Computed tomographic enterography adds information to clinical management in small bowel Crohn's disease.

BACKGROUND: CT enterography yields striking findings in the bowel wall in Crohn's disease. These images may help to evaluate whether small bowel narrowing results from active disease requiring anti-inflammatory therapy. However, the clinical relevance of these images is unknown. It is also not known if these radiologic findings correlate with objective biomarkers of inflammation. METHODS: In a blinded and independent evaluation, IBD subspecialty gastroenterologists reviewed clinical data, and CT radiologists reviewed CT enterography scans of 67 consecutive patients with Crohn's disease and suspicion of either small bowel inflammation or stricture. Comparisons were made between (1) clinical and radiologic assessments of inflammation and stricture, (2) clinical assessments before and after computed tomographic enterography (CTE) reports were revealed, and (3) radiologic findings and objective biomarkers of inflammation. RESULTS: (1) Individual CTE findings correlated poorly (Spearman's rho < 0.30) with clinical assessment; (2) clinicians did not suspect 16% of radiologic strictures, and more than half the cases of clinically suspected strictures did not have them on CTE; (3) CTE data changed clinicians' perceptions of the likelihood of steroid benefit in 41 of 67 cases; (4) specific CTE findings correlated with CRP, and a distinct set of CTE findings correlated with ESR in the subset of patients who had these biomarkers measured. CONCLUSIONS: CTE seems to add unique information to clinical assessment, both in detecting additional strictures and in changing clinicians' perceptions of the likelihood of steroids benefiting patients. The biomarker correlations suggest that CTE is measuring real biologic phenomena that correlate with inflammation, providing information distinct from that in a standard clinical assessment.

Hyperthyroidism without triiodothyronine excess: an effect of severe non-thyroidal illness.

Serial changes in thyroid hormone levels are described in two patients in whom hyperthyroidism was associated with transient non-thyroidal illness. In a 74-year-old woman with mild hyperthyroidism, two episodes of cholecystitis were associated with subnormal concentrations of serum T3 and increased concentrations of serum rT3; T3 became elevated during recovery, associated with a simultaneous fall in rT3. The TSH response to TRH was undetectable on three occasions. A cholecystectomy was performed after preparation with Lugol's iodine and subsequent tests showed evolution through T3 toxicosis to classical hyperthyroidism. In the second case, symptoms and signs of classical hyperthyroidism were noted during an undiagnosed illness characterized by severe abdominal pain and fever. Six days after the onset of this illness, an elevated level of serum T4 was associated with a normal total T3 concentration and increased concentration of rT3. After resolution of abdominal symptoms, serum T3 was markedly increased, associated with persistent T4 and rT3 excess. These findings indicate that the changes in T3 and reverse T3 described in non-thyroidal illness also occur in hyperthyroid patients, and suggest that the fall in T3 may be of sufficient magnitude to make T3 measurement diagnostically unreliable in the presence of non-thyroidal illness.

Familial euthyroid thyroxine excess: an appropriate response to abnormal thyroxine binding associated with albumin.

Responses of the pituitary-thyroid axis and T4 binding to plasma proteins were studied in three kindreds with familial euthyroid T4 excess, an autosomal dominant condition in which affected subjects have high concentrations of plasma T4 with a high free T4 index, but normal free T4 by equilibrium dialysis. Treatment of affected subjects with exogenous T4 or T3 led to gradual suppression of TSH secretion when the free level of T4 or T3 increased above normal. When total T4 was reduced toward normal by potassium iodide treatment or previous subtotal thyroidectomy, the findings suggested mild hormone deficiency. In affected subjects from all three families, equilibrium dialysis showed increased [125I]T4 binding, with evidence of abnormal high capacity binding when an excess of unlabeled T4 was added. In contrast, T3 binding showed no major abnormality. Serum concentrations of T4-binding globulin, prealbumin, and albumin were normal, but gel electrophoresis and immunoprecipitation of binding proteins indicated that 25-30% of tracer [125I]T4 was albumin bound (normal, 10-12%). Abnormal binding, studied by an adsorption separation system in the presence of T4 excess, was inhibited by increments of barbitone. These findings suggest that T4 excess is an appropriate response to abnormal T4 binding so as to maintain normal free T4. The excess bound T4 is associated with a normal quantity of albumin. The basis for increased T4-albumin binding remains to be determined.

Carcinocythemia (carcinoma cell leukemia). An acute leukemia-like picture due to metastatic carcinoma cells.

Observation of a unique population of cells on a Wright-stained blood smear of a patient with metastatic breast carcinoma prompted a study to determine their origin. The primary carcinoma contained a marker, the presence of "signet cells." These were demonstrated in direct peripheral smears and buffy coat preparation of peripheral blood and confirmed histochemically by showing positive periodic acid-Schiff, alpha-napthol and beta-glucuronidase reactions. "Carcinocythemia" is suggested as a name for this unusual process observed over a six month period. Studies of the patient's immunocompetence, of circulating cell surface immunoglobulins and karyotype analysis were made. Postmortem examination revealed retroperitoneal fibrosis, splenic atrophy and extensive metastatic carcinoma but no evidence of leukemia. The cells will be contrasted to those seen in a second patient who appeared to have acute myelocytic leukemia complicating extensive cancer involving the bone marrow. The observations suggest that a leukemia-like blood picture due to circulating cancer cells may occur during the course of metastatic breast carcinoma.

Warm ischemic injury of the lung.

Canine left lower lobes which were subjected to 3 hours of warm ischemia in an atelectatic condition were compared to lobes which had not been stored. During short-term reimplantation studies, the injured lobes were characterized by marked weight gain, diminution in blood flow, increased vascular resistance, and peak airway pressure. The ventilation/perfusion ratios were high and considerable dead-space ventilation was present. Hypoxic vasoconstriction occurred in both control and stored lobes, and shunt determinations did not vary because of the low blood flows observed. Some or all of these physiological changes may serve to develop a simple screening method to evaluate techniques of pulmonary preservation.

Flow cytofluorimetry in routine diagnostic cytology. A pilot study.

A simple procedure for disrupting cell clumps may aid in the automation of gynecologic cytology by flow cytofluorimetry. Such a procedure, using enzymatic digestion and fluorescent staining, was applied to aliquots of 264 gynecologic exfoliative specimens. Results were compared with cytopathologic diagnoses. A fluorimetric criterion of hypertetraploidy was used to detect abnormality. One quarter of the specimens fulfilled this criterion, including 15 of 17 specimens rated cytologically as premalignant. Two thirds of the falsely abnormal results were attributable to aggregated microorganisms, glandular clumps, and pusbound clumps.

A study of variability in cytologic diagnoses based on pulmonary aspiration specimens.

Reproducibility of cytologic diagnoses of malignancy and accuracy and variability of diagnoses of malignant cell types were assessed in a study of pulmonary aspirates from 100 patients. Original cytologic diagnoses were positive for 60 of the 80 patients who had malignancy (true-positive rate 75%). No false-positive diagnosis was made. Original cytologic diagnoses were negative for 15 of the remaining 20 patients (true-negative rate 75%). In "blindly" reviewing the slides, the pathologist who had made the original diagnoses (Observer A) and another pathologist (Observer B) confirmed the 60 original positive diagnoses. Observer A added four cases, Observer B 11 cases to the positive category. Cell types of original positive cytologic diagnoses and those of subsequent histologic diagnoses agreed for 23 of 33 malignancies (70%). Although two observers increased the proportion of positive cytologic diagnoses, the percentages of agreement with respect to histologic malignant cell types remained similar. For cytologic specimens, intraobserver agreement as to malignant cell types was 83% (50 of 60); interobserver agreement was 80% (48 of 60).

Cytology of 575 young women with prenatal exposure to diethylstilbestrol.

The vaginal and cervical cellular changes encountered in 575 postpubertal females exposed prenatally to diethylstilbestrol (DES) were compared with those of an unexposed population with particular reference to the role of cytology in the detection of vaginal adenosis and cervical ectropion (erosion). Several methods of obtaining specimens were utilized, the most effcacious of which was scraping of the vagina, especially the fornices, and the portio vaginalis of the cervix. With this technic, columnar cells of the mucinous type and metaplastic squamous cells were observed in 34% of the vaginal scrapes and 54% of the scrapes of the cervical portio. A higher incidence was apparent among those patients in whom iodine staining of the vaginal mucosa was abnormal or vaginal adenosis was proven by biopsy. Moderate to severe dysplasia of the squamous cells or atypical glandular cells were found in 1% of the exposed subjects. This study indicates that the presence of mucinous columnar or metaplastic squamous cells in vaginal scrapes is suggestive of vaginal adenosis but that vaginal cytology cannot be considered a uniformly reliable screening technic for detecting the presence of this disorder.

Squamous cell dysplasia and carcinoma in situ of the cervix and vagina after prenatal exposure to diethylstilbestrol.

Squamous cell abnormalities of the vagina and cervix were evaluated in 1424 women exposed to diethylstilbestrol (DES) in utero. The prevalence of dysplasia was 2.1% and the incidence 0.85/100 person-years of followup. The dysplastic epithelial changes were almost always mild in women with no prior history of dysplasia and was slightly more frequent in the cervix than the vagina. Severe dysplasia and carcinoma in situ (CIS) were encountered only in those subjects specifically referred because of those abnormalities. The most common problem in the diagnosis of these squamous cell changes was the misinterpretation of mature and immature metaplastic cells for dysplastic squamous cells. Discordance between biopsy and cytology was common-place in the detection and followup of dysplasia, especially when it was mild. There were no instances in the study where cytology and biopsy samples from the vagina were both abnormal concurrently. Colposcopically directed biopsies did not increase the frequency of confirmation of cytologic findings. These data suggest that both cytology and biopsy of abnormal segments of the vagina and cervix remain an integral part of the examination of the DES-exposed female during long-term follow-up studies.

Cytologic diagnosis of intraventricular hemorrhage in a neonate.

A neonate with autoimmune thrombocytopenia presented with megacephaly and hydrocephalus. The cause remained obscure until hemosiderin-laden macrophages were found in the ventricular cerebrospinal fluid (CSF), indicating prenatal intracranial hemorrhage. The literature on the diagnosis of intraventricular hemorrhage by the cytologic examination of CSF is reviewed and discussed. The cytologic evaluation of CSF may be helpful in cases of central nervous system dysfunction when the cause is obscure.

Quantitative cytocentrifugation in the evaluation of cerebrospinal fluid.

Five hundred sixteen samples of cerebrospinal fluid (CSF) were subjected to cytocentrifugation to determine whether this technique is reliable in quantifying the cells present while simultaneously allowing precise cytologic identification of the types of malignant and atypical cells present. Cell counts obtained by the cytocentrifuge method were comparable to those obtained by the standard hemocytometer method. Because of the larger volume of fluid used in cytocentrifugation, cells (0.2/cu mm) were found in 264 specimens that would have been considered devoid of cells by hemocytometry. Six of these samples contained malignant cells. The Wright's-stained cytocentrifuged specimens also allowed precise identification of hematopoietic cell types. CSF cytocentrifugation offers the advantages of (1) a simple and rapid method of quantifying the number of cells present, (2) use of larger volumes than the hemocytometer method, thereby minimizing the possibility that the specimen will be classified as acellular, and (3) improved morphology of hematopoietic cell types by use of the Wright's stain. We conclude that the cytocentrifugation method is useful in the routine quantification and diagnosis of CSF specimens.

The action and uses of insulin.

Diabetes is a metabolic state consequent upon insulin deficiency, in which catabolism exceeds anabolism. Where anabolism cannot be restored by dietary or oral agents, insulin treatment is necessary.

Principles of management of maturity onset diabetes.

By far the largest group of diabetics coming under treatment are those falling into the category maturity onset. While symptoms of thirst and polyuria, or symptoms or signs of complications may bring cases to attention, many are asymptomatic. The final proof, glycosuria being the presentation, should be sought by glucose tolerance test since it is essential to have confirmation of diagnosis prior to commitment by doctor and patient to life long treatment.