Repreoducibility of a method for a graded stenosis in tubes and vessels of small calibres. An in vitro and in vivo experiment.

The reproducibility of a previously described method for graded stenosis has been tested in a model experiment and by repeated stenosis of the portal vein in rats. In the model experiment, the method was tested in terms of flow variations; in the animal experiment, in terms of prestenotic pressure variations. In the model experiment, the coefficient of variation in repeated stenosis was less than 3%. In the animal experiment, repeated stenosis constantly produced the same high level of pressure. The present method is discussed in relation to a theoretical optimal standard and found to be satisfactory.     

Thymectomy in nonthymoma early-onset myasthenia gravis in correlation with disease severity and muscle autoantibodies

OBJECTIVE: To study the clinical effect of thymectomy in a well-defined early-onset MG subgroup and to correlate it to MG severity, the presence of circulating muscle autoantibodies, and the need for pharmacological treatment in a long-term setting. METHODS: Fifty-two consecutive AChR antibody-positive early-onset MG patients (34 thymectomized and 18 nonthymectomized) were included. Severity was assessed and the pharmacological treatment monitored on a yearly basis, starting from the year of MG onset, for 5, 10, 15, and 20 consecutive years; AChR, titin, and RyR antibodies were assayed. RESULTS: In the four follow-up groups, MG severity was significantly higher in nonthymectomized compared to thymectomized MG patients. The postthymectomy MG improvement was significant and persistent. There were 21/34 remissions in thymectomized patients and only 4/18 in the nonthymectomized group. Patients with initially high or low AChR antibody concentration had a similar thymectomy outcome. Only 6 patients had titin antibodies, and none had RyR antibodies. CONCLUSION: The present study indicates a benefit of thymectomy in early-onset MG. The muscle autoantibody concentration does not influence the outcome of thymectomy in early-onset MG.     

Splanchnic extraction of oestrone and oestradiol and production of oestrone sulphate in man

The plasma concentrations of oestrone (Oe1), oestradiol (Oe2) and oestrone sulphate (Oe1S) were measured in the femoral artery (FA), femoral vein (FV) and hepatic vein (HV) in seven men and three postmenopausal women undergoing catheterization for the evaluation of cardiac arrhythmias. None of the persons had congestive heart failure; conventional liver function tests were normal, and they were without any medication. The plasma concentration (mean +/- SD) for Oe1 was 34.6 +/- 19.5 pM in HV, 134 +/- 71.6 pM in FV and 93.4 +/- 48.5 pM in FA. The plasma concentration of Oe2 was 29.9 +/- 19.7 pM in HV, 80.3 +/- 42.7 pM in FV and 55.2 +/- 28.1 pM in FA. The results support the concept of peripheral formation of Oe1 and Oe2 and hepatic removal. The plasma concentration of Oe1S was 980 +/- 469 pM in HV, 945 +/- 463 pM in FV and 937 +/- 461 pM in FA. The small difference in plasma level of Oe1S between FA and FV was insignificant. In all persons the plasma level of Oe1S was higher in HV than in FA and FV (2P less than 0.01) indicating a net formation of Oe1S in the splanchnic area.     

Evaluation of new serum and urine tests in cases of suspected pathologic early pregnancy

Two pregnancy tests, ModEL serum hCG Assay and ModEL Urine hCG Assay, were evaluated using sera and urine from 46 patients suspected of pathologic early pregnancy, of whom 22 patients had spontaneous abortion and 9 an ectopic pregnancy. ModEL Serum hCG Assay had a 100% sensitivity and specificity, thus demonstrating its value in these cases. With a sensitivity of 94% and a specificity of 87%, ModEL Urine hCG Assay gave poorer results. Both tests have a relative high "detection limit" of 25 U/l (serum) and 50 U/l (urine) which may impair their ability to distinguish between presence and absence of pregnancy by very low levels of hCG.     

Maturity-onset diabetes of the young. Studies in a Norwegian family

A Norwegian family showed 20 cases of verified or suspected diabetes in 5 generations, 13 being females and 7 males. In 12 patients the diagnosis was established at 26 years of age or earlier. Fourteen patients were definitely non-insulin-dependent. A high frequency of severe diabetic ophthalmopathy was noted, five patients were blind, two had proliferative retinopathy, and one simplex retinopathy and cataract. Five patients from the last 3 generations were islet cell antibody negative and C-peptide positive. In selected patients the serum insulin response to oral glucose was markedly reduced. HLA determinations in these patients showed absence of DR3 and DR4, and presence of DR2. The inheritance of diabetes in this family is compatible with an autosomal, dominant trait, and the majority of cases fulfilled the criteria of maturity-onset diabetes of the young. The high frequency of severe ophthalmopathy underscores that this disease may have an unfavourable evolution.     

A community-based long-term follow up of women undergoing obstetric fistula repair in rural Ethiopia

Objectives  To assess urinary and reproductive health and quality of life following surgical repair of obstetric fistula.
Design  Follow-up study.
Setting  A newly established fistula clinic (2004) at Gimbie Adventist Hospital, a 71-bedded district general hospital in West Wollega Zone, in rural Western Ethiopia.
Population  Thirty-eight women (86%) of 44 who had undergone fistula repair were identified in their community.
Methods  Community-based structured interviews 14–28 months following fistula repair, using a customised questionnaire addressing urinary health, reproductive health and quality of life.
Main outcome measures  Urinary health at follow up was assessed as completely dry, stress or urge incontinence, or fistula. King's Health Questionnaire was modified and used for the quality-of-life assessment.
Results  At follow up, 21 women (57%) were completely dry, 13 (35%) suffered from stress or urge incontinence and three (8%) had a persistent fistula. Surgery improved quality of life and facilitated social reintegration to a level comparable to that experienced before fistula development for both women who were dry and those with residual incontinence ( P  =   0.001). For women still suffering from fistula no change was seen ( P  =   0.1). Four women became pregnant following their surgery, among which there was one maternal death, three stillbirths and one re-occurrence of fistula.
Conclusion  Community-based, long-term follow up after fistula repair succeeded in Western rural Ethiopia. Despite one-third still suffering stress or urge incontinence, the women reported improved quality of life and social reintegration after fistula closure.     

p53 mutations in defined structural and functional domains are related to poor clinical outcome in non-small cell lung cancer patients.

The prognostic value of p53 status in non-small cell lung cancer has been investigated in 148 patients with clinical stage I-IIIB disease. Tumor tissues were examined for mutations in exons 4-9, with emphasis on defined structural and functional domains. Eighty-four mutations were detected in 83 (54%) of the patients. Eighty-eight percent of the mutations were within exons 5-8, and 12% of the mutations were within exons 4 and 9. Missense mutations occurred in 67% of the tumors, and 30% were null mutations (10% stop mutations, 15% frameshift mutations, and 5% splice site mutations). Patients with mutations in p53 had a significantly higher risk for lung cancer-related death and for death from all causes than those with wild-type p53 [hazard ratio (HR) = 2.09 and 95% confidence interval (CI) = 1.20-3.64 and HR = 1.69 and 95% CI = 1.06-2.70, respectively]. Mutations in p53 related to even still poorer lung cancer-related prognosis were found at the following locations: (a) exon 8 (HR = 3.5; 95% CI, 1.59-7.71)]; (b) the structural domains L2 + L3 (HR = 2.36; 95% CI, 1.18-4.74), and (c) codons involved in zinc binding (HR = 11.7; 95% CI, 3.56-38.69). Together, the biologically functional group of severe flexible mutants (codons 172, 173, 175, 176, 179, 181, 238, 245, and 267) and severe contact mutants (248, 282) were significantly related to shorter lung cancer-related survival (HR = 4.16; 95% CI, 1.93-8.97). Squamous cell carcinoma was the dominant histological type in tumors involved in poor prognosis in exon 8 (HR = 3.19; 95% CI, 1.07-9.45). These results indicate that mutations in defined structural and functional domains of p53 may be useful molecular biological markers for prognosis and treatment strategy in non-small cell lung cancer patients.     

Human chorionic gonadotropin in maternal serum in relation to fetal gender and utero-placental blood flow

BACKGROUND: To investigate whether fetal gender differences in human chorionic gonadotropin (hCG) in maternal serum and the presence of hCG receptors in the wall of the uterine arteries influence the utero-placental blood flow. METHOD AND MATERIAL: Sixty-six healthy women with singleton uncomplicated pregnancies were examined at 8-10, 16-19 and 31-37 weeks of gestation. The pulsatility index (PI) was measured in the uterine arteries, simultaneously with sampling of peripheral maternal blood for hCG determination. Volume flow in the uterine arteries was determined in the second and third trimesters only. RESULTS: In the first and second trimesters no gender differences in the hCG levels were observed. From the second to the third trimester the hCG levels increased significantly in pregnancies with female fetuses (P < 0.05), while in pregnancies with male fetuses the hCG levels tended to decline. The PI declined significantly from the first to the third trimester in both genders (P < 0.001). In the first and third trimesters no gender differences were seen. In the second trimester the PI values were significantly higher in pregnancies with male fetuses than in those with female fetuses (P < 0.02). The flow volume increased significantly in both genders from the second to the third trimester (P < 0.001). In the third trimester the flow volume was higher in pregnancies with female fetuses than in those with male fetuses (P = 0.05). CONCLUSION: The gender differences in uterine artery PI and flow volume were not correlated to maternal serum hCG levels.