A case of gastroduodenal lipomatosis.

Although sporadic lipomas are not uncommon in the upper gastrointestinal tract, diffuse gastroduodenal lipomatosis is a rare clinical entity. Medical literature reveals a limited number of such cases presenting with upper gastrointestinal obstruction or bleeding. We present the management experience of a 43-year-old woman who presented with intussusception causing high small-bowel obstruction secondary to jejunal lipomatosis. Computed tomography showed diffuse fatty thickening of the gastric wall in addition to multiple lipomas in stomach, duodenum and in the jejunum with jejunal intussusception. As complete resection of the affected segment was not possible, a side-to-side jejunal bypass was made. The patient remains well on review after 18 months.

The MR imaging appearances and natural history of seromas following excision of soft tissue tumours.

Fluid collections (seromas) may accumulate at the site of surgery following excision of musculoskeletal soft tissue tumours. The aim of this retrospective study was to review the magnetic resonance (MR) imaging features of postoperative seromas identifying changes over time on follow-up scans. A total of 170 MR scans from 80 patients were reviewed showing one or more seromas. All patients had undergone previous surgery for a musculoskeletal soft tissue tumour. The typical MR appearances of a seroma were shown to be a well-defined oval or rounded (54%) soft tissue mass, arising at the site of previous surgery, with a thin, dark pseudocapsule, surrounding soft tissue oedema (80%), homogeneous contents that are hypointense (relative to adjacent muscle) on T1-weighted images (74%) and hyperintense on T2-weighted and STIR images (79%). Approximately one-quarter of cases revealed atypical features including hyperintense contents on T1-weighted (26%) and/or heterogeneous contents on T2-weighted images (21%), reflecting the breakdown of blood products and organization of the fluid collection. A distinctive fine feathery pattern arising from the inner surface of the seroma or from septations was identified in 10% of cases. In those patients who underwent one or more follow-up scans, the volume of the seromas decreased in 66% cases, remained unchanged in 15% and increased in 19%. Seromas are not an uncommon finding (<10% of cases) following surgery for a soft tissue tumour. The majority of cases show the typical MR features of a fluid collection. The pitfalls in differentiating an atypical seroma from a recurrent soft tissue sarcoma are discussed.

Identification of microsatellites in expressed muscle genes: assessment of a desmin (CT) dinucleotide repeat as a marker for meat quality.

We investigated the presence of dinucleotide repeats (microsatellites) in a porcine skeletal muscle cDNA library. In total, microsatellites were found in nearly 4% of all muscle cDNA clones, of which CT- and TG-repeats were the most prevalent. We found a near full-length desmin cDNA clone with a CT-repeat sited downstream from its stop codon. From 44 commercially reared pigs, six allelic length polymorphisms were identified at this microsatellite locus (128, 131, 134, 135, 136, and 138 bp), whose desmin genotypes were associated with pH change after slaughter (P=0.031) and colour variation of meat (P<0.001 for hue, P<0.005 for lightness, and P=0.014 for b colour). Two of the genotypes (131/131 bp and 131/135 bp) were consistent with paler meat. This finding indicates the usefulness of the cDNA library approach to generate markers for marker-assisted selection and suggests that the desmin microsatellite could be a possible selection marker.

62Cu-PTSM and PET used for the assessment of angiotensin II-induced blood flow changes in patients with colorectal liver metastases.

The aim of this study was to establish a quantitative positron emission tomography (PET) method for investigating angiotensin II (AII)-induced changes in blood flow distribution in the liver. This was in order to evaluate the role of vascular manipulation applied to locoregional chemotherapy treatment in patients with colorectal liver metastases. The tracer selected was copper-62 (II) pyruvaldehyde bis-(N4-methyl)thiosemicarbazone (62Cu-PTSM), which exhibits high first-pass extraction and tissue retention following intra-arterial administration. The short half-life of the tracer and its availability from a 62Zn/62Cu generator enabled short-interval repeat PET scans on patients in a single imaging session. Distribution of tracer within the liver was imaged in a single view using a PET camera with rotating large-area detectors. By optimisation of the acquisition protocol, it was possible to acquire sufficient data to produce good-quality images and to quantify tracer uptake with an accuracy of <10%. Reproducibility of the imaging method was assessed in a single patient in whom three consecutive 62Cu-PTSM PET scans were obtained, and in whom no vascular manipulation was performed. Sets of scans (before, during and immediately after a 45-min AII infusion) were obtained in nine patients to assess blood flow changes associated with prolonged vascular manipulation. Significant individual responses, varying in both the magnitude and the duration of flow change, were observed in the majority of cases (7/11 lesions; 7/9 patients). These findings illustrate the potential of 62Cu-PTSM and PET for pharmacological studies. The wide range of individual patient responses to AII infusion suggests that PET blood flow assessment would be of value for selecting patients in whom this procedure may be effective.

An investigation into the practice and benefits of statutory aftercare in an inner city psychiatric service.

The implementation of statutory aftercare for psychiatric inpatients, as outlined in Section 117 of the Mental Health Act 1983 (England and Wales), was studied by examining current practice in an inner city psychiatric service. Seventy-seven per cent of patients received Section 117 aftercare; 56% of patients did not have an identified key worker. A significant proportion of those receiving statutory aftercare did not have evidence of adequate forward planning. General practitioners did not attend any meetings. Patients who had Section 117 aftercare were compared with those who did not. Using the Cox regression model, it was found there was no significant difference between these two groups in terms of time between discharge and first readmission, readmission rate, and length of first readmission.

General practitioners' views of an open referral system to a community mental health service.

The satisfaction of general practitioners with a community mental health service operating an open referral system was compared to that with two services both operating a closed referral system covering the same inner-city district. The open referral system allows any agency (including patients) to contact the service by letter or by telephone, and priority is given to patients with serious mental illness. General practitioners' satisfaction with all aspects of the open referral system was greater than that with either of the closed referral systems. In particular, speed of assessment of referrals was preferred in the open referral system.

Doctors' holding power in practice: section 5(2) of the Mental Health Act 1983.

Section 5(2) of the Mental Health Act 1983 (England and Wales) is a commonly used short term power of detention often implemented by junior medical staff, which has no statutory right of appeal. There is little published analysis of its use in clinical practice. A detailed case note study of its use in a psychiatric service with a large catchment area is presented. Fifty-seven per cent of the patients detained under s.5(2) were female. Affective psychosis was over-represented in detained females, while schizophrenia and paranoid states were over-represented in males. Eight per cent of s.5(2) detentions were initiated via the nurses' holding power, s.5(4). None of these patients were subsequently regraded to s.2 or 3, which may be accounted for by the finding that personality disorder and alcohol dependence were more commonly diagnosed in this subgroup. Of s.5(2) detainees, none of those with a non-psychotic disorder were regraded to s.2 or 3. Three patients had not accepted in-patient admission prior to implementation of s.5(2). Moreover, 38 per cent of all s.5(2) detentions took place within 24 hours of admission. Patients with a psychotic disorder were more likely to be detained within 24 hours of admission. Doubts regarding the validity of consent to voluntary admission in these patients are raised.

Cerebral hemiatrophy and schizophrenia.

BACKGROUND: Neuroimaging of a treatment-resistant patient with schizophrenia revealed the existence of cerebral hemiatrophy. The association of schizophrenia with cerebral hemiatrophy has not previously been reported. RESULTS: Neuroimaging with X-ray computerised tomography showed marked reduction in the volume of the left cerebral hemisphere with secondary enlargement of the left lateral fissure and cortical sulci. High resolution cranial single-photon emission computerised tomography showed a functional deficit of the regional cerebral blood flow in the left lateral parietal and left temporal lobes. CONCLUSIONS: Cerebral hemiatrophy may belong to the lengthening list of neurodevelopmental cerebral anomalies associated with schizophrenia.

Synthesis, physicochemical properties, and biological evaluation of N-substituted 2-alkyl-3-hydroxy-4(1H)-pyridinones: orally active iron chelators with clinical potential.

The synthesis of a range of novel bidentate ligands containing the chelating moiety 3-hydroxy-4(1H)-pyridinone is described. The pKa values of the ligands and the stability constants of their iron(III) complexes have been determined. The crystal structures of one of the ligands and one of the iron(III) complexes are presented. The distribution coefficients of the ligands are reported and are related to the ability of the ligands to remove iron from hepatocytes. The influence of 3-hydroxy-4(1H)-pyridinones on oxidative damage to cells is described. In contrast to the iron chelator in current therapeutic use, desferrioxamine-B, many of the bidentate ligands described in this study are orally active in iron-overloaded mice.

Growth and development of Haemonchus contortus in jirds, Meriones unguiculatus.

Growth and development of Haemonchus contortus were examined in jirds and were compared to these processes in lambs. Number, sex, size, and stage of development were determined for worms recovered at necropsy at various times postinoculation (PI) from immunosuppressed jirds inoculated with approximately 1,000 exsheathed infective larvae (L3) of H. contortus. In addition, gastric tissue samples from jirds were examined histologically. Parallel studies were done in lambs inoculated with approximately 7,500 L3. Typically, 5-30% of the inoculum established and survived in jirds at reasonably stable numbers to day 14 PI. By day 21 PI, worm numbers in jirds decreased dramatically. Although the parasite was similar in size and development on day 4 PI in jirds and lambs, from day 7 PI on, worms were significantly smaller and less developed in jirds. On histological examination, the parasite was found only in the glandular portion of the stomach of jirds (anatomically similar to its predilection site in the abomasum of lambs), and histological changes were consistent for both host species. Although growth and development of H. contortus are slower and incomplete in jirds, the parasite establishes, grows, and develops (at anatomically comparable sites in both hosts) in this model. Thus, the model appears to provide a useful laboratory host to study H. contortus.

The interaction of hydroxypyridinones with human serum transferrin and ovotransferrin.

The interaction of hydroxypyridinones with human serum transferrin and ovotransferrin has been studied by analyzing the distribution of iron between the chelator and the proteins as a function of both ligand concentration and transferrin saturation. The kinetics of iron removal by 3-hydroxypyridin-4-ones from both transferrins is slow; in ovotransferrin it appears to be monophasic, in contrast to that observed for serum transferrin. After 24 hours incubation at a 40:1 chelator:protein molar ratio, the percentage of iron removed from Fe(III)-ovotransferrin is 50%-60%, and is somewhat higher in the case of serum transferrin, in line with the respective affinity constants for the metal. The 3-hydroxypyridin-2-ones and the 3-hydroxypyran-4-ones, both of which have lower affinities for Fe(III), remove smaller proportions of the metal. The percentage of desaturation obtained with bidentate and hexadentate pyridinones appears to be similar for both transferrin classes at chelator:protein molar ratios from 40:1. The degree of transferrin saturation influences the extent of chelator mediated iron mobilization in the case of serum transferrin, but not of ovotransferrin. 59Fe competition studies demonstrate that bidentate pyridin-4-ones are capable of donating iron to serum apotransferrin; the relative concentrations of ligand and protein influence the distribution of iron because their effective binding constants (at pH 7.4) for Fe(III) are similar.

The interaction of orally administered iron with levodopa and methyldopa therapy.

The ability of methyldopa and levodopa to interact with both ferrous and ferric iron under a variety of conditions likely to be encountered physiologically has been examined. Spectrophotometric studies of ferrous sulphate in the presence of methyldopa indicate that no complexation occurs below pH2, whilst between pH 4-9, a variety of iron-methyldopa complexes is formed. The formation of these complexes is fast at high pH (pH 9: t1/2 less than 5 s), whilst the rate slows as the pH is lowered (pH 4: t1/2 greater than 30 min). These complexes are characteristic of iron-catecholate species, indicating that in the presence of methyldopa (and levodopa) ferrous iron undergoes autoxidation to the ferric form. The tight binding of ferric iron to methyldopa is predicted to alter the biodistribution characteristics of the complex with respect to the unchelated components. Furthermore, under the acid conditions of the stomach, redox cycling can occur. This will result in both catechol oxidation and production of the toxic hydroxyl radical. The findings suggest that care should be exercised when simultaneous administration of either methyldopa or levodopa with ferrous sulphate is indicated.

Infectious complications during therapy of acute leukaemia in Saudi Arabia.

In 40 febrile neutropenic episodes during the induction and consolidation chemotherapy of acute leukaemia in Riyadh, 51% of organisms causing septicaemia were gram-negative, 26% gram-positive, 8% anaerobes and 15% fungi. In 21 (52%) febrile episodes there were pulmonary infiltrates; of the 12 where aetiology was known, six were due to fungi. Pulmonary infiltrates progressed to adult respiratory distress syndrome and death in nine instances. There was no significant occurrence of parasitic and tropical infections. The results show that the pattern of infection, during therapy of acute leukaemia in developing countries, may have important differences when compared with western centres. Empiric amphotericin B may need to be introduced at an earlier stage in patients with persistent fever or progressive pulmonary infiltrates.

Combination chemotherapy for primary small intestinal lymphoma in the Middle East.

Twelve patients with primary small intestinal lymphoma were followed prospectively for 3 years. Endoscopic abnormalities were diagnostic of lymphoma in all cases where the duodenum was involved (83%). In three cases (25%) the disease extended to the stomach. One patient (8%) had diffuse small cell cleaved and 11 (92%) diffuse large cell lymphoma stages I (8%), II (25%), III (58%) and IV (8%). Nine of them were unresectable and primarily treated with combination chemotherapy; 67% achieved complete remission, 22% partial response and 11% no response. Only one patient relapsed and achieved a second remission. All complete remission patients are currently alive and free of disease at a median follow-up of 36 months. Overall survival for all patients is 58%, and disease-free survival is 50%. No instance of chemotherapy-related bleeding or perforation was seen. Tetracycline was necessary for the treatment of IPSID-associated diarrhea and malabsorption in spite of cytotoxic chemotherapy.

Interactions between inhibitors of dihydrofolate reductase.

The binding of substrates and inhibitors to dihydrofolate reductase was studied by steady-state kinetics and high-field 1H-n.m.r. spectroscopy. A series of 5-substituted 2,4-diaminopyrimidines were examined and were found to be 'tightly binding' inhibitors of the enzyme (Ki less than 10(-9) M). Studies on the binding of 4-substituted benzenesulphonamides and benzenesulphonic acids also established the existence of a 'sulphonamide-binding site' on the enzyme. Subsequent n.m.r. experiments showed that there are two binding sites for the sulphonamides on the enzyme, one of which overlaps the coenzyme (NADPH) adenine-ring-binding site. An examination of the pH-dependence of the binding of sulphonamides to the enzyme indicated the influence of an ionizable group on the enzyme that was not directly involved in the sulphonamide binding. The change in pKa value from 6.7 to 7.2 observed on sulphonamide binding suggests the involvement of a histidine residue, which could be histidine-28.

Leaving group dependence in the phosphorylation of Escherichia coli alkaline phosphatase by monophosphate esters.

Values of kcat and Km have been measured for the Escherichia coli alkaline phosphatase catalyzed hydrolysis of 18 aryl and 12 alkyl monophosphate esters at pH 8.00 and 25 degrees C. A Brønsted plot of log (kcat/Km) (M-1 s-1) vs. the pK of the leaving hydroxyl group exhibits two regression lines: log (kcat/Km) = -0.19 (+/- 0.02) pKArOH + 8.14 (+/- 0.15) log (kcat/Km) = -0.19 (+/- 0.01) pKROH + 5.89 (+/- 0.17) Alkyl phosphates with aryl or large lipophilic side chains are not correlated by the above equations and occupy positions intermediate between the two lines. The observed change in effective charge on the leaving oxygen of the ester (-0.2) is very small, consistent with substantial electrophilic participation of the enzyme with this atom. Cyclohexylammonium ion is a noncompetitive inhibitor against 4-nitrophenyl phosphate substrate at pH 8.00, and neutral phenol is a competitive inhibitor (Ki = 82.6 mM); these data and the 100-fold larger reactivity of aryl over alkyl esters are consistent with the existence of a lipophilic binding site for the leaving group of the substrate. The absence of a major steric effect in kcat/Km for substituted aryl esters confirms that the leaving group in the enzyme--substrate complex points away from the surface of the enzyme. Arguments are advanced to exclude a dissociative mechanism (involving a metaphosphate ion) for the enzyme-catalyzed substitution at phosphorus.

Therapeutic abortions following rubella infection in pregnancy: the potential impact on the incidence of congenital rubella syndrome.

In 1977, a large rubella outbreak occurred in Hawaii. Because attack rates were high among women of childbearing age, we conducted extensive surveillance efforts to detect both pregnancies complicated by rubella and cases of congenital rubella syndrome (CRS). Initial surveillance included a survey of physicians and hospitals, review of fetal death and birth certificates, and cord blood screening for rubella-specific IgM of infants born following the epidemic. Two years after the outbreak, the medical community was again surveyed to identify affected children who were missed initially. No case of CRS was identified either shortly after the outbreak or in the ensuing two years. In addition, none of the 5,605 cord serum samples obtained was found to contain rubella-specific IgM antibody. Through active surveillance, we received 12 reports of rubella in pregnant women, of whom 11 elected to terminate their pregnancies. The extensive use of therapeutic abortion by exposed women may have prevented the birth of infants with CRS. Surveillance for rubella-related abortions is an important component in assessing the health impact of rubella in a community.