Indications for caesarean sections at ≥34 weeks among nulliparous women and differential composite maternal and neonatal morbidity.

OBJECTIVE: To compare composite maternal and neonatal morbidities (CMM, CNM) among nulliparous women with primary indications for caesarean section (CS) as acute clinical emergency (group I; ACE), non-reassuring fetal heart rate (group II) and arrest disorder (group III). DESIGN: A multicentre prospective study. SETTING: Nineteen academic centres in the USA, with deliveries in 1999-2002. POPULATION: Nulliparous women (n = 9829) that had CS. METHODS: Nulliparous women undergoing CS for three categories of indications were compared using logistic regression model, adjusted for five variables. MAIN OUTCOME MEASURES: CMM was defined as the presence of any of the following: intrapartum or postpartum transfusion, uterine rupture, hysterectomy, cystotomy, ureteral or bowel injury or death; CNM was defined as the presence of any of the following: umbilical arterial pH <7.00, neonatal seizure, cardiac, hepatic, renal dysfunction, hypoxic ischaemic encephalopathy or neonatal death. RESULTS: The primary reasons for CS were ACE in 1% (group I, n = 114) non-reassuring FHR in 29% (group II; n = 2822) and failed induction/dystocia in the remaining 70% (group III; n = 6893). The overall risks of CMM and CNM were 2.5% (95% confidence intervals, CI, 2.2-2.8%) and 1.9% (95% CI 1.7-2.2), respectively. The risk of CMM was higher in group I than in group II (RR 4.1, 95% CI 3.1, 5.3), and group III (RR 3.2, 95% CI 2.7, 3.7). The risk of CNM was also higher in group I than in group II (RR 2.8, 95% CI 2.3, 3.4) and group III (RR 14.1, 95% CI 10.7, 18.7). CONCLUSIONS: Nulliparous women who have acute clinically emergent caesarean sections are at the highest risks of both composite maternal and neonatal morbidity and mortality.

Hepatotoxicity with antiretroviral treatment of pregnant women.

BACKGROUND: Hepatotoxicity in adults with human immunodeficiency virus (HIV) infection has been associated with all classes of antiretroviral drugs and coinfection with hepatitis B and C virus. We treated two HIV-infected pregnant women in whom hepatotoxicity developed after initiating antiretroviral therapy. CASES: The first woman developed icterus, jaundice, hyperbilirubinemia, and elevated serum aminotransferase levels approximately 5 months after beginning combination antiretroviral therapy with zidovudine, lamivudine, and efavirenz. Serum aminotransferase abnormalities improved after discontinuation of antiretroviral medications. The second woman had similar symptoms and laboratory abnormalities 3 months after initiation of zidovudine, lamivudine, and nelfinavir. Despite initial improvement after discontinuing her antiretroviral medications, fulminant hepatic failure developed and she died. Both patients tested negative for hepatitis A, B, and C; Epstein-Barr virus; and cytomegalovirus. There was no history of illicit drug use, alcohol use, or blood transfusions in either case. CONCLUSION: We emphasize the need for careful monitoring for hepatotoxicity after initiation of antiretroviral therapy.

Acute dentoalveolar infections: an investigation of the duration of antibiotic therapy.

OBJECTIVE: To evaluate shortened courses of antibiotics in the management of dentoalveolar abscesses. DESIGN: Prospective clinical study over a 3-year period. SETTING: Examinations department of the Liverpool University Dental Hospital. SUBJECTS: 759 patients, with acute dentoalveolar abscesses associated with swelling, and an elevation of axillary temperature to above 38.5 degrees C, were included in the investigation. The minimum age of the patients was 16 years. INTERVENTIONS: The initial treatment was to drain the abscess by incision (124 patients), or extraction (635). The patients were prescribed amoxycillin (250 mg every 8 hours), clindamycin (150 mg every 6 hours) or erythromycin stearate (250 mg every 6 hours) and instructed to drink plenty of fluid. All the patients were seen 2 or 3 and 10 days later; only patients who were seen at these times were included in the trial. MAIN OUTCOME MEASURES: Resolution of the swelling and a normal axillary temperature. RESULTS: At first review 748 patients (98.6%) had normal temperatures, marked resolution of the swelling and the antibiotic was discontinued. None of these 748 patients required further antibiotic therapy. CONCLUSIONS: The duration of antibiotic therapy in most patients with acute dentoalveolar infections can safely be 2-3 days, provided that drainage has been established. It is not, therefore, necessary for the majority of patients to complete a 5-day course of antibiotics.

A deletion in the long arm of chromosome 18 in a child with serum carnosinase deficiency.

The dipeptides carnosine and anserine, found exclusively in meats, are hydrolyzed in serum by the enzyme carnosinase. Several reports of serum carnosinase deficiency describe a variable phenotype, which ranges from normal to severe psychomotor retardation, hypotonia, and myoclonic seizures in the first year of life. We report the case of a 30-mo-old girl with hypotonia, developmental delays, and tremor. Although consuming nominal quantities of meal, she excreted large amounts of carnosine and anserine. A strict meat-free diet ameliorated, but did not eliminate, these abnormalities. Serum carnosinase activity was found to be extremely low. Analysis of this child's chromosomes revealed a terminal deletion of chromosome 18 with breakpoint at q21.3. Neither parent exhibited this deletion, suggesting it was generated de novo in the patient or in a parental germ cell. Molecular studies showed that the patient's paternal chromosome 18 was deleted. Urinary carnosine excretion and serum carnosinase activity were normal in the patient's father. The mother had low carnosinase activity. The patient's brother exhibited moderate hypercarnosinuria and intermediate enzyme activity, consistent with the carrier state for carnosinase deficiency. Cumulatively, these findings suggest that the locus for this enzyme resides on the distal long arm of chromosome 18, and they are consistent with an unusual mechanism for the inheritance of this, typically autosomal recessive, condition. We conclude that this patient is likely hemizygous for the defect, having received the deficiency allele from her mother and, by virtue of the chromosomal deletion, no allele from her father. This represents the first report of a chromosomal abnormality in association with serum carnosinase deficiency and should aid in further localization of the gene encoding serum carnosinase.

Human chorionic gonadotropin directly and indirectly alters uterine arteriolar diameters in cycling rats.

OBJECTIVE: Our purpose was to investigate whether uterine microvascular responses to human chorionic gonadotropin application depend on route of administration and estrous cycle day. STUDY DESIGN: One uterine horn was exteriorized in pentobarbital-anesthetized cycling and ovariectomized rats and superfused with Krebs solution Uterine arterioles (64 +/- 2.1 microns) were viewed by videomicroscopy. Diameters were measured during a 20-minute baseline period and for 60 minutes during human chorionic gonadotropin suffusion (20 IU/60 ml) or 60 minutes after intraperitoneal injection of 50 IU of human chorionic gonadotropin. Papaverine (100 mumol/L) suffusion maximally dilated the uterine arterioles (80 +/- 2.6 microns). RESULTS: Suffusion of human chorionic gonadotropin-dilated arterioles on diestrus-1 (122% +/- 2% baseline) and diestrus-2 (118% +/- 4% baseline) but constricted arterioles on proestrus (78% +/- 7% baseline). Intraperitoneal injection of human chorionic gonadotropin resulted in arteriolar constriction on diestrus-2 (76% +/- 5% baseline) and proestrus (82% +/- 3% baseline). Ovariectomy eliminated the effects of injected but not suffused human chorionic gonadotropin. All results are significant at p < 0.05. CONCLUSIONS: Results indicate estrous cycle day-dependent direct and indirect effects of human chorionic gonadotropin on the resistance of uterine arterioles.

Increased urinary excretion of LTE4 after exercise and attenuation of exercise-induced bronchospasm by montelukast, a cysteinyl leukotriene receptor antagonist.

BACKGROUND: A study was undertaken to determine whether montelukast, a new potent cysteinyl leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction. The relationship between the urinary excretion of LTE4 and exercise-induced bronchoconstriction was also investigated. METHODS: Nineteen non-smoking asthmatic patients with a forced expiratory volume in one second (FEV1) of > or = 65% of the predicted value and a reproducible fall in FEV1 after exercise of at least 20% were enrolled. Subjects received placebo and montelukast 100 mg once daily in the evening or 50 mg twice daily, each for two days, in a three-period, randomised, double blind, crossover design. In the evening, approximately 20-24 hours after the once daily dose or 12 hours after the twice daily dose, a standardised exercise challenge was performed. Data from 14 patients were available for complete analysis. RESULTS: The mean (SD) maximal percentage decrease in FEV1 after exercise was 29.6 (16.0), 17.1 (8.2), and 14.0 (9.4) for placebo, once daily, and twice daily regimens, respectively. The mean (95% CI) percentage protection was 37 (15 to 59) for the group who received 50 mg twice daily and 50 (31 to 69) for those who received 100 mg once daily. Active treatments were not different from each other. The mean (SD) plasma concentrations of montelukast were higher after the twice daily regimen (1.27 (0.81) microgram/ml) than after the once daily regimen (0.12 (0.09) microgram/ml); there was no correlation between the percentage protection against exercise-induced bronchoconstriction and plasma concentrations. After exercise urinary excretion of LTE4 increased significantly during placebo treatment (from 34.3 to 73.7 pg/mg creatinine; p < 0.05) but did not correlate with the extent of exercise-induced bronchoconstriction. CONCLUSIONS: Montelukast protects similarly against exercise-induced bronchoconstriction between plasma concentrations of 0.12 and 1.27 micrograms/ml. The increase in the urinary excretion of LTE4 after exercise and the protection from exercise-induced bronchoconstriction with a cysteinyl leukotriene receptor antagonist provide further evidence of the role of leukotrienes in the pathogenesis of exercise-induced bronchoconstriction.

A new technique for studying the uterine microvasculature in the rat.

OBJECTIVE: Our purpose was to develop a method for direct measurement of rat uterine microvessels and to test their viability. STUDY DESIGN: In anesthetized female Sprague-Dawley diestrus rats, one uterine hom was isolated from the body cavity with its nerve and blood supply intact. A small fiberoptic probe inserted into the lumen of the uterus served as a light source for transillumination of uterine vessels. Diameters of circumferential arterioles were observed while increasing concentrations of vasoactive agonists were suffused over the uterus. RESULTS: No significant diameter changes occurred in circumferential arterioles of the control group (100-minute suffusion of Krebs solution). Dilation with papaverine (100 mumol/L) demonstrated that vessels possessed basal tone. Circumferential arterioles showed concentration-dependent constriction to phenylephrine and angiotensin II and dilation to acetylcholine and serotonin. CONCLUSIONS: This uterine microcirculatory preparation provides a stable, reproducible model of a unique microcirculatory bed that responds to vasoactive agents in a manner similar to other microcirculatory beds.

Effect of human chorionic gonadotropin on reproductive organ blood flow in cycling rats.

Recent characterization of luteinizing hormone++ (LH)/human chorionic gonadotropin (hCG) receptors in uterine vascular tissue, evidence that expression of these receptors is cyclic in nature, and demonstration of a correlation between hCG level and uterine vascular resistance lead us to investigate the effect of hCG administration on blood flow in reproductive organs of cycling and ovariectomized Sprague-Dawley rats. Blood flow (ml/min/g dry wt/cardiac output +/- SEM) was determined by microsphere spectroscopy (57Co, 113Sn, 95Nb, 141Ce). Baseline uterine (0.5842 +/- 0.1037) and cervical (0.7785 +/- 0.1199) blood flows were greater in diestrus-2 rats than in every other group. Diestrus-2 (0.4530 +/- 0.0584) and estrus (0.4692 +/- 0.0848) rats had greater baseline ovarian blood flow than proestrus rats (0.2521 +/- 0.0279). A single intraperitoneal injection of 50 IU hCG on each day of the 4-day estrus cycle decreased uterine flow by more than 30% within 20 min (P<0.05), but did not alter uterine flow in ovariectomized rats. This dose of hCG also decreased ovarian flow in diestrus-2 rats (0.5219 +/- 0.0857 to 0.4207 +/- 0.0753), decreased liver flow in diestrus-2 (0.0282 +/- 0.0060 to 0.0231 +/- 0.0051) and estrus (0.0301 +/- 0.0029 to 0.0203 +/- 0.0038 rats, and increased liver flow in ovariectomized rats (0.0279 +/- 0.0054 to 0.0325 +/- 0.0050). Injection of 0.10 IU hCG did not alter blood flow to reproductive organs in any group, but decreased liver flow in estrus rats (0.0469 +/- 0.0121 to 0.0326 +/- 0.0088). Neither dose of hCG altered cervical, kidney, or skeletal muscle flow in any group. Our results indicate an organ specific, dose-dependent blood flow response to hCG in cycling rats, which appears, in the case of uterine flow, to be attenuated by removal of the ovaries. The present findings suggest high doses of hCG given clinically may decrease uterine flow and potentially lead to implantation failure.

Phase II trial of menogaril in metastatic adenocarcinoma of the prostate. A Southwest Oncology Group study.

Menogaril, a semisynthetic anthracycline antibiotic, was administered to patients with metastatic adenocarcinoma of the prostate. Forty-five patients with measurable disease and 45 patients with evaluable disease received 150-200 mg/m2 over 1 hour every 28 days. There were three partial responses (PR) among 87 patients evaluable for response. Myelosuppression was dose limiting. There were two deaths related to leukepenia. Other toxicities included phlebitis, alopecia, nausea and vomiting. One patient developed acute nonlymphocytic leukemia. Menogaril at these doses and schedule is toxic and has no significant antitumor activity in metastatic adenocarcinoma of the prostate.

Does alpha-melanocyte-stimulating hormone from the pars intermedia regulate suckling-induced prolactin release? Supportive evidence from morphological and functional studies.

Recent evidence suggests that substances derived from the hypophyseal intermediate lobe (IL) play a crucial role in the regulation of suckling-induced PRL secretion. The purpose of the present study was to explore this possibility further by determining whether the suckling stimulus acutely increases the secretory activity of the IL and whether alpha MSH, a major secretory product of the IL, plays a specific role in suckling-induced PRL release. Light microscopic morphometric analysis of serial pituitary sections obtained from lactating rats revealed that as little as 1 min of suckling caused a significant increase in the proportion of the IL that was in secretory configuration (11.8 +/- 0.7% vs. 6.7 +/- 0.5%; 1-min suckled vs. nonsuckled control; mean +/- SE). Moreover, the fraction of the IL in secretory configuration continued to increase after 5 and 10 min of nursing (to 16.0 +/- 0.8% at 5 min and 18.2 +/- 0.7% at 10 min). In contrast, serum PRL was not significantly elevated above the control level after 1 min of suckling (18.1 +/- 13.5 vs. 9.9 +/- 6.5 ng/ml, 1-min suckled vs. control). In fact, a significant rise in PRL levels (to 314.4 +/- 19.4 ng/ml) could be detected only after 10 min of nursing. Thus, secretion by the IL in response to suckling preceded the release of adenohypophyseal PRL, suggesting that a secretory product(s) from the pars intermedia is involved in the modulation of nursing-induced PRL release. Having established a sequential temporal relationship between these two phenomena, we next investigated whether alpha MSH was the IL factor involved in the regulation of suckling-induced PRL secretion. To this end, lactating rats were injected either with antiserum to alpha MSH or preimmune serum and then allowed to nurse their pups. Serial blood samples were taken from the mothers 15, 30, 60, and 90 min after the litters were returned, and serum PRL was measured by RIA. We found that the suckling-induced rise in serum PRL was severely attenuated in animals that received anti-alpha MSH serum. This suppression was most evident at 15 min (70.1 +/- 13.4 vs. 323.5 +/- 127.0 ng/ml, antibody treated vs. preimmune serum control) and persisted throughout the entire 90-min test period. When taken together, our results suggest that suckling-induced PRL secretion is mediated at least in part by alpha MSH released from the hypophyseal IL.

Antithyroid effects of coal-derived pollutants.

Endemic goiter in iodide-sufficient areas of the United States and Colombia has been linked to watersheds rich in coal and shale, which several reports suggest are the source of water-borne goitrogens. In this report the potential antithyroid activities of aqueous coal and shale extracts and of compounds identified in aqueous effluents from coal conversion processes were assayed in thyroid peroxidase (TPO) and thyroid slice systems. Aqueous extracts of coal and black shale were potent inhibitors of TPO or 125I organification by thyroid slices. The most abundant water-soluble compounds derived from coal are dihydroxy-phenols, thiocyanate, disulfides, and hydroxypyridines. The dihydroxyphenols resorcinol, 2-methylresorcinol, and 5-methylresorcinol (orcinol) were 26.7, 22.5, and 7.2 times more potent, respectively, than the antithyroid drug 6-propylthiouracil (PTU). Other dihydroxyphenols and thiocyanate were less potent but comparable in activity to PTU. All dihydroxypyridines and 3-hydroxypyridine produced inhibitory effects comparable to PTU. None of the disulfides inhibited TPO. The antiperoxidase effects of combinations of two dihydroxyphenols or one dihydroxyphenol and SCN were additive, whereas the effects of a combination of four dihydroxyphenols at threshold inhibitory concentrations were synergistic, resulting in net effects equivalent to or greater than the sum of the individual effects. Thus, antithyroid effects may be greatly amplified by exposure to multiple coal-derived goitrogens and could be many times that produced by any one of the contributing pollutants. These results demonstrate that potent water-borne goitrogens are derived from coal and shale and that their contamination of water supplies could pose a serious threat of thyroid disorders.

Suckling reverses mammotrope responsiveness to TRH.

It is well established that suckling can alter the responsiveness of mammotropes to the prolactin (PRL) releasing actions of thyrotropin-releasing hormone (TRH). The purpose of the present study was to more critically characterize this phenomenon and to determine whether this effect was manifested at the point of TRH receptor binding and effector coupling. Cultured anterior pituitary (AP) cells from suckled and nonsuckled rats were subjected to reverse hemolytic plaque assays for PRL in the absence or presence of TRH. Treatment with TRH (100 nM for 2 h) significantly stimulated PRL secretion by pituitary cells from transiently suckled females (to 147.0 +/- 0.7% of control value; P < 0.05). Surprisingly, this same dose of the secretagogue caused a 30% inhibition (P < 0.05) of PRL release by AP cells obtained from nonsuckled lactators. In order to gain some insight into the possible mechanisms that govern these drastic changes in mammotrope responsiveness to TRH, we evaluated the ability of this secretagogue to activate the phosphoinositidase pathway. To this end, we chose to measure the intracellular accumulation of inositol monophosphate (IP1), a degradative metabolite of the inositol 1,4,5-triphosphate (Ins 1,4,5-P3) second messenger molecule, in the presence of LiCl (10 mM) which prevents further metabolism of IP1. We found that a 2 h exposure to 100 nM TRH resulted in a 3-fold increase in IP1 accumulation by AP cultures derived from both suckled and nonsuckled dams. Our results indicate that TRH effectively activates its receptor and couples to the phosphoinositidase pathway in AP cells from both nonsuckled and suckled females. Thus, we conclude that the suckling-induced increase in mammotrope responsiveness to TRH is regulated subsequent to TRH receptor activation.

Indium-111 monoclonal antibody B72.3 scintigraphy in colorectal cancer. Correlation with computed tomography, surgery, histopathology, immunohistology, and human immune response.

As part of an open-labeled nonrandomized multi-institutional Phase III study, the authors compared the results of In-111 (In-111) B72.3 glycyl-tyrosyl-n-diethylenetriaminepentaacetic acid lysine (GYK-DTPA) monoclonal antibody scintigraphy with computed tomography (CT), surgery, histopathology, immunohistology, and human antibody response in 23 patients with primary colorectal carcinoma. There were no significant adverse reactions to 1 mg of In-111-labeled antibody. Planar imaging identified 16 of 23 primary colon lesions, whereas single photon emission computer tomography (SPECT) imaging identified 21. SPECT also correctly identified lymphatic involvement in four patients. (There were two false-positive results.) Liver metastases were identified with SPECT imaging. Twenty-six percent of patients developed human anti-mouse antibody (HAMA). These preliminary results demonstrate that In-111 B72.3 GYK-DTPA is a safe monoclonal antibody conjugate that has a high sensitivity for identifying primary colorectal cancer. Regional lymphatic and distant liver metastases also can be imaged, but false-positive results can occur.

Suckling unmasks the stimulatory effect of dopamine on prolactin release: possible role for alpha-melanocyte-stimulating hormone as a mammotrope responsiveness factor.

Mounting evidence indicates that dopamine (DA) can stimulate as well as inhibit PRL release when given in appropriately low doses. In the present study, we investigated whether the suckling stimulus could influence this response. Pituitary cultures from suckled or nonsuckled rats were exposed to DA (10(-16) - 10(-6) M) during a reverse hemolytic plaque assay for PRL. Pituitary cells from nonsuckled rats exhibited only the inhibitory response to DA; exposure to high-dose DA (10(-6) M) reduced plaque area to 42.3 +/- 7.2% (mean +/- SEM) of control. A low dose of DA (10(-12) M) had no effect on PRL secretion (79.3 +/- 13.3% of control). In striking contrast, a brief suckling stimulus (10 min) rendered the mammotropes responsive to stimulation by low-dose DA (to 152.7 +/- 12.5% of control). Thus, suckling appears to be a requirement for expression of the stimulatory effect of DA in lactators. In a subsequent series of experiments we explored the possibility that a hypophysial factor, released during nursing, might mimic the effects of suckling on mammotrope responsiveness. Accordingly, we tested the effects of alpha-melanocyte-stimulating hormone (10(-7) M) and low-dose DA, alone or in combination, on pituitary cells from nonsuckled rats. Although neither agent alone had a dramatic effect on PRL secretion, concurrent administration of both of these significantly stimulated PRL release to 130.0 +/- 4.2% of control. Taken together, these results demonstrate that suckling renders mammotropes responsive to the stimulatory effects of DA. Moreover, our data indicate that alpha-melanocyte-stimulating hormone could function as a responsiveness factor in this phenomenon.

Treatment of advanced-stage massive mediastinal Hodgkin's disease: the case for combined modality treatment.

In the initial series of 198 patients treated at the National Cancer Institute (NCI) with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy for Hodgkin's disease, a review of presenting chest radiographs available on 192 of these patients showed 49 patients with mediastinal masses greater than one third the greatest posteroanterior chest diameter. Five patients had stage IIB disease, and 44 had stage III or IV disease. Thirty-five (71%) patients achieved a complete remission with MOPP chemotherapy. Fourteen (40%) of the complete responders relapsed, but four of these achieved durable remissions in response to subsequent therapy. Thirty (61%) patients have died (14 induction failures, nine relapsed patients, seven complete responders in remission). Thus, with a median follow-up of 20 years (range, 15 to 23), the overall survival for the group is 39%, and the disease-free survival for the complete responders is 60%. A subset of 10 patients received mantle radiation therapy after maximal response to MOPP. One of these patients failed to achieve complete remission, but among the nine complete responders only one has relapsed. In contrast, 13 of 26 (50%) patients achieving a complete response to MOPP alone have relapsed (P2 = .0536). Although MOPP alone was not prospectively compared with MOPP plus radiation therapy in the treatment of advanced-stage massive mediastinal Hodgkin's disease in this series, the retrospective analysis shows a nearly significant difference in disease-free survival favoring combined modality treatment. The difference in tumor mortality between MOPP-treated (44%) and combined modality-treated patients (80%) was also nearly significant (P2 = .055). However, overall survival differences between patients treated with MOPP alone and those treated with combined modality therapy were not significantly different (P2 = 0.23) because of the mortality related to late complications of combined modality treatment.

Is the mammosomatotrope a transitional cell for the functional interconversion of growth hormone- and prolactin-secreting cells? Suggestive evidence from virgin, gestating, and lactating rats.

Serum concentrations of PRL and GH increase and decrease, respectively, during the progression from nonpregnancy through lactation. However, it is unknown whether the secretory capacities and/or relative abundance of cells that release PRL or GH are altered during these physiological states. In the present study anterior pituitaries from adult virgin, gestating, and early or late lactating female rats were dispersed with trypsin and subsequently assayed for PRL and GH release using reverse hemolytic plaque assays. We found that the relative abundance of PRL-secreting cells was greater and that of GH cells lower in pituitaries from lactating females than in those from virgins. Moreover, the relative amounts of both PRL and GH released per cell were diminished in gestating and lactating females. For PRL, this decrease could be accounted for by an increase in the number of cells that released small quantities of hormone. We then performed simultaneous plaque assays to determine whether the shifts in the relative proportions of PRL and GH secretors were due to changes in the percentages of cells that secrete each hormone alone or in the fraction that releases both PRL and GH concurrently. Variations in both single and dual hormone-secreting cells appear to contribute to the overall fluctuations in the relative abundance of PRL and GH cells during these physiological transitions. We conclude that the additional PRL secretors present during lactation may arise from cells that previously released only GH, and that this functional interconversion of GH and PRL secretors might involve an intermediate cell type, the mammosomatotrope.

Relative importance of newly synthesized and stored hormone to basal secretion by growth hormone and prolactin cells.

It is generally accepted that under basal conditions there is preferential release of newly synthesized hormone by a number of endocrine cell type, including those that secrete GH or PRL. However, the cellular basis for this phenomenon along with the relative contribution of stored hormone to basal secretion has yet to be clearly established. In the present study, we employed reverse hemolytic plaque assays to monitor basal and stimulated release of GH and PRL from individual cells in which de novo protein synthesis had been blocked. Monodispersed pituitaries from adult male rats were cultured for 21 h in the absence or presence of maximally effective doses of puromycin (100 microM) or cycloheximide (36 microM) and were then subjected to separate plaque assays for GH or PRL. Treatment with puromycin reduced the percentage of GH or PRL secretors (plaque formers) by about half. Coincubation with stimulatory secretagogues did not increase the percentages of GH or PRL secretors in control cultures, but returned the proportion in puromycin-treated cells to normal, demonstrating that cells which failed to secrete basally could still release hormone from their stored pools when stimulated. Very similar results were obtained when these experiments were repeated with cycloheximide. Taken together, these results demonstrate that only a fraction of the cells that release GH or PRL are dependent upon newly synthesized hormone for basal secretion; the remainder appear capable of mobilizing stored hormone for this purpose even in the absence of stimulation.

Evaluation of fludarabine phosphate in small cell carcinoma. A Southwest Oncology Group Study.

Fludarabine phosphate was given as a 5 day bolus infusion to eleven evaluable patients with recurrent small cell lung carcinoma. Patients had failed on one prior treatment regimen. There were no responses in the eleven evaluable patients. Severe neurologic toxicity occurred in one patient. Fludarabine phosphate as given in this protocol was not an effective agent in recurrent small cell lung carcinoma.