A comparison of pre-operative nerve stimulator-guided femoral nerve block and fascia iliaca compartment block in patients with a femoral neck fracture.

We undertook a randomised, controlled trial to compare the analgesic efficacy and opioid sparing effect of nerve stimulator-guided femoral nerve block with fascia iliaca compartment block in patients awaiting surgery for fractured neck of femur. Ten-centimetre visual analogue pain scores were measured before and 2 h after the block and opioid consumption was recorded in the 12-h period after the block. One hundred and ten patients were randomly assigned. Femoral nerve block provided superior pre-operative analgesia for fractured neck of femur compared with fascia iliaca compartment block. The difference in the mean reduction of pain score after the block was 0.9 (95% CI 0-1.8); p = 0.047. Patients receiving a femoral nerve block required less morphine after the block than those receiving fascia iliaca compartment block (p = 0.041).

Encephalitis and neuronal necrosis in a 3-month-old suckled beef calf.

A 3-month-old suckled beef calf from the west coast of Scotland showed neurologic clinical signs for 1 week and was euthanized after failing to respond to treatment. Blood and tissue samples, including the brain, were submitted for diagnosis. Histologic examination of the brain showed neuronal chromatolysis and necrosis in the hind brain and loss of Purkinje cells in the cerebellum, accompanied by mild nonsuppurative encephalitis in the hind brain with a striking lack of inflammation in the cerebellar layers. Other microscopic lesions present were mild nonsuppurative meningitis with perivascular cuffs, diffuse hypergliosis, and occasional foci of neuronophagia. Polymerase chain reaction amplification of viral nucleic acids and specific immunohistochemical labeling allowed the identification of louping ill virus, and serology showed high titers of immunoglobulin M, indicating a recent infection.

Distribution and possible sources of polycyclic aromatic hydrocarbons (PAHs) and metals in marine surface sediments off northern Mozambique.

Liquid natural gas (LNG) exploration has started off the coast of northern Mozambique, in the Rovuma Basin, East Africa. In advance of gas production, we collected in 2018 over 100 samples of surface sediments from 40 locations in the pristine and exploration areas at water depths of 5-2000 m. We have determined the levels of hydrocarbons (total hydrocarbon contents (THC) and 49 individual PAHs), heavy metals, arsenic, grain size and total organic carbon. While sediment composition varied strongly from coarse sediment to high mud contents (<63 µm), background levels of hydrocarbons and metals were found in most samples. We found anthropogenic contamination at one site in Pemba harbor. We observed no petroleum-related contamination, including the Palma area with numerous exploration wells. Elevated concentrations of barium and THC at some locations in this area are attributed to drilling activities but are not considered to be of environmental concern.

Combining site specificities of mouse hybridoma antibodies to dextran B1355S.

The combining sites of 12 mouse hybridoma antibodies to dextran B1355S have been characterized by quantitative precipitin assay. All antibodies preferentially bind the immunizing antigen B1355S and two other class I dextrans, B1498S and B1501S, but show substantial differences in the extents to which they cross react with class I dextrans, suggesting their clustering into five groups. Three myeloma proteins, CAL20 TEPC1035, J558, and MOPC104E, which bind dextran B1355S, each fall into a different group. There appears to be a substantial, but imperfect, correlation of DH region structure and individual idiotypic determinants with dextran binding patterns. Proteins with RY DH segments and IdI (J558) idiotypes are in groups 1 or 3, and proteins with YD DH segments and IdI (MOPC104E) idiotypes are exclusively in group 5. However, identical patterns of precipitin curves accompany very different sequences in CDR3. Antibodies of group 1, which react only with class II dextrans, differ the most in primary sequence, a finding suggesting that subsites responsible for cross reactivity with class I dextrans may be blocked and that this may be effected by side chains of different amino acids. This finding delineates a new aspect of the relationship of variability in amino acid sequence to antibody complementarity.

Prevalence of upper-body symptoms following breast cancer and its relationship with upper-body function and lymphedema.

This investigation describes the prevalence of upper-body symptoms in a population-based sample of women with breast cancer (BC) and examines their relationships with upper-body function (UBF) and lymphedema, as two clinically important sequelae. Australian women (n=287) with unilateral BC were assessed at three-monthly intervals, from six to 18 months post-surgery (PS). Participants reported the presence and intensity of upper-body symptoms on the treated side. Objective and self-reported UBF and lymphedema (bioimpedance spectroscopy) were also assessed. Approximately 50% of women reported at least one moderate-to-extreme symptom at 6- and at 18-months PS. There was a significant relationship between symptoms and function (p < 0.01), whereby perceived and objective function declined with increasing number of symptoms present. Those with lymphedema were more likely to report multiple symptoms, and presence of symptoms at baseline was associated with an increased risk of lymphedema (ORs > 1.3, p = 0.02), although presence of symptoms explained only 5.5% of the variation in the odds for lymphedema. Upper-body symptoms are common and persistent following breast cancer and are associated with clinical ramifications, including reduced UBF and increased risk of developing lymphedema. However, using the presence of symptoms as a diagnostic indicator or prognosticator of lymphedema has its limitations.

The First Record of Aedes vittatus (Diptera: Culicidae) in the Dominican Republic: Public Health Implications of a Potential Invasive Mosquito Species in the Americas.

Aedes vittatus Bigot is distributed throughout Africa, tropical Asia, and southern Europe and occurs in sylvatic as well as peridomestic environments where it readily feeds on humans. Although the vectorial capacity of Ae. vittatus is not well understood, this species is known to play a role in the maintenance and transmission of yellow fever, Zika, chikungunya, and dengue virus within its native range. In October 2019, after a routine inspection of mosquito-breeding containers in Jarabacoa, Dominican Republic, two Ae. vittatus females were captured via human landing catch method. After this finding, a CDC miniature light trap was deployed at the point of initial detection from 18:00 to 08:00 h, 2 d/wk from 3 to 31 October 2019. Potential larval habitats were also sampled via traditional dip method once per week spanning a 150 m radius from point of initial detection. In addition to the 2 adult females, 10 female and 2 male Ae. vittatus were captured. One Ae. vittatus larva also was found in a small puddle formed by an animal hoof print. Conventional PCR and Sanger sequencing were used to confirm morphological identification of collected specimens. This is the first detection of Ae. vittatus in the Dominican Republic as well as the Americas. Therefore, enhanced surveillance is needed to better understand the range and public health risks this potential invasive mosquito species may pose in the Dominican Republic, other Caribbean Islands, and/or the Americas.

Coordinated expression of matrix Gla protein is required during endochondral ossification for chondrocyte survival.

Matrix Gla protein (MGP) is a 14-kD extracellular matrix protein of the mineral-binding Gla protein family. Studies of MGP-deficient mice suggest that MGP is an inhibitor of extracellular matrix calcification in arteries and the epiphyseal growth plate. In the mammalian growth plate, MGP is expressed by proliferative and late hypertrophic chondrocytes, but not by the intervening chondrocytes. To investigate the functional significance of this biphasic expression pattern, we used the ATDC5 mouse chondrogenic cell line. We found that after induction of the cell line with insulin, the differentiating chondrocytes express MGP in a stage-specific biphasic manner as in vivo. Treatment of the ATDC5 cultures with MGP antiserum during the proliferative phase leads to their apoptosis before maturation, whereas treatment during the hypertrophic phase has no effect on chondrocyte viability or mineralization. After stable transfection of ATDC5 cells with inducible sense or antisense MGP cDNA constructs, we found that overexpression of MGP in maturing chondrocytes and underexpression of MGP in proliferative and hypertrophic chondrocytes induced apoptosis. However, overexpression of MGP during the hypertrophic phase has no effect on chondrocyte viability, but it does reduce mineralization. This work suggests that coordinated levels of MGP are required for chondrocyte differentiation and matrix mineralization.

Linkage of early-onset familial breast cancer to chromosome 17q21.

Human breast cancer is usually caused by genetic alterations of somatic cells of the breast, but occasionally, susceptibility to the disease is inherited. Mapping the genes responsible for inherited breast cancer may also allow the identification of early lesions that are critical for the development of breast cancer in the general population. Chromosome 17q21 appears to be the locale of a gene for inherited susceptibility to breast cancer in families with early-onset disease. Genetic analysis yields a lod score (logarithm of the likelihood ratio for linkage) of 5.98 for linkage of breast cancer susceptibility to D17S74 in early-onset families and negative lod scores in families with late-onset disease. Likelihood ratios in favor of linkage heterogeneity among families ranged between 2000:1 and greater than 10(6):1 on the basis of multipoint analysis of four loci in the region.

Clinical detection of caries in the primary dentition with and without bitewing radiography.

BACKGROUND: Inadequate detection of caries in the primary dentition due to non-use of bitewing radiography is commonly encountered in paediatric practice. The present study investigated the increased benefits of using bitewing radiography in addition to the visual-tactile examination technique for detection of primary dentition caries in a non-fluoridated community, and determined the prevalence of "hidden" occlusal caries in the primary dentition. METHODS: Primary teeth were scored for caries at the restorative threshold using a visual-tactile technique followed by bitewing radiographic examination in a sample of 611 schoolchildren aged 6.4 +/- 0.5 yrs to 12.1 +/- 0.8 yrs residing in a non-fluoridated city. RESULTS: Overall, at the restorative threshold, the visual-tactile technique could detect 62 per cent of occlusal caries compared to 74 per cent for bitewing radiography (p < 0.001). The prevalence of "hidden" occlusal caries was 12 per cent. In contrast, for primary molar proximal surface caries, the visual-tactile technique could detect only 43 per cent of caries compared with 91 per cent for bitewing radiography (p < 0.001). CONCLUSIONS: In the primary dentition, use of bitewing radiography increases the detection rate of proximal surface caries substantially. It is recommended that bitewing radiography be included as part of the routine examination of children with proximal surfaces that cannot be visualized.

A controlled study of risk factors for enamel hypoplasia in the permanent dentition.

PURPOSE: The purpose of this study was to investigate risk factors for enamel hypoplasia (EH) and enamel opacity (EO) in the permanent teeth of healthy schoolchildren from a nonfluoridated community in Australia. METHODS: Children with EH (N=104) or EO (N=104) were compared with matched controls without enamel defects (N=105). Subjects who previously resided in on optimally fluoridated town provided data on the effects of drinking fluoridated water. RESULTS: The main risk factors for EH were low socioeconomic status (P < .04), respiratory infections (P < .001), exposure to cigarette-smoking (P = .001), asthma (P = .007), otitis media (P = .01), urinary tract infection (UTI; P = .03) and chickenpox (P = .001). Combinations of either chickenpox and UTI or chickenpox and exposure to cigarette-smoking were associated with relatively high numbers of EH. While use of adult toothpaste (1000 ppm) at 0 to 3 years old increased risks for EH, there were less EO in children who used child toothpaste (300 ppm fluoride, 86% vs. 95%; P = .02) or who drank optimally fluoridated water compared to those who did not (4% vs. 29%; P < .001). CONCLUSIONS: Children with low socioeconomic status, histories of respiratory or chickenpox infections, exposure to cigarette-smoking, urinary tract infections, otitis, and use of adult toothpaste are predisposed to enamel hypoplasia. By contrast, drinking optimally fluoridated water at 0 to 3 years old reduces the risk for enamel opacities.

Treatment for upper-limb and lower-limb lymphedema by professionals specializing in lymphedema care.

Up to 60% of patients with cancer of the vulva, and between 20 and 30% of patients with breast or abdominal cancers may develop lymphedema following treatment. The aims of this study were to assess health professionals' knowledge about treatment, diagnostic procedures, advice and confidence in treatment of patients with either upper-limb (ULL) or lower-limb lymphoedema (LLL), and whether these differed by health professionals' background or for patients with ULL compared with LLL. A cross-sectional telephone interview was undertaken in 2006, of 63 health professionals (response rate 92.6%) known to treat lymphedema. Sixty-three per cent of the health professionals were physiotherapists; the majority were university-trained, with 20 years' experience or more. Ninety-five per cent of health professionals used circumferential measurements to establish lymphedema status, and most health professionals advised avoiding scratches and cuts (100%), insect bites (98.4%), sunburn (98.4%) and excessive exercise (65.1%) on the affected limb. Health professionals reported that compared with patients with LLL, patients with ULL were more likely to present within the first 3 months of being symptomatic (P < 0.01). Patients with LLL were more likely to present with swelling (P = 0.001), heaviness (P = 0.003), tightness (P = 0.007) and skin problems (P < 0.001) compared with patients with ULL. Treatment and advice differed according to health professionals' background, but not location of lymphedema (ULL vs. LLL). Assessment, treatment and advice for lymphedema vary across professional groups. Our results suggest that improvements should be attempted in the early detection of lymphedema, in particular of LLL among cancer patients.

Lymphedema secondary to breast cancer: how choice of measure influences diagnosis, prevalence, and identifiable risk factors.

Research on secondary lymphedema primarily uses indirect methods for diagnosis. This paper compares prevalence and cumulative burden following breast cancer surgery, as well as personal, treatment, and behavioral characteristics associated with lymphedema, using different assessment techniques. Lymphedema status was assessed at three-monthly intervals between six- and 18-months post-surgery in a population-based sample of Australian women with recently diagnosed, unilateral, invasive breast cancer, using three methods: bioimpedance spectroscopy (BIS), difference between sum of arm circumferences (SOAC) and self-report. Depending on the method, point prevalence ranged between 8 to 28%, with 1 in 5 to 2 in 5 women experiencing lymphedema at some point in time. Of those with lymphedema defined by BIS, almost 40%-60% went undetected, and 40%-12% were misclassified as having lymphedema, based on self-report and SOAC, respectively. The choice of measure also had significant implications for identified risk factors. Over 10 characteristics were associated with lymphedema, however only one, experiencing other upper-body symptoms at baseline, influenced odds of lymphedema across all three methods. These findings highlight that secondary lymphedema poses a significant public health problem. Utilizing the most accurate and reliable method for assessment is crucial to advance our understanding of preventive and treatment strategies.

Spontaneous resolution of acute cranial subdural hematomas.

Acute cranial subdural hematoma (SDH) represents a common consequence of traumatic brain injury. The vast majority of acute SDHs larger than 10mm in thickness require immediate surgical evacuation. In rare occasions, however, spontaneous resolution may occur. In our current communication, we present four cases of spontaneous resolution of acute cranial SDH. Further more, the proposed theories explaining spontaneous resolution of acute SDH, as well as, clinical parameters and imaging characteristics that might predict such phenomenon, are also reviewed. The possibility of spontaneous resolution of an acute SDH, although remote, may impact the decision making process regarding the management of these patients under certain conditions.

Phase I trial of Taxotere: five-day schedule.

BACKGROUND: Taxotere, a semisynthetic compound structurally related to taxol, has a broad spectrum of activity in murine transplantable tumors; in the B16 melanoma model, it caused a total log cell kill 2.5 times greater than that caused by taxol at equitoxic doses. PURPOSE: We conducted a phase I study of Taxotere (a) to determine its qualitative and quantitative toxic effects and a starting dose for phase II trials, (b) to investigate its clinical pharmacology, and (c) to document its antitumor activity. METHODS: Taxotere was given as a 1-hour infusion at a starting dose of 1 mg/m2 per day for 5 consecutive days. The 5-day course of therapy was repeated every 21 days. Thirty-nine cancer patients with advanced disease were entered in the study; at least three patients were entered at each dose level. Initial dose escalations were planned at 100% increments until biologic activity was observed; subsequent escalations were planned at 50% increments until grade 2 toxicity (the National Cancer Institute's Common Toxicity Criteria) occurred and then at 25% increments until the maximum tolerated dose was established. RESULTS: Thirty-nine patients were entered in the study. Successive dose levels used were 1, 4, 8, 16, 12, and 14 mg/m2 per day. The dose-limiting toxic effects were granulocytopenia and concurrent mucositis. Grade 4 granulocytopenia associated with grade 3 mucositis developed in six of 12 patients treated at a dose of 16 mg/m2 per day, two of 10 treated at 12 mg/m2 per day, and two of eight treated at 14 mg/m2 per day. Because these toxic effects occurred concurrently, all patients so affected developed neutropenic fevers and required hospitalization. Neither cardiac nor neurologic toxic effects were noted. Anti-tumor activity was observed in six patients with ovarian cancer and in one with breast carcinoma. Although pharmacokinetic parameters were consistent between day 1 and day 5 for individual patients, considerable variation existed among those treated at the same dose level. A relationship was observed between the area under the curve for plasma concentration of drug x time (AUC) on day 1 and the percentage decrease in absolute granulocyte counts. CONCLUSION: Granulocytopenia associated with oral mucositis is the dose-limiting toxicity of this schedule. We recommended a starting dose of 14 mg/m2 per day for phase II studies of this 5-day schedule. Dose modifications on days 2-5 based on the day-1 AUC may allow individualized dosing.

Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 and association with breast cancer among African Americans.

We examined the role of constitutional genetic variation at the UDP-glucuronosyltransferase (UGT) 1A1 locus in breast cancer susceptibility. The UGT1A1 enzyme is a major UGT involved in estradiol glucuronidation. To date, four UGT1A1 variant alleles characterized by a variation in the number of TA from five through eight repeats in the atypical TATA box region have been described in the African-American population. Functional analyses of the transcriptional activity in breast and liver cells revealed that the transcription activation of a reporter gene is inversely correlated with the number of repeats. Reverse transcription-PCR analysis confirmed the expression of UGT1A1 in human liver in the hepatocarcinoma cell line HepG2 and provided evidence of the expression of UGT1A1 in breast cancer tissue, where a positive signal was observed in 11 of 12 breast cancer cell lines tested. The population-based case-control study involved 200 women with breast cancer and 200 female controls of African ancestry. We postulated that breast cancer cases might have a higher prevalence of low activity allele-containing genotypes than controls (alleles presenting seven and eight repeats in the A(TA)nTAA motif of the TATA box). The age-adjusted odds ratio (OR) for breast cancer comparing women with seven and eight allele-containing genotypes versus 5/5, 5/6, and 6/6 genotypes was 1.8 [95% confidence interval (CI), 1.0-3.1; P = 0.06] in premenopausal women and 1.0 (95% CI, 0.5-1.7; P = 0.9) in postmenopausal women. The observed 1.8-fold elevated risk in premenopausal women with invasive breast cancer is highly suggestive of a possible interaction between UGT genotype and hormones. Additional analyses suggested a stronger association of UGT1A1 genotype with estrogen receptor (ER)-negative breast cancer. Among premenopausal women, the association was stronger for ER- breast cancer (OR, 2.1; 95% CI, 1.0-4.2; P = 0.04) than ER+ breast cancer (OR, 1.3; 95% CI, 0.6-3.0; P = 0.5). The OR was slightly stronger among women who used oral contraceptives, and the association remained null in postmenopausal women, regardless of whether they took hormone replacement therapy. Our current findings suggest that further investigations are warranted to elucidate the role of UGT1A1 in breast cancer risk.

Phase I trial and clinical pharmacology of elsamitrucin.

Elsamitrucin (BMY-28090) is an antitumor antibiotic first described in 1985 that has significant oncolytic activity against a number of murine tumors including P388, L1210, B16 and M5076, as well as against MX1 and HCT116 xenografts. Preclinical toxicology studies of elsamitrucin revealed edema of multiple organs associated with hypoproteinemia and, at lethal doses, severe multiorgan toxicity. We conducted a phase I clinical trial (31 patients) of elsamitrucin administered as a 10-min i.v. infusion every 3 weeks. The starting dose (0.6 mg/m2) was 1/3 of the dog low toxic dose. The maximum tolerated dose was 30 mg/m2. Dose-limiting toxicity was reversible hepatic dysfunction manifested by elevated transaminase levels not associated with bilirubin, alkaline phosphatase, or lactate dehydrogenase elevations. Other toxicities included nausea, vomiting, malaise, and phlebitis. Because the hepatic toxicity was brief and reversible, a subsequent study (18 patients) was conducted with elsamitrucin administered every 2 weeks. Reversible grade 3 hepatotoxicity was again observed at 30 mg/m2. Plasma and urine samples from patients receiving doses of 0.6-36 mg/m2 were analyzed for drug content. The maximum plasma concentration and area under the plasma concentration versus time curve values increased linearly with doses up to 25 mg/m2 but not at higher doses. The terminal half-lives, total body clearances, and volume of distribution were 36-60 h, 10-19 liters/h/m2, and 400-1100 liters/m2, respectively. Less than 5% was excreted in the urine in 24 h as parent compound. Bile was collected from one patient with an indwelling biliary catheter. Approximately 22% of the dose was excreted in 48 h, suggesting that biliary excretion of elsamitrucin may be an important route of drug elimination. Based on reversible hepatic toxicity, the phase II recommended dose of elsamitrucin is 25 mg/m2 every 2 weeks.

Identification and characterization of two novel SH2 domain-containing proteins from a yeast two hybrid screen with the ABL tyrosine kinase.

To further our understanding of the molecular mechanism of Bcr-Abl mediated transformation, a yeast two hybrid screen was used to identify proteins binding to the Abl tyrosine kinase. Two partial cDNAs encoding novel SH2 domain-containing proteins were cloned and designated Shd and She. Both have homology to Shb, a previously reported SH2 domain-containing protein. Northern blot analysis showed that She is expressed in heart, lung, brain, and skeletal muscle, while expression of Shd is restricted to the brain. The deduced amino acid sequence of the full length mouse Shd cDNA contains an amino-terminal proline-rich region, and a carboxyterminal SH2 domain. A bacterially expressed Shd domain bound multiple tyrosine-phosphorylated proteins with relative molecular weights of 200, 170, 130, 100, 90, 78, 72 and 32 kDa from K562 cell lysates. Shd contains five YXXP motifs, a substrate sequence preferred by Abl tyrosine kinases. Shd was tyrosine phosphorylated in COS-7 cells co-transfected with Shd and c-Abl or Bcr-Abl. These results suggest that Shd may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system.

Linkage of the cholesteryl ester transfer protein (CETP) gene to LDL particle size: use of a novel tetranucleotide repeat within the CETP promoter.

BACKGROUND: A preponderance of small, dense LDL particles, elevated levels of plasma triglycerides (TG), and low levels of HDL characterize the atherogenic lipoprotein phenotype, which is associated with increased coronary artery disease (CAD) risk. Genetic and environmental factors influence LDL size, cholesteryl ester transfer protein (CETP) being one of the candidate genes. CETP mediates the transfer of cholesteryl ester from HDL to apolipoprotein (apo) B-containing lipoproteins in exchange for TG, promoting reverse cholesterol transfer and remodeling of lipoprotein particles. METHODS AND RESULTS: We have identified a tetranucleotide repeat (fragment sizes from 324 to 464 bp; heterozygosity index = 0.74) within the CETP promoter and used it in quantitative sib-pair linkage analysis in 119 female dizygotic (DZ) twins. Linkage was found to LDL size (P<0.001), TG (P<0.005), and plasma apoB (P = 0.02). The distribution of the tetranucleotide repeats was bimodal, and there was strong allelic association of the "short" alleles with the B2 allele of CETP TaqIB polymorphic site (P<0.001). CONCLUSIONS: This report of linkage of the CETP gene to LDL particle size adds to the list of candidate genes linked to LDL size, supporting the hypothesis of multigenic determination of LDL size heterogeneity. Whether this promoter variation is itself functional or is a marker for a functional site in the CETP gene remains to be determined.

Self-adhesive preapplied electrode pads for defibrillation and cardioversion.

The efficacy of self-adhesive electrode pads for defibrillation and cardioversion was assessed in 80 patients who received 267 shocks from self-adhesive pads. In all but two patients, defibrillation or cardioversion was achieved at least once. The pads were equally effective when used in the apex-anterior or apex-posterior position. The transthoracic impedance using self-adhesive pads was 75 +/- 21 ohms (mean +/- standard deviation), which is similar to previously reported transthoracic impedance in defibrillation, using standard hand-held electrode paddles of 67 +/- 36 ohms. It is concluded that self-adhesive electrode pads are effective for defibrillation and cardioversion.