A targeted parathyroidectomy using guide wire technique in a pregnant patient with primary hyperparathyroidism.

Primary hyperparathyroidism may cause fetal demise in pregnant patients if prompt diagnosis and treatment is not initiated. The paper describes a novel guide wire technique for a targeted parathyroidectomy, which may reduce the risk to mother and fetus and be useful in other related circumstances.

NF-kappa B-mediated chemoresistance in breast cancer cells.

BACKGROUND: Nuclear factor-kappa B (NF-kappa B) is a known survival pathway, and it may explain differential sensitivity to tumor necrosis factor-alpha (TNF-alpha) and chemotherapeutic-induced apoptosis in apoptotically sensitive (APO+) and apoptotically resistant (APO-) Michigan Cancer Foundation-7 breast cancer cells. METHODS: Crystal violet viability and luciferase reporter gene assays were used to determine the inhibitory concentration of viability at 50% (IC(50)) and the inhibitory concentration of activity at 50% (EC(50)) values in APO- and APO+ cells with the selective NF-kappa B inhibitor, BAY 11-7082 (BAY). The apoptotic reporter assay was used to determine the effects of the transfection of the inhibitory kappa B-dominant negative (I kappa B-DN) construct in conjunction with TNF, paclitaxel, or doxorubicin treatments in these cells. RESULTS: The concentrations at which 50% of cell viability is inhibited (IC(50)) and at which 50% of NF-kappa B activity is inhibited (EC(50)) for BAY in APO- and APO+ cells were 95.24 micromol/L and 1.53 micromol/L, respectively, and 7.62 micromol/L and 2.64 micromol/L, respectively. The IC(50) and the EC(50) values were equivalent for the APO+ cells (P =.665), but not for the APO- cells (P =.025). I kappa B-DN--transfection alone, or with TNF, doxorubicin, or paclitaxel treatments resulted in cell death of both APO- and APO+ cells as compared with vector-control; however, greater cytotoxicity was seen in the APO+ cells. Direct comparison of the APO+ cells versus the APO- cells revealed that these differences were significant (P =.05). CONCLUSIONS: Pharmacologic or molecular inhibition of the NF-kappa B pathway blocked cell survival in MCF-7 APO+ cells, while only molecular inhibition induced cytotoxicity in the APO- cells. Selective manipulation of the NF-kappa B pathway in combination with standard chemotherapeutic agents may lead to an increased potency and efficacy of these agents.

Esophageal carcinosarcoma.

Carcinosarcoma is an uncommon malignancy of the esophagus that presents as a bulky intraluminal polypoid lesion of the esophagus. Histologically, both carcinomatous and sarcomatous components are seen. Because of accelerated intraluminal growth, esophageal carcinosarcoma often presents relatively early. This report describes a 64-year-old man with carcinosarcoma who was successfully treated with an esophagectomy. As in typical squamous cell carcinoma, early detection and treatment by surgical resection are needed to produce significant long-term survival.

Glutamine is essential for nitric oxide synthesis by murine macrophages.

BACKGROUND: Recent studies suggest an interaction between l-arginine (Arg) and l-glutamine (Gln) in the control of nitric oxide (NO) synthesis. Endotoxemia enhances Gln demand and NO production. This study was initiated to investigate the effects of altered Gln availability on the capacity of macrophages to produce NO and the interaction of Gln with l-citrulline (Cit) and Arg in the regulation of endotoxin-stimulated NO synthesis. METHODS: Cultures of RAW 264.7 macrophages in MEM containing Gln (0 to 100 mM) or Arg (0 or 0.6 mM) and supplemented or not with Cit (0.31 to 10 mM) were exposed to Escherichia coli lipopolysaccharide (LPS) at 0.001 and 1 microg/ml. After 24-h incubation, supernatants were evaluated for nitrite concentrations by Greiss reaction as a measure of NO synthesis. RESULTS: LPS stimulated nitrite synthesis in a dose-dependent fashion. Macrophages cultured in Gln-free medium containing Arg (0.6 mM) did not produce NO when stimulated with LPS. In contrast, in the presence of Arg and 0.001 microg/ml LPS, adding as little as 0.31 mM Gln resulted in a 23-fold increase in NO production (from 0.13 +/- 0. 02 to 2.92 +/- 0.06 nmol/ml) (P < 0.0001). Furthermore, a dose-dependent increase in LPS-stimulated nitrite release was observed with increasing amounts of Gln to as much as 1 mM. LPS-stimulated macrophages cultured in Arg-free medium containing Gln (0.31-10 mM) did not produce significant amounts of nitrite. However, in the absence of Arg, increasing extracellular Gln levels to 100 mM in the culture medium resulted in nitrite synthesis (2.39 +/- 0.11 nmol/ml). Detectable levels of nitrite (2.84 +/- 0.21 nmol/ml) were also documented when stimulated macrophages were incubated in culture medium lacking Arg but containing Cit (0.31 mM) and Gln (2 mM). Increasing Cit levels (0.63 to 10 mM) significantly augmented nitrite release (P < 0.05). Once again, no detectable levels of nitrite were observed when macrophages were cultured in Gln-free medium, even when Arg and Cit were present. CONCLUSION: These results suggest that Gln is an essential amino acid for NO synthesis by macrophages and raise the strong possibility that Gln acts with nitric oxide synthase to catalyze the conversion of Arg to NO. The consumption of Gln during sepsis may represent NO production.

Parathyroid preservation during thyroid surgery.

PURPOSE: Even though thyroid surgery is generally quite safe, permanent hypoparathyroidism is a very distressing complication. The incidence of hypoparathyroidism is directly proportional to the extent of thyroidectomy, and inversely proportional to the experience of the surgeon. It is also related to the extent of invasion of thyroid cancer and of the degree of dissection in the tracheo-esophageal groove. The incidence reported in the literature varies between 1% to 29%. Total thyroidectomy results in a higher incidence of hypoparathyroidism. MATERIALS AND METHODS: This report describes experiences with 600 thyroidectomies over a period of 11 years. The major indications for surgery included suspicion or proof of malignancy, compression symptoms, and substernal goiters. Twenty-six patients underwent surgery for Graves' disease. There were 221 men and 379 women, ranging in age from 16 to 89 years; 88% of the patients had benign disease, whereas 12% of the patients had malignant pathology. The surgical procedures included 62 total thyroidecotmies, 188 subtotal thyroidectomies, and lobectomy and isthmectomy in 350 patients. RESULTS: Meticulous tracheo-esophageal groove dissection, identification of parathyroids and their preservation, including the blood supply, was routine in each case. Even in patients undergoing unilateral lobectomy, every effort was made to preserve the parathyroids. If any of the parathyroids or its blood supply was injured, it was autotransplanted in the sternomastoid muscle. Only two patients developed temporary hypoparathyroidism. CONCLUSION: Parathyroid autotransplantation is performed whenever one or more of the parathyroids are damaged. Parathyroid preservation during thyroid surgery is crucial in the overall management of thyroid diseases.

Histopathologic changes in human small intestine during storage in Viaspan organ preservation solution.

OBJECTIVE: To evaluate the histopathologic changes that occur in human small intestine or time when preserved in Viaspan organ preservation solution. DESIGN: Short segments of human small intestine were placed in standard organ preservation solution (Viaspan) and stored in conditions that mimic the clinical situation associated with clinical organ procurement, preservation, and transplantation. The intestinal segments were removed at sequential time points and placed in 10% formalin. Specimens underwent histopathologic examination to determine time-related changes. SPECIMENS: Short intestinal segments were obtained from seven multiorgan cadaver donors. Specimens were obtained in a way that exactly mimicked small intestinal organ retrieval. RESULTS: Small intestinal histology remained normal for the first 6 hours. After 6 hours, vacuolar separation began to occur between the epithelium and the basement membrane in the upper half of the villi. After 9 hours of cold preservation, epithelial detachment extended deep into the crypts with occasional shedding of cells and villi. CONCLUSIONS: Currently used small intestinal preservation using Viaspan results in considerable histopathologic changes in human jejunum after 9 hours of cold storage. The histopathologic pattern appears normal for the first 6 hours and suggests that preservation times should be limited to this time period when possible.

Effects of luminal nutrients and small bowel transplants on congenital indirect hyperbilirubinemia.

The Gunn rat is an excellent model of Crigler-Najjar syndrome, type 1. In previous studies we demonstrated that heterotopic 15-20-cm jejunal transplants from Wistar rats lowered serum bilirubin levels by 40%, and the reduction was transient (6 weeks). In contrast, orthotopic transplants decreased bilirubin levels by 60% and the effect persisted throughout the 8-week study. This study was initiated to identify the luminal substance(s) which are responsible for the persistent bilirubin-lowering effect of jejunal transplants. Thirty-one Wistar to Gunn 15-20-cm jejunal transplants were randomized to receive daily Thiry-Vella graft irrigation with 5 ml of normal saline (n = 8); bile salts (cholate + deoxycholate, 40 mg/ml, n = 5; fats (Microlipid, 20 mg/ml, n = 5); proteins (Casec caseinate, 40 mg/ml, n = 5); and sugars (Moducal + Polycose, 40 mg/ml, n = 8). Bilirubin levels were measured spectrophotometrically at weekly intervals. At 4 and 8 weeks, enzyme-induced bilirubin conjugation activity was measured using added known amounts of added bilirubin. Irrigation of the transplants with saline, protein, and sugar resulted in moderate (40%) lowering of serum total and indirect bilirubin levels. Fat was significantly more effective, lowering mean total bilirubin levels from 9.6 +/- 0.4 to 1.6 +/- 0.2 mg/dl at 6 weeks. After this time, bilirubin levels increased slightly. Bile salts were slightly less effective, lowering bilirubin levels at 6 weeks by only 75%. However, this effect persisted and at 8 weeks levels averaged 2.4 +/- 0.2 mg/dl. Conjugating enzyme activity in the transplants increased from 1.4 +/- 0.3 to 2.5 +/- 0.5 mg bilirubin conjugated/mg tissue/hr. Luminal fats and bile salts appear to augment enzyme-induced bilirubin conjugation in heterotopic jejunal transplant recipients.

The use of jejunal transplants to treat a genetic enzyme deficiency.

INTRODUCTION: The Gunn rat is an excellent animal model of Crigler-Najjar syndrome, type 1. The liver and small intestine synthesize no functional bilirubin uridine diphosphoglucuronosyl transferase and, consequently, the animals cannot conjugate bilirubin. In prior studies, the authors have shown that 15- to 20-cm jejunal transplants from normal Wistar rats lowered but did not normalize serum bilirubin levels. Phenobarbital has been used to increase enzyme conjugation of bilirubin. HYPOTHESIS: Phenobarbital treatment of Gunn recipients of jejunal transplants from Wistar rats normalizes serum bilirubin levels. METHODS: Forty-three Gunn recipients of jejunal transplants from Wistar rats were divided into four groups: 1) heterotopically placed grafts (Thiry-Vella loops), saline-treated, n = 14; 2) heterotopically placed grafts, phenobarbital-treated (80 mg/kg/day), n = 17; 3) orthotopically placed (in intestinal continuity) grafts, saline-treated, n = 5; and 4) orthotopically placed grafts, phenobarbital-treated, n = 7. Serum was collected before operation and weekly for 8 weeks for measurement of serum total, indirect, and direct bilirubin levels. Animals received cyclosporine, 5 micrograms/kg, daily intramuscularly. RESULTS: Phenobarbital significantly augmented the bilirubin-lowering effect of heterotopic jejunal transplants (group 2). Mean total serum bilirubin fell from 9.14 +/- 0.01 to a nadir of 1.63 +/- 0.11 mg/dL at 6 weeks, after which time, levels began to rise toward baseline (as noted previously). Serum indirect bilirubin levels behaved in a similar fashion. Phenobarbital treatment "normalized" serum bilirubin levels in recipients of orthotopic Wistar jejunal grafts (group 4). Mean total serum bilirubin plummeted from 8.41 +/- 0.20 to 0.76 +/- 0.15 mg/dL at 1 week, and levels remained within the normal range for the entire 8-week study period. Identical changes were observed for serum indirect bilirubin levels. CONCLUSIONS: The combination of phenobarbital treatment and orthotopic small bowel transplantation may be an appropriate therapeutic alternative to liver transplantation in the management of Crigler-Najjar syndrome, type 1.

Islet cell tumors of the pancreas.

Pancreatic endocrine neoplasms are a heterogeneous group of tumors that produce active hormones and result in distinct clinical syndromes. For the most part, they are malignant and require sophisticated diagnostic and localization techniques in order to identify their presence. Delays in diagnosis are the rule rather than the exception. Improvements in the diagnosis of gastrinomas and insulinomas appear to result in an increase in resectability rates. The widespread availability of intraoperative ultrasonography, as well as improved knowledge of the location of these tumors, has also had an impact on improved cure rates. With heightened awareness of these syndromes, increasing numbers of patients can be identified and more effective treatments developed for the refractory and recurrent tumors.

Lymphokine mRNA expression by transplantable murine B lymphocytic malignancies. Tumor-derived IL-10 as a possible mechanism for modulating the anti-tumor response.

In vitro and in vivo expressions of cytokine mRNAs by four transplantable murine B lymphocytic malignancies designated A20, MOPC 315, 2PK-3, and RAW 8.1 were determined using sensitive reverse-transcribed (RT)-PCR. Despite significant differences in both the stage of B cell differentiation represented by each cell line and the method used to induce the original B lymphocytic tumors, IL-6 and IL-10 mRNAs were detected in each of the cultured cell lines. Whereas IL-2, IL-4, IL-5, and IL-12 mRNAs were not detected in cultured cells, expression of cytokine mRNAs in solid tumor tissue was quite different. RT-PCR of poly(A)+ RNA isolated from each of the four solid tumors demonstrated the presence of IL-4, IL-5, IL-6, IL-10, TGF-beta 1, and TNF-alpha mRNAs. There was a noticeable lack of significant IL-2 mRNA expression in any of the solid tumors. Using RT-PCR, it was clear that each of the malignant B lymphocytes expressed IL-6, IL-10, TGF-beta 1, and TNF-alpha, with limited expression of IL-4 and IL-5. To explore the mechanisms that might contribute to the lack of IL-2 mRNA in these solid tumors, quantitative competitive (QC)-RT-PCR was used to quantify expression of IL-10 mRNA. MOPC 315 tumor expressed the most IL-10 mRNA (23.2 pg/micrograms of poly(A)+ RNA), whereas 2PK-3, A20, and RAW 8.1 tumors expressed 7.4, 2.6, and 0.6 pg/micrograms of poly(A)+ RNA, respectively. Secretion of IL-10 into culture supernatants or into sera and ascitic fluid of tumor-bearing animals correlated with mRNA expression. This dysregulated IL-10 production in animals with B lymphocytic tumors suggested a mechanism that may account for the lack of IL-2 mRNA expression in solid tumors, and suggested a possible mechanism by which malignant B lymphocytes may limit cell-mediated antitumor responses.

Correction of congenital indirect hyperbilirubinemia by small intestinal transplantation.

INTRODUCTION: Crigler-Najjar syndrome, type I, is a disease characterized by complete absence of hepatic bilirubin glucuronidation. The congenital indirect hyperbilirubinemia is due to an autosomal recessive deficiency of the enzyme, uridine diphosphate glucuronosyl transferase (UDPGT). The inbred homozygous Gunn rat is also deficient in UDPGT, exhibits unconjugated hyperbilirubinemia, and is an excellent animal model of the Crigler-Najjar syndrome. This study was performed to test the ability of transplanted intestine from normal Wistar rat donors to correct the deficiency in hepatic bilirubin conjugation. MATERIALS AND METHODS: In phase 1, Gunn rats underwent 40-cm heterotopic small-bowel transplants from either Wistar (experimental) or Gunn (control) rats. In phase 2, 15- to 20-cm Wistar-to-Gunn jejunal transplants were placed either heterotopically or orthotopically (in intestinal continuity). All rats were treated with cyclosporin A (CsA), 5 mg/kg per day. Serum bilirubin levels were determined spectrophotometrically at weekly intervals posttransplantation. In phase 2, UDPGT activity was quantitated at 0, 2, 4, and 8 weeks using known quantities of bilirubin as substrate. RESULTS: Total bilirubin levels decreased significantly in the 40-cm heterotopic transplant recipient rats. From the initial values of 7.12 +/- 0.59 mg/dL, levels reached the nadir of 4.23 +/- 0.27 mg/dL. A parallel drop in serum levels of indirect bilirubin was noted (5.04 +/- 0.54 mg/dL to 2.74 +/- 0.23 mg/dL). After 6 weeks, bilirubin levels began to rise toward pretransplant values. In contrast, there was no significant change in bilirubin levels in the control Gunn-to-Gunn rats. Fifteen- to 20-cm heterotopic Wistar-to-Gunn transplants caused a qualitatively similar drop in total and indirect bilirubin levels. Orthotopic (in continuity) Wistar-to-Gunn transplants lowered serum bilirubin levels more rapidly, and the effect was sustained throughout the 8-week study period. By 1 week posttransplantation, total bilirubin levels dropped from 5.11 +/- 0.48 mg/dL to 2.41 +/- 0.16 mg/dL (P < 0.05); data at 8 weeks averaged 1.84 +/- 0.35 mg/dL. Respective data for indirect bilirubin levels were 4.81 +/- 0.45 mg/dL, 2.26 +/- 0.18 mg/dL, and 1.35 +/- 0.39 mg/dL. Wistar rat UDPGT activity in intestine and liver averaged 0.61 +/- 0.05 and 1.88 +/- 0.06 mg bilirubin conjugated/mg tissue per hour, respectively. Enzyme activity in the transplanted intestine persisted throughout the course of the study. CONCLUSION: Transplants of small intestine with known UDPGT activity partially corrected the deficiency in Gunn rats and allayed the hyperbilirubinemia. Since the small intestine is known to contain small but significant amounts of a large number of predominantly hepatic enzymes, bowel transplantation may be an appropriate treatment for this and other similar genetic enzyme deficiencies.

Practical management of post-thyroidectomy hematoma.

Thyroid diseases and surgery for thyroid neoplasms are both very common. Several complications of thyroidectomy are well known. Some of these are quite disturbing, such as recurrent laryngeal nerve injury and permanent hypoparathyroidism. However, postoperative hematoma often in the recovery room may be fatal. Close observation and early intervention are of utmost necessity in the post-thyroidectomy period. In a series of 600 thyroidectomies performed over a period of 11 years, eight patients developed postoperative hematoma. Seven of them underwent re-exploration, while one patient was treated conservatively. Two patients had second re-exploration for hematoma reaccumulation. All patients recovered very well after re-exploration except one elderly patient who required ventilatory support due to poor pulmonary reserve; after a week of ventilatory support and a tracheostomy, she too recovered well. One patient had the hematoma re-explored as late as 24 hours after the operation, while the remainder were re-explored within 4-6 hours after the initial procedure. Because of the extent of edema of the larynx and pharyngeal wall, it is very important that a senior, experienced person perform intubation in these patients. It is also very important to recognize that when the patients lie down flat, they may develop acute airway distress; hence, one must be prepared to intubate them emergently. We recommend close recovery room observation after thyroidectomy and early exploration and evacuation of hematoma in all patients who develop postoperative hematoma. A conservative approach may be considered in selected patients with minimal hematoma and no progression. However, it generally takes a long time for the hematoma to resorb. A better understanding of the complications of thyroidectomy will minimize morbidity and make thyroidectomy a safer procedure and a surgical triumph.

5-HT receptor subtypes involved in luminal serotonin-induced secretion in rat intestine in vivo.

The purpose of this study was to compare the 5-hydroxytryptamine (5-HT) receptor subtypes involved in secretion of water and electrolytes (sodium, potassium, and chloride) induced by luminally administered serotonin in rat jejunum and ileum in vivo. Ketanserin partially inhibited and ICS 205-930 totally inhibited serotonin-evoked secretion. Ketanserin induced mild basal secretion while ICS 205-930 alone reduced basal absorption. There were no differences in the effects of ketanserin or ICS 205-930 on serotonin-induced secretion by rat jejunum versus ileum. Neither N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophanamide nor methysergide altered the secretory effect of serotonin in rat ileum. The substituted benzamides, cisapride, and BRL 24924, and the 5-HT4 agonist, 5-methoxytryptamide, induced water and electrolyte secretion. While BRL 24924 did not alter the subsequent serotonin-induced secretory fluxes, cisapride slightly inhibited the induced secretion. These results suggest that (1) in both segments of the intestine, 5-HT2, 5-HT3, and/or 5-HT4 receptor subtypes are involved in the regulation of intestinal transport of water and electrolytes under basal conditions; (2) serotonin-induced water and electrolyte secretion is mediated by pathways involving 5-HT2, 5-HT3, and 5-HT4 receptor subtypes in both rat jejunum and ileum; (3) 5-HT1 receptors do not seem to be involved in the mediation of intestinal water and electrolyte transport; (4) these effects are similar to those described for systemically administered 5-HT.

Benign lymphoepithelial lesions of the parotid.

Persistent generalized lymphadenopathy has been well described in patients with seropositivity to the human immunodeficiency virus (HIV). Moreover, isolated enlargement of the parotid gland and parotid lymphadenopathy have been noted much more frequently over the past few years. Histologically, these lesions demonstrate follicular hyperplasia, cystic dilatation of the ducts lined by pseudo-stratified squamous epithelium, and lymphocytic infiltrates. They are generally considered to be benign lymphoepithelial lesions of the parotid or hyperplastic periparotid lymph nodes. The relationship of this entity to the AIDS-related complex (ARC) and the subsequent development of AIDS is not clear. Over the past 7 years, we have seen 50 patients with parotid enlargement in whom the diagnosis of benign lymphoepithelial lesion was made. Fine-needle aspiration was performed in 32 patients. Although not conclusively diagnostic, needle aspirates ruled out primary salivary glandular pathology. Most patients gave a history of intravenous drug abuse. HIV tests have been performed on a routine basis only in the last 2 years, and these were positive in the majority of the patients. Thirty-five patients underwent surgical excision. In the initial 20 patients, we routinely performed parotid exploration, identification of the facial nerve, and superficial parotidectomy. In the last 15 patients, we changed our surgical approach to parotid exploration and excision of the mass in the tail of the parotid. The exposure of the posterior belly of the digastric muscle, with identification and removal of the deep jugular node, has become routine. In each case, we found an enlarged lymph node in the deep jugular region, which was not clinically palpable preoperatively. The rate of surgical complications was minimal, and, after resection of the mass, patients improved symptomatically. If the patient shows obvious signs of AIDS, a nonsurgical approach with repeated aspirations should be considered, and treatment with zidovudine offered.

Parathyroid localization prior to primary exploration.

The success of parathyroid surgery is based on accurate localization of normal and abnormal parathyroid glands, knowledge of the pathologic conditions, and meticulous dissection during removal of the abnormal glands. Although parathyroid localization is essential in cases requiring re-exploration, there is considerable controversy regarding the indications for localization studies prior to primary exploration, since the success rate for surgery exceeds 90% to 95%. However, in specific circumstances, including diagnostic problems, technical considerations, and high-risk patient factors, preoperative parathyroid localization assists the operating surgeon even during the primary cervical exploration. The purpose of this paper is to define these specific circumstances and discuss the appropriate studies.

Involvement of eicosanoids and inositol 1,4,5-trisphosphate in serotonin-induced secretion in rat ileum in vivo.

1. The possible involvement of eicosanoids, cyclic adenosine monophosphate (c-AMP), and inositol 1,4,5-trisphosphate (IP3) in serotonin-(5-hydroxytryptamine-) induced secretion in rat ileum in vivo was studied. 2. Serotonin caused a significant increase in mean IP3 levels. Indomethacin reduced serotonin-induced secretion of water by 28%. Thus, IP3 and eicosanoids appear to be intracellular mediators of serotonin-induced secretion in rat ileum. 3. Serotonin, BRL 24924, and cisapride all inhibited theophylline-induced increases in c-AMP concentrations in rat ileal segments. Neither BRL 24924 nor cisapride caused any change in IP3 levels. 4. These data suggest that a 5-HT2 receptor dependent on IP3 and eicosanoids is involved in mediating in serotonin-induced secretion in rat small intestine.