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Biomedical subjects

C B Alexander

Publications and source records attributed to C B Alexander.

At least 19 recordsLinked to original sources
PubMed2001

Trends in pathology graduate medical education.

Comprehensive data show trends in graduate medical education in pathology with regard to the numbers of accredited programs, persons certified from those programs, and demographics of the population of first year-trainees in pathology. Experience with US seniors and foreign-trained physicians in the PGY match process for pathology from 1991 through 2000 is presented, along with data on the types of medical schools generating pathology trainees for the PGY-1 year and the top medical schools of origin of US medical graduates who completed the program and became certified in pathology between 1995 and 1999. The impact of reimbursement of the credentialing year is also addressed through data collected from the PRODS Survey 2000, and those results are reviewed. Finally, turnover rates among pathology program directors of combined AP/CP programs and subspecialty programs since 1994 are presented. An analysis of these trends is provided, along with suggestions to improve both the perception of careers in pathology and the actual choice of a career in pathology.

Accreditation↗
PubMed2001

Association of reactive nitrogen species metabolites, myeloperoxidase, and airway inflammation in lung transplants.

BACKGROUND: We have previously reported that patients who had single or double lung transplants had higher concentrations than controls of nitrite and nitrate, which are metabolites of reactive nitrogen species (RNS), in bronchoalveolar lavage fluid (BALF) and serum. METHODS: This study investigates implications of RNS metabolites as markers of airway inflammation in a distinct group of lung transplant patients (n = 40). All patients underwent spirometry, routine surveillance transbronchial lung biopsies, and bronchoalveolar lavage as required by clinical protocol. Four normal controls also had bronchoscopy for measurement of BALF nitrite (NO2-) and nitrate (NO3-). BALF NO2- and NO3-, myeloperoxidase (MPO), protein, and urea were assayed. Total nitrite (NO2- plus enzymatically reduced NO3-) and urea were measured in serum. RESULTS: BALF RNS metabolites were mainly NO3-. Forced expiratory volume in 1 s (FEV1) obtained near bronchoscopy was compared with best postoperative FEV1. Total nitrite in transplant patients' BALF and serum were 3.8 +/- 0.2 and 49 +/- 5 microM, respectively. Total nitrite in controls' BALF and serum were 2.2 +/- 0.7 and 19 +/- 2 microM, respectively (P < 0.05 compared with transplant values). Serum total nitrite correlated (Pearson product moment) with percentage of neutrophils in BALF (R = 0.650, P < 0.0001), MPO (R = 0.431, P = 0.0055), change in FEV1 from baseline (deltaFEV1) (R = -0348, P = 0.0298), and days after transplantation (R = 0.345, P = 0.0294). None of the associated variables, airway inflanmmation (quantified as a score, "B"), deltaFEV1, serum, or BALF total nitrite, were explained by infection. Univariate analysis of airway inflammation in patients showed that it was associated with BALF neutrophils, deltaFEV1, and serum total nitrite. CONCLUSIONS: Serum nitrite appears to reflect the degree of airway inflammation in this lung-transplant study group.

Adult↗
PubMed2000

The utility of open lung biopsy following lung transplantation.

BACKGROUND: Most pulmonary complications associated with lung transplantation have non-specific clinical characteristics. Furthermore, common diagnostic modalities, including bronchoscopy with transbronchial biopsy (TBB), often do not render a definitive diagnosis. In this study, we reviewed our experience with open lung biopsy (OLB) following lung transplantation, specifically regarding its ability to safely provide clinically relevant information that affects therapeutic decisions. METHODS: From October 1989 to March 2000, 202 patients underwent lung transplantation at our institution. We reviewed the clinical course of the 42 patients who received 48 OLBs. Of these patients, we determined the pre-operative clinical condition, preceding TBB histologic information, OLB histology, treatment changes, and procedural complications as a result of the OLB. RESULTS: A new, clinically unsuspected diagnosis was made in 14 biopsies (29% of all OLB), and all of these resulted in therapy changes. Thirty-two biopsies (67% of all OLB) confirmed our clinical suspicions, and new therapy was initiated in 30 of these patients. Two patients (4% of all OLB) had non-diagnostic OLB. Four biopsies (8% of all OLB), including the 2 non-diagnostic OLBs, did not result in any therapy changes or initiation of new therapy. Complications occurred in 3 patients, all of whom had an air leak for >7 days. CONCLUSION: Open lung biopsy in lung transplant patients renders a new, unsuspected diagnosis in nearly one third of patients and leads to specific, directed therapy in the vast majority of patients. Open-lung biopsy can be performed safely and should be considered when diagnosis is uncertain in clinically deteriorating patients.

Biopsy↗
PubMed1998

Further studies on anti- and proconvulsant effects of inhibitors of nitric oxide synthase in rodents.

We confirmed that the effects of inhibitors of nitric oxide (NO) synthase, such as Nomega-nitro-L-arginine methyl ester and Nomega-nitro-L-arginine, differ depending on several experimental factors. Both compounds but not their less active enantiomers delayed picrotoxin-induced clonus in mice yet increased the incidence of clonus following low-dose picrotoxin. Nomega-nitro-L-arginine methyl ester significantly reduced the latencies of both myoclonus and clonus in older but not younger Sprague-Dawley rats receiving pentylenetetrazol s.c. By contrast, there was no significant change in the latencies for myoclonus and clonus in Wistar rats (older and younger). However, when pentylenetetrazol was administered i.p. rather than s.c., Nomega-nitro-L-arginine methyl ester dramatically increased latencies of convulsive indicators, including tonus, in both Sprague-Dawley and Wistar rats. Nomega-nitro-L-arginine methyl ester also delayed tonus but not myoclonus or clonus in mice, regardless of the systemic route of administration of pentylenetetrazol. Both Nomega-nitro-L-arginine methyl ester and NG-nitro-L-arginine increased the tonic CD50 of pentylenetetrazol in mice and Nomega-nitro-L-arginine methyl ester delayed 4-aminopyridine-induced tonus. However, Nomega-nitro-L-arginine methyl ester reduced the tonic CD50 of both picrotoxin and 4-aminopyridine in mice and failed to suppress tonus following maximal electroshock. Evidently, inhibitors of NO synthase are not universally effective antitonic drugs.

Animals↗
PubMed1998

A review of carisoprodol deaths in Jefferson County, Alabama.

BACKGROUND: Carisoprodol is a skeletal muscle relaxant with the potential for abuse. A carisoprodol overdose is rarely considered fatal. Nevertheless, we encountered carisoprodol in several cases, prompting review of our experience. METHODS: We did a retrospective study of cases examined at the Jefferson County Coroner/Medical Examiner Office from January 1, 1986, to October 31, 1997, reviewing investigative reports and autopsy findings. RESULTS: Carisoprodol was present in 24 cases. Seventeen decedents died of acute drug intoxication. Carisoprodol was never the sole drug detected at autopsy, nor was it ever the sole cause of death. Propoxyphene was a co-intoxicant in 8 of the 24 cases. CONCLUSIONS: Carisoprodol causes respiratory depression. Since the mechanism of death was respiratory depression in 82% of the decedents who died of acute intoxication, we consider that carisoprodol was probably responsible, in part, for those deaths. The simultaneous use of propoxyphene and carisoprodol seems to be especially dangerous.

Acute Disease↗
PubMed1997

A 15-year review of railway-related deaths in Jefferson County, Alabama.

A retrospective computer search of the records of the Jefferson County Coroner/Medical Examiner Office covering the 15-year period from 1981 to 1995 revealed 86 cases in which either a train caused death or in which a body was found dead by the tracks. The average age of the decedents was 39 years (range, 3 weeks-87 years). Men accounted for 88% of the deaths. The manners of death were as follows: three natural, 64 accident, seven suicide, six homicide, and six undetermined. Six decedents were found dead by the tracks, but death was not caused by a train. Six decedents were railroad employees who died on the job. In 47 cases, the decedents were trespassing on railroad property. Five trespassers were riding the rails, and 42 were pedestrians struck by a train. Motor vehicle collisions with trains claimed 27 lives--19 drivers and eight passengers. All together, 45% of the decedents were intoxicated. Intoxication was greatest by far in individuals witnessed to have been lying on the tracks before being hit by a train. The nature of individuals riding the rails has changed in the past few decades. Freight trains today are being used by illegal immigrants as transportation within the United States. The majority of traffic fatalities occurred because the driver intentionally tried to beat the train to the crossing. These drivers were seldom intoxicated, and only two were teenagers. Lives of such impatient drivers might be spared by the installation of a crossing guard-rail that cannot be circumvented.

Accidents↗
PubMed1996

Rabbit DQ52 and DH gene expression in early B-cell development.

Rabbits predominantly rearrange the most 3'VH gene (VH1); thus combinatorial diversity is very limited. In man and mouse, the most 3'DH gene, DQ52, is preferentially rearranged early in B-cell development. To test whether this preference for rearranging a DH gene segment based on 3' end proximity exists in rabbit, we cloned and sequenced the rabbit DQ52 gene. The 11 base pair coding region sequence is identical to a published mouse DQ52, and 81.8% similar to the human sequence. It is localized approximately 805 bp upstream of the JH1 gene. However, the 3' recombination signal sequence has an atypical nonamer. We prepared mRNA from 15- to 28-day fetal rabbits and amplified expressed VDJ sequences of mu mRNA by RT-PCR. The PCR products with VDJ rearrangements were cloned and sequenced. As expected, 44 of 45 VDJ sequences reflected use of the 3' VH1a2 gene, but the DQ52 gene was utilized very infrequently, if at all. We found only one VDJ sequence from 28-day fetal liver B-cells with 8 bp that matched the germline DQ52 sequence. Instead of expressing DQ52, another DH gene, Df was frequently expressed. We cloned the genomic Df gene and localized it about 32 kb upstream of the JH region. Thus, in contrast to man and mouse, rabbits preferentially express a DH gene located in the middle of the DH region early in B cell ontogeny. This may correlate with more frequent initial rearrangement of VH to DH in rabbit B cells.

Amino Acid Sequence↗
PubMed1995

Characterization of a rabbit germ-line VH gene that is a candidate donor for VH gene conversion in mutant Alicia rabbits.

Normal rabbits preferentially rearrange the 3'-most VH gene, VH1, to encode Igs with VHa allotypes, which constitute the majority of rabbit serum Igs. A gene conversion-like mechanism is employed to diversify the primary Ab repertoire. In mutant Alicia rabbits that derived from a rabbit with VHa2 allotype, the VH1 gene was deleted. Our previous studies showed that the first functional gene (VH4) or VH4-like genes were rearranged in 2- to 8-wk-old homozygous Alicia. The VH1a2-like sequences that were found in splenic mRNA from 6-wk and older Alicia rabbits still had some residues that were typical of VH4. The appearances of sequences resembling that of VH1a2 may have been caused by gene conversions that altered the sequences of the rearranged VH or there may have been rearrangement of upstream VH1a2-like genes later in development. To investigate this further, we constructed a cosmid library and isolated a VH1a2-like gene, VH12-1-6, with a sequence almost identical to VH1a2. This gene had a deleted base in the heptamer of its recombination signal sequence. However, even if this defect diminished or eliminated its ability to rearrange, the a2-like gene could have acted as a donor for gene-conversion-like alteration of rearranged VH genes. Sequence comparisons suggested that this gene or a gene like it could have acted as a donor for gene conversion in mutant Alicia and in normal rabbits.

Amino Acid Sequence↗
PubMed1993

VH gene expression and regulation in the mutant Alicia rabbit. Rescue of VHa2 allotype expression.

Rabbits of the Alicia strain, derived from rabbits expressing the VHa2 allotype, have a mutation in the H chain locus that has a cis effect upon the expression of VHa2 and VHa- genes. A small deletion at the most J-proximal (3') end of the VH locus leads to low expression of all the genes on the entire chromosome in heterozygous ali mutants and altered relative expression of VH genes in homozygotes. To study VH gene expression and regulation, we used the polymerase chain reaction to amplify the VH genes expressed in spleens of young and adult wild-type and mutant Alicia rabbits. The cDNA from reverse transcription of splenic mRNA was amplified and polymerase chain reaction libraries were constructed and screened with oligonucleotides from framework regions 1 and 3, as well as JH. Thirty-three VH-positive clones were sequenced and analyzed. We found that in mutant Alicia rabbits, products of the first functional VH gene (VH4a2), (or VH4a2-like genes) were expressed in 2- to 8-wk-olds. Expression of both the VHx and VHy types of VHa- genes was also elevated but the relative proportions of VHx and VHy, especially VHx, decreased whereas the relative levels of expression of VH4a2 or VH4a2-like genes increased with age. Our results suggest that the appearance of sequences resembling that of the VH1a2, which is deleted in the mutant ali rabbits, could be caused by alterations of the sequences of the rearranged VH4a2 genes by gene conversions and/or rearrangement of upstream VH1a2-like genes later in development.

Amino Acid Sequence↗
PubMed1992

Bronchiolitis obliterans organizing pneumonia associated with systemic lupus erythematosus.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a pathologic entity characterized by the formation of plugs of fibrous tissue in bronchioles and alveolar ducts. It has been described in association with several connective tissue diseases including rheumatoid arthritis, polymyositis-dermatomyositis, and mixed connective tissue disease. Well-documented reports of BOOP in patients with systemic lupus erythematosus (SLE) are limited. We report two patients with SLE who presented with subacute respiratory illnesses due to BOOP, adding further strength to the association of this entity with SLE.

Adult↗
PubMed1992

Intrapulmonary teratoma: a case report and review of the literature.

Intrapulmonary teratomas are rare; only 30 cases have been reported in the world literature. These tumors are thought to originate from the third pharyngeal pouch. They occur equally in men and women and usually are diagnosed in the second to fourth decade of life. They are more often benign than malignant, although malignant lesions may have a favorable postoperative prognosis and benign lesions may exhibit high morbidity and mortality because of their size and location. These tumors present radiographically as lobulated masses that may contain calcification or peripheral collections of air. They most often occur in the upper lobes. The computed tomographic findings of intrapulmonary teratoma are less well known but have been described in two cases. An additional case is presented with a review of the literature and a tabular summary of the characteristics of this unusual entity.

Adult↗
PubMed1991

Preferrential rearrangement in normal rabbits of the 3' VHa allotype gene that is deleted in Alicia mutants; somatic hypermutation/conversion may play a major role in generating the heterogeneity of rabbit heavy chain variable region sequences.

The rabbit is unique in having well-defined allotypes in the variable region of the heavy chain. Products of the VHa locus, (with alleles a1, a2, and a3), account for the majority of the serum immunoglobulins. A small percentage of the serum immunoglobulins are a-negative. In 1986, Kelus and Weiss described a mutation that depressed the expression of the Ig VH a2 genes in an a1/a2 rabbit. From this animal the Alicia rabbit strain was developed and the mutation was termed ali. We previously showed, using Southern analysis and the transverse alternating field electrophoresis technique, that the difference between the ali rabbit and normal is a relatively small deletion including some of the most 3' VH genes. The most JH proximal 3' VH1 genes in DNA from normal rabbits of a1, a2 and a3 haplotypes encode a1, a2 and a3 molecules respectively, and it has been suggested that these genes are responsible for allelic inheritance of VHa allotypes. The present study suggests that the 3' end of the VH locus probably plays a key role in regulation of VH gene expression in rabbits because VH gene(s) in this region are the target(s) of preferential VDJ rearrangements. This raises the possibility that mechanisms such as somatic gene conversion and hypermutation are at work to generate the antibody repertoire in this species. Our data support the view that the 3' VH1 gene may be the preferred target for rearrangement in normal rabbits, and for the normal chromosome in heterozygous ali animals. However, homozygous ali rabbits with a deletion that removed the a2-encoding VH1 on both chromosomes do survive, rearrange other VH genes and produce normal levels of immunoglobulins as well as a significant percentage of B cells which bear the a2 allotype. This challenges the view that one VH gene, VH1, is solely responsible for the inheritance pattern of VHa allotypes.

Animals↗
PubMed1991

Molecular analysis of recombination sites within the immunoglobulin heavy chain locus of the rabbit.

Previously, recombinations involving genes of the rabbit immunoglobulin heavy chain locus have been documented serologically. These data indicated that the sites at which the causative recombination events occurred could have been anywhere from within the VH gene cluster up to, or 3' of, C mu. Since these sites could not be localized further by serological methods, we attempted to do this using techniques of molecular biology. DNAs from homozygous recombinant rabbits and from the appropriate non-recombinant parental haplotypes were characterized using Southern blots hybridized with a panel of probes derived from cloned regions of the rabbit immunoglobulin heavy chain gene complex. In all three recombinants, the site was downstream of the entire VH cluster and upstream of the JH cluster within an approximately 50 kilobase (kb) region containing expanses of repetitive-sequence DNA as well as DH genes. DH-specific probes further showed that in two of the recombinants, the recombination appears to have occurred within or 5' of DH1 and 5' of DH2 genes; in the third it occurred 3' of the DH2 genes but at least approximately 5 kb 5' of the JH region.

Animals↗
PubMed1991

Evolutionarily conserved organization and sequences of germline diversity and joining regions of the rabbit T-cell receptor beta 2 chain.

We previously reported that there are three different copies of T-cell receptor beta chain constant region (C beta) genes in some rabbits, two of which are present on an approximately 16-kb and one on an approximately 6-kb Eco RI fragment. We also reported that one of the C beta genes on the approximately 16-kb fragment was chimeric, with a 5' cluster of J beta 2 segments and a 3' untranslated region of beta 1 type. Here we report the complete genomic sequences of the D beta 2 and J beta 2 segments associated with the chimeric C beta gene. The rabbit D beta 2 gene segment has very strong similarity to both its human and mouse counterparts. The sequence similarity also extends rather far from the coding region in both 5' and 3' directions. The content and organization of rabbit J beta 2 gene segments is similar to those found in both human and mouse. The rabbit J beta 2 cluster has six functional segments and one pseudogene, as well as a remnant of another pseudogene between J beta 2.2 and J beta 2.3 equivalent to the one found in man in the same location. The J beta 2.5 gene segment of rabbit has lost the splice signal and is a pseudogene unlike its counterparts in man and mouse. Overall analysis of the rabbit D beta 2-J beta 2 region reveals a closer similarity to human than mouse. However, the general organization of the gene segments in the D beta 2-J beta 2 regions of all three species is remarkably conserved over long stretches of DNA sequence.

Amino Acid Sequence↗