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.

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.

Toxicity of D-penicillamine in rheumatoid arthritis. A report of 63 patients including two with aplastic anemia and one with the nephrotic syndrome.

To assess toxicity of D-penicillamine a retrospective chart review was performed on 63 patients with rheumatoid arthritis receiving penicillamine. These patients had a total of 83 courses of therapy. The mean age of patients was 52 years and the mean duration of disease was 10.07 years. Laboratory data showed an increase in hematocrit values from 36 per cent to 40 per cent and a decrease in the erythrocyte sedimentation rate from an average of 50 to 29 mm/hour. The platelet count also decreased with treatment from 394,000 to 267,000/mm3. The over-all complication rate was 53 per cent. Life-threatening complications occurred in two patients including one case of aplastic anemia and one case of nephrotic syndrome. One additional patient was referred with aplastic anemia. Minor complications include rash in 18 per cent, loss of taste in 6 per cent, dyspepsia in 11 per cent, oral ulceration in 7 per cent and proteinuria of less than 3 g/day in 8 per cent. In summary, 53 per cent of the courses of penicillamine were associated with toxicity including one episode of aplastic anemia and one case of nephrotic syndrome. Therapy was stopped due to complications in 39 per cent of the patients in this series.

Intraocular cysticercosis.

Two intravitreal Taenia cysts were removed intact by pars plana vitrectomy from a 59-year-old woman who had never left the continental United States. The intraocular course of the cysts progressed from an initial chorioretinal location, accompanied by an intense focal inflammatory reaction, to free floating in the vitreous cavity within two months; thereafter, there was only a low-grade vitritis for an additional five months until removal. Light and electron microscopic studies suggested Cysticercus cellulosae as the infecting agent, although mature hooklets were absent. Local pork products were considered to be the source of the infection. Preretinal fibrosis and posterior subcapsular vacuoles were the final residua and did not progress after removal of the cysts. Although uncommon in the United States, cysticercosis should be considered in cases of focal necrotizing chorioretinitis.

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.

Chemotherapy of hydatid disease (Echinococcus granulosus) in mice with mebendazole and bithionol.

We treated female Swiss Webster mice with heavy, long standing infections of Echinococcus granulosus with mebendazole, 50 mg/kg body weight daily for 10 days and bithionol, 70 mg/kg every other day for four doses. Necropsy performed 6 weeks after completion of therapy showed no gross or histologic differences between untreated controls and bithionol-treated mice or their cysts. Mebendazole-treated mice had a significant decrease in the total number of cysts (15 vs. 100), with many of those present being ruptured. Electron microscopy of intact, mebendazole-treated cysts revealed a marked increase in vacuolization and disarray of the distal cytoplasm, dilated and degenerating microtubules, increase in the size and number of lysosomes, a decrease in the number of normal appearing golgi, and increased density of mitochondria. Several mice died shortly after the termination of mebendazole therapy, all with ruptured cysts. Due to the large volume of the cysts, the presumed cause of death was acute volume overload, but toxic or anaphylactic reactions could not be excluded. We suggest that any proposed chemotherapy of humans with hydatid disease be done cautiously, with careful monitoring.

Long term follow-up of human hydatid disease (Echinococcus granulosus) treated with a high-dose mebendazole regimen.

Fifteen patients with inoperable hydatid disease (Echinococcus granulosus) were treated with an initial 6-week high-dose mebendazole regimen with a follow-up ranging from 3-7 years. Ten of 15 patients showed both objective and clinical improvement, although two of these 10 relapsed 1-6 years after completing therapy. Simple, single cysts in the lung and liver showed the best response. Multiple, complex cysts and bone cysts showed little or no objective improvement. One patient developed reversible neutropenia. Overall results were no better than those obtained by others with smaller doses.

Chemotherapy of experimental Echinococcus granulosus infection. Trials in CF1 mice and jirds (Meriones unguiculatus).

Mice and jirds with experimental secondary hydatidosis (Echinococus granulous) were treated at various post-infection periods with eight different drugs; iodinized oil of thymol, ethyl-N-dimethyl ether of thymol fumarate, chloroguanide, rifampin, pentamidine isethionate, amphotericin B, suramin, and methotrexate. In initial experiments with methotrexate, mice treated after 99 days of infection had significantly fewer infections at necropsy than did controls (33% and 100%, respecitively). However, in subsequent studies at three dose levels of methotrexate in mice 10 days after infection and in mice and jirds 240 days post infection, no significant differences were found in the percentage of animals infected, cyst size, or number between treated and control animals. The other drugs tested were similarly without effect under the experimental conditions used.

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.

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.

The hypertensive surgical patient. Controversies in management.

The authors use data gathered from recent clinical and laboratory studies to deal with the following six questions often facing the physician caring for hypertensive patients before, during, and after surgery. Which hypertensive patient is at increased surgical risk? When must elective surgery be delayed? Should antihypertensive medication be discontinued preoperatively? What is the ideal intraoperative blood pressure? What anesthetic techniques are best suited for hypertensive patients? Which patients are at most risk of a postoperative hypertensive crisis?

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.

Clonorchiasis in New York City Chinese.

Among 150 Chinese-born residents of New York City a single stool examination showed 26% were infected with C, sinensis. Most of those infected were immigrants from the Kwangtung Province of China. The possibility of clonorchiasis in Oriental-born residents is emphasized.

[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.