Video-assisted thoracoscopic discectomy and fusion.

Anterior discectomies and fusions are performed on patients who have anteriorly herniated discs. Fusions are accomplished using bone grafts harvested from the patient or by using cadaveric bone grafts that are inserted into the disc space for stability. This procedure traditionally has been performed through an open incision, but now can be accomplished using a video-assisted thoracoscope. The benefits of this minimally invasive technique for patients include decreased blood loss, less postoperative pain, and a shorter hospital stay.

Electrocerebral inactivity associated with obstructive sleep apnea.

We report a child who demonstrates near electrocerebral silence secondary to obstructive apnea during polysomnography. The mechanism of this suppression of cortical activity appears to be related to hypoxemia in the absence of a malignant arrhythmia.

Familial lichen sclerosus et atrophicus in association with CREST syndrome: a case report.

Lichen sclerosus et atrophicus is an uncommon disease which appears to be multifactorial in aetiology. We describe a case of a young woman with CREST syndrome (calcinosis, Raynaud's phenomenon, oesophageal dysfunction, sclerodactyly and telangiectasia) who has a documented family history of two sisters with lichen sclerosus et atrophicus. She presented with vulvar pruritus in association with dyspareunia, and biopsy of atrophic white vulvar lesions was consistent with lichen sclerosus et atrophicus. Lichen sclerosus et atrophicus has been previously noted to occur in association with morphoea and lichen planus, although it has never been reported in conjunction with CREST syndrome.

Homozygosity for the Min allele of Apc results in disruption of mouse development prior to gastrulation.

Mutation of the APC (adenomatous polyposis coli) gene is an early event in colon tumor development in humans. Mice carrying Min (multiple intestinal neoplasia), a mutant allele of Apc, develop intestinal and mammary tumors as adults. To study the role of the Apc gene in development, we have investigated the phenotype of embryos homozygous for ApcMin (Min). Development of the primitive ectoderm fails prior to gastrulation in homozygous Min embryos. By midgestation, the presumed homozygotes consist of a mass of trophoblast giant cells with an additional cluster of much smaller embryonic cells. These results indicate that functional Apc is required for normal growth of inner cell mass derivatives.

Dextromethorphan inhibits ischemia-induced c-fos expression and delayed neuronal death in hippocampal neurons.

BACKGROUND: Dextromethorphan (DM), a widely used antitussive agent, has been shown to possess both anticonvulsant and neuroprotective properties functionally related to its inhibitory effects on glutamate-induced neurotoxicity. The current study was designed to determine whether DM administration prevents delayed neuronal degeneration in central nervous system areas after global forebrain ischemia and whether this correlates with inhibition of induction of the immediate early gene c-fos. METHODS: Mongolian gerbils, anesthetized with 2% halothane in air at 37 degrees C, received either 0.9% sodium chloride (vehicle, n = 9) or 50 mg/kg DM in vehicle (n = 9) by intraperitoneal injection before bilateral carotid artery occlusion. After 1 h of reperfusion under anesthesia, the animals were killed and the brains removed. Immunohistochemistry was used to detect neurons expressing Fos protein. Computer-assisted image analysis quantified changes in the number of labeled neurons as a function of drug treatment. To determine the extent of delayed neuronal degeneration within the hippocampus, other animals were treated with either DM (n = 7) or vehicle (n = 6) before carotid artery occlusion and allowed to survive for 1 week. RESULTS: Global forebrain ischemia produced consistent patterns of Fos-like immunoreactivity in the hippocampus and neocortex of vehicle-treated animals. DM inhibited the induction of c-fos from 65% to 91%. DM also protected against delayed neuronal degeneration in the CA1 region of the hippocampus (P < 0.001). CONCLUSIONS: The induction of nuclear-associated Fos protein represents a sensitive marker of cellular responses to ischemia and a method to assay the effectiveness of pharmacologic interventions. DM markedly inhibited ischemia-induced Fos expression and prevented cell death in CA1. DM given before conditions of ischemia or decreased central nervous system perfusion may be highly beneficial.

A 1.2-Mb YAC contig spans the quaking region.

We describe here a 1.2-Mb yeast artificial chromosome (YAC) contig within the region of mouse chromosome 17 between Brachyury (T) and D17Rp17e, and spanning the quaking (qk) region. We describe six new probes distributed across 1.2 Mb: D17Leh502, D17Leh503, D17Leh504, D17Leh505, D17Leh506, and D17Leh507. Probes D17Leh502 and D17Leh507 are at the extreme ends of the YAC contig. With the exception of D17Leh507, all of these probes are within a deletion associated with the quaking(viable) (qkv) allele of quaking. We have positioned these probes on a detailed YAC physical map together with two previously published probes, D17Leh508 and D17Aus119. We show here that D17Leh508 is also within the qkv deletion. Genetic mapping of D17Leh504 and D17Leh507 on two high-resolution genetic crosses carrying qkv and quaking(lethal-1) (qkl-1) alleles shows that these probes do not recombine with quaking and are therefore within 0.04 cM of qkv and 0.05 cM of qkl-1 mutations. The deletion breakpoint contained within the YAC contig has been positioned to within 90 kb by restriction mapping of wildtype and mutant DNA. This contig will form the basis for identification and mapping of expressed sequences and for an investigation of genome organization.

Detailed physical and genetic mapping in the region of plasminogen, D17Rp17e, and quaking.

We present here a detailed physical map encompassing over 600 kb of mouse Chromosome (Chr) 17 in the region of plasminogen, D17Rp17e, and quaking. This region is cloned in yeast artificial chromosomes (YACs). We have identified several CpG islands within this region from pulsed field gel mapping of mouse genomic DNA and YAC DNA. Five new DNA probes have been generated. One, D17Leh514, is a minimum of about 90 kb distal to plasminogen. Four, D17Leh513, D17Leh512, D17Leh511, and D17Leh510, are proximal to D17Rp17e, the closest previously described genetic marker to quaking viable and quaking lethal-1 mutations. We have genetically mapped D17Leh511 to within 0.15 cM of these mutations. The genetic distance to D17Rp17e from D17Leh511 is also 0.15 cM; the physical distance of less than 360 kb (minimum 200 kb) is consistent with an approximation of 2 Mbp per cM.

Cell-specific expression of a recombinant rat glutathione S-transferase Ya gene in transgenic mice.

Transgenic mice have been generated which carry a cDNA encoding the rat Ya isozyme of glutathione S-transferase (GST) under the transcriptional control of the SV40 early region promoter-enhancer. Expression of the GST transgene was highly tissue-specific, with the highest expression detected in the convoluted tubular epithelium of the mouse kidney cortex. GST Ya mRNA abundance in these cells was greater than that found for GST Ya mRNA in normal rat liver. GST Ya protein was observed in the convoluted tubule cells of the founder mouse as well as an F1 offspring. The transmission of the foreign gene was followed for two generations, and an erratic pattern of inheritance was observed. These animals provide a model for the in vivo study of GST modulation of carcinogenesis and drug toxicity.

Selective in situ hybridization histochemical analyses of alternatively spliced mRNAs encoding beta- and gamma-preprotachykinins in rat central nervous system.

The present study describes the development of an in situ hybridization histochemistry (ISHH) procedure which was employed to selectively monitor cellular distributions of the 2 major alternatively spliced beta- and gamma-species of mRNA encoding preprotachykinin (PPT) molecules found in rat CNS. For these purposes, 2 custom-designed oligodeoxynucleotide probes were synthesized corresponding to complementary sequences of beta- and gamma-PPT mRNAs. In particular, the gamma-selective probe was demonstrated to hybridize to the contiguous regions of RNA flanking the splice site formed by exclusion of exon 4. Initially, Northern blot analyses performed in conjunction with appropriate specificity controls demonstrated selective hybridization of the 32P-labeled beta- and gamma-selective probes to single bands of approximately 1.2-1.3 kilobases in size, consistent with previously established values for rat brain beta- and gamma-PPT mRNAs. In anatomical studies, results obtained from absorptions using competing nonradiolabeled oligonucleotides defined the specificity and selectivity of both probes for targeting their respective species of mRNA immobilized within sections of brain tissue. Extensive ISHH analyses using both beta- and gamma-selective probes demonstrated similar patterns of cellular labeling in all of the examined CNS areas. In addition, data obtained from analyses of adjacent thin sections of the dorsal root ganglia (DRG) indicated that beta- and gamma-PPT mRNAs were colocalized within individual DRG neurons, thereby suggesting generalized coexpression at the cellular level of both forms of mRNA. These data were complemented by semi-quantitative analyses which yielded cellular or intrinsic molar ratios of beta- to gamma-PPT mRNA of approximately 1:2-1:3, consistent with those values previously determined by nuclease protection analyses. In sum, a reasonable hypothesis evolving from the anatomical studies in combination with previous biochemical data supports the existence of a strong homeostatic mechanism involved in the maintenance of relatively constant intrinsic molar ratios of beta- to gamma-PPT mRNA by tachykinin-expressing neurons. The biological relevance of this putative fundamental relationship is discussed in the context of posttranslational processing of PPT molecules and of expression of mature tachykinins.

Development of an antiserum to the midportion of substance P: applications for biochemical and anatomical studies of substance P-related peptide species in CNS tissues.

This report describes the generation and biochemical characterization of a high-affinity antiserum that recognizes an epitope contained in the midportion sequence of substance P, i.e., substance P4-10. Designated A47, this reagent bound a variety of related peptide species containing the substance P4-10 sequence with apparent equipotency. A double radioimmunoassay procedure was developed that utilized A47, in combination with a traditional high-affinity COOH-terminally directed anti-substance P serum, to provide quantification of mature and immature forms of substance P in CNS tissues. Across most rat CNS areas, levels of substance P-like immunoreactivity were consistently 15% higher when monitored by analyses using A47 versus anti-substance P serum. In the dorsal root ganglia, an apparent enhancement in levels of substance P-like immunoreactivity of approximately 40%, when quantified by analyses using A47 versus anti-substance P serum, was observed; this most likely reflected the presence of an active biosynthetic pool of intermediate processing forms of substance P in this tissue. Coordinated HPLC/radioimmunoassay analyses of extracted dorsal root ganglia tissues demonstrated multiple peaks of immunoreactivity corresponding to mature substance P and to several of its precursor forms found in the normal biosynthetic pathway. Of the total recovered HPLC-fractionated immunoreactivities, that corresponding to the putative immediate precursor to substance P, i.e., substance P-glycine, was the predominant peak. In an additional series of HPLC/radioimmunoassay analyses, selective decreases in immunoreactive peaks corresponding to precursor forms of substance P were observed in dorsal root ganglia tissues from rats treated with the neurotoxic agent capsaicin. These results indicated decreased turnover of substance P as a consequence of drug treatment. Finally, initial immunohistochemical analyses employing affinity-purified A47 produced an unusual pattern of labeling characterized by well defined punctate terminal elements within the superficial aspects of the dorsal horn of the spinal cord.

Should nonsteroidal anti-inflammatory drugs be stopped before elective surgery?

PURPOSE: --To determine if perioperative use of nonsteroidal anti-inflammatory drugs (NSAIDs) might be associated with increased postoperative morbidity. PATIENTS AND METHODS: --Records from 165 patients undergoing total hip arthroplasty from 1984 to 1987 were reviewed. Patients taking NSAIDs at hospital admission were compared with those who were not. RESULTS: --Patients taking NSAIDs had more postoperative bleeding complications (gastrointestinal tract bleeding and/or hypotension) than did patients not taking those agents. Complications were more frequent in patients using NSAIDs with half-lives longer than 6 hours. CONCLUSION: --Patients undergoing elective surgery should stop taking NSAIDs in time to allow elimination of the drug; those patients who need to take these agents perioperatively should use drugs with short half-lives.

The role of transgenic animals in the analysis of various biological aspects of normal and pathologic states.

The introduction of foreign genes into the germ line of mammals has been a practical reality now for a number of years. This form of experimentation allows the creation of lines of animals tailor-made to answer specific molecular genetic questions. Manipulation of the mammalian embryos has been enormously important in developmental biology in recent years and that experience has brought about the possibility of new experiments allowing the molecular analysis of many biological processes. The methodologies involved in constructing transgenic animals have been published extensively in a number of comprehensive reviews. In typical experiments, pronuclear stage (one cell) embryos are collected after fertilization, but prior to the onset of cleavage. Exogenous cloned linearized DNA is injected into one of the two pronuclei by means of a finely drawn injection pipet. The manipulated embryo is transferred into the oviduct or ovarian bursal space of a surrogate mother previously mated with a sterile male. Alternative methods include retroviral transfection of cleavage stage embryos or insertion of genetically engineered embryo-derived embryonal stem cells into blastocysts. Offspring from these procedures are screened by standard molecular analyses to determine presence of the foreign genetic material. The present report explores the application of this methodology to a specific set of problems: (i) regulation of gene expression in vivo, (ii) the establishment of disease models for the study of pathogenesis, (iii) the use of exogenous genetic elements to correct specific genetic defects, (iv) the role of insertional mutagenesis in disruption of normal development, (v) analysis of genetic ablation, (iv) the use of transgenic animals to modulate carcinogens.

Profile of a meeting: how abstracts are written and reviewed.

We analyzed submissions to a recent scientific program to determine (1) how abstracts were reviewed and (2) what constituted a successful abstract. We found that (1) reviewers' gradings varied from 2-29%, in some instances differing significantly; (2) many (<74%) abstracts had inadequacies in form, title, introduction, aims, methods, results, and conclusions(collectively termed "content") or lacked numerical or statistical data; (3) accepted abstracts had fewer inadequacies and better "content"; and (4) abstract grades correlated closely with "content". The quality of preparation and of individual features of abstracts led to favorable review. This information is of potential value to scientists preparing and reviewing abstracts and planning programs.

Disruption of embryonic and fetal development due to preimplantation chemical insults: a critical review.

Descriptive teratology has developed several fundamental precepts, two of which can now be challenged on the basis of experimental evidence. The first is that prior to implantation the developing embryo is not susceptible to survivable defects from chemical injury. The second is that developmental defects cannot be due to mutational events since rare events seem unlikely to explain alterations in large populations of cells. This review presents current experimental evidence demonstrating that the effects of chemical exposure on blastocyst stage embryos may be manifest long after the time of insult and that subtle nonlethal mutations may have a role in poor fetal performance after early chemical exposures.