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Biomedical subjects

J Crow

Publications and source records attributed to J Crow.

At least 19 recordsLinked to original sources

Relation between human papillomavirus type 16 and potential for progression of minor-grade cervical disease.

We have previously reported that among 200 women referred for colposcopy with smears suggesting mild dyskaryosis, medium or high copy numbers of human papillomavirus type 16 (HPV16) DNA identified patients with current high-grade cervical disease. We have followed up 95 women from that group who had histologically proven mild-grade cervical disease (cervical intraepithelial neoplasia grade 1, n = 37) or wart virus infection (n = 12) or who had no evidence of cervical abnormality at study entry (n = 43). Kaplan-Meier survival analysis of the 70 months' follow-up was used to identify baseline features that might affect the risk of progression. 3 women were lost to follow-up; data were available for the remaining 92. Among the whole group the probability of remaining free of high-grade cervical disease was 0.71. Women with a histological diagnosis of minor-grade disease were more likely to progress to high-grade disease than those with no evidence of abnormality (proportion disease-free 0.52 vs 0.90, p = 0.004). Stratification of the group according to median age (28 years) revealed a weak association between age and disease progression (p = 0.04). There was no difference in disease-free probability between HPV16-positive and HPV16-negative women (0.75 vs 0.65, p = 0.19). Nor was there a significant difference in disease-free probability when the group was stratified by HPV16 viral burden. These data show that a histological diagnosis of minor-grade cervical disease is a better long-term predictor of disease progression than is HPV16 positivity, irrespective of copy number. These findings do not support the simple view that HPV16 alone is the cause of high-grade cervical disease, including cancer.

Adolescent

Mesenteric defects as a cause of intestinal volvulus without malrotation and as the possible primary etiology of intestinal atresia.

Mesenteric defects can lead to intestinal volvulus even when the midgut is normally rotated. There are two types of mesenteric defects: basilar, in which the entire base of the mesentery is involved, and segmental, in which only an isolated portion of the mesentery is affected. These defects can present at any age, and the clinical symptoms depend on the extent of the disease and the amount of intestine involved in the volvulus. In the newborn, the basilar defects have clinical signs and symptoms similar to those of midgut volvulus secondary to malrotation. Similar to midgut volvulus secondary to malrotation, this is a surgical emergency. In older patients, basilar defects can be misdiagnosed because of the normal placement of the ligament of Treitz and because of failure to consider mesenteric defects as a possible cause. The treatment for basilar mesenteric defects is intestinal fixation. Intestinal volvulus secondary to segmental defects always presents as intestinal obstruction. In the newborn, these lesions may be indistinguishable from intestinal atresia. Older children present with intestinal obstruction of an unknown cause. Resection of the affected intestine is the treatment for segmental mesenteric defects. Intestinal mesenteric abnormalities as a cause of intestinal atresia unifies under one etiology all the lesions observed in intestinal atresia. Although this theory does not rule out other causes of intestinal atresia, intestinal mesenteric defects may be the primary condition under which intestinal atresia occurs.

Child

Morphology and ultrastructure of fallopian tube epithelium at different stages of the menstrual cycle and menopause.

The Fallopian tube has been reported to undergo cyclical changes. However, many studies of tubal ultrastructure have either examined one segment of the tube only or studied animal oviducts. The aim of this study was to document in detail the combined morphological and ultrastructural features of the epithelial lining along the length of the tube in women at different stages of the menstrual cycle. We report an increase in the proportion of ciliated cells along the tube, being highest in the fimbriae, but no substantial difference between the follicular and luteal phases of the menstrual cycle. In the late follicular phase, fragments of cytoplasmic and cellular material were seen in the isthmic lumen but not in the outer tubal segments. Similarly, surface domes and secretory granules were more prominent in the mid-tube and ampullary sections than in the fimbriae. This surface activity was followed by relative quiescence in the early/mid luteal phase with reversion to a more active surface but with little secretory activity in the late luteal phase. These findings along the Fallopian tube substantiate the concept of functional differentiation between the different segments and necessitate further studies to determine its clinical relevance.

Cytoplasmic Granules

A comparative morphological and ultrastructural study of endometrial gland and fallopian tube epithelia at different stages of the menstrual cycle and the menopause.

Cyclical ultrastructural changes in the endometrium and Fallopian tube have been reported previously but in different subjects. The aim of this study is to compare cyclical changes in endometrial gland and tubal (isthmic, mid-tube, ampulla, and fimbria) epithelia in the same subjects with a view to identifying any similarities or differences which may have clinical implications for assisted reproduction treatment. Endometrial and Fallopian tube samples were obtained from women undergoing hysterectomy and salpingectomy. We report similar epithelial surface changes taking place in the endometrial glandular and endosalpingeal epithelia with the exception of the fimbriae. Secretions within endometrial gland lumen and the isthmus increase throughout the late follicular phase and before ovulation, then dissipate in these two regions simultaneously in the early/mid luteal phase. Similarly, in the late follicular and pre-ovulatory phases, the process of granule secretion is similar in the glandular epithelium, isthmus and ampulla. In the fimbriae, no comparable activity is noted during these phases of the menstrual cycle. The differences reflect the functional differentiation between these regions. Equally, the observed similarities highlight the need for further comparative studies to determine the role of these secretions in early embryonic development and their clinical relevance.

Cytoplasmic Granules

Comparative immunohistochemical study of oestrogen and progesterone receptors in the fallopian tube and uterus at different stages of the menstrual cycle and the menopause.

Oestrogen and progesterone are known to require their corresponding steroid receptors to manifest structural and functional effects in the Fallopian tube, uterus and other target organs. This study compares cyclical variations of these receptors in the uterus and in different segments of the Fallopian tube in the same subjects using an immunocytochemical technique. The results show that in the Fallopian tube, isthmic and ampullary epithelial and stromal oestrogen receptors increased in the follicular phase to a peak at mid cycle and then declined in the late luteal phase. The intensity of immunostaining of oestrogen receptors was less in the Fallopian tube than in endometrial glandular epithelium. The fimbrial end demonstrated an opposite pattern of staining to other segments of the tube. Progesterone receptor immunostaining was more intense than that for oestrogen receptors in the follicular phase, and, whereas it disappeared completely from the endometrial glandular epithelium in the late luteal phase, positive staining was clearly visualized in the tubal epithelium and stroma and endometrial stroma at this stage of the menstrual cycle. These differences in the steroid receptor content may reflect the changing and different functional roles of these regions and may have important implications on human reproduction.

Endometrium

Comparison of cervical cytology and the polymerase chain reaction for HPV 16 to identify women with cervical disease in a general practice population.

A comparison of the ability of cervical cytology and the polymerase chain reaction (PCR) for human papilloma virus type 16 (HPV 16) to identify women with cervical disease has been performed in a general practice population of 249 women, none of whom were believed to have current cervical disease prior to examination. Within this population, 29 women were found by colposcopy and subsequent histopathology to have evidence of cervical disease [5 with cervical intraepithelial neoplasia (CIN) 3; 8 with CIN 2; and 16 with CIN 1]. The prevalence of HPV 16 in this population was 18.9% (CIN 3, 80%; CIN 2, 50%, CIN 1, 12.5%, normal, 16.8%). Women with severe disease (CIN 2 and CIN 3) had a significantly higher incidence of HPV 16 DNA than those with mild cervical disease (CIN 1) or no cervical abnormality (P = 0.001). There was no significant difference in the ability of either PCR for HPV 16 or cytology to identify women with cervical disease. The combination of screening by cytology and the presence of HPV 16 DNA resulted in the identification of a higher proportion of the women with disease, but this observation did not reach statistical significance. Although the failure to detect disease by the two screening methods was similar, HPV 16 DNA positivity was associated with a higher false-positive rate for disease detection than cytology (P less than 0.03). The PCR assay for detecting HPV 16 in this investigation was shown to have a false-positive rate of 2.4% and a false-negative rate of 10.4%. The prospect of screening women for cervical disease using PCR for HPV 16 is discussed.

Adolescent

Mast cells in granulomatous liver disease.

Mast cells are known to be present in normal liver tissue but the data on their association with diseases of the liver are limited. In this study we used a long toluidine blue technique to investigate the mast cell numbers in 20 normal and 45 diseased liver biopsies containing granulomas (20 tuberculosis, 14 sarcoidosis, 4 schistosomiasis, 4 neoplasia-associated, 3 drug idiosyncrasy). Our results show that the mast cells are regular constituents of normal portal tracts and the amount of mast cells in the diseased samples corresponds to the area occupied by non-parenchymal tissues. As compared to normal controls, significantly less mast cells were present in biopsies from tuberculosis patients (p less than 0.025). Highest numbers were found in the schistosomiasis group. No link between the mast cell numbers and the cause of the granulomas could be demonstrated.

Adolescent

Pronuclear, cleavage and blastocyst histories in the attempted preimplantation diagnosis of the human hydatidiform mole.

We report a study of fertilization, syngamy and embryonic development in 14 oocytes from a woman with four previous pregnancies involving complete hydatidiform moles. Serial observations of pronuclear movements and syngamy were compared to those in a group of 10 multipronucleate embryos from other patients. One embryo and possibly two others developed normally or near-normally. The others displayed immediate cleavage or had one or three pronuclei. The tripronucleate eggs displayed various anomalous forms of growth. The unipronucleate eggs passed through a double form of syngamy, which might have involved chromosome doubling, and could have developed as androgenetic diploids. We suggest a hypothesis to explain these unusual observations.

Adult

Hodgkin's disease of the liver; prognosis and possible indications for radiotherapy.

A retrospective analysis of 56 patients presenting with Hodgkin's disease involving the liver between 1970 and 1984 revealed a 10-year survival probability of 44%. The actuarial 10-year continuous progression free survival was 42%. Presentation variables predicting for relapse in the liver included hepatomegaly (P less than 0.025) or focal lesions on isotope, ultrasound or CT scan (P less than 0.01). These factors may define a context for investigation of adjuvant hepatic irradiation following chemotherapy.

Antineoplastic Combined Chemotherapy Protocols

The influence of in-vitro development upon post-thaw survival and implantation of cryopreserved human blastocysts.

Blastocysts from 198 patients were frozen using glycerol as cryoprotectant. No difference in the post-thaw survival of blastocysts or implantation rates was found between 177 patients (122 transfers) with all surplus embryos cultured to blastocysts before freezing and 20 patients (12 transfers) whose embryos were considered unsuitable for freezing during cleavage and were then frozen as blastocysts. Nineteen pregnancies were achieved, of which six aborted. Pre-freezing morphology was similar in blastocysts of patients in groups 1 and 2 and did not relate to their survival after cryopreservation. A significantly lower proportion with suspected damage after thawing was present among patients becoming pregnant after transfers of single blastocysts (P less than 0.01) and implanting embryos were in general more expanded at the time of transfer. No differences were detected between blastocysts resulting in normal development and those leading to abortion. The developmental consequences of damage to human blastocysts are discussed.

Adult

Mast cells in the female genital tract.

Mast cells in the human uterus and adnexa have been studied using basic lead acetate fixation and a long toluidine-blue technique to maximise the numbers of cells stained. Counts were performed on measured areas of tissue and the numbers of mast cells related to clinical and pathologic variables. Considerable variation in numbers was found among individual cases at all the sites studied. In the endometrium and myometrium, a drop in the number of mast cells has been demonstrated with advancing age, particularly after menopause. In leiomyomas the highest counts were in the smaller and more cellular lesions. It is concluded that the numbers of mast cells are at least partly related to the degree of cellularity or atrophy of the surrounding tissues. No significant association was found with menorrhagia or with the presence of leiomyomas.

Adnexa Uteri

Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Results of a randomized trial.

STUDY OBJECTIVE: To determine the efficacy of continuous intravenous infusion of prostacyclin (epoprostenol) in primary pulmonary hypertension. DESIGN: Randomized trial with 8-week treatment periods and nonrandomized treatment for up to 18 months. SETTING: Four referral centers. PATIENTS: Sequential sample of 24 patients with primary pulmonary hypertension. Nineteen patients completed the study. Four patients died and one left the study because of adverse effects (pulmonary edema). INTERVENTIONS: Continuous intravenous prostacyclin administered by portable infusion pump at doses determined by acute responses during baseline catheterization in ten patients. Nine patients were treated with anticoagulants, oral vasodilators, and diuretics. MEASUREMENTS AND MAIN RESULTS: Starting with a baseline value for total pulmonary resistance of 21.6 units, there was a decrease of 7.9 units (95% CI, -13.1 to -2.2; P = 0.022) in the prostacyclin-treated group after 8 weeks; there was virtually no change in the conventional therapy group (from 20.6 to 20.4 units, not significant). Six of ten prostacyclin-treated patients who completed the 8-week study period had reductions in mean pulmonary artery pressure of greater than 10 mm Hg, whereas only one of nine in the conventional treatment group had a similar response (P = 0.057). Nine patients receiving prostacyclin for up to 18 months have persistent hemodynamic effects, although dose requirements have increased with time. Complications have been attributable to the drug delivery system. CONCLUSIONS: Prostacyclin produces substantial and sustained hemodynamic and symptomatic responses in severe primary pulmonary hypertension and may be useful in the management of some patients with this disease.

Adolescent

The influence of extent and local management on the outcome of radiotherapy for brain metastases.

The results of cranial irradiation for brain metastases in 164 consecutive patients have been reviewed to evaluate a policy of localized high dose irradiation for solitary metastases. Fifty of the 164 patients receiving whole brain irradiation (35 Gy in 15 daily fractions) were selected for boosts delivering 15 Gy in 8 daily fractions to the site of solitary deposits. No difference in overall survival or the incidence of death from progressive brain metastases was seen between the patients receiving a boost and those who did not. Overall median survival was 112 days with 62% of patients dying from metastatic disease outside the brain. Factors associated with increased survival were early response to radiotherapy and, in breast cancer patients, a disease-free interval of 2 years. Palliation of presenting symptoms was achieved in 86% of patients at 3 weeks from starting radiotherapy. It is concluded that whereas whole brain irradiation results in useful symptom control, there is no advantage for high dose treatment in the majority of patients with solitary metastases even in the absence of metastatic disease elsewhere.

Adult

Radical radiotherapy for carcinoma of the anal canal.

The treatment of squamous cell carcinoma of the anal canal remains controversial, and recent reports have recommended combined chemotherapy and radiotherapy rather than radiotherapy alone as primary treatment. In order to define the role for more aggressive local therapy we have performed a retrospective analysis on patients with squamous cell carcinoma of the anal canal treated at the Royal Marsden Hospital between 1958 and 1986. Among 42 patients who received radical radiotherapy (RRT) the overall 5-year caused specific survival (CSS) was 52%. Tumour stage and node involvement were the most important prognostic factors. The 5 year CSS were T1 100%, T2 59%, T3 40% and T4 0% (P less than 0.05). The 5-year CSS for node-negative patients was 64% compared to 23% for node-positive patients (P less than 0.095). A minimum tumour dose of 60 Gy in 30 fractions over 6 weeks was essential to achieve local control and was associated with minimal late morbidity and with the retention of anal continence in all patients locally controlled.

Adult

Prostacyclin and acetylcholine as screening agents for acute pulmonary vasodilator responsiveness in primary pulmonary hypertension.

Epoprostenol sodium (prostacyclin) administered intravenously is considered the standard for assessing the ability of the pulmonary circulation to vasodilate. At present, epoprostenol sodium is an investigational drug that has limited availability. In contrast, acetylcholine, also a pulmonary vasodilator, is readily available. Therefore, we assessed the feasibility of using acetylcholine as an alternative to prostacyclin in testing for the capacity of the pulmonary vasculature to vasodilate. Twenty-three patients with primary pulmonary hypertension (mean pulmonary arterial pressure, 58.5 +/- 13.4 mm Hg) received incremental infusions of prostacyclin and acetylcholine to predetermined maximal infusion rates as part of a battery of vasodilator agents administered according to standard protocols (mean, 5.4 +/- 1.2 agents/patient; range, 3-8 agents/patient); the administration of the different agents was timed to avoid synergistic effects. Of all the agents tested, prostacyclin and acetylcholine were most consistently effective in evoking acute pulmonary vasodilation, and both seemed to distinguish patients capable of manifesting acute pulmonary vasodilation from those who were not. However, at maximal doses set by protocol, prostacyclin generally elicited a greater vasodilator response than acetylcholine. The difference in magnitude of response may have been due to use of prescribed dosages of acetylcholine that were submaximal. In other respects, the two agents were similar; both were equally well-tolerated, and side effects were mild and resolved rapidly when the vasodilator infusions were stopped. We conclude that in the majority of patients with primary pulmonary hypertension, acetylcholine appears to be an effective and available substitute for prostacyclin in screening for pulmonary vasodilator responsiveness.

Acetylcholine