Using a relative health indicator (RHI) metric to estimate health risk reductions in drinking water.

When a new drinking water regulation is being developed, the USEPA conducts a health risk reduction and cost analysis to, in part, estimate quantifiable and non-quantifiable cost and benefits of the various regulatory alternatives. Numerous methodologies are available for cumulative risk assessment ranging from primarily qualitative to primarily quantitative. This research developed a summary metric of relative cumulative health impacts resulting from drinking water, the relative health indicator (RHI). An intermediate level of quantification and modeling was chosen, one which retains the concept of an aggregated metric of public health impact and hence allows for comparisons to be made across "cups of water," but avoids the need for development and use of complex models that are beyond the existing state of the science. Using the USEPA Six-Year Review data and available national occurrence surveys of drinking water contaminants, the metric is used to test risk reduction as it pertains to the implementation of the arsenic and uranium maximum contaminant levels and quantify "meaningful" risk reduction. Uranium represented the threshold risk reduction against which national non-compliance risk reduction was compared for arsenic, nitrate, and radium. Arsenic non-compliance is most significant and efforts focused on bringing those non-compliant utilities into compliance with the 10 µg/L maximum contaminant level would meet the threshold for meaningful risk reduction.

What's next after 40 years of drinking water regulations?

The quality of drinking water in the United States has continued to improve over the past 40 years. The formation of the U.S. Environmental Protection Agency (USEPA) in 1971, the passage of the initial Safe Drinking Water Act (SDWA, PL 93-523) in 1974, and the passage of the 1996 SDWA Amendments (PL 104-208) represent significant progress in drinking water quality. While the widespread adoption of filtration and disinfection in the early 1900s virtually eliminated waterborne typhoid fever, some residual risks still remained 40 years ago. These national regulatory developments compelled USEPA and the drinking water community to address these remaining risks in drinking water and optimize risk reduction for the public.

Analytical specificity and sensitivity of a real-time polymerase chain reaction assay for identification of bovine mastitis pathogens.

Intramammary infection (IMI), also known as mastitis, is the most frequently occurring and economically the most important infectious disease in dairy cattle. This study provides a validation of the analytical specificity and sensitivity of a real-time PCR-based assay that identifies 11 major pathogen species or species groups responsible for IMI, and a gene coding for staphylococcal beta-lactamase production (penicillin resistance). Altogether, 643 culture isolates originating from clinical bovine mastitis, human, and companion animal samples were analyzed using the assay. The isolates represented 83 different species, groups, or families, and originated from 6 countries in Europe and North America. The analytical specificity and sensitivity of the assay was 100% in bacterial and beta-lactamase identification across all isolates originating from bovine mastitis (n = 454). When considering the entire culture collection (including also the isolates originating from human and companion animal samples), 4 Streptococcus pyogenes, 1 Streptococcus salivarius, and 1 Streptococcus sanguis strain of human origin were identified as Streptococcus uberis, and 3 Shigella spp. strains were identified as Escherichia coli, decreasing specificity to 99% in Strep. uberis and to 99.5% in E. coli. These false-positive results were confirmed by sequencing of the 16S rRNA gene. Specificity and sensitivity remained at 100% for all other bacterial targets across the entire culture collection. In conclusion, the real-time PCR assay shows excellent analytical accuracy and holds much promise for use in routine bovine IMI testing programs. This study provides the basis for evaluating the assay's diagnostic performance against the conventional bacterial culture method in clinical field trials using mastitis milk samples.

Key attributes of health ministries in African American churches: an exploratory survey.

BACKGROUND: Church leaders are considered instrumental in the successful implementation of church-based health programs. However it is unknown which program attributes they perceive as important and which program attributes exist in their congregations. OBJECTIVE: To explore the perceived importance and existence of health ministry-related attributes in predominately African American churches. METHODS: Cross-sectional survey, with a convenience sample of 98 registered church leaders attending a conference on health and spirituality in Raleigh, NC. Attendees were asked to complete a brief survey assessing perceived importance (very important vs. somewhat or not important) and existence (yes vs. no) of 20, health ministry-related attributes in their churches. Percent perceived as very important, percent existence, and their differences were assessed for each attribute. RESULTS: Seventy-two (73.5%) of the attendees completed the survey. Attributes perceived as very important were: displaying health information in churches (73.6%); hosting health fairs for church members (73.2%); pastoral, church-based Internet access (70.8%); willingness to receive foundation funding for activities (66.7%); and incorporating health messages in Sunday bulletins (65.3%). For each of these program attributes, there was a gap between the proportion rating them "very important" and existence of the attribute in their own congregations (range diff in %: -8.3 to -22.2). LIMITATIONS: Lack of generalizability due to sample selection and homogeneity. CONCLUSIONS: Among leaders surveyed, despite perceived importance, attributes did not exist for all. Future studies should evaluate whether attributes considered important by church leadership parallel an increase in the development and maintenance of health program activities, and are associated with congregation health behaviors and health outcomes.

Hematologic responses in captive white-winged doves (Zenaida asiatica), induced by various radiotransmitter attachments.

White blood cell counts, heterophil-lymphocyte ratios, and leukocyte differentials of captive white-winged doves (Zenaida asiatica) from Texas equipped with different radiotransmitter attachment packages were monitored. Doves were segregated by gender and age by males, females, and hatching year; individuals housed in 30 large outdoor pens in groups of seven. Treatments consisted of controls, glue-on transmitters, body loop harnesses, surgically implanted intracoelomic transmitters, surgically implanted subcutaneous transmitters, intracoelomic surgery without implants, and subcutaneous surgery without implants. We used multivariate analysis of variance with pen as a blocking variable and gender nested and repeated measures analysis of variance to identify differences among any of the transmitter attachment techniques and the control for dependent variables. We found no difference in blood parameters between transmitter attachment technique versus a control.

Osseous and central nervous system sarcoidosis: scintigraphic and radiographic findings.

We present a case of painful osseous sarcoid involving the tibiae bilaterally. Lesions were initially found on plain radiographs and on a 99mTc-MDP bone scan. The patient was also found to have CNS involvement of sarcoidosis in the form of diabetes insipidus and panhypopituitarism. CNS lesions were demonstrated on CT and MR images.

Potent and specific inhibition of HIV envelope-mediated cell fusion and virus binding by G quartet-forming oligonucleotide (ISIS 5320).

We have previously reported identification of a phosphorothioate oligonucleotide TTGGGGTT (ISIS 5320) as a potent inhibitor of HIV infection in vitro. The oligonucleotide forms a parallel-stranded, tetrameric guanosine quartet (G-quartet) structure that specifically binds to the HIV envelope glycoprotein (gp120) and inhibits both cell-to-cell and virus-to-cell infection at submicromolar concentrations. In the current study we demonstrate that the tetramer inhibits the infection of laboratory-derived isolates of HIV-1 and HIV-2 in a variety of phenotypically distinct, established human cell lines and a panel of biologically diverse clinical isolates in fresh human peripheral blood lymphocytes and macrophages. The compound was also active against all drug-resistant virus isolates tested. In combination with AZT, ISIS 5320 exhibits additive to slightly synergistic anti-HIV activity. Cell-based mechanism of action studies demonstrate that the compound inhibits the binding of infectious virus and virus-infected cells to uninfected target cells by binding to the cationic V3 loop of the envelope glycoprotein. The G-quartet structure is a potential candidate for use in anti-HIV chemotherapy.

Efficacy, pharmacokinetics, and in vivo antiviral activity of UC781, a highly potent, orally bioavailable nonnucleoside reverse transcriptase inhibitor of HIV type 1.

A series of compounds related to oxathiin carboxanilide has been identified as nonnucleoside reverse transcriptase inhibitors (NNRTIs) of HIV-1, and structure-activity relationships have been described (Buckheit RW, et al.: Antimicrob Agents Chemother 1995;39:2718-2727). Three new analogs (UC040, UC82, and UC781) inhibited laboratory and clinical isolates of HIV-1, including isolates representative of the various clades of HIV-1 found worldwide, in both established and fresh human cells. Virus isolates with the amino acid changes L100I, K103N, V106I, and Y181C in the reverse transcriptase were partially resistant to these compounds. However, UC781 inhibited these virus isolates at low nontoxic concentrations, presenting a broad in vitro therapeutic index. As with other NNRTIs, each of the compounds synergistically interacted with AZT to inhibit HIV-1 replication. UC781 possesses a favorable pharmacokinetic profile in mice with a high level of oral bioavailability. Plasma concentrations reached maximum levels within 2 to 4 hr of oral administration and remained in excess of those required for in vitro anti-HIV activity for at least 24 hr after a single oral dose. When evaluated in a murine hollow fiber implant model of HIV infection, UC781 dosed orally or parenterally was able to suppress HIV replication completely in this model system, providing evidence of the in vivo efficacy of the compound.

Interstitial deletion of chromosome 10, del(10) (q11.2q22.1) in a boy with developmental delay and multiple congenital anomalies.

We describe a 4-year-old boy with an interstitial deletion of the long arm of chromosome 10: del(10) (q11.2q22.1). Frontal bossing, hypertelorism, bright blue iris color, up-slanting palpebral fissures, a flat nasal bridge, a broad nose, apparently low-set ears, micrognathia, deep philtrum, and hypotonia were noted neonatally. A murmur was noted at age 5 1/2 months and surgical repair of subaortic stenosis was required at 4 years. At 4 years micrognathia was no longer evident, but the palate was high-arched. The pattern of abnormalities included postnatal-onset slow growth, short stature, mental retardation, and cardiac anomalies.

Mother and son with deletion of 3p25-pter.

We report on a mother and son with a 3p25-pter deletion. Both have postnatal growth retardation, mental retardation, apparently low-set or malformed ears, and telecanthus. The mother also has ptosis and multiple joint pains, while the son has a long philtrum and anteverted nares. These phenotypes are compared to those of other 3p- patients. Both patients have many manifestations previously described. The son appears to be more severely affected than the mother.

Duplication 6q21q23 in two unrelated patients.

We report on two patients with rare 6q duplications. The karyotype of patient 1 is 46,XY,dup(6)(q21q23.3). The karyotype of patient 2 is 46,XX,dup(6)(q21.15q23.3). These two patients have some nonspecific physical findings in common including a depressed nasal bridge, epicanthal folds, mild heart defects, and developmental delay, but each had other congenital anomalies.

Ullrich-Turner syndrome with a small ring X chromosome and presence of mental retardation.

Since some patients with Ullrich-Turner syndrome (UTS) have mental retardation, we reviewed our experience to look for a high-risk subgroup. Among 190 UTS and gonadal dysgenesis patients with X chromosome abnormalities, 12 had mental retardation. All of the six (100%) with a small ring X were educable (EMI) or trainable mentally impaired (TMI) with more severe delay than expected in UTS. Among the 184 with other X abnormalities, only 6 had similar delays (2 from postnatal catastrophes), for a frequency of 3.3% mental retardation among those without a small ring X; only 2.2% of these had unexplained mental retardation. Polymerase chain reaction studies showed no Y-derived material in the 2 patients who were evaluated, and in situ hybridization confirmed X origin of the ring in the 6 subjects who were evaluated. We describe the phenotype of the 6 individuals with a small ring X, and an additional 2 patients with a small ring X who were identified outside the survey. The subjects with a small ring X comprised a clinically distinct subgroup which had EMI/TMI and shorter stature than expected in UTS. Seizures and a head circumference less than 10th centile were observed in half of the patients with a small ring X, and strabismus, epicanthus, and single palmar creases were present in more than half. A "triangular" face in childhood, pigmentary dysplasia, sacral dimple, and heart defects were also common. Neck webbing appeared to be less frequent than in 45,X. We hypothesize that the high risk of mental retardation in this form of the UTS results from lack of lyonization of the ring X due to loss of the X inactivation center. Excluding those with a small ring X, mental retardation is not significantly increased in patients with UTS.

In vivo drug screening applications of HIV-infected cells cultivated within hollow fibers in two physiologic compartments of mice.

Previous studies demonstrated that human cell lines can be cultivated in hollow fibers in the subcutaneous and intraperitoneal compartments of mice. We have extended the range of cell lines to include cells infected with the human immunodeficiency virus (HIV). Furthermore, these HIV-infected cells have been shown to replicate in the hollow fibers located in both physiologic compartments (intraperitoneal and subcutaneous) of SCID mice. Treatment of the host mice with antiviral agents can suppress virus replication in these hollow fiber cultures. The potential use of this system for early in vivo screening of anti-HIV compounds is discussed.

Comparative anti-HIV evaluation of diverse HIV-1-specific reverse transcriptase inhibitor-resistant virus isolates demonstrates the existence of distinct phenotypic subgroups.

We have biologically and biochemically evaluated a structurally diverse group of HIV-1-specific reverse transcriptase (RT) inhibitors and determined that the members of this class share many common properties. These include reproducible and selective antiviral activity against a panel of biologically distinct laboratory and clinical strains of HIV-1, activity against HIV-1 in a wide variety of cultured and fresh human cells, and potent inhibition of HIV-1 RT when evaluated using a heteropolymeric ribosomal RNA template assay. Each of the HIV-1-specific compounds was capable of inhibiting HIV replication when challenged at high m.o.i., further distinguishing them from the nucleoside analogs 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (ddC). When tested in combination with AZT, each of the HIV-1-specific compounds synergistically inhibited the replication of HIV-1. HIV-1 isolates resistant to different HIV-1-specific inhibitors exhibited heterogeneous patterns of cross-resistance to other members of this pharmacologic class. Four distinct phenotypic classes have been defined through the use of drug-resistant virus isolates which derive from distinct mutations in the RT. These results indicate that the various subgroups of HIV-1-specific inhibitors interact differently with HIV-1 RT, suggesting important potential implications for drug combination therapeutic strategies.

Biological and biochemical anti-HIV activity of the benzothiadiazine class of nonnucleoside reverse transcriptase inhibitors.

A series of benzothiadiazine derivatives were screened against the human immunodeficiency virus (HIV) and certain structure-activity relationships were defined for anti-HIV activity in this chemical class. The selected representative NSC 287474 was a highly potent inhibitor of HIV-induced cell killing and HIV replication in a variety of human cell lines, as well as in fresh human peripheral blood lymphocytes and macrophages. The compound was active against a panel of biologically diverse laboratory and clinical strains of HIV-1, including the AZT-resistant strain G910-6. However, the agent was inactive against HIV-2, and also against both nevirapine- and pyridinone-resistant strains (N119 and A17) of HIV-1, which are cross-resistant to several structurally diverse nonnucleoside reverse transcriptase inhibitors. The compound selectively inhibited HIV-1 reverse transcriptase, but not HIV-2 reverse transcriptase. Combination of NSC 287474 with AZT synergistically inhibited HIV-1-induced cell killing in vitro. The compound did not inhibit the replication of the Rauscher murine leukemia retrovirus or the simian immunodeficiency virus. The benzothiadiazine class of compounds represents a new active anti-HIV-1 chemotype within the diverse group of nonnucleoside reverse transcriptase inhibitors.

Variable expressivity of familial medullary thyroid carcinoma (FMTC) due to a RET V804M (GTG-->ATG) mutation.

BACKGROUND: Multiple endocrine neoplasia type 2 (MEN 2) and familial medullary thyroid carcinoma (FMTC) are autosomal dominantly inherited cancer syndromes that predispose to C-cell hyperplasia and MTC. MEN 2A and FMTC are caused by mutations in the RET proto-oncogene. METHODS: We used a multiplex polymerase chain reaction-based assay to screen exons 10, 11, 13, and 14 of RET for mutations in 2 families with FMTC. We correlated mutation status with calcitonin and pathologic studies to determine genotype-phenotype correlations. RESULTS: We identified a mutation in codon 804 in exon 14 (GTG-->ATG; V804M) in both families. An 86-year-old person who was a gene carrier and other individuals over age 70 who were suspected by pedigree analysis to be gene carriers had no overt clinical evidence of MTC. Four of 21 patients who underwent a thyroidectomy also had papillary thyroid cancer. One individual in each family had metastatic MTC at age 30 and 32 years, and all 26 people having thyroidectomies had either MTC or C-cell hyperplasia, leading us to continue to recommend prophylactic thyroidectomy for all identified patients who were gene carriers. CONCLUSIONS: Because of active MTC in younger members of these families, including metastases, we have continued to advocate thyroid surgery in mutation-positive individuals. While DNA diagnosis of gene carriers and subsequent genetic counseling was relatively straightforward, the acceptance of surgical recommendations was more difficult for some individuals. These families demonstrate that the search for RET mutations should include exons 13, 14, 15, and 16 in patients whose studies in exons 10 and 11 are negative.

Porous-coated femoral components in a canine model for revision arthroplasty.

UNLABELLED: Six dogs had a total hip arthroplasty during which the femoral component was coated with methacrylate and inserted in the femoral canal, after the canal had been reamed to a larger diameter than that of the femoral stem (including the coating). Thus, the implant was loose and motion was present between it and the femur in each animal. Five dogs had a revision to a prosthesis with a porous polysulfone-coated stem. This prosthesis was not cemented in place. One dog was killed before the revision for the purpose of histological examination. Although bone was present in the porous surface of all five stems at the revision, the amount was scant in three. CLINICAL RELEVANCE: A model is described for the study of cemented hip-replacement prostheses that have failed. Although variable amounts of ingrowth of bone were observed after the revision to the porous-coated prostheses without bone cement, further study is needed to determine whether adequate ingrowth of bone occurs in this model.

Total hip arthroplasty in patients who have sickle-cell hemoglobinopathy.

Eleven patients who had a form of sickle-cell hemoglobinopathy had a total hip arthroplasty for avascular necrosis of the hip. Four patients had a revision and three had a resection arthroplasty. Four had a serious infection postoperatively. Both acute and late complications were numerous. We concluded that patients who have a sickle-cell hemoglobinopathy are at markedly increased risk for complications after total hip replacement arthroplasty, yet that over-all the results are favorable.

Implementation of a clinical pathway in management of the postoperative vestibular schwannoma patient.

OBJECTIVE: The purpose of the study was to evaluate the effectiveness of a new clinical pathway in management of patients with postoperative vestibular schwannoma. The impact on duration of hospitalization and quality of care was evaluated. STUDY DESIGN: The study was a retrospective review of 59 consecutive patients undergoing surgical intervention for vestibular schwannoma between January 1995 and July 1999. METHODS: A new clinical pathway for management of postoperative vestibular schwannoma patients was implemented at The California Ear Institute at Stanford (Palo Alto, CA) in January 1995. All patients undergoing surgical intervention subsequent to initiation of the pathway were included in the study. Data including surgical approach, patient age, sex, and tumor size were included. Duration of hospitalization and postoperative complications were recorded. During the same time period, data for patients undergoing radiation therapy for vestibular schwannomas were evaluated for length of hospital stay and in-hospital complications. Data were compared with norms recorded in the literature for duration of hospitalization and complications following surgical intervention. RESULTS: Fifty-nine patients underwent 35 middle fossa approaches and 24 translabyrinthine approaches to their tumors. The average patient age was 53 years; there were 34 female and 25 male patients. The average length of hospital stay was 3.83 days (SD = 1.4 days) with a range from 2 to 10 days. Postoperative complications were observed in 19% of patients, including eight (13%) cerebrospinal fluid (CSF) leaks, two requiring lumbar drains (3.4%); one hematoma (1.6%), one postoperative fever (1.6%), and one dural tear with associated hyponatremia (1.6%). These results compared favorably with previously recorded average hospital stays of 5.95 to 9.5 days 1,5-7 and CSF leak complication rates of 7% to 15%.9,10 CONCLUSIONS: Implementation of a clinical pathway for management of the patient with postoperative vestibular schwannoma improves efficiency of patient care, allowing decreased duration of hospitalization. This goal is achieved without increasing complication rates and, in our experience, actually improving the quality of clinical care. The cost-effectiveness of clinical pathways may become increasingly important in a managed care-driven environment.