Signalling in cell growth and death: adequate nutrition alone may not be sufficient for ciliates. A minireview

The initial inoculum level of Tetrahymena in a chemically defined medium determines whether the cells are capable of exponential growth. Below 750 cells ml-1, the cells fail to go into exponential growth and will die within about 20 hours. By adding certain growth stimulants, death can be postponed and the cells begin to grow after a delay which depends on the intensity of the signal. The implication is that autocrine growth factor expression might be required for cells to grow, and that these stimulants either assist its production or lower the cell threshold to its action. The findings in Tetrahymena are reviewed, and the advantages of having a cell system in which all the components of the medium can be carefully controlled is recognised.     

Preliminary investigation of the efficacy of sublingual verapamil in the management of acute atrial fibrillation and flutter

The antiarrhythmic properties of sublingual verapamil were investigated in seven patients with acute fast atrial flutter (n = 2) or fibrillation (n = 5). A rapid and significant (P < 0.05) reduction in the ventricular rate was achieved in all seven patients. The ventricular rate at peak plasma verapamil concentration (+/- s.d.) was significantly slower than on admission (101.6 +/- 11.3 and 159 +/- 5.3 beats min-1 respectively, P < 0.01). The ventricular rate remained controlled for over 4 h. Sublingual verapamil was rapidly absorbed with the maximum peak plasma concentration (153.3 +/- 15.5 ng ml-1) being achieved after 1.21 +/- 0.18 h. Side-effects of sublingual verapamil were limited to one report of a bitter taste. The sublingual administration of verapamil may provide an alternative method for the control of acute fast atrial fibrillation and flutter in selected patients.     

Ovariectomy-induced bone loss and the hematopoietic system

To investigate the relationship of the hematopoietic system to the loss of bone due to ovarian hormone deficiency, we examined the effects of ovariectomy and estrogen administration on the thymus, spleen and the bone marrow, and on the proliferation of marrow progenitors of osteoclasts. We also assessed the effects of daily administration of interleukin-1 receptor antagonist (IL-1ra) on bone loss due to ovarian hormone deficiency. Ovariectomy resulted in decreased cancellous bone volume, increased trabecular osteoblast and osteoclast numbers, and increased serum alkaline phosphatase levels that were prevented by 17 beta-estradiol treatment. Thymus weight, spleen weight, thymus and spleen lymphocytes, and bone marrow monocytes and lymphocytes also increased significantly following ovariectomy, and the increases were suppressed by 17 beta-estradiol. Ovariectomy, in addition, caused a 4-fold increase in the number of tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells formed in cultures of marrow cells and the increase was partially inhibited by 17 beta-estradiol. IL-1ra administration did not prevent the bone loss due to ovariectomy. Our findings indicate that ovariectomy-induced bone loss in the rat is accompanied by marked changes in the hematopoietic system, and that these changes are modulated by estrogen administration. In spite of the negative finding with IL-1ra, the nature of the involvement of the hematopoietic system in the pathogenesis of bone loss due to ovarian hormone deficiency merits continued exploration.     

Fertility issues and their management in men with testis cancer

Although a curable malignancy, testis cancer and its treatment have unique associated morbidities that largely affect reproductive dysfunction. In this focused review, the factors that contribute to infertility in men with testis cancer are outlined. The treatment-specific risks to fertility that accompany cancer management are also discussed. Contemporary methods of overcoming infertility in testis cancer patients are addressed, and several exciting and promising experimental approaches to the preservation or restoration of fertility for men with testis cancer are presented.     

Aged-rodent models of long-term growth hormone therapy: lack of deleterious effect on longevity

Studies were carried out to examine the effects of long-term recombinant human growth hormone (GH) therapy on longevity in rodents. In the first study, 150 18-month-old female F344 rats were divided into three groups of 50 rats per group: Group 1, solvent vehicle; Group 2, 10 microg GH/kg body weight three times per week; Group 3, 50 microg GH/kg body weight three times per week. GH and solvent vehicle therapies were started at 18 months of age and continued until all the animals died spontaneously. Serum insulin-like growth factor (IGF)-I was measured at 18 and 29 months of age and on 3-month-old rats. Serum IGF-I level decreased between 3 and 29 months of age. GH therapy reversed the decrease in a dose-dependent manner, with the 50 microg GH dose returning the serum IGF-I level to that of 3-month-old animals. However, statistical analysis revealed no significant effect of GH therapy on median life span, 10th percentile life span, or maximum life span. Similar observations on longevity were made on aged F344 male rats and on aged Balb/c mice, even when the dose of GH was increased to 1.0 mg/kg body weight two times per week. The main pathologic lesions in control animals were nephropathy, cardiomyopathy, leukemia, and testicular interstitial cell tumor; the prevalence of these lesions was not significantly altered by GH therapy. We conclude that long-term low-dose GH therapy that includes doses in the range that is given to humans in clinical trials in GH deficiency and to revert age-related physiologic declines has no overt deleterious effects on longevity and pathology in aged rodents.     

The epidemic of gang-related homicides in Los Angeles County from 1979 through 1994

OBJECTIVE: To determine trends in gang homicides and the population at greatest risk for homicide by reviewing all gang-related homicides in Los Angeles County, California, from January 1979 to December 1994. DESIGN: Homicide files of the Los Angeles Police Department and the Los Angeles County Sheriff's Department from 1979 to 1994 involving violent street gang activity were reviewed. Gang files were reviewed for demographic data, weapons used, homicides by drive-by shootings, and times and geographic areas of occurrence. SETTING: Los Angeles County from January 1, 1979, to December 31, 1994. MAIN OUTCOME MEASURES: Age, race, and sex of gang-related homicide victims; frequency of weapon use; and the change in gang-related homicide rates during the study period. RESULTS: A total of 7288 gang-related homicides occurred in Los Angeles County from 1979 through 1994; 5541 of these homicides occurred in Los Angeles Police Department and Los Angeles County Sheriff's Department jurisdictions. During the study period, the proportion of all homicides that were gang related increased from 18.1% to 43.0% (P < .001). Of the 5541 gang-related homicide victims, 4580 (85.6%) were aged 15 to 34 years, 93.3% were African American or Hispanic, 5157 (93.2%) were male, 3559 (64.2%) were gang members, and 1408 (25.4%) occurred during drive-by shootings. Firearms were used in an increasing proportion of homicides, from 71.4% in 1979 to 94.5% in 1994. Homicides by semiautomatic handguns dramatically increased during the study period. Gang-related homicide rates for African-American males aged 15 to 19 years increased from 60.50 per 100,000 population per year in 1979 to 1981 to 192.41 per 100,000 population per year in 1989 to 1991. CONCLUSIONS: Gang-related homicides in Los Angeles County have reached epidemic proportions and are a major public health problem. To prevent gang violence, the root causes of violent street gang formation must be alleviated, the cycle of violent street gang involvement must be broken, and access to firearms must be limited.