Improved detection of amyloid in fat pad aspiration: an evaluation of Congo red stain by fluorescent microscopy

Amyloid fat pad aspiration specimens for cases with a clinical suspicion of amyloid typically are stained with Congo red and examined by brightfield microscopy. Congophilia with apple-green birefringence by polarization microscopy (PM) is considered diagnostic for amyloid. Examination of Congo red-stained slides by fluorescent microscopy (FM) is considered by some to be a more sensitive detection method. In this study, we assessed the utility of this technique in cytopathology archival slides from abdominal fat pad aspirations previously stained with Congo red dye. Seventy-eight cases of abdominal fat pad aspirations collected during the last 5 yr and stained with the Congo red procedure were obtained from archival files. Additionally, 20 adipose tissue material slides prepared from the surgical pathology specimens were examined as controls. One representative smear was examined in each case using FM equipped with rhodamine excitation/absorption (540/570 nm) filters. Relevant clinical information was obtained in all cases. Twelve cases (15.4%) of the 78 fat pad aspiration cases were reported originally as positive by Congo red stain using polarization and apple-green birefringence as diagnostic criteria. On review, four cases were deemed unsatisfactory. By FM examination 29 of the 74 (39.2%) cases were reclassified as positive for amyloid. The results were confirmed by immunohistochemical stain for amyloid P protein and electron microscopy. A number of similar distinct fluorescence and immunohistochemical patterns were recognized in the positive cases. Minimally weak fluorescence in the adipose tissue was observed in the control cases. The use of FM in Congo red-stained fat pad smears can improve the detection of amyloid in cytology preparations.     

Grandparental genotyping enhances exome variant interpretation

Trio exome sequencing is a powerful tool in the molecular investigation of monogenic disorders and provides an incremental diagnostic yield over proband‐only sequencing, mainly due to the rapid identification of de novo disease‐causing variants. However, heterozygous variants inherited from unaffected parents may be inadvertently dismissed, although multiple explanations are available for such scenarios including mosaicism in the parent, incomplete penetrance, imprinting, or skewed X‐inactivation. We report three probands, in which a pathogenic or likely pathogenic variant was identified upon exome sequencing, yet was inherited from an unaffected parent. Segregation of the variants (in NOTCH1, PHF6, and SOX10) in the grandparent generation revealed that the variant was de novo in each case. Additionally, one proband had skewed X‐inactivation. We discuss the possible genetic mechanism in each case, and urge caution in data interpretation of exome sequencing data. We illustrate the utility of expanding segregation studies to the grandparent generation and demonstrate the impact on exome interpretation strategies, by showing that objective genotype data can overcome subjective parental report of lack of symptoms.     

Immunization with cholinergic cell bodies induces histopathological changes in rat brains

We have previously shown that sera from patients with Alzheimer’s disease (AD) contain antibodies to the cell bodies (perikarya; PK) of purely cholinergicTorpedo neurons, and that repeated immunization of rats with this neuronal preparation for over a year induces learning and memory impairments. In the present study, we examined the brain morphology of cholinergic PK immunized rats relative to controls. Immunohistochemical studies of the brains of these rats revealed the accumulation of IgG in specific areas, such as, the hippocampus. Parallel histochemical studies demonstrated significant changes in the hippocampus, and in white matter areas. They included large vacuoles and necrotic nuclei in the granular layer of the dentate gyrus, tangle-like appearance in some pyramidal neurons of the hippocampus, and vacuolar degeneration accompanied by oligodendroglia hypertrophy in white matter tracts, such as, the corpus callosum and fimbria. In contrast, immunization withTorpedo cholinergic nerve terminals, that has no cognitive effects on the rat, also did not induce brain morphological changes. These findings suggest that the learning and memory deficits induced by immunizing rats with cholinergic PK are related to the observed brain morphological changes, and support the hypothesis that the antibodies to cholinergic neurons found in the sera of AD patients may play a role in neuronal degeneration in this disease.     

Stigmatization, self-esteem, and coping among the adolescent children of lesbian mothers

Purpose: To examine perceived stigma, coping, disclosure, and self-esteem among adolescents with lesbian mothers.

Method: Interviews were conducted with 76 adolescents ages 11–18 years. Standardized measures of self-esteem and coping skills were used. A measure of stigma was adapted for this study and a measure of disclosure was developed. The relationship between perceived stigma and self-esteem was examined. General coping skills and level of disclosure about the adolescents’ mothers’ sexual orientation were assessed as potential moderators of the relationship between perceived stigma and self-esteem.

Results: Adolescents who perceived more stigma had lower self-esteem in five of seven self-esteem areas, compared to those who perceived less stigma. In addition, coping skills moderated the effect of stigma on self-esteem in three self-esteem areas. However, only one subtype of coping skills, that of decision-making coping, was found to moderate the relationship of perceived stigma and self-esteem in such a way that adolescents using more decision-making coping had higher self-esteem in the face of high perceived stigma. For social support coping, in the face of high perceived stigma, the adolescents with more effective coping skills had lower self-esteem. In the face of high perceived stigma, adolescents who disclosed more about their mother’s sexual orientation had higher self-esteem in the subscale of close friendship than those who disclosed less.

Conclusions: Results suggest that stigma is related to self-esteem among the adolescent children of lesbian mothers. The results indicate that this relationship is moderated by coping skills. These results have implications for intervention and prevention of stigmatization by the establishment of effective coping skills as well as through educational efforts to eradicate stigmatizing attitudes.     

Sternal wound infections in patients after coronary artery bypass grafting using bilateral skeletonized internal mammary arteries

OBJECTIVES: This study evaluated the risks of sternal wound infections in patients undergoing myocardial revascularization using bilateral skeletonized internal mammary arteries (IMAs). BACKGROUND: The skeletonized IMA is longer than the pedicled one, thus providing the cardiac surgeon with increased versatility for arterial myocardial revascularization without the use of vein grafts. It is isolated from the chest wall gently with scissors and silver clips, and no cauterization is employed. Preservation of collateral blood supply to the sternum and avoidance of thermal injury enable more rapid healing and decrease the risk of sternal wound infection. METHODS: From April 1996 to August 1997, 545 patients underwent arterial myocardial revascularization using bilateral skeletonized IMAs. The right gastroepiploic artery was used in 100 patients (18%). The average age of the patients was 65 years; 431 (79%) were men and 114 (21%) were women; 179 (33%) were older than 70 years of age; 166 (30%) were diabetics. The average number of grafts was 3.2 per patient. RESULTS: The 30-day operative mortality rate was 2% (n = 11). There were six perioperative infarcts (1.1%) and six strokes (1.1%); 9 patients had sternal infection (1.7%) and 15 (2.8%) had superficial infection. Risk factors for sternal infection were chronic obstructive pulmonary disease and emergency operation. Superficial sternal wound infections were more common in women and in patients with chronic obstructive pulmonary disease, renal failure, or peripheral vascular disease. The 1-year actuarial survival rate was 97%. Two of the six late deaths were not cardiac-related. Late dehiscence occurred in three patients (0.6%). The death rate (early and late) of patients with any sternal complication was higher than that of patients without those complications (33% vs. 2.7%). CONCLUSIONS: Routine arterial myocardial revascularization using bilateral skeletonized IMAs is safe, and postoperative morbidity and mortality rates are low, even in elderly patients and those with diabetes. Chronic obstructive pulmonary disease and emergency operations were found to be associated with an increased risk of sternal infections, and the authors recommend avoiding the use of bilateral skeletonized IMAs in patients with these preoperative risk factors.     

Rigiscan versus snap gauge band measurements: is the extra cost justifiable?

Both RigiScan and the Snap Gauge band devices are used to objectively measure penile rigidity. The Snap Gauge band is the more simple and inexpensive of the two techniques. We investigated the correlation between the results obtained by both devices in order to evaluate whether the Snap Gauge band could be employed as the sole method of rigidity evaluation while not affecting the quality of diagnosis. Forty eight patients who were presented to our erectile dysfunction clinic used the two devices simultaneously, each according to the accepted protocols. Breakage of two and three strings of the Snap Gauge (good rigidity) correlated well with good tip and average rigidity as evaluated by the RigiScan. Snap gauge results also correlated with duration of erection, number of erections, the number of adequate erections, and the longest duration of erection measured by the RigiScan. Therefore, good rigidity according to the Snap Gauge test correlated well with the results of functional erections (number, rigidity, duration) as obtained by the RigiScan. The Snap Gauge band can be used to adequately evaluate penile rigidity. RigiScan measurements, which are more complicated and more expensive, should be reserved for selected patients in whom the results of the Snap Gauge band are inconclusive or when more detailed information is required.     

Myocardial injury without heart failure following envenomation by the scorpion Leiurus quinquestriatus in children

The enzymatic activity of creatine kinase-MB isoenzyme (CK-MB), a sensitive and specific marker of myocardial damage, was measured in 32 children following scorpion envenomation. CK-MB activity, total creatine phosphokinase (CPK) and serum glutamine oxalacetic transaminase (SGOT) levels were examined for relationship with electrocardiographic (ECG) results and the clinical state of the children. Twenty-seven out of the 32 children had signs of systemic intoxication ("symptomatic" cases), while the other five children had only local signs ("asymptomatic" cases). Thirteen out of the 27 symptomatic children had enzymatic myocardial involvement characterized by high total CPK level, elevated CK-MB level and a CK-MB/CK ratio exceeding 6%. Six of these 13 children had ECG changes consistent with myocardial damage, and only one child had clinical signs of myocardial injury. None of the asymptomatic children, nor five healthy control children, had any evidence of myocardial damage as judged by CK-MB levels, clinical signs and ECG. Our study suggests that CK-MB activity is specific and highly sensitive in detecting myocardial damage in children following scorpion envenomation, and appears superior to ECG and clinical parameters. We speculate that the myocardial lesions are too small to cause heart failure in most cases, but they may account for the cardiovascular changes frequently seen in scorpion envenomation.     

Is obesity a risk factor for psychopathology among adolescents?

BACKGROUND: Although several studies have documented the existence of psychopathology in obese adolescents, disagreement remains regarding the extent and nature of this psychopathology. The aim of the present study was to explore the type and frequency of psychopathology in a clinical as well as a non-clinical sample of obese adolescents, and in a normal weight control group. METHODS: The study sample consisted of a clinical study group of 30 obese adolescents, a non-clinical obese group of 30 obese adolescents, and a control group of 30 normal weight adolescents. Psychological assessment was performed using a non-structured psychiatric interview, the Child Behavior Checklist (CBCL), Children Depression Inventory (CDI), Rosenberg Self-esteem scale (SES) and the Eating Attitude Test (EAT). RESULTS: More than half of the clinical obese adolescents (16/30) had a DSM-IV diagnosis, often involving major depressive disorder (n = 10). The mean scores of anxiety-depression, social problems, social withdrawal and total problem in the CBCL scale of the clinical obese group were significantly higher than the non-clinical obese group and the normal weight control group. The mean total scores of the SES and the CDI of the clinical obese group were higher than the normal weight control group. The mean total score of EAT of the clinical obese group was significantly higher than the normal weight control group, and the mean score of EAT of the non-clinical obese group was significantly higher than the normal weight control group. CONCLUSIONS: The results support previously published reports which show a higher ratio of psychopathology (depression, behavioral problems, low-esteem) among clinical obese adolescents than among non-clinical obese adolescents. Findings provided evidence for a psychosocial at-risk population in a subgroup of obese adolescents.     

Diagnostic uncertainty and recall bias in chronic low back pain

Patients’ beliefs about the origin of their pain and their cognitive processing of pain-related information have both been shown to be associated with poorer prognosis in low back pain (LBP), but the relationship between specific beliefs and specific cognitive processes is not known. The aim of this study was to examine the relationship between diagnostic uncertainty and recall bias in 2 groups of chronic LBP patients, those who were certain about their diagnosis and those who believed that their pain was due to an undiagnosed problem. Patients (N = 68) endorsed and subsequently recalled pain, illness, depression, and neutral stimuli. They also provided measures of pain, diagnostic status, mood, and disability. Both groups exhibited a recall bias for pain stimuli, but only the group with diagnostic uncertainty also displayed a recall bias for illness-related stimuli. This bias remained after controlling for depression and disability. Sensitivity analyses using grouping by diagnosis/explanation received supported these findings. Higher levels of depression and disability were found in the group with diagnostic uncertainty, but levels of pain intensity did not differ between the groups. Although the methodology does not provide information on causality, the results provide evidence for a relationship between diagnostic uncertainty and recall bias for negative health-related stimuli in chronic LBP patients.