Development of a novel autoantibody assay for autoimmune gastritis in type 1 diabetic individuals.

BACKGROUND: Autoimmune atrophic body gastritis (ABG) and pernicious anaemia are prototypical, organ-specific autoimmune diseases whose prevalence in the general population is 2.0 vs 2 and 0.15-1%, respectively. The incidence of disease increases with age and is frequently associated with other autoimmune disorders such as type 1 diabetes mellitus (T1DM). Early diagnosis of ABG/pernicious anaemia is essential for the prevention and/or treatment before manifestations of chronic disease become irreversible. Parietal cell autoantibody detection via enzyme-linked immunosorbent assay is currently the most widely used biomarker of disease with diagnosis confirmed by subsequent immunohistochemistry via biopsy. METHODS: To improve the assay we designed a specific, molecularly defined radioimmunoprecipitation assay for early detection of ABG, targeting its major antigen, the gastric H+/K+ ATPase 4A subunit ATP4A. RESULTS: The major antigenic domain in ATP4A was tested against a panel of sera from new onset patients with T1DM which tested positive for the gold standard T1DM autoantibodies (IAA, IA2A, GAD65A, and ZnT8A). Significant immunoreactivity to ATP4A was measured (25%) while 6% of first-degree relatives of subjects with T1DM who were sero-negative for T1DM autoantigens were positive for ATP4A autoantibodies. ATP4A antibody prevalence increased with age of onset of T1DM, which is atypical of other T1DM autoantibodies. Immunoreactivity to ATP4A, unlike that of T1DM antigens, demonstrates a significant gender bias in newly diagnosed individuals with T1DM. CONCLUSION: Although the utility of the assay as a biomarker for T1DM is likely limited, it may serve as an improved indicator of ABG.

First trimester diagnosis of forked cord in monoamniotic twin pregnancy.

A 29-year-old healthy woman at 10 weeks gestation was suspected for monoamniotic twin pregnancy, thus referred for evaluation and treatment. Ultrasound examination confirmed intrauterine monoamniotic twin gestation with central insertion of both umbilical cords by brief conjoined part (9 mm) - comprising a forked umbilical cord. Early diagnosis, planned prenatal care and close surveillance allowed preventing perinatal mortality.

Kinetics of the post-onset decline in zinc transporter 8 autoantibodies in type 1 diabetic human subjects.

CONTEXT: Zinc transporter 8 (ZnT8) is a newly discovered islet autoantigen in human type 1A diabetes (T1D). OBJECTIVE: The objective was to document changes in ZnT8 autoantibody (ZnT8A) titer and prevalence after onset of disease in relationship to 65 kDa glutamate decarboxylase antibody (GADA) and islet cell antigen antibody (IA2A). DESIGN/PATIENTS: Autoantibody radioimmunoprecipitation assays were performed on sera from three groups: 21 individuals monitored every 3 months from diagnosis for 2.5 yr; 61 individuals monitored at six monthly intervals for 5-12 yr; and a cross-sectional study of 424 patients with T1D of 20-57 yr duration. Circulating C-peptide was determined as an index of residual ß-cell function. RESULTS: ZnT8A titers declined exponentially from clinical onset of T1D with a t(1/2) ranging from 26 to 530 wk, similar to C-peptide (23-300 wk). Life-table analysis of antibody prevalence to 12 yr indicated that ZnT8A measured with either Arg325 or Trp325 probes persisted for a shorter interval than IA2A. Although prevalence of ZnT8A, IA2A, and GADA were comparable at disease onset (70.4 vs. 73.4 vs. 64%), only 6.7% of individuals remained ZnT8A positive after 25 yr compared with 19.5% for IA2A and 25.9% for GADA. Titers of ZnT8A and IA2A in seropositive individuals decreased progressively, whereas GADA remained elevated consistent with periodic reactivation of GADA humoral autoimmunity. CONCLUSIONS: ZnT8 humoral autoreactivity declines rapidly in the first years after disease onset and is less persistent than IA2A or GADA in the longer term. ZnT8A determination may be a useful measure of therapeutic efficacy in the context of immune-based clinical interventions.

Management and outcomes after multiple corneal and solid organ transplantations from a donor infected with rabies virus.

BACKGROUND: This article describes multiple transmissions of rabies via transplanted solid organ from a single infected donor. The empirical Milwaukee treatment regimen was used in the recipients. METHODS: Symptomatic patients were treated by deep sedation (ketamine, midazolam, and phenobarbital), ribavirin, interferon, and active and passive vaccination. Viral loads and antibodies were continuously monitored. RESULTS: Recipients of both cornea and liver transplants developed no symptoms. The recipient of the liver transplant had been vaccinated approximately 20 years before transplantation. Two recipients of kidney and lung transplants developed rabies and died within days of symptomatic disease. Another kidney recipient was treated 7 weeks before he died. The cerebrospinal fluid viral load remained at constant low levels (<10,000 copies/mL) for approximately 5 weeks; it increased suddenly by almost 5 orders of magnitude thereafter. After death, no virus was found in peripheral compartments (nerve tissue, heart, liver, or the small intestine) in this patient, in contrast to in patients in the same cohort who died early. CONCLUSIONS: Our report includes, to our knowledge, the longest documented treatment course of symptomatic rabies and the first time that the virus concentration was measured over time and in different body compartments. The postmortem virus concentration in the periphery was low, but there was no evidence of a reduction of virus in the brain.

Novel T*2-weighted contrast preparation scheme for segmented k-space myocardial imaging.

A novel T*(2)-weighted contrast-preparation scheme is described for use with segmented k-space cardiac sequences. This approach frees the imaging phase from the requirement of a long TE and, hence, a relatively long TR. A [90 degrees (x)-tau-90 degrees (rho)] preparation scheme is used to acquire four image data sets with the phase rho of the second pulse set to x, y, -x, and -y. The rho = x raw data is subtracted from the rho = -x data to form the "x" image, with a similar subtraction to generate the "y" image. These images are added in quadrature to obtain the T*(2)-weighted image. The method results in reduced artifact compared to a simple two-image scheme with rho = x, and y. T*(2) was measured in the myocardial septum in six normal volunteers by comparing tau = 7 and 28 ms images, and it was found to be 44 +/- 5 ms at 0.95 T.

Corneal tattooing: an alternative treatment for disfiguring corneal scars.

BACKGROUND: The performance and results of corneal tattooing are described in a case series of 11 patients suffering from a disfiguring corneal scar using a technique similar to conventional dermatography. METHODS: Drawing ink in different shades was applied into the anterior corneal stroma by punctures performed with a conventional spatula needle. RESULTS: Up to 4 years after surgery all patients still had satisfactory staining of the formerly cosmetically disfiguring corneal scar. CONCLUSION: Tattooing of unsightly corneal scars proved to be an efficient and easy to perform technique, yielding acceptable results during follow up.

[Diagnosis and therapy of LASIK-induced neurotrophic epitheliopathy]. / Diagnostik und Therapie der LASIK-induzierten neurotrophen Epitheliopathie.

Laser in situ keratomileusis (LASIK) has emerged as the standard surgical procedure for the correction of refractive errors and in the last years a lot of experience has been gained. Consequently, the amount of intraoperative, early and late postoperative complications have significantly decreased. Keratitis punctata superficialis and dry eye symptoms are the most frequent postoperative complications. A decreased corneal sensitivity attributable to the cutting of the corneal sensory nerves has been described after LASIK. In addition pathological tear secretion tests and typical dry eye symptoms have been reported. Until know it has not been completely evaluated, if these symptoms are a combination of the dry eye disease and LASIK-induced symptoms or if they are due to an independent LASIK complication, the so-called LASIK-induced neurotrophic epitheliopathy. Independently of the incompletely understood etiology, much care and a sufficient therapy with artificial tears should be applied to such patients. To increase the comfort of LASIK, adequate intra- and postoperative treatment is necessary to enhance the patient satisfaction.

Itinerant surgical and medical specialist care in Kansas: report of a survey of rural hospital administrators.

In most rural areas, specialist nonprimary care, when available, is provided by "itinerant" physicians and surgeons who periodically visit from a distant home base. Little is known about current usage and acceptability of itinerant specialists in rural communities. Administrators of hospitals in rural and frontier Kansas counties were asked to report the frequency of itinerant care in their facilities, the home base of each specialist and a listing of procedures performed during specialist visits. Administrators were also asked to respond on a Likert scale to six questions inviting their assessment of itinerant care. Responses were received from 53 of 56 hospitals. All offered at least one monthly session of itinerant medical or surgical care. The most common specialties represented were cardiology (in 87 percent of hospitals), urology (68 percent), orthopedics (68 percent) and radiology (60 percent). General surgeons consulted in over 80 percent of responding hospitals. Psychiatrists, dermatologists and neurologists were rarely available in the hospitals surveyed. Administrators generally rated itinerant care highly, though some expressed concern about revenue lost when specialists performed procedures in their home-base office or hospital. No associations were found between amount of care offered and potential explanatory variables such as hospital size, distance from subregional centers, or percentage of patients hospitalized locally. Further study is needed to better understand differences in itinerant specialist utilization and acceptance among rural Kansas hospitals. Because Kansas demographics are similar to those of many other American rural areas, such study may offer insights applicable to other regions.

Fetal biometry: a comparison of family physicians and radiologists.

BACKGROUND AND OBJECTIVES: While performance and reading of obstetric sonograms is a skill widely taught in family practice residency programs, no prior studies have compared ultrasound performance and interpretation in residency programs with that of hospital radiologists. This study compares results of fetal biometry for gestational age determination performed sequentially by faculty-supervised residents and radiologists. METHODS: This retrospective chart review selected cases from among all gravidas who had ultrasound performed in a family practice residency clinic between January 1992 and April 1999. Biometry was performed by residents under the supervision of faculty preceptors who had ultrasound training and experience. A patient was included if (1) results of both a family practice ultrasound and a radiologist-read hospital ultrasound were present in the chart, (2) both studies were done before 36 weeks gestation, and (3) the family practice examination preceded the hospital study. The difference in expected date of confinement between resident and radiologist ultrasound was calculated, and this difference was evaluated for statistical significance by a paired sample t test. RESULTS: Ninety-two ultrasound pairs were assessed, a sample size that provided .90 power to detect a gestational age estimate difference of 3 days between family practice and radiologist interpretations. The normally distributed observed mean difference in gestational age estimates was only 1.5 days. CONCLUSIONS: This study found no difference in gestational age assessment performed by closely supervised family practice residents in comparison to radiologists.

Social influences on Pap smear screening frequency.

Incidence and mortality rates of cervical cancer among Native American women is two to five times that of comparable Whites. Social and cultural differences contribute to this problem. We studied thirty age 40 and older American Indian women, half of whom had obtained at least one Pap in the past three years, the other half of whom had not. We asked: Do the two groups differ in their attitudes concerning Pap tests and those with whom they interact concerning Pap tests? and: Do they interact differently with different social groups concerning Pap tests? Data were obtained from chart audits and Given's Health Belief Questionnaire. The groups did not differ as to who they discussed Pap tests with or whose opinions they respected. They respected healthcare professionals most, family/friends less, and co-workers/others least. These findings suggest that the advanced practice nurse has an opportunity to improve Pap screening rates in this population.

Does a family physician who offers colposcopy and LEEP need to refer patients to a gynecologist?

BACKGROUND: Many family physicians perform colposcopy and provide treatment when biopsy reveals dysplasia. Before the adoption of loop electrical excision procedure (LEEP) gynecologic referral following colposcopy was required for a small percentage of women--most commonly for cold cone procedures. The use of LEEP and LEEP cones may obviate the need for cold conization, so we sought to assess the pattern of gynecologic referral in the practice of family physicians skilled in this procedure. METHODS: We reviewed the referral practices of a family medicine residency practice that routinely provides LEEP for biopsy-proven cervical intraepithelial neoplasia requiring treatment. Colposcopy and, when indicated, LEEP were performed primarily by the senior author or by residents under close faculty supervision. The computerized clinic log was reviewed for all patients from its 1993 inception through November 1999, and all treatment decisions were evaluated. RESULTS: During the study period, 283 women were seen in the clinic, and 26 individuals (9%) were referred by the family physician colposcopist to a consulting gynecologist. CONCLUSIONS: Despite use of LEEP, a minority of patients continues to need gynecologic referral. Large acetowhite lesions extending onto the vaginal fornix accounted for the majority of referrals, and some patients were referred exclusively for cold cone biopsy. Although LEEP can allow family physicians to manage cases previously requiring referral, we urge that this procedure be employed only by those with the technical and decision-making skills required for safe and effective treatment.

Smokers over age 35 continue to receive oral contraceptives. Survey of patients in a family practice residency practice.

OBJECTIVE: To assess the frequency with which women over age 35 report both current oral contraceptive use and current cigarette smoking. DESIGN: Cross-sectional survey of women in a single practice setting. SETTING: Primary care teaching practice in a mid-sized US city. PATIENTS: 142 women aged 35-55 who had not reached menopause and had not had hysterectomy. MAIN OUTCOME MEASURES: Smoking status in current oral contraceptive users. RESULTS: 19 women (13%) were current oral contraceptive users and 46 (32%) were current smokers. Four of the oral contraceptive users (21%) reported current smoking. CONCLUSIONS: Despite reported cardiovascular risk, women who smoke continue to receive prescriptions for oral contraceptives. Physicians should redouble efforts to record smoking status and offer smoking cessation treatment to women over age 35 who smoke and wish to take oral contraceptives.

Enhancing influenza immunization. Postcard and telephone reminders and the challenge of immunization site shift.

OBJECTIVE: To determine if postcard and telephone reminders increased the rate of influenza immunization of Medicare beneficiaries. DESIGN: Before and after trial (postcard reminders) with systematically allocated control group (telephone reminder intervention). SETTING: A semirural family practice residency program. PATIENTS AND OTHER PARTICIPANTS: All 475 noninstitutionalized persons older than 65 years who had received at least 1 office service in the previous 2 years. INTERVENTION: In September 1996, each of 475 patients received a postcard urging prompt influenza immunization. Those not responding within 1 month were systematically allocated either to a group receiving further telephone contact or to a control group. At the time of telephone contact, any offered information about influenza immunization received outside the Smoky Hill Family Practice Center, Salina, Kan, was recorded. MAIN OUTCOME MEASURES: We measured the percentage of change in practice-administered influenza immunizations compared with the baseline rate of the preceding 2 years; the difference in immunization rates between the telephone intervention group and controls; and the number of patients contacted by telephone who reported receiving influenza immunization at a site other than the Family Practice Center. RESULTS: Twenty-eight percent of patients who received a postcard obtained office influenza immunizations within 1 month, but no additional immunizations could be attributed to the telephone intervention. Thirty-five percent of patients contacted by telephone reported receiving influenza immunization at a site other than the Family Practice Center. CONCLUSIONS: The postcard intervention was associated with a significant increase in the office immunization rate. This increase may have been confounded by "site shift" in which individuals came to the office for an immunization that they might otherwise have received at other community sites.

[Bilateral simultaneous LASIK. Pro and contra]. / Bilaterale simultane LASIK. Pro und Kontra.

Until recently simultaneous bilateral laser in situ keratomileusis (LASIK) was regarded as contraindicated in Germany. However, the procedure was sporadically performed, because it offers patient comfort and is more cost effective than sequential LASIK. Even though the complication rate is below the calculated rate of 0.01%, bilateral complications may have catastrophic effects on the patient. In addition, there is the theoretical disadvantage that the results from the first eye cannot be used for the second eye. However, this effect has yet to be clinically proven.

Baseline thyroid hormones in depressed and non-depressed pre- and early-pubertal boys and girls.

OBJECTIVE: To examine baseline thyroid hormones in a large group of well-characterized pre- and early-pubertal boys and girls who met criteria for major depressive disorder (MDD) and a comparison group of normal children without psychiatric disorders. METHODS: 45 children with MDD (10.6 years +/- 1.4 year) and 56 healthy controls (10.0 +/- 1.7 year) who participated in a large, psychobiologic protocol are included in this report. As part of the screening for eligibility, baseline samples were drawn for thyroxine (T4), triiodothyronine (T3) uptake, and thyroid stimulating hormone (TSH). Free thyroxine index (FTI) also was computed. RESULTS: Between-group analyses were carried out controlling for various demographic variables significantly related to thyroid hormones [e.g. age, gender, body mass index (BMI) and their interactions]. For many hormones there were significant effects for age and gender. For T4, MDD boys had lower T4 compared with boys in the normal group. No differences were noted between MDD girls and normal girls. For TSH, MDD boys had lower concentrations compared with normal boys while no differences were noted in girls. For T3 uptake, the MDD group had lower uptake compared with the normal group. For FTI, there were no group differences. Similar to most studies of adults with depression, all our subjects were euthyroid. Unlike the adult studies, we found lower T4 concentrations in the MDD group rather than higher. Group differences in thyroid hormones were noted primarily in boys. The large sample size of this study allowed for the control of multiple variables, which has not been done in past studies. Without such controls, true findings may be masked in other studies of depression. Thus, our findings suggest the possibility of developmental differences in the relation of thyroid hormone and depression.