Endosalpingiosis in female peritoneal washings: a diagnostic pitfall

Endosalpingiosis in female peritoneal washings can be a source of false-positive diagnoses, especially in patients with known ovarian carcinoma. In this article we report the features of endosalpingiosis in the peritoneal washings of four patients, three of whom were initially reported as "suspicious for malignancy." Two of the patients had ovarian serous tumor of borderline malignancy; however, the tumors were confined to the ovaries with no evidence of disseminated peritoneal malignancy. All four patients had histologic evidence of pelvic endosalpingiosis. It is important to recognize this entity cytologically to avoid a misdiagnosis of recurrent or disseminated malignancy.     

The correction of anemia in severe resistant heart failure with erythropoietin and intravenous iron prevents the progression of both the heart and the renal failure and markedly reduces hospitalization

Both Congestive Heart Failure (CHF) and Chronic Renal Failure (CRF) are increasing steadily in the community. We propose that there is a vicious circle established whereby CHF and CRF both cause anemia and the anemia then worsens both the CHF and CRF causing more anemia and so on. We call this the Cardio Renal Anemia (CRA) syndrome. By the combination of active treatment of the CHF and control of the anemia with subcutaneous erythropoietin and intravenous iron, the progression of both the CHF and the CRF can be slowed or stopped in most cases, the quality of life improved and the need for recurrent hospitalization reduced. This will involve cooperation between internists, cardiologists, and nephrologists to allow early and maximal therapy of both the CHF and the anemia.     

Tryptophan scanning mutagenesis in TM4 of the GABA(A) receptor alpha1 subunit: implications for modulation by inhaled anesthetics and ion channel structure

Previous studies have shown that amino acid residues in trans-membrane (TM) segments 1, 2 and 3 of the alpha subunit are critical for the enhancement of GABA(A) receptor function by inhaled anesthetics. In this study we used tryptophan (Trp) scanning mutagenesis between Ile 406 and Asn 417 in the alpha1 subunit to determine the effects of Trp substitution in the fourth transmembrane segment (TM4) on receptor gating and anesthetic modulation. Wild-type and mutant alpha1 subunits were transiently expressed in HEK 293 cells with wild-type beta2 and gamma2s subunits and GABA-activated currents were recorded using whole-cell voltage clamp. The potentiation by three inhaled anesthetics (isoflurane, halothane and chloroform) of responses elicited by a submaximal concentration of GABA were also examined.EC(50) values for GABA at the mutant receptors were in the range 4-60 microM (wild-type=20 microM), indicating that Trp substitution can alter the apparent affinity of the receptor for GABA positively or negatively, dependent on position. The variation of the calculated EC(50) value for GABA exhibited an interesting periodicity, with the cycle length for each repeat corresponding to approximately 3.6 amino acids. These data are consistent with an alpha-helical structure for the TM4 segment of the alpha subunit. Several of these Trp point mutations altered the ability of one or more of the three inhaled anesthetics to modulate receptor function; four of the 12 mutations abolished receptor modulation by one or more of the anesthetics tested. These data are consistent with a role for these residues at the extracellular end of TM4 in anesthetic modulation of GABA(A) receptors.     

Sun protection education in the United States: what we know and what needs to be taught

The incidence of skin cancers in the United States is rising. This has correlated with a life-time of sun exposure and cumulative damage of repetitive sun-related injuries such as tanning and sunburning. It is estimated that 80% of sun damage occurs before the age of 18 years. This relates to excessive tanning, blistering sunburns, and ineffective sun protection. It has been demonstrated that children can be taught to protect themselves from the sun. However, teaching of sun protection needs to begin at an early age. Such education requires that parents enforce protection in the household and through their actions in sunny situations. It has become apparent from the literature in the United States that we have made strides in sun education, but we have not yet instituted an effective nationwide education plan. This article reviews the data we have in the United States on sun protection, with a focus toward helping to design better education programs for the future. Based on the literature, it would seem that sun education should combine teaching mothers about sun protection in the nursery and teaching schools how to educate youngsters on the need for sun protection, beginning in nursery school. Improvements in education will have a latency of many years for reducing skin cancer incidence but will be an excellent investment in the future cutaneous health of today's children.     

Metabolic basis of pediatric heart disease

We review cardiomyopathies and their classification due to inborn errors of metabolism. An overview of their clinical presentations, diagnosis, treatment, and long-term outcome is provided. Due to the expansion of newborn screening programs and the widespread availability of genetic testing, many patients are now diagnosed earlier in life allowing for timely initiation of symptomatic or even curative treatment and providing opportunities for long-term survival. Hence, it is important that clinicians are familiar with the evaluation, diagnostic approach, and management of these hitherto often lethal pediatric cases. In addition, clinicians need a basic understanding of genetic concepts to provide for appropriate first tier counseling of patients and their families.     

Mitotic activity and apoptosis in endocervical glandular lesions.

To evaluate the significance of mitotic activity and apoptosis in the differential diagnosis of endocervical glandular lesions, we examined the frequency of mitoses and apoptosis in 89 endocervical glandular lesions from 78 patients, which consisted of benign reactive changes (7 cases), lobular or diffuse laminar endocervical glandular hyperplasia (4), microglandular hyperplasia (3), tunnel clusters (7), nabothian cysts (2), mesonephric remnants (3), tubal metaplasia (3), endocervical glandular dysplasias (including atypical tubal metaplasia) (EGD) (7), adenocarcinoma in situ (AIS) (31), microinvasive adenocarcinoma (7), frankly invasive adenocarcinoma (12), and minimal deviation adenocarcinoma (3). Mitotic index (MI; mitotic figures per 1000 cells) was significantly higher in AIS, microinvasive adenocarcinoma, and frankly invasive adenocarcinoma than any other lesions examined. Microinvasive adenocarcinoma showed the highest MI. Apoptosis was detected consistently and frequently in AIS, microinvasive adenocarcinoma, and frankly invasive adenocarcinoma. AIS showed the highest apoptotic index (AI; apoptoses per 1000 cells). Frequent apoptotic bodies and mitotic figures are a common feature of endocervical glandular malignancies (except for minimal deviation adenocarcinoma) and are an important feature that can facilitate their differentiation from benign and borderline lesions. High MI in microinvasive adenocarcinoma might aid the distinction of microinvasive adenocarcinoma from AIS. Although both MI and AI of EGD were between those of benign reactive changes and of AIS, MI and AI alone are not sufficient to differentiate EGD from benign reactive changes. MI and AI are not helpful in the differential diagnosis between minimal deviation adenocarcinoma and its benign mimics.     

Immunohistochemical staining in the distinction between primary endometrial and endocervical adenocarcinomas: another viewpoint.

Several studies have reported on the use of antibodies to monoclonal carcinoembryonic antigen (CEA) and vimentin (VIM) to distinguish between adenocarcinomas of endometrial (EM) and endocervical (EC) origin, with variably enthusiastic results. It is still unclear whether site of origin or pathway of differentiation (endometrioid [em] versus mucinous [m]) is more important in predicting immunohistochemical differences. In the present study, paraffin blocks from adenocarcinomas of known origin were retrieved and immunostained with monoclonal antibodies to VIM and CEA, as well as cytokeratins (CK) 4, 18, and 20, estrogen receptor (ER), and progesterone receptor (PR). Positivity was scored on a scale from 0 to 12, with emphasis on the pattern of differentiation (tumors with mixed patterns received separate scores for the em and m foci). Mean CEA scores for emEM (n = 27), mEM (17), mEC (10), and emEC (6) were 0.4, 0.9, 5.1, and 1.2, respectively. VIM scores were 6.9, 1.3, 0, 4.4; ER, 5.7, 4.2, 0, 1.6; PR, 7.6, 2.8, 0.1, 6.0; CK4, 9.2, 4.4, 8.5, 10.6; CK18, 6.4, 3.4, 5.5, 8.4; CK20, 0.7, 0, 0.5, 0.4. Both site and differentiation influenced these results, with the latter more important for VIM and PR, the former for ER, both for CEA (only mEC was frequently strongly positive), and neither for the CKs studied. No one stain or combination reliably distinguished endometrial from endocervical origin. The only immunostaining pattern that might identify a site of origin with more accuracy than hematoxylin & eosin evaluation alone is the combination of high VIM and ER scores in an endometrioid carcinoma, suggesting with about 95% accuracy in this series an endometrial origin of the tumor.