Benign biliary strictures associated with recurrent pyogenic cholangitis: treatment with expandable metallic stents

OBJECTIVE: The purpose of this study was to determine the long-term effectiveness of expandable metallic stents in benign biliary strictures associated with recurrent pyogenic cholangitis and the differences in primary patency of the various types of stents deployed. SUBJECTS AND METHODS: During a 20-month period, 26 metallic stents (19 Gianturco-Rosch Z stents and seven Strecker stents) were used to treat benign biliary strictures associated with recurrent pyogenic cholangitis in 23 patients (11 men and 12 women; mean age, 42 years; range, 30-78 years). Insertion routes were percutaneous transhepatic biliary drainage tracts for 16 stents, T-tube tracts for seven stents, and retrograde endoscopic routes for three stents. The deployed locations were common hepatic or common bile ducts for 11 stents, right or left hepatic ducts for 10 stents, and segmental ducts for five stents. RESULTS: The initial technical success rate was 100%. Two stents in one patient migrated spontaneously. Primary stent patency for the remaining 24 stents was 34 months (range, 3-58 months). Primary stent patency of the Gianturco-Rosch Z and Strecker stents was 50 and 10 months, respectively (p < .05). Primary stent patency for the intrahepatic and extrahepatic ducts was 50 and 18 months, respectively (p = .05). Primary patency rates for all stents at 6, 12, 24, and 36 months were 92%, 75%, 67%, and 46%, respectively. The causes of stent obstruction were recurrent stone or sludge in eight stents and epithelial hyperplasia in five stents. CONCLUSION: We believe that metallic stent placement is not an effective long-term treatment technique for benign biliary stricture associated with recurrent pyogenic cholangitis.     

The role of thyroid resection during reoperation for persistent or recurrent hyperparathyroidism

BACKGROUND: The role of "blind" thyroid lobectomy in the surgical management of patients with persistent or recurrent primary hyperparathyroidism is not known. We reviewed our experience with reoperation for hyperparathyroidism to determine the utility of blind thyroid resection in this setting. METHODS: From 1982 to 1995, 269 patients underwent reoperation for hyperparathyroidism at our institution. All patients had biochemical confirmation of hyperparathyroidism and underwent noninvasive and if necessary invasive localization studies. Patients who underwent thyroid lobectomy in an attempt to extirpate the hyperfunctioning parathyroid gland form the basis of this report. RESULTS: Thirty-two of 269 patients (12%) underwent thyroid lobectomy to remove a parathyroid gland. Intrathyroidal parathyroids were confirmed in 19 of 32 patients (59%). In 18 of 19 patients (94%), preoperative or intraoperative ultrasonography correctly identified an intrathyroidal lesion suspicious or a parathyroid. Only 1 of 6 patients (17%) undergoing a blind thyroidectomy had an intrathyroidal gland identified. Ultrasonography had a sensitivity of 95% and a negative predictive value of 99.5% in detecting an intrathyroidal parathyroid gland. CONCLUSIONS: The prevalence of an intrathyroidal parathyroid gland in our series is low (19 of 269, 7%). Ultrasonography can be used reliably to select patients for thyroid resection, reducing the need to perform a blind thyroid lobectomy and avoiding the potential morbidity of thyroid resection in this clinical setting.     

Outcome analysis of vesicoureteral reflux in children with myelodysplasia

PURPOSE: Vesicoureteral reflux in children with myelodysplasia is usually secondary to abnormal bladder storage. The purpose of this study was to assess the outcome of vesicoureteral reflux in children with myelodysplasia. MATERIALS AND METHODS: We retrospectively analyzed the records of 319 children with myelodysplasia who presented to our institution between 1978 and 1985. Of these children 95 presented with or had reflux during followup and they were treated with prophylactic antibiotics. Clean intermittent catheterization and anticholinergic medication were added to the regimen when indicated. RESULTS: Reflux resolved in 63% of these patients with nonsurgical management. Temporary cutaneous vesicostomy was performed in 23 children (24%) with persistent high grade reflux or evidence of upper tract deterioration. Ureteral reimplantation and augmentation cystoplasty were performed in 18 (20%) and 8 (8%) patients, respectively. No patient had progression to chronic renal failure and scars developed in only 14 kidneys (10%). CONCLUSIONS: In the majority of cases (63%) reflux resolved with nonsurgical management. Reflux in these patients should not be treated in isolation. The management of reflux is primarily aimed at improving bladder storage. The combination of aggressive nonsurgical therapy and close observation is recommended. This regimen leads to the satisfactory resolution of reflux with minimal renal morbidity.     

Thalidomide: lack of mutagenic activity across phyla and genetic endpoints

The human and rabbit teratogen thalidomide has been tested for mutagenicity in a wide range of assays, ranging from bacterial gene mutation assays conducted in vitro to in vivo cytogenetic assays conducted using rabbits, and including a variety of human-derived tissues. Thalidomide was not mutagenic to 6 strains of Salmonella when tested both in the presence and absence of Aroclor-induced rat liver S9 mix. This inactivity was confirmed in strains TA98 and TA100 using a 1-h pre-incubation assay protocol with the same S9 mix (10% S9), and additionally, in strain TA98 using 3 concentrations of S9 (4%, 10% and 30% S9 in S9 mix). Thalidomide was not clastogenic either to cultured human lymphocytes (whole blood cultures, minus S9 mix) or to Chinese hamster ovary (CHO) cells treated in vitro. Further, no cytotoxicity was observed in purified human lymphocytes when exposed to thalidomide up to the limit of its solubility in the medium in the presence and absence of liver S9 from Aroclor-induced pregnant rabbit. The CHO assays were conducted without metabolic activation and in the presence of a variety of sources of auxiliary metabolic activation (PB/beta NP-induced rat liver S9 mix, pooled male and female human liver S9 mix, uninduced and Aroclor-induced pregnant rabbit liver S9 mix and foetal rabbit S9 mix). Thalidomide did not induce micronuclei in isolated human lymphocytes (minus S9 mix) and it was non-mutagenic to mouse lymphoma L5178Y TK+/- cells when tested to the limits of its solubility in the culture medium (+/- S9 mix). No indication of recombinogenic or clastogenic activity was observed for thalidomide when tested in Drosophila. In addition, it failed to induce chromosome aberrations in grasshopper neuroblasts when tested in the presence and absence of Aroclor-induced rat liver S9 mix. Some unusual chromosome morphologies were observed in the grasshopper cytogenetic preparations indicating a potential of thalidomide to interact with chromosomal proteins. However, this potential was not evident in the human lymphocyte micronucleus assay, and thalidomide was apparently not reactive to the proteins of the mouse skin, as it gave negative results in a mouse local lymph node assay for skin sensitizing agents. Thalidomide was inactive in bone marrow micronucleus assays conducted using males and females from two strains of mice, and female New Zealand white rabbits. It is concluded that thalidomide is neither a mutagen nor an aneugen. This conclusion is discussed within the context of the results of earlier mutagenicity studies, the recent claim that thalidomide may be a heritable germ cell mutagen to humans, and the current interest in thalidomide for the treatment of immune system-related diseases.     

Nitric oxide synthase-, N-methyl-D-aspartate receptor-, glutamate- and aspartate-immunoreactive neurons in the mouse arcuate nucleus: effects of neonatal treatment with monosodium glutamate

Glutamate-, aspartate-, N-methyl-D-aspartate receptor (NMDAR1 and 2 subunits)-, and nitric oxide synthase (NOS)-immunoreactive neurons were studied in the arcuate nucleus (AN) of mice treated neonatally with monosodium glutamate (MSG) which is known to cause extensive neuronal loss in this hypothalamic nucleus. It was found that intensely stained glutamate- and aspartate-immunoreactive neurons present in the AN of control mice were completely absent in the MSG-lesioned AN as well as the ventromedial nucleus lateral to the AN. Similarly, NMDAR1-immunoreactive neurons were mostly absent in the MSG-lesioned AN but remained intact in the ventromedial nucleus. There was also a substantial loss of NMDAR2 immunoreactivity within the AN. In contrast, NOS-immunoreactive neurons in the AN survived the neonatal glutamate treatment, although they appeared to be less intensely stained.     

Antibody-directed enzyme prodrug therapy: pharmacokinetics and plasma levels of prodrug and drug in a phase I clinical trial

OBJECTIVE: The objective of the study was to determine the major factors that underlie auditory/audiological performance measures in an elderly population, with particular emphasis on finding those factors responsible for speech understanding under specific conditions of interference. DESIGN: Audiological status and auditory performance of a group of elderly (60- to 81-yr-old) and normal-hearing young (18- to 30-yr-old) individuals was determined through a test battery. When present, the hearing loss of elderly subjects was symmetrical in the two ears and, at most, moderate. The battery included tests of speech intelligibility on the word and sentence levels, with and without the presence of interfering speech. In addition to pure-tone and speech reception thresholds, perception of spectrally or temporally distorted speech as well as auditory resolution of frequency, time, and space were tested. Two tests received special consideration: the Speech Perception In Noise Test and the Modified Rhyme Reverberation Test. Taking the overall results as well as various subsets of the results, principal component analyses were conducted to identify major factors underlying auditory performance. RESULTS: The factors extracted by the principal component analyses present a portrayal of the auditory performance profile in which effects of interference, high-frequency hearing, and basic auditory function play a major role. Interference factors include general susceptibility to noise as well as segregation of concurrent speech sounds on the basis of temporal dissimilarities and spatial separation. Comparison of factors extracted from various subsets of tests indicate that factors underlying the decline of the "cocktail party effect" in the elderly are addressed mostly by tests specifically designed to assess speech understanding in spatially distributed babble or in a reverberant environment. CONCLUSIONS: Factor analysis of test measures obtained from a group of elderly individuals with normal hearing or mild-to-moderate hearing loss led to two main findings. First, it portrayed hearing loss as a component of different factors rather than as a factor on its own. Second, the independence of measures of speech understanding in babble or reverberation from other measures suggests that such tests should become an integral part of audiological test batteries designed to assess auditory functions in aging.     

Effect of immune activation on the dynamics of human immunodeficiency virus replication and on the distribution of viral quasispecies

Virus replication in a human immunodeficiency virus (HIV)-infected individual, as determined by the steady-state level of plasma viremia, reflects a complex balance of viral and host factors. We have previously demonstrated that immunization of HIV-infected individuals with the common recall antigen, tetanus toxoid, disrupts this steady state, resulting in transient bursts of plasma viremia after immunization. The present study defines the viral genetic basis for the transient bursts in viremia after immune activation. Tetanus immunization was associated with dramatic and generally reversible shifts in the composition of plasma viral quasispecies. The viral bursts in most cases reflected a nonspecific increase in viral replication secondary to an expanded pool of susceptible CD4(+) T cells. An exception to this was in a patient who harbored viruses of differing tropisms (syncytium inducing and non-syncytium inducing [NSI]). In this situation, immunization appeared to select for the replication of NSI viruses. In one of three patients, the data suggested that immune activation resulted in the appearance in plasma of virus induced from latently infected cells. These findings illustrate certain mechanisms whereby antigenic stimulation may influence the dynamics of HIV replication, including the relative expression of different viral variants.