Negative Reactors Research Articles

COMPARISON OF MULTIPLE PUNCTURE LIQUID TUBERCULIN TEST WITH MANTOUX TEST

Two studies were performed to compare the disposable liquid tuberculin PPD 'Imotest' with the Mantoux test. While there was a tester effect in the first study indicating the need for accurate application of the imotest, the results of the second study showed that the two tests were comparable in selecting truly positive and negative tuberculin reactors. Results were compared both by conventional methods and by a method new to tuberculin testing, the maximum likelihood technique. This method gives a more accurate estimate of false reaction rates. A significant difference was found between reading at 48 and 72 h for both tests. The acceptability and ease of reading of the imotest, with a tuberculin selectivity comparable to the Mantoux method, make it a suitable alternative tuberculin test, especially for screening large populations.

Intravenous hyperalimentation. Effect on delayed cutaneous hypersensitivity in cancer patients.

Effects of nutritional repletion with intravenous hyperalimentation (IVH) on sequential skin test reactivity were evaluated in 160 malnourished cancer patients undergoing chemotherapy (76 patients), surgery (49 patients), radiation therapy (20 patients) and supportive care (15 patients). In the chemotherapy group, 45 patients had negative reactions initially, and 25 patients (55%) had at least one skin test convert to positive in an average period of 19 days of IVH. In the surgery group, 23 patients (46%) were initially positive and remained positive, 13 patients (24%) converted from negative to positive, and 13 patients (30%) remained negative or converted to negative. Postoperative complications occurred in 25% of positive reactors, compared with 69% (p < 0.01) of negative reactors. In the radiation therapy group, the skin tests of six patients (30%) remained positive, three patients (15%) converted from negative to positive and the skin tests of nine patients (45%) remained negative. In the supportive care group, the skin tests of 73% of the patients either remained positive or converted to positive with IVH within an average period of 11 days of treatment. Nutritional therapy with IVH was associated with restored skin test reactivity in 51% of malnourished cancer patients undergoing oncologic therapy. Radiation therapy was generally immunosuppressive despite adequate nutritional repletion. In surgical patients, positive skin test reactivity correlated directly with a favorable response to operative therapy.

Toluene di‐isocyanate‐induced asthma II. Inhalation challenge tests and bronchial reactivity studies

In sixty-three workers exposed to toluene di-isocyanate (TDI), no overall differences in bronchial reactivity to histamine inhalation and to exercise testing were found between the total groups of positive and negative TDI reactors to provocation tests. A subgroup of TDI highly sensitive subjects reacting to very low concentrations (less than or equal to 0.001 p.p.m.) were more sensitive to both histamine and exercise than the group who were less sensitive to TDI, and who reacted to higher concentrations (0.002--0.02 p.p.m.) than the group of non-reactors. There were, however, in the last group a number of subjects with high degrees of histamine reactivity who did not react to the TDI. These findings suggest that, on the one hand, the asthmatic reactions to TDI cannot be attributed solely to non-specific mechanisms and, on the other, that in subjects with high degrees of specific sensitivity non-specific mechanisms may also be playing a part.

Cephalometric comparisons of the results of the Wardill-Kilner and Von Langenbeck palatoplasties: Samir E. Bishara, Hans Enemark, and Rosemary F. TharpCleft Palate J. 13:319–329, October, 1976

Although little is yet known about tuberculosis in Nepal itself because no records can bestudied there and no survey within the country has yet been carried out, the prevalence of radiographic tuberculous lesions and of positive tuberculin reactions in would-be Gurkha recruits suggests that the disease must be quite common in the districts of Nepal whence the British army draws its Gurkha recruits.In the army, the incidence of tuberculosis in Gurkhas is still high in spite of strict measures enforced to reduce it. Even in men who joined the army scince 1951, amongst whom all negative reactors on enlistment have been vaccinated with BCG, the incidence has been high compared with the rates shown by troops of other nationalities serving in the same area.A particularly high incidence is demonstrated in Gurkha recruits during their firstyear of army service. This has been due mainly to the large number of cases of primary tuberculosis which have occurred. It is suggested that many recruits are primarily infected on the journey they make from their homes to the recruiting depots in Nepal where they enlist. The conditions on this journey are highly conducive to the spread of respiratory infection, and tuberculosis is known to exist among the inmates of the rest houses along the routes and around the depots.Most cases in the Brigade of Gurkhas now occur in men who are already tuberculin positive when they enlist, having already acquired their primary infections in Nepal before joining the army. It is estimated that by the end of 1966, if the present rates continue, about 46 new cases of tuberculosis will occur each year, of which 40 will be in positive reactors and only five or six in vaccinated men. If future incidence is to be reduced it is on the positive reactors that particular attention must be directed.In the positive reactors a relationship is demonstrated between strong tuberculin sensitivityon enlisment and subsequent disease incidence. Not only has the incidence been considerably higher in the strong reactors, but they have provided the bulk of the disease which has occurred in the reactor group. The recruit who reacts strongly to tuberculin on enlistment appears to be at special risk of developing tuberculosis during his army service, and it is recommended that special measures, namely isoniazid prophylaxis, be taken to prevent the emergence of overt manifestations of tuberculous disease.The various factors which might have been responsible for the occurrence of disease in the positive reactors are examined. It is estimated that one in four cases in positive reactors has been due to exogenous infection acquired after contact with another infectious person. The sources of such infection are believed to exist most commonly in the following situations and in the following order: in Nepal itself, where soldiers return on leave once every three years; in the wives and families of soldiers; in the civilians of the countries where Gurkhas serve, and in other (infectious) soldiers.The endogenous exacerbation of already-existing latent foci has been responsible for three in four of the cases occurring in positive reactors. Such exacerbation can occur because individual resistance is low, or because environmental factors such as fatigue, stress and privation have upset the equilibrium existing between resistance and bacterial virulence.Since the various ‘environmental’ factors have been affected for the better rather thanfor the worse by military service, the conditions of life in the army cannot be held mainly responsible for the disease which has occurred in the positive reactors. It may be the case that the primary factor responsible for endogenous breakdown in Gurkhas is that many of them possess low levels of native or natural resistance. This may be because Nepal as a country is comaparatively young in its experience of tuberculosis and stocks still exist amongst the Gurkhas who are immunologically ill equipped to deal with endogenous progression of naturally acquired primary lesions.

Halothane sensitivity as a field test for stress-susceptibility in the pig

ABSTRACTThe possible use of a pig's reaction to the anaesthetic halothane as a field test for Porcine Stress Syndrome in genetic improvement pro-grammes was investigated. A standard 3-min halothane test gave incidences of positive reaction of 20% in a composite Pietrain/Hampshire line, 5% in Norwegian Landrace, 1% in Hampshires and zero in Durocs, Large Whites and N. American Yorkshires. In the Pietrain/Hampshire population, two generations oftwo-way selection on the test gave a divergence in incidence of positive reaction of 85%, and the frequencies of affected progeny supported the hypothesis of monogenic recessive inheritance. From second tests made 20 days after the first, the probability of misclassifying a pig's reaction on one test was 5 ± 1%. Positive reactors had significantly shorter and leaner carcasses, fewer pigs born alive, poorer meat quality, higher mortality and greater plasma creatine phosphokinase activity than negative reactors.

Immune-allergic survey with spherulin in a general hospital from São Paulo, Brasil.?

A skin-test survey for sensitivity to Coccidioides immitis was carried out at the Hospital das Clinicas da Faculdade de Medicina da Universidade de S~o Paulo among 347 patients aged above 11 and from various eastern areas of the country. Commercial spherulin (Berkeley Biological, California, USA) was used; 194 (599%) negative reactors were retested with a high strength antigen (10-fold concentrate). An adult female, who reacted also to paracoccidioidin and sporotrichin, was the only reactor to spherulin. Spherulin has been shown to be more sensitive than coccidioidin and equally specific. The present study thus confirms the earlier report from Lacaz et al. (2) showing that coccidioidomycosis does not occur in north, middle or southeast Brazil, and confirming previous investigations from Versiani (3) and Lacaz (1), that spherulin does not cross-react in patients with South American Blastomycosis.

Tuberculin testing in hospital personnel

Tuberculin testing of 176 personnel in a Liverpool hospital showed a total incidence of 68% negative reactors. This remarkably high percentage was similar for each of the various groups of workers tested. We did not find the Tine test to be a satisfactory method of screening for tuberculin sensitivity because 30% were doubtful reactors. In these, further tuberculin testing by the Mantoux reagent was always positive.

TETANUS SKIN TEST: DOES IT ASSESS DELAYED HYPERSENSITIVITY?

To determine if the tetanus skin test (TST) is a valid procedure for the evaluation of delayed hypersensitivity we correlated the results of skin testing with in vitro lymphocyte transformation to tetanus (TTx), antibody titers to tetanus by hemagglutination (TAB), and monocyte chemotaxis (MCTX). We tested 6 unimmunized infants less than 10 weeks of age, 6 patients with X-linked agammaglobulinemia (AGG) and 35 immunized controls(8 weeks-35 years) with 0.1 ml of a 1:5 dilution of fluid tetanus toxoid; a positive TST at 48 hours was induration >5 mm in diameter. A transformation index (cpm of 2 × 105 stimulated cells/cpm unstimulated cells) of >2 and a TAB >1:4 were considered positive. MCTX was performed by the agarose gel technique. All 6 unimmunized infants had negative TST and TTx despite TAB from 1:2 to 1:32. 5/6 AGG had positive TTx and 4/6 had positive TST. In immunized controls 19/35 (54%) had a positive TST, including 14/17 over age 2 and 5/18 under 2. Among the 19 positive reactors all had positive TTx and TAB >1:4. Among the 16 negative reactors 16/16 had positive TTx and 15/16 had TAB >1:4. Of the patients with positive TTx and negative TST 6/6 studied had low MCTX while 11/12 with both positive TTx and TST had normal MCTX. There was a significant correlation between TST reactivity and TTx and MCTX but not between TST and TAB. We conclude that a positive TST is independent of TAB, that TST measures T-cell immunity but is less sensitive than TTx and that a positive TST necessitates both intact TTx and MCTX.

Dinitrochlorobenzene skin sensitization and peripheral lymphocyte count: predictors of survival in head and neck cancer.

Dinitrochlorobenzene (DNCB) is a simple chemical useful to evaluate both afferent (sensitizing) and efferent (reacting) limbs of the delayed, cell-mediated immune system. This system invokes the small lymphocyte (T cell) and is apparently part of the host defense against cancer. Severnty-two patients with new primary squamous cell carcinomas of the larynx, hypopharynx and oropharynx were sensitized to DNCB by contact application, and delayed cutaneous hypersensitivity tested. The T cells were also assessed in this study by lymphocyte count. All patients were treated for cure. Ninety-one percent of DNCB reactors were alive and tumor-free at two years. Forty-five percent of negative reactors had recurrent tumor and died of carcinoma. Cases grouped by site among glottic, supraglottic and inferior hypopharynx showed identical results. Lymphocyte counts showed a trend in the same direction. On statistical analysis, all differrences were significant. Eighty-five percent of recurrent tumors occurred in patients who were nonresponders. The present data suggest DNCB reactivity is helpful in predicting outcome after surgery, or combined radiation and surgery, for mucosal squamous carcinoma of the head and neck.

Delayed hypersensitivity in patients treated by curative radiotherapyIts relation to tumor response and short-term survival

Delayed hypersensitivity, as determined by skin reactivity to 2-4 dinitrochlorobenzene (DNCB), was tested in 112 patients prior to their undergoing curative radiotherapy. Of the strong DNCB reactors, 84% had an excellent radiation tumor response, while only 48% of the negative reactors had an equivalent response. Almost twice as many strong DNCB reactors were alive and free of disease (NED) at 6 months (70% vs. 38% for nonreactors). Similarly, the positive DNCB reactors had a median survival of 18 months, compared to 10 months for the nonreactors.

Values of intradermal test and multiple sputum examinations for Diagnosis of paragonimiasis

This study was conducted on 4,003 inhabitants of six villages, Southern County of Che Ju lsland from April 18 to July 30, 1974 with purpose of studying. Relationship between intradermal reaction and egg detection rate, Egg detection rate by the number of sputum examination on the same subject, Comparison of direct sputum examination method (Whole volume of sputum in vinyl bag pressed between petri dishes) with concentration (2% NaOH) method, Estimation of sensitivity and specificity of the intradermal test in screening paragonimiasis. The results obtained are as follows: 1. Overall positive skin reaction rate was 57.7 % and egg positive rate regardless of skin reaction was 17.1 % the population studied. 2. Egg positive rate for negative skin reactors(wheal size smaller than 70mm(2)) was l0.l %, and that of positive reactors was 22.8 %. 3. Positive skin reaction rate increased as age increased, egg positive rate, however, revealed rather inconsistent distribution by age. 4. The egg positive rate showed a tendency of increase by increase of wheal size, though not so remarkably. 5. 2.9 % of egg positives by direct sputum examination method was negative when re-examined by concentration method; 2.6 % of egg negative sputum by direct method was egg positive by concentration method. It was found that the sputa showing discrepant result by two different methods had only a few eggs in whole sputum collected. 6. Egg positive rate by single sputum examination was 8.l %, by two examinations 14.6 % by three 19.2 %, by four 24.5 %, and by five examinations on the same individual was 20.5 %. 7. The estimated sensitivity and specificity of the skin test were 76.5 % and 42.7 % respectively under the postulation that all infected persons could be detected by four sputum examinations.

Study of the placebo effect with a self-administered placebo test

An attempt was made to develop a self-administered test of placebo reactivity that combined the reliability of a test of suggestibility with the clinical validity of reaction to the placebo effect. Response to the Placebo Test was determined by a patient's response to a placebo tablet, which was taken by the patient at home for the ostensible purpose of determining which medicine would be most helpful to him. The Placebo Test and other information were collected after the patient's initial intake evaluation at a psychiatric clinic. A series of independent variables were related to the Placebo Test as dependent variables, and an attempt was made to predict clinical course for patients in psychiatric treatment. Although the Placebo Test had high internal-consistency reliability of measurement, it may have had low validity as a test of placebo-proneness, as evidenced by the difficulty of selecting relevant parameters for measurement of the placebo effect. Depending on the method of measurement, 32 to 36 patients had positive reactions, 36 to 49 had neutral reactions, and 14 to 30 had negative reactions. Thirty-eight patients had side effects from the placebo, and 15 refused to take the test. In general, the results obtained varied with the method of scoring the Placebo Test, except for the major finding that negative placebo reactors were clearly differentiated from positive reactors and nonreactors, who were not significantly different from one another. The conclusion, now supported by two studies, is that analysis of placebo studies requires that positive reactors not be compared to a pooled group of negative reactors and nonreactors. In addition, analysis should include patients who refuse to take the placebo. The relationship between patient improvement and the likability measures is the strongest relationship among variables and improvement, and it warrants further study.

Tuberculin skin testing in a chronically sick aged population.

ABSTRACT:Two hundred and thirty‐seven chronically sick aged patients were skin tested with Tuberculin PPD, Intermediate Test Strength. Healthy younger staff members constituted a control group. The percentage of negative reactors among the patients appeared to be directly related to the severity of their chronic illness, as represented by the various ward categories. The percentage of negative reactors among the patients who subsequently showed a positive reaction to Tuberculin PPD, Second Test Strength, was directly related to the state of health of the patients. In sick old persons, a negative reaction to Tuberculin PPD, Intermediate Test Strength, should be followed by testing with Second Test Strength before it can be confirmed that the person is a negative reactor. The significance of a negative reaction to even very large doses of Tuberculin PPD should be viewed in the context of the overall clinical picture when dealing with a chronically sick aged patient.

The relationship between tuberculin reactions and the later development of tuberculosis: An investigation among edinburgh school children in 1960–1970

Tuberculosis notifications during the years 1960–1970 have been related to the results of tuberculin tests and of BCG vaccination of 13-year-old children at school during the same period. Among those with any grade of reaction to the multiple-puncture test notification rates were highest during the first year of observation. When the first year was excluded, those with Heaf grade III or IV reactions had a notification rate of l·61 per l,000 per year. The corresponding rate for those with grade II reactions was 0·43. Children with grade I reactions had a relatively low notification rate of 0·09 per l,000 per year, almost the same as for negative reactors who were vaccinated with BCG (0087). The risk of tuberculosis developing in groups of children with grade I reactions is small and most of the children have acquired their skin sensitivity from agents other than tubercle bacilli; but it is important to recognise that some of them may in fact have tuberculous infections or even manifest tuberculous lesions.

Studies on the allergenic fungal spores of the Delhi, India, metropolitan area: Clinical aspects

A comprehensive investigation was done to evaluate the allergenic fungi in India. Results of 11,773 skin tests on 1,079 patients with nasobronchial allergy and 1,165 skin tests on 55 healthy persons with 29 antigens of fungi common in Delhi, India, are presented and compared. There were 5.9 per cent markedly positive (2+ to 4+) skin reactions in patients but none in healthy control subjects, who showed only 5.1 per cent 1+ reactions as compared with 8.9 per cent in patients. If 1+ reactions are included, there were 14.7 per cent positive skin reactions in the allergic patients. Bronchial tests were positive in about 66 per cent and conjunctival tests were positive in 38 per cent of the patients who had given positive skin reactions to the same antigens. The bronchial and conjunctival tests were negative in negative skin reactors, and conjunctival tests were also negative in 1+ skin reactors. About 29 fungi found in our environment are arranged in order of allergenicity based on the frequency of markedly positive skin reactions (2+ to 4+) produced by them.

Ischemic arm pain and dexoxadrol

In nine subjects representing a majority (75 percent) of the population tested, ten milligrams of Dexoxadrol combined with 600 mg of acetylsalicylic acid (ASA) was essentially equivalent to 20 or 30 mg of Dexoxadrol pooled sample when tested by ischemic arm method, both doses being significantly more potent than ASA alone one hour after dosage. Three hours after dosage, all doses of Dexoxadrol were still significantly above ASA alone or lactose placebo indicating a more prolonged action of this drug. The stimulating effect of lactose placebo is postulated to explain the temporary rise (1 h) noted by use of this substance. When all twelve subjects are considered, because of three negative reactors, only statistically significant differences between ten milligrams of Dexoxadrol plus 600 mg of ASA are distinguishable from ASA alone or placebo at the end of one hour. At all dosage levels some side effects similar to alcohol were noted, numbness, dizziness, drowsiness, etc., as described by (LASAGNA and PEARSON, 1965). The 30 and 20 mg dosage produced more prominent psychic effects, while the 10 mg dosage with ASA produced a minimum of such effects and was virtually as effective as the higher dosage in nine of twelve subjects.

Serological Diagnosis of Babesia bigemina Infection in Cattle by the Indirect Fluorescent Antibody Test

An indirect fluorescent antibody (IFA) test is described for the detection of Babesia bigemina antibodies in bovine serum. A method is described for the preparation of antigen smears which virtually eliminates confusing background fluorescence. A microstaining technique is used affording considerable economy of test reagents. The test is considered to be highly specific and accurate (100% in 100 known control sera) and sufficiently sensitive to detect reactors infected 2 years previously. Susceptible and immune clinical responses are obtained when groups of negative and positive reactors to the IFA test are challenged with B. bigemina infected blood, demonstrating, in addition to test reliability, a correlationship between protective antibodies and those detectable by immunofluorescence. IFA tests of sera collected regularly over 6 months show initial responses following rapidly the pre-patent period, reaching peaks at 21 days after infection, with maximum titres up to 1:1,280 waning gradually thereafter, but still above minimum levels at the end of the period. Some evidence is produced indicating a continued downward trend with minimum positive IFA responses still detectable 18 to 24 months after a single experimental infection.

Studies with the purified protein derivative of human and avian tuberculins in south queensland

734 children at a secondary school in South Queensland had their sensitivities to human and avian PPD investigated by a simultaneous intradermal injection using first a small (5 TU human and 4 TU avian) dose on each child then a large (100 TU human and 80 TU avian) dose on negative reactors of 4 mm. or less diameter of induration. The results were analysed according to whether the individual had not had a previous skin test or a BCG vaccination (non-BCG group), or had had a previous BCG vaccination because of a negative Heaf test (BCG group). The non-BCG children with no previous skin test as a group had a much higher sensitivity rate to the avian PPD than to the human PPD; and the reactions were larger to the avian than the human antigen. This was similar to the pattern of Brisbane children two years previously. The BCG children also had a larger mean reaction size to the avian PPD than the human PPD, but this was not so marked as in the non-BCG children. This larger reaction to the avian antigen bore no relation to the time since BCG vaccination, the pattern of the correlation of reaction sizes remaining similar from five months since vaccination to several years afterwards. In a second study, school children with an average age of 13 years were skin tested with low dose PPD human and PPD avian by the intradermal (Mantoux) method prior to routine BCG vaccination. Correlation of reaction sizes three days after the tests gave a pattern. indicating a high rate of sensitization amongst these children to avian PPD and some cross sensitization to human PPD. The sensitizing agent is thought to be a Battey Group III organism which is commonly isolated from human sources in Queensland and is also widely distribution in nature. This also has a close antigenic relationship with the avian bacillus. All children with a reaction size of 4 mm. or less of induration to the human PPD were given BCG vaccination, the size of the reaction to avian PPD being ignored. The BCG vaccine was the Danish strain manufactured in Melbourne. Seven weeks after vaccination, retesting showed that reactions to both antigens were larger and more frequent, but that those to avian PPD were larger than those to human PPD. It is suggested that the effect of this particular BCG vaccine in these children, who have some experience of mycobacterial infection, possibly with a Battey Group III organism, had a greater cross-sensitizing effect than direct sensitizing effect. The results may also be influenced by human PPD not being the homologous antigen of BCG.

Study of the placebo effect with a placebo test

This paper briefly reviewed several methodological problems in studies of the placebo effect. The importance of finding appropriate measures of placebo effect was emphasized. This led to an attempt to develop a more valid and reliable test of placebo reactivity. Use of the placebo test led to the following tentative conclusions: Inferences made about placebo effects vary with the method of scoring placebo reactions. The placebo effect consists of a group of nonreactors to the placebo, and a second group of reactors but without regard to positive or negative direction. The reactive group is subdivided into predominantly positive or negative groups. Thus, comparing positive reactors with a combined group of nonreactors and negative reactors obscures important differences among groups. Patients with positive reactions to placebo tend to improve more rapidly and have a better prognosis than patients with neutral and negative reactions. Patients with absent and negative responses may respond to treatment eveually but not as predictably as positive reactors. Other confirmed predictions were that positive and negative placebo reactions would be unrelated to older age, lower intelligence, authoritarianism, duration and severity of illness, and diagnosis, and that placebo reaction would be related to anxiety and depression. The placebo test may combine the best features of a simple, standardized, quantitative, and reliable laboratory test of suggestibility with the clinical relevance and validity of the placebo effect. These conclusions are qualified by the limitations of the study, particularly the small sample. This paper should be considered a report of preliminary findings which should be investigated further.

Tuberculosis as a Military Epidemic Disease and its Control by the Navy Tuberculosis Control Program

1. That outbreaks of tuberculosis can and do occur in isolated, close contact situations as microepidemics is well authenticated by previous reported episodes. 2. In the United States, with a diminishing infection rate and an increasing number of negative tuberculin reactors, the setting exists for the development of such from an active case of tuberculosis. 3. The experiences of the U. S. Navy with six shipboard tuberculosis outbreaks is related, with illustration of their development, detection and control. 4. A broad tuberculosis control program, such as is in force in the U. S. Navy is the major factor in the early detection of and control of such outbreaks. 5. The U. S. Navy Tuberculosis Program is described, its implementation outlined, along with the implication of the importance of maintaining tuberculin skin test negativity in the Navy personnel for best control.