Diagnosing anal sphincter injury with transanal ultrasound and manometry

PURPOSE: This study was undertaken to evaluate how well anorectal manometry and transanal ultrasonography diagnose anal sphincter injury. METHODS: Anorectal manometry and transanal ultrasonography were performed in 20 asymptomatic nulliparous women and 20 asymptomatic parous women, and the results were compared with those obtained in 31 incontinent women who subsequently underwent sphincteroplasty and, thus, had operatively verified anal sphincter injury. By using computerized manometry analysis, mean maximum resting and squeeze pressures, sphincter length, and vector symmetry were determined in all women. All transanal ultrasounds were interpreted blinded as to the patient's history, physical examination, and manometry results. RESULTS: Manometric resting and squeeze pressures were significantly higher in the asymptomatic nulliparous women than in the asymptomatic parous women, and both groups had significantly higher pressures than the incontinent women ( P <0.001). Anal sphincter length and vector symmetry index were significantly decreased in incontinent women compared with asymptomatic women ( P <0.01). Decreased resting and squeeze pressures suggestive of possible sphincter injury were found in 90 percent of incontinent women with known anal sphincter injury. Decreased anal sphincter length and vector symmetry were found in only 42 percent of women with known anal sphincter injury. Transanal ultrasound was able to identify 100 percent of the known sphincter injuries but also falsely diagnosed injury in 10 percent of the asymptomatic nulliparous women with intact anal sphincters. False identification of sphincter injury increased when transanal ultrasound scanning was performed proximal to the distal 1.5 cm of the anal canal. CONCLUSION: Although nonspecific, decreased resting and squeeze pressures were found in 90 percent of patients with anal sphincter injury. Decreased anal sphincter length or vector symmetry index were present in only 42 percent of patients with known sphincter injury. When limited to the distal 1.5 cm of the anal canal, transanal ultrasound identified all known sphincter injuries but falsely identified injury in 10 percent of women with intact anal sphincters. Transanal ultrasound in combination with decreased anal pressures correctly identified all intact sphincters and 90 percent of known anal sphincter injuries.Read at the meeting of The American Society of Colon and Rectal Surgeons, Orlando, Florida, May 8 to 13, 1994. Winner of the New England Society of Colon and Rectal Surgeons Award.     

Estrogen receptor (ER) modulators each induce distinct conformational changes in ER alpha and ER beta

Estrogen receptor (ER) modulators produce distinct tissue-specific biological effects, but within the confines of the established models of ER action it is difficult to understand why. Previous studies have suggested that there might be a relationship between ER structure and activity. Different ER modulators may induce conformational changes in the receptor that result in a specific biological activity. To investigate the possibility of modulator-specific conformational changes, we have applied affinity selection of peptides to identify binding surfaces that are exposed on the apo-ERs alpha and beta and on each receptor complexed with estradiol or 4-OH tamoxifen. These peptides are sensitive probes of receptor conformation. We show here that ER ligands, known to produce distinct biological effects, induce distinct conformational changes in the receptors, providing a strong correlation between ER conformation and biological activity. Furthermore, the ability of some of the peptides to discriminate between different ER alpha and ER beta ligand complexes suggests that the biological effects of ER agonists and antagonists acting through these receptors are likely to be different.     

Congenital transmission of Schistosoma japonicum in pigs

Congenital transmission of Schistosoma japonicum in pigs was investigated by experimentally infecting sows at four weeks gestation (n = 3), 10 weeks gestation (n = 3), or a few weeks prior to insemination (n = 2). None of the piglets born to sows infected prior to insemination or in early pregnancy were found to be infected. However, all of the piglets (n = 26) born to sows infected at 10 weeks gestation were found to harbor schistosomes with S. japonicum eggs recovered from both their feces and livers. The findings show that congenital S. japonicum infection of pigs can occur if sows are infected during mid-to-late pregnancy and may have important implications not only for pigs but also for other mammalian hosts of schistosomes, including humans.     

Linear reduction of clonal cells in stem cell enriched grafts in transplanted multiple myeloma

In 30 patients with multiple myeloma who were scheduled for peripheral blood stem-cell transplantation, a quantitative analysis of the stem cells following enrichment by anti-CD34 was carried out. To detect the cells of the specific myeloma clone, polymerase chain reaction (PCR) was performed using unique allele-specific oligo primers for the immunoglobulin heavy chain rearrangement. The clonogenic cells before and after stem-cell enrichment, were quantified by a limiting dilution assay and a highly sensitive semi-nested PCR combined with a real-time quantitative PCR. In order to accomplish a statistically adequate end-point analysis, a large number of PCR analyses (40 per sample) were performed. By this technique the lowest detection limit observed was one myeloma cell per 106 cells. Myeloma cells were detected in 29/30 samples from the CD34-enriched fraction. The CD34 selection procedure resulted in a median 28-fold enrichment of CD34+ haemopoietic precursor cells. The stem-cell selection reduced the median concentration of clonal cells per million total cells by half, with a highly significant linear relationship between the number of myeloma cells before and after stem cell enrichment. The median depletion of clonal cells by the overall procedure was 2.15 log units, corresponding to a reduction of the total quantity of clonal cells reinfused into the patients by at least 99.3%. We conclude that CD34+ cell enrichment led to a reliable tumour cell depletion of the order of 2 log, which may not be sufficient since the total number of tumour cells in the leukapheresis product was 7.2 log (median).     

Colorectal cancer in hereditary breast cancer kindreds

PURPOSE: This study compared characteristics of colorectal cancer between families with dominant breast cancer inheritance and the general population. The cumulative incidence of colorectal cancer was also studied in genetically determined breast cancer syndrome subjects with BRCA1 and BRCA2 mutations and compared with the general population. METHODS: Subjects included 42 patients with colorectal cancer from 32 clinically determined hereditary breast cancer kindreds based on the autosomal dominant inheritance of breast cancers and early age of onset. The general population colorectal cancer cohort was composed of 755 patients from a tumor registry. Lifetime risk of colorectal cancer was determined in 164 BRCA1 and 88 BRCA2 gene mutation carriers and compared with the general population. Mean age of colorectal cancer onset, anatomic site distribution, histologic stage at presentation, and five year stage-stratified survival rates were compared between clinically determined hereditary breast cancer family members and the general population. RESULTS: The lifetime risk of colorectal cancer in male BRCA1 and BRCA2 mutation carriers was 5.6 percent, which was not different from 6 percent in males from the general population. Likewise, the lifetime colorectal cancer risk in female BRCA1 and BRCA2 mutation carriers was 3.2 percent, which was not different from 5.9 percent in females from the general population. Mean age of onset ± standard error for patients with colorectal cancer was 60±2 years for hereditary breast cancer kindreds compared with 67±0.4 years for the general population (P=0.0004). Colorectal cancer site distribution did not vary between hereditary breast cancer and the general population. Overall colorectal cancer stage distribution was significantly different, with more Stage I and fewer Stage IV cancers in subjects with hereditary breast cancer compared with the general population (P=0.01). Overall five year stage-stratified colorectal cancer survival rate ± standard error was 66±8 percent for hereditary breast cancer kindreds and 46±2 percent for the general population (P=0.023). CONCLUSION: Lifetime cumulative colorectal cancer incidence in subjects with BRCA1 and BRCA2 gene mutations was not different from the general population. However, significant differences in colorectal cancer were noted between hereditary breast cancer family members and the general population. Hereditary breast cancer-associated colorectal cancer had an earlier age of onset, lower tumor stage, and better survival rate than the general population. Except for age of onset, colorectal cancer in hereditary breast cancer kindreds exhibited more favorable characteristics than colorectal cancer in the general population.Read at the meeting of The American Society of Colon and Rectal Surgeons, San Antonio, Texas, May 2 to 7, 1998.     

Left ventricular performance in alcoholic patients without chronic liver disease

Left ventricular performance was studied non-invasively in 24 chronic alcoholics without liver disease. Twelve patients who had abstained from drinking for at least one month (group A) and 12 sex and age matched patients who had ceased drinking during the preceding 24 hours (group B) were studied at rest and during 50% submaximal exercise. Cardiac output and stroke volume were measured by first passage and left ventricular ejection fraction by multigated radionuclide cardiography. Twelve healthy sex and age matched controls were also studied. Haemodynamic variables were similar in group A and the controls, except that in group A left ventricular end systolic volume index did not decrease during exercise. In group B the heart rate was increased both at rest and during exercise and plasma noradrenaline concentrations were increased. The stroke volume index did not increase significantly during exercise in group B. In addition, the increase in left ventricular ejection fraction was smaller in group B than in controls. End systolic contraction was reduced in group B patients and diastolic blood pressure was increased. These results suggest that cardiac abnormalities in chronic alcoholics may be reversed after cessation of drinking if no chronic liver disease is present. Recent alcohol consumption increases sympathetic nervous activity, impairs cardiac contractility, and increases afterload during physical stress.     

The role of diabetes on the clinical manifestations of pulmonary tuberculosis

Objective Diabetes is associated with pulmonary tuberculosis (TB), possibly due to impaired immunity, and diabetes may exacerbate the clinical manifestations of TB. Our aim was to assess the role of diabetes in the clinical manifestations of TB. Methods We studied 1250 patients with pulmonary TB in an urban population in a cross‐sectional study in Tanzania. All participants were tested for diabetes and HIV co‐infection, and TB culture intensity was assessed. Levels of white blood cells, haemoglobin, acute phase reactants, CD4 count and HIV viral load were measured, and a qualitative morbidity questionnaire was used to identify the prevalence of disease‐related symptoms. Results Tuberculosis patients with diabetes had a higher neutrophil count (B 0.5 × 10⁹ cells/l, 95% CI 0.2; 0.9, P = 0.001) than non‐diabetic TB patients. Serum C‐reactive protein (B 18.8 mg/l, CI 95% 8.2; 29.4, P = 0.001) and alpha‐1‐acid glycoprotein (B 0.2 g/l, CI 95% 0.03; 0.3, P = 0.02) were similarly higher in patients with diabetes. Diabetes did not affect culture intensity or HIV status, but self‐reported fever was three times higher among participants with diabetes than in those without diabetes (OR 2.9, CI 95% 1.5; 5.7, P = 0.002). Conclusion Diabetes is associated with small changes in the manifestations of TB, but may have little clinical significance.