Azoospermia and maturation arrest: malfunction of valves in erect poster of humans leads to hypoxia in sperm production site.

Maturation arrest (MA) of spermatogenesis is diagnosed on histology as interruption of spermatogenesis before the final stage without impairment of Sertoli or Leydig cells. It is considered a condition of irreversible or absolute infertility. Varicocele, which represents impairment in the testicular venous drainage system, has been shown to be a bilateral disease. Malfunction of the valves increase the hydrostatic pressure in the testicular venous system that exceeds the pressure in the arterial system leading to hypoxia in the testicular microcirculation and in the seminiferous tubules, the sperm production site. Sperm production deteriorates, and ultimately progresses to azoospermia. Our prediction was that MA, if genetic factors are excluded, is the final stage of long standing hypoxia. This would indicate that MA is not always an independent disease entity, but may represent progressive process of deterioration of the testicular parenchyma beyond azoospermia. By histology and electron microscopy, our prediction confirmed, at least partially, that MA is associated with degenerative ischaemic changes in the seminiferous tubules. Adequate treatment of bilateral varicocele by microsurgery or super-selective sclerotherapy of the internal spermatic veins including associated network of venous bypasses, vertically oriented, may resume the flow of oxygenated blood. If irreversible damages did not occur and ischaemia is not too long standing, limited sperm production may be restored, at least partially.

Azoospermia and Sertoli-cell-only syndrome: hypoxia in the sperm production site due to impairment in venous drainage of male reproductive system.

Sertoli-cell-only (SCO) syndrome, or germ cell aplasia, is diagnosed on testicular biopsy when germ cells are seen to be absent without histological impairment of Sertoli or Leydig cells. It is considered a situation of irreversible infertility. Recent studies have shown that varicocele, a bilateral disease, causes hypoxia in the testicular microcirculation. Destruction of one-way valves in the internal spermatic veins (ISV) elevates hydrostatic pressure in the testicular venules, exceeding the pressure in the arteriolar system. The positive pressure gradient between arterial and venous system is reversed, causing hypoxia in the sperm production site. Sperm production deteriorates gradually, progressing to azoospermia. Our prediction was that, if genetic problems are excluded, SCO may be the final stage of longstanding hypoxia which deteriorates sperm production in a progressive process over time. This would indicate that SCO is not always an independent disease entity, but may represent deterioration of the testicular parenchyma beyond azoospermia. Our prediction is confirmed by histology of the seminiferous tubules demonstrating that SCO is associated with extensive degenerative ischaemic changes and destruction of the normal architecture of the sperm production site. Adequate treatment of bilateral varicocele by microsurgery or by selective sclerotherapy of the ISV resumes, at least partially, the flow of oxygenated blood to the sperm production site and restored sperm production in 4 out of 10 patients. Based on our findings the following statements can be made: (i) SCO may be related in part of the cases to persistent, longstanding testicular parenchymal hypoxia; (ii) germ cells may still exist in other areas of the testicular parenchyma; and (iii) if genetic problems are excluded, adequate correction of the hypoxia may restore very limited sperm production in some patients.

Prostate cancer: a newly discovered route for testosterone to reach the prostate : Treatment by super-selective intraprostatic androgen deprivation.

The prostate, an androgen-regulated exocrine gland, is an integral part of the male reproductive system which has an essential function in sperm survival and motility in its long hostile route to meet and fertilise the egg in the Fallopian tube. Testosterone is known to be the key, obligatory regulator of the prostate that promotes the development and progression of prostate cancer (PCa). Yet, the pathophysiological mechanism of PCa remains unclear and its causal relation to serum testosterone has not been established. Here, we report on the discovery of a previously unrecognized route of flow of free testosterone (FT), at a concentration of 130 times the physiological levels, reaching the prostate via the testicular and prostate venous drainage systems, bypassing the systemic circulation. This condition results from the malfunction of the vertically oriented testicular venous drainage system in humans, a phenomenon with a prevalence that increases rapidly with age, which causes deviation of the testicular venous flow from its normal route. Early results of an interventional radiological procedure, super-selective intraprostatic androgen deprivation therapy are discussed. This treatment has resulted in decrease in prostate volume, and serum PSA, with disappearance of cancerous cells on repeat biopsies in five of six patients. Some of the unresolved biological enigmatic questions associated with PCa are discussed. We conclude that pathological flow of FT from the testes directly to the prostate in an extremely high concentration via the testicular-prostate venous drainage systems was identified may explain the mechanism for the development of PCa. We suggest a time-window for eradication of localised, androgen-sensitive, PCa cells. We anticipate that this treatment may retard, stop or even reverse the development of the disease. A mechanism for the evolution of PCa is discussed.

Reversal of benign prostate hyperplasia by selective occlusion of impaired venous drainage in the male reproductive system: novel mechanism, new treatment.

The prostate is an androgen-regulated exocrine gland producing over 30% of the noncellular components of the semen and promoting optimal conditions for survival and motility of sperm in the vagina. Benign prostate hyperplasia (BPH) is the most common benign neoplasm in men. Its aetiology is not clear, and therefore, current medical treatments are directed towards the symptoms. Though testosterone is known to be the promoter of prostate cell proliferation, no causal relation between serum testosterone levels and BPH has been found. In this study, we propose a novel and tested pathophysiological mechanism for the evolution of BPH and suggest a tested and effective treatment. We found that in all BPH patients, the one-way valves in the vertically oriented internal spermatic veins are destroyed (clinically manifested as varicocele), causing elevated hydrostatic pressure, some 6-fold greater than normal, in the venous drainage of the male reproductive system. The elevated pressure propagates to all interconnected vessels leading to a unique biological phenomenon: venous blood flows retrograde from the higher pressure in the testicular venous drainage system to the low pressure in the prostatic drainage system directly to the prostate (law of communicating vessels). We have found that free testosterone levels in this blood are markedly elevated, with a concentration of some 130-fold above serum level. Consequently, the prostate is exposed to: (i) increased venous pressure that causes hypertrophy; (ii) elevated concentration of free testosterone causing hyperplasia. We have treated 28 BPH patients using a technique that restores normal pressure in the venous drainage in the male reproductive system. The back-pressure and the back-flow of blood from the testicular to the prostate drainage system were eliminated and, consequently, a rapid reduction in prostate volume and a regression of prostate symptoms took place.

Is varicocele prevalence increasing with age?

Varicocele is a bilateral vascular disease which occurs when the one-way valves in the internal spermatic veins, the testicular venous drainage system, malfunction. Based on new findings and fluid-mechanics analysis we showed that this process results in vertical blood columns, which cause pathological hydrostatic pressure in the testicular venous microcirculatory system. Ultimately, these pressures exceed the pressure in the arteriolar system. This unique phenomenon of reversal of pressures gradient between the arteriolar and venular systems leads to persistent hypoxia in the testosterone production site, namely, the Leydig cells. The result of bilateral varicocele is decreased testosterone production. Adequate treatment of bilateral varicocele significantly elevates the testosterone production. We found that the prevalence of varicocele increases with age with a rise of about 10% for each decade of life with the incidence reaching 75% in the eight decade of life. Based on our findings the following statements can be made: (1) varicocele prevalence is increased over time. (2) The rise of the incidence is about 10% for each decade of life. (3) 75% of men in the eight decade of their life have varicocele. As varicocele decreases testosterone production and it is reversible by appropriate treatment, it raises two interesting and important issues to be studied: (i) it is possible that varicocele accelerates the process of the ageing male. (ii) It is possible to retard, at least partially, the process of ageing in men by adequate treatment of bilateral varicocele.

Effect of normal ageing on the sites of aortic bifurcation and inferior vena cava confluence: a CT study.

The object of this retrospective study was to determine the sites of abdominal aortic bifurcation and inferior vena cava confluence in relation to age and sex. The study group comprised 180 subjects (90 males and 90 females) divided into 9 groups by age (in decades). The positions of the aortic bifurcation and the inferior vena cava confluence were evaluated by CT, and linear regression models were fitted to the data. The positions of the aortic bifurcation and venous confluence showed a highly significant downward shift with increasing age (p = 0.0001). The shift was more pronounced in women. The mean site of the aortic bifurcation for the whole group was at lower L4 (range, upper L3 to upper S1); in males, it was at upper L4 (range, upper L3 to upper L5), and in females at lower L4 (range, upper L3 to upper S1). The mean site of the venous confluence for the whole group was at disc L4-L5 (range, lower L3 to upper S1); in males, it was at disc L4-L5 (range, upper L4 to disc L5-S1), and in females at disc L4-L5 (range, lower L3 to upper S1). Thus, the aorta and the inferior vena cava can extend as low as the level of S1. These data are of relevance in laparoscopic procedures, especially in laparoscopic lumbar discectomy.

Intravenous immunoglobulin treatment in multiple sclerosis. Effect on relapses.

We conducted a double-blind, placebo-controlled study of 40 patients (aged 19 to 60 years) with clinical definite relapsing remitting (RR) MS and brain MRI confirmed. Patients were randomly assigned to receive a loading dose of immunoglobulin IgG (0.4 g/kg/body weight per day for 5 consecutive days), followed by single booster doses (0.4 g/kg/body weight) or placebo once every 2 months for 2 years. The primary outcome measures were change in the yearly exacerbation rate (YER), proportion of exacerbation-free patients, and time until first exacerbation. Neurologic disability, exacerbation severity, and changes in brain MRI lesion score were the secondary outcome measures, all determined at baseline, 1 year, and on completion. Treated patients showed a reduction in YER from 1.85 to 0.75 after 1 year and 0.42 after 2 years versus 1.55 to 1.8 after 1 year and to 1.4 after 2 years in the placebo group (p = 0.0006, overall), reflecting a 38.6% reduction in relapse rate. Six patients in the IVIg group were exacerbation free throughout the 2-year period of the study, whereas none were exacerbation free in the placebo group. The median time to first exacerbation was 233 days in the IVIg group versus 82 days in the placebo group (p = 0.003). Neurologic disability as measured by the Expanded Disability Status Scale (EDSS score) decreased by 0.3 in the IVIg group and increased by 0.15 in the placebo group. Total lesion score evaluated by brain MRI did not show a significant difference between groups. Side effects were minor and occurred in only 19 of 630 (3.0%) infusions administered in both groups. Our results suggest that IVIg may be safe and effective in reducing the frequency of exacerbations in RR-MS.

[Malignant epidural cord compression].

Malignant epidural spinal cord compression (MSCC) may appear in 5-10% of adults and 3-5% of children with active malignant disease. Early diagnosis and treatment are imperative to prevent irreversible neurological damage below the level of cord compression. Unfortunately such procedures are often subjected to patient and/or doctor delay, when the emergency nature of MSCC is not understood. 3 women and 2 men, aged 17-74, are described, who illustrate both the variability of the presentation of MSCC and of its clinical course, and also problems related to imaging studies necessary to reach appropriate therapeutic decisions. These cases should increase physicians' awareness of the necessity for its early diagnosis and treatment. In addition, it is suggested that a multidisciplinary team approach be followed when MSCC is suspected (in accord with flow chart in Hebrew text).

Atypical skeletal tuberculosis.

Tuberculosis remains a major cause of skeletal infection in many parts of the world. With the advent of acquired immune deficiency syndrome (AIDS) and mass emigration from underdeveloped to industrialized nations this past decade, a new patient population is being encountered in which extrapulmonary tuberculosis is not uncommon and atypical presentations may confuse the diagnosis. Our recent experience with an unusual presentation has prompted this report.

Progressive spinocerebellar degeneration "plus" associated with Langerhans cell histiocytosis: a new paraneoplastic syndrome?

Langerhans cell histiocytosis (LCH), formerly known as histiocytosis-X, manifests by granulomatous lesions consisting of mixed histiocytic and eosinophilic cells. The hallmark of LCH invasion into the CNS is diabetes insipidus, reflecting local infiltration of Langerhans cells into the posterior pituitary or hypothalumus. In five patients who had early onset LCH with no evidence of direct invasion into the CNS, slowly progressive spinocerebellar degeneration accompanied in some by pseudobulbar palsy and intellectual decline was seen. Neurological impairment started 2.5 to seven years after the detection of LCH. No correlation was found between the clinical syndrome and location of LCH or its mode of treatment. An extensive search for metabolic, toxic, neoplastic, and hereditary aetiologies for progressive cerebellar degeneration was negative. It seems that the clinical entity described here may be considered a new paraneoplastic syndrome related to LCH. It may be induced by the eosinophil derived neurotoxin, which was shown to cause damage to Purkinje cells and pyramidal neurons.

Meningiomas of the anterior cranial fossa floor. Review of 67 cases.

The authors report 67 cases of meningioma of the anterior cranial fossa floor treated surgically between 1978 and 1992. The olfactory groove and tuberculum sellae were the most frequent locations. Mean duration of the clinical history was 30 months. Seventy-three percent of the tumors were large (> 4 cm). All patients were examined with computed tomography and 18 with magnetic resonance imaging as well. Complete removal was performed in 56 cases (84%); in the remaining 11 (16%), partial removal was performed because of encasement of the carotid artery, cavernous sinus, or optic nerves by the tumour. Mortality was 9%. Results at follow-up of the 61 survivors were good in 56 (84%), fair in four (6%), and poor in one (1%). The clinical results were correlated to tumor location and dimension. After review of the literature, the management of these difficult tumours and the preferred surgical technique are discussed. The authors stress the importance of early diagnosis for improving the surgical results.

Brain imaging in late-onset GM2 gangliosidosis.

We describe brain CT and MRI characteristics of 10 patients with late-onset GM2 gangliosidosis. Cerebellar atrophy, particularly of the vermis, was a prominent feature in all patients with normal-appearing cerebral hemispheres. The severity of these findings did not correlate with the age of onset, disease duration, severity of neurologic impairment, or mode and distribution of the various clinical presentations. In particular, no cerebral abnormality was found by neuroimaging in seven patients with intellectual decline and in six patients with recurrent psychosis, while prominent cerebellar atrophy was present in the only patient who was free of cerebellar signs.

The value of precise preoperative localization of colonic arteriovenous malformation in childhood.

Massive hemorrhage from the gastrointestinal tract in a 12-yr-old boy caused by a congenital atypically located colonic arteriovenous malformation is described. Guided and "clean" resection of the involved colon was possible due to preoperative selective angiography, which proved to be the most efficient diagnostic tool. Histologic documentation of this rare pathology in childhood is presented, and the classification and features of the disease are briefly reviewed.

Lupus anticoagulant: correlation with magnetic resonance imaging of brain lesions.

Brain magnetic resonance imaging (MRI) was performed in 21 patients with systemic lupus erythematosus (SLE) with and without lupus anticoagulant (LAC), one lupus-like patient and 5 patients with primary antiphospholipid antibody syndrome. Thirteen patients had white matter focal brain lesions on MRI, 10 of whom had LAC (p = 0.03). We found no correlation between these lesions and neurologic manifestations, nor any clinical or serologic indices of activity of SLE. Our MRI lesions were similar to those described in multiple sclerosis and may indicate a similar pathologic process.

Epignathus. Case report of long-term survival with no surgery.

Clinical and radiological features of an epignathus of the soft palate and oropharynx are presented. The case was conservatively treated and followed for 8 years.

Internal carotid artery thrombosis after blunt maxillofacial trauma.

Two cases of internal carotid artery thrombosis associated with a maxillary Le Fort III and mandibular angle fractures after maxillofacial blunt injuries are described. Both patients had delayed neurologic deficit and hemiparesis. The diagnosis was made by carotid angiography after clinical evidence of thromboembolism. Clinical aspects and etiology, with special attention to mechanism of injury, are discussed.

Cerebral sinus thrombosis as a potential hazard of antifibrinolytic treatment in menorrhagia.

We describe a 42-year-old woman who developed superior sagittal and left transverse sinus thrombosis associated with prolonged epsilon-aminocaproic acid therapy for menorrhagia. This antifibrinolytic agent has been used in women with menorrhagia to promote clotting and reduce blood loss. Although increased risk of thromboembolic disease has been reported during treatment with epsilon-aminocaproic acid, cerebral sinus thrombosis has not been previously described. Careful use of epsilon-aminocaproic acid therapy is recommended.