Recovery of sperm production following radiation therapy for Hodgkin's disease after induction chemotherapy with mitoxantrone, vincristine, vinblastine, and prednisone (NOVP)

PURPOSE: The effect on human male fertility of radiotherapy following chemotherapy for the treatment of Hodgkin's disease (HD) is unknown. The impact of radiation therapy, given after mitoxantrone, vincristine, vinblastine, and prednisone (NOVP) chemotherapy, on sperm production is the focus of this study. PATIENTS: Serial semen analyses were performed on 34 patients with HD Stages I-III before NOVP chemotherapy, after chemotherapy prior to radiation, and after radiation therapy. The most inferior radiation portals for patients were: mantle, 1 patient; paraaortic-spleen, 3 patients; upper abdomen, 24 patients; abdominal spade, 4 patients; and pelvic, 2 patients. Testicular radiation dose measurements were available for 20 of these patients. RESULTS: Before the start of radiation, 90% of patients were normospermic. The magnitude of the decline in sperm counts was related to the measured testicular dose and/or radiation fields employed. The minimum postradiotherapy counts, expressed as a fraction of pretreatment counts, for the various treatment groups are as follows: paraaortic-spleen, 20%; upper abdomen, testicular dose < 30 cGy, 4%; upper abdomen, testicular dose 30-39 cGy, 0.9%; abdominal spade, 0.02%; and pelvis, 0%. The time to nadir of sperm counts averaged 4.5 months. Recovery to normospermic levels occurred in 96% of patients, with most recovering to that level within 18 months. CONCLUSION: The effect of radiation following NOVP chemotherapy on sperm counts was no greater than would be expected with radiation therapy alone. In most patients, sperm counts recovered to levels compatible with normal fertility.     

Differential affinity of anti-Pr-β-hCG-TT antibodies for hCG and hLH

Sera from four women immunized with the vaccine Pr-β-hCG-TT have been analysed for binding with hCG and hLH. Resolution of Scatchard plots showed the presence of more than one population of antibodies in these sera. In each case the Association Constants (Ka) of a population of antibodies for binding with hCG were distinctly higher than those for hLH. Results indicate the likely presence in β-hCG of determinants and/or conformations immunologically unique to hCG besides common regions.     

Possible psychopharmacological agents. Part 3: Synthesis and CNS activity of some new fluorine-containing pyrazolo[3,4-e][1,4]thiazepines

A series of new fluorine-containing pyrazolo [3,4-e][1,4]thiazepines has been synthesized by the condensation of 5-amino-3/1, 3-substituted pyrazole with appropriate arylaldehydes or ketones and mercaptoacetic acid in dry toluene. All synthesized compounds have been characterized by their m.p.'s elemental analysis, IR, H-NMR and F-NMR. A representative number of compounds has also been screened for their CNS activity and found to act as mild stimulants.     

Patient preferences in choosing chemotherapy regimens for advanced non-small cell lung cancer

The major difference between cisplatin-based chemotherapy doublets for advanced non-small cell lung cancer (NSCLC) is not in the outcomes of their use--rather, it is in the side effects and toxicities that they cause.The degree to which oncologists involve lung cancer patients in discussions regarding the selection of chemotherapy is unknown. A questionnaire regarding patient concerns about chemotherapy and physician discussions was sent to patients registered in the Alliance for Lung Cancer Advocacy, Support, and Education (ALCASE) database from 2000--2002. About three-quarters of the respondents reported that if they were given the option, they would consider side effects important in choosing a particular regimen--and nausea was the most important side effect that would influence that decision. Female patients were more likely to worry about infection and hair loss resulting from therapy than were men. Further, about two-thirds of patients reported that they had discussed differences in chemotherapy side effects with their physicians, particularly if the physicians were female, although less than half of those patients recalled discussing the selection of a particular regimen based upon its side-effect profile. Different chemotherapy regimens with varied side-effect profiles have been developed, but medical oncologists do not present options for chemotherapy uniformly to their patients based on possible or probable adverse reactions. Better communication between physician and patient about the likelihood of side effects may reduce chemotherapy-related stress for patients.     

Estradiol metabolites attenuate renal and cardiovascular injury induced by chronic nitric oxide synthase inhibition

Our previous studies in rodent models of nephropathy demonstrate that 2-hydroxyestradiol (2HE), an estradiol metabolite with little estrogenic activity, exerts renoprotective effects. In vivo, 2HE is readily converted to 2-methoxyestradiol (2ME), a major estradiol metabolite with no estrogenic activity. The goal of this study was to determine whether 2ME has renal and cardiovascular protective effects in vivo. First, the acute (90 minutes) and chronic (14 days) effects of 2ME (10 microg/kg/h) on blood pressure and renal function were examined in normotensive and spontaneously hypertensive rats (SHR). Second, a rat model of cardiovascular and renal injury induced by chronic nitric oxide synthase inhibition (N-nitro-L-arginine; 40 mg/kg/d; LNNA group) was used to examine the protective effects of estradiol metabolites. Subsets of LNNA-treated rats were administered either 2HE or 2ME (10 microg/kg/h via osmotic minipump; LNNA+2ME and LNNA+2HE groups, respectively. 2-Methoxyestradiol had no acute or chronic effects on blood pressure or renal function in normotensive animals or on hypertension in SHR. Prolonged, 5-week NOS inhibition induced severe cardiovascular and renal disease and high mortality (75%, LNNA group). 2ME, but not 2HE, significantly decreased elevated blood pressure and attenuated the reduction in GFR. 2HE delayed the onset of proteinuria, whereas no proteinuria was detected in the 2-ME group. 2HE and 2ME reduced mortality rate by 66% and 83%, respectively (P < 0.001). In the kidney, 2HE and 2ME abolished LNNA-induced interstitial and glomerular inflammation, attenuated glomerular collagen IV synthesis, and inhibited glomerular and tubular cell proliferation. In the heart, 2HE and 2ME markedly reduced vascular and interstitial inflammation and reduced collagen synthesis and vascular/interstitial cell proliferation. This study provides the first evidence that, in a model of severe cardiovascular and renal injury, 2-methoxyestradiol (a major nonestrogenic estradiol metabolite) exerts renal and cardiovascular protective effects and reduces mortality.     

Short-term effect of complementary feeding frequency on total ad libitum consumption in 6- to 10-month-old breast fed Indian infants

OBJECTIVE: To evaluate the short-term effect of frequency of complementary feeding on total ad libitum consumption in breast fed infants. METHODS: Twenty infants between 6 to 10 months of age were studied in a tertiary hospital in New Delhi for 48 hours. A traditional gruel made of rice and pulses (mean (SD) caloric density 54.22 (7.08) kcal/100 g) was offered in a randomized manner three (n = 10) or four (n = 10) times per day to the subjects over the first 24 hours with the subjects crossing over in the next 24 hours. They were allowed ad libitum breast feeding with no other food or fluid during the study period. Total caloric intake from breast milk and semisolids was computed for each day. RESULTS: There was no difference in the total caloric consumption with a semisolid feeding frequency of three or four times per day. The frequency of breast feeding and the breast feeding duration were also comparable (P > 0.05). However, breast milk intake was lower with a semisolid feeding frequency of 4 times/day (mean difference -61.2 g/d [95% confidence interval (CI) -122.2-0.32]; P = 0.051). The time required for feeding was higher (mean difference 14.75 min; P < 0.001), whereas the per meal intake of semisolids was lower with four semisolid feeds per day (mean difference -5.5 kcal/meal; [95% CI -10.19 to -0.81]; P = 0.024). CONCLUSION: In the short term, a change in semisolid feeding frequency from three to four times per day does not result in enhanced energy consumption because of lower breast milk intake.     

Adenosine inhibits PDGF-induced growth of human glomerular mesangial cells via A(2B) receptors

The objectives of the present study were to determine whether adenosine attenuates proliferation of glomerular mesangial cells (GMCs), which adenosine receptor (AR) mediates the antimitogeneic actions of adenosine, and the cellular mechanisms by which adenosine inhibits growth of GMCs. Studies were conducted in both human and rat GMCs. Platelet-derived growth factor (PDGF)-BB (25 ng/mL) increased DNA synthesis ([3H]thymidine incorporation), cellular proliferation (cell number), collagen synthesis ([3H]proline incorporation), and mitogen-activated protein kinase (MAPK) activity, and these effects were attenuated by 2-chloroadenosine (nonselective AR agonist) and 5'-N-methylcarboxamidoadenosine (MECA; nonselective AR agonist), but not by N6-cyclopentyladenosine (selective A1 AR agonist), AB-N-MECA (selective A3 AR agonist), or CGS21680 (selective A(2A) AR agonist). KF17837 (selective A(2A/B) AR antagonist) and 1,3-dipropyl-8-p-sulfophenylxanthine (nonselective AR antagonist), but not 8-cyclopentyl-1,3-dipropylxanthine (selective A1 AR antagonist), blocked the growth-inhibitory effects of 2-chloroadenosine and 5'-N-MECA. Antisense, but not sense or scrambled, oligonucleotides to the A(2B) receptor increased both basal and PDGF-induced DNA synthesis, cell proliferation, and collagen synthesis, and the growth-inhibitory effects of 2-chloroadenosine, 5'-N-MECA, and erythro-9-(2-hydroxy-3-nonyl)adenine (inhibitor of adenosine deaminase) plus iodotubercidin (inhibitor of adenosine kinase) were abolished by antisense, but not scrambled or sense, oligonucleotides to the A(2B) receptor. We conclude that adenosine causes inhibition of GMC growth by activating A(2B) receptors coupled to inhibition of MAPK activity. A(2B) receptors may play an important role in regulating glomerular remodeling associated with GMC proliferation. Pharmacological or molecular biologic activation of A(2B) receptors may prevent glomerular remodeling associated with glomerulosclerosis, renal disease, and abnormal growth associated with hypertension and diabetes.