Clinical governance and external audit.

This paper describes a model of clinical governance that was developed at South Auckland Health during the period 1995 to 2000. Clinical quality and safety are core objectives. A multidisciplinary Clinical Board is responsible for the development and publicising of sound clinical policies together with monitoring the effects of their implementation on quality and safety. The Clinical Board has several committees, including an organization-wide Continuous Quality Improvement Committee to enhance the explicit nature of the quality system in terms of structure, staff awareness and involvement, and to develop the internal audit system. The second stream stems from the Chief Medical Officer and clinical directors in a clinical management sense. The Audit Committee of the Board of Directors covers both clinical and financial audit. The reporting lines back to that committee are described and the role of the external auditor of clinical standards is explained. The aim has been to create a supportive culture where quality initiatives and innovation can flourish, and where the emphasis is not on censure but improvement.

3,4-anhydro-1,2-O-isopropylidene-beta-D-tagatopyranose and 4,5-Anhydro-1,2-O-isopropylidene-beta-D-fructopyranose.

3,4-Anhydro-1,2-O-isopropylidene-beta-D-tagatopyranose (8) and 4,5-anhydro-1,2-O-isopropylidene-beta-D-fructopyranose (10) have been prepared by treatment of 3,5-di-O-acetyl-1,2-O- isopropylidene-4-O-toluene-p-sulfonyl-beta-D-fructopyranose with methanolic sodium methoxide. The structures of 8 and 10 were assigned by 1H and 13C NMR spectroscopy and that of 10 by X-ray crystallography; both exist in half-chair conformations. Compounds 8 and 10 interconvert in aqueous sodium hydroxide, giving a ratio of 1:2 at equilibrium. The monoacetates of 8 and 10 (5-O-acetyl-3,4-anhydro-1,2-O-isopropylidene-beta-D-tagatopyranose and 3-O-acetyl-4,5-anhydro-1,2-O-isopropylidene-beta-D-fructopyranose) undergo stereospecific epoxide ring opening in 80% acetic acid to give mainly the axial monoacetates 5-O-acetyl-1,2-O-isopropylidene-beta-D-fructopyranose and 4-O-acetyl-1,2-O-isopropylidene-beta-D-tagatopyranose, respectively.

Polycythemia vera and water-induced pruritus: evidence against mast cell involvement.

The mechanism of water-induced pruritus in patients with polycythemia vera is unknown. Evidence has been presented previously that bathing or showering may trigger mast cell degranulation and that release of a mediator by mast cells may be responsible for the pruritus. Tryptase is a specific marker of human mast cell secretory granules and its presence in body fluids indicates mast cell degranulation. In this study, serum tryptase levels were measured both before and one hour after showering in 11 patients suffering from polycythemia vera and water-induced pruritus. Tryptase was not found in the serum of any of the subjects one hour after showering, when levels would be expected to be near peak had significant mast cell degranulation occurred. These results argue against mass cell degranulation with systemic release of a mast cell product as the mechanism for water-induced pruritus in patients with polycythemia vera.

Synthesis of nucleosides as potential inhibitors of purine biosynthesis.

The synthesis of analogues of 4-carboxy-5-amino-1-beta-D-ribofuranosylimidazole-5'-phosphate (CAIR) in which the carbonyl group is replaced by a grouping of tetrahedral geometry is described. These are planned as transition state inhibitors of SAICAR synthetase, the enzyme which converts CAIR into its amide with L-aspartic acid.

Globin genes are useful markers to identify genetic similarities between Fijians and Pacific Islanders from Polynesia and Melanesia.

DNA mapping studies in Fijians have enabled the identification of rearrangements and RFLPs involving the alpha-, zeta-, and gamma-globin genes. Comparisons of these data with corresponding gene markers in Polynesians and Melanesians of Papua New Guinea show considerable overlap between the three population groups. The utility of globin genes as population markers is further confirmed.

Mononucleosis-like-syndrome associated with acute AIDS retrovirus infection.

A 47-year-old man developed an acute infectious mononucleosis-like illness with a moderate lymphocytosis and numerous atypical lymphocytes in the peripheral blood. Seroconversion to the AIDS-associated virus occurred between 14 and 20 days following the onset of the acute illness. He was found to have reduction of the T4:T8 ratio, low mitogenic response to PHA and cutaneous anergy when tested at 25 and 136 days. These tests had returned to normal by 262 days.

An introduction to clinical decision analysis: bone marrow transplantation for aplastic anemia.

Clinical decision analysis is a systematic and rigorously logical approach to medical decision making under conditions of uncertainty. The structuring of a clinical problem in a decision analytic framework enables the clinician to focus on one aspect of a complex decision at a time without losing sight of the whole. The concepts of clinical decision analysis are explained and the technique is applied to compare bone marrow transplantation with supportive care for the treatment of a patient with severe aplastic anemia. The advantages and disadvantages of clinical decision analysis are discussed. The technique is intended to complement, but not replace, clinical judgement.

Iron deficiency and anemia among Indian women in Fiji.

In June 1979, 245 Hindu and 240 Moslem women of childbearing age (14-45 yr) living in a semi-rural area north of Lautoka were tested for anemia and for iron-deficiency. Ninety-six (39%) of the 245 Hindu women and 77 (32%) of the 240 Moslem women were anemic according to World Health Organization criteria. Most of the cases of anemia were due to iron-deficiency. The prevalence of anemia did not change significantly with advancing age or increasing parity. Hookworm ova were found on examination of a single specimen of feces in 27 (14%) of 195 Hindu and 50 (24%) of 209 Moslem women. The presence of hookworm did not correlate with anemia. The red cell folate level was less than 160 micrograms/l in 117 (24%) of 478 women and the serum vitamin B12 level was less than 100 ng/l in 47 (10%) of 476 women. Subnormal levels of these vitamins did not correlate with anemia. The serum ferritin was determined to assess tissue iron stores. Two-hundred-and-twenty-four (46%) of 484 Indian women tested had serum ferritin values of less than 10 microgram/l; 400 (83%) had ferritin values of less than 26 microgram/l. The high prevalence of iron deficiency appears to be due predominantly to dietary factors.

Improved survival from acute lymphoblastic leukemia in adolescents and adults.

Nineteen adult patients with acute lymphoblastic leukemia were treated with combination chemotherapy to induce remission in the period from 1971 to 1979. Those patients achieving remission received intensive post-remission therapy with central nervous system (CNS) prophylaxis, followed by two-drug maintenance therapy, and reinduction courses of chemotherapy every six months. Remissions were achieved in 17 of the 19 patients (89%). Twelve patients (63%) are alive, 11 currently in complete remission. Two patients who experienced relapses in recent months have successfully undergone transplantation with allogeneic marrow from sex-matched, HLA-compatible sibling donors. The median survival and median duration rates of first remissions have not yet been reached, but to date are 36+ months and 29+ months, respectively with a predicted five-year survival rate of 61%. These results not only are significantly better than those achieved in the years 1968 to 1971 in our institution, but also are superior to others reported in the world medical literature. The combination of optimal treatment protocols with allogeneic marrow transplantation for patients with poor prognoses is expected to improve the survival of adult patients even further in the next decade.

The proliferative activity of leukaemic myeloblasts following the intravenous infusion of cytarabine.

Serial bone marrow aspirates were obtained from 16 adults with acute myeloid leukaemia (AML) before and after a single infusion of cytarabine (5.0 mg/kg i.v. over 30 min). Changes in the proliferative activity of the leukaemic myeloblasts were monitored by determination of the labelling index (LI) and the mitotic index (MI). There was a significant fall in both LI and MI within a few hours of the administration of cytarabine (P = 0.005). In 14 of the 16 cases the LI subsequently rose to observed maxima 0.3% to 14.1% (mean 5.0%) above the preinfusion LI, 11 to 77 hours (mean 40.8 h) after the infusion (P less than 0.05). The MI returned to the mean pretreatment level within the period of observation in 11 of the 16 cases. In general, the changes in MI followed those in LI; the results are consistent with cytarabine-induced arrest or death of leukaemic blast cells in S phase. Because of the variability in timing of kinetic changes in leukaemic myeloblasts following cytarabine, it is not possible to institute remission induction therapy consistently at the time of maximum synchronization with any fixed chemotherapeutic schedule. Furthermore, the degree of synchronization attained is, in general, small, limiting the prospect of exploiting synchronization with cytarabine as a means of improving the remission rate for AML.

The prevalence and nature of anemia among apparently normal subjects in Fiji.

A total of 4939 apparently healthy Fijian and Indian subjects living in Fiji were tested for anaemia by determination of the microhaematocrit of a sample of capillary blood. The prevalence of anaemia during childhood varied with age but was similar for Fijians and Indians of either sex. The overall prevalences were: 0-4 years, 20.3%; 5-9 years, 3.7%; 10-14 years, 23.5%. The prevalence of anaemia among Indian women (33.3%) was substantially higher than that for Indian men (6.9%), Fijian women (8.1%) or Fijian men (6.8%). Iron deficiency was the most common cause of anaemia and was established by laboratory studies in 203 (68%) of 298 anaemic subjects who were followed up. Iron deficiency was an important aetiological factor in 91 (93%) of 98 subjects with moderate or severe anaemia. Folate deficiency was found, usually in combination with iron deficiency, in 44 or 141 anaemic indian adults were followed up. Folate deficiency was uncommon in Fijian adults and among children of either race. Two cases of nutritional vitamin B12 deficiency, one case of pernicious anaemia, 6 cases of heterozygous thalassaemia and one case of heterozygous haemoglobin E were found among the anaemic Indian subjects. No cases of vitamin B12 deficiency anaemia, thalassaemia or haemoglobinopathy were detected among the Fijians. In 5 Indians and 7 Fijians the anaemia was associated with an underlying chronic disorder. This study emphasizes that in Fiji, as in other developing countries, nutritional anaemia is prevalent among asymptomatic subjects. Iron deficiency is by far the most common cause.

Bilateral trephine bone marrow biopsies in Hodgkin's and non-Hodgkin's lymphoma.

This study was undertaken to investigate the usefulness of bilateral rather than unilateral iliac trephine biopsies in demonstrating Hodgkin's disease and non-Hodgkin's lymphoma in the bone marrow. One hundred and seventy adequate bilateral biopsies were obtained from 145 patients. Among 76 bilateral trephine biopsies from 65 patients with Hodgkin's disease, tumour was found bilaterally in 3 cases and on only one side in 2 cases. Among 94 bilateral biopsies from 80 patients with non-Hodgkin's lymphoma, tumour was found bilaterally in 17 cases and on only one side in 12. Considering all of the cases in the series, the performance of bilateral biopsy increased the yield of positive marrows from an estimate of 27 to 34, an increase of 26%. We conclude that bilateral trephine biopsy is superior to unilateral biopsy for the demonstration of bone marrow involvement by Hodgkin's disease or non-Hodgkin's lymphoma and recommend that bilateral trephine biopsies be performed when a knowledge of the state of the bone marrow is important for clinical decision making.

The synthesis of D-ribofuranosyl derivatives of methyl propiolate and a study of the activating influence of the ester group in cycloaddition reactions.

2,3,5-Tri-O-benzyl-D-ribofuranosyl bromide (17) has been converted into methyl 3-(2,3,5-tri-O-benzyl-beta-D-ribofuranosyl) propiolate (8) and its alpha anomer 10 in 21 and 42% yields, respectively, by reaction with the silver salt of methyl propiolate. Attempts to prepare 8 from (beta-D-ribofuranosyl)ethyne (1) by standard methods were unsuccessful. The reactions of the esters 8 and 10 and the ethyne 1 with several 1,3-dipoles have been examined. With diazomethane, 8 and 10 gave the pyrazole esters 20 and 28, respectively, whereast the ethyne 1 reacted more slowly to give a mixture of 23 (37%) and 26 (31%). The ester 10 was converted into the triazoles 32 (51%) and 36 (34%) by reaction with benzyl azide. Treatment of the ester 10 with phenylhydrazine gave the pyrazolone 38 in 71% yield. A number of the products of dipolar addition have been converted into new D-ribofuranosyl-pyrazoles and -triazoles by hydrogenolysis.