Bovine parathyroid tissue: a model to compare the biosynthesis and secretion of parathyroid hormone and parathyroid hormone-related peptide.

Bovine parathyroid tissue was evaluated as a model to compare parathyroid hormone-related peptide (PTH-rP) and parathyroid hormone (PTH) secretion. Tissue was incubated in variable calcium levels (n = 5). A parathyroid cell digest was prepared from collagenase-treated glands. PTH-rP and PTH levels were determined by radioimmunoassay. PTH-rP bioactivity was determined by 3H-cAMP production in a UMR 106 cell bioassay. PTH-rP levels in the incubation medium were 2.0 ng/mg protein (0.25 mmol Ca++), 2.2 ng/mg protein (1.25 mmol Ca++), and 1.9 ng/mg protein (2.5 mmol/L Ca++). PTH levels were 321 ng/mg protein (0.25 mmol/L Ca++) and 200 ng/mg protein (2.5 mmol Ca++). Therefore, calcium significantly inhibited PTH but not PTH-rP secretion (p = 0.03). Addition of incubation medium to the bioassay resulted in 3H-cAMP levels that were 8 to 10 times greater than basal levels. Greater than 50% of the activity persisted after addition of PTH antibody, demonstrating that a significant amount of the activity was caused by PTH-rP. Tissue PTH-rP was 5.1 ng/mg protein, compared with 2080 ng/mg protein for PTH. We conclude that (1) bovine parathyroid tissue contains bioactive PTH-rP and is a useful model to compare the biosynthesis and secretion of PTH-rP and PTH in normal tissue and (2) unlike PTH, PTH-rP secretion is not regulated by calcium.

Local recurrence following breast conservation therapy in African-American women with invasive breast cancer.

BACKGROUND: African-American women have a lower survival rate than white women following a diagnosis of invasive breast cancer. Limited information is available regarding the impact of race on results of breast conservation therapy (BCT). METHODS: Local recurrence rates were compared in 71 African-American patients (73 breasts) and 204 white patients (208 breasts) with stage I and II breast cancer treated with BCT. RESULTS: Overall 5-year actuarial recurrence rates were 13% in African-Americans and 4% in whites (P = 0.075). These rates were 9% and 4%, respectively, if patients with local skin/soft tissue recurrences were excluded (P = 0.587). Exclusion of these skin/soft tissue failures eliminated any significant difference seen in recurrence between stage II African-American and white patients (P = 0.163). African-American women had less favorable recurrences, including tumor in more than one quadrant or local skin/ soft tissue involvement (P = 0.001). CONCLUSIONS: Overall actuarial recurrence rates were slightly higher, but not significantly different, in African-American and white women following BCT. A much less favorable pattern of local recurrence was seen in the African-American patients (P = 0.001), which may represent the presence of more biologically aggressive tumors in these women.

Radioiodine therapy for differentiated thyroid carcinoma.

Radioiodine (iodine 131) is an effective form of adjuvant therapy that is frequently underutilized. A review of our recent experience was undertaken to assess the role of this treatment modality in the routine management of thyroid carcinoma. Over a 2-year period, 29 patients received adjuvant iodine 131 therapy. Ten of these patients (35 percent) were found to have local or distant metastasis by iodine-131 scan, and 7 (24 percent) had a metastatic lesion not suspected by operative findings or chest radiography. A complete response was obtained in 70 percent of the patients with metastatic disease. This study supports more frequent use of adjuvant radioiodine therapy in the management of differentiated thyroid carcinoma.

Significance of tumor spread in adenocarcinoma of the ampulla of Vater.

Twenty-eight patients with ampullary carcinoma were treated between 1965 and 1988: 22 underwent pancreaticoduodenectomy with 1 operative death (5 percent), 1 had local excision, 3 had bypass, and 2 were not explored. Of the 21 patients who survived pancreaticoduodenectomy, 4 had tumor confined to the ampulla, 7 had tumor extending into the duodenum, and 10 had tumor invasion beyond the duodenum. Nine of these patients had positive lymph nodes and 12 had negative lymph nodes. The patient who had local excision was disease-free at last follow-up 104 months postoperatively. Each of the three bypassed patients died of tumor progression within 15 months. The estimated 5-year survival rate for resected patients was 60 percent and was independently related to lymph node metastases (p = 0.031) and to tumor size (p = 0.039). This experience suggests that long-term survival is possible in patients with lymph node metastases or invasive tumors extending beyond the duodenal wall and that curative pancreaticoduodenectomy can be performed with a low operative mortality; therefore, aggressive surgical resection is recommended for all patients with ampullary carcinoma.

Effect of biliary decompression on morbidity and mortality of pancreatoduodenectomy.

To evaluate the effect of levels of serum bilirubin on morbidity and mortality after pancreatoduodenectomy, a prospective study was designed to compare patients who underwent preoperative biliary decompression to those who did not. Preoperative biliary decompression decreased the mean serum bilirubin level from 15.8 to 5.8 mg/dl in one group of 10 patients (Group A). The only statistical differences between this group and the two other groups of patients (Groups B and C) who were not treated with preoperative biliary decompression was the level of serum bilirubin before pancreatoduodenectomy (5.8, 22, and 1.3 mg/dl in Groups A, B, and C, respectively). Only one death occurred in each group of patients. The numbers of nonfatal complications were comparable. These results suggest that there is no decrease in morbidity or mortality after pancreatoduodenectomy when the serum bilirubin level is decreased by preoperative biliary drainage.

Genetic selection alters thermoregulatory response to ethanol.

The present study examined the effect of ethanol on the regulated temperature of two lines of mice selected in replicate for a smaller (HOT1 and HOT2) or greater (COLD1 and COLD2) decline in rectal temperature after IP ethanol. Mice were implanted with indwelling telemetry devices for remote monitoring of internal temperature and trained in a temperature gradient (8-40 degrees C). Both internal and selected temperature were tracked and recorded with a computer after injections of NaCl or various doses of ethanol. All animals responded similarly to control injections, with a transient rise in body temperature. After an effective dose of ethanol, mice showed clear evidence of a regulated decline in body temperature, as evidenced by selection of low temperatures in the gradient at the same time internal temperatures were falling. COLD mice were more sensitive than HOT mice; this was apparent in both replicates of the selected lines, indicating that a difference in the CNS regulator of body temperature has been selected for in these animals.

The effect of ethanol on temperature selection in the goldfish, Carassius auratus.

The effect of ethanol on behavioral thermoregulation in the goldfish, Carassius auratus, was studied by adding ethanol to a horizontal aquatic temperature gradient which allowed each fish to select its preferred temperature within a range of about 9 degrees C to 33 degrees C. Alternating exposure to 1.0% (v/v) ethanol and water showed that fish (10 to 15 g) responded to ethanol by selecting lower temperatures. Onset and disappearance of the effect occurred within 10 min of exposure to or removal from ethanol. Fish exposed to 1.0% ethanol for 3 hr did not show acute tolerance. When fish were exposed to increasing concentrations of ethanol from 0.0% to 1.7%, the lowest concentration to elicit a response was 0.5% ethanol. The magnitude of the response plateaued at 0.7% ethanol. At this concentration and above, selected temperatures remained about 2 degrees C below temperatures selected by controls. Because thermoregulatory responses of fish are behavioral and relatively easy to observe and quantify, goldfish offer a useful model for the study of ethanol effects on central nervous system control of thermoregulation. Ethanol produces a prompt, stable, and reproducible depression of selected temperature by lowering the thermoregulatory set point in the goldfish.

The effect of ethanol on behavioral temperature regulation in mice.

Mice were injected with 20% ethanol in 0.9% NaCl, or with 0.9% NaCl without ethanol during sessions of behavioral thermoregulation in a tubular temperature gradient (ambient temperature range approximately 9-38 degrees C). Internal temperature was monitored with an implanted telemetry device. An imaging system recorded the position (selected temperature) of the mouse within the gradient every 5 sec. A dose of either 2.25 or 2.60 g ethanol/kg body wt. produced significantly lower body temperatures than control (NaCl) injections. The 2.60 g/kg dose produced significantly lower selected temperatures than either the NaCl or 2.25 g/kg injections. Doses of 2.75 g ethanol/kg and above incapacitated the mice, precluding accurate behavioral thermoregulation. Utilizing a thermoregulatory index to compare the responses following experimental and control injections indicated that 2.25 or 2.60 g ethanol/kg leads to a decrease in the regulated temperature of mice.

Pitfalls in the diagnosis of pheochromocytoma.

Two patients were diagnosed as having pheochromocytoma based upon clinical findings, abnormal biochemical assays, and the presence of an adrenal mass. However, adrenalectomy in both cases revealed nonfunctioning cortical adenomas. Although both patients had some evidence of catecholamine excess, the early finding of an adrenal mass in each case appeared to confirm the diagnosis. In addition, selective venous assays resulted in false positive results in these patients. Interestingly, the selected venous assays falsely localized the catecholamine excess to the same side as the lesions found on CT. These cases demonstrate that localization studies should not be obtained prior to documentation of an unequivocal biochemical diagnosis of pheochromocytoma. If this principle is violated, an incidental cortical adenoma found on CT may be mistaken for a pheochromocytoma. Since there are multiple sources of error during selective venous sampling, it should not be used routinely in the initial evaluation of patients with pheochromocytoma.

Prostaglandin F2 alpha, sexual behavior and ovarian estrogen synthesis in garter snakes (Thamnophis sirtalis parietalis).

1. High levels of prostaglandin F2 alpha (PGF2 alpha; 10-18 ng) were detected in copulatory material removed from the cloacae of female Thamnophis sirtalis parietalis immediately after mating. 2. In vitro, ovarian fragments treated with PGF2 alpha secreted significantly more estrogen than control fragments. 3. Together these results suggest that a post-mating surge in estrogen secretion that occurs in this species may be influenced by a substantial rise in PGF2 alpha that occurs after mating. 4. These findings are consistent with the hypothesis that post-mating elevations in plasma levels of PGF2 alpha in females are derived from male copulatory material.

Temperature regulation in mice during withdrawal from ethanol dependence.

Temperature regulation during withdrawal from ethanol dependence was studied in mice. Dependence was induced utilizing ethanol vapor inhalation combined with injections of pyrazole, an alcohol dehydrogenase inhibitor. One control group received vehicle (0.9% NaCl); another received pyrazole (68.1 mg/kg) in vehicle. During withdrawal, mice were placed in a thermal gradient, with core temperature (Tc) and preferred temperature (Tpref) continuously recorded for 26 h. During the period of maximal withdrawal severity (4-10 h after removal from ethanol vapor), the withdrawal group was more active than controls. Withdrawal group Tc [36.4 +/- 0.1 (SE) degrees C] was similar to that of NaCl (36.2 +/- 0.1 degrees C) and pyrazole (36.3 +/- 0.2 degrees C) controls. Withdrawal group Tpref (30.5 +/- 0.5 degrees C) was significantly lower than either NaCl (33.5 +/- 0.3 degrees C) or pyrazole (32.9 +/- 0.5 degrees C) controls. Analysis of covariance with activity as covariate indicated that the difference between Tc and Tpref was greater for the withdrawal group and was due to more than increased activity. Mice withdrawing at constant temperature (29.5 degrees C) did not show Tc different from that of controls. These results support the conclusion that regulated body temperature is not altered during withdrawal. We propose that the lower Tpref of withdrawing mice represents a means of dissipating excess heat that is partly generated by the hypermetabolic state accompanying withdrawal from ethanol dependence.

Intracranial ethanol and ambient anoxia elicit selection of cooler water by goldfish.

Goldfish were either subjected to anoxia for 5 h at 10 degrees C, normoxia for 5 h at 10 degrees C, or were implanted with an intracranial microinjection cannula. All groups were subsequently tested in a temperature gradient. The previously anoxic goldfish selected cooler temperatures (12.8 +/- 1.0 degrees C; mean +/- SE) than the corresponding normoxic control group (17.5 +/- 0.7 degrees C) for the first 20 min in the gradient. Intracranial microinjections of 0.0475 ng ethanol in 0.2 microliter 0.7% NaCl led to the immediate selection of water 8.7 +/- 1.5 degrees C below that of base-line levels, whereas control animals injected with 0.7% NaCl selected water 0.9 +/- 1.0 degree C cooler. Increased effects were obtained with higher concentrations of ethanol. The effective site was limited to the anterior aspect of the nucleus preopticus periventricularis; injections into 54 other loci were without effect. Goldfish tolerate anoxia by the conversion of lactate to ethanol, which diffuses across the gills. As the lost ethanol cannot be oxidatively metabolized, this process is energetically inefficient. Because the concentration of the ethanol injections was considerably lower than reported ethanol concentrations in the tissues of anoxic goldfish, endogenously produced ethanol may have induced the selection of cooler water by the anoxic goldfish. This alteration in thermoregulatory behavior would lead to a lower metabolic rate, significantly increasing survival time during anoxia.

Ethanol disrupts and decreases the regulated body temperature differentially in C57BL/6J and DBA/2J mice.

Two inbred mouse strains, C57BL/6J (B6) and DBA/2J (D2), were evaluated for effects of ethanol on thermoregulation. Continuous recording of core temperature (Tc) from undisturbed animals at an ambient temperature (Ta) of 27 degrees C indicated Tc was similar for both strains during active (approximately 38.0 degrees C) and inactive (approximately 36.7 degrees C) periods. Ethanol-injections of 1.5, 2.5, 3.5, and 4.5 g/kg in an environment where Ta rose and fell at 6-min intervals, reaching extremes of 14 and 42 degrees C, produced dose-dependent falls in Tc for both strains. The changes in Ta produced fluctuations in Tc under all conditions. The amplitude of these fluctuations in Tc was used as a measure of physiological disruption. Dose-dependent increases in disruption were found for both strains. At a constant 26 degrees C Ta, ethanol produced dose-related increases in tail temperature. Responses after ethanol administration were different for B6 and D2 mice. The results indicate regulated temperature is similar for B6 and D2 strains. Regulated temperature is decreased more by ethanol for B6 mice, whereas disruption of thermoregulation by ethanol is greater for D2 mice.