The use of ultrasound for placement of intravenous catheters

Ultrasound has been used to aid cannulation of veins of the neck, chest, antecubital fossa, and femoral vein. This investigation compared the traditional method of peripheral intravenous (IV) cannulation of veins of the hands and forearms with ultrasound-guided IV cannulation of these veins. After obtaining institutional review board approval and written informed consent, 35 adult subjects with a history or suspicion of difficult IV cannulation were prospectively enrolled with 16 subjects randomly assigned to the traditional group and 19 to the ultrasound group. Time taken for successful venous cannulation and number of attempts between the groups were compared using a Mann-Whitney U test. The number of subjects in whom IV cannulation was successful on the first attempt was compared between the groups using the Fisher exact test. No significant differences were noted between groups in demographics, time to successful cannulation, number of attempts, and number of subjects in whom IV cannulation was successful on the first attempt. Ultrasound was as efficacious as the traditional method of IV cannulation in this subset of patients. Future investigations should examine the efficacy of the ultrasound-guided technique of IV cannulation of these veins in patients in whom the traditional method failed.     

Feasibility of flow cytometry for measurements of Plasmodium falciparum parasite burden in studies in areas of malaria endemicity by use of bidimensional assessment of YOYO-1 and autofluorescence

The detection and quantification of Plasmodium falciparum in studies of malaria endemicity primarily relies upon microscopy. High-throughput quantitative methods with less subjectivity and greater reliability are needed for investigational studies. The staining of parasitized erythrocytes with YOYO-1 for flow cytometry bears great potential as a tool for assessing malaria parasite burden. Capillary blood was collected from children presenting to the pediatric ward of the Manhiça District Hospital in Mozambique for parasitemia assessment by thick and thin blood films, flow cytometry (YOYO-1_530/585), and quantitative real-time PCR (qRT-PCR). Whole blood was fixed and stained with YOYO-1 for acquisition on a cytometer to assess the frequency of infected erythrocyte events. qRT-PCR was used as the gold standard for the detection of P. falciparum. The YOYO-1_530/585 method was as sensitive and specific as conventional microscopy (area under the receiver operating characteristic, 0.9 for both methods). The interrater mean difference for YOYO-1_530/585 was near zero. Parasite density using flow cytometry and complete blood counts returned density estimates with a mean difference 2.2 times greater than results by microscopy (confidence interval, 1.46 to 3.60) but with limits of agreement between 10 times lower and 50 times higher than those of microscopy. The YOYO-1_530/585 staining pattern was established exactly as demonstrated in animal models, but the assay was limited by the lack of appropriate negative-control samples for establishing background levels and the definition of positives in areas in which malaria is endemic. YOYO-1_530/585 is a high-throughput tool with great potential if the limitations of negative controls and heterogeneous levels of background signal can be overcome.     

Image analysis of soft-tissue in-growth and attachment into highly porous alumina ceramic foam metals

The detailed quantitative characterization of soft-tissue in-growth into highly porous artificial implants is critical to understanding the biophysical processes that will lead to the best structural scaffolding construct. Previous studies have performed mechanical peel tests and mostly qualitative histological analyses of soft-tissue. The goal of this paper is to report the results obtained from applying two image analysis algorithms to quantify the morphological structure found in histological images of stained soft-tissue in-growth into alumina ceramic foam metal implants using a canine model. Three different pore sizes were used and three different post-operative time points were considered. Using the 2D Wavelet Transform Modulus Maxima method and 2D Fourier Transform analysis, a strong anisotropic signature (directional preference) is detected in early (4-week) histological samples. The direction of preference is towards the center of the implants. The strength of the anisotropy at later time points (8 and 16 weeks) becomes gradually weaker. Our interpretation is that after a short period of time, the main tissue growth activity has been concentrated on filling the artificial implant by growing towards its center. The weaker anisotropic signature found at later time points is interpreted as the tissue growth activity strengthening its structure by growing in more random directions.     

Migraine with unilateral motor symptoms: a case-control study

Objective

To characterise the clinical features of non‐familial migraine with unilateral motor symptoms (MUMS) and compare these features with those of migraine without weakness.

Methods

24 patients with MUMS and 48 matched controls were identified from a tertiary care headache centre. Using a structured interview, the migraine symptoms of both groups were characterised. Results of previously administered Beck Depression Inventories (BDI), Minnesota Multiphasic Personality Inventories and psychiatric diagnoses were collected, when available, and compared between groups.

Results

9 patients had episodic migraine and 15 had chronic migraine. Patients with MUMS always had weakness involving the arm subjectively, and both arm and leg objectively. A give‐way character was always present. Only 17% of patients with MUMS reported facial weakness; 58% reported persistent interictal weakness; 92% reported sensory symptoms. A rostrocaudal march of sensory and motor symptoms was frequently reported. Weakness was ipsilateral to unilateral headache in two thirds of the patients. Compared with controls, patients with MUMS had had similar pain intensities, but were more likely to report other migrainous symptoms, including allodynia. 38% of patients with MUMS were told they had had a stroke, and 17% believed they had had a stroke despite normal brain imaging. Patients with MUMS reported fewer affective disorders and more adjustment disorders than controls, and had similar BDI scores.

Conclusions

A syndrome of severe migraine with accompanying give‐way weakness is common in tertiary care headache centres. It is accompanied by other neurological symptoms.Migraine has a variety of subtypes, some of which are associated with hemiplegia. Aura is highly variable and is thought to be generated from many areas of the cortex or brain stem. A recent epidemiological study estimated the prevalence of both familial and sporadic hemiplegic migraine in Denmark to be 0.01%.¹ By contrast, Couch et al² reported the rate of hemiplegic symptoms to be 10% in a large tertiary care headache practice. In all, 11 of 78 patients admitted to the Thomas Jefferson University Hospital (Philadelphia, Pennsylvania, USA) for the treatment of headache reported hemiplegic symptoms, and six had hemiparesis on admission.³Of 205 subjects in Fisher''s studies of patients with late‐life migraine accompaniments, 45 had motor weakness.^4,5 All cases were accompanied by visual symptoms, paraesthesias and speech disturbances. Of 22 cases of migraine and cluster headache with limb pain accompanying the headache, six also had recurrent weakness.⁶ Sensorimotor disturbances often accompany chronic pain syndromes. Complex regional pain syndrome is often associated with allodynia, weakness and dystonia.⁷ These symptoms, along with non‐dermatomal sensory loss, have been labelled “psychogenic pseudoneurological dysfunction” by some authors.⁷ Motor impairments correlate with allodynia in complex regional pain syndrome type I.⁸Our study was designed to confirm and further characterise previous observations on motor weakness accompanying migraine headache. We postulated that unilateral motor symptoms are common in patients with migraine in a tertiary care centre, and that their presence may be due to the activation of sensorimotor programme related to the pain and presence of allodynia.     

Plasmodium falciparum-Specific Cellular Immune Responses after Immunization with the RTS,S/AS02D Candidate Malaria Vaccine in Infants Living in an Area of High Endemicity in Mozambique

Results from clinical trials in areas where malaria is endemic have shown that immunization with RTS,S/AS02A malaria vaccine candidate induces partial protection in adults and children and cellular effector and memory responses in adults. For the first time in a malaria vaccine trial, we sought to assess the cell-mediated immune responses to RTS,S antigen components in infants under 1 year of age participating in a clinical phase I/IIb trial of RTS,S/AS02D in Mozambique. Circumsporozoite protein (CSP)-specific responses were detected in approximately half of RTS,S-immunized infants and included gamma interferon (IFN-γ), interleukin-2 (IL-2), and combined IL-2/IL-4 responses. The median stimulation indices of cytokine-producing CD4⁺ and CD8⁺ cells were very low but significantly higher in RTS,S-immunized infants than in infants that received the comparator vaccine. Protection against subsequent malarial infection tended to be associated with a higher percentage of individuals with CSP-specific IL-2 in the supernatant (P = 0.053) and with higher CSP-specific IFN-γ-producing CD8⁺ T-cell responses (P = 0.07). These results report for the first time the detection of malaria-specific cellular immune responses after vaccination of infants less than 1 year of age and pave the way for future field studies of cellular immunity to malaria vaccine candidates.Malaria remains one of the major world heath problems affecting between 200 and 400 million people annually and causing 2 to 3 million deaths, mostly children and pregnant women living in sub-Saharan Africa (37). Infections by Plasmodium falciparum, one of the four species of plasmodia that affect humans, cause 80 to 90% of the malaria cases and are responsible for 95% of all malaria-associated deaths (14). Since most of the worldwide malaria burden is due to P. falciparum, efforts for prevention and eradication of malaria have focused on this parasite, and a P. falciparum-customized malaria vaccine is one of most promising tools (12, 25, 26).The most abundant and immunogenic antigen on the surface of Plasmodium sporozoites is the circumsporozoite protein (CSP), which is a target for vaccine development (9, 10, 17, 27). In vaccines based on irradiated sporozoites and CSP in human and mouse models, antibodies to circulating sporozoites, followed by cell-mediated responses to the protein after invasion of hepatocytes, have been described as crucial for the generation of protective responses (7, 11, 13, 28, 29).RTS,S is a subunit malaria vaccine candidate based on the CSP of P. falciparum that has been under study for many years. The chimeric vaccine contains a portion of the NANP-repeats, all four NVDP-repeats, and the complete carboxyl-terminal region of CSP suggested to be targets for humoral and cellular immunity, along with the amino-terminal region of HbsAg (HBS) (16). The malaria vaccine candidate RTS,S (GlaxoSmithKline, Rixensart, Belgium) formulated with the adjuvant system AS01 or AS02 has proven to confer partial protective immunity against malaria infection in malaria-naive adults (20, 21, 41), as well as in adults and infants in areas where malaria is endemic (2-6). Clinical safety, immunogenicity, and efficacy trials in infants and children have shown RTS,S/AS02 to be safe and protective and to induce high antibody titers (2, 4, 6, 34).Although the induction of a CSP-specific humoral response after RTS,S vaccination has been well described, the generation of cellular immune responses has not yet been addressed in infants or young children immunized with the RTS,S vaccine candidate. In adults, protection conferred by the RTS,S vaccine has been associated with acquisition of strong antibody and cellular responses to the CSP fragment of RTS,S (20, 22). Malaria naive volunteers immunized with RTS,S/AS02 frequently develop strong proliferative and IFN-γ-producing T-cell responses to peptides representing T-cell epitopes (Th2R and Th3R) present in the vaccine (22). A correlation between protection against experimental challenge and the CSP-specific production of IFN-γ by CD4⁺ and CD8⁺ T cells has been described in a limited number of individuals (42).Current efforts are under way to proceed to phase III clinical trials with the RTS,S vaccine, despite no currently identified immune correlates of protection for vaccination with RTS,S in infants or young children. The present study was integrated into a phaseI/IIb clinical trial of the RTS,S/AS02D candidate vaccine in infants in a rural area of malaria endemicity in Mozambique (4). We sought here to examine the cellular responses in infants vaccinated with RTS,S/AS02D and further the development of assays for use in malaria vaccine trials in infants and young children, the population most vulnerable to severe malaria.     

Ginkgo biloba and ovarian cancer prevention: epidemiological and biological evidence

There is considerable interest in herbal therapies for cancer prevention but often with little scientific evidence to support their use. In this study, we examined epidemiological data regarding effects of commonly used herbal supplements on risk for ovarian cancer and sought supporting biological evidence. 4.2% of 721 controls compared to 1.6% of 668 cases regularly used Ginkgo biloba for an estimated relative risk (and 95% confidence interval) of 0.41 (0.20,0.84) (p=0.01); and the effect was most apparent in women with non-mucinous types of ovarian cancer, RR=0.33 (0.15,0.74) (p=0.007). In vitro experiments with normal and ovarian cancer cells showed that Ginkgo extract and its components, quercetin and ginkgolide A and B, have significant anti-proliferative effects ( approximately 40%) in serous ovarian cancer cells, but little effect in mucinous (RMUG-L) cells. For the ginkgolides, the inhibitory effect appeared to be cell cycle blockage at G0/G1 to S phase. This combined epidemiological and biological data provide supportive evidence for further studies of the chemopreventive or therapeutic effects of Ginkgo and ginkgolides on ovarian cancer.