Cisplatin-5-fluorouracil chemotherapy for advanced inoperable squamous carcinoma of the head and neck

Patients with locally advanced, inoperable squamous cell carcinoma of the head and neck were offered three courses of cisplatin and 96-h 5-fluorouracil (5-FU) infusion. Subsequent therapy included surgery when feasible, irradiation therapy, and a maintenance program of methotrexate (MTX)-5-FU. Thirty-three patients were evaluated prospectively. Seven patients underwent a single course of chemotherapy. Five patients underwent two courses of chemotherapy. Twenty-one patients underwent three courses of adjuvant chemotherapy. The overall response rate was 48% (16 of 33). Fifteen of 21 patients (76%) receiving three courses of chemotherapy evidenced a response; this included three complete responses (CRs) (9%). No responses were seen in patients receiving only one or two courses of chemotherapy. Among responding patients, the initial favorable response to chemotherapy was apparent after the first course of chemotherapy. Patients who failed to demonstrate any response after two courses of chemotherapy did not respond after a third course. A significant group of patients fail to respond and should be offered participation in other investigational protocols as they become available.     

The surgical risk of colectomy in patients with cirrhosis

The records of 54 patients with documented cirrhosis who underwent colectomy between January 1970 and January 1984 were studied to assess the operative risk and to determine the preoperative predictive risk factors. In-hospital mortality was 24 percent (13 patients), and postoperative complications occurred in 48 percent (26 patients). The risk of surgical intervention was significantly increased if encephalopathy, ascites, anemia, or hypoalbuminemia was present before operation. A simple operative risk index involving the presence of encephalopathy and ascites and the levels of hemoglobin and albumin is proposed to help distinguish a low-risk subgroup in whom postoperative mortality was 12.8 percent from a high-risk subgroup in whom postoperative mortality was 53.3 percent.     

Embolization of nonvariceal portosystemic collaterals in transjugular intrahepatic portosystemic shunts

Percutaneous embolization of large portosystemic collaterals was performed in three patients following placement of a transjugular intrahepatic portosystemic shunt in order to improve hepatopetal portal flow. Improved hepatic portal perfusion was achieved in these cases, thereby theoretically reducing the risk of chronic hepatic encephalopathy.     

Familial hemiplegic migraine and autosomal dominant arteriopathy with leukoencephalopathy (CADASIL)

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently described familial cerebrovascular disorder shown to map to chromosome 19q12. Familial hemiplegic migraine has also been shown in some families to map close to the CADASIL locus. The fully developed CADASIL phenotype consists of recurrent strokes developing in the fourth decade, progressing to a pseudobulbar palsy, spastic quadriparesis, and subcortical dementia. In an Irish family 15 members were fully investigated by magnetic resonance scanning; 10 had typical magnetic resonance features of CADASIL. Five members of this family had familial hemiplegic migraine and 4 of these had magnetic resonance evidence of CADASIL. Two other members had migraine with and without aura as a presenting clinical symptom of CADASIL. This disorder has been shown by linkage analysis to map to the CADASIL locus at chromosome 19. The phenotype at presentation of CADASIL in this family was variable and age related and included familial hemiplegic migraine, migraine with and without aura, transient ischemic attacks, strokes, and spinal cord infarction. This family study increases our understanding of the spectrum of clinical manifestations of this underrecognized familial cerebrovascular disorder.     

A rapid and sensitive method for measuring monooxygenase activities in hepatocytes cultured in 96-well plates

Summary Measurement of biotransformation activities in cells is of great importance for drug metabolism and toxicologic studies. It is currently done by measuring the enzymatic activities in partially purified microsomes. In the present work we report on a rapid, easy, sensitive, and reproducible fluorimetric assay for quantifying cytochrome P450-dependent monooxygenase activities (P450IA1, P450IIB1) in hepatocytes cultured in 96-well plates. The procedure involves the direct determination of enzymatic activities in intact hepatocytes while avoiding cell homogenization, thereby permitting use of a the reduced number of cells and allowing cultured cells to be used in later experiments. Substrates (7-ethoxyresorufin, 7-pentoxyresorufin) are added to culture medium and metabolized by hepatocytes. After enzymatic deconjugation, the fluorescent resorufin present in culture medium is quantified by means of a microplate fluorimetric reader. Major advantages of this technique, as compared to other available methods, are: a) no cell disruption is required; b) activity can be measured with a very small number of cells; c) rapid processing time; and d) possibility of performing repeated assays with the same cell monolayer.     

An Interdisciplinary Clinical Advancement Program Within a Patient-Centered Care Model

Restructuring in health care does not have to compromise the pursuit of clinical excellence and quality patient care. The clinical advancement program (CAP) at the Hospital for Special Care is a newly developed multidisciplinary reward and recognition program for clinical staff. The program is integrated into the hospital's structure of service line management and, unlike traditional advancement programs, is open to all levels of care providers: professional personnel, technical staff, and aides. This article describes the basic features of the CAP model and how it was developed by a multidisciplinary task force.     

Enhanced dispersion of atrial refractoriness as an electrophysiological substrate for vulnerability to atrial fibrillation in patients with paroxysmal atrial fibrillation.

Atrial electrical remodeling plays a part in recurrence of atrial fibrillation (AF). It has been related to an increase in heterogeneity of atrial refractoriness that facilitates the occurrence of multiple reentry wavelets and vulnerability to AF. AIM: To examine the relationship between dispersion of atrial refractoriness (Disp_A) and vulnerability to AF induction (A_Vuln) in patients with clinical paroxysmal AF (PAF). METHODS: Thirty-six patients (22 male; age 55+/-13 years) with > or =1 year of history of PAF (no underlying structural heart disease--n=20, systemic hypertension--n=14, mitral valve prolapse--n=1, surgically corrected pulmonary stenosis--n=1), underwent electrophysiological study (EPS) while off medication. The atrial effective refractory period (AERP) was assessed at five different sites--high (HRA) and low (LRA) lateral right atrium, high interatrial septum (IAS), proximal (pCS) and distal (dCS) coronary sinus--during a cycle length of 600 ms. AERP was taken as the longest S1-S2 interval that failed to initiate a propagation response. Disp_A was calculated as the difference between the longest and shortest AERP. A_Vuln was defined as the ability to induce AF with 1-2 extrastimuli or with incremental atrial pacing (600-300 ms) from the HRA or dCS. The EPS included analysis of focal electrical activity based on the presence of supraventricular ectopic beats (spontaneous or with provocative maneuvers). The patients were divided into group A--AF inducible (n=25) and group B--AF not inducible (n=11). Disp_A was analyzed to determine any association with A_Vuln. Disp_A and A_Vuln were also examined in those patients with documented repetitive focal activity. Logistic regression was used to determine any association of the following variables with A_Vuln: age, systemic hypertension, left ventricular hypertrophy, left atrial size, left ventricular function, duration of PAF, documented atrial flutter/tachycardia and Disp_A. RESULTS: There were no significant differences between the groups with regard to clinical characteristics and echocardiographic data. AF was inducible in 71% of the patients and noninducible in 29%. Group A had greater Disp_A compared to group B (105+/-78 ms vs. 49+/-20 ms; p=0.01). Disp_A was >40 ms in 50% of the patients without A_Vuln and in 91% of those with A_Vuln (p=0.05). Focal activity was demonstrated in 14 cases (39%), 57% of them with A_Vuln. Disp_A was 56+/-23 ms in this group and 92+/-78 ms in the others (p=0.07). Using logistic regression, the only predictor of A_Vuln was Disp_A (p=0.05). CONCLUSION: In patients with paroxysmal AF, Disp_A is a major determinant of A_Vuln. Nevertheless, the degree of nonuniformity of AERP appears to be less important as an electrophysiological substrate for AF due to focal activation.