Symptoms Of Active Disease Research Articles

ENVIRONMENTAL CONTROL OF ASTHMA

Environmental control is an important step in the control of asthma. Mites, cats and other pets, cockroaches, molds, and cigarette smoke are all important in the etiology of asthma. By decreasing exposure to these factors, one can reduce the symptoms of active disease. In addition, one can decrease the incidence of asthma by avoiding exposure to mites from infancy.

ENVIRONMENTAL CONTROL OF ASTHMA

Environmental control is an important step in the control of asthma. Mites, cats and other pets, cockroaches, molds, and cigarette smoke are all important in the etiology of asthma. By decreasing exposure to these factors, one can reduce the symptoms of active disease. In addition, one can decrease the incidence of asthma by avoiding exposure to mites from infancy.

Similia similibus obscurantur: the pharmacological clinical activity bias I. A prototype model to correct a disease‐drug interaction leading to misestimations of drug‐attributable side effects

Drugs have side effects that manifest as signs or symptoms which are sometimes undistinguishable from signs or symptoms of active disease. The conventional approximation of the rate of side effects of drugs is by subtracting the rate of signs and symptoms in the placebo group from that in the drug group. This measures net side effects and is adequate in studies with healthy volunteers, in which no interaction between drug and disease exists. For ethical and practical reasons, however, volunteer studies cannot be large and the frequency of non-rare side effects must be estimated in large-scale clinical trials. In the latter, biasing drug disease interactions may occur. We report on such a hitherto undescribed interaction: the pharmacological clinical activity bias. If one is interested in estimating not the net, but the direct or intrinsic, ie, drug-attributable side effects, the conventional approximation is biased whenever, in clinical trials, both of two conditions apply. The first is that the variable on the scale of which a sign or symptom is recorded as a putative side effect, is also in the absence of drug affected by uncontrolled disease. The second is that the drug has pharmacological clinical activity (A) on that sign or symptom, thus reducing the contribution of disease (D) to what is measured. In this case the drug affects the variable under study both directly, through its intrinsic side effect, and indirectly, through its clinical activity, and the rate of attributable side effects differs from the rate of net side effects as calculated by the conventional approximation. We present a simple deterministic model, which assumes that disease remains stable if untreated, additivity of the relative contributions of drug, placebo and disease to the total rate of the sign or symptom, and no other interaction between intrinsic properties of the drug and active disease than pharmacological clinical activity. This theoretical model quantifies the bias as DO(Ad-Ap), in which DO is the baseline frequency of the sign or symptom in the studied patients, and Ad and Ap are the intrinsic clinical activities of drug and placebo, respectively, on the sign or symptom under study. The model confirms that the conventional approximation of drug side effects is unbiased only in healthy volunteers or with drugs devoid of clinical activity. Without correction by such a model, any clinical activity of the drug or manifestation of active disease will cause the conventional approximation of side effects to be biased. This may manifest as artifacts such as attribution of a side effect when there is none, and as under- or overestimation, pseudotachyphylaxis, or pseudo-delayedness of attributable side effects.

Use and misuse of biomarker tests in “environmental conditions”

Use and misuse of biomarker tests in “environmental conditions”

Serum procollagen-III-peptide level correlates with disease activity in myelofibrosis with myeloid metaplasia.

In 78 patients with myelofibrosis with myeloid metaplasia (MMM) the serum procollagen III peptide activity (s-PIIIP) had a higher mean value than in 22 normal adult volunteers (22.5 v. 10 ng/ml). Nevertheless, 21.8% of the patients had s-PIIIP within the 95th percentile of the normal control group (16 ng/ml): with respect to those whose concentrations exceeded this limit, patients with normal s-PIIIP levels were younger (55.8 v. 61.2 years), had a higher Hb value (12.3 v. 10.5 g/l), a lower serum ferritin level (106 v. 464 micrograms/l) and a higher platelet count (390 v. 216 x 10(9)/l). In the overall patient population, s-PIIIP was significantly higher in those with symptoms of active disease (fever, sweating, weight loss) than in subjects with non-active disease (28 v. 16.9 ng/ml). At univariate analysis s-PIIIP correlated (at the 5% level) with increasing WBC, serum ferritin and number of transfusions and with decreasing Hb and platelet count. At multivariate analysis increasing WBC, serum ferritin and age proved to be independently associated with s-PIIIP. No relationship was found between the s-PIIIP level and morphometric grading of bone marrow fibrosis, megakaryocyte number, or lymphoid infiltration. Longitudinal studies showed that s-PIIIP increased with disease progression. The conclusion of the study is that s-PIIIP correlates more with overall disease activity than with the extent of bone marrow fibrosis.

Phorbol ester-induced production of beta-2-microglobulin in B-CLL cells: relation to IgM secretory response and disease activity.

Earlier studies have indicated that serum beta 2m levels correlate with the disease activity, estimated tumour cell mass and prognosis of CLL. We have therefore analysed the spontaneous and phorbol ester (TPA)-induced capacity of CLL cells to produce beta 2m in vitro in relation to disease activity. Cell cultures (greater than 90% B cells) from 15 patients with active disease contained significantly higher (P less than 0.001) levels of beta 2m (0.22 +/- 0.09 mg/l) than cultures from 17 patients with inactive CLL (0.08 +/- 0.06). When TPA-induced CLL cell cultures were compared, this difference was even more striking (0.48 +/- 0.18 versus 0.13 +/- 0.09). The capacity of TPA-treated B-CLL cells to export beta 2m was positively correlated with their capacity to secrete monoclonal IgM (r = 0.73; P less than 0.001). Cell depletion experiments showed that the beta 2m export by B-CLL cells is enhanced by accessory T cells. Four individual CLL patients were followed for 14 months and repeatedly investigated for signs and symptoms of active disease, and the CLL cells were tested for in vitro production of beta 2m. Fluctuations in the clinical activity of the leukaemia were paralleled by similar switches in CLL cell production of beta 2m.

Serum bone GLA-protein is not a sensitive marker of bone turnover in Paget's disease of bone.

Serum bone Gla-protein (sBGP) was measured in 32 patients with untreated Paget's disease of bone. Despite clinical and biological symptoms of active disease in all patients, sBGP was normal in 13/32 patients (41%). There was a striking discrepancy between the moderate increase of sBGP above normal values (11.4 +/- 4.5 vs 6.0 +/- 2.1 ng/ml) and the marked increase of both serum alkaline phosphatase (sAP) and urinary hydroxyproline (uOHP). sBGP was weakly correlated with sAP (r = 0.50, p less than 0.01), uOHP (r = 0.48, p less than 0.01) and with the extension of the disease (r = 0.48, p less than 0.01). We conclude that sBGP is not a sensitive marker of bone turnover in patients with Paget's disease of bone, and should be interpreted with caution in this condition.

Dopaminergic treatment of acromegaly: different effects on hormone secretion and tumor size.

We studied the effects of long term treatment with bromocriptine (Br) or lisuride (L) on GH secretion and tumor size in 19 acromegalic patients with large pituitary adenomas. In 22 additional patients with smaller adenomas, only plasma GH levels were monitored during treatment. All patients underwent an acute test with 2.5 mg Br or 0.3 mg L and, on the basis of GH changes, were classified as responders, i.e. reduction in circulating GH concentrations by at least 50% below baseline, or as nonresponders. The chronic treatment was 5-20 mg/day Br in 26 patients or 0.3-2.0 mg/day L in 15 patients. Treatment was given for 4-26 months (mean +/- SE, 13.3 +/- 2.8 months). Plasma GH levels (baseline, 46.3 +/- 8.3 ng/ml) were significantly lower in the group as a whole (22.7 +/- 3.6 ng/ml; P less than 0.01) after the first month of treatment with dopamine agonist agents. GH levels decreased significantly in those acromegalic patients who responded to the acute test (P less than 0.001), but were unchanged in the nonresponders. In addition, there was a significant correlation between the maximal percent GH decrease in the acute test and the response during chronic treatment (r = 0.73; P less than 0.01). Computed tomography failed to show any tumor size changes in any of the GH nonresponders who had a macroadenoma . However, in two patients in the acute responder group with macroadenomas, chronic dopamine agonist therapy resulted in reduction of the extrasellar portion of the tumor (-30% and -40% of tumor area, respectively). These data show that although dopaminergic drugs lower GH levels and reverse signs and symptoms of active disease in those acromegalic patients who are responsive to an acute challenge, tumor size reduction occurred in a minority of such patients.

Cold lymphocytotoxic antibodies in systemic lupus erythematosus.

Optimum conditions were established for the assay of cold lymphocytotoxic antibodies (cLCTA) in serum from patients with systemic lupus erythematosus (SLE). The optimum temperature of the incubation step with complement was 15 degrees C. For target cells incubated with dextran a significantly higher percentage of damaged cells (p less than 0.005), a faster rate of cell damage (p less than 0.001) and a requirement for less complement was observed than for target cells not incubated with dextran. Under optimum conditions in the cytotoxicity assay, 62% of SLE sera damaged more than 60% of the target cells, whereas 73% of the sera from control donors damaged less than 20% of the target cells. In multiple serum samples obtained during follow-up of 30 patients with SLE, the serum cytotoxic activity or titer of cLCTA fluctuated and did not relate to clinical symptoms of disease activity. In sera obtained during active disease the cytotoxic activity was related to the anti-dsDNA antibody level and with levels of circulating immune complexes measured by the Raji cell assay and the indirect granulocyte phagocytosis test. We found no restricted reactivity of cLCTA against phenotypically distinct T-lymphocyte subpopulations with different immunoregulatory functions. The reactivity pattern of cLCTA towards the various T-lymphocyte subpopulations was not related to disease activity. We conclude that cLCTA in patients with SLE represent an epiphenomenon, being the result of a hyperreactive B-cell system rather than the cause of the disease.

A unique type of calcification in chronic brucellosis

A unique type of calcification in chronic brucellosisJP Arcomano, NF Pizzolato, R Singer and SM ZuckerAudio Available | Share

STAPHYLOCOCCAL PNEUMONIA IN INFANCY AND CHILDHOOD

Staphylococcal pneumonia appears to be increasing in frequency and is a particularly important problem in early infancy when the disease tends to be specially severe and may prove fatal. Only early recognition and prompt treatment can reduce the high mortality rate in this age group. A high index of suspicion must exist for this type of pneumonia in any infant who presents with signs or symptoms of infection of the lower respiratory tract and who fails to respond to adequate doses of penicillin or one of the cyclines in a period of 24 to 36 hours. Frequent and careful observations of any such infant to detect the appearance of empyema fluid and, more particularly, tension pneumothorax are vitally important. Once the presence of empyema has been established, prompt and effective drainage with a closed system should, in our opinion, be instituted without delay; it is also our feeling that the local administration of an antibiotic, such as bacitracin, may be useful and we recommend its use in this manner. Chloramphenicol and erythromycin, used together, in an effort to delay the emergence of resistant organisms, are the antibiotics of choice in the treatment of pneumonia due to penicillin-resistant strains of staphylococci. In view of our experience with this disease, we recommend therapy as follows: All infants with a tentative diagnosis of staphylococcal pneumonia who have not received any prior antibiotic therapy should receive penicillin, erythromycin and chloramphenicol immediately after cultures are obtained; then administration of the antibiotic or antibiotics shown by in vitro tests to be least effective against the strain of staphylococcus causing the disease, is discontinued. If the patient has been receiving penicillin prior to admission to the hospital and history shows no evidence of response or improvement, one may infer that the organism is pencillin-resistant and chloramphenicol and erythromycin alone are given. While triple therapy of this condition may not be ideal, the employment of this combination is considered justified until a satisfactory etiologic diagnosis can be obtained or until antibiotic sensitivity tests are completed. Dowling and his colleagues agree with such therapy in principle especially in the treatment of serious staphylococcal infections, and state that antibiotics when used under such circumstances, as outlined above, "should be used in full (italics ours) doses," and we should like to emphasize the importance of this principle. Satisfactory clinical evidence of antagonism among antibiotics is lacking and most authorities agree that antagonism between antibiotics "is of little or no consequence in the management of human infections." While some admit the possibility that antagonism may exist occasionally, they feel this is a rare phenomenon. When satisfactory evidence becomes available that there is antagonism among these three antibiotics in the treatment of staphylococcal infections, our present recommendations will be altered but until such time the triple combination is urged in view of the fact that this infection progresses extremely rapidly and every hour counts. Finally, antibiotics must not be discontinued too early, but should be administered for an average period of 2 to 3 weeks after the patient has become afebrile, or until all signs and symptoms of active disease have disappeared. The use of a potent bactericidal agent such as bacitracin locally may be extremely important in a severely ill infant with empyema. It is our practice at present in patients with empyema to instill 5,000 to 10,000 units of bacitracin at the time of the initial thoracentesis.

VIENNA

<h3>The Danger of Tuberculous Infection in Schools</h3> An interesting problem was presented by Dr. Peyser recently at a meeting of the Society for Pediatrics; he called attention to the possibilities for transmission of tuberculosis offered by the present method of teaching in public schools. It happens frequently, especially among the poorer classes, that a child showing manifest symptoms of active disease (cough, anemia, slight temperature, night sweats) is not kept at home, and thus may disseminate disease among the children in his classroom. Dr. Peyser made investigations in a school in Vienna from the third form of which two children with manifest pulmonary affection had been brought to his dispensary. He first of all obtained permission from the parents to make a tuberculosis test on the pupils by using Moro's ointment three times within a week and then injecting 1 mg. of tuberculin. By these means, patients that are unusually

Further Studies on "Blackhead" in Turkeys, with Special Reference to Transmission by Inoculation

Although the parasite causing the disease in* turkeys popularly known as was discovered many years ago, the mode of its transmission has not been satisfactorily demonstrated. Several distinct problems are involved in this question of transmission: (1) the source of the parasite; (2) the route by which it enters the body of the turkey, and (3) its pathogenic properties or virulence. Whether the parasite of blackhead, Histomonas meleagridis, occurs only in association with the disease, and is thus to be regarded as uniformly pathogenic, or is widely prevalent in the cecal contents of normal turkeys, and only invades the tissues under conditions which lower the host's resistance, has, up to the present, been regarded as a more or less open question. The possibility that this organism, while pathogenic for the turkey, may occur commonly in the intestinal tract of other species, such as the common fowl in which it may rarely produce lesions, should also be considered. The determination of any of these various points concerned in the transmission of blackhead may prove of practical importance in the rearing of turkeys. Source.?Considerable information is already available as to the sources of the infection. That the disease may be acquired by the exposure of normal turkeys to those which have shown evidence of infection, has been experimentally demonstrated by Theobald Smith,1 and Tyzzer.2 Smith3 concludes that turkeys which have passed through an attack are more dangerous as sources of infection than are those showing symptoms of active disease. Blackhead occurs chiefly in young turkeys during the summer months, and acute cases are often lacking throughout the greater portion of the year. It is obvious, therefore, that other sources of infection exist. We are not warranted, however, in assuming from Smith' s results that the acute