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Urokinase plasminogen activator (uPA) is a serine protease involved in cancer invasion and metastasis. uPA mediates its action while attached to a membrane-bound receptor (uPAR). In this investigation we show that uPAR levels correlate with uPA levels in human breast cancers. uPAR levels, however, do not correlate with other components of the plasminogen activator system such as tissue-type plasminogen activator (t-PA), PAI-I or PAI-2. In addition, uPAR levels showed no correlation with tumor size, axillary-node status or estrogen-receptor status. On the basis of an optimum cut-off point, patients with breast cancers containing high levels of uPAR had a worse prognosis than patients with low levels of the receptor. However, as a prognostic marker in breast cancer, uPAR was not as strong as uPA. Our results are consistent with data from model systems suggesting that both uPA and uPAR are necessary for metastasis.

Objective: To familiarize the surgeon with problem-based learning (PBL) and to discuss the current and future role of PBL in undergraduate surgical education., Data Sources: Two meta-analyses comparing the outcome of a PBL curriculum with a traditional curriculum and other studies in the English-language literature., Study Selection: Data on the effectiveness of PBL can best be assessed by a meta-analysis in which the conclusions of many studies are reviewed and combined to provide a more comprehensive picture. The studies chosen represent those from the only two recent meta-analyses of the problem that have appeared in reputable journals., Data Extraction: Results reported are those obtained using appropriate techniques and published in reputable journals. Information relevant to the major issues in undergraduate surgical training was selected for inclusion., Data Synthesis: PBL depends on self-directed learning, triggered by a clinical problem. The students meet in small groups led by a facilitator and discuss carefully designed clinical cases. At the conclusion, the students will have encountered all the information necessary to solve the case and, in so doing, will have gained knowledge that in a conventional curriculum would usually have been disseminated by lecture. There were only small differences between graduates from the two types of curricula. Those from a PBL curriculum had comparable examination results to those from a traditional curriculum on both basic science and clinically based examinations but were happier with their educational experiences., Conclusions: Centres that have adopted a PBL approach have found improved student motivation and enjoyment, but there has been no convincing evidence of improved learning. An intelligent combination of both traditional and PBL approaches will likely provide the most effective training for undergraduate surgical clerks.

Aim: To determine the prevalence of antibodies to Ross River and dengue viruses in sera from New Zealand residents and travellers and to assess the potential of local mosquitoes to act as vectors of these viruses., Method: Serum specimens from several population groups were examined by haemagglutination-inhibition and neutralisation tests for antibodies to Ross River and dengue viruses between 1975 and 1993. During this period dengue was active in South East Asia, Australia and the Pacific, and a major epidemic of Ross River infection occurred in the Pacific. Two New Zealand mosquito species were tested for their ability to transmit by bite after they had been fed or injected with these viruses., Results: Ten percent of 1869 sera from patients suspected of contracting dengue, and 43% of 183 patients suspected of contracting Ross River virus, while overseas, were antibody positive. Many patients showed antibody rises which indicated that they were probably viraemic on entry to this country. Dengue viruses were isolated in Dunedin from two patients with dengue haemorrhagic fever contracted overseas. Antibody studies of persons who had not travelled outside New Zealand provided no evidence of local transmission of these viruses. Two local mosquitoes, Aedes notoscriptus from the Auckland area, and Aedes australis from the Otago area, were able to transmit one or both these viruses under laboratory conditions., Conclusions: The serological studies showed that both Ross River and dengue viruses have probably been introduced into New Zealand by viraemic travellers on many occasions. Although some local mosquitoes can transmit these viruses in the laboratory, there is no evidence of local spread of virus from these imported cases. Changing environmental conditions such as global warming with concomitant effects on vector distribution, increasingly rapid air travel by viraemic persons and the accidental introduction of new vector mosquitoes, particularly Aedes albopictus, could pose a threat in view of the high percentage of New Zealand residents with no protective antibody.

An assessment of 26 patients, taking theophylline for COAD or asthma, was undertaken in a Belfast Community pharmacy. Patients had peak flow rate and serum theophylline concentration monitored. Based on these findings patients were counselled and, where appropriate, theophylline dosage was adjusted using a pharmacokinetic computer program. A statistically significant improvement was found between the number of patients who had a serum theophylline concentration in the therapeutic range at the initial assessment and at 3 months and 12 months. This was accompanied by a statistically significant improvement in peak expiratory flow rates.

The double-stranded replicative form of dengue 2 virus (DEN-2) RNA (Tonga strain) was used as a substrate to produce DNA clones of the NS1-NS2A genes via reverse transcriptase synthesis of full length cDNA followed by polymerase chain reaction amplification of the NS1-NS2A region. Products were cloned into pTZ18R for sequencing and into baculovirus for expression studies. The deduced amino acid sequence of the NS1-NS2A was almost identical to that of the S1 attenuated strain of DEN-2 Puerto Rico 159, differing in only four amino acids. The NS1 protein expressed in insect cells [Spodoptera frugiperda (Sf-9)] from the baculovirus recombinant was indistinguishable from authentic NS1 of DEN-infected Aedes albopictus cells in glycosylation, dimerization, cellular presentation and antigenicity. Mice injected with the expressed protein developed NS1-specific complement-fixing antibodies and were partially protected against neurological residua after intracranial challenge. The protective effect was mouse strain- and gender-specific.

A method is described for cloning large fragments (1.5 kb to 2 kb) of dengue virus cDNA from replicative-form viral RNA. Aedes albopictus cells (C6/36 clone) infected with dengue virus contain double-stranded, replicative-form RNA molecules which were used as a template for an initial reverse transcription using a primer containing sequence homologous to regions of the genome at or near the 3' end of the gene being studied. The product was then used as a template for polymerase chain reaction (PCR) amplification using the same 3' primer and a second which hybridized to a region at the 5' end of the sequence to be cloned. Both primers were engineered to contain specific restriction enzyme cutting sites which enabled the PCR product to be cut and cloned directly into plasmids for sequencing and expression studies. We have used this method to construct clones of the envelope glycoprotein gene (E) and the non-structural genes 1 and 2a (NS1/2a) and 3 (NS3) of dengue type 2, Tonga 1974 strain, and E and NS1/2a from dengue type 3, H-87 strain, either as discrete genes or as constructs with long and short leader sequences, with or without anchor sequences. The method could be applied to the cloning of any gene from any flavivirus, directly from infected cell extracts, without the necessity for tedious virus purification steps.

The Alberta Infant Motor Scale (AIMS), an observational assessment scale, was constructed to measure gross motor maturation in infants from birth through independent walking. Based upon the literature, 58 items were generated and organized into four positions: prone, supine, sitting and standing. Each item describes three aspects of motor performance--weight-bearing, posture and antigravity movements. Content validation of the instrument was accomplished through a mail survey of Canadian pediatric physical therapists and consultation with an international panel of experts. Five hundred and six infants, age-stratified from birth through 18 months, participated in the reliability and validity testing of the AIMS. In addition, 20 infants who were experiencing abnormal motor development and 50 infants at risk for motor disorders were assessed and compared with the results of the full-term sample. Results to be presented include: 1) test-retest and inter-rater reliability estimates; 2) correlations between the AIMS and the Bayley and Peabody motor scores; and 3) scaling of the items along the age continuum for normal motor development.

Enteroviral infections are potentially serious in man causing a variety of syndromes and a viraemic phase is probable in most patients. However, virological diagnosis is usually indirect by isolation of the agent from throat or stools when possible, and/or slow due to the need to titrate antibodies in paired sera. Because of its high sensitivity the polymerase chain reaction (PCR) offers the possibility of rapid detection of even low-grade viraemia. We have developed a 2-step PCR procedure adapted for enteroviruses and applied it to stored sera from patients with enteroviral meningitis. The acute sera from 7/12 patients were positive but the 4 convalescence sera tested, 2 of which had been positive at the acute phase, were negative. The assay should now be tested prospectively on serum and cerebrospinal fluid and could be developed for routine diagnosis.

Hair samples from 20 documented heroin users contained 6-acetylmorphine, a unique metabolite of heroin, in all samples. Heroin was identified in smaller amounts in seven of these samples. The identity of 6-acetylmorphine and heroin was established by comparison of full scan spectra of extracts to standard reference materials. The presence of 6-acetylmorphine generally predominated over heroin, morphine, and codeine. The mean concentrations of analytes were as follows: 6-acetylmorphine, 0.90 ng/mg, N = 20; heroin, 0.17 ng/mg, N = 7; morphine, 0.26 ng/mg, N = 20; codeine, 0.18 ng/mg, N = 15. Analysis of hair samples obtained from 10 drug-free control subjects were negative for 6-acetylmorphine, morphine, and codeine. However, a small interfering peak was observed at the retention time for heroin. Control samples soaked in aqueous solutions of heroin and 6-acetylmorphine were found to be contaminated, even though an initial wash step was included in the analysis. These data suggest that hair analysis for 6-acetylmorphine can be used to differentiate heroin users from other types of opiate exposure (e.g., poppy seed, licit morphine, and codeine); however, environmental contamination can potentially produce false positives during opiate testing.

Two unique metabolites of cocaine, cocaethylene and norcocaine, were identified by GC/MS in the hair of cocaine users. Their presence cannot be explained by environmental contamination; thus, their presence together with cocaine provides convincing evidence that cocaine is excreted in hair after active cocaine administration. The amount of cocaine in hair predominated over all metabolites generally by a factor of 5-10. Two washing procedures were evaluated for their efficiency in removal of cocaine from environmentally contaminated hair. Neither procedure completely removed cocaine, suggesting that false positives can result from environmental contamination. Analysis of the methanolic wash of the hair of cocaine users also revealed the presence of cocaine metabolites, indicating that washing removes cocaine from the interior as well as from the exterior surface of hair during decontamination procedures.

A dengue epidemic due to type 2 virus involving some 3,400 cases began in Fiji early in 1971, had a peak during May, June and July, and cases have continued to occur with a low incidence during 1972 and 1973. Many of the notified cases showed classical dengue fever symptoms and there were no confirmed cases of haemorrhagic fever. A serological survey indicated that there had been at least 20,000 subclinical infections. It is probable that the virus was introduced to Fiji either through the port of Lautoka or Nadi international airport in February 1971. The normal travel patterns of residents must have spread the virus to all the more accessible localities but, with the exception of Rotuma, it caused infections only in areas where Aedes aegypti was available as a vector. There was no evidence that pre-existing dengue type 1 serum antibody gave any protection during this epidemic.

Ranitidine and cimetidine were compared with respect to their effect on preventing the continuation or recurrence of acute upper gastrointestinal bleeding secondary to peptic ulcer disease. Fifty patients were randomly allocated to treatment with either ranitidine or with cimetidine. The two groups were comparable for age, sex, and severity of hemorrhage. There was no statistically significant difference in outcome between the groups when assessing need for surgery, total number of units in blood required, days in hospital, incidence of rebleeding, or deaths. However, there was a trend in favor of ranitidine: only one ranitidine-treated patient went to operation versus four of the cimetidine group. In addition, the number of rebleeds was higher in the cimetidine group (14) compared to the ranitidine group (1). Two patients in each group died. Therefore, ranitidine appears to be comparable to cimetidine in the management of patients with acute upper gastrointestinal tract bleeding. However, this study did not include a placebo group, and thus the generalized use of H2-receptor blockers in all patients with acute upper gastrointestinal tract bleeding has not been proven.

An epidemic of dengue fever type 3 occurred on the island of Niue late in 1985 and during the first quarter of 1986. Just over 18% of the population reported for medical attention, the disease predominantly affecting teenagers and young adults, with equal sex distribution. The epidemic was of the classical dengue syndrome and there were no deaths. There were some unusual features. The magnitude of antibody rise was unusually high in many of those with no preexisting antibody. Despite the large proportion of the population with preexisting dengue type 2 antibodies, no cases of dengue haemorrhagic fever/dengue shock syndrome were observed, confirming the observations made in many other epidemics that these serious complications do not always follow in sequential epidemics caused by two different types. A high level of awareness, combined public health measures and active community involvement helped to control the epidemic early.

An explosive epidemic of dengue occurred in Fiji between January and July 1975. All laboratory evidence indicated that type 1 dengue was the only prevalent dengue virus. This type had probably not been in Fiji for 30 years and over 70% of the population was susceptible. Aedes aegypti appeared to be the major vector in urban areas, but circumstantial evidence indicated that Aedes rotumae was a vector in at least one remote area. All forms of the clinical spectrum of dengue were seen and reported in all age groups. Overt clinical symptoms tended to be less frequent among children under age 10 and adults over age 30. Approximately 16% of persons reporting dengue-like illness had some type of bleeding associated with their disease with little difference by age, sex, or ethnic group. Epistaxis and gingival bleeding were the most commonly reported and observed hemorrhagic manifestations, but internal bleeding was reported in about 25% of hemorrhagic cases. The proportion of hemorrhagic cases was the same among primary and secondary dengue-infected persons. These and other epidemiologic observations did not support the hypothesis that the hemorrhagic complications seen with dengue occur only in secondary infections.

Sera from 1283 patients and 73 staff members from Cherry Farm Psychiatric Hospital were screened for hepatitis B antigen over a five year period, following a single confirmed case of type B hepatitis in one villa. Apart from the presenting case, 10 asymptomatic carriers of hepatitis B antigen were detected, three of these being from the same villa and possessing the same antigen subtype as the presenting patient. Only two of 26 Down's syndrome patients and two of 44 Polynesian patients were positive. No staff members were positive. A case of frank hepatitis B occurred in a male nurse accidentally pricked with a needle contaminated with blood from one of the carriers. The low prevalence of hepatitis B antigen in this population for the mentally ill is possibly related to the reduced patient contact resulting from the isolated villa type of accommodation.

Coxsackie A 6 virus, strain V 29, originally isolated from Aedes polynesiensis in Fiji, was found to survive in A. australis for 5 days after intrathoracic injection and for 6 days after feeding on viraemic mice, and in Culiseta tonnoiri for 8 days after feeding.The virus level in both fed and injected mosquitoes fell steadily after infection and never exceeded the original level.No virus transmission was obtained in 46 successful second feedings on days 10-14 with A. australis, but three transmissions were obtained with C. tonnoiri, two on day 10 and one on day 13, from 12 successful second feedings.

Surveys of arbovirus activity in Fiji were conducted over a 10-year period from December 1959 to December 1969. No arboviruses were isolated from over 200,000 mosquitoes, 9000 ticks, or 575 serum samples. Eight thousand human and 1117 bird, bat and animal sera were tested for haemagglutination-inhibiting arbovirus antibody using a variety of group A, group B and Bunyamwera group antigens. Only a small number of low-titre reactions were found among the non-human sera, but 14% of all human sera were found to contain Group B antibody. The antibody prevalence increased with increasing age, from less than 1% for persons born since 1950, to 70% for persons born before 1900. The age differences in prevalence could be used to estimate the time and size of previous epidemics. Differences were found in antibody prevalence between the sexes, between ethnic groups and between persons from different regions. These differences could be explained in terms of climate, location and custom.Historical and serological evidence both suggest that all the antibody detected was due to past exposure to dengue virus. The very high proportion of the population with no dengue antibody makes Fiji a high-risk area for a further dengue epidemic. Dengue virus is known to be active in the Pacific and South-East Asia.