A diagnosis of eosinophilic esophagitis is associated with increased life insurance premiums.

Eosinophilic esophagitis (EoE) is a chronic disease that can be diagnosed at any age, but is not associated with malignancy and does not shorten lifespan. It remains unknown whether an EoE diagnosis affects insurability or insurance premium costs. We therefore aimed to determine whether a diagnosis of EoE affects the costs of life insurance. Our investigation was a secret shopper audit study whereby we contacted national insurance companies in the United States to evaluate the effect of a diagnosis of EoE on life insurance premiums. We constructed standardized case scenarios for males and females, including a 25-year-old and a 48-year-old without other comorbid conditions, who either had or did not have a diagnosis of EoE. Companies were asked for their best estimate for a $100,000 whole life insurance policy. Comparisons between median premiums were made using the Mann-Whitney U test. There were 20 national life insurance companies contacted and a total of 73 quotes were obtained. The median premium rate was similar for EoE and non-EoE cases at the younger age ($828 [IQR $576-1,020] vs. $756 [IQR $504-$804]; P = 0.10). However, the premium for the older case without EoE was 19% less expensive compared to a case with EoE ($1990 [IQR $1,248-2,350] vs. $2,375 [IQR $2,100-2568; P = 0.02]. This finding was not explained by sex or state of residence. Based on these findings, we conclude that life insurance premiums are significantly more expensive in the older patient case with EoE when compared to the same case without EoE. Patients with EoE and their providers should be aware of the additional cost associated with this diagnosis.

Modulation by thyroid status of hepatic low Km phosphodiesterase.

The effects of thyroid status on the activity of hepatic cAMP phosphodiesterase (PDE) were studied in the rat. Male rats were rendered hyperthyroid by treatment with T3 or hypothyroid by treatment with propylthiouracil. The hepatic particulate low Km PDE was solubilized, and its activity was measured at concentrations of 0.12-1.3 microM cAMP. The Km decreased in hypothyroidism and tended to increase in hyperthyroidism with respect to individual controls. The maximal velocity (Vmax) was unaffected by changes in thyroid status. The increases in Km correlated with increasing plasma T3, whereas the Vmax did not. Concentrations of cAMP increased in the livers from hyperthyroid rats and decreased in those from hypothyroid, in comparison with euthyroid rat livers. The effects of thyroid status on various aspects of hepatic lipid metabolism reported from this laboratory may, in part, have resulted from alterations in hepatic cAMP concentrations. These alterations, may have resulted secondarily from changes in the activity of hepatic PDE by changes in the Km for cAMP with little change in the Vmax.

Cimetidine inhibition of ethmozine metabolism.

Ethmozine, a phenothiazine antiarrhythmic, is effective in atrial and ventricular arrhythmias. Because of the extensive hepatic metabolism of ethmozine, we investigated the effects of the potent hepatic enzyme inhibitor cimetidine on the kinetics and dynamics of ethmozine. Eight healthy men 22 to 40 years old (means = 27.6 years) received a single, oral, 500 mg dose of ethmozine. Ethmozine dosing was repeated 15 days later after cimetidine, 300 mg four times a day for 7 days. Plasma samples were drawn over the next 24 hours for measurement of ethmozine. ECGs were obtained 1, 2, 4, 8, and 24 hours after each dose. After cimetidine, ethmozine clearance fell from 38.2 +/- 10.7 to 19.7 +/- 4.2 ml/kg/min and the t1/2 increased from 3.3 +/- 1.3 to 4.6 +/- 1.6 hours. Ethmozine prolonged the PR and QRS intervals, but there was no detectable further increase after cimetidine. Heart rate and blood pressure were not altered by ethmozine either alone or in the combination. We conclude that cimetidine increases plasma concentrations of ethmozine but did not induce any detectable further increase in the PR or QRS intervals.

Effect of cirrhosis and debrisoquin phenotype on the disposition and effects of pinacidil.

Pinacidil is an investigational vasodilator currently undergoing clinical trials as an antihypertensive agent. It is metabolized in humans to pinacidil N-oxide. To determine whether pinacidil's metabolism or effects were influenced by either liver disease or the subject's debrisoquin phenotype, eight patients with chronic stable cirrhosis and 13 healthy subjects were studied. Seven of the healthy volunteers were extensive metabolizers of debrisoquin, whereas six were of the poor metabolizer phenotype. Neither the clearance of pinacidil nor the production of the N-oxide was altered by the subjects' debrisoquin phenotype. Cirrhosis produced a 50% reduction in pinacidil's clearance (20.7 +/- 1.4 vs. 42.1 +/- 5.1 L/hr; P less than 0.0005) and a prolongation in the elimination t1/2 from 3.9 +/- 0.3 to 6.1 +/- 0.6 hours (P less than 0.01). Less pinacidil was metabolized to the N-oxide metabolite in the patients with cirrhosis than in the normal individuals. Thus pinacidil's metabolism and clearance are reduced in patients with cirrhosis but are independent of debrisoquin phenotype.

Influence of debrisoquin phenotype on the inducibility of propranolol metabolism.

The effects of rifampin (600 mg) once daily for 22 days on the total and fractional metabolic clearances of propranolol were determined in a group of six genetically extensive (EM) and six poor metabolizers (PM) of debrisoquin. The impaired ability of PMs to metabolize propranolol to the ring-oxidized metabolite 4-hydroxypropranolol was confirmed. The total oral clearance of propranolol increased about fourfold in both phenotypes from 219.2 +/- 52.8 to 976.7 L/hr in the EMs and from 75.0 +/- 12.6 to 289.8 +/- 78.2 L/hr in the PMs. The extent of induction of glucuronidation was similar in the two groups. 4-Hydroxylation was induced in both phenotypes but the increase was fifteenfold greater in EMs than in PMs. This would imply that the cytochrome P-450 determined by the debrisoquin allele or some coinherited 4-hydroxylase(s) was induced to a greater extent in EMs than PMs.

Reduction of liver plasma flow by caffeine and theophylline.

Caffeine and theophylline block the vasodilating effects of adenosine and may act to enhance sympathoadrenal discharge and activate the renin-angiotensin system. To determine if these methylxanthines might thereby have effects on regional blood flow, we studied the influence of caffeine and theophylline on apparent liver plasma flow (LPF) in normal subjects as assessed by indocyanine green clearance. Oral caffeine, 250 mg, reduced LPF by 19% from 630 +/- 150 to 510 +/- 120 ml/min (P less than 0.001). Intravenous theophylline (4.3 mg/kg) reduced LPF by 15% from 550 +/- 50 to 470 +/- 90 ml/min (P less than 0.05). These methylxanthine-induced falls in LPF may alter the disposition of concomitantly administered drugs. Because of their widespread use in Western society, caffeine and theophylline may be major determinants of liver blood flow in the general population. They may therefore prolong the t1/2 and increase steady-state levels of hepatically eliminated drugs.

Technetium-99m (v) dimercaptosuccinic acid uptake in patients with head and neck squamous carcinoma: experience in imaging.

A recently developed imaging agent, technetium-99m (v) dimercaptosuccinic acid (99mTc (v) DMSA), has been used to assess head and neck squamous carcinoma (SCC). We have prospectively studied 62 patients of whom 53 had a histologically proven head and neck SCC. The remaining nine had benign lesions. The results of planar imaging in patients with primary disease yielded an 85% sensitivity and 78% specificity. Planar imaging in patients with cervical lymphadenopathy revealed a 59% sensitivity. Nineteen patients also had single photon emission computed tomography imaging which improved the image quality, spatial resolution and sensitivity of the investigation. Twenty-seven patients were scanned before and after radiotherapy and, of these, 96% showed positive uptake in the salivary glands with no evidence of tumor recurrence. This study has shown 99mTc (v) DMSA imaging provides a cheap and rapid method of investigating head and neck SCC and further studies are necessary to evaluate its role in the management of patients with this disease.

Malignant hemangiopericytoma of the parapharyngeal space.

Hemangiopericytoma is a rare vascular neoplasm, occasionally occurring in the head and neck region. Diagnosis is made histologically, but even then, it is difficult to predict the behavior of the tumor in an individual patient. The patient described in this report presented with symptoms of parapharyngeal compression due to such a tumor. It is believed that malignant hemangiopericytoma has not been previously reported in this site.

Effects of glucagon on cAMP accumulation and ketogenesis in hepatocytes from euthyroid and hypothyroid rats.

The resistance to the effects of glucagon was studied in isolated hepatocytes prepared from male rats treated with 6N-propyl-2-thiouracil (PTU). Incorporation of [14C]oleate into ketone bodies in response to various concentrations of glucagon (10(-5) to 10(-10) M) was reduced in hepatocytes from hypothyroid rats compared with the euthyroid group. The reduced sensitivity to the effects of glucagon on ketogenesis after treatment with PTU was associated with a reduced ability of those hepatocytes to maintain cyclic adenosine-3',5'-monophosphate (cAMP) at levels required to stimulate ketogenesis. The concentration of cAMP in response to glucagon (10(-5) to 10(-10) M) was diminished in hepatocytes from hypothyroid rats, compared with those from euthyroid animals.

Experience in the surgical management of medullary thyroid carcinoma.

The management of 12 patients with medullary thyroid carcinoma is reviewed. All patients underwent total thyroidectomy. Local nodal and extracapsular spread was aggressively resected, followed by radiotherapy. No patient died from uncontrolled local disease. Prolonged survival after radical treatment is demonstrated even in the presence of distant metastases.

The management of thyroid swellings.

All cold solid nodules should be pursued relentlessly and all cancers of the thyroid, with the possible exception of anaplastic tumours, should be treated radically. The majority of differentiated cancers of the thyroid may carry a good prognosis but those which recur constitute a group of cases which are very difficult to manage and cure.

The management of tumours of the middle ear.

On the basis of a small number of cases, the majority of which were advanced, it would seem that extended surgery has a very definite place in the management of advanced glomus jugulare tumours, but very little place in the management of cancer of the middle ear with obvious signs of spread to adjacent parts.

Arterial epistaxis.

If arterial ligation is contemplated and the site of bleeding has not been identified it is reasonable to ligate the external carotid or maxillary artery, on the basis that this vessel supplies the major part of the nose. If bleeding persists in spite of ligation, this does not mean that the wrong vessel has been tied off but that arterial anastomoses are allowing blood to seep from the ethmoidal to the sphenopalatine area of the nose. If the anterior ethmoidal artery is to be ligated it is worth remembering that in 14-3 per cent of cases the anterior ethmoidal artery is absent unilaterally and in 2-4 per cent of cases absent bilaterally (Shaheen, 1967). The presence of a foramen with a periosteal cuff going through it does not necessarily mean that there is an artery present (Fig. 23). Finally, the blood vessel changes which occur and which are responisble for the persistence of nose bleeds in the elderly are a collagenous change in the muscle coat of medium and small arteries and calcification (not atheroma) in the larger feeding vessels.

Preservation of the accessory nerve in block dissection of the neck.

The signs and symptoms resulting from division of the accessory nerve are discussed. The anatomical arguments for conservative neck dissection are also described. A method of preserving the nerve during radical neck dissection is described. A comparison of the symptomatology and functional results of two groups of patients follows, one group having had preservation and the other having had conventional neck dissection. It was shown that the group with conservative neck dissection had no symptomatic or functional abnormalities.

The treatment of acromegaly by Yttrium implantation.

Yttrium implantation is one of the many ways of treating acromegaly. The advantages are the minor nature of the procedure and the fact that pituitary replacement is not as commonly required as after hypophysectomy. Thus in young female patients menstruation may be resumed following treatment and pregnancy has occurred. The procedure is not as free from complications as external irradiation but the response is more satisfactory.

On the immunology of head and neck cancer--a prognostic index. Preliminary communication.

A pilot study on the immune response in patients with carcinoma of the head and neck has been made. The clinical behaviour of such neoplasia is reasoned as being partly determined by the immunological response. If prognosis is related to competence of the immune system then this parameter should be assessed. DNCB (di-nitro-chloro-benzene) skin sensitization and serial lymphocyte transformation studies were performed on all patients whose progress was studied for at least two years. On analysing the results of survival, patients could be divided into two groups--DNCB positive and DNCB negative. The negative patients could be further subdivided; those with a lymphocyte stimulation index of over fifteen; and those beneath this level--the former had a much better prognosis than the latter. Also, such cancer patients were shown to have both cellular and serum factors causing depression of lymphocyte transformation. In the light of all findings, a future programme of investigation is proposed.

Malignant vagal paraganglioma.

Vagal paraganglioma is a rare usually benign tumour of neural crest origin. The malignant form of this tumour is very uncommon and the diagnosis is made on the basis of its clinical behaviour rather than its histological appearance. We report a case of vagal paraganglioma metastatic to adjacent cervical nodes and discuss the diagnosis and management of this tumour.

Atypical ameloblastoma: report of 3 cases and a review of the literature.

This paper presents 3 atypical ameloblastomas which had a fatal outcome. One had histological features indicative of malignancy but without metastasis, another developed pulmonary metastasis and the third died of extensive infiltration of the skull base. The features of malignant ameloblastoma are discussed and reported cases of malignant ameloblastoma between 1966 and 1993 are reviewed.