Serum and follicular fluid insulin like growth factors I and II during growth hormone co-treatment for in-vitro fertilization and embryo transfer

OBJECTIVE: We wished to assess the changes in serum IGF-I and IGF-II concentrations during gonadotrophin treatment alone or with additional GH treatment and to compare follicular fluid IGF-I and IGF-II concentrations in the two treatment groups. DESIGN: We performed an open study of co-treatment with GH and subsequently a randomized double blind comparison of addition of placebo or GH to clomiphene citrate and gonadotrophins. PATIENTS: We studied previously poor responders to superovulation regimens for in-vitro fertilization and embryo transfer, six women in an open study, four of whom had ultrasound diagnosed polycystic ovaries, and 17 women in a double blind study, 12 of whom had polycystic ovaries. MEASUREMENTS: We measured serum IGF-I and IGF-II concentrations throughout treatment cycles. Follicular fluid concentrations were measured at the time of oocyte recovery. RESULTS: Neither serum IGF-I nor IGF-II concentrations were altered by gonadotrophin treatment alone. However, co-treatment with GH led to a significant rise in serum IGF-I concentrations in women with ultrasound diagnosed polycystic ovaries. Concentrations of IGF-I and IGF-II in follicular fluid were lower than in serum, although follicular fluid IGF-I concentrations were higher in women receiving GH than in those receiving placebo. CONCLUSIONS: Poor responders to superovulation regimens may have an abnormality of growth factor response. GH co-treatment leads to an increase in circulating IGF-I concentrations in women with polycystic ovaries but our results do not support the hypothesis that GH stimulates IGF-I production in the human ovary.     

Intracardiac metastases from germ cell tumours--an unusual but important site of metastasis.

Two cases of intracardiac deposits from testicular teratomas diagnosed by echocardiography and angiocardiography, respectively, are described. The importance of recognizing this as an uncommon site of metastasis from germ cell tumours is discussed.     

Occupational Hydrocarbon Exposure and Diabetic Nephropathy

Exposure to hydrocarbons has been implicated in the pathogenesis of glomerulonephritis but its role in the development of diabetic nephropathy remains unknown. Three groups of patients with Type 1 diabetes of over 10 years duration were studied. Group 1 comprised 45 patients (23 F) with no diabetic nephropathy (urinary albumin excretion (AER) –30 mg 24 h^?1), group 2 comprised 37 patients (17 F) with incipient diabetic nephropathy (AER between 30–300 mg 24 h^?1), and group 3 comprised 31 patients (15 F) with overt diabetic nephropathy (AER >300 mg 24 h^?1). The groups were comparable for age, sex, duration of diabetes, recent glycaemic control, social class, and residential area. Patients were assessed blindly by a validated questionnaire and interview for hydrocarbon exposure, consumption of tobacco, analgesic agents, and alcohol. Exposure scores to hydrocarbons derived from the questionnaire were significantly higher in patients with incipient and overt diabetic nephropathy with smoking adjusted odds ratios of 3.6 and 5.2, respectively. The consumption of alcohol, analgesic agents, tobacco, and smoking habits were similar in the three groups. In conclusion, hydrocarbon exposure may be a key environmental factor in the development of diabetic nephropathy in patients with Type 1 diabetes.     

Effect of cyclosporine on endothelial albumin leakage in rats.

Short-term treatment of rats with cyclosporine (cyclosporine A [CsA]; Sandimmune) results in a marked reduction in intravascular plasma volume, a factor that might contribute to the renal dysfunction associated with this potent immunosuppressant. To examine the role of plasma extravasation in CsA-induced hypovolemia, intravascular plasma volumes (PV), blood volumes, [125I]albumin disappearance, and changes in hematocrit (Hct) were measured in Inactin-anesthetized rats subjected to minimal surgery. The rats were treated for 3 wk with either 25 mg/kg/day of CsA s.c. or vehicle. Plasma creatinine and urea were significantly elevated, and magnesium was reduced in the CsA group (N = 6) as compared with controls (CON) (N = 6). CsA treatment had no effect on urinary protein and albumin excretion. Blood volume was significantly lower in CsA than in CON (8.4 +/- 0.5 versus 10.6 +/- 0.3 mL/100 g body wt) as was PV (4.3 +/- 0.2 versus 5.5 +/- 0.2 mL/100 g body wt). Two hours after injection, plasma [125I]albumin concentration had fallen by 41 +/- 4% in CsA versus 23 +/- 5% in CON. Because Hct, and, hence PV, was unchanged in both groups during these 2 h, these data indicate enhanced endothelial albumin leakage in the CsA group. In two additional groups of six rats each, acute volume expansion with fresh whole blood (2 mL/100 g body wt) resulted in extravasation of plasma. Hct rose by 8.0 +/- 0.2% in CsA versus 3.8 +/- 0.2% in CON after 150 min, corresponding to 27 +/- 3 and 15 +/- 2% decreases in total PV, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of computed tomography in the diagnosis and management of human immunodeficiency virus (HIV)-related pulmonary diseases

This review summarizes the current role of CT in the diagnosis and management of respiratory disease in human immunodeficiency virus (HIV)-positive patients. Recommendations are made concerning optimum technique for diagnostic CT as well as practical considerations concerning the use of CT in biopsy and thoracic interventional procedures in acquired immune deficiency syndrome (AIDS)-related thoracic disease. Clinical scenarios discussed include the use of CT when the chest radiograph is normal in a patient with a high clinical suspicion of pulmonary disease, utility of CT in the differential diagnosis of parenchymal abnormalities and in the assessment of patients with airways disease, hemoptysis, progressive lung disease, and intrathoracic complications. Finally, the use of thoracic CT in the staging of AIDS-related neoplastic conditions involving the chest is discussed.     

Lumbar but not cervical intrathecal DAMGO suppresses extrasegmental nociception in awake rats

The effect of intrathecally administered [d-Ala²,N-Me-Phe⁴,Gly⁵-ol]-enkephalin (DAMGO) on withdrawal latencies evoked by noxious heat applied to either cervical or lumbar dermatomes was studied in awake rats. Administration of DAMGO to the lumbar intrathecal space produces a dose-dependent suppression of withdrawals evoked by noxious thermal stimulation in either lumbar or cervical dermatomes. Administration of the same doses of DAMGO to the cervical spinal cord produces a suppression of withdrawals evoked by stimulation in cervical but not lumbar dermatomes. Control experiments provide evidence that the drugs administered intrathecally to either enlargement do not spread to the other enlargement.     

Chemical mutagenesis testing in Drosophila: VIII. Reexamination of equivocal results.

Twelve percent of the chemicals tested for mutagenicity by the National Toxicology Program (NTP) using the Drosophila sex-linked recessive lethal assay have been classified as producing equivocal results. We have reexamined the published data and the criteria used to determine mutagenicity in light of the historical distribution of the concurrent negative controls for this project. Many of the chemicals that originally produced equivocal results have been retested under code. As a result of changes to incorporate a comparison with the historical control in the algorithm used to determine mutagenicity and as a result of new data accumulated, 4 of the 25 chemicals that gave equivocal results are judged to be mutagenic, and 11 others are judged to be nonmutagenic under our test conditions.     

Sequential cycles of high-dose carboplatin administered with recombinant human granulocyte-macrophage colony-stimulating factor and repeated infusions of autologous peripheral-blood progenitor cells: a novel and effective method for delivering multiple courses of dose-intensive therapy.

PURPOSE: The trial was undertaken to study the effect of administering granulocyte-macrophage colony-stimulating factor (GM-CSF) with and without peripheral-blood progenitor cells (PBPC) on the hematologic and nonhematologic toxicity observed with multiple cycles of high-dose carboplatin chemotherapy. PATIENTS AND METHODS: Eighteen patients with a variety of solid tumors received a total of 40 cycles of carboplatin, 1,200 mg/m2 per cycle, administered by continuous infusion over 96 hours. All 40 courses were administered with a daily 4-hour intravenous (IV) infusion of either 5 or 10 micrograms/kg/d of recombinant human Escherichia coli-derived GM-CSF. The first 20 courses were administered without PBPC support (treatment A). Because of severe neutropenia and thrombocytopenia, the next 20 courses of therapy were administered with GM-CSF, PBPC, and oral antibiotic prophylaxis (treatment B). RESULTS: The addition of PBPC support led to a significant reduction in the duration of neutropenia (10.5 v 7.5 days; P = .027) and thrombocytopenia (12.4 v 5.2 days; P = .001), number of RBC transfusions (six v three; P = .01) and platelet transfusions (10.3 v 3.7; P = .013), number of hospital days (12.6 v 2.9; P = .01), and days of IV antibiotics (11.8 v 2.4; P = .007) per cycle. Significant increases in the weekly dose intensity (206 v 285 mg/m2/wk; P = .014) and total dose (2,287 v 3,600 mg/m2; P = .018) of carboplatin delivered were also observed with treatment B. The overall response rate in this study was 70%, with 11 of 16 assessable patients achieving either a complete (three patients) or partial (eight patients) remission. CONCLUSION: This combination of GM-CSF and PBPC infusion represents an effective method for delivering multiple cycles of high-dose carboplatin chemotherapy and may serve as a model for the administration of high-dose chemotherapy in future trials.