COVID-19 impact on screening test volume through the National Breast and Cervical Cancer early detection program, January-June 2020, in the United States.

Women from racial and ethnic minority groups face a disproportionate burden of cervical and breast cancers in the United States. The Coronavirus Disease 2019 (COVID-19) pandemic might exacerbate these disparities as supply and demand for screening services are reduced. The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides cancer screening services to women with low income and inadequate health insurance. We examined COVID-19's impact on NBCCEDP screening services during January-June 2020. We found the total number of NBCCEDP-funded breast and cervical cancer screening tests declined by 87% and 84%, respectively, during April 2020 compared with the previous 5-year averages for that month. The extent of declines varied by geography, race/ethnicity, and rurality. In April 2020, screening test volume declined most severely in Health and Human Services Region 2 - New York (96% for breast, 95% for cervical cancer screening) compared to the previous 5-year averages. The greatest declines were among American Indian/Alaskan Native women for breast cancer screening (98%) and Asian Pacific Islander women for cervical cancer screening (92%). Test volume began to recover in May and, by June 2020, NBCCEDP breast and cervical cancer screening test volume was 39% and 40% below the 5-year average for that month, respectively. However, breast cancer screening remained over 50% below the 5-year average among women in rural areas. NBCCEDP programs reported assisting health care providers resume screening.

[Perioperative approach to restless legs syndrome]. / Perioperatives Vorgehen bei Restless-legs-Syndrom.

Restless legs syndrome (RLS) is one of the most common neurological disorders. The key feature is the urge to move, especially in the legs. New onset RLS can develop perioperatively or an existing RLS can be exacerbated. Severe insomnia, forced immobilization and acute iron deficiency are common trigger factors. Medicinal treatment can also be an important triggering or exacerbating factor. Drugs with dopamine antagonistic, serotonergic and opioid antagonistic effects should be avoided. The long-term medicinal treatment should be terminated as quickly as possible and if necessary bridged non-orally. For diseases which can be associated with secondary RLS a provocation or an exacerbation of RLS should be taken into consideration. This is particularly true for Parkinson's disease, diabetes mellitus, terminal renal insufficiency, spinal cord lesions and pregnancy. So far, there is not sufficient evidence that any form of anesthesia has a negative influence on RLS.

[Clinically relevant pharmacokinetic drug interactions in the intensive care unit: an overview]. / Klinisch relevante pharmakokinetische Arzneimittelinteraktionen in der Intensivmedizin: Eine Übersicht.

Critically ill patients in the intensive care unit (ICU) are predisposed to pharmacokinetic drug interactions because of the complexity of the drug regimens received in the intensive care setting. Drugs may affect the absorption, distribution, metabolism and/or elimination of an object drug and consequently alter the intended pharmacologic response and potentially lead to an adverse event. The paper presents an overview of pharmacokinetic drug-drug interactions which can occur with commonly used drugs in the ICU and outlines the underlying types and mechanisms.

Intravenous and oral antibiotics in respiratory tract infection: an international observational study of hospital practice.

BACKGROUND: Hospitalised patients with respiratory tract infections (RTI) frequently receive intravenous (i.v.) antibiotics followed by a short course of oral treatment. OBJECTIVES: To observe antibiotic use in hospitals in Germany, Spain, France, Italy and the UK and the reasons for choosing the i.v. route and switching to oral treatment. METHODS: Research pharmacists sought the opinions of physicians and senior nurses in the completion of a semi-structured questionnaire on the treatment of RTI with i.v. antibiotics. Questions focussed on antimicrobials of choice, reasons for choosing i.v., reasons for changing to oral administration, and duration of treatment. RESULTS: This study recruited 796 patients with RTI, usually pneumonia. Prescribing patterns varied widely between the five hospitals. Accepted clinical criteria were only commonly cited in Germany, Spain and the UK as reasons for choosing the i.v. route at the beginning of the study. These were more commonly cited at the time of switch, although other criteria such as improved condition, were other significant reasons. The mean duration of i.v. treatment ranged from 4 days in the UK to 10 days in Italy, where most patients received the full course of treatment by the i.v. route. Unlike the other hospitals studied, the few patients in Italy who were switched to another form of treatment were as likely to receive intramuscular as oral administration (13% and 11%, respectively). CONCLUSIONS: The practice of and reasons for prescribing i.v. antibiotics varied in the hospitals studied. Objective clinical criteria were inconsistently cited as reasons for administering i.v. antibiotics and in general these reasons were unrelated to those given for the switch from i.v. to oral administration. In order for guidelines for switching from i.v. to oral antimicrobials to be routinely employed, explicit physiological criteria need to be recorded in a routine fashion. Closer co-operation between pharmacists and physicians may help in developing and implementing guidelines at a local level.

Elucidating the pathophysiology of syringomyelia.

OBJECT: Syringomyelia causes progressive myelopathy. Most patients with syringomyelia have a Chiari I malformation of the cerebellar tonsils. Determination of the pathophysiological mechanisms underlying the progression of syringomyelia associated with the Chiari I malformation should improve strategies to halt progression of myelopathy. METHODS: The authors prospectively studied 20 adult patients with both Chiari I malformation and symptomatic syringomyelia. Testing before surgery included the following: clinical examination; evaluation of anatomy by using T1-weighted magnetic resonance (MR) imaging; evaluation of the syrinx and cerebrospinal fluid (CSF) velocity and flow by using phase-contrast cine MR imaging; and evaluation of lumbar and cervical subarachnoid pressure at rest, during the Valsalva maneuver, during jugular compression, and following removal of CSF (CSF compliance measurement). During surgery, cardiac-gated ultrasonography and pressure measurements were obtained from the intracranial, cervical subarachnoid, and lumbar intrathecal spaces and syrinx. Six months after surgery, clinical examinations, MR imaging studies, and CSF pressure recordings were repeated. Clinical examinations and MR imaging studies were repeated annually. For comparison, 18 healthy volunteers underwent T1-weighted MR imaging, cine MR imaging, and cervical and lumbar subarachnoid pressure testing. Compared with healthy volunteers, before surgery, the patients had decreased anteroposterior diameters of the ventral and dorsal CSF spaces at the foramen magnum. In patients, CSF velocity at the foramen magnum was increased, but CSF flow was reduced. Transmission of intracranial pressure across the foramen magnum to the spinal subarachnoid space in response to jugular compression was partially obstructed. Spinal CSF compliance was reduced, whereas cervical subarachnoid pressure and pulse pressure were increased. Syrinx fluid flowed inferiorly during systole and superiorly during diastole on cine MR imaging. At surgery, the cerebellar tonsils abruptly descended during systole and ascended during diastole, and the upper pole of the syrinx contracted in a manner synchronous with tonsillar descent and with the peak systolic cervical subarachnoid pressure wave. Following surgery, the diameter of the CSF passages at the foramen magnum increased compared with preoperative values, and the maximum flow rate of CSF across the foramen magnum during systole increased. Transmission of pressure across the foramen magnum to the spinal subarachnoid space in response to jugular compression was normal and cervical subarachnoid mean pressure and pulse pressure decreased to normal. The maximum syrinx diameter decreased on MR imaging in all patients. Cine MR imaging documented reduced velocity and flow of the syrinx fluid. Clinical symptoms and signs improved or remained stable in all patients, and the tonsils resumed a normal shape. CONCLUSIONS: The progression of syringomyelia associated with Chiari I malformation is produced by the action of the cerebellar tonsils, which partially occlude the subarachnoid space at the foramen magnum and act as a piston on the partially enclosed spinal subarachnoid space. This creates enlarged cervical subarachnoid pressure waves that compress the spinal cord from without, not from within, and propagate syrinx fluid caudally with each heartbeat, which leads to syrinx progression. The disappearance of the abnormal shape and position of the tonsils after simple decompressive extraarachnoidal surgery suggests that the Chiari I malformation of the cerebellar tonsils is acquired, not congenital. Surgery limited to suboccipital craniectomy, C-I laminectomy, and duraplasty eliminates this mechanism and eliminates syringomyelia and its progression without the risk of more invasive procedures.

Quantification and pharmacokinetics of blood-brain barrier disruption in humans.

Hyperosmolar blood-brain barrier disruption (HBBBD), produced by infusion of mannitol into the cerebral arteries, has been used in the treatment of brain tumors to increase drug delivery to tumor and adjacent brain. However, the efficacy of HBBBD in brain tumor therapy has been controversial. The goal of this study was to measure changes in vascular permeability after HBBBD in patients with malignant brain tumors. The permeability (K1) of tumor and normal brain blood vessels was measured using rubidium-82 and positron emission tomography before and repeatedly at 8- to 15-minute intervals after HBBBD. Eighteen studies were performed in 13 patients, eight with glioblastoma multiforme and five with anaplastic astrocytoma. The HBBBD increased K1 in all patients. Baseline K1 values were 2.1 +/- 1.4 and 34.1 +/- 22.1 microl/minute/ml (+/- standard deviation) for brain and tumor, respectively. The peak absolute increases in K1 following HBBBD were 20.8 +/- 11.7 and 19.7 +/- 10.7 microl/minute/ml for brain and tumor, corresponding to percentage increases of approximately 1000% in brain and approximately 60% in tumor. The halftimes for return of K1 to near baseline for brain and tumor were 8.1 +/- 3.8 and 4.2 +/- 1.2 minutes, respectively. Simulations of the effects of HBBBD made using a very simple model with intraarterial methotrexate, which is exemplary of drugs with low permeability, indicate that 1) total exposure of the brain and tumor to methotrexate, as measured by the methotrexate concentration-time integral (or area under the curve), would increase with decreasing infusion duration and would be enhanced by 130% to 200% and by 7% to 16%, respectively, compared to intraarterial infusion of methotrexate alone; and 2) exposure time at concentrations above 1 microM, the minimal concentration required for the effects of methotrexate, would not be enhanced in tumor and would be enhanced by only 10% in brain. Hyperosmolar blood-brain barrier disruption transiently increases delivery of water-soluble compounds to normal brain and brain tumors. Most of the enhancement of exposure results from trapping the drug within the blood-brain barrier, an effect of the very transient alteration of the blood-brain barrier by HBBBD. Delivery is most effective when a drug is administered within 5 to 10 minutes after disruption. However, the increased exposure and exposure time that occur with methotrexate, the permeability of which is among the lowest of the agents currently used clinically, are limited and the disproportionate increase in brain exposure, compared to tumor exposure, may alter the therapeutic index of many drugs.

Clinical features and therapeutic management of subglottic stenosis in patients with Wegener's granulomatosis.

OBJECTIVE: To determine the clinical features and optimal treatment of subglottic stenosis (SGS) in patients with-Wegener's granulomatosis (WG). METHODS: Review of 43 patients with SGS and treatment of 20 patients with intratracheal dilation-glucocorticoid injection therapy. RESULTS: SGS developed in 43 of 189 patients with WG who were followed up at the National Institutes of Health Clinical Center. The diagnosis of SGS occurred in the absence of other features of active. WG in 21 of 43 patients (49%). In 21 patients (49%), SGS began while the patient was receiving systemic immunosuppressive therapy for disease activity involving other sites. Tracheostomy was required in 10 of 18 patients (56%) who were treated with systemic immunosuppressive therapy. In 20 patients treated with intratracheal therapy, none required tracheostomy and 6 with previous tracheostomies were decannulated. CONCLUSION: SGS often occurs independently of other features of active WG and is frequently unresponsive to systemic immunosuppressive therapy. Intratracheal dilation-injection therapy provides a safe and effective treatment for WG-associated SGS and, in the absence of major organ disease activity, should be used without concomitant systemic immunosuppressive agents.

Genetic analysis of the effects of re-transformation of transgenic lines of the moss Physcomitrella patens.

Genetic analysis of the progeny of crosses involving strains of the moss Physcomitrella patens obtained by re-transforming a stable transgenic line, indicates that the plasmid used for re-transformation inserts at or near the chromosomal location of the related plasmid used to obtain the original transgenic line. The resulting structure may be subject to gene silencing.

Importance of supplemental vitamin C in determining serum ascorbic acid in controls from a cervical cancer case-control study: implications for epidemiological studies.

Classification of individuals by their vitamin C intake was investigated in 493 control subjects from a cervical cancer case-control study. The influence of dietary and supplemental sources of vitamin C, as well as demographic and life-style factors, on serum ascorbic acid were examined. Usual dietary intakes of vitamin C were determined from a food frequency questionnaire and recent intakes from a 24-hour recall taken at the time of blood collection. Vitamin supplement information was obtained at both times. In a regression analysis, the factors found to predict serum ascorbic acid were total recent vitamin C intake, an indicator variable for supplement use, body mass index, number of cigarettes smoked per day, race, education, and age. Higher levels of serum ascorbic acid were found among older nonsmoking highly educated leaner white women. Consideration of supplements, in addition to dietary sources of vitamin C, improved correlation coefficients between serum ascorbic acid and usual vitamin C intake from 0.19 to 0.32 and between serum ascorbic acid and recent intake from 0.36 to 0.56. Furthermore, whereas only a twofold difference between the first and fourth quartiles of serum ascorbic acid was observed using recent dietary vitamin C without supplements, this range increased to sixfold with addition of supplement data. Epidemiological studies should consider use of total vitamin C intakes from supplement and food sources to permit accurate classification of individuals.

Echinococcal disease.

Diagnosis of infection by the larval stages of Echinococcus granulosus, E. multilocaris, and E. vogeli, has increased in most parts of the world because of improved diagnostic technology, active surveillance, and increasing rates of transmission. Specific immunodiagnostics and sophisticated imaging techniques have made diagnosis more sensitive and specific. Surgery, performed by an experienced team with adequate postoperative support, remains the mainstay of therapy; however, alternative treatments, including chemotherapy and percutaneous cyst drainage, are used increasingly to aid in the management of inoperable echinococcal disease and, in some cases, for primary therapy. This article incorporates data from widely disparate sources and attempts a summary of the state-of-the-art diagnosis and treatment of echinococcal disease.

Expression of myb-related genes in the moss, Physcomitrella patens.

Three cDNA clones encoding proteins containing a myb-related DNA binding domain have been isolated from a cDNA library prepared from protonemal tissue of the moss, Physcomitrella patens. The three cDNA clones between them encode two different classes of myb-like proteins, termed Pp1 and Pp2, that, outside of the myb domain, show no regions of significant homology. Acidic domains, capable of forming alpha-helical structures, are present in the carboxy-termini of the derived amino acid sequences from Pp1 and Pp2cDNAs suggesting that, like other myb genes, these proteins probably function as transcriptional activators. In contrast to other plants, where extensive myb-related gene families are present in the genome, a relatively small family is present in P. patens. Analyses of transcript levels during development of P. patens showed that maximum levels of transcription of the two genes occurred in young wild-type protonemal tissue that correlated with the time of maximum mitotic index. A decline in the expression of both genes occurs with increasing age of the wild-type tissue. Aberrant levels of expression of the two genes were observed in developmental mutants of P. patens which, as well as carrying specific morphological mutations, have greatly retarded protonemal growth rates. Transformation of wild-type P. patens with antisense constructs derived from Pp1 and Pp2 cDNA clones led to a dramatically reduced frequency of transformants when the expression of the reporter gene within the constructs was selected. Taken together, the data strongly suggest that expression of Pp1 and Pp2 is essential for cell growth during normal gametophytic development of P. patens.

The management of subglottic stenosis in patients with Wegener's granulomatosis.

Wegener's granulomatosis (WG) is a multisystem inflammatory disease characterized by vasculitis, granuloma formation, and necrosis. Among 158 patients treated at the National Institutes of Health during the past 24 years, 145 (92%) had an otolaryngologic manifestation of their disease and 25 (16%) had subglottic stenosis (SGS). SGS varied from asymptomatic to life-threatening. Sixteen (80%) of 20 patients with fixed SGS required surgical intervention, including manual dilations, carbon-dioxide laser resections, and laryngotracheoplasty (LTP). LTP was performed with and without microvascular reconstruction. Thirteen of the patients required tracheostomy and all 13 were ultimately decannulated. Five patients who repeatedly failed dilations and/or endoscopic laser surgery underwent LTP. Since 1987, two patients have undergone LTP with microvascular free flaps. Both patients were subsequently decannulated. The authors' experience demonstrates that management of SGS in WG is complex, requiring individualized frequent multimodality interventions to achieve satisfactory results. Microvascular laryngotracheal reconstruction should be considered in the surgical armamentarium for patients with persistent stenoses.

Developmental genetic studies of the moss, Physcomitrella patens.

The development of the haploid gametophyte stage of Physcomitrella patens presents excellent opportunities for the detailed study of plant morphogenesis at the cellular level. The filamentous protonema undergoes a number of developmental transitions that can be observed directly in living material using time-lapse video microscopy and that can be manipulated both by treatment with phytohormones and by environmental stimuli. Mutants affecting these processes can be isolated and can be analysed using conventional as well as parasexual methods. Molecular biological techniques are now being established since these will be essential if the mechanisms that bring about morphogenetic processes are to be understood at the molecular level. A technique for genetic transformation has been devised and is being exploited to attempt to tag developmentally-relevant genes using maize transposons. Changes in gene activity associated with developmental transitions and in response to treatment with phytohormones and environmental stimuli are being studied using cDNA library subtraction techniques. Heterologous genes involved in the control of transcription and of the cell cycle are being used to probe the P. patens genome to identify possible homologues involved in developmental regulation.

Enflurane metabolism produces covalently bound liver adducts recognized by antibodies from patients with halothane hepatitis.

The existence of a rare syndrome of "enflurane hepatitis" similar to that described for halothane and of a cross-sensitization between halothane and enflurane has been controversial, largely due to equivocal clinical case reports and a lack of a plausible molecular mechanism for the hepatotoxicity. The present study suggests a possible hypersensitivity basis for enflurane hepatitis and the apparent cross-sensitization between halothane and enflurane involving covalently bound liver microsomal adducts. Immunoblotting studies have revealed that antibodies in the sera of six patients with halothane hepatitis recognize liver microsomal antigens of Mr = 100,000, or both 100,000 and 76,000, formed in rats treated with enflurane or halothane. These antigens were not detected in microsomes from isoflurane- or sesame oil-treated rats. The recognition of these antigens could be abolished by preincubation of the sera with microsomes from halothane-treated rats. These data suggest that the difluoromethoxydifluoroacetyl halide metabolite of enflurane, as well as the trifluoroacetyl halide metabolite of halothane, covalently bind to similar hepatic proteins, and may become immunogens in susceptible patients. This mechanism may also account for the apparent cross-sensitization between halothane and enflurane anesthesia, and the development of hepatic necrosis.

Large-scale preparation of a DNA fragment containing the strong promoter A1 of the phage T7.

A procedure has been developed to isolate DNA fragments on a large scale. A DNA fragment of 130 base-pairs containing the strong promoter A1 of the phage T7 was purified to homogeneity in amounts of 10 mg. The procedure includes the rapid purification of gram amounts of plasmid DNA, a new, simple method to separate small DNA fragments from the vector by a phenol/water partitioning system, and a liquid-liquid PEG-dextran partition chromatography for the final purification of the fragment. The fragment was cloned in two vector systems: The vector pDS1, to1+ (1), containing an efficient terminator downstream from the promoter integration site, gives high yields, 3-4 mg plasmid DNA per liter medium. In the plasmid pWH802 (2), which is not specially designed for the amplification of a strong promoter, the integration of the promoter was possible but the yield decreased by a factor of about 50. The stability of the inserts was tested in both systems. Monomeric inserts were stable in both plasmids, multimeric inserts up to a tetramer were only stable in pWH802. Only one orientation of the fragment was found.

Nonobstetric surgery in pregnancy.

Diagnostic and judgmental uncertainty that results in operative delay, leading to a more severe degree of illness and more complex surgery, is the major factor effecting both maternal and fetal morbidity and mortality in pregnant surgical patients. The acute abdomen is responsible for most errors in diagnosis and therapy. An understanding of anatomic, physiologic, and laboratory changes occurring in pregnancy and a timely interdisciplinary approach will expedite management and optimize outcome.

Promoters of Escherichia coli: a hierarchy of in vivo strength indicates alternate structures.

The strength in vivo of 14 promoters was determined in a system which permits the quantitation of RNA synthesis with high accuracy. Up to 75-fold differences in promoter strength were measured and the most efficient signals are promoters from coliphages T7 and T5. Their activity approaches the strength of fully induced promoters of the rRNA operons which may be close to the functional optimum of a single sequence. By contrast, a synthetic 'consensus promoter' belongs to the less efficient signals. Our data show that optimal promoter function can be achieved by alternate structures and strongly suggest that information outside of the 'classical' promoter region contributes to promoter activity.