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Biomedical subjects

M Goble

Publications and source records attributed to M Goble.

At least 19 recordsLinked to original sources

Quantitative measurement of drug susceptibility of Mycobacterium tuberculosis for monitoring chemotherapy response.

Changes in the degree of drug susceptibility of the bacterial population in tuberculosis patients during chemotherapy can be monitored by testing Mycobacterium tuberculosis isolates against various concentrations of drugs in 7H12 broth to determine radiometrically the minimal inhibitory concentration (MIC). The MICs were determined for multiple cultures isolated from 13 patients, of whom nine responded to chemotherapy within a few months, and four failed to respond at all. No changes in MICs were observed with the isolates obtained from the patients with a favorable response to chemotherapy. Determination of the MICs indicated that the failure in two cases out of four was associated with a steady increase in the degree of resistance of the patients' bacterial population. In two other failure cases, lack of change in the MIC values for multiple cultures suggests that the failure was associated with factors other than drug resistance. During the period of chemotherapy, quantitation of the degree of drug susceptibility in terms of broth-determined MICs may help to identify promptly those patients whose bacterial population is becoming resistant to the administered antimicrobial agents. For those patients who do not respond to chemotherapy, lack of change in the degree of resistance of their bacterial population may alert the physician to attempt to identify causes other than drug resistance for the chemotherapy failure.

Adult↗

Treatment of 171 patients with pulmonary tuberculosis resistant to isoniazid and rifampin.

BACKGROUND AND METHODS: The frequency of infection with multidrug-resistant Mycobacterium tuberculosis is increasing. We reviewed the clinical courses of 171 patients with pulmonary disease due to M. tuberculosis resistant to rifampin and isoniazid who were referred to our hospital between 1973 and 1983. The patients' records were analyzed retrospectively. Their regimens were selected individually and preferably included three medications that they had not been given previously and to which the strain was fully susceptible. RESULTS: The 171 patients (median age, 46 years) had previously received a median of six drugs and shed bacilli that were resistant to a median of six drugs. Thus, their regimens were frequently not optimal. Of 134 patients with sufficient follow-up data, 87 (65 percent) responded to chemotherapy (as indicated by negative sputum cultures for at least three consecutive months); 47 patients (35 percent) had no response, as shown by continually positive cultures. The median stay in the hospital was more than seven months. In a multivariate analysis, an unfavorable response was significantly associated with a greater number of drugs received before the current course of therapy (odds ratio, 4.0; 95 percent confidence interval, 1.6 to 9.9; P < 0.001) and with male sex (odds ratio, 2.5; 95 percent confidence interval, 1.1 to 6.2; P < 0.03). Twelve of the patients with responses subsequently had relapses. The overall response rate was 56 percent over a mean period of 51 months. Of the 171 patients, 63 (37 percent) died, and 37 of these deaths were attributed to tuberculosis. CONCLUSIONS: For patients with pulmonary tuberculosis that is resistant to rifampin and isoniazid, even the best available treatment is often unsuccessful. Only about half of such patients eventually have negative sputum cultures despite carefully selected regimens administered for extended periods. Failure to control this resistant infection is associated with high mortality and ominous implications for the public health.

Adolescent↗

Ten-year experience with artificial pneumoperitoneum for end-stage, drug-resistant pulmonary tuberculosis.

Artificial pneumoperitoneum is a form of collapse therapy that was used in the treatment of cavitary pulmonary tuberculosis before the availability of antimycobacterial chemotherapy. We report a series of cases of far-advanced pulmonary disease due to multiple-drug-resistant Mycobacterium tuberculosis, wherein artificial pneumoperitoneum with or without subsequent surgical extirpation was used as an adjunct to chemotherapy. Overall, among these desperate cases, therapeutic pneumoperitoneum provided no clear benefit.

Adult↗

Surgical management of resistant mycobacterial tuberculosis and other mycobacterial pulmonary infections.

Between August 1983 and October 1990, 42 patients with resistant Mycobacterium tuberculosis underwent 44 pulmonary resections. During the same time, 38 patients with mycobacterial infections other than tuberculosis had 41 pulmonary resections. All patients either were poor candidates for medical therapy alone or had existing complications requiring surgical intervention. There was one operative death in each group, both from adult respiratory distress syndrome (postpneumonectomy pulmonary edema). Complications were high, with bronchopleural fistula most commonly occurring after right pneumonectomy in patients infected with Mycobacterium avium with superimposed infection with nonmycobacterial pathogens. In patients undergoing pneumonectomy for resistant Mycobacterium tuberculosis, the left lung was most often resected. It is recommended that if localized disease is present and medical treatment is likely to fail, pulmonary resection should be performed for resistant Mycobacterium tuberculosis infection after 3 months of drug-specific therapy. Muscle flaps were used frequently to avoid residual space and bronchial stump problems. Earlier resection in patients with indolent nontuberculous mycobacterial pulmonary infections is advocated before extensive polymicrobial contamination and right lung destruction.

Adult↗

Pharmacokinetic evaluation of ethionamide suppositories.

The absorption and elimination of ethionamide (ETA) after oral tablets and rectal suppositories were determined in 12 healthy, adult male volunteers. A randomized, double-blind, double-dummy, crossover design was used. Treatments compared 250-mg ETA tablets and a placebo suppository to a 500-mg ETA suppository and two placebo tablets, given 7 days apart. Blood samples were collected at predetermined intervals for 12 hours after the dose. Serum concentrations of ETA were determined using high-performance liquid chromatography. The area under the serum concentration-time curve was used to compare the relative bioavailability of ETA from the two preparations. Relative bioavailability after rectal administration was 57.3% of that after oral administration. The maximum serum concentration after rectal administration was 33% of that after oral administration. Higher doses of ETA and serum concentration monitoring are recommended whenever the suppositories are used.

Administration, Oral↗

Lignin peroxidase from Phanerochaete chrysosporium. Molecular and kinetic characterization of isozymes.

Five isozymes of lignin peroxidase from Phanerochaete chrysosporium were purified and their physical, molecular and kinetic properties determined. The isozymes differ from each other in terms of their isoelectric point, molecular mass, sugar content, spectral characteristics, substrate specificity and stability. The N-terminal sequence of amino acids was different for each isozyme suggesting they are different gene products. The isozyme with the highest carbohydrate level was most sensitive to changes in environmental factors. The kinetic behaviour of the isozymes varied clearly when tert-butyl hydroperoxide instead of hydrogen peroxide was used as the oxidant. Two out of five isozymes had very similar substrate specificity. The results are discussed in relation to the role which lignin peroxidase isozymes may play in lignin biodegradation.

Amino Acid Sequence↗

Quantification of prostatic cancer metastatic disease using prostate-specific antigen.

The serum prostate-specific antigen (PSA) of 58 men with benign prostatic hypertrophy (BPH) and 17 men with carcinoma of the prostate (CaP) was correlated with the weight of prostatic tissue resected at transurethral prostatectomy (TURP). A significant correlation was identified between the weight of resected BPH tissue and the serum PSA (p less than or equal to 0.001; r = 0.54). No such correlation was seen in the CaP patients. By arbitrarily dividing the serum PSA by the prostate weight, it was possible to devise an index. This index corrected PSA in relation to prostatic size and unlike PSA in isolation did not differ significantly between normal controls and those with BPH. The index in CaP was significantly greater than that of either controls or BPH (p less than or equal to 0.001). Furthermore the index of metastatic CaP (M1) was significantly higher than that of nonmetastatic disease (MO) (p = 0.05). The higher index found in CaP would seem to be related to the bulk metastatic tumor, either manifest or occult. Comparing the index of CaPs to that found in normal and benign disease (a constant) offers a possible means of estimating the extent of local and metastatic tumor mass.

Antigens, Neoplasm↗

Surgical intervention in the treatment of pulmonary disease caused by drug-resistant Mycobacterium tuberculosis.

Of 99 patients with pulmonary disease caused by multiple-drug-resistant strains of Mycobacterium tuberculosis admitted to the National Jewish Center for Immunology and Respiratory Medicine from 1983 to 1988, 29 were selected for resection to supplement chemotherapy. All patients had organisms with high levels of resistance to all of the first line medications, including rifampin and isoniazid. Although the patients were treated preoperatively with multidrug regimens in an effort to reduce the mycobacterial burden, 20 of 29 were still sputum-culture-positive at the time of surgery. The bulk of the disease was manifest in one lung, but lesser amounts of contralateral disease were demonstrated in 27 of 29. Pneumonectomy was done in 15 patients; lobectomy or lobectomy plus was done in 14. Although physiologic studies before surgery indicated significant respiratory impairment in many of the patients, there were no operative deaths. There were two unrelated deaths in this series. Of the 27 survivors, 25 have remained sputum-culture-negative for a mean duration of 36 months. Compared with historical controls, resectional surgery appears to offer benefit to selected patients with pulmonary disease caused by M. tuberculosis with extensive levels of drug resistance.

Adult↗

Drug-resistant tuberculosis.

Management of drug-resistant tuberculosis (TB) is challenging. In areas with high prevalence of drug-resistant TB, we recommend starting all patients with active TB on the standard four or five drug regimens. For patients with acquired drug resistance due to prior inadequate therapy, we advocate thorough evaluation of history and drug susceptibility followed by individualized regimens of at least three drugs. Drugs are most effective if the patient has never received them before and if the patient's tubercle bacilli are susceptible to them in vitro. Retreatment regimens are of long duration and often there are adverse drug reactions. These factors must be put into perspective because options for alternate therapy may be limited. Compliance must be assured.

Antitubercular Agents↗

The myth of the clean catch urine specimen.

Urine specimens obtained from unprepped ambulatory females who voided into an unsterile disposable plastic cup showed a 95-per cent correlation with a catheterized specimen collected from a prepped patient through a sterile cystoscope. From these data, it appears that the midstream urine specimen and its unpleasant collection routine can be eliminated. We have found that specimens collected at anytime during voiding in unsterile disposable plastic cups result in reliable urine cultures.

Adult↗

Treatment of disease due to Mycobacterium intracellulare.

During eleven and one-half years, 122 patients with M. intracellulare disease were treated at National Jewish Hospital and Research Center, Denver, Colorado. Of the 81 patients treated with multiple drug chemotherapy, 63 (78%) were considered to be treatment successes. On follow-up (averaging 55 months) 40 of the 63 patients had remained clinically stable or improved and 12 had grown worse. Ten of these 63 patients had relapsed. Of the 63 patients considered to be treatment successes, 23 (36.5%) had died during follow-up, mostly of pulmonary disease. Of the 18 patients who failed to respond to chemotherapy, 2 were later successfully treated with surgery, 5 patients were clinically worsening, and 8 (44%) had died during a follow-up period averaging 43 months. A group of 41 patients had indeterminate results with chemotherapy. Eight had died while in the hospital. Follow-up information after an average of 43 months indicated that 9 patients became treatment successes (5 with chemotherapy, 4 with surgery), 12 were clinically stable or improving, and an additional 13 had died for a total of 21 deaths (51%). The overall success of treatment in the 122 patients was 61%. Fifty-two (43%) died during the study. Many patients will respond to drug therapy and remain clinically well for years. Because of the potential seriousness of this disease in some patients, multiple drug chemotherapy should be used.

Adult↗