Heart failure: molecular, genetic and epigenetic features of the disease.

Factors that compete to establish heart failure (HF) are not completely known. In the last years the several technological improvements allowed us to deeply study the molecular and genetic aspects of this complex syndrome. This new approach to HF based on molecular biology new discoveries shows us more clearly the pathophysiological bases of this disease, and a future scenery where the genetics may be useful in the clinical practice, as screening of high risk populations, as well as in the diagnosis and therapy of underlying myocardial diseases. The purpose of this review was to analyse the molecular, genetic and epigenetic factors of HF. We described the molecular anatomy of the sarcomere and the pathogenesis of the heart muscle diseases, abandoning the previous monogenic theory for the concept of a polygenic disease. Different actors play a role to cause the illness by themselves, modifying the expression of the disease and, eventually, the prognosis of the patient.

The timing of child physical maltreatment: a cross-domain growth analysis of impact on adolescent externalizing and internalizing problems.

In a sample of 578 children assessed in kindergarten through the eighth grade, we used growth modeling to determine the basic developmental trajectories of mother-reported and teacher-reported externalizing and internalizing behaviors for three physical maltreatment groups of children-early-harmed (prior to age 5 years), later-harmed (age 5 years and over), and nonharmed--controlling for SES and gender. Results demonstrated that the earlier children experienced harsh physical treatment by significant adults, the more likely they were to experience adjustment problems in early adolescence. Over multiple domains, early physical maltreatment was related to more negative sequelae than the same type of maltreatment occurring at later periods. In addition, the fitted growth models revealed that the early-harmed group exhibited someswhat higher initial levels of teacher-reported externalizing problems in kindergarten and significantly different rates of change in these problem behaviors than other children, as reported by mothers over the 9 years of this study. The early-harmed children were also seen by teachers, in kindergarten, as exhibiting higher levels of internalizing behaviors. The later-harmed children were seen by their teachers as increasing their externalizing problem behaviors more rapidly over the 9 years than did the early- or nonharmed children. These findings indicate that the timing of maltreatment is a salient factor in examining the developmental effects of physical harm.

Relationship between quality of life and depression in patients with head and neck cancer.

OBJECTIVE: This study describes the relationship between health-related quality of life (HRQOL) and depression in patients following major surgery for head and neck cancer. DESIGN: Cross-sectional study using medical chart review, patient interview, and test administration. METHOD: Fifty patients were evaluated 6 months to 6 years following surgery using one global HRQOL measure (The Functional Assessment of Cancer Therapy-General [FACT-G]); three disease-specific measures of HRQOL (the HN module of the FACT [FACT-HNS], The University of Washington Quality of Life Scale [UWQOL], and The Performance Status Scale for Head and Neck Cancer); and one measure of depression (The Beck Depression Inventory [BDI]). RESULTS: The study population showed a high occurrence of depressive symptoms (22%). A negative correlation existed between the BDI and HRQOL as measured by the FACT-G (r = -0.49, P < .001) and the UWQOL (r = -0.44, P = .003). When somatic symptoms of depression were removed, the BDI remained correlated with HRQOL and was most highly correlated with the Emotional Well-Being (EWB) subscale of the FACT-G (r = -0.42, P = .003). There was no correlation between clinician judgments of EWB and any patient-rated measures of HRQOL or depression. CONCLUSIONS: Results demonstrate an inverse relationship between patient-reported HRQOL and depression. The lack of correlation between physician and patient ratings of HRQOL and EWB stresses the importance of obtaining patient ratings in addition to traditional clinician ratings when assessing outcomes. Finally, the multidimensional construction of the FACT with its specific subscales may make it a useful clinical tool for assessing patient status and augmenting patient interviews.

Factors related to quality of life and functional status in 50 patients with head and neck cancer.

Quality of life (QOL) and functional status (FS) have become important outcome measures in cancer therapy. Valid and reliable instruments recently have been developed for examining QOL and FS in patients with head and neck (HN) cancer. The present study evaluated the relationships of QOL and FS to physical and psychological variables assumed to affect QOL and FS. Fifty patients were evaluated up to 6 years after HN cancer surgery using one general QOL instrument and three HN-specific instruments. Analysis of variance showed physical variables such as tumor site to be related to HN-specific scores, while psychosocial variables such as marital status were related to general QOL scores (P < or = .05). Several relationships were seen between physical or psychosocial variables and FS or QOL measures; however the relationships were not as strong or direct as expected.

Parathyroid imaging.

Radionuclide scanning for hyperparathyroidism is an accurate cost-effective preoperative test that can provide the basis for more effective surgery.

Unilateral parathyroidectomy: the value of the localizing scan.

Surgery for correction of primary hyperparathyroidism utilizing a standard bilateral neck exploration has a success rate of approximately 90 to 95%. With the inception of pre-operative localization studies that were 90% accurate in localizing the diseased gland, the concept arose that a unilateral exploration could be as successful as a bilateral exploration. Bilateral exploration of the neck for hyperparathyroidism exposes the patient to a greater potential of morbidity for hypoparathyroidism and recurrent laryngeal nerve injury. It is our feeling based on personal experience that unilateral parathyroidectomy in selective cases can be as successful as the bilateral operation and be more cost effective, saving over $1,100 (U.S.) per case.

Nonpenetrating clips successfully replacing sutures in base of skull surgery.

Reconstructive challenges engendered by skull base surgery are critical determinants of outcome. A novel nonpenetrating, arcuate-legged clip has proven to be both technically and biologically effective for management of these difficult closures. Clips have facilitated reconstructions associated with the surgical management of eight skull base cases: leiomyosarcoma of the orbit, middle fossa, ptyergopalatine fossa, two meningiomas (petrotentorial, cavernous sinus), vagus nerve paraganglioma, complex traumatic orbital dural tear, and one basilar and two vertebral artery aneurysms.

Treatment of thyroid carcinoma.

In a review of thyroid surgery performed at Loma Linda University and its affiliated hospitals during the past 20 years, 254 (26%) of the thyroid surgery patients had thyroid carcinoma. The majority of these patients underwent total thyroidectomy and received postoperative radioactive iodine. At the present time, there is considerable disagreement in the literature regarding the extent of treatment needed for what, in many cases, is a low-grade malignancy. In the present series, there are a significant number of patients with extensive disease in which aggressive treatment is warranted to improve the chance of cure. We believe that total thyroidectomy with central node dissection is the minimum surgical procedure required.

Transantral sphenoethmoidectomy: a procedure for the 1990s?

Currently, among otolaryngologists, much attention is focused on the surgical management of paranasal sinus disease. However, transantral sphenoethmoidectomy is rarely mentioned in the literature of the past several decades. We reviewed a consecutive series of 98 patients over a 12-year period who underwent transantral sphenoethmoidectomy in the treatment of severe chronic hyperplastic pansinusitis. The major and minor complications encountered are tabulated, as are the clinical outcomes. A description of the operative technique is followed by a discussion of the indications for this approach. We believe transantral sphenoethmoidectomy has a useful place in modern paranasal sinus surgery.

Hyperparathyroidism.

Primary hyperparathyroidism can be caused by a solitary parathyroid adenoma and sometimes by hyperplastic parathyroid glands, multiple adenomas, or carcinoma. In the majority of patients, the diagnosis is made tentatively by chemistry profiles that show elevated serum calcium. It is confirmed by repeated serum calcium values and PTH determination. The parathyroid abnormality, if an adenoma, can usually be localized preoperatively by thallium-technetium scan, ultrasound, or computed tomography. In the case of persistent disease with hypercalcemia, an angiogram with selective venous sampling for PTH is helpful. At exploration, both sides of the neck may need exploration. A unilateral procedure may be sufficient, if the preoperative localization tests are confirmatory and if biopsy of another "normal" gland shows normal histologic findings. During the postoperative period, suction drains will lessen the likelihood of hematoma formation and serum calcium levels are monitored for the first 3 to 5 days. Symptomatic patients with low calcium levels receive intravenous and oral calcium supplements until values are brought to the low-normal range. Supplements are tapered as the calcium in the serum rises. The majority of patients who undergo parathyroid surgery will benefit both symptomatically and metabolically.

The pitfalls of technetium Tc 99m/thallium 201 parathyroid scanning.

Technetium Tc 99m/thallium 201 parathyroid scanning has been proved to be effective by multiple researchers. A review of 54 patients who underwent scanning and operations at an institution showed the scans to be accurate in 83%. There were 15% false-negative and 2% false-positive scans. The pitfalls of parathyroid scanning can be related to false-positives and false-negatives.

Total thyroidectomy in the treatment of thyroid disease.

In a review of thyroid surgery during the past 12 years, total thyroidectomy was performed in 20% of the cases. Forty percent were done for malignant disease and 60% for benign disease. Our indications for using this operation in benign thyroid disease include bilateral nodular goiter, Graves' disease, chronic thyroiditis, and cases in which the rapid frozen diagnosis is equivocal for carcinoma. We feel that the risks of reoperation for recurrent thyroid disease are greater than the risks of a total thyroidectomy as the initial surgical procedure. With the increased use of total thyroidectomy the incidence of permanent hypoparathyroidism can be decreased. We reviewed our preoperative work-up, indications for total thyroidectomy, surgical technique, diagnostic accuracy of needle biopsy, accuracy of rapid frozen section reports, and postoperative complications.

Adjuvant methotrexate escalated to toxicity for resectable stage III and IV squamous head and neck carcinomas--a prospective, randomized study.

To determine if adjuvant methotrexate (MTX), escalated weekly to toxicity, could improve disease-free survival (DFS) and overall survival by preventing recurrent disease, 60 patients with potentially resectable stage III or IV squamous head and neck carcinomas were stratified by primary site, stage, and nutritional status, then randomized by pairs to receive or not receive adjuvant MTX. All received standard surgery and postoperative radiation therapy. Five patients were taken off study because of unresectability at the time of surgery, leaving 55 evaluable patients. There were no statistically significant imbalances in known prognostic factors between the two treatment arms. MTX was begun at 40 mg/m2 and escalated 10 mg/m2 weekly (four doses preoperatively; four doses postoperatively, preradiation therapy; eight doses postradiation therapy) to mucosal or hematologic toxicity. The median peak MTX dose achieved was 80 mg/m2. Although three patients were hospitalized with MTX toxicity, none died of MTX toxicity. No patient receiving MTX had disease progression during treatment, and there was no increase in postoperative complications. Thirty-two patients died (median survival, 19 months); 23 patients are alive with median follow-up of 43 months. There was no statistically significant difference in actuarial DFS (P = 1.0) or overall survival (P = .61). Although patients on the MTX arm appeared to have less local and regional recurrences at first recurrence (thus more distant metastases), this did not reach statistical significance (P = .06). There was no significant difference between the sites of recurrence at death or last follow-up (P = .38).

Parathyroid carcinoma: two new cases--diagnosis, therapy, and treatment.

Carcinoma of the parathyroid gland is a disease only rarely encountered in clinical practice. As most of these tumors retain the ability to manufacture active parathyroid hormone, most patients with the disease present with hypercalcemia, many times symptomatic. Since the tumor accounts for only 0.5% to 4.0% of cases of primary hyperparathyroidism, the diagnosis of parathyroid carcinoma may be unsuspected and delayed. The clinical index of suspicion should be elevated if there is a palpable neck mass, an exceptionally high serum calcium level, and/or recurrence of hypercalcemia following surgery. We review two patients with parathyroid carcinoma who presented with hypercalcemia. In both, the diagnosis of malignancy was made only after microscopic examination of the operative specimen. Surgery consisted of wide local excision in both cases; radiation therapy was administered in one. Postoperative disease-free status is now 23 and 37 months. One of the patients had a history of radiation therapy to the larynx 20 years prior to the development of parathyroid carcinoma. Also reviewed in this paper are the clinical and histopathologic criteria for making the diagnosis of parathyroid carcinoma and the therapeutic approaches and prognosis of this unusual tumor.