Health policy in Europe.
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European Union↗
Biomedical subjects
P Berman
Publications and source records attributed to P Berman.
Non-steroidal anti-inflammatory drug usage and requirement in elderly acute hospital admissions.
There is a strong feeling that despite the increasing awareness of their adverse effects, non-steroidal anti-inflammatory drugs (NSAIDs) are not always used appropriately. To examine this problem amongst elderly patients who may be at particular risk, 500 acute admissions to Health Care of the Elderly wards were studied prospectively. Sixty-five patients were currently receiving NSAIDs; 56 had medical conditions possibly caused by, or aggravated by NSAIDs. Indications for NSAIDs were often no longer apparent, and these drugs were successfully discontinued in 56; in 22 no alternative therapy was required. Importantly, following discharge the majority of patients remained off NSAIDs. These data support the need for continual review of NSAID requirements and regular monitoring for adverse effects, particularly in this high risk group.
Aged↗
Evaluation of a method for clinically assessing osteoarthritis of the knee.
A system for assessing symptoms (pain, stiffness, gelling) and signs (local temperature, effusion, tenderness, synovial swelling, popliteal cyst, crepitus) of osteoarthritis of the knee has been developed. The system has been assessed for intra- and interobserver variation using normal and osteoarthritic knees. Intraobserver variability is low for all indices but interobserver variability is high for physical signs. It is suggested that the components within this system, when applied by a single observer, may provide a reasonable framework for clinical assessment of osteoarthritis of the knee.
Aged↗
Maternal tetanus immunization in Aceh Province, Sumatra: the cost-effectiveness of alternative strategies.
This paper compares the cost per completed maternal tetanus immunization and an estimate of the cost per death averted in the routine EPI program with similar results from an experimental mass campaign in Aceh Province, Indonesia. The cost-effectiveness of the mass campaign in achieving complete immunization is similar to the routine program. However, the mass campaign is probably less cost-effective in averting neonatal tetanus deaths, due to its broader targetting. Factors affecting efficiency, coverage, and financing of tetanus immunization programs are assessed. While expansion of the routine EPI program is the preferred goal, mass campaigns are judged to be a reasonable part of the multi-year strategy for tetanus control in the province. Recent experiments with an accelerated routine program may provide further alternatives.
Adolescent↗
Septic arthritis complicating apatite associated destructive arthropathy.
Septic arthritis can complicate many forms of arthritis. Two cases of apatite associated destructive arthropathy (AADA) complicated by sepsis are described. Diagnosis of this complication in the setting of severe joint damage is difficult as AADA and sepsis share certain characteristics--an initial, rapidly progressive, severely painful course and radiographs which show rapidly destructive changes with marked cartilage loss, bone attrition, and virtual absence of osteophyte or cyst response.
Aged↗
A hospital study of community acquired pneumonia in the elderly.
Studies on community acquired pneumonia in the United States in patients over the age of 65 years have shown that Gram negative bacilli account for an appreciable proportion of cases, in addition to usual pathogens such as Streptococcus pneumoniae and Haemophilus influenzae. There have been no reports of community acquired pneumonia in the elderly in the United Kingdom. We undertook such a study to determine the clinical features, aetiology, and outcome. Seventy three patients (38 men) with ages ranging from 65 to 97 (median 79) years were studied prospectively. Pneumonia was defined as an acute lower respiratory tract infection with new, previously unrecorded shadowing on a chest radiograph. Patients with severe chronic illness in whom pneumonia was an expected terminal event were excluded. Nearly all the patients (96%) had respiratory symptoms or signs but many had features that might obscure the true diagnosis of pneumonia. Over half the patients had non-respiratory symptoms and over a third had no systemic signs of infection. A pathogen was identified in 43% of patients, most commonly Streptococcus pneumoniae, Haemophilus influenzae and influenza B virus. Gram negative bacilli were not seen. The mortality rate was high (33%). Early deaths were due to infection whereas later deaths were associated with other factors, such as stroke (two patients) and pulmonary embolism (two patients). Prognostic indicators for mortality were apyrexia, systolic hypotension, increasing hypoxaemia, and new urinary incontinence. As the range of pathogens causing pneumonia was the same in the elderly in this study as in other age groups it is suggested that initial antibiotic treatment for patients in this age group should always cover S pneumoniae and H influenzae.
Aged↗
Diagnostic value of ascites adenosine deaminase in tuberculous peritonitis.
The value of ascitic fluid adenosine deaminase activity in distinguishing tuberculosis from other causes of ascites was examined in a retrospective study of 41 patients with bacteriologically confirmed tuberculous peritonitis and 41 control patients, matched for age and sex, with ascites of other causes (12 alcoholic cirrhosis, 5 cryptogenic cirrhosis, 12 malignant disorders, 3 pancreatitis, and 9 miscellaneous causes). The mean ascites adenosine deaminase activity was 99.8 (SD 49.1) in tuberculous patients and 14.8 (8.4) U/l in control patients (p less than 0.0001). A cutoff of 32.3 U/l had a sensitivity of 95% and specificity of 98% in distinguishing between the two groups. In a subsequent prospective study of 64 patients with ascites, 11 were found to have tuberculosis. Of the others, 23 had cirrhosis (18 alcoholic, 5 cryptogenic), 17 malignant disorders, 3 pancreatitis, 5 cor pulmonale, 3 congestive cardiac failure, 1 systemic mastocytosis, and 1 renal failure and hypothyroidism. The mean ascites adenosine deaminase activity was 112.6 (45.0) U/l in the patients with tuberculous ascites and 16.3 (36.7) U/l (p less than 0.0001) in those with ascites of other causes. In this study, adenosine deaminase had a sensitivity of 100% and specificity of 96% in discriminating tuberculosis from other causes of ascites. These findings suggest that the ascitic fluid adenosine deaminase activity may be used to identify patients in whom the diagnosis of abdominal tuberculosis must be pursued.
Adenosine Deaminase↗
Recognition of HIV glycoprotein gp120 by T cells. Role of monocyte CD4 in the presentation of gp120.
The HIV envelope glycoprotein gp120 binds with high affinity to CD4 and is responsible for the tropism of HIV for CD4+ T cells and monocytes. Efforts to develop HIV vaccines have focused on gp120 and, therefore, a detailed molecular understanding of human immune responses to gp120 is essential. In this report, we have used human T cell clones specific for gp120 to examine the processing and presentation of gp120 to T cells. In particular, we examined the role of the CD4 that is expressed at low levels on the surfaces of human monocytes in the presentation of gp120 by monocytes. The presentation of gp120 to gp120-specific human T cell clones was blocked by pretreatment of monocytes with anti-CD4 mAb. Blocking of monocyte CD4 with anti-CD4 did not inhibit presentation of other Ag or of synthetic peptides representing epitopes within gp120 recognized by gp120-specific T cell clones. These results indicated that the anti-CD4-mediated inhibition occurred at the level of the monocyte, was specific for the gp120 response, and was operative at the initial Ag uptake phase of the Ag-processing pathway. Definitive confirmation that monocyte CD4 functions in the initial uptake step of the gp120-processing pathway was obtained by using soluble CD4 to block the interaction of gp120 with monocyte CD4. These results demonstrate that gp120 expressed by human monocytes plays an important role in the initial uptake of gp120 by monocytes and that gp120 taken up via CD4 is subsequently processed to allow for exposure of epitopes recognized by gp120-specific human T cells. At limiting gp120 concentrations, uptake via CD4 is essential for the presentation of gp120.
Antigen-Presenting Cells↗
Geriatric outpatient clinics: an audit of clinical action, transport and general practitioners' views.
An audit was performed of patients attending geriatric outpatient clinics for review during a calendar month. Patients were asked to complete a brief questionnaire and 93% of case notes were available for study. In 97 attendances, management was altered in 36, a new medical problem found in 16, and 49 patients were discharged. Forty-seven attendances followed recent discharge from hospital; 19 of these patients had no evident clinical benefit from attendance, although the majority were discharged. There may be scope for a liaison nurse to take over the follow-up of some patients to save their attending a clinic. A survey of local general practitioners suggested they would welcome this.
Aged↗
The costs of public primary health care services in rural Indonesia.
Described are the results of a cost study of national rural health services carried out in Indonesia between November 1986 and March 1987. Detailed costings of government inputs to all public health services below the district hospital level were made for 41 subdistricts in five provinces that were representative of the different regions of the country. The total costs of services as well as the average costs for specific service functions were estimated for the whole country as well as for the different provinces. The results indicate a low overall level of government spending on rural primary health care. Regional differences in this respect were not significant, suggesting that the government policy of encouraging regional balance in allocations has been successful. The average costs for most services were much greater than the charges made to patients, and this provided information on the current level of government subsidies. There was a large variability in the average costs, indicating that the existing system is inefficient, that some districts were able to attain much higher levels of efficiency than others within the existing constraints, and that improvements in this respect are possible.
Community Health Services↗
Characterization of GP120 binding to CD4 and an assay that measures ability of sera to inhibit this binding.
There is evidence that the initial interaction between HIV-1 and the host that is essential for infection is the specific binding of the viral envelope glycoprotein, gp120, to the CD4 molecule found on certain T cells and monocytes. Most individuals infected with HIV develop antibodies against the gp120 protein. Although in vitro treatment of CD4+ T cells with mAb to a specific epitope of the CD4 molecule (T4a) blocks virus binding, syncytia formation, and infectivity, it is unclear if antibodies to gp120 from an infected individual that can inhibit the binding of gp120 to CD4 is in any way related to the clinical course of disease. Our present study characterizes the binding of 125I-labeled rgp120 to CD4+ cells, and describes an assay system that measures a potentially relevant form of immunity to HIV infection, i.e., the blocking of HIV binding to CD4+ cells. Optimal binding conditions included a 2-h incubation at 22 degrees C, 4 x 10(6) CD4+ cells, and 1 nM gp120. The dissociation constant (KD) for gp120 binding to cell surface CD4 was 5 nM, and was inhibited by soluble CD4 and by mAb to T4a but not to T3 or T4. For the binding inhibition assay, negative controls included healthy seronegatives, seronegatives with connective tissue diseases, patients with HTLV-1 disease, and patients infected with HIV-2. In studying over 100 sera, the assay was highly sensitive (98%) and specific (100%). The majority of HIV+ sera could inhibit binding at dilutions of 1/100 to 1/1000. No correlation was noted between binding inhibition (BI) titer in this assay and clinical stage of HIV infection. In addition, there was no correlation between BI titer and HIV neutralizing activity. The BI titer was correlated with the titer of anti-gp160 (r = 0.63) and the titer of anti-gp120 (r = 0.52) antibodies determined by Western blot dilution. As with neutralizing antibodies and other forms of immune response to HIV, it is unclear what role antibody blocking of HIV binding to CD4+ cells may play in active immunity to HIV in infected individuals. This activity may prove to have some value in protection against initial HIV infection and, thus, the assay may be of use in monitoring vaccine trials.
Animals↗
Analysis of host-virus interactions in AIDS with anti-gp120 T cell clones: effect of HIV sequence variation and a mechanism for CD4+ cell depletion.
The primary human T cell response to HIV was analyzed by isolating from seronegative donors T cell clones specific for HIV gp120. T cell epitopes restricted by different MHC elements were identified within gp120, and synthetic peptides were used to address the fundamental problem of how HIV sequence variability affects T cell recognition. Even one conservative substitution can drastically reduce recognition; thus the interaction of gp120 epitopes with T cell receptors and MHC is precise and poorly crossreactive. Importantly, a subset of CD4+ gp120-specific clones manifest cytolytic activity and lyse uninfected autologous CD4+Ia+ T cells in the presence of gp120 in a process that is strictly dependent upon CD4-mediated uptake of gp120 by T cells. Assuming gp120 is shed from HIV-infected cells in vivo, this novel CD4-dependent autocytolytic mechanism may contribute to the profound depletion of CD4+ cells in AIDS.
Acquired Immunodeficiency Syndrome↗
T cells can present antigens such as HIV gp120 targeted to their own surface molecules.
To trigger class II-restricted T cells, antigen presenting cells have to capture antigens, process them and display their fragments in association with class II molecules. In most species, activated T cells express class II molecules; however, no evidence has been found that these cells can present soluble antigens. This failure may be due to the inefficient capture, processing or display of antigens in a stimulatory form by T-cells. The capture of a soluble antigen, which is achieved by nonspecific mechanisms in macrophages and dendritic cells, can be up to 10(3) times more efficient in the presence of surface receptors, such as surface immunoglobulin on B cells that specifically bind antigen with high affinity. We asked whether T cells would be able to present soluble antigens that bind to their own surface molecules. Here we show that such antigens can be effectively processed and presented by both CD4+- and CD8+-bearing human T cells. This indicates that T cells are fully capable of processing and displaying antigens and are mainly limited in antigen presentation by their inefficiency at antigen capture.
Antibodies, Monoclonal↗
Acute extrapyramidal syndrome in methylmalonic acidemia: "metabolic stroke" involving the globus pallidus.
We report four patients with methylmalonic acidemia who developed acute extrapyramidal disease after metabolic decompensation. The neurologic findings resulted from bilateral destruction of the globus pallidus with variable involvement of the internal capsules. This complication was unrelated to a specific gene defect responsible for methylmalonic acidemia or to cyanocobalamin administration. These lesions constitute a "metabolic stroke," probably because of the accumulation of toxic organic acid metabolites, because they cannot be accounted for by hypoxemia or vascular insufficiency.
Adolescent↗
Austin Flint--America's Laennec revisited.
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Auscultation↗
Sequence analysis, cellular localization, and expression of a neuroretina adhesion and cell survival molecule.
A cDNA for purpurin, a secreted 20,000 dalton neural retina cell adhesion and survival protein, has been sequenced and expressed in mammalian cells. Purpurin mRNA is found in both embryonic and adult retina, but not the brain, heart, or liver. The protein is highly concentrated in the neural retina between the pigmented epithelium and the outer segments of the photoreceptor cells; it is synthesized by photoreceptor cells. The predicted purpurin sequence contains 196 residues, has approximately 50% sequence homology with serum retinol binding protein, and is a member of the alpha-2 mu-globulin superfamily. Purpurin binds retinol and may play a major role in retinol transport across the interphotoreceptor cell matrix.
Amino Acid Sequence↗
Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor.
The primary event in the infection of cells by HIV is the interaction between the viral envelope glycoprotein, gp120, and its cellular receptor, CD4. A recombinant form of gp120 was found to bind to a recombinant CD4 antigen with high affinity. Two gp120-specific murine monoclonal antibodies were able to block the interaction between gp120 and CD4. The gp120 epitope of one of these antibodies was isolated by immunoaffinity chromatography of acid-cleaved gp120 and shown to be contained within amino acids 397-439. Using in vitro mutagenesis, we have found that deletion of 12 amino acids from this region of gp120 leads to a complete loss of binding. In addition, a single amino acid substitution in this region results in significantly decreased binding, suggesting that sequences within this region are directly involved in the binding of gp120 to the CD4 receptor.
Antibodies, Monoclonal↗
4-Aminosalicylic acid retention enemas in treatment of distal colitis.
Forty-five of 47 patients with distal ulcerative colitis completed a two-week double-blind, randomized, controlled trial to determine if 4-aminosalicylic acid (4-ASA) enemas, 1 g bid or 2 g bid, were therapeutically effective compared to placebo. Forty-one patients enrolled because they were refractory to or had side effects during conventional therapy with sulfasalazine or corticosteroids. Proctoscopic examination was done before and after two weeks of treatment. Patients kept daily diaries assessing: blood in stools, mucus in stools, tenesmus, abdominal pain, loss of appetite, fatigue, weight loss, and malaise. Severity of each symptom ranged from 0 (absent) to 3 (severe). A total severity score was calculated from the above for each patient. At the end of the two-week study, 35 patients elected to take 4-ASA in an open-label trial for one year. 4-ASA enemas in the 1-g bid but not the 2-g bid dosage were significantly more effective in improving symptoms than placebo: P less than or equal to 0.05. Neither dose of 4-ASA enema was better than placebo in improving the sigmoidoscopic appearance at the end of two-weeks. Forty-six percent of patients had complete resolution of all signs and symptoms in the open-label trial and 31% were better but still had sigmoidoscopic evidence of disease, a total response rate of 77%. Side effects were similar in the placebo and 4-ASA groups. We conclude that 4-ASA enemas in a dose of 1 g bid are safe and effective in the treatment of distal ulcerative colitis.
Adult↗