Changes in local free-living parasite populations in response to cleaner manipulation over 12 years.

Predation on parasites is an important ecological process, but few experimental studies have examined the long-term impacts on the prey. Cleaner fish prey upon large numbers and selectively feed on the larger individuals of the ectoparasitic stage of gnathiid isopods. Removal of cleaner fish Labroides dimidiatus for 1.5-12.5 years negatively affects coral reef fishes, but the mechanism is unclear. A reduction in local parasite populations or the size of individual parasites would benefit all susceptible fishes. We tested whether cleaner presence reduces local gnathiid populations using 18 patch-reefs distributed between two sites (both at Lizard Island, Great Barrier Reef) which were maintained cleaner-free or undisturbed for 12 years. Using emergence traps (1 m2), free-living gnathiid stages were sampled before and after cleaner fish were removed during the day and night, up to 11 times over the course of the experiment. There were effects of the removal in the predicted direction, driven largely by the response at one site over the other involving 200% more gnathiids, but manifested only in the daytime sampling after 4 months. There was also a main effect (36%) for the shared sample dates at both sites after 12 years. Gnathiid size occasionally differed with cleaner presence, but in no consistent way over time. Contrary to our predictions, changes in free-living gnathiid population numbers and their size structure rarely reflected the changes in fish populations and individuals observed on cleaner-free reefs. Therefore, evidence that this predator alone regulates gnathiids remains limited, suggesting other contributing processes are involved.

Phenotypic characterization of the KK/HlJ inbred mouse strain.

Detailed histopathological diagnoses of inbred mouse strains are important for interpreting research results and defining novel models of human diseases. The aim of this study was to histologically detect lesions affecting the KK/HlJ inbred strain. Mice were examined at 6, 12, and 20 months of age and near natural death (ie, moribund mice). Histopathological lesions were quantified by percentage of affected mice per age group and sex. Predominant lesions were mineralization, hyperplasia, and fibro-osseous lesions. Mineralization was most frequently found in the connective tissue dermal sheath of vibrissae, the heart, and the lung. Mineralization was also found in many other organs but to a lesser degree. Hyperplasia was found most commonly in the pancreatic islets, and fibro-osseous lesions were observed in several bones. The percentage of lesions increased with age until 20 months. This study shows that KK/HlJ mice demonstrate systemic aberrant mineralization, with greatest frequency in aged mice. The detailed information about histopathological lesions in the inbred strain KK/HlJ can help investigators to choose the right model and correctly interpret the experimental results.

Depletion of the cap-associated isoform of translation factor eIF4G induces germline apoptosis in C. elegans.

During mammalian programmed cell death, cleavage of the translation initiation factor 4G proteins (eIF4GI and eIF4GII) by caspase-3 induces the cap-independent synthesis of pro-apoptotic proteins. Apoptosis occurs naturally in the gonad to remove germ cells that are not selected to grow as oocytes and mature into eggs. Here, we describe two major isoforms of Caenorhabditis elegans eIF4G that are derived from a single gene (ifg-1) and their separate roles in germline homeostasis. Full length IFG-1 protein (170 kDa isoform) differs from the shorter isoform (130 kDa) by the inclusion of the N-terminal domain containing the putative eIF4E-binding site required for mRNA cap recognition. Depletion of the cap-associated p170 isoform induced CED-4 expression in oocytes and markedly increased germline apoptotic events, but did not prevent early mitotic germ cell proliferation. Loss of both p170 and p130 suppressed germ cell proliferation and arrested larval development. Evidence suggests that eIF4G isoforms are differentially utilized during oogenesis to regulate germ cell apoptosis. We propose that an alternative mechanism to eIF4G cleavage may be employed in germ cells by changing the availability of the p170 isoform.

Acupuncture-point stimulation for chemotherapy-induced nausea or vomiting.

BACKGROUND: There have been recent advances in chemotherapy-induced nausea and vomiting using 5-HT(3) inhibitors and dexamethasone. However, many still experience these symptoms, and expert panels encourage additional methods to reduce these symptoms. OBJECTIVES: The objective was to assess the effectiveness of acupuncture-point stimulation on acute and delayed chemotherapy-induced nausea and vomiting in cancer patients. SEARCH STRATEGY: We searched MEDLINE, EMBASE, PsycLIT, MANTIS, Science Citation Index, CCTR (Cochrane Controlled Trials Registry), Cochrane Complementary Medicine Field Trials Register, Cochrane Pain, Palliative Care and Supportive Care Specialized Register, Cochrane Cancer Specialized Register, and conference abstracts. SELECTION CRITERIA: Randomized trials of acupuncture-point stimulation by any method (needles, electrical stimulation, magnets, or acupressure) and assessing chemotherapy-induced nausea or vomiting, or both. DATA COLLECTION AND ANALYSIS: Data were provided by investigators of the original trials and pooled using a fixed effect model. Relative risks were calculated on dichotomous data. Standardized mean differences were calculated for nausea severity. Weighted mean differences were calculated for number of emetic episodes. MAIN RESULTS: Eleven trials (N = 1247) were pooled. Overall, acupuncture-point stimulation of all methods combined reduced the incidence of acute vomiting (RR = 0.82; 95% confidence interval 0.69 to 0.99; P = 0.04), but not acute or delayed nausea severity compared to control. By modality, stimulation with needles reduced proportion of acute vomiting (RR = 0.74; 95% confidence interval 0.58 to 0.94; P = 0.01), but not acute nausea severity. Electroacupuncture reduced the proportion of acute vomiting (RR = 0.76; 95% confidence interval 0.60 to 0.97; P = 0.02), but manual acupuncture did not; delayed symptoms for acupuncture were not reported. Acupressure reduced mean acute nausea severity (SMD = -0.19; 95% confidence interval -0.37 to -0.01; P = 0.04) but not acute vomiting or delayed symptoms. Noninvasive electrostimulation showed no benefit for any outcome. All trials used concomitant pharmacologic antiemetics, and all, except electroacupuncture trials, used state-of-the-art antiemetics. AUTHORS' CONCLUSIONS: This review complements data on post-operative nausea and vomiting suggesting a biologic effect of acupuncture-point stimulation. Electroacupuncture has demonstrated benefit for chemotherapy-induced acute vomiting, but studies combining electroacupuncture with state-of-the-art antiemetics and in patients with refractory symptoms are needed to determine clinical relevance. Self-administered acupressure appears to have a protective effect for acute nausea and can readily be taught to patients though studies did not involve placebo control. Noninvasive electrostimulation appears unlikely to have a clinically relevant impact when patients are given state-of-the-art pharmacologic antiemetic therapy.

Evidence for a tetrahydrobiopterin deficit in schizophrenia.

Tetrahydrobiopterin (BH(4)) is a vital cofactor maintaining availability of the amine neurotransmitters [dopamine (DA), noradrenaline (NA), and serotonin (5-HT)], regulating the synthesis of nitric oxide (NO) by nitric oxide synthase (NOS), and stimulating and modulating the glutamatergic system (directly and indirectly). These BH(4) properties and their potential relevance to schizophrenia led us to investigate the hypothesis of a study group (healthy controls, n=37; schizophrenics, n=154) effect on fasting plasma total biopterin levels (a measure of BH(4)). Study analysis showed a highly significant deficit of total biopterins for the schizophrenic sample after partialling out the effects of potential confounds of gender, age, ethnicity, neuroleptic use history and dose of current use, 24-hour dietary phenylalanine/protein ratio (a dietary variable relevant to BH(4) synthesis), and plasma phenylalanine (which stimulates BH(4) synthesis). A mean decrement of 34% in plasma total biopterins for schizophrenics from control values supports clinical relevance for the finding. In a subsample (21 controls and 23 schizophrenics), sequence analysis was done of the GTP cyclohydrolase I feedback regulatory gene and no mutations were found in the coding region of the gene. A deficiency of BH(4) could lead to hypofunction of the systems of DA, NA, 5-HT, NOS/NO, and glutamate, all of which have been independently implicated in schizophrenia psychopathology. Further, evidence has been accumulating which implicates the critical interdependence of these neurotransmitter systems in schizophrenia; this concept, along with the present study finding of a biopterin deficit, suggests that further study of the BH(4) system in schizophrenia is warranted and desirable.

Utility of the HIV dementia scale in assessing risk for significant HIV-related cognitive-motor deficits in a high-risk urban adult sample.

Considerable literature reflects the range of HIV-related neurocognitive complications, including relatively poor performance on tests of: movement and coordination; attention and concentration; reaction time; and mental flexibility. Efforts to develop appropriate screening techniques include the HIV Dementia Scale (HDS), a brief measure that has demonstrated promise but is lacking extensive independent evaluation. The present study examines the utility of the HDS in a sample of HIV-seropositive adults with a co-morbid history of psychiatric and substance use disorders. Forty subjects (65% male; mean age 41 years; mean education 12.2 years; 55% African American, 30% Caucasian) recruited for a study of the impact of brief psychotherapy on adherence to medications and medical appointments, relapse prevention, and/or enhancement of mental health functioning completed a battery of neuropsychological measures, including the HDS. Forty percent were identified as at high risk for significant cognitive-motor disorder (HDS total score < or =10). After controlling for age, education, illness (absolute CD4), and depressed mood, high-risk participants performed significantly worse on measures of simple and sustained divided attention, psychomotor speed, and working memory. However, only 25 of 40 (63%) were correctly classified based on their performance on traditional tests of neuropsychological functioning. Implications and limitations of the study are discussed.

Effects of glycemic control on target organ responses to epinephrine in type 1 diabetes.

Severe hypoglycemia occurs in intensively treated patients with type 1 diabetes mellitus (T1DM) due in part to deficient epinephrine counterregulatory responses. Previously, we have found that T1DM patients demonstrated a spectrum of altered responses to epinephrine at a variety of target organs compared with nondiabetic healthy subjects. What is not known is whether intensive glycemic control further modifies target organ responses in individuals with T1DM. Therefore, the aim of this study is to assess whether there is tissue specific (liver, muscle, adipose tissue, pancreas and cardiovascular) resistance to epinephrine in intensively controlled (IC) T1DM compared with those with conventional control (CC). Eight IC patients (age 33 +/- 4 yr, BMI 24 +/- 2 kg/m2, Hb A1C 6.7 +/- 0.1%), and 11 CC patients (age 35 +/- 3 yr, BMI 25 +/- 1 kg/m2, Hb A1C 9.6 +/- 0.1%) underwent two separate randomized, single-blind, 2-h hyperinsulinemic euglycemic clamp studies with (EPI) and without (NO EPI) epinephrine infusion. Epinephrine levels during EPI were similar in all groups (5,197 +/- 344 pmol/l). Glucose (5.3 +/- 0.1 mmol/l) and insulin levels (515 +/- 44 pmol/l) were similar in all groups during the glucose clamps. Endogenous glucose production (EGP) and glucose uptake (R(d)) were determined using [3-H3]glucose. Muscle biopsy was performed at the end of each study. IC had a significantly reduced EGP and R(d) responses to EPI compared with CC. Glucagon responses to EPI were similarly blunted in both IC and CC. Free fatty acid and glycerol response to EPI was greater in CC compared with IC. There was a significantly greater systolic blood pressure response to EPI in CC. We conclude that, despite similar epinephrine, insulin, and glucose levels, intensively treated T1DM patients had reduced cardiovascular, skeletal muscle, hepatic, and adipose target organ responses to EPI compared with conventionally treated T1DM patients.

Differing physiological effects of epinephrine in type 1 diabetes and nondiabetic humans.

Acute increases of the key counterregulatory hormone epinephrine can be modified by a number of physiological and pathological conditions in type 1 diabetic patients (T1DM). However, it is undecided whether the physiological effects of epinephrine are also reduced in T1DM. Therefore, the aim of this study was to determine whether target organ (liver, muscle, adipose tissue, pancreas, cardiovascular) responses to epinephrine differ between healthy subjects and T1DM patients. Thirty-four age- and weight-matched T1DM (n = 17) and healthy subjects (n = 17) underwent two randomized, single-blind, 2-h hyperinsulinemic euglycemic clamp studies with (Epi) and without epinephrine infusion. Muscle biopsy was performed at the end of each study. Epinephrine levels during Epi were similar in all groups (4,039 +/- 384 pmol/l). Glucose (5.3 +/- 0.06 mmol/l) and insulin levels (462 +/- 18 pmol/l) were also similar in all groups during the glucose clamps. Glucagon responses to Epi were absent in T1DM and significantly reduced compared with healthy subjects. Endogenous glucose production during the final 30 min was significantly greater during Epi in healthy subjects compared with T1DM (8.4 +/- 1.3 vs. 4.4 +/- 0.6 micromol.kg(-1).min(-1), P = 0.041). Glucose uptake showed almost a twofold greater decrease with Epi in healthy subjects vs. T1DM (Delta31 +/- 2 vs. Delta17 +/- 2 nmol.kg(-1).min(-1), respectively, P = 0.026). Glycerol, beta-hydroxybutyrate, and nonesterified fatty acid (NEFA) all increased significantly more in T1DM compared with healthy subjects. Increases in systolic blood pressure were greater in healthy subjects, but reductions of diastolic blood pressure were greater in T1DM patients with Epi. Reduction of glycogen synthase was significantly greater during epinephrine infusion in T1DM vs. healthy subjects. In summary, despite equivalent epinephrine, insulin, and glucose levels, changes in glucose flux, glucagon, and cardiovascular responses were greater in healthy subjects compared with T1DM. However, T1DM patients had greater lipolytic responses (glycerol and NEFA) during Epi. Thus we conclude that there is a spectrum of significant in vivo physiological differences of epinephrine action at the liver, muscle, adipose tissue, pancreas, and cardiovascular system between T1DM and healthy subjects.

Laparoscopic excision of a Brunner's gland hamartoma of the duodenum.

Brunner's gland hamartoma (adenoma) was first described in 1876. It is a rare hamartomatous lesion, with only 100 cases reported in the world literature. Treatment has been by endoscopic snaring. Open surgical excision was reserved for cases where snaring had failed. We report a case of a Brunner's gland hamartoma (2.4 cm) that was successfully resected by laparoscopic techniques. Postoperative hospital stay was brief (2 days), and there were no complications. This is the second reported case to be resected laparoscopically.

Biopharmacologic and herbal therapies for cancer: research update from NCCAM.

During the past decade, use of complementary and alternative medicine (CAM) by the American public increased from 34% in 1990 to 42% in 1995 with related out-of-pocket expenditures estimated at $27 billion. Among cancer patients, use of CAM ranges between 30 and 75% worldwide and includes dietary approaches, herbals and other biologically based treatments such as melatonin, mushrooms, shark cartilage and high dose vitamins and minerals. Concerns about herb-nutrient-drug interactions and product quality and standardization emphasize the need for rigorous research. In 1998, Congress mandated the creation of the National Center for Complementary and Alternative Medicine (NCCAM) to conduct and support such research of CAM therapies. The NCCAM portfolio for oncology is rapidly growing. As of July 2001, 26 projects are underway, two specialized centers are funded for cancer research and four botanical centers are cofunded with the Office of Dietary Supplements. Investigations are targeting herbals and complex herbal formulas; single dietary supplements and complex dietary regimens; biological agents; and mind-body, body-based and frontier approaches. Of these, biopharmacologic and herbal therapies are a major focus of research. The NCCAM portfolio illustrates how research of CAM, particularly studies of biopharmacologic and herbal approaches for cancer, is developing systematically and rigorously.

Brain blood flow changes in depressed patients treated with interpersonal psychotherapy or venlafaxine hydrochloride: preliminary findings.

BACKGROUND: Functional brain imaging studies in major depression have suggested abnormalities of areas, including the frontal cortex, cingulate gyrus, basal ganglia, and temporal cortex. We hypothesized that venlafaxine hydrochloride and interpersonal psychotherapy (IPT) might each alter brain blood flow in some or all of these areas on sequential single photon emission computed tomography (SPECT) scans. METHODS: Twenty-eight men and women aged 30 to 53 years with a DSM-IV major depressive episode, a 17-item Hamilton Rating Scale for Depression (HAM-D) rating of 18 or higher, and antidepressant-naive for at least 6 months were studied. After baseline (99m)technetium-hexa-methyl-propylene-amine-oxime scan, 1-T magnetic resonance imaging, and psychometric ratings, patients were assigned to different treatments. Thirteen patients had 1-hour weekly sessions of IPT from the same supervised therapist (E.M.). Fifteen patients took 37.5 mg twice-daily of venlafaxine hydrochloride. Single-photon emission computed tomography scans and ratings were repeated at 6 weeks. RESULTS: Both treatment groups improved substantially, more so with venlafaxine (mean [SD] HAM-D scores at pretreatment: IPT, 22.7 [2.7], and venlafaxine, 22.4 [3.1]; and posttreatment: IPT, 16.2 [7.1], and venlafaxine, 10.9 [8.6]). No patients had structural brain abnormalities. On analysis with statistical parametric mapping 96, the venlafaxine group showed right posterior temporal and right basal ganglia activation (P =.01), while the IPT group had limbic right posterior cingulate and right basal ganglia activation (P =.01). CONCLUSIONS: This preliminary investigation has shown limbic blood flow increase with IPT yet not venlafaxine, while both treatments demonstrated increased basal ganglia blood flow. This was, however, a short trial with a small sample, no control group, and different symptom reduction in the 2 groups.

Assessment of outcomes at alternative medicine cancer clinics: a feasibility study.

OBJECTIVE: This pilot study tested the feasibility of performing outcomes and more advanced research regarding cancer patients at two complementary and alternative (CAM) clinics. The primary objectives were to determine the feasibility of (1) obtaining and collecting data from medical records, (2) determining 5-year survival, and (3) comparing 5-year survival to that of conventional treatment. In addition, in this paper we present the barriers and recommend strategies to facilitate high-quality research. SETTINGS/LOCATION: The Bio-Medical Center in Tijuana, Mexico, and the Livingston Foundation Medical Center in San Diego, California. SUBJECTS: New patients who were treated for cancer during 1992 at the Livingston Foundation Medical Center and during the first quarter of 1992 at the Bio-Medical Center. RESULTS: Charts were available for 89.6% of the 307 new patients treated at the Bio-Medical Center; 149 (54%) patients were treated for cancer and 65 (43.6%) cases were confirmed by pathology reports. In contrast, all records were available for 193 new patients treated for cancer at the Livingston Clinic; 152 (78.8%) cases had pathology confirmation. At both clinics, patients were equally divided by gender and were predominantly Caucasian, were married, and were U.S. residents. On average, patients were 51-54 years old and within 1 year of diagnosis for breast, colorectal, lung, or male genital cancer. Most patients (61.1%-63.7%) arrived with distant or regional disease after conventional surgery and/or chemotherapy/radiotherapy. Survival at 5 years was determined for 57.0% at the Bio-Medical Center (11.4% were alive and 45.6% were deceased) and 94.8% at Livingston (14.5% were alive and 80.3% were deceased). The limited number of cases by cancer site prevented comparison to conventional treatment. CONCLUSIONS: Historical, widespread use of clinics such as these with anecdotal reports of extraordinary survival merit prospective, systematic monitoring of patient outcomes. For data to be meaningful, however, disease status must be pathologically confirmed and patient follow-up improved.

Differential mechanisms of plasminogen activator inhibitor-1 gene activation by transforming growth factor-beta and tumor necrosis factor-alpha in endothelial cells.

Plasminogen activator inhibitor-1 (PAI-1) is a serine protease inhibitor (SERPIN) specific for tissue-type and urokinase-like plasminogen activators. High plasma PAI-1 activity is a risk factor for thrombotic diseases. Due to the short half-life of PAI-1, regulation of PAI-1 gene expression and secretion of active PAI-1 into the blood stream is important for hemostatic balance. We have investigated transcriptional control of PAI-1 gene expression in bovine aortic endothelial cells (BAECs) and human cell lines using PAI-1 5' promoter-luciferase reporter assays. Contrary to the cytokine-induced up-regulation of PAI-1 mRNA and protein levels, we found that only transforming growth factor-beta (TGF-beta) was efficient in inducing PAI-1 promoter activation. Tissue necrosis factor-alpha (TNF-alpha) induced a small luciferase activity with the 2.5 kb PAI-1 promoter, but not with the PAI-800/4G/5G and p3TP-lux promoters. Next we investigated whether a lack of response to TNF-alpha was due to deficient signaling pathways. BAECs responded to TNF-alpha with robust NFkappaB promoter activation. TGF-beta activated the p38 MAP kinase, while TNF-alpha activated both the SAPK/JNK and p38 MAP kinases. The ERK1/2 MAP kinases were constitutively activated in BAECs. BAEC therefore responded to TNF-alpha stimulation with activation of the MAP kinases and the NFkappaB transcriptional factors. We further measured the messenger RNA stability under the influence by TGF-beta and TNF-alpha and found no difference. PAI-1 gene activation by TNF-alpha apparently is yet to be defined for the location of the response element and/or the signaling pathway, while TGF-beta is the most important cytokine for PAI-1 transcriptional activation through its 5' proximal promoter.

17beta-estradiol, but not raloxifene, decreases thrombomodulin in the antithrombotic protein C pathway.

Raloxifene is a nonsteroidal selective estrogen receptor modulator (SERM) that mimics the effects of estrogen on some plasma lipids and may have direct effects on the vascular wall. The objective of this study was to determine the effects of 17beta-estradiol, raloxifene, and LY139,478 (a related benzothiophene SERM) on the anticoagulant protein C pathway. In human vascular endothelial cells activated with interleukin-1 (IL-1), we demonstrated decreased thrombomodulin-dependent protein C activation. 17beta-estradiol reduced the anticoagulant properties of both unstimulated and IL-1-activated endothelial cells by decreasing thrombomodulin expression. In contrast, raloxifene and LY139,478 enhanced the anticoagulant properties of both unstimulated and IL-1-activated endothelial cells through upregulation of thrombomodulin. Regulation of the protein C pathway via thrombomodulin on vascular endothelium may be a novel mechanism by which SERMs could potentially confer cardioprotective effects and reduce the thrombotic risk associated with HRT in compromised patients.

Esophagogastric fistula secondary to teflon pledget: a rare complication following laparoscopic fundoplication.

Laparoscopic fundoplication has become the standard operation for gastroesophageal reflux disease. In our service, a laparoscopic fundoplication is performed as a 2-cm floppy 360 degrees wrap with division of the short gastric vessels and the fundoplication is sutured using a prolene 2/0 mattress suture (Ethicon, USA) and buttressed laterally with two teflon pledgets (PTFE 1.85 mm; low porosity, Bard, USA). We report a patient with post-operative dysphagia due to an esophagogastric fistula caused by erosion of a teflon pledget. This is the first such case in 734 laparoscopic fundoplications performed between January 1991 and December 1998. Reoperation was required, resulting in a prolonged convalescence. A review of current literature has not revealed any similar cases. Causes for this rare complication are postulated.

Complementary/alternative medicine use in a comprehensive cancer center and the implications for oncology.

PURPOSE: Oncologists are aware that their patients use complementary/alternative medicine (CAM). As cancer incidence rates and survival time increase, use of CAM will likely increase. This study assessed the prevalence and predictors of CAM use in a comprehensive cancer center. SUBJECTS AND METHODS: Subjects were English-speaking cancer patients at least 18 years of age, attending one of eight outpatient clinics at The University of Texas M.D. Anderson Cancer Center, Houston, TX, between December 1997 and June 1998. After giving written informed consent, participants completed a self-administered questionnaire. Differences between CAM users and nonusers were assessed by chi(2) and univariate logistic regression analysis. A multivariate logistic regression model identified the simultaneous impact of demographic, clinical, and treatment variables on CAM use; P values were two-sided. RESULTS: Of the 453 participants (response rate, 51.4%), 99.3% had heard of CAM. Of those, 83.3% had used at least one CAM approach. Use was greatest for spiritual practices (80.5%), vitamins and herbs (62.6%), and movement and physical therapies (59.2%) and predicted (P <.001) by sex (female), younger age, indigent pay status, and surgery. After excluding spiritual practices and psychotherapy, 95.8% of participants were aware of CAM and 68.7% of those had used CAM. Use was predicted (P <.0001) by sex (female), education, and chemotherapy. CONCLUSION: In most categories, CAM use was common among outpatients. Given the number of patients combining vitamins and herbs with conventional treatments, the oncology community must improve patient-provider communication, offer reliable information to patients, and initiate research to determine possible drug-herb-vitamin interactions.

HIV-1, cocaine, and neuropsychological performance in African American men.

The purpose of this study was to examine the independent and interactive effects of HIV-1 serostatus and cocaine on neuropsychological (NP) performance in a sample of 237 gay and bisexual urban-dwelling African American men. Consistent with current evidence, it was expected that the greatest neuropsychological performance deficits would be evident (1) in the symptomatic seropositives (SSPs), especially in domains affected by HIV (i.e., memory and psychomotor speed), and on tests that are sensitive to subtle slowing; (2) in those who are recent and frequent cocaine abusers; and (3) in those who are both HIV seropositive and cocaine abusers. Multivariate analyses controlling for age and alcohol use confirmed expectations, with symptomatic seropositives (SSPs) evidencing significantly poorer psychomotor speed than the seronegatives (SNs), and slower reaction time and poorer nonverbal memory than the asymptomatic seropositives (ASPs). Moderate to heavy recent cocaine use was associated with slower psychomotor speed. However, contrary to expectations, no interaction of serostatus and cocaine was noted for any NP domain, and the expected serostatus and cocaine effects on verbal memory and frontal systems were not obtained. Level of alcohol consumption exacerbated the detrimental effects of HIV-1 on a computerized reaction time test which is especially sensitive to subtle slowing. This study provides one of the first descriptions of the neuropsychological effects of HIV-AIDS in a non-injection drug-using community sample of gay and bisexual African American men.

Functional expression in Pichia pastoris of human and rat intrinsic factor.

Intrinsic factor (IF) has been expressed previously in Baculovirus with a yield (0.1-1 mg/l) that was inadequate for structural and metabolic studies. IF cDNAs were cloned into the shuttle vector pPIC9 of P. pastoris, and the proteins were induced and purified by cobalamin (Cbl) affinity chromatography. Expression of recombinant proteins revealed a major band of 49 kDa for both human and rat IF. Expression of human IF was achieved at 1040 mg/l, but of rat IF at only 1-2 mg/l. Reaction of human IF with a photo-activatable derivative of Cbl was demonstrated by Western blotting, and detection of IF fragments by anti-Cbl monoclonal antibody and by amino-terminal sequencing revealed at least three regions (residues 129-151, 234-254, and +294) linked to Cbl. Both recombinant human and rat [125I]IF-Cbl bound to rat and guinea pig brush border membranes with similar affinity, but the binding capacity of human IF for the rat receptor was only 10% compared with rat IF. All six amino acids within the previously identified N-terminal binding region of human IF were mutated to be identical to rat IF, but the resulting chimeric IF still bound poorly to rat membranes. Mutations of residues 26/27 (Glu26 to Asp and Asn27 to Gln) and 32/34 (Ser32 to Thr and Tyr34 to Arg) showed changes in both Ka and Vmax, with great effects on Vmax. In conclusion, P. pastoris is an expression system that produces functional human IF at a higher yield than in the baculovirus system. Cbl binding was directly demonstrated at multiple sites along the linear sequence of human IF. The receptor binding function of the amino terminal sequence 25 62 has been confirmed, but it is insufficient to reproduce all the features of IF-Cbl binding.

Percutaneous endoscopic gastrostomy: a review of indications, complications and outcome.

Percutaneous endoscopic gastrostomy (PEG) was first described in 1980 as an effective method of feeding via the stomach in situations where oral intake is not possible. Its simplicity has led to its potential use in areas of dubious clinical benefit. Our unit has faced a major increase in referrals for PEG insertion over the last 2 years. For this reason we decided to audit our PEG insertion procedures with regard to indications, complications, outcome and follow up. We studied 168 patients who had an initial PEG insertion during the period 1 February 1996-31 January 1998. The medical records of these patients were reviewed with regard to the procedure, antibiotic use and complications. All patients (or carers or next of kin) were contacted by telephone to provide details regarding late complications and follow up. There were 87 females and 81 males (aged 16-98 years, median age 70 years). At 2 years, 67% were alive. The most frequent indication for PEG insertion was a neurological condition, the commonest being stroke. Most patients received either ticarcillin/clavulanic acid or cephazolin antibiotic prophylaxis before and after the procedure. In six patients (3.6%) infection at the PEG site required intravenous antibiotics. Four of these six patients did not have antibiotic prophylaxis. Only two deaths could be directly related to the procedure. Three died within 7 days of the procedure due to unrelated medical complications. Sixteen patients died within 1 month, the majority of these patients did not leave hospital. One-fifth of the patients (35/168) had their PEG removed due to the re-establishment of oral feeding, with median time of use, 4.3 months. It is a safe, effective feeding method in the elderly, but experience with case selection, the procedure and careful follow up remain essential. The use of prophylactic antibiotics resulted in few significant infections of the PEG site. Up to one-fifth of patients will require their PEG only for a short term.