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The phylogenetic relationships of some angiosperm families have remained enigmatic despite broad phylogenetic analyses of rbcL sequences. One example is the aquatic family Podostemaceae, the relationships of which have long been controversial because of major morphological modifications associated with their aquatic habit. Podostemaceae have variously been associated with Piperaceae, Nepenthaceae, Polygonaceae, Caryophyllaceae, Scrophulariaceae, Rosaceae, Crassulaceae, and Saxifragaceae. Two recent analyses of rbcL sequences suggest a possible sister-group relationship of Podostemaceae to Crassulaceae (Saxifragales). However, the branch leading to Podostemaceae was long, and use of different outgroups resulted in alternative placements. We explored the phylogenetic relationships of Podostemaceae using 18S rDNA sequences and a combined rbcL + 18S rDNA matrix representing over 250 angiosperms. In analyses based on 18S rDNA data, Podostemaceae are not characterized by a long branch; the family consistently appears as part of a Malpighiales clade that also includes Malpighiaceae, Turneraceae, Passifloraceae, Salicaceae, Euphorbiaceae, Violaceae, Linaceae, Chrysobalanaceae, Trigoniaceae, Humiriaceae, and Ochnaceae. Phylogenetic analyses based on a combined 18S rDNA + rbcL data set (223 ingroup taxa) with basal angiosperms as the outgroup also suggest that Podostemaceae are part of a Malpighiales clade. These searches swapped to completion, and the shortest trees showed enhanced resolution and increased internal support compared to those based on 18S rDNA or rbcL alone. However, when Gnetales are used as the outgroup, Podostemaceae appear with members of the nitrogen fixing clade (e.g., Elaeagnaceae, Ulmaceae, Rhamnaceae, Cannabaceae, Moraceae, and Urticaceae). None of the relationships suggested here for Podostemaceae receives strong bootstrap support. Our analyses indicate that Podostemaceae are not closely allied with Crassulaceae or with other members of the Saxifragales clade; their closest relatives, although still uncertain, appear to lie elsewhere in the rosids., (Copyright 1999 Academic Press.)

Alzheimer's Disease presents extreme challenges not only to the individuals afflicted with it and their families, but also to both our legal and healthcare systems. The nature of the disease is such that current legal standards and requirements simply fail to function in an appropriate manner. So too, the health system currently is not in a position to handle the anticipated influx of Alzheimer's patients over the next several decades. This Article examines some of the challenges presented by this disease, and suggests several possible methods to improve our response to it.

The recent finding that Cpe(fat)/Cpe(fat) mice, which lack carboxypeptidase E (CPE) activity because of a point mutation, are still capable of a reduced amount of neuroendocrine peptide processing suggested that additional carboxypeptidases (CPs) participate in this processing reaction. Searches for novel members of the CPE gene family led to the discovery of CPD, CPZ, AEBP1, and CPX-2. In the present report, we describe mouse CPX-1, another novel member of this gene family. Like AEBP1 and CPX-2, CPX-1 contains an N-terminal region of 160 amino acids with sequence similarity to the discoidin domain of a variety of proteins. The 410-residue CP-like domain of CPX-1 has 54% to 62% amino acid sequence identity with AEBP1 and CPX-2 and 33% to 49% amino acid identity with other members of the CPE subfamily. However, several active-site residues that are important for catalytic activity of other CPs are not conserved in CPX-1. Furthermore, CPX-1 expressed in either the baculovirus system or the mouse AtT-20 cell line does not cleave standard CP substrates. Northern blot analysis showed the highest levels of CPX-1 mRNA in testis and spleen and lower levels in salivary gland, brain, heart, lung, and kidney. In situ hybridization of CPX-1 mRNA in embryonic and fetal mouse tissue showed expression throughout the head and thorax, with abundance in primordial cartilage and skeletal structures. In the head, high levels of CPX-1 mRNA were associated with the nasal mesenchyme, primordial cartilage structures in the ear, and the meninges. In the thorax, CPX-1 mRNA was expressed in multiple developing skeletal structures, including chondrocytes and perichondrial cells of the rib, vertebral, and long-bone primordia. Taken together, these findings suggest that it is unlikely that CPX-1 functions in the processing of neuroendocrine peptides. Instead, CPX-1 may have a role in development, possibly mediating cell interactions via its discoidin domain.

Unlabelled: We examined the effects of several opioids that vary in intrinsic efficacy at the mu-opioid receptor alone and in combination with morphine in a rat warm water tail withdrawal procedure using 50 degrees C and 52 degrees C water (i.e., low- and high-stimulus intensities). Morphine, levorphanol, dezocine, and buprenorphine produced dose-dependent increases in antinociception using both stimulus intensities. Butorphanol produced maximal levels of antinociception at the low, but not at the high, stimulus intensity, whereas nalbuphine failed to produce antinociception at either stimulus intensity. For cases in which butorphanol and nalbuphine failed to produce antinociception alone, these opioids dose-dependently antagonized the effects of morphine. When levorphanol, dezocine, and buprenorphine were combined with morphine, there was a dose-dependent enhancement of morphine's effects. Similar effects were obtained at the low-stimulus intensity when butorphanol was administered with morphine. In most cases, the effects of these combinations could be predicted by summating the effects of the drugs when administered alone. These results indicate that the level of antinociception produced by an opioid is dependent on the intrinsic efficacy of the drug and the stimulus intensity. Furthermore, the level of antinociception produced by the opioid, not necessarily the opioids' intrinsic efficacy, determines the type of interaction among opioids., Implications: Compared with high-efficacy opioids, lower efficacy opioids produce lower levels of pain relief, especially in situations of moderate to severe pain. When opioids are given in combination, the effects can only be predicted on the basis of the antinociception obtained when the drugs are administered alone.

This article examines the most recently published scientific literature on arthritis therapy options and available mucosal-protective agents. Emphasis is placed on the risks of current nonsteroidal anti-inflammatory drug (NSAID) therapy, the options for reducing such risks, and the published information that either supports or refutes current thinking in these areas. A comprehensive evaluation is made of clinical data related to the use of Arthrotec (diclofenac/misoprostol) in the treatment of arthritis. A recent meta-analysis of the prophylaxis of NSAID-associated upper gastrointestinal complications is reviewed. The results of this meta-analysis should help to consolidate much of the current scientific literature on the safe and effective treatment of arthritis.

The purpose of the present study was to determine the relative intrinsic efficacy of various opioids using the irreversible mu opioid antagonist beta-funaltrexamine (betaFNA). To this end, pigeons were trained to discriminate 3.0 (n=6) or 1.8 (n=1) mg/kg morphine from distilled water in a two-key, food-reinforced, drug discrimination procedure. The mu opioids fentanyl, l-methadone, buprenorphine, butorphanol, nalorphine, nalbuphine and levallorphan, as well as the delta opioid BW373U86, substituted completely for the morphine stimulus. The stimulus effects of morphine were antagonized (i.e., produced a significant increase in the ED50 value) by a 10 mg/kg but not a 5 mg/kg dose of betaFNA. Antagonist effects of betaFNA were observed following a 2-h pretreatment, but not following 26-, 50-, 74-, 98- or 146-h pretreatments. The stimulus effects produced by fentanyl, l-methadone and buprenorphine were not antagonized by doses of betaFNA as high as 20, 10 and 10 mg/kg, respectively. The lowest dose of betaFNA required to antagonize the stimulus effects of butorphanol was 10 mg/kg, whereas the effects of nalorphine, nalbuphine and levallorphan were antagonized by a dose of betaFNA as low as 5 mg/kg. The delta BW373U86 substituted for the morphine stimulus, and this effect was not antagonized by 10 mg/kg betaFNA. The pkB values for naloxone (1.0 mg/kg) against the stimulus effects of fentanyl (6.70) and morphine (6.52) were considerably higher than that for BW373U86 (4.60), indicating further that the morphine-like stimulus effects produced by BW373U86 were not mediated by activity at the mu opioid receptor. These findings indicate that the strategy of irreversible antagonism can be used effectively to differentiate opioids with varying degrees of intrinsic efficacy at the mu opioid receptor in a pigeon drug discrimination procedure. In particular, the ranking of these drugs by relative intrinsic efficacy at the mu opioid receptor is: l-methadone=fentanyl> or =buprenorphine> or =morphine> or =butorphanol>nalorphine=nalbuphine=levallorphan. Additionally, the short-acting effect of betaFNA in the pigeon suggests that the recovery of mu opioid receptor function varies across species.

Transgenic mice expressing heme oxygenase-1 (HO-1) using the neuron-specific enolase promoter were impaired in learning the Morris water maze compared to nontransgenic littermates. The memory of the HO-1 mice for the location of the platform was similarly impaired when tested using a probe trial after 7 training blocks, but performance on visible platform trials was similar for both groups of mice. Importantly, both HO-1 and nontransgenic mice had normal sensorimotor function, and performed the same on a Y-maze alternation task, highlighting the specificity of memory deficit in the spatial navigation task. These results suggest that carbon monoxide, one product of HO-1 activity, interferes in the development of spatial navigation memory, and may play a role in normal memory function., (Copyright 1998 Published by Elsevier Science B.V.)

Visceral left-right asymmetry occurs in all vertebrates, but the inversion of embryo turning (inv) mouse, which resulted following a random transgene insertion, is the only model in which these asymmetries are consistently reversed. We report positional cloning of the gene underlying this recessive phenotype. Although transgene insertion was accompanied by neighbouring deletion and duplication events, our YAC phenotype rescue studies indicate that the mutant phenotype results from the deletion. After extensively characterizing the 47-kb deleted region and flanking sequences from the wild-type mouse genome, we found evidence for only one gene sequence in the deleted region. We determined the full-length 5.5-kb cDNA sequence and identified 16 exons, of which exons 3-11 were eliminated by the deletion, causing a frameshift. The novel gene specifies a 1062-aa product with tandem ankyrin-like repeat sequences. Characterization of complementing and non-complementing YAC transgenic families revealed that correction of the inv mutant phenotype was concordant with integration and intact expression of this novel gene, which we have named inversin (Invs).

The most common cytogenetic abnormalities associated with myelodysplastic syndromes are deletions of chromosomes 5 and 7 and trisomy 8. Reciprocal translocation is relatively uncommon in refractory anemia. We describe a case of refractory anemia associated with trisomy 8 and a derivative chromosome 22 resulting from t(1;22)(q11;q11.2). The diseases and the role of the various genes that are mapped to these breakpoints are discussed. The prognostic significance of karyotypic abnormalities in refractory anemia are reviewed.

Replication-defective adenoviral (RDAd) vectors can be generated at high titers and infect both dividing and nondividing cells. Long term expression in the transduced tissue, however, has been a problem because of the cellular immune responses against the infected cells. We demonstrate that mice injected with RDAd vectors containing mouse leptin gene reduce food intake and lose weight for only 7 to 10 days. Splenocytes obtained from infected mice are able to lyse target cells infected with RDAd vectors. Surprisingly, target cells infected with psoralen-treated, UV-crosslinked, biologically inactive RDAd also were lysed efficiently by the effector cells. Furthermore, splenocytes obtained from mice injected with inactive RDAd vectors efficiently lysed target cells infected with RDAd vectors. Whether RDAd vectors were injected i.m. or i.v. or through an i.p. route, the extent of lysis was similar. We propose that cells infected with RDAd vectors present antigens for recognition by class 1 major histocompatibility complex-restricted cytotoxic T lymphocytes by a mechanism that does not require viral replication or de novo protein synthesis. These results should prompt reevaluation of the use of RDAd vectors for gene therapy when long-term expression is required.

Aims: The purpose of this study was to examine, in chronically treated heart failure patients vs control subjects, the influence of neurohumoral activation and aldosterone escape on arterial elastic behaviour, assessed by non-invasive mathematical lumped-parameter modelling of the compliance of the arterial system., Methods and Results: Radial arterial pulse waves were recorded non-invasively for 30 s with an arterial tonometer sensor array in 13 chronic heart failure patients (mean age, 59 +/- 2.5 years) in New York Heart Association class II. The patients had been taking digoxin, furosemide, captopril and aspirin for more than 3 months. Thirteen healthy subjects (mean age, 50 +/- 4.0 years) acted as controls. Compliance of the proximal (aorta and major branches, C1) and distal parts (C2) of the circulation were derived from a third order four-element modified Windkessel model which can reproduce arterial pressure waveforms, including both exponential and oscillatory sections. Active renin, angiotensin II and aldosterone levels were determined on venous blood samples in the supine position and after 30 min active standing. There was decreased proximal (C1, 1.51 +/- 0.11 ml x mmHg(-1), P<0.01) and distal (C2, 0.050 +/- 0.011 ml x mmHg(-1)) arterial compliance in the chronic heart failure patients vs controls (C1, 1.71 +/- 0.16 ml x mmHg(-1); C2, 0.054 +/- 0.006 ml x mmHg(-1)). The chronic heart failure patients were characterized by an aldosterone escape phenomenon which was inversely correlated with the proximal arterial compliance in both supine (r= - 0.795, P=0.002) and standing (r= - 0.628, P=0.029) positions., Conclusions: In chronically treated heart failure patients with full angiotensin-converting enzyme-inhibition and diuretics, there is decreased compliance of the aorta and its major branches, which is inversely correlated with the aldosterone escape phenomenon.

Objective: To compare the commissioning of contraception services by London health authorities with accepted models of good practice., Design: Combined interview and postal surveys of all health authorities and National Health Service (NHS) trusts responsible for running family planning clinics in the Greater London area., Main Outcome Measures: Health authority commissioning was assessed on the presence of four key elements of good practice--strategies, coordination, service specifications, and quality standards in contracts--by monitoring activity and quality., Results: Less than half the health authorities surveyed had written strategies or service specifications for contraception services. Arrangements for coordination of services were limited and monitoring was underdeveloped., Conclusion: The process of commissioning services for contraception seems to be relatively underdeveloped despite the importance of health problems associated with unplanned pregnancy in London. These findings raise questions about the capacity of health authorities to improve the quality of these services through the commissioning process.

Background: While human immunodeficiency virus (HIV)-related causes of death have been well documented in developed countries, in Africa data are scanty and mainly based on autopsy studies from city hospitals which are highly selective and may not represent causes of HIV-associated deaths in the general population. This study, from a rural population, describes the causes of death in HIV-positive people and their HIV-negative controls., Methods: A natural history cohort comprising HIV-1 infected participants and HIV-negative controls was established in rural Uganda in 1990. Causes of death were determined by reviewing the premorbid clinical and laboratory findings and from information obtained from relatives. Blindness to the deceased's HIV serostatus was maintained throughout., Results: In all, 78 deaths occurred over a 6-year period: 63 deaths occurred in the HIV-positive cases (53 prevalent and 10 incident cases) and 15 deaths in the HIV-negative controls. Of the prevalent cases, 56%, and 9% the incident cases enrolled died, compared with 7% of the HIV-negative controls. Of the 55 HIV-positive cases with sufficient data to establish cause of death, 52 (95%) were assessed as having HIV-associated deaths and 48 (87%) died in WHO stage 4 (AIDS). The main causes of death were wasting syndrome (31%), chronic diarrhoea (22%), cryptococcal meningitis (13%) and chest infection (11%)., Conclusions: Our results represent an unbiased selection of deaths in a rural area. The HIV-positive cases have high death rates and die of HIV-related pathologies. The main causes of death reflect the WHO clinical case definition of AIDS. Cryptococcal meningitis is also a common cause of death in this population.

Site-directed mutagenesis of the platelet-derived growth factor (PDGF) B-chain was conducted to determine the importance of cationic amino acid residues (Arg160-Lys161-Lys162; RKK) located within the loop III region in mediating the biological and cell-association properties of the molecule. Binding to both PDGF alpha-and beta-receptors was inhibited by the conversion of all three cationic residues into anionic glutamates (RKK-->EEE), whereas an RKK-->SSS mutant also exhibited a modest loss in affinity for beta-receptors. Replacements with serine at either Arg160 (RKK-->SKK) or at all three positions (RKK-->SSS) had little effect on binding to alpha-receptors. Replacements with either glutamic or serine residues at any of the three positions also resulted in significant inhibition of heparin-binding activity. Furthermore, the RKK-->EEE mutant exhibited decreased association with the cell surface and accumulated in the culture medium as 29-32 kDa forms. Stable transfection of U87 astrocytoma cells with RKK-->EEE mutants of either the A-chain or the B-chain inhibited malignant growth in athymic nude mice. Despite altered receptor-binding activities, each of the loop III mutants retained full mitogenic activity when applied to cultured Swiss 3T3 cells. CD spectrophotometric analysis of the RKK-->EEE mutant revealed a secondary structure indistinguishable from the wild type, with a high degree of beta-sheet structure and random coil content (50% and 43% respectively). These findings indicate an important role of the Arg160-Lys161-Lys162 sequence in mediating the biological and cell-associative activities of the PDGF-BB homodimer, and reveal that the mitogenic activity of PDGF-BB is insufficient to mediate its full oncogenic properties.

Wound dressings guidelines promote rational prescribing. The development of such guidelines is described, including how to get started, the collection of data, format, contents and avoiding the pitfalls. After implementation, the guidelines require on-going monitoring, review, updating and audit.

Objective: We have previously shown that brief myocardial ischemia impairs neural conduction in cardiac sympathetic efferent fibers. However, attenuation of the activity of afferent sympathetic nerves, which may contribute to impaired ischemic nociception and reflex hemodynamic responses, is not well understood. Therefore, we studied the electrophysiological effects of brief myocardial ischemia on the mechano-, chemo- and ischemia-sensitive properties of cardiac sympathetic afferent fibers., Methods: Single unit activity of sympathetic afferent A delta and C fibers innervating the left ventricle (LV) was recorded from the thoracic chain or rami communicantes in 16 anesthetized cats. We tested the response of impulse activity to (1) mechanical LV probing, (2) epicardial application of bradykinin (10 microg), H2O2 (1.5%) or adenosine (500 microg), and (3) 1 min of coronary occlusion. Repeat tests were performed in 11 of 16 fibers after 15 min of coronary occlusion and 15 min of reperfusion. Control responses were measured in five fibers before and after a 30-min interval without ischemia., Results: Afferent fibers responded with increased activity to LV probing (16/16 fibers), bradykinin (13/16 fibers), H2O2 (7/11 fibers), adenosine (1/11 fibers), and to a 60 s period of coronary occlusion (11/16 fibers). The unit impulse activity to 1 min of coronary occlusion was markedly attenuated after 15 min of myocardial ischemia and 15 min of reperfusion (P < 0.05). This attenuation was associated with reduced sensitivity to mechanical and chemical stimuli, while in separate time-control studies (n = 5) no attenuation was observed in absence of ischemia., Conclusion: A brief period of myocardial ischemia is capable of attenuating mechano-, chemo- and ischemia-sensitive activity of cardiac afferent sympathetic nerves. This may have important implications for the mechanism of silent myocardial ischemia.

Adipose tissue leptin mRNA levels are decreased by food deprivation or induction of insulin-deficient diabetes. To determine whether plasma leptin concentrations are similarly affected, whether treatment of diabetes with insulin restores plasma leptin, and whether this requires restoration of body weight (lost as a result of diabetes) and/or normalization of glycemia, we measured plasma leptin concentrations in control, untreated streptozotocin (STZ)-diabetic, and insulin-treated STZ-diabetic rats. Plasma leptin was markedly reduced in untreated STZ-diabetic rats. Insulin treatment for 4 to 17 days increased plasma leptin approximately twofold above control levels. However, despite the hyperleptinemia, insulin-treated diabetic rats gained weight at a rate equal to that of sham-treated controls. Epididymal adipose tissue leptin mRNA levels in 17-day insulin-treated diabetic rats were equal to but did not exceed sham-control levels, unlike plasma leptin. Plasma glucose concentrations in insulin-treated STZ-diabetic rats were lower than in sham controls. Therefore, to determine whether hypoglycemia may be important in increasing plasma leptin, we measured plasma leptin levels in diabetic rats infused with insulin for 3 hours along with a variable-rate glucose infusion targeting glycemia to 200 or 40 mg/100 mL. Plasma leptin rapidly increased in these rats irrespective of target glycemia. Plasma leptin also increased rapidly in normal rats infused with insulin and glucose (target glycemia, 200 mg/100 mL). We conclude that plasma leptin concentrations are markedly reduced under conditions of insulin deficiency and rapidly increased by insulin treatment. The increase in plasma leptin does not require restoration of body weight and, under glucose clamp conditions, does not depend on target glycemia. Hyperleptinemia in insulin-treated diabetic rats is not explained on the basis of steady-state leptin mRNA levels, at least as reflected in epididymal fat.

Human B cells stimulated through both their immunoglobulin and CD40 receptors up-regulate 745 +/- 51 interleukin (IL)-13 ligand binding sites with an affinity of 0.91 +/- 0.08 nM within 24 h. IL-13 binds primarily to the IL-13Ralpha1 with subsequent sequestration of the IL-4Ralpha into the complex. IL-13Ralpha1 may also be found in those receptors capable of binding IL-4. gamma chain (gammac) participates in receptors capable of binding IL-4 but is not found in association with bound IL-13. Dimeric receptors composed of the IL-4Ralpha complexed with either the IL-13Ralpha1 or gammac occur simultaneously within defined B cell populations. mRNAs for all receptor constituents are increased subsequent to immunoglobulin stimulation alone, while maximal expression of IL-13Ralpha1 is more dependent upon co-stimulation of immunoglobulin and CD40 receptors. mRNA levels for IL-13Ralpha1 vary over a wider range subsequent to surface stimulation than other receptor components. Although gammac is not bound to IL-13 in B cells under the conditions evaluated, it may influence IL-13 binding by competing with IL-13Ralpha1 for association/sequestration with the IL-4Ralpha chain. IL-13Ralpha2 does not participate in the IL-13 receptor that is up-regulated upon activation of quiescent tonsillar B lymphocytes, although mRNA for the protein may be found in the centroblastic fraction of tonsillar cells.

Objectives: To describe the early manifestations of HIV-1 infection before the development of AIDS, in a rural Ugandan population., Methods: Three monthly follow-up of HIV-1-infected and uninfected participants in an HIV-1 natural history cohort from the start of the cohort in 1990 to the end of 1996., Results: A total of 107 persons with prevalent infection and 104 persons with incident infection were enrolled. Eighty (75%) prevalent and 89 (86%) incident individuals were asymptomatic on enrollment. Of the 91 persons with incident infection seen within 2 years of their estimated date of seroconversion, 51% [95% confidence interval (CI), 40-61] were still asymptomatic 2 years after seroconversion. At 4 and 5 years after seroconversion, only 26% (95% CI, 17-36) and 11% (95% CI, 4-22), respectively, remained asymptomatic. A total of 89 participants entered World Health Organization (WHO) stage 2, and their main stage-defining conditions were weight loss <10% (and > 5%) and minor mucocutaneous manifestations. The median CD4 lymphocyte count for participants entering WHO stage 2 was 516 x 10(6) cells/l (interquartile range, 360-884 x 10(6)/l). A total of 94 participants entered WHO stage 3 and the main reasons were weight loss >10%, unexplained chronic diarrhoea, fever for more than 1 month, and severe bacterial infection. The median CD4 lymphocyte count for participants entering WHO stage 3 was 428 x 10(6) cells/l (interquartile range, 276-736 x 10(6)/l). The rates of all conditions reported under the WHO staging system were significantly more frequent in HIV-positive persons than HIV-negative controls with the exception of fever for more than 1 month and oral hairy leukoplakia (which was seen in only three individuals)., Conclusion: These are the first data from a non-selected African population describing the early manifestations of HIV infection. The main early manifestations were weight loss, minor mucocutaneous features, chronic diarrhoea, chronic fever and severe bacterial infections. The apparent rapid development of HIV-related signs and symptoms is probably indicative of the high background level of these conditions in our study area, as reflected by the rates of these conditions in the HIV-negative controls.

We compared treatment of patients with episodic, severe, migraine-vascular headaches in three outpatient settings associated with a major medical center: the Charlton Outpatient Therapy Center (COTC), a dedicated transfusion and injection facility which provides treatment based on physician orders written in advance of the patient's visit; a walk-in Urgent Care Center (UCC); and a traditional hospital emergency trauma unit (ETU). For a 7-month period in 1995, all patient visits for acute migraine headache to the COTC, UCC, and ETU were reviewed. Data collected included the treatment and charges. After the study period, a sample of patients was surveyed regarding their outcome and satisfaction with care at each of the three facilities. During the study period, 15 patients visited the COTC 446 times for the treatment of acute migraine, 80 patients visited the UCC 233 times, and 182 patients visited the ETU 238 times. The average charges per visit were $39.93 for the COTC, $57.28 for the UCC, and $317.71 for the ETU. Average time spent in order to obtain care was 35 minutes in the COTC, 62 minutes in the UCC, and 105 minutes in the ETU. Intramuscular meperidine with either promethazine or hydroxyzine was the most commonly administered treatment in all three settings. Patients treated in the COTC reported greater satisfaction than the patients seen in the UCC or ETU. A dedicated outpatient facility with extended hours of operation and the capability of treating acute headache patients with parenteral medications based on standing orders has provided a community of migraine sufferers with cost-effective care.

Indirect molecular diagnosis of X linked hypohidrotic ectodermal dysplasia (XLHED), a congenital disorder of hair, teeth, and eccrine sweat glands, has been possible by linkage analysis. Direct mutation detection would enable carrier detection in female relatives of sporadic cases, as well as help distinguish XLHED from the rarer, clinically indistinguishable, autosomal recessive disorder ARHED. Recently, a candidate gene for XLHED has been identified. Genomic DNA from 162 affected males and 21 females, who were either obligate carriers or had manifestations of the disorder, were screened by SSCP analysis. A subset of the patients had been previously screened for large genomic deletions and had limited screening of a single exon by SSCP analysis. The two known exons were amplified using flanking primers. Approximately 7% of patients, all males, had putative mutations identified within exon 1, but no variants were found within exon 2. Ten different putative mutations and four probable polymorphisms were identified. Both of the known exons were sequenced in 10 patients who had no detectable SSCP changes, but no additional mutations were found. No correlation between phenotype and genotype was evident between either affected subjects or subjects with or without detectable mutations. The results of the study indicate that only a small minority of affected males can be diagnosed by direct mutation analysis, and that the remainder of the patients are likely to have mutations in as yet unidentified exons of the EDA gene. Linkage analysis, in informative situations, therefore remains the only practical diagnostic option available.

Genetic causes of Alzheimer's disease (AD) include mutations in the amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2) genes. The mutant APP(K670N,M671L) transgenic line, Tg2576, shows markedly elevated amyloid beta-protein (A beta) levels at an early age and, by 9-12 months, develops extracellular AD-type A beta deposits in the cortex and hippocampus. Mutant PS1 transgenic mice do not show abnormal pathology, but do display subtly elevated levels of the highly amyloidogenic 42- or 43-amino acid peptide A beta42(43). Here we demonstrate that the doubly transgenic progeny from a cross between line Tg2576 and a mutant PS1M146L transgenic line develop large numbers of fibrillar A beta deposits in cerebral cortex and hippocampus far earlier than their singly transgenic Tg2576 littermates. In the period preceding overt A beta deposition, the doubly transgenic mice show a selective 41% increase in A beta42(43) in their brains. Thus, the development of AD-like pathology is substantially enhanced when a PS1 mutation, which causes a modest increase in A beta42(43), is introduced into Tg2576-derived mice. Remarkably, both doubly and singly transgenic mice showed reduced spontaneous alternation performance in a "Y" maze before substantial A beta deposition was apparent. This suggests that some aspects of the behavioral phenotype in these mice may be related to an event that precedes plaque formation.

Despite differences in their tissue of origin, many tumors share high level expression of certain tumor-associated proteins. Our laboratory has focused on the possibility of utilizing antigenic components of these proteins as a focus for T-cell immunotherapy of cancer. The advantage of targeting such commonly expressed proteins is the fact that such therapy could be of value in eliminating many different types of tumors. A potential barrier in the identification of T-cell epitopes derived from these proteins and presented by tumor cells is the fact that these proteins are also expressed at low levels in some normal tissues, and therefore, self-tolerance may eliminate T cells that are capable of recognizing these epitopes with high avidity. We have utilized two different murine model systems to explore the extent to which self-tolerance may limit the immune response to a tumor-specific antigen. The first compared the ability of mice deficient in expression of murine p53 (p53 knock-out mice) and normal mice, to respond against several epitopes of the p53 protein. The second model compares the ability of conventional mice with transgenic mice that express the influenza hemagglutinin in the periphery to respond to a dominant antigenic peptide of this transgene product. In both models we have investigated the effect self-tolerance has on elimination of tumors expressing the toleragen.

Purpose: To report the ocular findings in HIV-1 seropositive individuals and HIV-negative controls in a population-based cohort in rural Uganda., Methods: Participants were examined by an ophthalmologist, who was unaware of their HIV-status., Results: 238 participants were examined, 43 were HIV-1 prevalent cases (infected prior to 1990); 62 were HIV-1 incident cases and 133 were HIV-negative controls. Eleven of the HIV-positive participants had AIDS, and a further 8 had a CD4 count of less than 200 cells/mm3. Bilateral low vision was recorded in 9 participants and cataracts were the main cause of bilateral low vision. The mean intra-ocular pressure (IOP) was 12.6 mm Hg, and no association was found between IOP and CD4 lymphocyte count. Although significantly more HIV positives had some sign of intraocular inflammation compared to the negatives (p = 0.02) there was no significant linear trend in the HIV positives with decreasing CD4 count. Overall, 11 (26%) prevalent, 6 (10%) incident cases and 8 (6%) HIV-negatives controls had some evidence of intraocular inflammation, however, only one person had reduced visual acuity attributable to these lesions. Punctate epithelial erosions and keratic precipitates in the anterior chamber were seen significantly more frequently in HIV-positives compared to the HIV-negative controls. Cotton wool spots were not seen., Conclusions: A substantial proportion of HIV-infected persons had ocular findings which may have been attributable to their infection, however in only one case did this result in reduced visual acuity. Although the ocular complications of AIDS seem to comprise a large extra element in the work load of tertiary care hospitals dealing with eye problems, on a population basis such cases are infrequent.

The association of immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) with Hodgkin's disease has been known for many years. Autoimmune cytopenia has also been described in patients that have undergone allogeneic or autologous bone marrow transplantation. We report a rare case of Evans syndrome in a patient 3 years after autologous bone marrow transplantation for recurrent Hodgkin's disease.

Discharge planning has received much attention in the nursing literature over the past few years, and there has been particular concern over the discharge of older people back into their domestic environment. The practical and logistical problems of managing such a discharge are considerable, but in this paper we argue that discharging older people from hospital to care homes is equally problematic, though in different ways. This is a neglected area of research, perhaps because discharge into a care home seems to present fewer organizational problems. There is, however, an extensive body of literature from a range of different disciplines which suggests that the loss of home and entry into a strange environment can be very stressful. This paper outlines this literature and explores the implications for nursing practice.

Twenty-seven patients with non-small cell lung cancer were recruited into a phase II study of single-agent vinorelbine using a 25 mg/m(2) weekly dose schedule. All patients were inoperable (stage III disease - 11 patients; stage IV disease - 16 patients). Median age was 64 years (range: 37-72 years). Histological sub-types were squamous cell carcinoma (15 patients), adenocarcinoma (8) and large cell carcinoma (4). Partial response was documented in 4 (16%) of 25 evaluable patients, and stable disease in 13 (52%) patients. Median duration of response was 6.5 months (range 3-16 months) and median overall survival for patients with stable disease/partial response was 8 months (range 1-20 months). Vinorelbine was generally well tolerated although WHO grade 3/4 toxicity was noted for lethargy, constipation, alopecia (2 patients each), headache and non-tumour related bone pain (1 patient each). Vinorelbine is a moderately active single-agent in non-small cell lung cancer and is currently undergoing evaluation as part of combination chemotherapy regimens.

Double minute chromosomes (dmin) occur in about 3.3-10.6% of acute leukemia, especially in the elderly. However, dmins are relatively rare in myelodysplastic syndrome (MDS). We describe a case of refractory anemia with excess blasts associated with complex cytogenetic abnormalities, dmins, and brief survival.

Purpose: To evaluate the effectiveness of alternating or sequential schedules of cyclophosphamide, doxorubicin, and etoposide (CDE) chemotherapy and irradiation in patients with previously untreated small-cell lung cancer (SCLC)., Materials and Methods: A total of 335 eligible patients were randomized between five courses of CDE chemotherapy followed by thoracic irradiation 50 Gy in 20 daily fractions (S) and the same total dose of chemotherapy and irradiation split into four courses of five daily fractions delivered on days 14 to 21 of the second and subsequent chemotherapy courses (A). Patients had a median age of 61 years (range, 33 to 75); 224 (66%) were male; the Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0 or 1 in 311; and 254 had weight loss less than 10%., Results: The overall median survival duration was 15 months, with 62% (95% confidence interval [CI], 57% to 67%) 1-year, 25% (95% CI, 20% to 30%) 2-year, and 14% (95% CI, 10% to 18%) 3-year survival rates. There was no significant difference between the arms. The median survival time was 14 months in A and 15 months in S. One-year survival was 60% in A (95% CI, 53% to 67%) and 64% in S (95% CI, 57% to 71%); 2-year survival was 26% in A (95% CI, 19% to 33%) and 23% in S (95% CI, 16% to 30%); and 3-year survival was 12% in A (95% CI, 6% to 18%) and 15% in S (95% CI, 9% to 21%). World Health Organization (WHO) grade 3 and 4 neutropenia occurred in 90% of A and 77% of S patients (P < .001) and WHO grade 3 and 4 thrombocytopenia in 33% of A and 20% of S patients (P < .001). Rates of other acute and late toxicities were similar in both arms. Hematologic toxicity compromised treatment dose delivery; less than 50% of A patients received greater than 95% of prescribed chemotherapy and 77% their full radiation course, compared with 60% and 93% for arm S (P < .009). Local relapse was the site of first failure in 60% of all patients and 75% of these suffered an in-field relapse; no difference could be seen between the two arms., Conclusion: This trial failed to confirm the superiority of an alternating schedule of delivery. For this combination of chemotherapy and irradiation, hematologic toxicity compromised treatment delivery and could have contributed to the overall result. The poor rates of local control are disappointing and require intensification of the radiation therapy strategy.

Background: The majority of people infected with HIV-1 live in Africa, yet little is known about the natural history of the disease in that continent. We studied survival times, disease progression, and AIDS-defining disorders, according to the proposed WHO staging system, in a population-based, rural cohort in Uganda., Methods: In 1990 we recruited a random sample of people already infected with HIV-1 (as prevalent cases) detected during the initial survey round of a general-population study to form a natural-history cohort. Individuals from the general-population cohort who seroconverted between 1990 and 1995 (incident cases) were also invited to enroll. Participants were seen routinely every 3 months and when they were III., Findings: By the end of 1995, 93 prevalent cases and 86 incident cases had been enrolled. Four patients in the prevalent group were in stage 4 (AIDS) at the initial visit. During the next 5 years, 37 prevalent cases progressed to AIDS. Seven incident cases progressed to AIDS and the cumulative progression to AIDS at 1, 3, and 5 years after seroconversion was 2%, 6%, and 22%, respectively. The cumulative probability of AIDS at 4 years from entering stages 1, 2, and 3 was 11%, 33%, and 58%, respectively. There were 47 deaths among prevalent cases and seven among incident cases during follow-up. The cumulative mortality 4 years after patients entered stages 1, 2, 3, and 4 was 9%, 33%, 56%, and 86%, respectively. The median survival after the onset of AIDS was 9.3 months., Interpretation: Our results are important for the setting of priorities and rationalisation of treatment availability in countries with poor resources. We found that progression rates to AIDS are similar to those in developed countries for homosexual cohorts and greater than for cohorts infected by other modes of transmission. However, we have found that the rates of all-cause mortality are much higher and the progression times to death are shorter than in developed countries.

This study tested various models of the effects of positive and negative exchanges on positive and negative affect using structural equation modeling. Based on a probability sample of middle-aged and older adults, the relationships between social exchanges and psychological well-being were examined both within the total sample and within subgroups of individuals who had experienced few vs many life events. Within the general population, the Domain Specific Model resulted in the best fit. That is, positive exchanges were associated with positive affect, and negative exchanges were associated with negative affect. However, among the subgroup that had experienced more life events, there was a significantly stronger relationship between negative exchanges and negative affect. These findings suggest that, to understand the effects of social exchanges, it is important to consider the context of life events.

While noninvasive studies of bone mass and turnover in blacks and whites abound, histologic evaluations are very rare. We have performed a comparative bone histomorphometric study of iliac biopsies from 55 healthy, premenopausal women including 21 blacks (mean age 33.4 + 1.2 years) and 34 whites (mean age 32.5 + 0.8 years) of comparable age, weight, body composition, education, and lifestyle. Biochemical indices of mineral metabolism: parathyroid hormone, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, serum ionized calcium, serum phosphorus, and urinary calcium/creatinine were measured in the fasting state. Blacks had lower 25-hydroxyvitamin D (315 +/- 3.36 vs. 63.21 +/- 3.79 nmol/l, p = 0.0001). Histomorphometric indices of bone volume, structure, and connectivity were not different between groups. The following indices of bone remodeling were also similar in both groups: eroded perimeter, osteoid width, mineralizing perimeter, tissue-based bone formation rate, osteoid maturation time, active formation period, and activation frequency. However, osteoid perimeter (black [B] = 15.85 +/- 1.30 vs. white [W] = 9.49 +/- 0.70%, p = 0.0002), osteoid area (B = 2.55 +/- 0.32 vs. W = 1.39 +/- 0.12%, p = 0.003), single-labeled perimeter (B = 5.46 +/- 0.54 vs. W = 4.04 +/- 0.33%, p = 0.03), mineralization lag time (B = 38.18 +/- 4.04 vs. W = 21.83 +/- 1.60 days, p < 0.009), and total formation period (B = 148.15 +/- 19.70 vs. W = 84.04 +/- 7.62 days, p = 0.0056) were higher in blacks than in whites. The quiescent perimeter (B = 76.91 +/- 1.40 vs. W = 84.25 +/- 0.91%, p = 0.0001), mineral apposition rate (B = 0.70 +/- 0.02 vs. W = 0.75 +/- 0.02 micron/day, p = 0.066), mineralizing osteoid perimeter (B = 0.49 +/- 0.04 vs. W = 0.75 +/- 0.04%, p = 0.0001) and adjusted apposition rate (B = 0.35 +/- 0.04 vs. W = 0.58 +/- 0.04 micron3/micron2/day, p = 0.0001) were all lower in blacks than in whites. These results indicate that there are no differences in bone volume, microstructure, or turnover between black and white premenopausal women. However, there are significant differences in the mechanism of bone formation between the two groups, with a lower rate of mineralized matrix apposition within each remodeling unit and a longer total formation period in blacks than in whites. The differences appear to the result of more frequent and/or longer inactive periods in the life span of the bone formation units in blacks. These differences may allow a greater overall deposition of bone mineral in black women and therefore help explain a higher bone mass and perhaps better bone quality in black than white women.

Background: Esophagectomy for esophageal cancer is associated with substantial operative morbidity and mortality. The effect of surgical experience on results of esophagectomy has received little attention in the medical literature., Methods: A retrospective review of esophagectomies for cancer was done., Results: Seventy-four patients underwent esophagectomy by 20 different surgeons. Three surgeons performed 6 or more esophagectomies per year ("frequent" surgeons), whereas the other 17 surgeons performed 5 or fewer esophagectomies per year ("occasional" surgeons). Forty-two patients were operated on by frequent surgeons. There were 3 (7%) anastomotic leaks and no deaths. In 32 patients operated on by occasional surgeons, there were 7 (22%) anastomotic leaks and 7 (22%) operative deaths. The anastomotic leak rates were not significantly different (P < .07), but frequent surgeons had a significantly lower operative mortality (P < .0014)., Conclusions: Esophagectomy for esophageal cancer should be performed by experienced esophageal surgeons with sufficient yearly volume of procedures to maintain competence.

Objective: To determine the effects of elevated endogenous E2 levels on in vitro platelet function in patients undergoing controlled ovarian hyperstimulation (COH)., Design: Women with normal ovulatory cycles and patients undergoing COH on cycle day 3 and near ovulation (preovulatory follicles were at least 16 mm in diameter) were studied. Serum E2, Thrombostat 4000, (V. d. Goltz, Seeon, Germany), von Willebrand factor antigen (vWF-Ag), and platelet aggregation and adenosine triphosphate (ATP) release to adenosine diphosphate (ADP), collagen (COL), and arachidonic acid (AA) were measured., Setting: University-based outpatient infertility clinic., Patient(s): Twenty-two consenting infertile women undergoing COH cycles and 14 women with documented ovulatory cycles., Main Outcome Measure(s): Whole blood platelet aggregation with ADP, COL, AA, and Thrombostat 4000., Results(s): Estradiol levels rose significantly at peak times (P = 0.011). No changes were noted in in vitro platelet function measured by the Thrombostat 4000 and by whole blood platelet aggregation with ADP and AA and in ATP release with ADP, COL, or AA. Aggregation with collagen was increased because of likely elevations in vWF-Ag levels., Conclusion(s): No significant changes in in vitro platelet function were noted in 19 women undergoing COH with E2 levels two to three times that observed in oral contraceptive or hormone replacement therapy users, suggesting no increased risk for arterial thromboembolism.

Objective: To describe a population-based rural cohort of HIV-1-seropositive and seronegative individuals established in 1990 in south-west Uganda, and determine survival times in the cohort., Design: Prospective cohort study., Methods: Participants were recruited from a large population study, and invited to attend a clinic every 3 months. They were seen by clinicians who administered detailed medical questionnaires and undertook a physical examination., Results: By the end of 1995, 390 (79%) of the 491 people asked to enrol in the natural history cohort (NHC) had done so. Ninety-three were prevalent cases of HIV infection detected during the initial survey round of the general population cohort in 1989/1990, 66 were subsequent incident cases, 177 were age-matched HIV-negative controls and 54 were HIV-negative spouses of HIV-positive individuals. Twenty participants seroconverted in the NHC. The age-standardized mortality rates per 1000 person-years for the prevalent, incident, and negative cases were 156.5 [95% confidence interval (CI), 115.8-211.4], 35.0 (95% CI, 16.4 75.0) and 13.5 (95% CI, 7.3-25.1), respectively. The median survival time from enrolment to death for the prevalent cases was 4.5 years (95% CI, 3.5- > 5.2); > 5.4 years from seroconversion for the incident cases; and > 5.2 years from enrolment for the HIV-negative cases. The 5-year cumulative survival for prevalents, incidents and HIV-negative participants was 46%, 83% and 94%, respectively., Conclusions: We have described an NHC of HIV-positive and HIV-negative participants which is representative of the general population. The NHC was established over 5 years ago; it is continuing and we are maintaining good compliance rates. Survival probabilities in the cohort were lower than most other reported studies.

Aspergillus infections in the pediatric bone marrow transplant (BMT) patients are usually fatal. We began the use of a prophylactic nasal spray of amphotericin in 1990. This nasal spray was provided in addition to low-dose intravenous amphotericin. During the time of this study, the number of fatal cases of aspergillus in the pediatric BMT population was reduced significantly from 13.8% to 1.8% (P < 0.0025) thereby suggesting that the use of nasal amphotericin in this population helps to prevent fatal aspergillus infections. The lack of significant side-effects and the ease of administration make this a very helpful preventive measure in the supportive care of pediatric bone marrow transplant patients.

Pulse-chase analysis of human platelet-derived growth factor (PDGF) B-chain was conducted in stably transfected Chinese hamster ovary cells to determine precisely the kinetics of processing, intracellular trafficking and secretion. Newly synthesized 31 kDa monomers of the B-chain (p31) dimerized rapidly via disulfide bonds to a p54 species (t1/2 < 30 min). The p54 dimer was processed to a group of intracellular, cell surface (suramin-releasable) and secreted forms whose rates of appearance and disappearance from the cell were measured over a 48 h period. The newly synthesized p31 species was quantitatively converted to p27 by treatment with endoglycosidase H, consistent with efficient N-glycosylation at a site in the N-terminal propeptide region (Asn63-Met64-Thr65). Interruption of B-chain glycosylation by oligodeoxynucleotide-directed mutagenesis resulted in a significant increase in suramin-releasable forms at the cell surface (p34-38) and a concomitant decrease in accumulation of an intracellular p24 species. The glycosylation-defective mutant exhibited slight increases in receptor binding and mitogenic activity. Our results suggest that N-linked glycosylation of the B-chain is not important for formation of mitogenically active protein, but that it plays a role in early intracellular sorting and proteolytic processing events.

We describe a case of acute myeloblastic leukemia with a novel isochromosome 18, i(18)(p10), preceded by aplastic anemia for six months. The patient is a cotton grower chronically exposed to pesticides. The significance of this chromosomal abnormality is unknown. The possible relationship to the preceding history of aplastic anemia and occupational pesticide exposure is speculated on. The possible mechanism of the association of acute leukemia and aplastic anemia is discussed.

We describe a case of non-pyothorax-associated primary pleural lymphoma with bone marrow and central nervous system involvement, and complex karyotypic abnormalities involving nullisomy chromosome 17 and multiple breakpoints that are commonly associated with acute leukemia and myeloproliferative diseases.

Mutations in the genes encoding amyloid-beta precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2) are known to cause early-onset, autosomal dominant Alzheimer's disease. Studies of plasma and fibroblasts from subjects with these mutations have established that they all alter amyloid beta-protein (beta APP) processing, which normally leads to the secretion of amyloid-beta protein (relative molecular mass 4,000; M(r) 4K; approximately 90% A beta1-40, approximately 10% A beta1-42(43)), so that the extracellular concentration of A beta42(43) is increased. This increase in A beta42(43) is believed to be the critical change that initiates Alzheimer's disease pathogenesis because A beta42(43) is deposited early and selectively in the senile plaques that are observed in the brains of patients with all forms of the disease. To establish that the presenilin mutations increase the amount of A beta42(43) in the brain and to test whether presenilin mutations act as true (gain of function) dominants, we have now constructed mice expressing wild-type and mutant presenilin genes. Analysis of these mice showed that overexpression of mutant, but not wild-type, PS1 selectively increases brain A beta42(43). These results indicate that the presenilin mutations probably cause Alzheimer's disease through a gain of deleterious function that increases the amount of A beta42(43) in the brain.

Endothelial injury is a central feature of vascular disease induced by cigarette smoking and may act as a precursor for future atherosclerosis. Using forearm occlusion plethysmography, we studied the vascular responses to methacholine (an endothelium-dependent vasodilator) and sodium nitroprusside (an endothelium-independent vasodilator) infused into the brachial artery of 35 long-term cigarette smokers and 16 nonsmoking subjects. NG-monomethyl-L-arginine (L-NMMA), a stereospecific inhibitor of nitric oxide production, was used to inhibit synthesis of nitric oxide in the endothelium. The reactive hyperemic response at peak and during recovery to the temporary interruption of forearm blood flow was also compared between groups. Smokers had elevated carboxyhemoglobin levels compared with nonsmokers (5.1 +/- 2.1% vs 0.8 +/- 0.4%; p < 0.001). No differences were found in the peak or late hyperemic responses between groups. In smokers, the incremental infusions of methacholine and sodium nitroprusside increased forearm blood flow from 3.6 +/- 1.2 to 12.9 +/- 9.0 ml.min-1 x 100 ml-1 and from 4.0 +/- 1.5 to 9.3 +/- 4.0 ml.min-1 x 100 ml-1, respectively, compared with 3.2 +/- 1.0 to 13.5 +/- 5.6 ml.min-1 x 100 mL-1 and from 2.9 +/- 0.7 to 8.6 +/- 4.2 ml.min-1 x 100 ml-1 in nonsmoking subjects (p = NS). L-NMMA (4 mumol/min for 5 minutes) significantly reduced forearm blood flow in both smokers and nonsmokers from 4.1 +/- 1.4 to 3.4 +/- 1.2 ml.min-1 x 100 ml-1 and 3.8 +/- 0.7 to 2.3 +/- 0.5 mL.min-1 x 100 ml-1, respectively (p < 0.01 for both); and the decrement in forearm blood flow in nonsmokers was significantly greater than that recorded in smoking subjects (p < 0.05). In this study, long-term cigarette smokers exhibited an impairment in basal, but not stimulated, nitric oxide-mediated vasodilation.

Objectives: To determine the feasibility of replacing a ureteral segment with a neointimized Gore-Tex graft., Methods: Seven adult mongrel dogs underwent a two-stage operative procedure. The first procedure involved arterializing the graft to stimulate spread of a luminal neoendothelium by transmural capillary growth. Eight weeks after the initial procedure, a segment of the ipsilateral ureter was replaced with a segment of the neointimized graft., Results: Histologic evaluation of a portion of the graft removed during the second procedure demonstrated transmural neocapillary ingrowth in all grafts; however, there was no neoendothelial growth on the luminal surface. In 5 dogs the graft was occluded with blood clot and was not suitable for a ureteral prosthesis. In 2 dogs the graft was patent and was successfully incorporated into the urinary system. After 1 year of observation, both of these dogs maintained a patent ureter and had no evidence of hydronephrosis on intravenous urogram., Conclusions: These data demonstrate that a Gore-Tex graft can be used as a ureteral prosthesis in the dog. The importance of preliminary arterialization, however, remains to be determined.

An increase in the number of human isolates of Salmonella virchow phage type (PT) 26 in England and Wales during 1994 was investigated. A national case control study was conducted which included 88 cases and 182 controls. The cases were mostly young adults (median age 26) and 13 (15%) were admitted to hospital. Acquisition of S. virchow PT 26 was associated with the consumption of any chicken (OR 2.5, CI 1.1-5.8), of chicken curry from restaurants and take aways (OR 2.9, CI 1.4-6.1), and of some other diverse types of pre-prepared chicken (OR 3.8, CI 1.9-7.6). Halal chicken was associated (P = 0.006) with illness in a subset. There were negative associations with contact with animals (OR 0.47, CI 0.23-0.95) and with the consumption of chicken cooked whole (OR 0.37, CI 0.21-0.66). The increase in S. virchow PT 26 may be due to changing epizoology and may be an indicator of what will become the dominant salmonella strain in poultry in future years. The increasing incidence of S. virchow PT 26 is of particular concern because of its association with more invasive disease in humans.