Aetiological factors for oral manifestations of HIV

OBJECTIVES: Describe the oral diseases in HIV-infected individuals in London, UK and identify social and medical factors related to the presence of specific oral diseases.
DESIGN: Cross-sectional analytic study.
SETTING: Dental clinics.
SUBJECTS: Consecutive sample of 456 patients with HIV infection.
METHODS: Social and medical history and clinical examinations. Univariate and logistic regression analysis.
OUTCOMES: Presence of HIV-associated oral disease.
RESULTS: 80% of patients with AIDS and 50% of patients with HIV had a specific oral disease. The most common diseases were hairy leukoplakia (30%), erythematous candidiasis (24%), pseudomembranous candidiasis (14%), angular chielitis (6%), necrotising periodontal disease (8%) and non-recurrent ulceration (6%).
CONCLUSIONS: The presence of erythematous candidiasis was not related to advanced HIV disease. Pseudomembranous candidiasis, hairy leukoplakia and mucosal ulceration were significantly associated with advanced HIV disease. Smoking was also identified as a strong aetiological factor in oral diseases. Longitudinal studies are required to further explore the prognostic significance of oral diseases in HIV infection.     

Referral sources to a weight management program: relation to outcome

OBJECTIVE: To examine the characteristics and outcomes of physician-referred weight management patients relative to self-referred patients. DESIGN: Review of clinic records of all individuals contacting a weight control program during a 2-year period with follow-up throughout consecutive levels of treatment (i.e., enrollment, completion, and outcome). SETTING: Medical school weight management center. PARTICIPANTS: A consecutive sample (N = 1,392) of overweight and obese callers was categorized as physician-initiated (n = 345), media (n = 653), or personal (n = 394) referrals. Attendees at initial consultation (n = 571) were age 41.7 +/- 12.8 years, weight 113.9 +/- 36.1 kilograms, and body mass index (BMI) 40.3 +/- 11.3 kg/m(2) (data expressed as mean +/- standard deviation). INTERVENTIONS: Low-calorie-diet and very-low-calorie-diet programs. MAIN OUTCOME MEASURES: Gender comparisons, attendance at initial consultation, body mass index, motivation, comorbidities, enrollment and completion rates, and weight loss. RESULTS: Compared to callers from other referral sources, physician referrals included a larger minority of males (25.2%) and were more likely to attend an initial consultation (63.5%; P < .001). Among consultation attendees, physician referrals were heavier (mean BMI = 44.8), reported more comorbidities, were less likely to join programs (16.9%), and scored as less motivated than other referrals (P < .007). Completion rates for physician referrals were higher than for self-referrals in the very-low-calorie-diet program (85.7%; P < .04) but not in the low-calorie-diet program (P > .05). Among completers, physician referrals did not differ on weight loss in either program (P > .05). CONCLUSIONS: Compared to self-referrals, physician-referred individuals are in greater need of weight loss, less motivated, less likely to enter treatment, but equally likely to profit from it. Therefore, physician referral for weight loss is beneficial for at least some patients and should be encouraged.     

Detection of homozygous deletions of the cyclin-dependent kinase 4 inhibitor (p16) gene in acute lymphoblastic leukemia and association with adverse prognostic features

A recently described putative tumor suppressor gene, the cyclin- dependent kinase 4 inhibitor (p16), has been shown to be altered by deletions and/or point mutations in various human cancers. To assess the incidence and clinico-biologic correlations of p16 homozygous deletion in hemopoietic tumors, we studied a panel of 244 DNA samples representative of distinct acute (99 cases) and chronic (57 cases) leukemia subtypes, myelodysplastic (22 cases) and myeloproliferative (15 cases) syndromes, and lymphomas (51 cases). A 361-bp probe complementary to the p16 exon 2 gene sequences was generated by polymerase chain reaction and used in Southern blot hybridization against these tumor DNAs. Homozygous deletions of p16 (p16-/-) were detected in 10 of 58 (17%) cases of acute lymphoblastic leukemia (ALL) of either B or T lineage and in no other tumors. Single-strand conformation polymorphism analysis of p16 exons 1 and 2 was also performed in 40 of the 58 ALL cases and in 16 lymphomas. In no cases were point mutations detected. The comparison of clinical features at presentation in p16-/- and in p16 germline ALL cases showed a greater leukemic cell mass (P = .001) and higher white blood cell counts (P = .01) in the former group. Two ALL cases in which diagnostic and relapse DNA samples were available showed p16-/- in both specimens. We conclude that homozygous p16 gene deletions characterize a subset of ALL with features of aggressive disease.     

Hemophilia A: carrier detection and prenatal diagnosis by DNA analysis

In this study, we used DNA polymorphisms for carrier detection and prenatal diagnosis of hemophilia A in a large group of Italian families. The restriction fragment length polymorphisms (RFLPs) investigated were the intragenic polymorphic Bc/I site within the factor VIII gene; the extragenic multiallelic Taq I system at the St14 locus; and the extragenic Bg/II site at the DX13 locus. The factor VIII probe was informative in 30%, St14 in 82%, and DX13 in 60% of obligate carriers. The combination of factor VIII-Bc/I and St14-Taq I showed that 91% of obligate carriers were heterozygotes for one or both; with all three probes, only 4% of obligate carriers were noninformative. In families clearly segregating for hemophilia A, RFLP analysis allowed us to define the carrier status for the hemophilia A gene in all 27 women tested. RFLP analysis allowed us to exclude the carrier status in 39 of 45 female relatives of sporadic patients. The combination of RFLP analysis and biological assay of factor VIII allowed us to identify a de novo mutation in the maternal grandfather in 7 of 12 of the families with sporadic cases, for which members of three generations were available for study. Nine of 10 couples requesting prenatal diagnosis provided informative RFLP DNA pattern. Carrier status was excluded in two women, two fetuses were shown to be female, and prenatal diagnosis was carried out in five pregnancies by DNA analysis. Prenatal testing was successful in three instances and failed in two because a sufficient amount of chorionic villous DNA was not obtained for the analysis.     

Physical activity and obesity: what we know and what we need to know*

Creating a negative energy balance by decreasing caloric consumption and increasing physical activity is a common strategy used to treat obesity. A large number of review and original research papers have considered the role of physical activity in weight loss and maintenance. However, their conclusions are at times conflicting. In this review, we have critically evaluated the findings of systematic reviews and meta‐analyses and supplemented their conclusions with recently published, high‐quality clinical trials. We have eliminated studies that were methodologically flawed in an attempt to reduce the ambiguity in the literature. We further sought, through selective review of these publications, to isolate the effects of various types of exercise, independent of dietary interventions, to further clarify their independent contributions. Thus, our review describes (i) combined calorie restriction with physical activity interventions, (ii) physical activity interventions without calorie restriction and (iii) the role of physical activity on maintenance of weight loss. Through this critical examination of the literature, we have provided conclusions to address certain ambiguities regarding the role of physical activity in obesity treatment that will inform clinical practice. We have also identified several long‐standing gaps in knowledge that will inform future research.     

Collection of peripheral blood hematopoietic progenitors (PBHP) from patients with severe aplastic anemia (SAA) after prolonged administration of granulocyte colony-stimulating factor

The aim of this study was to test whether prolonged administration of granulocyte colony-stimulating factor (G-CSF) would allow the collection by leukapheresis of PBHP in patients with SAA. For this purpose, nine SAA patients, 7 to 46 years old, six of whom were enrolled at diagnosis of their disease and three after previous immunosuppression had failed, were treated with antilymphocyte globulin (ALG) (day 1 to 5), cyclosporin A (5 mg/kg/d orally) (day 6 to 90) and G-CSF 5 micrograms/kg/d (day 6 to 90). A total of 40 leukaphereses were performed, (range 2 to 7 per patient), between days +10 and +168 from G- CSF treatment. White blood cell count at the time of harvest ranged from 1.2 to 18.1 x 10(9)/L. Results can be summarized as follows: the median number of cells collected per patient was 5.0 x 10(8)/kg (range 2.6 to 18.7), the median number of CD34+ cells was 1.8 x 10(6)/kg (range 0.27 to 3.8) and the median number of colony-forming units granulocyte-macrophage (CFU-GM) was 3.9 x 10(4)/kg (range 0 to 39). Twenty leukaphereses performed between days +33 and +77 of G-CSF treatment grew granulocyte macrophages and erythroid colonies in vitro. No colony growth was obtained from 20 leukaphereses performed before day +33 or after day +80. In six patients the total number of CFU-GM recovered were in the range described for autologous peripheral blood stem cell grafts. (2.6 to 39 x 10(4)/kg). In conclusion, this study suggests that circulating hematopoietic progenitors can be recovered after ALG priming and after at least 1 month of G-CSF treatment in a proportion of patients with SAA. Whether these cells will be suitable for autologous transplantation remains to be determined.     

Poikilocytic hereditary elliptocytosis associated with spectrin Alexandria: an alpha I/50b Kd variant that is caused by a single amino acid deletion

Hereditary elliptocytosis (HE) is a heterogeneous disorder of red blood cells frequently associated with abnormal limited tryptic digestion of the alpha I domain of spectrin and impaired spectrin dimer self- association. We studied two related individuals with poikilocytic hereditary elliptocytosis (HE) of different severity. Limited tryptic digestion of spectrin from these individuals showed the presence of a variant alpha I/50b Kd peptide at the expense of the normal alpha I/80 Kd peptide. Amino acid sequence analysis of the abnormal peptide showed that the proteolytic cleavage occurred after the arginine at position 470 of the alpha spectrin chain. Spectrin from these patients had an impaired ability to undergo self-association, as evidenced by increased amounts of spectrin dimers in 4 degrees C extracts of erythrocyte membrane from affected individuals. The polymerase chain reaction was used to study the DNA sequence of the alpha spectrin gene encoding the region of the alpha spectrin chain surrounding the abnormal proteolytic cleavage site. We detected the in-frame deletion of the trinucleotide CAT, encoding histidine 469, two amino acid residues to the N-terminal side of the abnormal proteolytic cleavage site between residues 470 and 471. Similar to many other defects of spectrin associated with HE, this deletion occurs in helix three of repeat 5 of the proposed triple helical model of spectrin repeats.     

Poverty and health promotion in primary health care: professionals' perspectives

This paper examines the effectiveness of current strategies for health promotion in the UK in the light of knowledge about the links between health, illness and poverty. The implications of recent policies which target health promotion within primary health care (PHC) settings are examined. The results of an exploratory study undertaken during 1993/94 in a city in South West England are discussed. This qualitative study used semi-structured interviews to investigate the perceptions of a range of PHC professionals. Fifty-four interviews were carried out amongst staff in 16 PHC practices. This paper reports on professionals' views and practice in relation to promoting health in areas of poverty and with low-income clients. These findings are discussed in relation to the literature and the constraints on effective health promotion in PHC are explored particularly in relation to issues of poverty and deprivation.