Idiopathic retroperitoneal fibrosis. A retrospective analysis of 60 cases

Sixty patients with idiopathic retroperitoneal fibrosis presenting between 1965 and 1984 are reviewed. Their mean age at presentation was 56 years and the male:female ratio was 3:1. The commonest presenting symptoms were flank and abdominal pain, weight loss, nausea and polyuria. Physical examination was usually normal, expect for the presence of hypertension. Anaemia and elevation of erythrocyte sedimentation rate were usually present. Proteinuria was found in less than a third of patients at presentation and significant bacteriuria was uncommon. The correct diagnosis was made or suspected in very few patients before referral. The cumulative actuarial survival rate was 86% at 1 year and 78% at 2 years. Seventeen patients died; they were significantly older and more uraemic at the time of referral than those who survived. A few patients did well with either corticosteroid therapy or ureterolysis alone. In the majority, both operation and steroid treatment were necessary. In bilateral obstruction with residual function in both kidneys, bilateral ureterolysis proved superior to unilateral operation (each followed by steroid therapy) in conserving renal function. Operation alone or steroid therapy alone should be considered in cases where steroids or surgery respectively present particular hazards. The less traumatic unilateral operation should be considered in poor risk patients and in those whose renal function is absent on one side. In many survivors, disease activity has persisted for many years. Life-long follow-up is recommended.     

Effects of left varicocele ligation in subfertile males with absent or atrophic right testes.

Fifteen subfertile males with absent or atrophic right testes underwent ligation of left varicoceles. Sperm concentration rose significantly with correction of scrotal thermographic abnormality and nine wives (60%) became pregnant.     

Detection and treatment of antispermatozoal antibodies in men

Autoimmunity to spermatozoa results in the production of antisperm antibodies that usually reduce the fertility of human males. Many laboratory tests have been devised to detect antisperm antibodies, but the results of such tests do not always correlate well with each other, particularly when the tests are conducted with patients' own spermatozoa rather than donor sperm. Experience over the past 12 years at Chelsea Hospital for Women and St Bartholomew's Hospital in London has led to at Chelsea Hospital for Women and St Bartholomew's Hospital in London has led to the development of an effective method for testing and treating subfertile males. This involves using the mixed antiglobulin reaction test and the post-coital test as initial screening tests, followed by serum and seminal plasma agglutination tests (both gelatin and tray) and the sperm-cervical mucus contact tests. Suitable patients are then put on one of three steroid regimens--long-term low-dose prednisolone, intermittent high-dose methylprednisolone, or intermediate graduated-dose prednisolone. Such treatment is useful not only in cases of spontaneous autoimmunity, but also in cases involving genital infection, testicular obstruction, and in vitro fertilization or gamete intrafallopian transfer.     

The myocardial contractile responses to protamine sulfate and heparin

The administration of protamine sulfate for the reversal of heparin anticoagulation has been associated with adverse hemodynamic changes including hypotension and decreased cardiac output. The possible direct toxic effect of protamine on human right atrial trabeculae contracting isometrically in vitro was studied. Muscles were stimulated to contract at 1 Hz in Tyrode's solution (maintained at 34 degrees C, pH 7.4) into which protamine was continuously added. Following a polynomial regression analysis, a parabolic dose-response curve resulted. The equation was: y = 95.13 + 38.76x - 278.71x2 where y = relative developed force and x = concentration of protamine (milligrams per milliliters) (r = 0.82). The estimated concentration of protamine resulting in 50% developed force was 0.48 mg/ml. In a second series of experiments, protamine was added to the bath along with a neutralizing amount of heparin. This resulted in a limited reduction in the fall of relative developed force. Thus, protamine in high concentrations alone or in complex with heparin has a direct toxic effect on human myocardial muscle mechanics, and care is warranted in its clinical use.     

The radiosensitivity of populations of murine hemopoietic colony-forming cells that respond to combinations of growth factors

Combinations of murine recombinant interleukin 3 (IL-3), purified murine macrophage colony-stimulating factor (M-CSF), and human recombinant interleukin 1 alpha (IL-1 alpha) were used to determine the effects of growth factors on the measured radiosensitivity of different populations of murine colony-forming cells (CFC). The data showed that combinations of growth factors resulted in different values of CFC radiosensitivity, being less than values observed when colony growth was stimulated using a single factor. For various combinations of growth factors, Do values ranged from 106 +/- 8 to 175 +/- 24 cGy for progenitor cells in normal bone marrow; 74 +/- 3 to 171 +/- 18 cGy for primitive multipotent CFC enriched using fluorescence-activated cell sorting; and from 46 +/- 4 to 131 +/- 10 cGy for more mature granulocyte-macrophage CFC, enriched by counterflow centrifugal elutriation. Only combinations of three factors produced the high values of Do reported in experiments using unpurified conditioned medium as a stimulus for colony formation.     

Seminal analysis after orchiectomy in stage I teratoma

Seminal analysis was performed within 2 months of orchiectomy on 97 patients with clinical Stage I malignant testicular teratoma managed by surveillance following orchiectomy. Relapse of malignant disease occurred in 28% of 47 patients with a sperm count less than 10 X 10(6)/ml and in 32% of 50 patients with a sperm count greater than or equal to 10 X 10(6)/ml. Of 11 patients with azoospermia, 4 relapsed and 1 developed contralateral testicular germ cell tumour. Of 35 patients with malignant teratoma undifferentiated the relapse rate was 68% in 16 patients with a sperm count less than 10 X 10(6)/ml and 42% in 19 patients with a sperm count greater than or equal to 10 X 10(6)/ml. It was concluded that sperm count analysis is non-contributory in estimating the risk of relapse in clinical Stage I teratoma.     

Binding and retrograde transport of leukemia inhibitory factor by the sensory nervous system.

Leukemia inhibitory factor (LIF), a peptide growth factor with multiple activities, has recently been shown to support the generation and survival of sensory neurons in cultures of mouse neural crest and dorsal root ganglia (DRG). We have conducted binding experiments with 125I-LIF on cultures of DRG to determine the receptor distribution for LIF on these cells and found that at least 60% of the sensory neurons in the cultures bound 125I-LIF, all of which could be eliminated by the addition of unlabeled LIF. The other cells in the culture, which morphologically appeared to be Schwann cells, did not bind appreciable quantities of 125I-LIF. In order to investigate whether LIF is retrogradely transported to sensory neurons in vivo, 125I-LIF was injected into the footpads and gastrocnemius muscles of newborn and adult mice, following sciatic nerve ligation. Radioactivity accumulated in the distal portion of the sciatic nerve, indicating retrograde transport of LIF. Subsequent experiments on mice with unligated sciatic nerves showed that 125I-LIF is specifically transported into the sensory neurons of the DRG. There was no apparent transport of 125I-LIF into motor neurons in the spinal cord. These experiments demonstrate that LIF can specifically bind to and be transported by sensory neurons and further support the idea that LIF acts as a target-derived neurotrophic factor, analogous to NGF.     

A monoclonal antibody to a parasympathetic neurotrophic factor causes immunoparasympathectomy in mice

A monoclonal antibody capable of blocking the biological activity of the ciliary neurotrophic factor purified from bovine cardiac muscle has been produced. This antibody, when administered perinatally to mice, causes a failure of the normal development of the parasympathetic innervation of the iris as determined by assay for the activity of the cholinergic marker enzyme choline acetyltransferase. The same treatment has no effect on the adrenergic neuronal marker, tyrosine hydroxylase. This immunoparasympathectomy suggests that the ciliary neurotrophic factor has an essential role in regulating the development of the mammalian parasympathetic nervous system.     

Human myocardial responses to antibiotics: gentamicin, tobramycin and cephalothin

Although myocardial toxicity of certain antibiotics has been suggested by animal studies, their effects on human cardiac muscle has not been established. Accordingly, human right atrial trabeculae contracting isometrically in vitro were exposed to increasing doses of the antibiotics gentamicin, tobramycin and cephalothin. Contractile responses were measured and dose-response curves calculated by a polynomial regression analysis. All three antibiotics demonstrated a dose-related decrease in relative developed force although resting force remained constant. Concentrations of gentamicin, tobramycin and cephalothin that caused 50% depression of developed force were 1.97, 1.92 and 52.75 mg/mL, respectively. These doses were 200, 200 and 2600 times the accepted serum toxic concentrations for gentamicin, tobramycin and cephalothin, respectively. The depression caused by cephalothin is probably related to ionic changes within the bath solution. In conclusion, gentamicin and tobramycin have myocardial toxicity at high concentrations which should not occur clinically when used judiciously.     

3,5-甾二烯化合物的合成及抗早孕活性

以18-甲基-17β-羟基-17α-乙炔基-雌甾-4-烯-3-酮(18-甲基炔诺酮),17β-羟基-17α-乙缺基-雌甾-4-烯-3-酮(炔诺酮),17β-羟基-17α-乙炔基-雄甾-4-烯-3-酮(妊娠素)和17a-羟基孕甾-4-烯-3,20二酮(17α-羟基黄体酮)为原料,经NaBH,还原、脱水、双键转位和酯化等反应合成一系列3,5-甾二烯化合物,用¹HNMR和MS证明了它们的结构。动物筛选结果表明,17β-丙酰氧基-17α-乙炔基-雌甾-3,5-二烯(IV_b2有明显的抗早孕活性。中断早期妊娠的作用似与其雌激素活性有关。