Diagnosis of benign thyroid lesions: fine-needle aspiration and histopathologic correlation

Fine-needle aspiration is now accepted as the initial procedure for diagnosing a thyroid nodule. General pathologists inevitably will be asked to interpret aspirates as this diagnostic tool continues to be more widely used. This procedure is relatively inexpensive, is safe, and nearly always provides information useful in deciding how to manage the patient. We emphasize the importance of obtaining a representative sample of good quality. This often occurs when the "interventional pathologist" performs the aspirations, but there is no reason that another practitioner cannot become expert. Both histologic and cytologic features are reviewed from normal thyroid tissue, autoimmune thyroiditis, adenomatoid nodules, and follicular neoplasms. We encourage the use of clear, simple, and uniform terminology to facilitate communication.     

Communicating do-not-resuscitate orders with a computer-based system

BACKGROUND: Do-not-resuscitate (DNR) orders for critically ill patients are frequently miscommunicated between attending physicians, house staff, and nurses. A computer-based system was developed to improve the communication of a procedure-specific DNR order form. METHODS: Concordance of understanding of patients' DNR status was measured with the use of unstructured DNR orders (period 1), procedure-specific DNR order forms (period 2), and procedure-specific DNR order forms administered with a computer-based communication system (period 3). The 3 components of the DNR order assessed were (1) the clinical events to which the DNR order applied, (2) whether the DNR order withheld all elements of cardiopulmonary resuscitation, and (3) whether other treatments were to be withheld. RESULTS: For the 147 patients, the computer-based system in period 3 (n = 71) improved concordance for attending physicians and nurses or residents for all 3 of the DNR components compared with period 1 (n = 40) and some of the DNR components compared with period 2 (n = 36). Concordance was "substantial" or "almost perfect" as measured by the K statistic during period 3. The proportion of agreement for the composite of all 3 components of the DNR order increased during each period (P<.001, period 3 vs period 1). Overall agreement between all caregivers for the composite DNR order also improved from period 1 (22.2%) to period 2 (47.8%) and period 3 (61.9%; P<.001 vs period 1). Errors in order entry were detected by physicians because of the computer system and corrected in 9.9% of DNR orders in period 3. Progress note documentation of DNR status did not improve during period 3. The procedures of period 3 were considered acceptable by the physician and nursing staff. CONCLUSION: A computer-based system combined with a procedure-specific DNR order form improves communication of patients' DNR status in a critical care setting.     

Processing of human intestinal prolactase to an intermediate form by furin or by a furin-like proprotein convertase

Human lactase-phlorizin hydrolase (human-LPH) is synthesized as a large precursor (prepro-LPH), then cleaved to a pro-LPH of 220 kDa which is further cut to a "mature-like LPH" of a size close to that of mature LPH, i.e. about 150 kDa (in the processing of rabbit pro-LPH the intermediate has a mass of approximately 180 kDa). By coexpression of human prepro-LPH with furin in COS-7 cells we show that furin generates a mature-like LPH. Radioactive amino acid sequence analysis reveals that furin recognizes the motif R-T-P-R832, a protein convertase consensus, to generate a NH2 terminus located 36 amino acids upstream of the NH2 terminal found in vivo at Ala869. This intermediate is ultimately cleaved to the mature LPH form by other proteases including the pancreatic ones. These data demonstrate that human pro-LPH, like the rabbit enzyme, is processed to the mature enzyme by furin or furin-like enzymes through at least an intermediate form that has, however, an apparent mass close to that of the mature enzyme.     

The incidence of drug-related problems as a cause of hospital admissions in children

OBJECTIVES: To determine the incidence of hospital admissions for drug-related problems (DRPs) among children, and to examine cases for causality, preventability and clinical severity. DESIGN: Prospective assessment involving review of case notes and parent interview to determine if an admission was associated with a DRP. PATIENTS AND SETTING: All patients admitted to a large university-affiliated paediatric hospital in Melbourne, Victoria, for medical reasons (i.e., not surgical, trauma or oncology patients) during 56 consecutive days from 24 June to 19 August 1996 for which a DRP could be identified. Patients whose parents or guardians could not communicate adequately in English were excluded. MAIN OUTCOME MEASURES: The incidence, type, causality, preventability and clinical severity of DRPs associated with admission. RESULTS: Of 1682 eligible patients admitted to the Royal Children's Hospital during the study period, 58 admissions (3.4%) were associated with DRPs. Non-compliance was implicated in 50%. Causality was ranked as "definite" (34.5%), "possible" (56.9%) and "doubtful" (8.6). Two-thirds of admissions associated with DRPs were deemed preventable. Although no patients died from DRPs, four were admitted to the intensive care unit. CONCLUSIONS: The incidence of DRPs as a cause of hospital admission in this study falls within the range of incidences published for the Australian adult population (range, 2.4%-22%). In contrast to findings among Australian adults, a high proportion of admissions for DRPs in this study were associated with non-compliance. The high percentage of preventable admissions indicates that further study is necessary to characterise risk factors within this population and to test prevention strategies.     

Pain threshold values during periodontal probing: assessment of maxillary incisor and molar sites

Probing pain threshold (PPT) assessments were conducted in the facial and oral sulci of maxillary central incisors and first molars of 10 periodontally healthy adults. All subjects were systemically healthy, free of pain, and reported no current medication usage. A computer-linked electronic probe, modified to deliver steadily increasing forces up to 200 grams, was used to collect the data. The system contained a subject operated "off-switch" which, upon activation, signaled the computer to record the subject's PPT. Assessments of each subject's PPTs were conducted on 3 separate occasions at 7-day intervals. Results indicated that the facial sulci of the incisors were the most pain sensitive. They displayed a mean PPT of 50.9 +/- 26.6 grams. The oral sulci of the incisors exhibited a mean PPT of 76.5 +/- 45.2 grams. Facial and oral sulci of the molars evidenced mean PPT values of 102.6 +/- 52.1 grams and 113.5 +/- 51.3 grams, respectively. These data suggest that sulci associated with incisor teeth are nearly twice as pain sensitive as sulci associated with molar teeth. In addition, facial sulci are significantly more pain sensitive than oral sulci. Data did not indicate a visit effect nor a side-of-mouth effect on PPT values.     

Functional correction of renal defects in a mouse model for ARPKD through expression of the cloned wild-type Tg737 cDNA

Autosomal recessive polycystic kidney disease (ARPKD) is characterized by the formation of large collecting tubule and ductular cysts that often result in renal insufficiency within the first decade of life. Understanding the process leading to cyst formation will require the identification and characterization of genes involved in the etiology of this disease. In this regard, we previously described the generation of a mouse model (TgN737Rpw) for ARPKD and the cloning of a candidate gene. Here we show direct involvement of the Tg737 gene in collecting duct cyst formation by expressing the wild-type Tg737 cDNA as a transgene in TgN737Rpw mutants. In contrast to TgN737Rpw mutants, the "rescued" animals survive longer, have normal renal function and normal localization of the EGFr to the basolateral surfaces of collecting duct epithelium.     

Helicobacter pylori does not migrate from the antrum to the corpus in response to omeprazole

BACKGROUND: Omeprazole is known to have an effect on Helicobacter pylori in vivo. One opinion is that H. pylori "migrates" from the antrum to the corpus in response to omeprazole therapy. METHODS: To determine whether H. pylori migrates in response to omeprazole, we assessed the presence of H. pylori in the antrum and corpus in duodenal ulcer patients receiving omeprazole for 4 wk. Culture and histological examination of antral biopsies (Genta stain) were performed before patients received omeprazole, at the end of therapy, and 4-6 wk later. The end points were presence or absence of H. pylori and the number of H. pylori colonies per biopsy. RESULTS: Seventy-two patients had H. pylori in both the antrum and corpus at entry and 4-6 wk after ending therapy. Three general patterns were prevalent at the end of omeprazole therapy: antrum- and corpus-positive (54%), antrum-negative and corpus-positive (24%), both antrum- and corpus-negative (21%), and one patient had antrum-positive with corpus-negative (1%). Evaluation of the number of colonies per biopsy in those who remained H. pylori-positive in both the antrum and corpus throughout showed that the number of H. pylori decreased in both the antrum and corpus during therapy (507 +/- 60 vs. 225 +/- 51, p < 0.01 and 415 +/- 58 vs. 290 +/- 46 0.1) for antrum and corpus, respectively, and tended to return to pre-therapy levels 4-6 wk later. The number of H. pylori in the corpus also decreased in the antrum-negative and corpus-positive group during therapy with omeprazole (433 +/- 87 vs. 185 +/- 61, p < 0.05). In most of the patients studied, the number of H. pylori in the corpus was less posttreatment than it was pretreatment. The decrease in H. pylori load was also reflected in the development of false-negative urea breath tests. CONCLUSIONS: Omeprazole is detrimental to H. pylori in both the antrum and the corpus; migration from the antrum to the corpus in response to omeprazole is a myth.