Use of a sensitive enzyme immunoassay for human thyrotropin in the diagnosis of hyperthyroidism

A sensitive, simultaneous sandwich enzyme immunoassay for TSH was evaluated especially for its ability to distinguish hyperthyroid patients from the euthyroid population. A total of 140 patient samples was analzyed by this assay as well as with a two-step sandwich radioimmunoassay. The diagnostic sensitivity of the thyrotropin assay was 92.5% and the specificity was 88%. False negatives by thyrotropin assay included two patients with Graves' disease who were being treated with propranolol at the time of testing and one patient who was considered hyperthyroid while receiving synthroid. Twelve patients with elevated free thyroxine index levels were considered euthyroid and 50% of these had thyrotropin values that were undetectable; most were elderly patients with nonthyroidal illnesses. Although the thyrotropin enzyme immunoassay had good sensitivity and precision for the detection of hyperthyroidism, our data suggest the limitation of a single thyrotropin determination in establishing the euthyroid state, especially in elderly patients with associated nonthyroidal illnesses and hyperthyroxinemia.     

ACR appropriateness criteria(®) ductal carcinoma in situ

Abstract: Ductal carcinoma in situ (DCIS) describes a wide spectrum of non‐invasive tumors which carry a significant risk of invasive relapse, thus prevention of local recurrence is vital. For appropriate patients with limited disease, management with breast conserving surgery (BCS) followed by whole‐breast radiation (RT) is supported by multiple Phase III studies, but mastectomy may be appropriate in selected patients. Omission of RT may also be reasonable in some patients, though which criteria are to be utilized remain unclear, and the existing data are contradictory with limited follow‐up. Various RT techniques such as boost to the tumor bed, partial breast radiation or hypofractionated, whole‐breast RT are increasingly utilized but the data to support their use specifically in DCIS is limited. Tamoxifen also increases local control for ER + DCIS, adding to the complexity of the local treatment management. This article reviews the existing scientific evidence, the controversies surrounding local management, and clinical guidelines for DCIS based on the group consensus by the ACR Breast Expert Panel. The American College of Radiology Appropriateness Criteria are evidence‐based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer‐reviewed journals and the application of a well established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.     

Upper cervical myelopathy due to arachnoiditis and spinal cord tethering from adjacent C-2 osteomyelitis. Case report and review of the literature

Myelopathy caused by a spinal cord infection is typically related to an adjacent compressive lesion such as an epidural abscess. The authors report a case of progressive high cervical myelopathy from spinal cord tethering caused by arachnoiditis related to an adjacent C-2 osteomyelitis. This 70-year-old woman initially presented with a methicillin-sensitive Staphylococcus aureus osteomyelitis involving the C-2 odontoid process. She was treated with appropriate antibiotic therapy but, over the course of 4 weeks, she developed progressive quadriparesis. A magnetic resonance image revealed near-complete resolution of the C-2 osteomyelitis, but new ventral tethering of the cord was observed at the level of the odontoid tip. She subsequently underwent open surgical decompression and cord detethering. Postoperatively she experienced improvement in her symptoms and deficits, which continued to improve 1 year after her surgery. To the authors' knowledge, this is the first reported case of progressive upper cervical myelopathy due to arachnoiditis and cord tethering from an adjacent methicillin-sensitive S. aureus C-2 osteomyelitis.     

Interferon‐Induced Protein with Tetratricopeptide Repeats 1 (IFIT1) as a Prognostic Marker for Local Control in T1‐2 N0 Breast Cancer Treated with Breast‐Conserving Surgery and Radiation Therapy (BCS + RT)

Interferon‐induced protein with tetratricopeptide repeats 1 (IFIT1) expression, involved in the regulation of translation, has been implicated to mediate resistance to chemotherapy and radiation in cancer cells in vitro. The purpose of this study was to evaluate the prognostic significance of IFIT1 protein expression in patients with breast cancer treated with Breast‐Conserving Surgery and Radiation Therapy (BCS + RT). A tissue microarray was constructed with specimens from 282 women with node‐negative, early‐stage (I/II) breast cancer who were treated with BCS + RT. Immunohistochemistry was used to stain for the IFIT1 protein. Cytoplasmic IFIT1 protein expression levels were correlated with clinicopathologic factors, local relapse‐free survival (LRFS), disease‐free survival (DFS), and overall survival (OS). IFIT1 positivity was found in 123 (49%) of cases. The median follow‐up time was 7.3 years. Eighty percent of the patients had T1 disease, 88% were human epidermal growth factor receptor 2 (HER2) negative, and 20% had triple‐negative breast cancer (TNBC). IFIT1 positivity was associated with estrogen receptor negative status (p = 0.002), progesterone receptor negative status (p = 0.02), TNBC (p = 0.01), and HER2‐positive status (p = 0.006). In univariate and multivariate analysis, IFIT1 positivity was associated with improved LRFS (p = 0.055 and p = 0.04, respectively). Using a log‐rank test, IFIT1 positivity was found to be associated with improved LRFS (94% versus 85%, p = 0.046) but not DFS or OS at 10 years. On subset analysis of the TNBC patients, IFIT1 positivity was found to correlate with improved LRFS (100% versus 53%, p = 0.004) and DFS in (87% versus 49%, p = 0.048) at 10 years. Elevated IFIT1 protein expression is associated with improved LRFS. In addition, our data suggest that IFIT1 expression may help risk stratify patients with TNBC who may benefit from more aggressive therapy. As there is limited data on IFIT1 in breast cancer, additional work is needed to ascertain its significance.     

Newer concepts of cancer of the colon and rectum: Clinical evaluation of a radioimmunoassay for CEA

Conclusions Using basically the same reagents and methodology, we have tried to duplicate the optimistic results of Goldet al. Of 578 samples submitted, 393 met the criteria for the study; results for these 393 are presented. Our results indicate that CEA can be detected not only in a smaller proportion of gastrointestinal malignancies than that found by Gold and associates, but also in a similar proportion of inflammatory bowel diseases. Furthermore, we found a significant number of positive in nongastrointestinal malignancies, as well as chronic inflammatory diseases and collagenoses. Therefore, we feel that the assay, in its present form, has limited value as a diagnostic tool in the detection of gastrointestinal malignancies. Better purification procedures, less sensitive methods of detection, or an entirely new approach may produce results of more clinical value than those we have obtained. Symposium presented at the meeting of the American Proctologic Society Las Vegas, Nevada, May 10 to 13, 1971. Presented in part at The Southern Medical Association Meeting, Dallas, Texas, November 16, 1970. Supported in part by grants from the American Cancer Society, Ohio Division, The Randall Foundation, and a donation from Mr. F. Ball.     

Putative roles of a proline–glutamic acid-rich protein (PE3) in intracellular survival and as a candidate for subunit vaccine against Mycobacterium tuberculosis

The proline–glutamic acid (PE) protein family of Mycobacterium tuberculosis (Mtb) plays diverse roles in the pathogenesis and modulation of host immune responses. The uniqueness of conserved regions of PE proteins may be useful to test and validate their corresponding functions. Hence, the present study has been undertaken to demonstrate the role of PE3 (Rv0159c) for persistence, host immune response and immunoprophylaxis. We have expressed Mtb-specific PE3 gene in M. smegmatis (MS) and used the strain to infect J774A.1 macrophage cells and BALB/c mice. It was observed that during the infection, the MS expressing PE3 showed higher bacterial load when compared to infection with wild-type MS. In hypoxic condition, the expression level of PE3 gene was induced in Mtb, which further showed its relevance in the cell survival during hypoxia-induced persistence. The expression level of PE3 in Mtb was markedly induced during chronic stage of murine infection, which reiterated its importance in mycobacterial persistence in the host. The immunization of mice with recombinant PE3 protein stimulated the secretion of TNF, IL-6 and IL-2 cytokines and generated strong protective immunity against challenge with live mycobacteria, which was evidenced by decreased viable bacilli in the lungs, histopathological changes and increased survival of PE3 immunized mice. Conclusively, the results indicated that PE3 plays significant roles in mycobacterial persistence during infection, modulate host immune response and hence could be a prospective candidate for the development of subunit vaccine against tuberculosis.     

A prolonged observational study of tracheal tube displacements: Benchmarking an incidence <0.5-1% in a medical-surgical adult intensive care unit

Background and Aims:

Tracheal tubes are commonly used in intensive care unit (ICU) and lead to complications like displacements. The primary aim of the study was to evaluate if the rate of tracheal tube displacement benchmarked at <1% per patient and <0.5% per tracheal tube day, could be sustained over a prolonged period. The secondary aim was to document the patterns of all forms airway accident and to evaluate their consequences.

Subjects and Methods:

This was a prospective observational study of Intubated and ventilated patients in a General Medical-Surgical Adult ICU. The incidence of accidental extubation, self extubation, partial displacement and blockages of tracheal tubes were recorded.

Results:

The overall tracheal tube displacement rate was 61/10,112 (0.6%) per patient and 61/28,464 (0.22%) per tracheal tube day. There were 30 additional incidents of blockage, kinking or biting of the tracheal tube. Physiological consequences-69 were mild, 10 moderate, 12 major and one death. Of the 91 accidents, 30 were partly and 30 were completely preventable. 76 incidents involved an endotracheal tube (54 displaced, 12 blocked and 10 bitten-kinked) and 15 a tracheostomy tube (seven displaced and eight blocked). Accidents were more common in medical than surgical patients (medical = 48, cardiac surgical = 17 and other surgical/trauma = 26).

Conclusion:

Tracheal tube displacement rate in a mixed medical-surgical adult ICU was maintained below the pre-set benchmark of <1% per patient and <0.5% per intubated day over nearly a decade.