Antituberculous therapy and acute liver failure.
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Adult↗
Biomedical subjects
A M Patel
Publications and source records attributed to A M Patel.
Degradation of Escherichia coli uncB mRNA by multiple endonucleolytic cleavages.
The mechanism of segmental decay of the uncB sequence near the 5' end of the 7-kb Escherichia coli unc operon mRNA was investigated. Northern (RNA) blots of mRNA expressed from a plasmid carrying the uncBE portion of the operon revealed that the uncB message was rapidly degraded by multiple internal cleavages which resulted in the formation of at least five discrete species having a common 3' end. Turnover studies indicated that processing rapidly converted all species to the smallest. Identification of the 5' ends by primer extension analysis revealed that the cleavages were made either in the uncB coding region or in the intercistronic region between uncB and uncE, the latter being the most 3' cleavage. An rne mutant strain contained much higher levels of the uncBE message, implying that RNase E, the product of the rne gene, is essential for the normal degradation of uncB, and a number of the 5' ends were not detected in the rne mutant. The cleavage sites in chromosomally encoded unc mRNA were also identified by primer extension. These studies reveal that the segmental decay of the uncB region of unc mRNA occurs rapidly through a series of endonucleolytic cleavages. The rapid decay of uncB is expected to play a role in limiting expression of this gene relative to that of the other genes of the operon.
Bacterial Proteins↗
Avoidance and management of adverse reactions to antituberculosis drugs.
Potent antibiotics are required to cure tuberculosis and reduce the burden of illness in the community. Minor adverse effects are commonly encountered and can be managed by reassurance and explanation. Significant hypersensitivity reactions require cessation of all antituberculosis drugs. Adverse effects should be treated appropriately. An effective antituberculosis regimen should be reestablished as soon as possible. Desensitisation may be necessary if suitable alternative drugs cannot be used. In the event of drug-induced hepatitis, all hepatotoxic drugs should be ceased until symptoms resolve and liver function tests return to normal. Other significant direct toxic effects should be promptly detected and appropriately treated. A thorough knowledge of potential adverse reactions and pharmacokinetics is essential for any physician using antituberculosis drugs.
Aging↗
Gossypibomas mimicking echinococcal cyst disease of the lung.
Gossypibomas, masses of retained cotton materials, may produce a variety of postoperative complications. This case report of hemoptysis of 18 months' duration and cavitating chest masses in a 62-year-old man with previous cardiac operations illustrates several salient features about the presentation, differential diagnosis, and management of gossypibomas.
Diagnosis, Differential↗
Clinical manifestations of lung cancer.
The initial clinical manifestations of lung cancer are diverse and may occur with or without symptoms. Manifestations of pulmonary malignant lesions are produced by local growth or invasion, metastatic disease, or paraneoplastic processes. Patterns of local invasion such as Pancoast's syndrome or the superior vena cava syndrome are relatively uncommon but well recognized. Metastatic lung cancer can involve almost any anatomic area by hematogenous, lymphatic, or, occasionally, interalveolar dissemination. Complications related to malnutrition, infection, electrolyte disturbances, and coexisting diseases influence the initial manifestations. Although individual tumor cell types are associated with characteristic features, no constellation of findings is pathognomonic for a specific histologic variant. Because successful treatment of pulmonary carcinoma depends on early detection, awareness of the typical clinical manifestations is important.
Humans↗
Paraneoplastic syndromes associated with lung cancer.
Paraneoplastic phenomena associated with primary lung cancer have diverse initial manifestations and epitomize the systemic nature of human malignant disease. The spectrum of clinical features in patients with paraneoplastic syndromes ranges from mild systemic or cutaneous disease to hypercoagulability and severe neuromyopathic disorders. Although the diagnosis is often one of exclusion, an improved understanding of the pathogenesis involved in some of these syndromes has provided another means of recognizing the disorders and perhaps treating the affected patients. Proposed mechanisms of paraneoplastic processes include the aberrant release of humoral mediators such as hormones and hormone-like peptides, cytokines, and antibodies. In this update, we review the potential mechanisms, diagnosis, and treatment of paraneoplastic syndromes associated with lung cancer.
Endocrine System Diseases↗
Staging systems of lung cancer.
The staging of lung cancer involves assessment of the anatomic extent of disease based on the best available data. Such a definition of neoplastic burden facilitates the systematic analysis and meaningful communication of diagnostic, therapeutic, and prognostic information. Clinical staging involves the best estimate of extent of disease before performance of surgical resection or biopsy procedures (or both). Surgical-pathologic staging is based on the histopathologic analysis of resected specimens, including determining the extent of local and regional disease. During the past 50 years, two major classification schemes for staging of lung cancer have evolved--one for non-small-cell lung cancers (the TNM system, indicating the status of primary tumor [T], regional lymph node [N], and metastatic [M] involvement) and the other for small-cell carcinoma of the lung (based on limited versus extensive disease). In this report, we review the evolution of the current staging systems used for primary lung cancer and their prognostic implications.
Carcinoma, Non-Small-Cell Lung↗
Angiosarcoma in the lung.
Angiosarcoma involving the lung is a rare disorder and its clinical features are not well known. We conducted a retrospective analysis of 15 patients seen at our institution from 1950 to 1990 in an attempt to better characterize the spectrum of clinical and radiographic findings of angiosarcoma in the lung. No documented case of primary angiosarcoma of the lung was seen. The diagnosis of metastatic angiosarcoma to the lung was made antemortem in 12 of 15 cases, either by lung biopsy specimen (5 patients), biopsy evidence of metastatic disease elsewhere with abnormal chest radiograph (4 patients), or a compatible clinical picture in a patient with previously documented angiosarcoma arising in an extrapulmonary site (3 patients). The median age at the time of diagnosis was 45 years with the most common presenting symptom being hemoptysis (7 of 15 patients). Other presenting complaints included weight loss (6 of 15), cough (4 of 15), and chest pain (4 of 15) occurring 6 weeks to 1 year prior to diagnosis. Chest radiographs frequently disclosed multiple pulmonary nodules (11 of 15). Primary origins of the angiosarcoma most commonly included the heart and breast. Metastatic sites other than the lung included the pericardium, liver, spleen, kidney, adrenal gland, bone, and brain. The prognosis is generally poor, with our study population surviving an average of 9 months after diagnosis.
Adolescent↗
The role of transcarinal needle aspiration in the staging of bronchogenic carcinoma.
Metastatic spread to subcarinal lymph nodes in patients with bronchogenic carcinoma generally indicates unresectability. Transcarinal needle aspiration of the main carina (TCNA) has been used to obviate the need for more invasive procedures, particularly thoracic surgery. Of 510 transbronchial needle aspirations performed at our institution from 1983 to 1991, 88 (17 percent) were from the main carina in patients with bronchogenic carcinoma. We reviewed these 88 TCNA procedures to assess our experience with TCNA in the staging of lung cancer. The TCNA results were positive in 32 of 88 (36 percent) patients (20 non-small-cell cancers, 12 small-cell lung cancers). Following bronchoscopy, TCNA was the only evidence of unresectability in all 20 patients with non-small-cell lung cancer and was the only mode of diagnosis in 5 of 12 (42 percent) patients with small-cell lung cancer. Thirteen patients with non-small-cell lung cancer and positive TCNA also had positive bronchial secretion cytologic studies. Five of these patients had further subcarinal sampling and in all cases metastatic involvement was confirmed. TCNA was positive in 29 of 67 (43 percent) patients with radiographic evidence of mediastinal adenopathy. Of the remaining 38 patients with radiographic evidence of mediastinal adenopathy and negative TCNA results, 23 patients had further mediastinal sampling with mediastinoscopy or thoracotomy and in all cases mediastinal spread of cancer was established. Nineteen of 58 (33 percent) patients with an endoscopically normal-appearing main carina had a positive TCNA, while 13 of 30 (43 percent) patients with broadening or widening of the main carina had positive TCNA results. There were no complications. We conclude that TCNA is often a safe and useful staging modality in patients with bronchogenic carcinoma.
Biopsy, Needle↗
Analysis of prostatic tumor cultures using fluorescence in-situ hybridization (FISH).
Analysis of ten primary prostatic tumor cultures using fluorescence in-situ hybridization (FISH) with pericentromeric probes for chromosomes 7, 8, 10, 16, 17, and 18 revealed aneusomies in nine of these specimens. Classical cytogenetics by G-banding indicated that only four of those same ten specimens had any (but not consistent) clonal abnormalities. This preliminary study suggests that aneusomy is a common event in early-stage prostatic tumors, and also supports the notion that multiple chromosomes are involved. In combination with routine cytogenetic analysis, FISH is thus likely to be a powerful tool in the evaluation of prostatic cancer.
Chromosome Aberrations↗
RNase E-dependent cleavages in the 5' and 3' regions of the Escherichia coli unc mRNA.
The endonucleolytic processing of the unc mRNA encoding the eight subunits of the Escherichia coli F1F0-ATPase was studied. Northern (RNA) blots of mRNA expressed from a plasmid which contained the 3'-terminal portion of the operon including the uncDC sequences revealed, in addition to the expected 2-kb mRNA, a 0.5-kb RNA species which hybridized to an uncC antisense RNA probe. An uncD antisense RNA probe hybridized to only the 2-kb mRNA, implying that the upstream 1.5-kb fragment is rapidly degraded. The 5' end of the 0.5-kb fragment was determined by primer extension analysis to be 11 bases into the coding region of the uncC gene. In RNase E-deficient strains, the amount of the 0.5-kb product was strongly reduced while the levels of the precursor uncDC transcript remained high. Similar RNase E-dependent processing was found in the chromosomally encoded unc mRNA. As this RNase E-dependent cleavage directly inactivates uncC and appears to leave uncD susceptible to degradation, it seems unlikely to play a role in differential expression of the gene products but may be an important event in unc mRNA degradation. RNase E mutants also showed altered processing of the chromosomally encoded unc mRNA in the uncB region near the 5' end. The expected full-length (7-kb) transcript was recognized when RNA from the RNase E-deficient strain was subjected to Northern blot analysis with uncB- and uncC-specific probes. RNA from strains with functional RNase E lacked the 7-kb transcript but had a 6.2-kb mRNA detectable with the uncC but not the uncB probe. RNase E is therefore implicated in multiple cleavages of the unc mRNA.
Base Sequence↗
Characterization of 10 marker chromosomes in a prostatic cancer cell line by in situ hybridization.
Marker chromosomes contain potentially valuable information about breakpoints in cancer. However, routine banding procedures, by themselves, provide only limited information about the identity of marker chromosomes. In this study, the use of fluorescence in situ hybridization (FISH) with chromosome-specific centromeric probes and whole-chromosome-specific DNA libraries greatly enhanced the identification of 10 marker chromosomes in the primary prostatic cancer cell line PPC-1. Centromeric probes for chromosomes 1, 2, 3, 4, 10, 12, and 17 and whole-chromosome paint libraries for chromosomes 1, 2, 3, 4, 8, and 12, in conjunction with analysis of G-banded metaphases, allowed the major portion(s) of these 10 PPC-1 marker chromosomes to be defined. The results increase the number of identifiable chromosomal breakpoints in this cell line from 9 to 28 sites.
Centromere↗
Cytogenetic evaluation of 20 cultured primary prostatic tumors.
We report the cytogenetic evaluation of 20 cultured cell strains derived from primary prostatic adenocarcinomas obtained from radical prostatectomies. The majority of the strains contained cells with only normal male karyotypes (46,XY), but cytogenetically abnormal clonal populations were found in five strains. Two of those strains contained aberrations involving the Y chromosome, one with a -Y and one with a +Y. Three strains (one of which also had the XYY karyotype) exhibited cells with double-minute chromosomes and four strains contained near tetraploid cells.
Adenocarcinoma↗
Nocturnal nasal ventilation for treatment of patients with hypercapnic respiratory failure.
We reviewed the Mayo Clinic experience with nocturnal nasal ventilation (NNV) and retrospectively assessed the clinical benefits, patient compliance, and complications. NNV had been instituted in 26 patients with daytime hypercapnia and nocturnal hypoventilation due to neuromuscular diseases or chronic obstructive pulmonary disease. After initiation of NNV, 21 of 26 patients continued to use this treatment regularly (81% compliance rate) and considered their life-style improved. In this subset of patients, the arterial partial pressure of carbon dioxide during unassisted breathing decreased from 64 +/- 13 to 51 +/- 7 mm Hg, and the arterial partial pressure of oxygen increased from 58 +/- 12 to 68 +/- 8 mm Hg. No significant change was noted in the forced vital capacity or maximal respiratory pressures. Four of the five patients in whom NNV had been discontinued cited discomfort related to the mask or severity and poor prognosis of the underlying illness as reasons for cessation of treatment. We conclude that NNV is well tolerated by most patients and may improve alveolar ventilation and arterial oxygenation in patients with chronic respiratory failure.
Adolescent↗
Frequency and pattern of karyotypic abnormalities in human prostate cancer.
The cytogenetic evaluation of 30 cultured primary prostatic cancer specimens obtained during radical prostatectomies of patients with relatively early stage disease is reported. The majority of specimens examined showed a normal male karyotype, 46,XY. Nine samples contained clonally abnormal populations including five specimens which were hyperdiploid (modal range, 65-92 chromosomes), one specimen containing double minute chromosomes, and three containing structural aberrations. Loss of the Y chromosome and a partial trisomy for chromosome 4 was observed in a sample from one patient. Another sample showed a translocation between the long arms of chromosomes 5 and 7. The only tumor obtained from a previously irradiated patient contained no normal cells, a modal chromosome number of 45, loss of chromosomes 2 and Y, and multiple structural rearrangements. The appearance of any clonal cytogenetic abnormality correlated in general with a poorly differentiated state of cancer. A survey of all available previous cytogenetic data on human prostate adenocarcinoma indicated that the loss of chromosomes 1, 2, 5, and Y, the gain of chromosomes 7, 14, 20, and 22, and rearrangements involving chromosome arms 2p, 7q, and 10q are the most common changes observed. This suggests that, although the assignment of a single chromosomal aberration as a marker for early stage prostatic cancer is unlikely, several consistent "hotspots" might be of significance in the etiology of this disease.
Chromosome Aberrations↗
The Escherichia coli unc transcription terminator enhances expression of uncC, encoding the epsilon subunit of F1-ATPase, from plasmids by stabilizing the transcript.
The effect of the unc transcription terminator on expression of uncC, encoding the epsilon subunit of Escherichia coli F1-ATPase, from plasmids was studied. The cloned sequence in pTK1 included the uncC ribosome binding site, the uncC structural gene, and the unc transcription terminator. The cloned region in pSD37 was similar, but lacked the unc transcription terminator. Transformants carrying pTK1 produced the epsilon subunit of F1-ATPase, encoded by uncC, in 10-fold greater abundance than transformants carrying pSD37. Northern blots revealed similar differences in the steady-state uncC mRNA levels. The half-life of the message transcribed from pTK1 was 90-100 seconds, while that from pSD37 was 25-30 seconds. These studies indicate the importance of message stabilization through features at the 3' end of the transcript in ensuring adequate production of epsilon. We have exploited this stabilization to develop a simple, efficient, and gentle method of purifying the overproduced epsilon subunit.
Blotting, Northern↗
Role of transesophageal echocardiography in the diagnosis of papillary muscle rupture secondary to myocardial infarction.
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Aged↗