Hepatobiliary pruritus: what are effective treatments?

Pruritus is a common symptom in patients with hepatobiliary disease. Numerous treatments have been attempted. We review published therapeutic trials for hepatobiliary pruritus and utilize statistical analysis to evaluate treatment results. Randomized placebo-controlled studies show cholestyramine, rifampin, naloxone, S-adenosylmethionine, prednisolone, and propofol to be effective. Suggestions for future studies of the treatment of hepatobiliary puruitus are proposed.

Analysis by gender and Visual Imagery Reactivity of conventional and imagery Rorschach.

Examined here are the effects of gender and Visual Imagery Reactivity in 80 consecutively selected psychiatric outpatients. The participants were grouped by gender and by the amounts of responsiveness to preceding therapy work using imagery (Imagery Nonreactors and Reactors). In the group of Imagery Nonreactors were 13 men and 22 women, and in the Reactor group were 17 men and 28 women. Compared were the responses to standard Rorschach (Conventional condition) with visual associations to memory images of Rorschach inkblots (Imagery condition). Responses were scored using the Visual Imagery Reactivity (VIR) scoring system, a general, test-nonspecific scoring method. Nonparametric statistical analysis showed that critical indicators of Imagery Reactivity encoded as High Affect/Conflict score and its derivatives associated with sexual or bizarre content were not significantly associated with gender; neither was Neutral Content score which categorizes "non-Reactivity." These results support the notion that system's criteria of Visual Imagery Reactivity can be applied equally to both men and women for the classification of Imagery Reactors and Nonreactors. Discussed are also the speculative consequences of extending the tolerance range of significance levels for the interaction between Reactivity and sex above the customary limit of p < .05 in borderline cases. The results of such an analysis may imply a trend towards more rigid defensiveness under Imagery and toward lesser verbal productivity in response to either the Conventional or the Imagery task among women who are Nonreactors. In Reactors, men produced significantly more Sexual Reference scores (in the subcategory not associated with High Affect/Conflict) than women, but this could be attributed to the effect of tester's and subjects' gender combined.

The effect of a no-smoking policy on recruitment and retention in outpatient cocaine treatment.

Historically, directors of substance abuse treatment programs have been reluctant to adopt a smoke-free policy because of the fear of patient attrition. According to a recent survey, however, a number of program directors now believe that such fears may be unwarranted. The purpose of the present study was to examine the impact on admissions and attendance of adopting a smoke-free policy at a cocaine treatment program offering outpatient group therapy sessions 3 half days a week. Results indicated that implementation of this policy had no impact on the number of patients who sought treatment at the facility or the number of group sessions patients attended. It was also noteworthy that for a sample of cases active in the month prior to and the month following the ban there were no changes in attendance patterns or in the proportion of patients failing to return from a 10-15 minute therapy break despite the fact that 89% of these patients were cigarette smokers.

Acute electrical stimulation increases extramyocardial collateral blood flow after a cardiomyoplasty.

We hypothesized that acute electrical stimulation of a latissimus dorsi cardiomyoplasty would augment the collateral blood flow delivered by the skeletal muscle to the heart. This hypothesis was tested in an animal model (13 goats) of coronary artery disease. Six weeks after a cardiomyoplasty was performed, myocardial collateral blood flow derived from the latissimus dorsi muscle was measured with colored microspheres when the muscle was at rest and during electrical stimulation of the thoracodorsal nerve at 1.25 Hz. The area at risk for ischemia averaged 13.37 +/- 2.08 g (mean +/- standard error), or 18.4% of left ventricular mass (n = 13). At rest, significant skeletal muscle-derived collaterals developed in 9 animals, and formed predominantly to chronic ischemic myocardium (mean +/- standard error, 0.07 +/- 0.02 mL.g-1 x min-1; n = 9), rather than infarct (0.03 +/- 0.02 mL.g-1 x min-1; n = 5), or normal myocardium (0.0005 +/- 0.0001 mL.g-1 x min-1; n = 9). Stimulation increased skeletal muscle-derived collateral blood flow to chronic ischemic areas to 0.38 +/- 0.09 mL.g-1 x min-1 (n = 9) (p < 0.05). During stimulation, the collateral flow was greater in the epicardium (0.46 +/- 0.11 mL.g-1 x min-1) than in endocardium (0.14 +/- 0.09 mL.g-1.min-1) (p < 0.05). This study demonstrates that electrical stimulation of a latissimus dorsi cardiomyoplasty increases extramyocardial collateral blood flow to chronic ischemic myocardium.

Clinical predictive factors for development of recurrence and metastasis in conjunctival melanoma: a review of 68 cases.

Sixty eight cases of histologically proved conjunctival melanoma were reviewed in order to determine the clinical factors that were predictive of local recurrence and distant metastasis. All patients were treated with surgical excision and most had supplemental cryotherapy. The mean follow up was 7.5 years. Histopathologically, the conjunctival melanoma arose from primary acquired melanosis in 56%, from naevus in 26%, and de novo in 18%. Of the 68 patients, 38 (56%) developed at least one local tumour recurrence and 22 (32%) developed more than one recurrence. The method of initial treatment and the eventual development of metastasis were the two parameters statistically associated with tumour recurrence. Those patients treated initially with tumour excision alone had a statistically significant higher recurrence rate than those treated initially with excision and supplemental cryotherapy (p = 0.001). Fourteen patients (21%) developed metastasis and the mean period between treatment and metastasis was 3.6 years. Twelve (18%) died from metastatic melanoma with a mean interval of 4.4 years from the time of initial surgery until death. The only clinical parameter that was statistically associated with distant metastasis was local tumour recurrence (p = 0.015). Based on these observations, the authors make recommendations regarding the treatment of conjunctival malignant melanoma. It appears that initial complete excision of the tumour with supplemental cryotherapy offers the patient the best chance of remaining free of recurrence and metastasis.

Iron enhances tumor growth. Observation on spontaneous mammary tumors in mice.

Iron is essential for the growth of all cells, including tumor cells. The authors previously reported that a variety of transplantable tumors grew faster and larger in mice that were on an iron-rich diet compared with those on an iron-deficient diet. In this study the authors examined the relationship between iron in the diet and development of tumors in mice that are known to develop spontaneous tumors--C3H/HeN-MTV+(C3H-MTV+) mice that were congenitally infected with mammary tumor virus. These mice have a greater than 96% chance of developing mammary tumors between the ages of 7.2 and 9.2 months. Fifteen C3H-MTV+ weanlings were given a low-iron diet (5 mg iron/kg diet), and 15 were given diets with normal amounts of iron (180 mg Fe/kg diet). Thirteen of the 15 mice from the low-iron group and all 15 mice from the normal-iron group developed tumors. The average tumor growth rate in the normal-iron group was 112%/wk, compared with 62%/wk for the low-iron group. The difference in tumor growth rate between the two groups was significant (P = 0.02 by Student's t test). In this study, low iron intake did not prevent tumor development, but the results confirm the authors' previous report that iron nutrition of the host affects tumor growth; tumors grow better in an iron-rich environment. High levels of iron in the diet may enhance tumor growth, and this should be considered when treating patients with cancer.

Uveal melanoma in teenagers and children. A report of 40 cases.

A review of 3706 consecutive patients with uveal melanoma revealed that 40 patients (1.1%) were age 20 years or younger at the time of diagnosis. The youngest patient was age 6 years but the majority of patients (78%) were between 15 and 20 years old. The tumor occurred in the iris in 5 cases (12%) and in the posterior uvea in 35 cases (88%). The mean largest tumor dimension and thickness was 10 mm and 5 mm, respectively. In all cases, the diagnosis of uveal melanoma was suspected before referral, and misdirected treatment was avoided. The tumor was initially treated by enucleation in 24 cases (60%), local resection in 7 (18%), plaque radiotherapy in 3 (8%), and observation in 6 (15%). Secondary treatment was required in 7 cases in the form of enucleation (4 cases), ablative laser (1 case), plaque radiotherapy (1 case), and exenteration (1 case). The mean follow-up period was 68 months (median, 48 months) from the time of treatment, and only one patient died of metastases (from a massive ciliochoroidal melanoma 33 months after treatment). The remainder of the group of young patients are alive and healthy. Cumulative survival rates show that 96% of young patients with uveal melanoma survive at the 5-year period.

Uveal melanoma and pregnancy. A report of 16 cases.

A review of 3706 consecutive patients with uveal melanoma over a 17-year period revealed that 16 patients (0.4%) were pregnant women at the time of diagnosis. The mean age at presentation in this group was 30 years and the mean months of gestation at the time of diagnosis of the posterior uveal melanoma was 6 months. Seven of the sixteen tumors were active uveal melanomas at the initial examination and were treated immediately, while the remaining nine tumors were initially diagnosed as suspicious choroidal nevi or dormant choroidal melanomas, seven of which grew into active melanomas during the course of the pregnancy, necessitating therapy. The tumors were managed by enucleation in 10 cases, plaque radiotherapy either during or after pregnancy in 4 cases, and observation in 2 cases. Histopathologically, the melanomas did not differ appreciably in cell type, mitotic activity, and other features when compared with a matched group of tumors in nonpregnant women. All of the patients who elected to carry the pregnancy to term (14 cases) delivered healthy babies with no placental or infant metastases. The 5-year survival rate using the life table method in these pregnant women with posterior uveal melanoma is 71% and is similar to the survival of nonpregnant women with posterior uveal melanoma reported in other series.

Enucleation after plaque radiotherapy for posterior uveal melanoma. Histopathologic findings.

A review of 1019 patients with posterior uveal melanomas, who were treated with episcleral plaque radiotherapy between April 1976 and December 1987, showed that 59 (6%) of these patients have thus far required enucleation of the affected eye. The most common clinical reasons for enucleation were tumor regrowth (51%) and neovascular glaucoma (31%). These irradiated melanomas were of mixed cell type in 40 cases (68%), spindle in 10 cases (17%), totally necrotic in 7 cases (12%), and epithelioid in 2 cases (3%). Some degree of tumor necrosis was seen in all cases. Overall, the median number of mitoses per 40 high-power fields in these irradiated tumors was 0. Most (64%) of the tumors had no identifiable mitosis in 40 high-power fields. A three-way simultaneous comparison of the following groups was made: irradiated eyes enucleated for tumor regrowth, irradiated eyes enucleated for neovascular glaucoma, and a matched group of nonirradiated posterior uveal melanomas. This comparison showed that the largest tumor dimension was significantly greater in the irradiated eyes enucleated for tumor regrowth than in the other two groups. Mitotic activity was significantly higher in the irradiated tumor regrowth and nonirradiated groups than in the irradiated neovascular group. There was no significant difference among the three groups in an analysis of height. The results suggested that mitotic activity may exist after plaque radiotherapy, especially when there is clinical evidence of tumor regrowth.

Central retinal vein obstruction and axial length.

The axial lengths of 24 consecutive adult eyes with unilateral central retinal vein obstruction (CRVO) were compared with those of contralateral unaffected eyes and those of a control population. The lengths of the two eyes of persons with a unilateral CRVO were not significantly different. By contrast, eyes of persons with CRVO averaged 0.67 mm (approximately 2 diopters) shorter than their control counterparts (P = .03). This anatomic difference may be a factor in the development of CRVO.

Tamoxifen and trifluoroperazine (Stelazine) potentiate cytostatic/cytotoxic effects of P-30 protein, a novel protein possessing anti-tumor activity.

P-30 protein, a novel protein isolated in our laboratory from fertilized Rana pipiens eggs, has been shown to possess significant anti-proliferative and cytotoxic activity against a variety of human tumour cell lines. This protein also shows a potent anti-tumour activity in vivo in animal tumour models and is currently undergoing Phase I human clinical trials in cancer patient volunteers. The present study describes the in vitro effects of the concerted action of this protein and two other agents which affect the cell proliferative cycle. A significant potentiation of the P-30 protein-induced cell growth inhibition by tamoxifen as well as trifluoroperazine (Stelazine) in both the human A-549 lung carcinoma and the ASPC-1 pancreatic adenocarcinoma systems at wide ranges of drug concentrations was observed. The effect was apparently due to the synergistic action of P-30 protein and the agents tested. This data may provide clues that can be useful in explaining the mechanism of its anti-tumour activity. The results are also helpful for the designing in vivo animal and, perhaps eventually, human studies, whereby the combination therapies utilizing P-30 protein with agents of relatively low toxicity such as tamoxifen and/or Stelazine could offer a promising treatment(s) for these notoriously refractory types of human cancer.

The ocular ischemic syndrome. II. Mortality and systemic morbidity.

The cases of 52 consecutive persons with ocular ischemic syndrome (ocular symptoms and signs attributable to severe carotid artery obstruction) were studied. Followup disclosed a five year mortality of 40%. In comparison, an age and sex matched control group from the Framingham study had a five year mortality of 11%. The leading cause of death was cardiac disease (63%), while stroke was second (19%). Other associated diseases included systemic arterial hypertension (73%), diabetes mellitus (56%) and peripheral vascular disease (19%).

Extracellular potassium ion dynamics and ventricular arrhythmias in the canine heart.

The relation between extracellular potassium ion activity [( K+]o) and ventricular tachyarrhythmias was studied in an open chest canine model with the use of two protocols. In Protocol I, potassium chloride was administered into the proximal left anterior descending coronary artery at a rate of 0.125 mEq/min for either 20 min or until [K+]o = 20 mEq/liter, whichever came first. In Protocol II, the proximal left anterior descending coronary artery was occluded in one step and was reperfused 20 min later. Fifteen dogs were subjected to Protocol I, nine of which were also subjected to Protocol II. In the latter group, a recovery period of greater than or equal to 1 h separated the two protocols. Local K+ and intramyocardial activities were recorded with use of bifunctional ion-sensitive plunge electrodes at multiple sites located in the region of the left ventricle perfused by the left anterior descending artery and at one site outside of this region. The following variables were recorded and analyzed: Lead II electrocardiogram, heart rate, systemic arterial blood pressure, local [K+]o and its time derivative (dK+/dt), local electrograms and ventricular arrhythmias. Maximal [K+]o and dK+/dt were 23 +/- 3 mEq/liter and 9 +/- 1 mEq/liter per min in Protocol I and 14 +/- 1 mEq/liter and 3 +/- 1 mEq/liter per min in Protocol II, respectively. In both protocols, the occurrence of ventricular arrhythmias correlated with [K+]o (p less than 0.02) as well as with dK+/dt (p less than 0.05). Ventricular arrhythmias were more frequent and more severe in Protocol II than in Protocol I (p less than 0.05). Therefore, whereas K+ dynamics were more pronounced in Protocol I, ventricular arrhythmias were more severe in Protocol II. This occurrence was apparently due, at least in part, to less heterogeneous changes in K+ gradients during constant K+ infusion. It was concluded that, in addition to the magnitude of [K+]o, the rate of change of this variable (that is, dK+/dt) apparently plays an important role in the genesis of ischemic ventricular arrhythmias.

Adenosine mediates the negative chronotropic action of adenosine 5'-triphosphate in the canine sinus node.

ATP exerts pronounced electrophysiologic effects in the mammalian heart. The present study tested the hypothesis that the negative chronotropic action of ATP in the canine sinus node is dependent on its degradation to adenosine. Increasing doses of the following compounds were administered in the sinus nodal artery of 12 open chest dogs (either sex, 30-35 kg) anesthetized with pentobarbital (30 mg/kg i.v.): adenosine, ATP, alpha,beta methylene-ATP (AMPCPP) and beta,gamma methylene-ATP (AMPPCP). Right atrial, His bundle and right ventricular electrograms as well as Lead II ECG and systemic arterial blood pressure were monitored continuously and recorded. The depressant effects of test compounds on the sinus node were assessed from the prolongation of sinus cycle length and the duration of junctional escape rhythm which they induced. Data were used to plot dose-response curves for the four test compounds. The order of potency was adenosine greater than or equal to ATP greater than or equal to AMPPCP much greater than AMPCPP = 0. In 3 of 12 dogs the emergence of junctional escape rhythm was observed after the highest dose of either adenosine, ATP or AMPPCP. In addition, aminophylline, a selective competitive inhibitor of adenosine at P1-purinoceptor site, reduced the effects of maximal doses of adenosine, ATP and AMPPCP by 52 +/- 7, 67 +/- 8 and 72 +/- 6%, respectively (each, P less than .05; AMPPCP vs. adenosine, P less than .05). The present data indicate that the negative chronotropic action of ATP is due to its rapid catabolism to adenosine and the action of adenosine at P1-purinoceptor sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors affecting outcome of sarcoidosis. Influence of race, extrathoracic involvement, and initial radiologic lung lesions.

Chest roentgenograms of 152 patients with type 2/3 disease observed 3 or more years were reviewed using modified ILO/UC nomenclature. After a mean length of observation of 9.3 years, clinical recovery was observed in 71.7% and radiologic recovery in 48.0% of the patients. Age; duration of observation; mediastinal adenopathy; and character (xyz, pgr, stu), size, extent, and profusion of pulmonary densities were similar in the 53 white and 99 black patients, who differed significantly only in sex distribution. White patients achieved clinical recovery (84.9%) more often than black patients (64.7%) (p = .05). Factors influencing clinical recovery were analyzed by means of stepwise logistic linear regression. The initial roentgenographic features were unrelated to outcome; only race and extrathoracic disease proved to have significant predictive value. The probability of clinical recovery is estimated to be .894 in white patients with disease limited to the chest, .697 in white patients with extrathoracic disease, and .760 in black patients without and .454 in black patients with extrathoracic sarcoidosis. Recovery appears to be related not to the severity of the initial pulmonary reaction but to racially associated factors that influence extrathoracic dissemination as well as lung damage.

Factors affecting descending binaural loudness balances as a manifestation of adaptation.

Three trained adults with normal hearing were exposed to a continuous 1-kc/s pure tone in both ears simultaneously at 100 db SPL. In the R ear the tone was attenuated at 1 db/sec until it was inaudible. In the L ear the tone was attenuated at 5 db/sec, and S was asked to adjust the loudness in the L ear by pushing and releasing a hand-switch as in Bekesy audiometry in order to maintain so far as possible a binaural loudness match. At every reduction of 10 db in the R ear (i.e., every 10 sec) the SPL to the L ear was measured from the Bekesy-type tracing which yielded binaural loudness match. While there were inter-subject variations, for all Ss the level of the tone in the L ear (5 db/sec) had to be increased above physical equality for equal loudness, indicating the presence of more rapid adaptation in that ear. The disparity in 2 Ss progressed regularly from near zero after 10 sec to 16-17 db after 1 min. For 1 S, a constant disparity of about 6 db existed throughout the session. Binaural loudness balances by this descending method may be considered a manifestation of normal adaptation, confirming a previous report (Harbert and Young, J. Acoust. Soc. Am., 1968, 43, 752-756) for threshold differences produced by various attenuation rates at various suprathreshold starting levels. An analogous ascending procedure with 1 S yielded results susceptible to the same interpretation.

A Bekesy descending-only procedure: effects of attenuation rate and step size, and starting level.

Bekesy fixed-frequency thresholds for pulsed and continuous tones at 1 kc/s yielded by a descending-only technique were compared for suprathreshold starting levels of 38, 58, 78, and 98 db SPL, and attenuation rates of 1, 2, 4, and 8 db/sec with associated attenuation steps of 0.25, 0.5, 1, and 2 db, respectively, with 3 normal-hearing adults. For pulsed tones of 250 msec (duty cycle 50%), thresholds were not significantly affected by attenuation rate/step size or by starting level. However, for continuous tones, increasing attenuation rate/step size yielded better thresholds for a given starting level. Decreasing starting level yielded better thresholds for a given attenuation rate/step size. Thus, deteriorated thresholds were yielded by the slower attenuations/step sizes and by the higher starting levels. These data may be explained as a manifestation of normal adaptation. The similar relative effects found here of attenuation rate/step size and of starting level, as compared to the data of an earlier study (Harbert and Young, 1968) which used the traditional up-down Bekesy method of threshold tracing lend support to the possible future clinical use of a descending-only technique.