Understanding pharmacy manpower in terms of society's needs.
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During the last 47 years an aggressive approach to the treatment of prostatic malignancies has been maintained at the Duke University Medical Center. Radical prostatectomy, usually by the perineal route and, more recently, by the retropubic technique in conjunction with pelvic lymphadenectomy, has been vigorously applied in patients with diffuse stages A, B and even C diseases. A 5-year survival rate of 80 per cent has been documented. Hormonal therapy has been equally vigorous, most often embracing orchietomy at the time of diagnosis with immediate initiation of estrogen therapy. Patients so treated exhibited a 5-year survival rate of 49 per cent, far greater than the average survival rates usually quoted. Radiation therapy had been used primarily in conjunction with other treatment measures, and multiple drug chemotherapy is now being used in patients who demonstrate disseminated and progressive disease, refractory to other measures previously instituted. By maintaining flexible combinations of all modalities of therapy our overall 5-year survival rate of 50 per cent has been achieved with all patients exhibiting all stages and classifications of prostatic carcinoma.
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The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch-seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.
Three elderly females presenting with iron deficiency anaemia and faecal loss of blood were found to have a macronodular cirrhosis of the liver and an unusual red spotty appearence of the prepyloric antral mucosa. One patient underwent antral resection and the surgical specimen revealed abnormalities of the (sub)mucosal blood vessels. Anaemia and occult faecal blood loss disappeared after operation. It is suggested that this type of antral vascular abnormality is aetiologically related to hepatic cirrhosis and may represent a gastric equivalent of cutaneous spider angiomata.
A viral inhibitor(s) is released in the supernate of mixed cultures containing human or mouse lymphocytes and cells from certain lines. The inhibitor is active against a variety of unrelated viruses and is a protein that is not toxic for cells. It does not inactivate viruses directly, but inhibits viral replication through an intracellular mechanism that involves synthesis by the cells of both RNA and protein. These characteristics identify the inhibitor as an interferon. The anti-viral activity is contained in at least two molecular species, of approximately 25,000 and 45,000 daltons, respectively. In addition to the anti-viral activity, the supernates of the mixed cultures display an anti-cellular activity, the inhibition of DNA synthesis and of cell multiplication. The anti-viral and the anti-cellular activities are positively correlated in supernates from various cultures and in partially purified preparations. The human cell population responsible for interferon production is composed mainly of Fc-receptor positive, surface immunoglobulin negative, non-T-cell lymphocytes. The ability of certain cell lines to induce interferon seems to be preferentially associated with tumor origin or with in vitro transformation by certain viruses (Epstein-Barr virus, murine sarcoma virus).
Bone marrow aspirates totaling 1,024 and trephine biopsies totaling 386 were obtained from 234 patients with various diagnoses of lymphoma. The study analyzed the morphologic patterns of bone-marrow involvement by each entity and compared the sensitivity of aspiration versus biopsy for detecting lymphomatous involvement of bone marrow. Lymphoma may appear in one of three forms: nodular, diffuse (packed bone marrow), and diffusely infiltrative. Trephine biopsy was superior to aspiration in most instances, especially for the nodular form. In some cases, however, examination of paraffin-embedded clot sections and smears was diagnostic of lymphoma whereas the biopsy section appeared negative.
The ultrastructure of tumors induced in kidneys of F344 rats by the carcinogen N-(4'-fluoro-4-biphenylyl)acetamide appeared similar in many aspects to that described in humans and other animal models. The neoplastic cells exhibited microvilli resembling brush border and other adaptations of the cell membrane. Tumor lobules were surrounded by basement membrane-like material, which also extended into the tumor mass between individual cells. The ultrastructure appeared to reflect a proximal tubular origin of these lesions.
The treatment results of the Rotterdam working group on esophageal cancer during the period January 1970-January 1978 were assessed. A total number of 328 patients were treated: 230 males and 98 females. Of the 133 patients eligible for a combined treatment modality i.e. preoperative radiotherapy and surgery, 52 showed irresectable or metastatic disease during operation. The five year actuarial survival rate of the 81 patients, in whom curative surgical resection of the tumor was performed, amounted to 21%. Females fared better than males, the five year survivals being 42% and 12% respectively. This female preponderance in survival is partly explained by the considerable postoperative mortality of the male patients: 28% vs 7.4% in females. Patients who received only radiation therapy, whether curative or palliative, had a very bad prognosis. It is concluded that preoperative irradiation followed by surgical removal of the tumor should be performed in all operable-curable patients.
Amoebae of the true slime mould Physarum polycephalum were cultured in two fully-defined liquid media containing amino acids, glucose, three vitamins and a buffered salts solution. Absolute requirements were demonstrated for methionine, haematin, thiamine and biotin, all of which were known to be specific requirements of the plasmodial stage. Methods are described for large-scale culture in three semi-defined media.
The penetration of gentamicin and tobramycin into the synovial fluid of 12 patients with nontraumatic joint effusions was studied. Simultaneous serum and synovial fluid specimens taken after the intramuscular or intravenous administration of an antimicrobial agent were assayed. Synovial fluid levels of antibiotic were >50% of serum levels in all subjects studied. In five patients, synovial fluid levels were equal to or exceeded simultaneous serum values. These results suggest that intra-articular injection of aminoglycoside antibiotics is not necessary in the treatment of infectious arthritis.
Macrolide antibiotics are commonly prescribed to treat Haemophilus influenzae respiratory tract infections. Studies have primarily focused on emerging H. influenzae strains with acquired macrolide resistance, while the bacterium's intrinsic resistance to antibiotics has been underexamined. Here, we used a genome-wide approach of transposon insertion-site sequencing to screen an H. influenzae mutant library grown in sub-inhibitory doses of the macrolide antibiotic clarithromycin (CLR) to identify 33 genes involved in intrinsic CLR resistance. Almost half of these genes are also needed for survival in the mouse lung. We focused on candidate genes necessary for both intrinsic macrolide resistance and lung survival. Two of these genes affect the outer-membrane composition of H. influenzae, orfH and omp26. Deletions of these genes in Rd and nontypeable H. influenzae clinical isolates, Hi375 and NT127, conferred sensitivity to CLR and polymyxin B and increased membrane permeability to ethidium bromide (EtBr). The omp26 mutant was sensitive to killing by human serum. Deletions of orfH or omp26 in an acrR mutant strain overexpressing a multidrug efflux pump abrogated resistance of the acrR mutant to CLR and restored permeability to EtBr. Thus, deletion of these genes not only mitigates the effects of an acquired resistance mechanism but also remarkably overrides it. Complementation of these deletion mutations restored CLR resistance and decreased permeability to EtBr. Our results indicate that the subset of genes with dual roles in intrinsic resistance and host lung survival may provide potential novel combination antimicrobial therapeutic targets.
The cellular fatty acid composition of Pseudomonas paucimobilis (IIk-1) and group IIk-2, Ve-1, and Ve-2 was determined by gas-liquid chromatography. The unnamed groups were readily distinguished from P. paucimobilis by cellular fatty acids. The data strongly suggest that these bacteria may be additional species of Pseudomonas and Flavobacterium.
The cellular fatty acid composition of OLDA, a rickettsia-like agent isolated in 1947, was essentially identical to that of the Legionnaires disease bacterium (LDB). WIGA, another rickettsia-like agent isolated in 1959, contained the same fatty acids as OLDA and other LDB but differed significantly from these strains in relative amounts of the major acids present. The major acid of OLDA and other LDB was i-16:0 whereas a-15:0 was the major acid of WIGA.
Prolonged storage of sera at -20 degrees C did not significantly affect anti-Candida precipitin titers measured by counterimmunoelectrophoresis when compared with the original determinations.
Detection of serum precipitins to Aspergillus fumigatus by counterimmunoelectrophoresis is compared with the immunodiffusion technique. Eight of nine (89%) sera from patients with proven A. fumigatus infection were positive by both methods. No serum from subjects with other systemic mycoses, bacterial infections, or healthy controls had detectable precipitins. The highest serum precipitin titers were found in sera of patients with the mycetomal and invasive forms of the disease. Detection of A. fumigatus serum precipitins by counterimmunoelectrophoresis compares favourably with immunodiffusion and has the advantage of significantly reducing the time required for results.