Influence of different hormonal regimens on endometrial microvascular density and VEGF expression in women suffering from breakthrough bleeding

BACKGROUND: The aim of this study was to quantify blood vessel density (BVD) and immunoreactive vascular endothelial growth factor (VEGF) levels in endometrial biopsies taken from women suffering breakthrough bleeding (BTB) under different exogenous hormonal regimes. METHODS: Endometrial biopsies from women in Melbourne with BTB were divided into four groups: combined-continuous hormone therapy (HT) (estrogen and progestin taken daily), cyclical HT (daily estrogen with progestin for 14 days each cycle), progestin-only, or no HT. Subjects from Barcelona were using the Mirena intrauterine levonorgestrel-releasing system for contraceptive purposes, with menstrual diaries for classification into four groups (amenorrhea, infrequent, regular and prolonged). Control biopsies from Melbourne were included in the study. Endometrial samples were immunostained for VEGF and blood vessel localization using an antibody to CD34. RESULTS: Results showed that BVD was significantly reduced in the progestin-only treated group compared with the other three treatment groups (P = 0.028). In addition, all four Mirena BTB groups had significantly reduced BVD compared with controls. Considerable heterogeneity was observed in VEGF immunostaining within and between individual samples with no major differences between HT or Mirena. CONCLUSION: These results provide strong evidence that unopposed progestins reduce endometrial BVD and that there is no link between VEGF immunostaining and BVD or BTB.     

Methodology to predict long-term cancer survival from short-term data using Tobacco Cancer Risk and Absolute Cancer Cure models

Three parametric statistical models have been fully validated for cancer of the larynx for the prediction of long-term 15, 20 and 25 year cancer-specific survival fractions when short-term follow-up data was available for just 1-2 years after the end of treatment of the last patient. In all groups of cases the treatment period was only 5 years. Three disease stage groups were studied, T1N0, T2N0 and T3N0. The models are the Standard Lognormal (SLN) first proposed by Boag (1949 J. R. Stat. Soc. Series B 11 15-53) but only ever fully validated for cancer of the cervix, Mould and Boag (1975 Br. J. Cancer 32 529-50), and two new models which have been termed Tobacco Cancer Risk (TCR) and Absolute Cancer Cure (ACC). In each, the frequency distribution of survival times of defined groups of cancer deaths is lognormally distributed: larynx only (SLN), larynx and lung (TCR) and all cancers (ACC). All models each have three unknown parameters but it was possible to estimate a value for the lognormal parameter S a priori. By reduction to two unknown parameters the model stability has been improved. The material used to validate the methodology consisted of case histories of 965 patients, all treated during the period 1944-1968 by Dr Manuel Lederman of the Royal Marsden Hospital, London, with follow-up to 1988. This provided a follow-up range of 20-44 years and enabled predicted long-term survival fractions to be compared with the actual survival fractions, calculated by the Kaplan and Meier (1958 J. Am. Stat. Assoc. 53 457-82) method. The TCR and ACC models are better than the SLN model and for a maximum short-term follow-up of 6 years, the 20 and 25 year survival fractions could be predicted. Therefore the numbers of follow-up years saved are respectively 14 years and 19 years. Clinical trial results using the TCR and ACC models can thus be analysed much earlier than currently possible. Absolute cure from cancer was also studied, using not only the prediction models which incorporate a parameter for a statistically cured fraction of patients C(SLN), C(TCR) and C(ACC), but because of the long follow-up range of 20-44 years, also by complete life analysis. The survival experience of those who did not die of their original cancer of the larynx was compared to the expected survival experience of a population with the same age, birth cohort and sex structure. To date it has been generally assumed for early stage disease that although for some 5-10 years after treatment the survival experience of this patient subgroup might be no different from that expected in the matched group, thereafter the death rate of this subgroup becomes lower than that of the matched group. This implies that surviving cancer patients cured of their disease tend to die of other conditions at a higher than normal rate as they become older, and therefore cancer is never totally cured. Our conclusion is that at least for cancer of the glottic larynx, the answer to the question: 'Can cancer totally be cured?' is 'Yes to at least 15-years post-treatment and also probably to 25 years.'     

Robert Schumann

Robert Schumann, one of the giants of early romantic music, was born in Saxony in 1810 and died in an asylum shortly after his 46th birthday. Early in life, he demonstrated extraordinary skills in both music and journalism; he remained active in both areas until his final illness. His marriage to the remarkable pianist, Clara Wieck, provided him with both much-needed emotional support and a highly effective champion of his music throughout her lengthy career. Schumann's plans to be a concert pianist were thwarted at least partially by an injury to his right hand, the nature of which has been the subject of much speculation. After considering what few facts are available, the author concludes that this may have represented focal dystonia. His compositional output waxed and waned dramatically over his professional life, reflecting to some degree his emotional state. It is considered most likely that he suffered from a major affective disorder, bipolar type. This ultimately led to a suicide attempt in February 1854, and to his eventual death in July 1856. Despite wide-spread and reasonable suspicion that he may have died from neurosyphilis, severe malnutrition from self-starvation seems more likely.     

Deletions in the ligand for CD40 in X-linked immunoglobulin deficiency with normal or elevated IgM (HIGMX-1)

Patients with X-linked Ig deficiency with normal or elevatedIgM (HIGMX-1) fail to switch from IgM/IgD to other Ig isotypes.Interaction between the B cell antigen CD40 and the CD40 ligandexpressed on activated T cells is critical for T cell drivenisotype switching. We have reported that T lymphocytes fromthree unrelated male patients with HIGMX-1 failed to expressCD40 ligand on their surface, but the mRNA for CD40 ligand wasof an apparently normal size and level. Analysis of CD40 ligandcDNA from two of the patients revealed deletions that alterthe reading frame. Patient 1 displayed two mutations: a C Atransversion at nucleotide 590 and the deletion of an adjacentC nucleotide. The second patient had a 58 bp deletion from nucleotides289–346. Furthermore, neither patient expressed a proteinproduct detectable by the CD40L mAb, 5c8.     

Does acupuncture treatment affect sperm density in males with very low sperm count? A pilot study

Classic therapies are usually ineffective in the treatment of patients with very poor sperm density. The aim of this study was to determine the effect of acupuncture on these males. Semen samples of 20 patients with a history of azoospermia were examined by light microscope (LM) and scanning electron microscope (SEM), with which a microsearch for spermatozoa was carried out. These examinations were performed before and 1 month after acupuncture treatment and revealed that the study group originally contained three severely oligoteratoasthenozoospermic (OTA), two pseudoazoospermic and 15 azoospermic patients. The control group was comprised of 20 untreated males who underwent two semen examinations within a period of 2-4 months and had initial andrological profiles similar to those of the experimental group. No changes in any of the parameters examined were observed in the control group. There was a marked but not significant improvement in the sperm counts of severely OTA males following acupuncture treatment (average = 0.7 +/- 1.1 x 10(6) spermatozoa per ejaculate before treatment vs. 4.3 +/- 3.2 x 10(6) spermatozoa per ejaculate after treatment). A definite increase in sperm count was detected in the ejaculates of 10 (67%) of the 15 azoospermic patients. Seven of these males exhibited post-treatment spermatozoa that were detected even by LM. The sperm production of these seven males increased significantly, from 0 to an average of 1.5 +/- 2.4 x 10(6) spermatozoa per ejaculate (Z = -2.8, P < or = 0.01). Males with genital tract inflammation exhibited the most remarkable improvement in sperm density (on average from 0.3 +/- 0.6 x 10(6) spermatozoa per ejaculate to 3.3 +/- 3.2 x 10(6) spermatozoa per ejaculate; Z = -2.4, P < or = 0.02). Two pregnancies were achieved by the IVF-ICSI procedure. It is concluded that acupuncture may be a useful, nontraumatic treatment for males with very poor sperm density, especially those with a history of genital tract inflammation.     

Stapled diverticulectomy for solitary caecal diverticulitis

Caecal diverticulitis is an uncommon phenomenon in western countries. The clinical diagnosis is often difficult as it mimics other acute abdominal conditions like appendicitis, colitis or neoplasia. Diagnosis is often made at operation. Operative strategy has been controversial and there is no broad consensus emerging. We report the case of a 71-year-old woman, known to have chronic obstructive pulmonary disease, who presented acutely with right iliac fossa pain. A clinical diagnosis of appendicitis was made. At laparoscopy, a solitary, inflamed, gangrenous caecal diverticulum was found. A laparoscopic stapled diverticulectomy was performed. The patient made a steady post-operative recovery. Histology confirmed diverticulitis. We conclude that stapled diverticulectomy for solitary caecal diverticulitis is a safe and effective surgical strategy when confronted with this scenario.     

Editor's Introduction to Recollections of Pioneers in Nutrition

In July 1990, new guidelines for nutrition during pregnancy were published by the National Academy of Sciences. The Subcommittee on Weight Gain During Pregnancy revised the weight gain recommended for pregnancy. During the process of developing new recommendations, the subcommittee considered several factors that might help to determine the appropriate weight gain for an individual pregnant woman. Some of these factors include demographic and biological changes that might influence the effect of weight gain. Clinical issues that must be considered in implementing the weight gain recommendations include the importance of accurate weight and height measurement, categorizing the woman's weight for height, determining rate of gain at different times during pregnancy, and evaluating the significance of deviations from the expected weight gain pattern. A review of prior studies reveals that body composition changes, which might be important to consider in conjunction with weight changes, have not been well studied. Data are presented from a current study that indicates the problems encountered if traditional methods of body composition measurement are used during pregnancy.     

Pulmonary arterial hypertension and its association with HIV infection: an overview

There has been substantial progress in our understanding of the pathogenesis and clinical consequences of infection with HIV since the virus was first identified more than 20 years ago. The details of the viral replication cycle are increasingly better understood as are the identification of host elements that both regulate viral replication and are necessary for it. Greater understanding of these events has resulted in the development of therapies for HIV infection and as a consequence there has been a dramatic improvement in overall survival in the era of HAART. With this improvement in survival has come an increasing recognition of the importance of many long-term sequelae of subclinical immune deficiency and the attendant immune activation that characterize HIV infection. One complication of chronic HIV infection for which the pathogenesis is obscure is pulmonary arterial hypertension (PAH). Cases of HIV-related PAH (PAH-HIV) have been recognized with increasing frequency in recent years. Although it is likely that PAH-HIV has an underlying etiology specifically related to HIV infection, it shares several key clinical and pathological similarities with other forms of PAH. This article outlines the features, classification and treatment of PAH, and recent theories about the underlying etiology of the disease. We will also discuss the occurrence of PAH in HIV infection and propose some hypotheses regarding pathogenesis that will be covered in more detail in the accompanying articles in this supplement.