Pathology of congenital Zika syndrome in Brazil: a case series

Zika virus is an arthropod-borne virus that is a member of the family Flaviviridae transmitted mainly by mosquitoes of the genus Aedes. Although usually asymptomatic, infection can result in a mild and self-limiting illness characterised by fever, rash, arthralgia, and conjunctivitis. An increase in the number of children born with microcephaly was noted in 2015 in regions of Brazil with high transmission of Zika virus. More recently, evidence has been accumulating supporting a link between Zika virus and microcephaly. Here, we describe findings from three fatal cases and two spontaneous abortions associated with Zika virus infection.

Long-term stability of the Leksell Gamma Knife® Perfexion™ patient positioning system (PPS).

PURPOSE: To assess the long-term mechanical stability and accuracy of the patient positioning system (PPS) of the Leksell Gamma Knife(®) Perfexion™ (LGK PFX). METHODS: The mechanical stability of the PPS of the LGK PFX was evaluated using measurements obtained between September 2007 and June 2011. Three methods were employed to measure the deviation of the coincidence of the radiological focus point (RFP) and the PPS calibration center point (CCP). In the first method, the onsite diode test tool with single diode detector was used together with the 4 mm collimator on a daily basis. In the second method, a service diode test tool with three diode detectors was used biannually at the time of the routine preventive maintenance. The test performed with the service diode test tool measured the deviations for all three collimators 4, 8, and 16 mm and also for three different positions of the PPS. The third method employed the conventional film pin-prick method. This test was performed annually for the 4 mm collimator at the time of the routine annual QA. To estimate the effect of the patient weight on the performance of the PPS, the focus precision tests were also conducted with varying weights on the PPS using a set of lead bricks. RESULTS: The average deviations measured from the 641 daily focus precision tests were 0.1 ± 0.1, 0.0 ± 0.0, and 0.0 ± 0.0 mm, respectively, for the 4 mm collimator in the X (left/right of the patient), Y (anterior/posterior of the patient), and Z (superior/inferior of the patient) directions. The average of the total radial deviations as measured during ten semiannual measurements with the service diode test tool were 0.070 ± 0.029, 0.060 ± 0.022, and 0.103 ± 0.028 mm, respectively for the central, long, and short diodes for the 4 mm collimator. Similarly, the average total radial deviations measured during the semiannual measurements for the 4, 8, and 16 mm collimators and using the central diode were 0.070 ± 0.029, 0.097 ± 0.025, 0.159 ± 0.028 mm, respectively. The average values of the deviations as obtained from the five annual film pin-prick tests for the 4 mm collimator were 0.10 ± 0.06, 0.06 ± 0.09, and 0.03 ± 0.03 mm for the X, Y, Z stereotactic directions, respectively. Only a minor change was observed in the total radial deviations of the PPS as a function of the simulated patient weight up to 202 kg on the PPS. CONCLUSIONS: Excellent long-term mechanical stability and high accuracy was observed for the PPS of the LGK PFX. No PPS recalibration or any adjustment in the PPS was needed during the monitored period of time. Similarly, the weight on the PPS did not cause any significant disturbance in the performance of the PPS for up to 202 kg simulated patient weight.

Cloning and expression of human HBP1, a high mobility group protein that enhances myeloperoxidase (MPO) promoter activity.

Factors which regulate transcription in immature myeloid cells are of great current interest for the light they may shed upon myeloid differentiation. In the course of screening for transcription factors which interact with the human myeloperoxidase (MPO) promoter we, for the first time, identified and cloned the cDNA and genomic DNA for human HBP1 (HMG-Box containing protein 1), a member of the high mobility group of non-histone chromosomal proteins. HBP1 cDNA was initially cloned from rat brain in 1994, but its presence in human cells or in myeloid tissue had not been described previously. The sequence of human HBP1 cDNA shows 84% overall homology with the rat HBP1 cDNA sequence. We have subsequently cloned the gene, which is present as a single copy, 25 kbp in length. Northern blotting reveals a single 2.6 kb mRNA transcript which is expressed at higher levels in human myeloid and B lymphoid cell lines than in T cell lines tested and is present in several non-myeloid human cell lines. Comparison of the mRNA and genomic sequences reveals the gene to contain 10 exons and 9 introns. The sequence of human HBP1 mRNA contains a single open reading frame, which codes for a protein 514 amino acids in length. The amino acid sequence specified by the coding region shows 95% homology with the rat HBP1 protein. The human protein sequence exhibits a putative DNA-binding domain similar to that seen in rat HBP1 and shows homology with the activation and repressor domains previously demonstrated in the rat protein. We have expressed human HBP1 protein both in vitro and in prokaryotic and eukaryotic cells. The expressed fusion protein binds to a sequence in a functionally important region within the basal human MPO promoter. In transient co-transfection experiments HBP1 enhances MPO promoter activity. Human HBP1 appears to be a novel transcription factor which is likely to play an important role in regulating transcription in developing myeloid cells.

Prevalence of hepatitis C virus seropositivity among hospitalized US veterans.

BACKGROUND: Hepatitis C virus (HCV) is a major cause of acute and chronic hepatitis in the United States and abroad. HCV antibody prevalences ranging from 10 to 90% have been reported in intravenous drug abusers, hemodialysis patients, and persons suffering from other liver diseases, whereas HCV seropositivity rates for volunteer-blood donor populations are generally under 1%. However no information has been available concerning the prevalence of HCV in general hospital populations in the United States. METHODS: We examined the rate of HCV seropositivity in 530 patients admitted to the Atlanta VA Medical Center between November 1993 and November 1994. The test population consisted of 400 random hospital admissions, 100 successive admissions to the surgical service, and 30 random admissions to the gastrointestinal service. Serum samples were assayed for HCV antibodies by a second generation EIA, and all repeat reactives were re-examined using a supplemental research assay to confirm the presence of HCV antibodies. Complete chart reviews were carried out on all HCV seropositive patients and on 100 HCV seronegative patients. RESULTS: Sixty-two of the 530 patients tested (11.7%) were repeatedly positive for HCV antibodies. Of these 62 repeat reactives, 56 (90.3%) were positive and 3 others (4.8%) indeterminate by the supplemental assay. The HCV seropositivity rate after supplemental testing was 11.8% for random admissions, 5.0% for surgical admissions, and 13.3% for patients admitted to the gastroenterology service. HCV-associated risk factors in HCV seropositive patients included a history of intravenous drug abuse, current or previous alcohol abuse, previous or concurrent liver disease, previous blood transfusions, hemodialysis, and multiple sex partners or unsafe sex. CONCLUSIONS: HCV infection may be more prevalent among hospitalized VA patients (and among other US hospital populations) than previously expected.

Comparison of carcinoembryonic antigen in tissue and serum with grade and stage of colon cancer.

BACKGROUND: Serial plasma carcinoembryonic antigen (CEA) levels are routinely used to detect postoperative recurrence of colon cancers. However, levels of intrinsic CEA production by individual tumors, which might be helpful for interpreting serum CEA levels, are not routinely available. MATERIALS AND METHODS: CEA levels were determined in twenty tissue biopsy specimens of colon carcinoma and sixteen normal colonic tissue specimens from India, by immunohistochemistry (IH) and by quantitative enzyme immunoassay (EIA). Serum samples from 62 colon cancer patients and 25 healthy blood donors were analyzed for CEA by EIA. RESULTS: Tissue CEA levels were highest for well differentiated adenocarcinomas (5.2-37 micrograms/g protein) with progressively lower levels seen in moderately differentiated and poorly differentiated tumors, and in normals. The intensity of immunostaining paralleled the levels determined quantitatively. Mean serum CEA levels were 1.5 ng/ml for normals and 4.2, 6.4, 23, and 102 ng/ml for Dukes' A, B, C and D stage tumors, respectively. CONCLUSION: Preoperative serum CEA levels do not, in themselves, take into account differences in CEA production between individual tumors. Determination of tumor CEA content by quantitative or immunohistochemical methods, could be a useful adjunct for the clinical management of colon carcinoma, by improving interpretation of serum CEA levels.

New procedures for tightening knee collateral ligaments in conjunction with knee realignment osteotomy.

Collateral ligament laxity has recently been recognized as an important component of frontal plane malalignment. The authors have developed new surgical techniques to re-tension lax collateral ligaments. Twenty-three collateral ligament re-tensioning with bony alignment were carried out in 17 patients, with 19 knees being graded excellent, 2 fair, and 2 poor. Recurrence of significant laxity was noted in one patient.

X-ray doses to patients undergoing full-spine radiographic examination.

Patients undergoing full-spine radiographic examinations receive x-ray doses of 115 mrad (1,150 microGy) to 85% of the body's total active bone marrow, 235 to 465 mrad (2,350 to 4,650 microGy) to the breasts, 165 mrad (1,650 microGy) to the embryo and ovaries, and 700 mrad (7,000 microGy) to the thyroid. These doses can be doubled for patients exposed to the x rays before and after treatment.

Single port technique of mantle field treatment in Hodgkin's disease using very high energy x-ray beams.

Treatment pd irradiation of Hodgkin's disease is described indicating the advantage of this energy range and the appropriate dose build-up modifications necessary to achieve a single port irradiation technique.

Variation of percentage depth dose with beam area of 43 MV roentgen ray beam from a betatron.

The central axis percentage depth dose of a 43 MV roentgen ray beam from a betatron, is found to decrease with increasing beam area at depths more than the depth of maximum dose build-up. At depths less than the depth of maximum dose build-up, a reverse trend is seen. This type of variation of central axis percentage depth dose with beam area is found due to the presence of extraneous radiation originating in the field flattening filter (compensator) and the collimator of the betatron.

Biological effects evaluated as a function of patient thickness, beam quality, SSD,and treatment schedule.

Continuing efforts are being made by clinical radiotherapists to evaluate radiationcomplications to normal tissue and organs by specific time-dose parameters. Currently,the NSD concept of Ellis is receiving wide application in the literature in the reporting of radiation complications and normal tissue tolerances. To afford an easy and broad application of the NSD concept to the evaluation of physiological, functional, or structural changes, the authors have evolved mathematical expressions for the calculations of NSD as a function of patient thickness, beam energy, SSD, and treatment schedule involving coplanar field arrangements whether the fields are treated alternately or simultaneously. Several interesting aspects evolving form the concepts of treatment planning interms of the NSD or biological effects indicate that 1) for beam energies above 22 MeV, treatment is more ideally performed by treating only one field per day, since the depth of electronic equiliberium provides more effective sparing of superficial organs andtissues; 2) large-field therapy, such as the total nodal irradiation of Hodgkin'sdisease, can be more effectively treated in terms of tissue sparing by higher energy beamsthan cobalt-60 or 4-MeV for practically all patient dimensions; 3) a new concept ofintegral biological dose,the "gram-ret", is proposed, which represents the quantitation of total biological effect; 4) a series of tables with multiplication factors programmed on a digital computeris presented, which very quickly make available the NSD in any fractionated radiation treatment cycle to any plane of the body as a fuction of the beam energy, SSD, patient thickness, and continuous or split-course therapy schedule.