Phase I study of capecitabine combined with radioembolization using yttrium-90 resin microspheres (SIR-Spheres) in patients with advanced cancer.

BACKGROUND: This was a prospective single-centre, phase I study to document the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended phase II dose for future study of capecitabine in combination with radioembolization. METHODS: Patients with advanced unresectable liver-dominant cancer were enrolled in a 3+3 design with escalating doses of capecitabine (375-1000 mg/m(2) b.i.d.) for 14 days every 21 days. Radioembolization with (90)Y-resin microspheres was administered using a sequential lobar approach with two cycles of capecitabine. RESULTS: Twenty-four patients (17 colorectal) were enrolled. The MTD was not reached. Haematologic events were generally mild. Common grade 1/2 non-haematologic toxicities included transient transaminitis/alkaline phosphatase elevation (9 (37.5%) patients), nausea (9 (37.5%)), abdominal pain (7 (29.0%)), fatigue (7 (29.0%)), and hand-foot syndrome or rash/desquamation (7 (29.0%)). One patient experienced a partial gastric antral perforation with a capecitabine dose of 750 mg/m(2). The best response was partial response in four (16.7%) patients, stable disease in 17 (70.8%) and progression in three (12.5%). Median time to progression and overall survival of the metastatic colorectal cancer cohort was 6.4 and 8.1 months, respectively. CONCLUSIONS: This combined modality treatment was generally well tolerated with encouraging clinical activity. Capecitabine 1000 mg/m(2) b.i.d. is recommended for phase II study with sequential lobar radioembolization.

Fractal Electronics for Stimulating and Sensing Neural Networks: Enhanced Electrical, Optical, and Cell Interaction Properties.

Imagine a world in which damaged parts of the body - an arm, an eye, and ultimately a region of the brain - can be replaced by artificial implants capable of restoring or even enhancing human performance. The associated improvements in the quality of human life would revolutionize the medical world and produce sweeping changes across society. In this chapter, we discuss several approaches to the fabrication of fractal electronics designed to interface with neural networks. We consider two fundamental functions - stimulating electrical signals in the neural networks and sensing the location of the signals as they pass through the network. Using experiments and simulations, we discuss the favorable electrical performances that arise from adopting fractal rather than traditional Euclidean architectures. We also demonstrate how the fractal architecture induces favorable physical interactions with the cells they interact with, including the ability to direct the growth of neurons and glia to specific regions of the neural-electronic interface.

A brief history of equine private practice in South Africa.

Horse breeding in South Africa started in 1652, shortly after the 1st European settlement in the Cape. African horsesickness posed a serious problem and after a devastating outbreak of the disease in 1719, horses were largely replaced by oxen for agricultural and transport purposes but remained important from a sporting and military point of view. Examples of the latter are the export of horses for military use to India in the mid-19th century and for use in the Crimean War in 1854, reaching a zenith in the Anglo-Boer war in which an estimated 450 000 horses succumbed. Research and disease control and initially also health services were the responsibility of state veterinary authorities. Private equine practice was pioneered by Jack Boswell in the late 1930s, mainly involving race horses and Thoroughbred studs as part of a general practice. Specialised equine private practices were only initiated 10 years later and developed further during the 2nd half of the 20th century. These developments are described in some detail, including resumes of the veterinarians involved, clinical challenges encountered, scientific advances as well as developments in the equine industry with the emphasis on Thoroughbreds and the racing community. The regulatory environment, especially regarding the import and export of horses, and the role of various organisations and associations are also briefly discussed.

Tolerance of nicotinamide and carbogen with radiation therapy for glioblastoma.

Nineteen patients with glioblastoma were treated with nicotinamide and carbogen and radiotherapy. Eight patients did not complete the protocol because of hepatic toxicity from phenytoin/nicotinamide drug interactions, persistent nausea or vomiting with nicotinamide, intolerance of the carbogen breathing apparatus, or other reason. In addition, early radiation neurotoxicity appeared increased.

Beta 2-glycoprotein-1 (apolipoprotein H) excretion in chronic renal tubular disorders: comparison with other protein markers of tubular malfunction.

Urinary beta 2-glycoprotein-1 was measured in 60 patients with conditions recognised as causing renal tubular impairment and compared with established markers of early tubular malfunction. Increased beta 2-glycoprotein-1 excretion was found in 49 (82%) of the subjects; raised excretion of alpha 1-microglobulin, retinol-binding protein, and beta 2-microglobulin was found in 46 (77%), 45 (75%), and 31 (52%), respectively, and increased urinary N-acetyl-beta-D-glucosaminidase activity in 32 of 54 of the subjects (59%). The increase was particularly pronounced in those with proximal tubule malfunction, although considerable variation occurred. beta 2-glycoprotein-1 was shown to be stable in urine over the physiological pH range, and it is concluded that its measurement provides a means of detecting chronic malfunction of the renal tubules that is marginally more sensitive than assays of alpha 1-microglobulin or retinol-binding protein, and more reliable than assays of beta 2-microglobulin or N-acetyl-beta-D-glucosaminidase.

A sandwich enzyme-linked immunosorbent assay for beta 2-glycoprotein I.

A solid-phase sandwich enzyme-linked immunosorbent assay for determining beta 2-glycoprotein I in urine has been developed. It has a working concentration range of 5-40 micrograms/L and a detection limit of approximately 1.4 micrograms/L. The within-plate coefficient of variation (CV) falls between 1.4% and 2.1%, and the between-batch CV ranges from 5.2 to 6.0%. Recovery of beta 2-glycoprotein I added to urine varies between 96 and 110%. The assay can also be used for determining beta 2-glycoprotein I in serum.

The use of a single case design to investigate the effect of a pre-performance routine on the water polo penalty shot.

The pre-performance routine (PPR) is proposed to assist the performance of closed skills by enhancing concentration (Crews and Boutcher, 1987) and the recall of optimal psychological and physiological states (Cohn, 1990). A multiple-baseline-across-individuals design was utilised to assess the effect of PPRs on water polo penalty shot performance. Three experienced male water polo players were assisted in designing a personalised multi-component PPR, which was rehearsed in accordance with a training program, and implemented prior to performing penalty shots in simulated trials. Mean performance scores increased for all players between pre and post intervention phases. A Split Middle analysis (White, 1974) further described performance trends and changes. Players 1 and 2 reversed negative baseline trends of -1.071 and -1.031 to positive post intervention trends of +1.011 and +1.011, producing respective positive changes in slope of +1.08 and +1.042. Player 3's baseline trend of +1.008 was reversed post intervention to -1.004, causing a negative change in slope of -1.012. Respective ratios of 1.38, 1.36 and 1.20, suggest a positive change in trend level immediately following PPR introduction. Binomial tests revealed improvements in all participant performances between stages (p<0.001). Results are reviewed in light of previous research and the utilisation of single-subject designs is discussed.

A field study of patterns of unobserved foetal loss as determined by rectal palpation in foaling, barren and maiden thoroughbred mares.

Records of 1,009 pregnancies in 574 foaling, barren and maiden Thoroughbred mares on a single stud farm, over a period of 12 years were examined. The farm is situated in the eastern Cape Province of South Africa, at an elevation of 1,800 m, and in an area of climatic extremes. Records of 604 pregnancies in 249 foaling Thoroughbred mares were examined. For these purposes, those pregnancies in which a mare conceived in the same breeding season during which she had foaled were considered as pregnancies in foaling mares. Pregnancy was confirmed by rectal palpation by a single experienced practitioner. Of the 604 pregnancies examined, conceptus attachment occurred in the horn opposite the previously gravid horn in 345 cases (57%), and in the previously gravid horn in 259 cases (43%; P less than 0.005). Unobserved foetal loss after pregnancy diagnosis amounted to 30 (9%) in the former group, while in the latter group (pregnancy established in the postgravid horn) 46 pregnancies were lost (18%; P less than 0.005). This study confirmed that conceptus attachment tends to occur in the uterine horn opposite the previously gravid horn in foaling Thoroughbred mares conceiving during the same season. A significantly higher incidence of foetal loss accompanied conceptus attachment in the postgravid horn. Of 242 pregnancies in 162 previously barren mares, 95 (39%) occurred in the left uterine horn and 147 (61%) in the right horn (P less than 0.005). The incidence of pregnancy failure in this group was 7%. The side of attachment did not affect the rate of loss. Evaluation of the records of 163 maiden mares revealed that conceptus attachment occurred in the left uterine horn in 58 (36%) pregnancies and in the right horn in 105 (64%) pregnancies (P less than 0.005), which is consistent with previously reported observations. Pregnancy failure was recorded in 4% of maiden mares. Side of attachment did not influence rate of loss in this group.

A survey of reproductive success in South African Thoroughbred horse breeding from 1975 to 1999.

The data and an analysis of the statistical summaries from the 'Return of Mares' of the General Stud Book of The Jockey Club of Southern Africa from 1975-1999 are presented. The total number of mares covered per season ranged from 7393 (1992) to 5180 (1995). The total living produce in the period surveyed was 95 317 foals. The categories of data examined include: the total number of mares covered per season; the total numbers and percentage of their living produce; the total numbers and percentage dead produce, 'slips' and foals born dead, barren and 'no return' mares; and the total number of live twins reported. The percentage live foals per season increased from 52 to 62% and the percentage barren and 'no return' mares declined from 35.50 to 28.40% over the period surveyed. The number of live twins reported showed a dramatic reduction from 156 to 5. These apparent improvements are ascribed to a combination of factors including advances in veterinary knowledge and technology. The findings are similar to those reported by similar surveys of national Thoroughbred populations from North America and Germany. There is an indication to broaden this annual survey by recording additional parameters more accurately reflecting reproductive efficiency rather than a cumulative annual total of live foals.

Suspected Tyzzer's disease in two foals.

Tyzzer's disease was diagnosed histologically in two foals, a 4-week-old Thoroughbred cross and a 6-week-old Arabian foal. Clinically both foals were in good health prior to a short illness lasting only a few hours. The liver lesions in both foals were characterized microscopically by multiple foci of necrosis. Variable numbers of elongated slender intracytoplasmic bacilli resembling Bacillus piliformis were demonstrated within hepatocytes bordering the necrotic foci.

A report on the consumption, composition and nutritional adequacy of a mixture of lush green perennial ryegrass (Lolium perenne) and cocksfoot (Dactylis glomerata) fed ad libitum to Thoroughbred mares.

Non-pregnant Thoroughbred mares were stabled and subjected to 2 trials, each 24 h in duration, to establish their total consumption of a mixture of freshly cut, lush green perennial ryegrass (Lolium perenne) and cocksfoot (Dactylis glomerata) in approximately equal proportions; and to compare the total intake of crude protein, calcium, phosphorus and mass of the grass mixture on a dry matter basis with their daily nutritional requirements. The body mass of each mare was calculated at the commencement of each trial. In the first trial 2 lactating mares with foals at foot, 65 days and 8 days of age, and one mature non-lactating mare, consumed 75,5 kg, 61,0 kg and 39,5 kg of the grass mixture, cut in the early vegetative stage, respectively. The perennial ryegrasss (L. perenne) contained 79,63% moisture, 1,67% crude protein, 0,75% calcium, 0.057% phosphorus and 20.37% dry matter. The cocksfoot (D. glomerata) contained 79,52% moisture, 2,27% crude protein, 0,051% calcium, 0,061% phosphorus and 20,48% dry matter. The younger foal did not eat the grass mixture. The mass of grass mixture consumed by the older foal was not determined. In the second trial conducted 3 weeks later, when oat straw (Avena sativa) was also fed ad lib itum, the same lactating mares, but a different mature non-lactating mare, consumed 54.5 kg, 56.0 kg and 40.5 kg of the grass mixture, cut in the mid bloom stage, respectively. The perennial ryegrass (L. perenne) contained 70,03% moisture, 2,37% crude protein, 0,086% calcium 0,068% phosphorus and 29,97 dry matter.(ABSTRACT TRUNCATED AT 250 WORDS)