Prescribing of benzodiazepines and opioids to individuals with substance use disorders.

BACKGROUND: Benzodiazepines are recommended for short-term use due to risk of dependence. This study examined characteristics associated with benzodiazepine and opioid dispensing of 7+ days in a Medicaid population with substance use disorder (SUD). METHODS: Using 2014 MarketScan® data, we performed zero-inflated negative binomial regression to ascertain characteristics associated with longer-term use of these medications. RESULTS: Nearly 14% of those with SUDs received 1+ fills of benzodiazepines of 7+ days. The highest rates were among those aged 45-64 (IRR=2.38, p<0.0001) and with non-alcohol SUDs (IRR=1.12, p<0.0001). Individuals with co-occurring psychiatric disorders, particularly anxiety and depression (IRR=1.41, p<0.0001), had high rates of benzodiazepine fills. Receiving a 7+ day oral opioid fill (IRR=1.30, p<0.0001) coincided with increased benzodiazepine dispensing. Similar results occurred for longer-term prescribing of opioids, with higher rates among those with non-alcohol SUDs (IRR=1.23, p< 0.0001). CONCLUSIONS: For many people with SUDs, receiving a benzodiazepine or opioid prescription of 7+ days is not a single occurrence; patients in our sample were more likely to receive 2+ fills than to receive one. Longer-term prescribing is most pronounced among those with co-occurring anxiety disorders. This suggests that anxiety in those with SUD should preferentially not be treated using benzodiazepines. Longer-term polypharmacy with benzodiazepines and opioids coincided. Overdoses among those using both drugs are growing and this study provides evidence that attention to the opioid epidemic should include attention to polypharmacy that includes benzodiazepines.

Posterior-variant alien hand syndrome: clinical features and response to rehabilitation.

PURPOSE: This case highlights the clinical features and course of recovery of a patient presenting to the rehabilitation service with posterior-variant alien hand syndrome (AHS) following thalamic stroke. METHODS: Single case report. RESULTS: Clinical signs and symptoms included mild hemiparesis, dyspraxia, dysmetria, primary sensory loss and hemispatial neglect. Autonomous movements and personification of the affected extremity which were ego-syntonic in nature were characteristic of posterior-variant AHS. The associated neurological impairments resolved early during the course of rehabilitation and the patient made excellent functional gains. CONCLUSION: This case highlights the distinguishing features differentiating posterior-variant AHS from more classical AHS and underscores the excellent prognosis of this variant.

Determination of halogenated hydrocarbons by helium microwave plasma torch time-of-flight mass spectrometry coupled to gas chromatography.

A helium microwave plasma torch (MPT) was coupled to time-of-flight mass spectrometry (TOFMS) for the detection of halogenated hydrocarbons separated by capillary gas chromatography (GC). The GC-MPT-TOFMS system offered excellent stability over the course of the experiments and avoided mass spectral peak distortions caused by spectral skew. In the initial studies, empirical formulas based on the halogen-to-carbon ratio were predicted utilizing a flow cell apparatus. The MPT proved to be very robust and could handle large amounts of organic vapor. Results from this study indicate that, for both aromatic and aliphatic halogenated hydrocarbons, the ratios of carbon to chlorine signals correlate well (r = 0.994) with the ones expected from their chemical composition. This study was later extended to include chromatographic separation. For a series of homologous aliphatic halogenated hydrocarbons, a correlation coefficient of 0.999 was obtained for both peak heights and peak areas obtained from a single chromatogram. A novel Nichrome wire-heated transfer line was developed to ensure that the capillary column was heated efficiently from the GC oven to the MPT and then through the length of the MPT up to the microwave plasma itself. No appreciable peak broadening and no detectable memory effects were associated with the heated transfer line. The GC-MPT-TOFMS system offered equal sensitivity for I, Br, and Cl. Absolute detection limits for the halogenated hydrocarbons ranged from 160 to 330 fg, constituting an improvement by a factor of 5-35 over earlier results obtained with MIPs supported in a TM010 cavity and combined with quadrupole-based mass spectrometry. In addition, the effect of molecular gases on the MPT performance was investigated. Up to about 1% (v/v) of either oxygen or hydrogen in the central channel helium flow attenuated the signal levels for both carbon and chlorine, with the larger loss seen in the chlorine signal.

Porcine zona pellucida ZP3 alpha glycoprotein mediates binding of the biotin-labeled M(r) 55,000 family (ZP3) to boar sperm membrane vesicles.

The two M(r) 55,000 glycoproteins, ZP3 alpha and ZP3 beta, of porcine zona pellucida copurify as a preparation designated ZP3. Gamete binding assays have implicated ZP3 alpha, but not ZP3 beta, as participating in sperm-zona recognition events. We now report that boar sperm contain membrane-associated binding sites with specificity for ZP3 alpha. Biotin-labeled (b-) preparations of ZP3 bind to intact boar sperm in a saturable manner, with localization on the anterior head region. Membrane vesicles obtained from capacitated sperm by nitrogen cavitation retain b-ZP3 binding sites as determined by an enzyme-linked method employing alkaline phosphatase-conjugated strepavidin. In competitive binding assays using b-ZP3 (0.1 microgram/ml) as probe, heat-solubilized zonae and ZP3 were effective competitors, whereas the nonzona molecules fetuin and fucoidin were not. Digestion of ZP3 with endo-beta-galactosidase, an enzyme that trims polylactosamines, enhanced its affinity for membrane receptors. In contrast treatments such as chemical deglycosylation, pronase digestion, or disruption of disulfide bonds abolished the ligand activity of ZP3. Finally, purified ZP3 alpha was an at least 100-fold better antagonist than purified ZP3 beta. The results demonstrate that binding of b-ZP3 to isolated boar sperm membranes is mediated by sperm receptors with specificity for the ZP3 alpha macromolecular component and reveal a complex contribution of both carbohydrate and protein moieties toward the ligand activity of this sperm adhesive zona molecule.

Porcine oocyte zona pellucida M(r) 55,000 glycoproteins: identification of O-glycosylated domains.

The distribution of O-linked oligosaccharides on the M(r) 55,000 glycoproteins, ZP3 alpha and ZP3 beta, of the porcine oocyte zona pellucida was examined. Purified preparations of endo-beta-galactosidase digested ZP3 alpha and ZP3 beta were reduced and carboxamidomethylated and digested with trypsin. When the trypsin digests were mapped by HPLC, each glycoprotein yielded only one N-acetylgalactosamine containing glycopeptide. Purification of the O-glycopeptides was achieved by a two-step protocol. Tryptic digests were applied to jacalin-agarose and specifically-bound O-glycopeptides (alpha OGP and beta OGP) were eluted with buffer containing 50 mM alpha-methylgalactoside as the haptenic sugar. Further purification of each O-glycopeptide was accomplished by reverse phase HPLC. Purified O-glycopeptides were characterized with respect to amino acid and carbohydrate compositions and sequenced by automated Edman degradation; alpha OGP was a 41-residue glycopeptide with three O-linked sugar chains. Sequence comparisons revealed a 75% identity between alpha OGP and a corresponding segment of rabbit rec55 zona protein; beta OGP was a 25-residue glycopeptide characterized by the presence of one N-linked and five O-linked sugar chains and a trypsin-resistant internal arginine residue. Sequence alignments revealed an 80% or greater identity between beta OGP and internal peptides of mouse, hamster and human ZP3 zona proteins. These studies demonstrate that in the case of ZP3 alpha and ZP3 beta, the pig homologues of rabbit rec55 and mouse ZP3, respectively, O-linked oligosaccharides are confined within delimited domains rather than widely dispersed on the polypeptide backbone. Such clustering of O-linked oligosaccharides may represent an essential determinant of the structure and biological activity of zona proteins.

Isolation, composition, and biological activity of sugar chains of porcine oocyte zona pellucida 55K glycoproteins.

ZP3, a preparation of the 55K families of porcine oocyte zona pellucida, possesses carbohydrate-dependent ligand activity for boar sperm. The aim of the present study was to analyze ZP3 N- and O-linked oligosaccharides with respect to size distribution, composition, and role in sperm-zona recognition events. Digestion of denatured ZP3 with peptide N-glycosidase F (PNGaseF) released the majority of N-glycans which fractionated on Sephadex G-75 resin as a polydisperse population with apparent molecular masses ranging from 1,900-8,200 Da. The higher molecular weight N-glycans were characterized by the presence of strongly anionic sulfated/sialylated polylactosamine structures. Alkaline-borohydride treatment of the PNGaseF-digested core proteins liberated O-glycans as a heterogeneous population of oligosaccharide alcohols, which were fractionated on a Sephadex G-50 column. Compositional analyses indicated sulfated polylactosamine units associated with the higher molecular weight O-glycans. Preincubation of boar sperm with ZP3 or purified O-glycans, but not N-glycans, inhibited subsequent attachment to zona-encased oocytes. Purified O-glycans were, however, 2 to 3 orders of magnitude less effective than ZP3 as competitive ligands. The results document the extreme heterogeneity of the ZP3 carbohydrate moiety, in large part attributable to a broad spectrum of variably sized N- and O-linked sulfated polylactosamines. Ligand competition bioassays suggest that O-glycans mediate, at least in part, the sperm adhesive properties of ZP3 and strongly imply that high-affinity interaction of ZP3 sugar chains with complementary sperm receptors is dependent upon their covalent association with core proteins.

Maternal serum hexosaminidase A in pregnancy: effects of gestational age and fetal genotype.

The diagnostic usefulness of sulfated fluorogenic substrates in carrier detection of Tay-Sachs disease in serum during pregnancy was assessed by testing coded samples. Gradual increase in serum hexosaminidase activities toward these substrates was observed throughout pregnancy in both carrier and non-carriers of the Tay-Sachs gene, but absolute discrimination between the 2 genotypes could not be achieved even when values were compared within the same gestational age. Examination of isolated isozyme fractions with the sulfated substrates showed that the increased activities during pregnancy were due to a genuine increase in hexosaminidase A and not associated with the elevation of hexosaminidase I (or P), which was evident only with unsulfated substrates. The extent of the increase was influenced by the genotype of the fetus as indicated by higher values in pregnant carriers who carried non-carrier fetuses. We conclude that determination of serum hexosaminidase A during pregnancy by sulfated fluorogenic substrates may have a prenatal diagnostic value when used in obligate heterozygotes for Tay-Sachs disease, but is unreliable for screening purposes.

Altered molecular size of N-acetylglucosamine 1-phosphotransferase in I-cell disease and pseudo-Hurler polydystrophy.

The size of the mutant N-acetylglucosamine 1-phosphotransferase in Golgi membranes from fibroblasts of patients with I-cell disease and classical pseudo-Hurler polydystrophy, which comprised one complementation group characterized by deficiency towards both artificial and natural acceptor substrates, was significantly smaller than the normal enzyme, 151-174 kDa compared with 225-278 kDa. The size of the mutant enzyme from cell lines of patients with variant forms of pseudo-Hurler polydystrophy, which comprised another complementation group characterized by normal activity towards mono- and oligo-saccharide substrates, was significantly larger than the normal enzyme, ranging from 321 to 356 kDa in two families and from 528 to 547 kDa in a third family. These findings suggest that the mutations in I-cell disease and classical pseudo-Hurler polydystrophy result in a missing enzyme component, which renders the enzyme catalytically inefficient toward any type of acceptor substrate. In contrast, the mutations in the variant forms of pseudo-Hurler polydystrophy produce a larger enzyme molecule which is active toward small substrates but is incapable of binding natural lysosomal glycoprotein substrates.

Survival and neurologic outcome of infants with medulloblastoma treated with surgery and MOPP chemotherapy. A preliminary report.

The results of treatment of infants with medulloblastoma using surgery and chemotherapy, without the use of radiation therapy, are reported. Both survival and outcome, in terms of growth, neurologic deficit, and intelligence are compared with the same parameters in children treated conventionally. Although preliminary, our results suggest that chemotherapy combined with surgery is a valid option for the treatment of infants with this type of neoplasm.

Lysosomal enzyme activities in fresh and frozen chorionic villi and in cultured trophoblasts.

Fifteen lysosomal enzyme activities were compared in 14 presumed normal chorionic villus specimens that were each divided, processed and analyzed as fresh tissue, tissue frozen for 1 week, and cultures established from minced whole villi. Most of the activities determined in the chorionic villus tissue were not affected significantly by freezing. However, activities for most enzymes were significantly different from those determined in the cultured cells. Our experience with first trimester prenatal evaluations for several lysosomal disorders showed that the limited amount of tissue obtained is not always sufficient for thorough analysis and thus, cultured trophoblasts derived from the tissue specimen should also be examined. The results of this study stress the importance of using appropriate tissue-type and cell-type controls to establish the normal range in the respective analyses.

Molecular size of N-acetylglucosaminylphosphotransferase and alpha-N-acetylglucosaminyl phosphodiesterase as determined in situ in Golgi membranes by radiation inactivation.

The radiation inactivation method was used to determine the molecular size of the two enzymes that participate in the synthesis of the phosphomannosyl recognition marker of lysosomal proteins. The determinations were carried out in situ, in Golgi membranes isolated from normal human placenta and cultured skin fibroblasts. A molecular size of 228 +/- 29 kDa was found for placental N-acetylglucosaminyl-phosphotransferase, and 129 +/- 11 kDa for placental alpha-N-acetylglucosaminyl phosphodiesterase. The values for the fibroblast enzymes were about 20% higher, 283 +/- 27 kDa and 156 +/- 14 kDa for the transferase and phosphodiesterase respectively. Triton X-100 had no effect on the molecular size of these enzymes.

Characterization of the mutant N-acetylglucosaminylphosphotransferase in I-cell disease and pseudo-Hurler polydystrophy: complementation analysis and kinetic studies.

Complementation was examined among various types of I-cell disease and pseudo-Hurler polydystrophy by monitoring N-acetylglucosaminylphosphotransferase activity in multinucleated cells produced by fusing pair combinations of cultured skin fibroblasts. Patients with the classical forms of these disorders (5 I-cell disease and 3 pseudo-Hurler polydystrophy cell lines) comprised one complementation group and 5 cell lines from patients with variant forms of pseudo-Hurler polydystrophy comprised a distinct complementation group. In the first group, total or partial deficiency of the transferase activity was demonstrated with both natural (lysosomal enzymes) and artificial (alpha-methylmannoside) acceptor substrates with low Vmax but apparently normal Km values for the donor (UDP-GlcNAc) and acceptor (alpha-methylmannoside) substrates. The activity toward artificial substrate could be inhibited by adding exogenous lysosomal enzyme preparations to the reaction mixture. In the second group, the cells demonstrated deficiency of the transferase activity toward lysosomal enzyme acceptors but had normal activity toward alpha-methylmannoside acceptor and this activity could not be inhibited by the addition of exogenous lysosomal enzyme preparations. These findings suggest that N-acetylglucosaminylphosphotransferase is composed of at least two distinct subunits, a catalytic subunit which is absent or defective in the first complementation group, and a recognition subunit which is altered or deficient in the second group.

A review of hospital-based health promotion programs in Michigan non-governmental hospitals.

In 1983, the 217 hospitals of the Michigan Hospital Association (MHA) were surveyed to learn more about their efforts in health promotion programming. Eighty percent (174 hospitals) responded to the survey, with 48% reporting on 532 programs. Those programs included 216 in health promotion as defined by the survey instructions, 110 in disease management, 66 in first aid and safety, 87 screening, and 53 miscellaneous education programs. Further particulars about the programs are presented, including information regarding program audience, times offered per year, median enrollment, median participant hours, program age, number and type of educational methods used, follow-up methods, and fees charged. Hospital administrators' perceptions regarding health promotion programs were also surveyed. They indicated a higher level of interest in providing such programs because they viewed them as a needed community service. Conversely, they did not see them as a revenue generator. Seventy-two percent of the responding administrators indicated they currently offered health promotion programs, although only 48% submitted information regarding them. Seventy percent said they planned to begin new health promotion programs within the next 12 months, while only 6% planned to discontinue programs in the new year.

A profile of sickle cell disease.

There is no cure for sickle cell disease. In management our emphasis is on maintenance and palliative treatment. Preventive care, which includes regular medical supervision, adequate nutrition, and sufficient fluid intake, is also desirable. They will be discussed throughout this symposium. We must be instrumental in helping people with sickle cell disease to live life to the fullest within their ability. Learning to accept the illness and cope with its unpredictable flare-ups should be an early goal for all patients and their families. Independence and realistic ambitions are also important areas to be included in our anticipatory guidance. It is encouraging that sickle cell anemia is getting the financial support and continuous attention that it needs as a chronic health problem. There are many questions about the illness that have to be answered, and there is still a cure to be found. These are the challenges of the 1980's.

Factors affecting criteria met by hospital-based patient-education programs: a Michigan experience.

A patient-education program model with 18 criteria was refined into a survey instrument and sent to 217 Michigan hospitals. Of these, 181 hospitals and one free-standing clinic responded, with 47 indicating they had no applicable programs and 135 providing data on 281 existing patient-education programs. A mean (+/- SD) of 12.1 +/- 3.9 criteria were met. The range included two programs that met only one criterion and 15 that met all 18. After it was established that the criteria operated independently of each other, six factors were analyzed to observe their impact on the number of criteria met by the 281 programs. Analysis of variation (ANOVA) showed that presence and type of program coordinator accounted for 17% of explained variance, subject for 8%, hospital size for 4.4%, existence of a defined budget for 4%, and geographic location for 3%. Because of unequal numbers, the full-time/part-time coordinator factor was not included in the ANOVA. More than one third of the variance affecting numbers of criteria met by patient-education programs was explained by these factors.

A model for assessing patient education.

Patient education is becoming a more visible activity. The Michigan Hospital Association and the Michigan state health planning and resource development agency (Office of Health and Medical Affairs) agreed to jointly pursue a patient-education project to determine its effectiveness. The overall goal of the project is to determine generically what constitutes a quality hospital-based patient-education program. This paper focuses on the development of a model for assessing patient-education programs. Through a multistep process 18 criteria were ultimately selected to serve for patient-education assessment. An analysis and description of the utility of the criteria is presented. The need for establishing and maintaining quality in patient-education programs has been established. The criteria developed for the project offer the potential of meeting this need.