Topical tretinoin prevents corticosteroid-induced atrophy without lessening the anti-inflammatory effect.
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Biomedical subjects
Publications and source records attributed to E Schwartz.
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Articular contact pressures in ten cadaveric knees with intact ligaments were measured with the use of film and a model that simulated non-weight-bearing resistive extension of the knee. The measurements were repeated after sequential sectioning of the posterior cruciate ligament and the posterolateral complex (the posterolateral capsule, the popliteus muscle and tendon, and the lateral collateral ligament). Patellofemoral pressures and quadriceps load were most significantly elevated after combined sectioning of the posterior cruciate ligament and the posterolateral complex. Medial compartment pressure was significantly elevated after sectioning of the posterior cruciate ligament. The results coincided with, and may partially explain, the clinical findings associated with these types of ligamentous injuries.
Arthroscopic camera bags are extremely practical because they allow multiple procedures to be performed in the same day. This is especially true for small community hospitals where equipment is limited. Unfortunately, the plastic creates a greenhouse effect, allowing any moisture that is present to condense and fog the camera and scope. By using sponges placed inside the camera bag to wipe the optical lenses, the surgeon can improve visualization during an arthroscopic procedure if fogging becomes a problem.
The effect of rotating magnetic field (RMF) was studied on the growth of Deals' guinea pig sarcoma (DGPS) transplanted subcutaneously into the inguen of guinea pigs. The 0.2 ml of transplanted suspension contained 1.5-2.0 x 10(6) of vital DGPS cells. Over a period of 24 days the animals were daily two times exposed to RMF for 3 hours. The animals were sacrificed in chloroform anesthesia, the inguinal tumors, lungs and hearts were removed and weighed. The following findings were recorded: 1. RMF inhibited the growth of DGPS cells in experimental guinea pigs compared to control animals (p < 0.001); 2. In the experimental animals DGPS cells did not metastasize into the lung parenchyma; 3. The pathological characteristics of the tumors in the experimental and control group of guinea pigs tended to be different. (Tab. 3, Ref. 14.)
The Fc gamma receptors (Fc gamma R) are glycoproteins that bind the Fc region of immunoglobulin G. Human hematopoietic cells express three biochemically distinct classes of Fc gamma receptors: Fc gamma RI (CD64), Fc gamma RII (CD32) and Fc gamma RIII (CD16). Complementary DNA (cDNA) clones for each of the human Fc gamma receptors have been isolated from myeloid and lymphoid cells. We describe the isolation and characterization of four Fc gamma RII clones from a cDNA library obtained from a megakaryocyte-like cell line, human erythroleukemia (HEL). Three clones encode the Fc gamma RIIA transmembrane (TM) form, while one novel clone lacks the TM region but retains the cytoplasmic domain. By conducting reverse transcription coupled to polymerase chain reaction (PCR), we found transcripts coding for this unique form of receptor in RNA from platelets, HEL cells and a second megakaryocyte-like cell line, CHRF-288-11. These results were confirmed by RNase protection analysis of RNA from HEL cells. The structure of the novel cDNA suggested that it codes for a soluble form of Fc gamma RIIA. A soluble Fc gamma RII protein was detected in the conditioned medium from HEL cells but not from the Fc gamma RII-negative T cell line, Jurkat, by immunoprecipitation with the anti-Fc gamma RII monoclonal antibody (mAb), IV.3. The immunoprecipitated protein was of the expected size for a soluble Fc gamma RII lacking the TM region but retaining the cytoplasmic domain. Soluble Fc gamma RIIA may be important in modulating the interaction between immune complexes and membrane-associated Fc gamma RII.
Regular red blood cell transfusions reduce the rate of recurrent cerebral infarction in sickle cell disease but lead to accumulation of excessive iron. We studied the effect on the prevention of recurrent stroke and the volume of blood transfused of a modified transfusion program in which the pretransfusion percentage of hemoglobin S (HbS) was maintained at 50%, rather than the conventional 30%. Fifteen patients with sickle cell disease and cerebral infarction who had been free of recurrent stroke for at least 4 years during which the pretransfusion HbS was maintained below 30% were assigned to a transfusion program in which the HbS was allowed to increase to 50%. Transfusion regimens included simple transfusion and manual and automated partial exchange transfusion. The duration of follow-up was 14 to 130 months with a median duration of 84 months. None of the 15 patients had a recurrent cerebral infarction during 1,023 patient-months in which the target pretransfusion HbS was 50%. Analysis of this finding, using a binomial distribution, indicates that there is less than a 5% chance that the risk per patient of recurrent stroke in the first year of the modified transfusion program is greater than 18%. One 23-year-old patient had a fatal intraventricular hemorrhage when the HbS was 30% and a 21-year-old patient had a fatal subarachnoid hemorrhage in the 40th week of pregnancy when the HbS was 29%. Blood requirements with simple transfusions decreased by 17% to 48% (mean 31%) when the target pretransfusion HbS level was increased from 30% to 50% (P less than .001). Manual or automated partial exchange transfusions and a target HbS level of 50% in eight patients reduced blood requirements by 33% to 99% (mean 67%) in comparison with simple transfusion and a target HbS level of 30% (P less than .001). This study offers evidence that a target pretransfusion HbS level of 50% affords a continuing high rate of protection against recurrent cerebral infarction in sickle cell disease after 4 years of a conventional transfusion program. Increasing the target HbS level from 30% to 50% provides a major reduction in blood requirements and lowers the rate of iron accumulation.
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A rapid, simple, nonradioactive method for detection of four common mutations causing cystic fibrosis (CF) has been developed combining multiplexing with allele-specific polymerase chain reaction amplification. This approach (MASPCR) provides an easy assay for direct genotyping of normal and mutant CF alleles in homozygotes and heterozygotes. The strategy involves multiplex PCR of exons 10, 11, and 21 within the cystic fibrosis transmembrane conductance regulator (CFTR) gene in a single reaction containing three common oligoprimers and either the four normal or four mutant oligos corresponding to the delta F508, G551D, G542X, and N1303K mutations. Primers are chosen so that the size of the four PCR products differ, thereby facilitating detection on agarose gels following amplification in the same reaction. Patient samples are primed with either four normal or four mutant oligo mixtures, and PCR products run in parallel on gels to detect band presence or absence. This approach provides a simple and potentially automated method for cost-effective population screening.
The nucleotide sequence of the rpoN gene, formerly designated hno, and flanking DNA regions of the aerobic hydrogen bacterium Alcaligenes eutrophus has been determined; rpoN codes for the RNA polymerase sigma factor sigma 54 involved in nitrogen regulation and diverse physiological functions of gram-negative bacteria. In A. eutrophus hydrogen metabolism is under control of rpoN. The Tn5-Mob insertion in a previously isolated pleiotropic mutant was mapped within the rpoN gene. The derived amino acid sequence of the A. eutrophus RpoN protein shows extensive homology to the RpoN proteins of other organisms. Sequencing revealed four other open reading frames: one upstream (ORF280) and three downstream (ORF130, ORF99 and ORF greater than 54) of the rpoN gene. A similar arrangement of homologous ORFs is found in the rpoN regions of other bacteria and is indicative of a conserved gene cluster.
The human Fc gamma receptor gene Fc gamma RIIA is expressed in platelets, neutrophils, monocytes and macrophages. Understanding the regulation of expression of Fc gamma RIIA will enhance our knowledge of regulated gene expression and immune function in these cells. We cloned a 3.65 kb region of the 5' end of the Fc gamma RIIA gene and characterized 3.4 kb of previously unreported sequence of the 5'-flanking region. Primer extension studies and RNase protection analyses of mRNA from HEL, K562 and U937 cells revealed multiple transcription start sites. One transcription start site mapped to a 5'-untranslated (5'UT) exon approximately 1 kb 5' to the ATG translation initiation codon, while a second start site mapped near the ATG codon. Reverse transcription combined with PCR (RT-PCR) employing an oligonucleotide in the putative 5'UT exon and an antisense oligonucleotide in the translated region yielded products which confirm that transcription starts in this 5'UT exon 881 bp upstream of the ATG codon. Sequence analysis of the RT-PCR products showed two related RNA splice products which use alternative 3'-consensus AG splice acceptor sites. Fc gamma RIIA mRNA thus has three distinct potential 5'UT regions, two alternatively spliced forms from the start site in the 5'UT exon and the third from the start site near the ATG codon. Comparisons of the human Fc gamma RIIA 5'-flanking region with human Fc gamma RI and mouse Fc gamma RII beta genes as well as with other genes expressed in megakaryocytes, neutrophils and monocytes reveal structural similarities and shared promoter elements.
Cystic fibrosis (CF) is a common genetic disorder in Caucasians, and in some populations 70% of cases are associated with a 3 base pair (bp) deletion (delta F508) in the CFTR gene. We have implemented a fluorescence-based, multiplex allele-specific polymerase chain reaction (MASPCR) assay for deletion of the delta F508 mutation. Different allele-specific fluorescently-tagged primers are used in the PCR reaction to distinguish between normal and delta F508 alleles. Fluorescent PCR products are then visualized in a single lane on an agarose gel following electrophoresis combined with real-time multicolour fluorescence detection. The approach simplifies diagnosis of the most common mutation in the CFTR gene, and holds promise for a multiplex allele-specific, fluorescence-tagged gene amplification strategy for detection of additional CF mutations which may result in more cost-effective testing without increasing the risk of missed or erroneous diagnoses.
STUDY OBJECTIVE: To compare the effects of water rinse with those of isopropyl alcohol, polyethylene glycol with industrial methylated spirits, or ethanol on cutaneous phenol burns. DESIGN: Controlled trial with all animals receiving all treatments applied to different cutaneous phenol burn sites. TYPE OF PARTICIPANTS: Swine weighing 9 to 18 kg. INTERVENTIONS: In phase 1, each burn site was treated with water rinse for zero, one, or five minutes combined with either isopropyl alcohol, polyethylene glycol with industrial methylated spirits, ethanol, or no other treatment. Biopsies of treatment sites were done at 30 minutes and at 48 hours. In phase 2, a pilot study, the effect of isopropyl alcohol, polyethylene glycol with industrial methylated spirits, or water treatment on serum phenol levels was noted in animals with 5%, 10%, and 15% body surface area burns. MEASUREMENTS AND MAIN RESULTS: In phase 1, on histological examination of biopsy specimens, significant differences in tissue damage occurred among the groups (P < .05). Isopropyl alcohol and polyethylene glycol with industrial methylated spirits were the most efficacious treatments; the duration of water rinse had no significant effect. In phase 2, the systemic absorption of phenol may be greater with water treatment than with isopropyl alcohol treatment. CONCLUSION: Isopropyl alcohol and polyethylene glycol with industrial methylated spirits are equally effective in the amelioration of phenol burns of less than 5% total surface area. The wider availability of isopropyl alcohol makes it potentially the most useful treatment for these small burns. Further studies of its risks are needed.
STUDY OBJECTIVE: To compare two related pharmacological agents used for the chemical restraint of agitated and combative patients. DESIGN AND SETTING: A randomized, double-blind, prospective study was carried out in patients requiring physical restraint in a university hospital emergency department. PARTICIPANTS: Sixty-eight violent or agitated adult patients whom the attending physician believed would benefit from chemical restraint to protect the patient and staff and to expedite evaluation. INTERVENTION: Twenty-one participants were administered 5 mg haloperidol IM; 26 were administered 5 mg droperidol IM; 12 were administered haloperidol IV; and nine were administered 5 mg droperidol IV. RESULTS: All patients were rated on a five-point combativeness scale at five, ten, 15, 30, and 60 minutes after the study drug was given. Vital signs also were recorded at these times. IM droperidol decreased combativeness significantly more than IM haloperidol at ten (P = .006), 15 (P = .01), and 30 (P = .04) minutes. There was no significant difference between the two drugs when given by the IV route (beta at the 5% confidence level, P = .78). CONCLUSION: In equal IM doses (5 mg), droperidol results in more rapid control of agitated patients than haloperidol, without any increase in undesirable side effects.
Human papillomavirus type 16 (HPV-16) transcription was analysed in one squamous cervical carcinoma by cDNA cloning and DNA sequencing, and in eight additional squamous cervical carcinomas and 11 precancerous lesions by RNA-RNA in situ hybridization. The nucleotide sequences of the cDNA clones revealed structures of early HPV-16 mRNAs (E6*-E7-E1 E4-E5) in agreement with data reported for other premalignant and malignant tumours. cDNA clones possibly representing viral RNA of antisense orientation were also detected. These RNAs included sequences of the upstream regulatory region, part of the early and the late region of the genome. In three of eight squamous cervical carcinomas examined by in situ hybridization, signals specific for viral antisense RNA were also found. The antisense RNAs had a predominantly nuclear localization. Viral antisense RNA could not be detected in any of 11 HPV-16-positive premalignant lesions. The expression of HPV antisense RNA is likely to be linked to viral integration into the host genome. The possible effects of viral antisense transcription with regard to tumour progression remain to be determined.
A rapid, simple, cost-effective, non-radioactive method for detection of the most common mutations causing beta-thalassemia in Mediterranean people has been developed by combining multiplexing with the amplification refractory system. This approach, the multiplex amplification refractory mutation system (MARMS), provides an easy assay for direct detection of normal and mutant beta-globin genes in homozygotes and heterozygotes. The strategy involves multiplex PCR of four of the five regions of interest within the beta-globin gene in a single reaction containing a common oligoprimer and either the normal or mutant oligonucleotides corresponding to IVS-1 nucleotide 1 or IVS-1 nucleotide 6, IVS-1 nucleotide 110, codon 39, and IVS-2 nucleotide 1 regions. Primers are chosen so that the sizes of the four PCR products differ, thereby facilitating detection on agarose gels following amplification. Patient samples are primed with either four normal or four mutant oligonucleotide mixtures and the common oligoprimer, and PCR products run in parallel on gels to detect band presence or absence. This approach simplifies mutation detection and shows promise for automation employing fluorescent-tagged primers.
One of the key enzymes in the chemolithoautotrophic metabolism of Alcaligenes eutrophus H16 is a dimeric, membrane-associated hydrogenase. The genetic determinants of this enzyme are located on the endogenous megaplasmid pHG1 (G. Eberz, C. Hogrefe, C. Kortlüke, A. Kamienski, and B. Friedrich, J. Bacteriol. 168:636-641, 1986). Complementation studies showed that the information required for the formation of active membrane-bound hydrogenase occupies more than 7.5 kb of megaplasmid DNA. We cloned and sequenced this region and identified the genes encoding the two hydrogenase subunits (hoxK and hoxG). The nucleotide sequence contains nine additional closely spaced open reading frames. Immunoelectron microscopy showed that the gene product of one of these open reading frames (hoxM) is involved in the process leading to the attachment of hydrogenase to the membrane. Other open reading frames may encode additional processing functions and components of a hydrogenase-linked electron transport chain. Analysis of Tn5-B21-mediated transcriptional fusions provided evidence that the structural genes and accessory functions belong to at least three coordinately regulated transcriptional units.
STUDY OBJECTIVE: The aim was to examine the epidemiology of unknown primary cancer mortality in the USA during 1979 to 1988 by age, sex, race, year, and geographical area. DESIGN: National (US) and state data were abstracted for deaths due to ill defined cancer (ICD-9 195.0 to 199.1) and all cancers combined (ICD-9 140.0-209.9). Age adjusted mortality rates were calculated using the 1980 USA population as the standard, and standardised rate ratios were derived. National total cancer incidence data were obtained from the surveillance, epidemiology and end results (SEER) program, and age and sex specific relative (black/white) cancer incidence rates were derived and compared to relative (black/white) mortality rates for ill defined cancer. State and regional median family income levels were obtained from the 1980 census and compared to corresponding mortality rates. SETTING: This study used data for the US population, the 50 states, and the District of Columbia. MEASUREMENTS AND MAIN RESULTS: During 1984-1988, ill defined cancers accounted for an average of 34,921 deaths each year in the USA (13.7 per 100,000 population). The mortality rate due to ill defined cancers is greater among blacks (19.3 per 100,000) than whites (13.2 per 100,000) (RR = 1.5) and has not declined since 1979. There is considerable geographical variation in the ill defined cancer mortality rate. Thus among blacks the highest rates were clustered in the central states (23 per 100,000) and the lowest rates were seen in the mountain and western states (17 per 100,000). The District of Columbia had the highest overall rate (21.7 per 100,000) when compared to all other states. The black/white relative mortality rate due to ill defined cancer was consistently greater than the black/white relative incidence of all cancers. CONCLUSIONS: Ill defined cancer mortality is the fourth leading site of cancer mortality in the USA, and accounts for 7.4% of cancer deaths annually. The large proportion of ill defined cancer deaths may have biased the accuracy of national and local cancer incidence and mortality statistics. The higher mortality of ill defined cancer among blacks is not explained by the higher overall cancer incidence among blacks and suggests the influence of socioeconomic or cultural barriers that may result in underutilisation of health services or substandard health care. Ill defined cancer mortality may be a sentinel indicator of deficiencies in the health care delivery system as well as a measure of progress against cancer.
Epidemiological surveillance of sentinel occupationally related deaths commonly relies on computerized analyses of mortality data obtained from vital statistics records. A computer search of death records in the District of Columbia for the period 1980 to 1987 identified 15 cases that noted asbestosis, silicosis, coal worker's pneumoconiosis, or primary cancer of the pleura/mesothelioma as the underlying cause of death. A manual review of the death certificates for the same period identified three times as many cases (n = 48) with any mention of these conditions. Problems with performing surveillance of these events using death certificates include the lack of sufficient information to identify mesotheliomas and the failure to code and computerize all contributing causes of death.