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PubMed2004

Transmission of transmissible mink encephalopathy to raccoons (Procyon lotor) by intracerebral inoculation.

To determine the transmissibility of transmissible mink encephalopathy (TME) agent to raccoons and to provide information about clinical course, lesions, and suitability of currently used diagnostic procedures for detection of transmissible spongiform encephalopathies (TSEs) in raccoons, 4 raccoon kits were inoculated intracerebrally with a brain suspension from mink experimentally infected with TME. One uninoculated raccoon kit served as a control. All 4 animals in the TME-inoculated group showed clinical signs of neurologic disorder and were euthanized between 21 and 23 weeks postinoculation (PI). Necropsy examinations revealed no gross lesions. Spongiform encephalopathy was observed by light microscopy, and the presence of protease-resistant prion protein (PrPres) was detected by immunohistochemistry and Western blot techniques. Scrapie-associated fibrils were observed by negative-stain electron microscopy in the brains of 3 of the 4 inoculated raccoons. These findings confirm that TME is experimentally transmissible to raccoons and that diagnostic techniques currently used for TSE in livestock detect prion protein in raccoon tissue. According to previously published data, the incubation period of sheep scrapie in raccoons is 2 years, whereas chronic wasting disease (CWD) had not shown transmission after 3 years of observation. Because incubation periods for the 3 US TSEs (scrapie, TME, and CWD) in raccoons appear to be markedly different, it may be possible to use raccoons for differentiating unknown TSE agents. Retrospective genotyping of raccoons using frozen spleens showed that the raccoon PrP gene is identical to the mink gene at codons 179 and 224. Further studies, such as the incubation periods of bovine spongiform encephalopathy and other isolates of scrapie, CWD, and TME in raccoons, are needed before the model can be further characterized for differentiation of TSE agents.

Animals↗
PubMedDate not supplied

[Estimation of the rate of mother-to-child HIV transmission: methodological problems and current estimates. Report of 2 study workshops (Ghent, Belgium, 17-20 February 1992 and 3-5 September 1993).The International Study Group on mother-child transmission of HIV].

In the last eight years, numerous cohort studies have been conducted to estimate the rate of mother-to-child (MTC) transmission of HIV. Many of these have faced problems in data collection and analysis. This made it difficult to compare transmission rates (TRs) between studies. Two workshops on methodological aspects of the study of MTC transmission of HIV-1 were held in Ghent (Belgium) in February 1992 and September 1993. Fourteen teams of investigators participated, representing studies from Central (5) and Eastern Africa (3), Europe (2), Haiti (1) and the USA (3). A critical evaluation of the projects was carried out, under four headings: 1) enrollment and follow-up procedures, 2) diagnostic criteria and case definitions, 3) measurement and comparison of MTC TRs and 4) determinants of transmission. Reported TRs ranged from 13 to 32% in industrialized countries and from 25 to 48% in developing countries. However, no direct comparisons could be made because methods of calculation differed from study to study. Based on this review, a common methodology was developed during the 1992 workshop. Agreement was reached on definitions of HIV-related signs/symptoms, paediatric Aids and HIV-related deaths. A classification system of children born to HIV-1 infected mothers according to their probable HIV infection status during the first 15 months of life allowed the elaboration of a direct method of computation of the TR and of an indirect method for studies with a comparison group of children born to HIV-seronegative mothers. This standardized approach was subsequently applied to selected data sets to update previous estimates and provide a comparison of the MTC TRs of HIV-1 in 13 different settings. TRs were calculated during the 1993 workshop by the participating teams, using the direct and indirect methods. TRs based on the intermediate estimate obtained with the direct method ranged between 12.7 and 42.1%. Estimates of TRs obtained with the indirect method ranged from 20.7 to 42.8%. TRs observed in developed countries ranged from 14 to 25% with the direct method. In the developing world, these rates ranged from 13 to 42% with the direct method, from 21 to 43% with the indirect method and most of the studies reported a TR in the range of 25 to 30%. In general, both methods provide a reasonable estimate of the true TR. The risk of MTC transmission of HIV-1 tends to be higher in children born to HIV-seropositive mothers in Africa than in Europe.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1993

The transmissible brain amyloidoses: a comparison with the non transmissible brain amyloidoses of Alzheimer type.

I report here the basic concepts of the transmissible and non-transmissible cerebral amyloidoses. The pathogenesis of both types of brain amyloidoses consist of a synthesis of amyloid precursor followed by its processing to yield a final postranslationally modified deposit. PrPc and APP serve as precursor proteins while modified PrP (PrPsc and PrP 27-30) and beta-A4 as final deposits in transmissible and non-transmissible brain amyloidoses, respectively. The hallmark of both types of brain amyloidoses is amyloid deposits immunoreactive to appropriate amyloids. Other, mostly unspecific, neuropathological phenomena as neurofibrillary tangles, dystrophic neurites and granulovacuolar degeneration are also discussed. The only disease-specific structure for transmissible cerebral amyloidoses are tubulovesicular structures of unknown biological significance. They may even be the infectious virus.

Alzheimer Disease↗
PubMed1993

[Transmissible and non-transmissible brain amyloidoses: neurodegenerative disorders of different etiologies and the same pathogenesis].

I report here the molecular, ultrastructural and immunohistochemical similarities between transmissible (scrapie, Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker syndrome) and non-transmissible (Alzheimer's disease, hereditary cerebral hemorrhage with amyloidosis--Dutch (HCHWA-D) and Icelandic (HCHWA-I) types) brain amyloidoses. The central pathogenic event in both types of amyloidoses is a synthesis and a processing of amyloid precursor followed by an accumulation of a final deposit. PrPc and APP are amyloid precursors and PrPsc and beta-A4 are final deposits in transmissible and nontransmissible cerebral amyloidoses of Alzheimer's disease type, respectively. In HCHWA-I, cystatin C serves the role of the amyloid precursor protein. The amyloid plaque composed of a different proportions of amyloid fibers, dystrophic neurites and astrocytes and microglia cells is the crucial neuropathological entity. The role of microglial cell as amyloid producer/processor cell seems to be analogous in both types of amyloidoses. The impairment of slow axoplasmic transport which leads to the accumulation of neurofilament triplet protein in the transmissible and tau protein in the non-transmissible cerebral amyloidoses causes the development of dystrophic neurites and neuropil threads. The other elements of neuropathology like Hirano bodies and granulovacuolar degeneration may be only secondary and non-specific phenomena.

Amyloidosis↗
PubMed1991

Oral transmission of transmissible gastroenteritis virus by muscle and lymph node from slaughtered pigs.

A study was conducted in the USA to determine whether transmissible gastroenteritis (TGE) virus could be transmitted from carcases of slaughtered pigs. Transmissible gastroenteritis virus was transmitted to 6-day-old piglets by dosing with homogenates of muscle and lymph node collected from 500 clinically normal pigs at the time of slaughter. All piglets in 2 separately housed litters showed clinical signs of TGE with 5 piglets dying within 10 d of oral dosing with homogenates. Transmissible gastroenteritis virus was isolated from 2 of these piglets and all piglets developed TGE antibody. Transmissible gastroenteritis virus was not isolated in tissue culture from muscle and lymph node homogenates, but was isolated from 4 (0.8%) of 500 tonsil samples collected from the same pigs. A survey of 250 serum samples provided an estimate of the prevalence of slaughtered pigs with TGE antibody of 34.8% in the sample population. The results indicate that carcases of some pigs from TGE endemic areas contain viable TGE virus, and that there would be a substantial risk of introducing TGE virus into Australia by the importation of uncooked pig meat from these areas.

Administration, Oral↗
PubMed1999

Influence of maternal CD4 levels on the predictive value of virus load over mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1). Study Group for Vertical Transmission.

Forty-four anti-HIV seropositive pregnant women were enrolled in a study of maternal factors related to mother-to-infant human immunodeficiency virus type 1 (HIV-1) transmission. HIV-1 infection was documented in 11 of 45 infants (24.4%). Obstetric factors, maternal CD4 counts, and disease stage were not related to the risk of transmission. HIV-1 RNA levels at delivery were significantly higher in mothers who transmitted the infection (P = .024). A strong relationship between viral load and risk of transmission was observed in women with stage A1 (P= .006), but not in those with stages A2-A3. These results suggest that vertical transmission of HIV-1 is multifactorial and that viral load plays a major role in mothers with early-stage HIV-1 infection.

Adult↗
PubMed2001

Condom effectiveness in reducing heterosexual HIV transmission.

BACKGROUND: The amount of protection that condoms provide for HIV and other sexually transmitted diseases is unknown. Cohort studies of sexually active HIV serodiscordant couples with follow-up of the seronegative partner, provide a situation in which a seronegative partner has known exposure to the disease and disease incidence can be estimated. When some individuals use condoms and some do not, namely some individuals use condoms 100% of the time and some never use (0%) condoms, condom effectiveness can be estimated by comparing the two incidence rates. Condom effectiveness is the proportionate reduction in disease due to the use of condoms. OBJECTIVES: The objective of this review is to estimate condom effectiveness in reducing heterosexual transmission of HIV. SEARCH STRATEGY: Studies were located using electronic databases (AIDSLINE, CINAHL, Embase, and MEDLINE) and handsearched reference lists. SELECTION CRITERIA: For inclusion, studies had to have: (1) data concerning sexually active HIV serodiscordant heterosexual couples, (2) a longitudinal study design, (3) HIV status determined by serology, and (4) contain condom usage information on a cohort of always (100%) or never (0%) condom users. DATA COLLECTION AND ANALYSIS: Studies identified through the above search strategy that met the inclusion criteria were reviewed for inclusion in the analysis. Sample sizes, number of seroconversions, and the person-years of disease-free exposure time were recorded for each cohort. If available, the direction of transmission in the cohort (male-to-female, female-to-male), date of study enrollment, source of infection in the index case, and the presence of STDs was recorded. Duplicate reports on the same cohort and studies with incomplete or nonsepecific information were excluded. HIV incidence was estimated from the cohorts of "always" users and for the cohorts of "never" users. Effectiveness was estimated from these two incidence estimates. MAIN RESULTS: Of the 4709 references that were initially identified, 14 were included in the final analysis. There were 13 cohorts of "always" users that yielded an homogeneous HIV incidence estimate of 1.14 [95% C.I.:.56, 2.04] per 100 person-years. There were 10 cohorts of "never" users that appeared to be heterogeneous. The studies with the longest follow-up time, consisting mainly of studies of partners of hemophiliac and transfusion patients, yielded an HIV incidence estimate of 5.75 [95% C.I.: 3.16, 9.66] per 100 person-years. Overall effectiveness, the proportionate reduction in HIV seroconversion with condom use, is approximately 80%. REVIEWER'S CONCLUSIONS: This review indicates that consistent use of condoms results in 80% reduction in HIV incidence. Consistent use is defined as using a condom for all acts of penetrative vaginal intercourse. Because the studies used in this review did not report on the "correctness" of use, namely whether condoms were used correctly and perfectly for each and every act of intercourse, effectiveness and not efficacy is estimated. Also, this estimate refers in general to the male condom and not specifically to the latex condom, since studies also tended not to specify the type of condom that was used. Thus, condom effectiveness is similar to, although lower than, that for contraception.

Cohort Studies↗
PubMed1997

Neuromuscular transmission and its pharmacological blockade. Part 1: Neuromuscular transmission and general aspects of its blockade.

Blockade of neuromuscular transmission is an important feature during anaesthesia and intensive care treatment of patients. The neuromuscular junction exists in a prejunctional part where acetylcholine is synthesized, stored and released in quanta via a complicated vesicular system. In this system a number of proteins is involved. Acetylcholine diffuses across the junctional cleft and binds to acetylcholinereceptors at the postjunctional part, and is thereafter metabolized by acetylcholinesterase in the junctional cleft. Binding of acetylcholine to its postjunctional receptor evokes muscle contraction. Normally a large margin of safety exists in the neuromuscular transmission. In various situations, apart from up-and-down regulation of acetylcholine receptors, adjustment of acetylcholine release can occur. Pharmacological interference can interrupt the neuromuscular transmission and causes muscle relaxation. For this reason both depolarizing and non-depolarizing muscle relaxants are clinically used. The characteristics of an ideal clinical muscle relaxant are defined. In the description of the pharmacology of the relaxants the importance of pharmacodynamic and pharmacokinetic parameters are defined. Stereoisomerism plays a role with the relaxants. Toxins and venoms also interfere with neuromuscular transmission, through both pre- and postjunctional mechanisms.

Down-Regulation↗
PubMed2000

Short-course antenatal zidovudine reduces both cervicovaginal human immunodeficiency virus type 1 RNA levels and risk of perinatal transmission. Bangkok Collaborative Perinatal HIV Transmission Study Group.

Human immunodeficiency virus (HIV) levels in cervicovaginal lavage (CVL) and plasma samples were evaluated in relation to perinatal transmission in a randomized placebo-controlled trial of brief antenatal zidovudine treatment. Samples were collected at 38 weeks' gestation from 310 women and more frequently from a subset of 74 women. At 38 weeks, after a 2-week treatment period, CVL HIV-1 was quantifiable in 23% and 52% of samples in the zidovudine and placebo groups, respectively (P<.001). The perinatal transmission rate was 28.7% among women with quantifiable CVL HIV-1 and high plasma virus levels (>10,000 copies/mL) and 1% among women without quantifiable CVL HIV-1 and with low plasma virus levels (P<.001). A 1-log increase in plasma HIV-1 increased the transmission odds 1.8 and 6.1 times (95% confidence interval, 0.9-3.5 vs. 2.4-15.4) for women with and without quantifiable CVL HIV-1, respectively (P=.03). CVL HIV-1 is an independent risk factor for perinatal HIV-1 transmission.

Cervix Uteri↗
PubMed1998

Neutralizing antibody and perinatal transmission of human immunodeficiency virus type 1. New York City Perinatal HIV Transmission Collaborative Study Group.

The major immunologic determinants for perinatal transmission of human immunodeficiency virus type 1 (HIV-1) remain largely unknown. The presence of maternal neutralizing antibodies has been proposed as an explanation for why the majority of infants born to untreated HIV-1-infected women do not become infected. Using maternal and infant specimens collected as part of a longitudinal cohort study of perinatal transmission in New York City between 1991 and 1995, we successfully obtained primary viral isolates from 10 of 20 perinatally nontransmitting (NTR) women, 14 of 20 perinatally transmitting (TR) women, and 13 of 13 of their HIV-1-infected infants. Neutralizing antibody titers were then determined using a titer reduction assay. TR and NTR women did not differ in their ability to neutralize autologous virus or laboratory strains LAI and MN. Infant viruses were not less sensitive to neutralization by maternal sera than autologous viruses. Similarly, TR and NTR isolates were neutralized equally well using a reference serum with broad neutralizing ability. Finally, a heteroduplex tracking assay (HTA) was used to analyze the degree of viral homology within 13 TR maternal-infant pairs. In eight pairs, maternal and infant isolates were highly homologous. In five pairs, lesser degrees of homology were observed, consistent with perinatal transmission of a minor species. However, these isolates were no more or less resistant to maternal sera than were homologous isolates. Thus we found no association between the presence of neutralizing antibody in maternal sera as measured by a titer reduction neutralization (inactivation) assay and perinatal transmission of HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed1994

The efficiency of male-to-female and female-to-male sexual transmission of the human immunodeficiency virus: a study of 730 stable couples. Italian Study Group on HIV Heterosexual Transmission.

To compare the efficiency of male-to-female and female-to-male sexual transmission of human immunodeficiency virus (HIV), we studied 524 female partners of HIV-infected men and 206 male partners of HIV-infected women in 16 Italian clinical centers. All of the partners had had a sexual relationship with the index case lasting for at least 6 months and presented no other risk factor than sexual exposure to the HIV-infected partner. Among the 730 couples, 24% of the female partners were HIV positive, in comparison with 10% of the male partners. Using logistic regression analysis, including gender and controlling for condom use, frequency of intercourse, anal sex, partner's CD4+ cell count and clinical stage, sexually transmitted diseases, genital infections, and contraceptive use, we found that the efficiency of male-to-female transmission was 2.3 (95% confidence interval = 1.1-4.8) times greater than that of female-to-male transmission. Between-gender differences in the contact surfaces and the intensity of exposure to HIV during sexual intercourse are possible reasons for the difference in efficiency of transmission.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Timing of maternal-infant HIV transmission: associations between intrapartum factors and early polymerase chain reaction results. New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVE: To investigate the hypothesis that labour and delivery events, perinatal characteristics, and maternal factors are only associated with intrapartum HIV transmission, and not with intrauterine HIV transmission. METHODS: In the New York City Perinatal HIV Transmission Collaborative Study 276 infants of HIV-infected women were followed prospectively and had results of early polymerase chain reaction (PCR) tests available. Among infected children, intrauterine infection was presumed if HIV DNA was detected by PCR in samples collected from children aged < or = 3 days, and intrapartum infection was presumed if HIV DNA was not detected in these early samples. The proportion of infants with presumed intrauterine and intrapartum infections were compared by selected intrapartum, perinatal and maternal characteristics. RESULTS: Presumed intrapartum infection was found in 7% of infants delivered by Cesarean section and, among infants delivered vaginally, those with longer duration of membrane rupture (> 4 h) were significantly more likely to have presumed intrapartum HIV infection (22%) than those with shorter duration (9%; P = 0.02). There were no differences in presumed intrauterine HIV infection by mode of delivery or longer duration of membrane rupture. Infants born preterm and small for gestational age had significantly higher risks of presumed intrapartum infection, but only those who were small for gestational age had higher risks of intrauterine infection. CONCLUSION: Our results support the notion that selected intrapartum conditions, long duration of membrane rupture prior to delivery in particular, are independent risk factors for maternal-infant transmission, and suggest that preterm infants may be especially vulnerable to intrapartum HIV exposure.

Birth Weight↗
PubMed1997

Potential risk factors for vertical HIV-1 transmission in Catalonia, Spain: the protective role of cesarean section. The Working Group on HIV-1 Vertical Transmission in Catalonia.

OBJECTIVE: To evaluate the roles of certain potential risk factors on the vertical transmission of HIV-1. DESIGN: Prospective registry of infants born to HIV-1-infected women in Catalonia (north-east Spain) from 1987 to 1992. METHODS: A total of 599 infants, born in Catalan hospitals to 520 women who were identified as being HIV-1-infected during gestation or at delivery, were included. Data on mode of delivery, birth weight, gestational age and breast-feeding as well as the mother's age, her route of HIV-1 infection, clinical stage and p24 antigenaemia, were recorded. HIV-1 infection status of 489 (82%) of the infants was determined according to the criteria of the US Centers for Disease Control and Prevention. Risk estimates and odds ratio (OR) were calculated and logistic regression was performed. RESULTS: The overall rate of vertical transmission was 18.6% (95% confidence interval, 15.2-22.0%). Multivariate analyses revealed that Cesarean section was associated with a lower rate of vertical transmission (OR = 0.3; P = 0.001), as was maternal HIV-1 infection via injecting drug use (OR = 0.44; P = 0.02). Breast-feeding (OR = 6.9; P = 0.001), very low birth weight (< 1500 g; OR = 6.3; P = 0.001) and p24 antigenaemia (OR = 4.6; P = 0.04) were all related to increased risk. The crude rate of HIV-1 transmission was 6% among Cesarean births compared with 21% for infants born via vaginal deliveries. The population-attributable risk for vaginal deliveries was 61.7%. CONCLUSIONS: The results show a protective effect of Cesarean section in the absence of zidovudine prophylaxis. However, current research should be directed towards the individual and combined effects that antiretroviral agents and Cesarean section may have on mother-to-child HIV-1 infection.

Adult↗
PubMed2000

Follow-up of transmission of hepatitis C to babies of human immunodeficiency virus-negative women: the role of breast-feeding in transmission.

BACKGROUND: The studies on hepatitis C virus (HCV) vertical transmission, the effect of potential risk factors and the role of breast-feeding have reported conflicting results. PATIENTS AND METHODS: Seventy-three infants of 63 anti-HCV-positive and anti-HIV-negative mothers were studied from 1993 to 1999 in the south of Spain. The mean period of follow-up in children was 29.2 +/- 19 months (range, 8 to 76 months); 6 (8%) children were lost to follow-up. Breast milk was studied for HCV-RNA in 68 samples of 35 mothers. RESULTS: Alanine aminotransferase was high in 19 (26%) and HCV-RNA was positive in 46 (63%) pregnant woman. Breast milk HCV-RNA was negative in nonviremic mothers and positive in 20% of the viremic mothers. The overall rate of vertical HCV transmission was 11.9% (n = 8) (95% confidence interval, 6 to 23%) if HCV-RNA was positive one or more times, but only 1.5% (n = 1) (95% confidence interval, 0.1 to 9%) if HCV-RNA was permanently positive. Seven HCV-infected children did not develop antibodies to HCV, and they had a spontaneous clearance of the virus. A 10-month-old baby was HCV-RNA-positive from birth to the end of the follow-up. The genotype in each of the infants was consistent with that of their mother. The rate of HCV transmission was higher for infants of mothers with higher HCV viremia (P < 0.01) and also for infants whose mothers were HCV-RNA-positive in breast milk (P < 0.05). There were no statistically significant differences between other risk factors. CONCLUSION: The presence of transitory viremia without seroconversion indicates that the vertical transmission of HCV is not important. This could be related to the viral charge and ingestion of milk of HCV-RNA-positive mothers. However, to advise avoidance of maternal breast feeding, it would be necessary to conduct larger studies.

Adult↗
PubMedDate not supplied

Volume transmission and wiring transmission from cellular to molecular networks: history and perspectives.

The present paper deals with a fundamental issue in neuroscience: the inter-neuronal communication. The paper gives a brief account of our previous and more recent theoretical contributions to the subject and also reports new recent data that support some aspects of our proposal on two major modes of communication in the central nervous system: the wiring and the volume transmission. There exist two competing theories on inter-neuronal communication: the neuron doctrine and the theory of the diffuse nerve network, supported by Cajal and Golgi, respectively (see their respective Nobel Lectures). The present paper gives a brief account of a view on inter-neuronal communication in the brain, the volume and wiring transmission concept that to a great extent reconcile these two theories. Thus, the theory of volume and wiring transmission are summarized and its recent developments that allow to extend these two modes of communication from the cellular network to the molecular network level is also briefly illustrated. The explanatory value of this broadened view is further enhanced by our recent proposal on the existence of a Global Molecular Network enmeshing the entire central nervous system. It may be interesting to note that also the Global Molecular Network theory is reminiscent of the old reticular theory of Apathy. Finally, the so-called 'tide hypothesis' for diffusion of signals in the brain is briefly discussed and its possible extension to the molecular level is for the first time introduced. Early indirect evidence supporting volume transmission in the brain was the discovery of transmitter-receptor mismatches. Thus, as an experimental part of the present paper a new approach to evaluate transmitter-receptor mismatches is given and evidence for inter-relationships between temperature micro-gradients and mismatches is provided.

Cell Communication↗
PubMed1996

Microwave treatment enhances the immunostaining of amyloid deposits in both the transmissible and non-transmissible brain amyloidoses.

The immunolocalization of amyloid deposits containing either protease-resistant prion protein (PrP) or amyloid beta protein (A beta) in the brains of patients with transmissible or non-transmissible cerebral amyloidoses has been greatly facilitated by the pretreatment of tissue sections with concentrated formic acid. We have investigated whether microwave processing of formalin-fixed tissue sections would obviate the need for formic acid pretreatment. Exposure of brain sections to microwaves, even for periods as brief as 1 sec, greatly enhanced the immunostaining of PrP and A beta amyloid deposits in both the transmissible and non-transmissible brain amyloidoses. Microwaving for 1 min yielded staining intensities similar to that following pretreatment with concentrated formic acid for 10 min. Moreover, the combination of formic acid pretreatment and microwave processing resulted in an even more intense staining of amyloid deposits. Microwave processing, which is easy to perform and comparatively inexpensive, makes exposure to the potentially toxic fumes of formic acid unnecessary.

Alzheimer Disease↗
PubMed1999

Establishing radiologic image transmission via a transmission control protocol/Internet protocol network between two teaching hospitals in Houston.

The technical and management considerations necessary for the establishment of a network link between computed tomography (CT) and magnetic resonance imaging (MRI) networks of two geographically separated teaching hospitals are presented. The University of Texas Medical School at Houston Department of Radiology provides radiology residency training at its primary teaching hospital and at a second county-run hospital located approximately 12 miles away. A direct network link between the two hospitals was desired to permit timely consultative services to residents and professional colleagues. The network link was established by integrating the county hospital free-standing imaging network into the network infrastructure of the Medical School and the main teaching hospital. Technical issues involved in the integration were reassignment of internet protocol (IP) addresses, determination of data transmission protocol compatibilities, proof of connectivity and image transmission, transmission speeds and network loading, and management of the new network. These issues were resolved in a planned stepwise fashion and despite the fact that the system has a rate-limiting T1 segment between the county hospital and the teaching hospital the transmission speed was deemed suitable. The project has proven successful and can provide a guide for planning similar projects elsewhere. It has in fact made possible several new services for the teaching and research activities of the department's faculty and residents, which were not envisaged before the implementation of this connection.

Computer Systems↗
PubMed2006

A note on the power to detect transmission distortion in parent-child trios via the transmission disequilibrium test.

Transmission distortion refers to deviation from the normal 50:50 transmission of alleles from parents to offspring. Identification of genomic regions which undergo distortion is necessary for the correct interpretation of linkage and association studies, since tests of linkage using affected relative pairs and family based tests of association will yield spurious results in the presence of transmission distortion. With the increasing availability of genome-wide high density SNP data (e.g. from the International HapMap project), identification of these loci is now a real possibility. Here we present an analytical formula which demonstrates that the power to detect transmission distortion is a simple function of the number of heterozygous parents in the sample and the level of distortion at the locus. Our results indicate that whilst it will be possible to identify loci undergoing major levels of distortion using tens or hundreds of trios, large sample sizes in the order of tens of thousands of trios will be necessary to detect minor levels of distortion with appreciable power. The corollary is that genome-wide searches are unlikely to identify loci where the level of distortion is small, although they may serve to identify interesting regions worthy of follow up.

Adult↗