULTS: There were no significant differences between the pregnant diabetic and non-diabetic women for any measures of folate metabolism after accounting for folate supplementation. In addition, among diabetic women, there were no associations among parameters of folate metabolism and glycemic control. CONCLUSIONS: Abnormal folate metabolism does not appear to occur in pregnant diabetic women. It is unlikely that deranged folate metabolism explains the higher incidence of major anomalies in infants of diabetic mothers. These results do not diminish the importance of periconception folate supplementation or preclude other possible scenarios that could restrict folate use by the embryo, leading to congenital anomalies.

TCPL delivery devices: endometrial changes associated with exogenous sustained release of ovarian hormones.

The specific objective of this study was to investigate the ultrastructural changes in the female reproductive system exposed to long-term sustained release of medroxyprogesterone acetate (MPA), and MPA plus estrogen (MPA + E). Emphases were given towards the vaginal, endometrial and ovarian changes. The microcrystals of tricalcium-phosphate lysine (TCPL) were prepared by following standard laboratory procedure. Adult female rats (BW 250-300 gm) were randomly divided into three groups (n = 3). Group I animals were implanted with TCPL loaded with MPA (50 mg) plus E (50 mg), and group II animals were implanted with TCPL loaded with MPA (200 mg). Group III animals were left as our intact and unimplanted controls. At the end of 21 days post-implantation, all animals were sacrificed by means of an overdose of Halothane and the reproductive, as well as, the vital organs were collected, weighed, fixed, embedded, sectioned, and stained (H & E) for histopathological evaluations. Vaginal smears were collected prior the implantation to assess the fertility events and subsequently taken on a daily basis for the entire period of the investigation. The data obtained from this study demonstrates the following: (1) TCPL delivery system was capable of releasing MPA, and MPA + E at a sustained level for 21 days, (2) the use of TCPL devices resulted in the cessation of the estrus cycle and that was achieved at the end of 24 hour post-implantation, (3) remarkable physiological changes were observed in animals implanted with MPA, and MPA + E compared to control group animals, (4) regression of the ovarian tissue was observed in all MPA treated animals compared to intact control animals, and (5) histopathological evaluation of the endometrium of animals treated with sustained delivery of MPA, and MPA + E revealed increased stratification, altered polarity, cytoplasmic vacuolation and papillary projections.

Histopathological evaluation of female reproductive tract exposed to sustained delivery of DHEA, and DHEA + E.

Dehydroepiandrosterone (DHEA) is a hormone produced by the adrenals that serves as a precursor for numerous steroid hormones. Conventional modes of DHEA administration were limited to injections and oral routes, which result in several drawbacks. This mandates the desire for the development of a different route of DHEA administration. Sustained delivery of DHEA by bioceramic capsules has not been fully explored. The objectives of this study were: (1) to deliver DHEA, and DHEA + estrogen in a sustained manner using tricalcium phosphate-lysine (TCPL) bioceramic capsules, and (2) to evaluate the morphological changes of reproductive and vital organs using female rats as a model. A total of twelve adult female rats (220-250 g) were randomly divided into four equal groups. Rats in Groups 1 and 2 were implanted with TCPL capsules containing 200 mg DHEA, and 600 mg DHEA (DHEA-HD), respectively. Group 3 animals were implanted with one TCPL capsule containing 200 mg of DHEA and a second TCPL capsule containing 50 mg estrogen, (DHEA + E). Group 4 represented the control group. Aseptic surgical techniques were utilized during i.p. implantation of the capsules. After implantation, body weights were recorded and blood (2 ml) samples were taken biweekly for 21 days. Pap smears were taken daily. At the end of 21 days, the animals were sacrificed using an overdose of halothane. The vital and reproductive organs were harvested, processed, embedded, sectioned and screened for cellular changes. Data obtained from these procedures revealed slight hypertrophy of the heart and kidneys. In DHEA + E implanted rats, a statistically significant increase (P < 0.05) was observed in the weights of the tubules, cervix, and uterine tissues compared to the control animals. Data obtained from this study demonstrates that the proliferative effect of sustained delivery of DHEA on the reproductive organs (ovary, cervix, uterus, and tubes) of female rats. This study provides more insights regarding the physiological alteration induced by sustained delivery of DHEA.

Coccidioidomycosis in Arizona: increase in incidence from 1990 to 1995.

The number of cases of coccidioidomycosis (incidence) reported to the Arizona Department of Health Services increased from 255 (7.0 per 100,000 population) in 1990 to 623 (14.9 per 100,000 population) in 1995 (P < .001). Four counties in the south central region of the state, which contained 80% of the state's population, had the largest increase and accounted for 95% of all cases in 1995. Cases in persons aged 65 years or older and men were reported more frequently (for both, P < .001). During 1995, 890 patients were discharged from Arizona hospitals with a diagnosis of coccidioidomycosis. Rates of hospitalization were greater among persons aged 55 years or older, men, and African-American (for all three, P < .01). Of the hospitalized patients, 48 died, and 12 (25%) of these patients had a concurrent diagnosis of human immunodeficiency virus infection. These data demonstrate that coccidioidomycosis is a growing health problem in Arizona.