Changes in the kinetics of the hemoglobin, total protein and DNA content in rat erythroid cells in experimental anemia. I. The peripheral blood

Cytophotometry of rat blood erythroid cells during anaemia, induced by phenylhydrazin (4-8 days from the beginning of injections), revealed that all forms of bone marrow containing haemoglobin were thrown into the blood. On its peak (4th day), the greatest contribution in blood haemoglobinization (50%) is made by microcytes. From the 5th day and up to the end of the restoration period the important role in this process is played by macrocytes. From the 6th day the role of normocytes increases, whose contribution by 8th day reaches 70% of the whole haemoglobin amount in blood. In contrary to anaemizated birds, whose erythroid cells ripen in blood, in rats all the transformations of erythron during anaemia are accomplished in bone marrow.     

Treatment with alendronate prevents fractures in women at highest risk: results from the Fracture Intervention Trial

BACKGROUND: The efficacy of antiresorptive therapy in preventing fractures in women at highest fracture risk, such as very elderly women or those with severe osteoporosis, is uncertain. PARTICIPANTS AND METHODS: Using data from a double-blind, randomized, placebo-controlled clinical trial that enrolled 2027 postmenopausal women aged 55 to 81 years with low femoral neck bone mineral density (BMD) and existing vertebral fractures, we examined the consistency of the effect of treatment with alendronate sodium in preventing fractures within a priori-specified risk subgroups defined at baseline by age, bone density, number of preexisting vertebral fractures, and history of postmenopausal fracture. The women were randomized to oral administration of alendronate or placebo and followed up for an average of 2.9 years. The initial dose of alendronate sodium was 5 mg/d; the dosage was increased from 5 to 10 mg/d at 24 months. New vertebral fractures, the primary end point of this arm of the trial, were defined by morphometry as a decrease of 20% and at least 4 mm in any vertebral height between baseline and a follow-up radiograph at 36 months. Incident clinical fractures, the secondary end point, included nonspine and clinical (symptomatic) vertebral fractures. All clinical fractures were confirmed with x-ray film reports or, in the case of clinical vertebral fractures, x-ray films. RESULTS: Overall, there was a 47% significant reduction in risk of new vertebral fractures in the alendronate group compared with the placebo group. The reduction in risk of new vertebral fracture was consistent across fracture risk categories including age (relative risk [RR], 0.49 in women < 75 years compared with 0.62 in those > or = 75 years), BMD (RR, 0.54 in women with a femoral neck BMD < 0.59 g/cm2 [median] compared with 0.53 in those with a BMD > or = 0.59 g/cm2), and number of preexisting vertebral fractures (RR, 0.58 in women with 1 vertebral fracture compared with 0.52 in those with > or = 2). The overall significant 28% reduction in risk of incident clinical fractures in the alendronate group compared with the placebo group was also observed within these subgroups. Compared with the number of lower-risk women, a similar or smaller number of high-risk women needed to be treated to prevent 1 fracture. For example, 8 women aged 75 years or older compared with 9 women younger than 75 years, or 4 women with 2 or more existing vertebral fractures compared with 16 women with 1 existing vertebral fracture, needed to be treated with alendronate for 5 years to prevent 1 new vertebral fracture. CONCLUSIONS: Alendronate effectively reduces fracture risk in postmenopausal women with vertebral fractures and low BMD, including those women at highest risk because of advanced age or severe osteoporosis. Since the risk reductions observed with alendronate treatment were consistent within fracture risk categories, more fractures were prevented by treating women at highest risk.     

Association between inflammatory bowel disease and sarcoidosis. Report of two cases and review of the literature

BACKGROUND: Common etiopathogenic factors may explain the association of systemic sarcoidosis with inflammatory bowel disease. METHODS: We report two cases of such an association: one of sarcoidosis that developed 2 years after proctocolectomy for ulcerative colitis and one of sarcoidosis and Crohn's colitis. Factors like increased cellular immunity or circulating immunocomplexes or autoantibodies may have a role. Exogenous agents or familiarity may also be involved. CONCLUSIONS: It is postulated that the association between sarcoidosis and inflammatory bowel disease (both ulcerative colitis and Crohn's disease) does not occur by chance alone and that the two conditions may share some genetic or immunologic alterations. The two diseases, however, follow an independent clinical course.     

Distal dorsal forearm flap

Reinstatement and spontaneous recovery of previously extinguished nicotine-taking behavior were examined in rats. Male subjects were trained to self-administer nicotine (30 microg/kg per infusion, IV; one 60-min session per day for 3 weeks). Extinction sessions were then given for 5-10 days during which saline was substituted for nicotine. Subsequently, in the first set of tests for nicotine seeking, the reinstatement of lever presses that previously delivered nicotine was examined after priming injections of saline and nicotine (75, 150 and 300 microg/kg, SC; and 30 and 60 microg/kg, IV). In the second set of tests for nicotine-seeking, rats were tested after an additional 21-day drug-free period during which they were not exposed to the self-administration chambers (a test for the spontaneous recovery of drug seeking), and after priming injections of nicotine (150 and 300 microg/kg, SC). Reinstatement of extinguished food-reinforced behavior after exposure to nicotine was also determined. Priming injections of nicotine reinstated nicotine seeking regardless of the route of administration. In addition, previously extinguished nicotine seeking recovered spontaneously after a 21-day period during which rats were not exposed to the drug-taking environment. Nicotine also reinstated extinguished food-reinforced behavior in rats with a history of nicotine self-administration, but not in drug-naive rats. The present results extend previous work with opioid and stimulant drugs on reinstatement of drug seeking by the self-administered drug. It also appears that, as with other positive reinforcers, the mere passage of time is a sufficient condition for the spontaneous recovery of extinguished nicotine seeking.     

Phase II trial of paclitaxel and granulocyte colony-stimulating factor in patients with pancreatic carcinoma: a Southwest Oncology Group study

PURPOSE: Pancreatic cancer is difficult to treat, with most patients surgically unresectable at the time of diagnosis. Radiotherapy and chemotherapy can offer palliation, but more effective therapy is needed. This trial evaluated the effects of an aggressive schedule of paclitaxel given with granulocyte colony-stimulating factor (G-CSF) to patients with advanced pancreatic cancer. PATIENTS AND METHODS: All patients were required to have a histologic diagnosis of pancreatic adenocarcinoma with measurable disease and no prior chemotherapy or radiation therapy. Patients had to have performance status of 0 to 2, pretreatment absolute granulocyte count > or = 1,500/microL, and platelet count greater than or equal to the institutional lower limit of normal. Following pretreatment with dexamethasone, diphenhydramine, and cimetidine, patients received paclitaxel at a dose of 250 mg/m2 by 24-hour infusion on day 1, repeated every 21 days. G-CSF was given at a dose of 5 microg/kg/d on days 3 to 18 or until two consecutive absolute neutrophil counts (ANCs) > or = 10,000/microL were obtained. Doses of paclitaxel were modified depending on nadir counts. RESULTS: Forty-five patients were entered onto this study, with six ineligible. For the 39 eligible patients, there was one complete response (CR) and two partial responses (PRs), five stable/no responses, 23 increasing disease, two early deaths, and six patients whose assessment was inadequate to determine response. The response rate was therefore three of 39 or 8% (95% confidence interval [CI], 2% to 21%). The median survival time for the 39 eligible patients was 5 months. The most common toxicities were anemia, leukopenia/granulocytopenia, malaise/fatigue, nausea/vomiting, alopecia, thrombocytopenia, paresthesias, and liver function abnormalities. There was one death due to sepsis. CONCLUSION: Single-agent paclitaxel in this dose and schedule has minimal activity in pancreatic adenocarcinoma patients.     

Recurrent hyperparathyroidism due to parathyroid autografts: incidence, presentation, and management

Recurrent hyperparathyroidism (HPT) occurs in a small percentage of patients undergoing parathyroidectomy for primary HPT and is usually due to inadequate excision of hyperfunctioning parathyroid tissue in the neck, a missed ectopic and hyperplastic parathyroid, or, less commonly, parathyroid carcinoma and parathyroid autografts. In order to determine the incidence, clinical characteristics, and outcome of patients with recurrent HPT due to parathyroid autografts, we reviewed our experience with 604 consecutive patients operated on for primary HPT between 1965 and 1989. One hundred of these patients received parathyroid autografts consisting of portions of one or more parathyroid glands. Three patients with autografts, placed in the sternocleidomastoid muscle, developed recurrent HPT due to their autografts for an incidence of 3 per cent. Recurrent disease was diagnosed between 62 and 113 months with an average of 89 months. The autotransplants in all three of these patients were from hyperplastic or adenomatous parathyroid tissue. Two patients had a history of neck irradiation. Preoperative thallium scans accurately localized the hyperfunctioning parathyroid tissue in all three patients. At operation, the hyperfunctioning autografts had grown into a discrete mass with a single vascular pedicle and were resected. Histologic examination disclosed either hyperplastic or adenomatous tissue, and corresponded to the histology and location of the original tissue transplanted in each case. Follow-up ranges from 12 to 67 months, with an average of 48 months. All patients remain cured and none require oral calcium supplementation. We conclude that graft-dependent recurrent HPT is due to the autotransplantation of hyperplastic or adenomatous parathyroid tissue and that thallium scanning is instrumental for diagnosis and localization.(ABSTRACT TRUNCATED AT 250 WORDS)