Detection of multiple passively acquired alloantibodies following infusions of IV Rh immune globulin.

BACKGROUND: Passively acquired blood group alloantibodies are detected regularly after infusions of IV Rh immune globulin (RhIG) for the treatment of immune thrombocytopenic purpura (ITP) in D+ patients. STUDY DESIGN AND METHODS: Blood samples from 16 D+ patients with ITP were tested after treatment with IV RhIG for the presence of passively acquired alloantibodies. Similar studies were conducted for three D- patients after injections of IM RhIG for Rh immunoprophyl-axis. Four production lots of IV RhIG and 2 lots of IM RhIG were tested for the presence of alloantibodies. RESULTS: All 16 D+ patients with ITP developed a positive DAT, as well as positive antibody detection test results, after infusions of IV RhIG. All postinfusion plasma samples contained anti-D, as well as one or more additional antibodies, usually anti-C, -E, -G, -V, or -Fy(a). Eluates from patients' RBCs with positive DAT results contained multiple passively acquired alloantibodies. Multiple alloantibodies were detected in samples of different production lots of IV RhIG or IM RhIG. No acute transfusion reactions were observed in five D+ patients with ITP who had been treated with IV RhIG and had been given serologically incompatible D+ RBCs. After injections of IM RhIG, the only passively acquired alloantibody detected was anti-D. CONCLUSION: Plasma samples from D+ patients with ITP treated with IV RhIG regularly contained anti-D and multiple other passively acquired Rh, Duffy, or Kidd system alloantibodies. Postinfusion RBC samples all had positive DAT results with eluates containing anti-D and multiple other Rh, Duffy, or Kidd system antibodies. The consistent detection of multiple passively acquired alloantibodies after IV RhIG, in contrast to the detection of anti-D only after IM RhIG, reflects the immediate effect of the entire (bolus) dose of RhIG by the IV route, the dose for treating ITP that is approximately 10 times the dose for Rh immunoprophylaxis, and the expected serologic incompatibility with recipients' D+ RBCs.

Teamwork in the operating department.

The Gynaecology theatre team of the Leicester Royal Infirmary NHS Trust were runners-up in the 1997 3M/NATN joint award. This article is a report of their work on the concept of teamwork and its benefits to the organisation and delivery of patient care in the operating department.

A comparison of the effect of growth factors on intestinal function and structure in short bowel syndrome.

BACKGROUND/PURPOSE: Epidermal growth factor (EGF) and Insulin like growth factor-1 (IGF-1) increase substrate absorption beyond the normal adaptive response after massive small bowel resection in the rat. However, the mechanism for this response is unknown. This study was designed to evaluate the ultrastructural features of the rat small intestine epithelium after exposure to EGF and IGF-1 and correlate any changes with a possible hypothesis regarding the mechanism for the increased absorption. METHODS: Male Sprague-Dawley rats underwent an 80% small bowel resection and jejunostomy tube placement. Seven days later an osmotic pump placed subcutaneously and containing the test substance was connected to the jejunostomy tube. The rats were assigned to one of three groups: group 1 received normal saline (control, n = 5); group 2 received EGF at 150 microg/kg/d (n = 5); and group 3 received IGF-1 at 20 mg/kg/d (n = 5). After a 14-day infusion, a portion of mid-small bowel was resected for light and electron microscopic evaluation from each of the animals. The following features were compared between the groups: villous length, crypt length, villous-crypt ratio, villi per millimeter mucosa, goblet cell distribution, eosinophilic infiltrates, number and distribution of organelles, length of microvilli, and completeness of microvillous surface. RESULTS: Ultrastructurally, the bowel epithelium was well preserved in all animals. There were no objective ultrastructural differences between the controls and growth factor-exposed animals. The mean villous-crypt ratio, mean number of villi per millimeter of mucosa (cross section), and mean microvillous height were not significantly different among the groups. However, there was a subjective increase in the number of lysosomes in the enterocytes exposed to EGF and IGF-1. CONCLUSIONS: Administration of EGF and IGF-1 after massive small bowel resection does not appear to significantly alter the small intestine epithelial ultrastructure when compared with the control group. The increase in lysosomes in some of the enterocytes of the animals exposed to growth factors may be important because this finding was not seen in any of the control electron photomicrographs. Studies to evaluate enterocyte gene and protein expression are necessary to determine the mechanism of EGF and IGF-1 enhancement of substrate absorption beyond intestinal adaptation.

A prospective study of patients with lung cancer and hyponatremia of malignancy.

This study was undertaken to define the impact of arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) on sodium homeostasis in patients with lung cancer. Patients had their serum and urine electrolytes and osmolality determined before and after a saline infusion of 500 ml. The plasma hormones, AVP, ANP, plasma renin activity (PRA), angiotensin II, and aldosterone were determined by radioimmunoassay every 15 min before, during and after the saline infusion. Fifty patients, 31 with small cell lung cancer and 19 with non-small cell lung cancer participated in this trial. All 11 patients (10 patients with small cell lung cancer and one patient with non-small cell lung cancer) who presented with hyponatremia had inappropriately elevated levels of AVP. Elevated plasma AVP levels were highly correlated with the presence of hyponatremia (p < 0.00001). Initial plasma ANP levels were not associated with hyponatremia (p = 0.73). Urinary sodium concentration increased during the saline infusion proportional to the initial plasma level of ANP (p = 0.0045). AVP appears to be elevated in nearly all patients with hyponatremia of malignancy. ANP plasma levels in patients with lung cancer are associated with the ability to excrete a sodium load but do not appear to downregulate renin, angiotensin II, and aldosterone production.

Ectopic production and processing of atrial natriuretic peptide in a small cell lung carcinoma cell line and tumor from a patient with hyponatremia.

BACKGROUND: Tumors and tumor cell lines from two patients with small cell lung carcinoma (SCLC) (one with and one without hyponatremia) were studied. Ectopic production and prohormone processing of atrial natriuretic peptide (ANP) were investigated to determine if a biologically active peptide was produced in a tumor cell line from a patient with hyponatremia and no evidence of arginine vasopressin (AVP) production. METHODS: Ribonuclease (RNase) protection assays were performed on mRNA isolated from tumors and tumor cell lines established from two SCLC patients, one with and one without hyponatremia. Cellular extracts and conditioned media were studied using reversed-phase high performance liquid chromatography (HPLC) to determine the immunoreactive form of ANP. Tumor cell line sonicates were studied for subcellular localization of enzymatic activity that cleaved pro-ANP peptide substrates. RESULTS: RNase protection assays showed a 200-base pair protected fragment in the mRNA isolated from the tumor and tumor cell line from the patient with hyponatremia (Patient 4). HPLC characterization of the cellular extract and conditioned medium from the tumor and tumor cell line from Patient 4 demonstrated ANP immunoreactivity in the same fraction as ANP- (S99-Y126). The tumor cell line extract that localizes to a subcellular fraction enriched for lysosomes and secretory organelles contains a 60-kilodalton molecular weight protein with enzyme activity that hydrolyzes synthetic pro-ANP substrates and catalyzes the formation of ANP-(S99-Y126). CONCLUSIONS: A tumor cell line from a patient with hyponatremia was able ectopically to produce, process, and secrete ANP in the same immunoreactive form as the biologically active molecule. Preliminary studies show that tumor cell line NCI-H1284 contains an enzyme that can cleave precursors at the same amino acid sequences needed to produce ANP-(S99-Y126) from pro-ANP.

Loose anagen hair syndrome mimicking the uncombable hair syndrome.

A 7-year-old female presented with messy, difficult to manage scalp hair and mild, diffuse alopecia. Hair pull specimens, diagnostic for loose anagen hair syndrome, also showed hair shaft abnormalities described in the uncombable hair syndrome. We suggest that dysmorphic hair shafts observed on our patient account for her clinically unmanageable hair. Pertinent clinical, pathologic, and diagnostic features of both syndromes are reviewed.

Estrogen and progesterone receptors in thyroid lesions.

BACKGROUND: Given the higher incidence and better prognosis of thyroid cancers in women, the possibility arises that these lesions may be influenced by sex hormones. With the development of monoclonal antibodies to the estrogen and progesterone receptor proteins, receptor status can now be determined by immunohistochemical methods that allow direct localization of receptors in tissue. METHODS: Using this technique, we have studied tissues of 11 patients, 2 of them pregnant, with thyroid lesions. Paraffin-embedded tissues were used. Positive controls consisted of known estrogen- and progesterone-positive breast carcinomas. RESULTS: Examination of both the thyroid lesions and adjacent uninvolved thyroid tissue showed no nuclear reactivity with either estrogen or progesterone receptor antibodies. Our study did not confirm the previously reported incidence of estrogen and progesterone receptors in thyroid lesions. CONCLUSIONS: We conclude that contrary to earlier indications, estrogen and progesterone receptor proteins are neither significantly detectable nor pertinent for follow-up or prognosis in the patient with thyroid neoplasia.

Estrogen receptor detection in paraffin sections of adenocarcinoma of the colon, pancreas, and lung.

We performed a retrospective analysis for the presence of estrogen receptors (ERs) in known cases of adenocarcinoma of the colon, pancreas, and lung. Estrogen receptor status was determined by immunohistochemical methods using the ER-ICA (Abbott Laboratories, North Chicago, Ill) antibody on paraffin sections. None of 43 colon and 18 pancreatic adenocarcinomas demonstrated ERs by this method. Three of 42 lung adenocarcinomas exhibited some degree of nuclear staining for ERs. When evaluating an adenocarcinoma of unknown primary site, the ER-ICA antibody can be useful when included in a panel of antibodies. Positive results tend to exclude colonic or pancreatic, but not pulmonary, primary sites.

Calcitonin elevation in small cell lung cancer without ectopic production.

To determine the relative contribution of ectopic calcitonin (CT) production versus nonectopic secretion of CT in patients with small cell lung cancer (SCLC), serum and urine immunoreactive CT (iCT) levels of 86 different subjects were measured by radioimmunoassay (RIA) using two polyclonal antisera (Ab3b and Ab4). The subjects included 49 previously untreated patients with SCLC, 17 smokers, and 20 nonsmokers. Serum and urine iCT values were highest in the patients with SCLC, intermediate in the smokers, and lowest in the nonsmokers (p < 0.0003). Sixteen of the 49 patients with SCLC had tumor cell lines available for determination of CT mRNA expression by RNase protection assay (RPA) and iCT production by RIA. CT mRNA was detected in nine of 16 subjects and iCT in eight of 16. The tumor cell lines of seven patients had undetectable CT by both RPA and RIA, and of these, five had elevated urine or serum iCT values compared with those of nonsmokers, and two had levels above all values in the smoker group. Immunohistochemical staining of formalin-fixed, paraffin-embedded tumor samples detected iCT in two of four tumors from patients whose tumor cell lines had CT mRNA by RPA and iCT by RIA, but in none of six whose tumor cell lines had undetectable CT mRNA. Thus, increased iCT values in some patients with SCLC are likely due to sources other than CT production by tumor cells.

Splenic metastasis in hairy cell leukemia.

BACKGROUND: Splenic metastasis is uncommon and usually occurs in the setting of widespread visceral metastasis. Splenic metastasis as an initial manifestation of disease and sole site of metastasis has not been reported previously. METHODS: The authors describe a patient with hairy cell leukemia (HCL) with the unexpected finding of metastatic adenocarcinoma in the spleen. Direct inspection at the time of laparotomy and subsequent radiographic studies did not show a primary or additional metastatic tumor. Eventually, he manifested evidence of pulmonary and hepatic metastases and died with fungal sepsis. RESULTS: The splenectomy specimen showed HCL and metastatic adenocarcinoma. Immunohistochemical studies showed adenocarcinoma with diffuse cytoplasmic staining for prostate-specific antigen and focally positive results with prostatic acid phosphatase antigen. Postmortem examination 9 months later showed HCL and widespread metastatic adenocarcinoma. No primary tumor was identified, and multiple tissue blocks of the prostate had negative findings for tumor. CONCLUSIONS: The immunohistologic features of the metastatic adenocarcinoma were interpreted as prostatic in origin. The pattern of isolated metastatic disease in the absence of primary tumor appears to represent another possible atypical disease presentation of prostatic cancer. Hairy cell-induced structural and immunologic alterations within the splenic microenvironment may have contributed to this unique clinical presentation.

Xanthomatized atypical T cells in a patient with mycosis fungoides and hyperlipidemia.

BACKGROUND: Lipoprotein-T-cell interactions are being reported with increasing frequency, and there is evidence that lipoproteins play a role in immunoregulation. We describe a patient with mycosis fungoides and hyperlipidemia who developed xanthomatization in one preexisting plaque. The case is unique in that some of the lipidized cells were atypical T cells. In previously reported cases of mycosis fungoides with dystrophic xanthomatosis, the lipid-containing cells have been identified only as histiocytes. OBSERVATIONS: Immunopathologic features, electron microscopy, and lipid stains of the xanthomatized plaque demonstrated that some of the lipid-laden cells were atypical T cells. CONCLUSIONS: In mycosis fungoides, malignant T cells may be intimately involved in processing of tissue lipids. We suggest that low-density lipoprotein receptors on activated T cells facilitated the cytoplasmic lipidization in this case.

Distant metastasis from a carcinoid tumor of the appendix less than one centimeter in size.

The presentation and management of a patient with liver metastasis from a 0.6 cm carcinoid tumor of the appendix is presented. This is the first documented case of distant metastasis from a carcinoid of the appendix less than 1 cm in size. Histopathologic, immunohistochemical, and electron microscopic studies support the appendiceal carcinoid as being the primary neoplasm. Invasion of the mesoappendix was the only finding to suggest potentially aggressive behavior. We reviewed the literature and found 414 previously reported cases that provided complete information regarding tumor size, mesoappendiceal invasion, and presence of metastasis. For the entire group the frequency of metastasis was related to tumor size greater than 2 cm (p less than 0.0001) and invasion of the mesoappendix (p less than 0.0001). After dividing the group based on size, mesoappendiceal invasion was related to metastasis in those tumors less than 2 cm in size (p less than 0.0001) but not in tumors larger than 2 cm (p = 0.1538).

Inverted papilloma of the urinary bladder with granular eosinophilic cells. An unusual neuroendocrine variant.

We report the morphologic, immunohistochemical, and electron microscopic characteristics observed in a case of an inverted papilloma that contained neuroendocrine cells resected from the urinary bladder of a 77-year-old woman. Additionally, we evaluated the incidence of neuroendocrine cells in eight cases of inverted papillomas of the urinary bladder obtained from the files of the Armed Forces Institute of Pathology, Washington, DC. To our knowledge, an in-depth study of neuroendocrine cells in this neoplasm and a comparison of the same with neuroendocrine cells observed in other conditions in the lower genitourinary tract have not been previously published, prompting this report.

The significance of gastrinomas found in peripancreatic lymph nodes.

A patient with Zollinger-Ellison syndrome (ZES) was found to have a solitary, extrapancreatic, extraintestinal gastrinoma in a peripancreatic lymph node. Preoperative studies did not show the location of the tumor. After excision of the gastrinoma the patient's fasting serum gastrin level dropped from preoperative levels of 596 pg/ml to 120 pg/ml (normal, less than 200 pg/ml). Fasting and stimulated gastrin levels have remained within the normal range at 18 months follow-up. This patient had previously undergone antrectomy, so it could not be determined if this tumor represented a primary lymph node gastrinoma or metastasis from an unrecognized tumor that may have been present in the resected stomach or duodenum. The outcome of this case confirms the previous reports that ZES can be controlled after resection of gastrinomas that were contained within abdominal lymph nodes, even if a primary enteropancreatic tumor is not found. Our results also support the use of an aggressive operative search aimed at eradication of the tumor in patients with ZES even if preoperative localization studies fail to identify the site of the gastrinoma.

Cytomegalovirus-infected cells express Leu-M1 antigen. A potential source of diagnostic error.

The authors examined cytomegalovirus (CMV)-infected tissues and Hodgkin's Disease (HD) cases with immunohistochemical assays for Leu-M1 and CMV. The cytologic characteristics were correlated with immunostaining patterns. Cytomegalovirus-infected cells in lymph node, lung, and esophagus sections showed Cowdry type A inclusions, and many had granular cytoplasmic inclusions. All infected cells showed nuclear staining with an anti-CMV antibody. Leu-M1 reacted with CMV-infected cells in cytoplasmic areas, particularly near the nucleus simulating the characteristic staining pattern of Reed-Sternberg (R-S) cells. Cytoplasmic staining intensified as the intranuclear inclusions increased in size. Reed-Sternberg cells showed characteristic Leu-M1 positivity along the cell membrane and golgi zone. At times, Leu-M1 staining of CMV-infected cells was indistinguishable from that of R-S cells. None of the R-S cells reacted with the antibody to CMV. Recognition of the reactivity of Leu-M1 with CMV-infected cells is important in avoiding misdiagnosis of CMV lymphadenitis as HD.

An Examination of the Leaf Quaking Adaptation and Stomatal Distribution in Populus tremuloides Michx.

The leaves of quaking aspen (Populus tremuloides Michx.) have a flattened petiole that allows them to quake (oscillate and roll) under low wind velocities. It was hypothesized that this adaptation might enable the plant to respond to windy conditions that would increase transpirational losses. No effects of wind with or without leaf quaking on stomatal resistance were observed under controlled conditions in the field. If wind and leaf quaking affect stomatal resistance, such effects must be small in comparison to those caused by other factors such as leaf water potential and ambient humidity.Aspen leaves are hypostomatal with stomata evenly distributed over the abaxial surface. This observation casts serious doubt on the hypothesis that quaking is an adaptation to increase bulk air flow through amphistomatal leaves.

Cardiovascular effects of benzquinamide.

The cardiovascular effects of benzquinamide were evaluated in anesthetized dogs. Intravenous benzquinamide, 0.5 to 5 mg/kg, caused tachycardia, elevated blood norepinephrine levels, frequent ventricular arrhythmias, and brief hypotension. Ganglionic blockade by hexamethonium prior to administration of benzquinamide prevented the tachycardia and alterations in norepinephrine levels but prolonged the period of hypotension. In isolated mesenteric arterial preparations benzquinamide interfered with contractile force generated by potassium chloride, norepinephrine, and prostaglandin F2 alpha. It is concluded that benzquinamide directly relaxes vascular smooth muscle thereby producing in vivo reduced peripheral vascular resistance and hypotension, which are compensated for by reflex sympathetic activation.