The endogenous organic acid metabolic acidoses that occur commonly in adults include lactic acidosis; ketoacidosis; acidosis that results from the ingestion of toxic substances such as methanol, ethylene glycol, or paraldehyde; and a component of the acidosis of kidney failure. Another rare but underdiagnosed cause of severe, high anion gap metabolic acidosis in adults is that due to accumulation of 5-oxoproline (pyroglutamic acid). Reported are four patients with this syndrome, and reviewed are 18 adult patients who were reported previously in the literature. Twenty-one patients had major exposure to acetaminophen (one only acute exposure). Eighteen (82%) of the 22 patients were women. Most of the patients were malnourished as a result of multiple medical comorbidities, and most had some degree of kidney dysfunction or overt failure. The chronic ingestion of acetaminophen, especially by malnourished women, may generate high anion gap metabolic acidosis. This undoubtedly is an underdiagnosed condition because measurements of serum and/or urinary 5-oxoproline levels are not readily available.
This article describes the care processes for a 64-year-old man with newly diagnosed advanced non-small-cell lung cancer who was enrolled in a first-line clinical trial of a new immunotherapy regimen. The case highlights the concept of multiteam systems in cancer clinical research and clinical care. Because clinical research represents a highly dynamic entity-with studies frequently opening, closing, and undergoing modifications-concerted efforts of multiple teams are needed to respond to these changes while continuing to provide consistent, high-level care and timely, accurate clinical data. The case illustrates typical challenges of multiteam care processes. Compared with clinical tasks that are routinely performed by single teams, multiple-team care greatly increases the demands for communication, collaboration, cohesion, and coordination among team members. As the case illustrates, the described research team and clinical team are separated, resulting in suboptimal function. Individual team members interact predominantly with members of their own team. A considerable number of team members lack regular interaction with anyone outside their team. Accompanying this separation, the teams enact rivalries that impede collaboration. The teams have misaligned goals and competing priorities that create competition. Collective identity and cohesion across the two teams are low. Research team and clinical team members have limited knowledge of the roles and work of individuals outside their team. Recommendations to increase trust and collaboration are provided. Clinical providers and researchers may incorporate these themes into development and evaluation of multiteam systems, multidisciplinary teams, and cross-functional teams within their own institutions.
Alterations of BRCA2 result in increased susceptibility to breast cancer in both men and women (relative lifetime risks of 0.06 and 0.8 respectively). BRCA2 maps to 13q12-q13 and encodes a transcript of 10 157 bp. Other cancers that have been described in BRCA2 mutation carriers include those of the larynx. Human chromosome 13q has been shown previously by LOH studies to harbor several tumor suppressor genes for head and neck squamous cell carcinoma (HNSCCs). We therefore examined the role of BRCA2 in the development of these cancers. Only 6/22 (27%) of the laryngeal cancers we examined demonstrated LOH of the BRCA2-containing region. These and 10 other HNSCCs of dierent origins that were demonstrated by LOH studies to have lost the region of chromosome 13 containing BRCA2 were examined for alterations in this gene. SSCP analysis failed to reveal any alterations leading us to conclude that BRCA2 alterations are not frequently involved in the pathogenesis of HNSCCs and that the observed LOH of chromosome 13 loci is due to other, as yet, unidenti®ed tumor suppressor gene(s). Interestingly tumors with LOH in this region (proximal to D13S118) were far more likely to be derived from women than men. This is unusual since HNSCCs are usually fourfold more common in men than in women.
CASE PRESENTATION HASKELL KIRKPATRICK, MD: A 50-year-old, previously healthy white man with right ear pain and hearing loss, right facial swelling, right hemisphere headaches, slurred speech, and right-sided facial paralysis was transferred to Baylor University Medical Center (BUMC) from one of its affiliated hospitals. The patient was in his usual state of health until 2 weeks prior to the first hospital admission. The patient claimed that during a camping trip, an insect thought to be a centipede crawled into his right ear. He spent approximately 1 hour removing the insect from his ear canal. Afterward, he began to experience increasing pain and swelling. The next day he was seen by his primary care physician, who prescribed an unknown antibiotic. The patient noted no improvement in symptoms and was evaluated 2 days later by an otolaryngologist who "drained his ear canal" and changed his
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