Comprehensive family practice clerkship in a minority institution

A comprehensive family practice clerkship program at Howard University College of Medicine has been conducted since 1970. This institution is one of three predominantly black institutions offering a family practice program. The senior clerkship is mandatory and at least 20 to 25 percent of each class elect to participate in a four-to six- week family practice preceptorship. As a result of the clerkship''s success, over 50 percent of the program''s graduates actively practice in primary medical manpower shortage or medically underserved areas.     

Analysis of pressure waves as a mean of diagnosing vascular obstructions

A feasibility study was made to examine whether pressure measurements can be used to diagnose vascular obstructions in blood vessels. Distortion of a pressure wave due to an obstruction in an elastic tube was investigated theoretically and experimentally. Linear theory and the method of characteristics were employed in developing mathematical expressions for the distortion of the pressure wave. The quality of the models developed was examined by performing experiments on a latex tube with rigid obstructions. A nonlinear model using the method of characteristics was in good agreement with the experiment data for obstructions with any severity, while a linear model was applicable to small obstructions. The nonlinear model is proposed as a mathematical model for the detection of vascular obstructions by analysing pressure waves.     

Pathogenesis and Autointerference in a Virus Disease of Crabs

The course of an infection apparently caused by a filterable virus of the blood of the shore crab. Carcinus maenas, has been experimentally studied in this host both at Roscoff, France. where it was originally found, and at Woods Hole, Mass., where the local species was also found susceptible. Although a portion of the infected animals die with the symptoms of inadequate blood clotting, recovery of this function occurred promptly in about two-thirds of the animals. Half of the animals that recovered this function did so within 4 to 6 days. Recovery was not accompanied by disappearance of the virus from the whole blood. In tests done as late as 40 days after recovery, virus was still present. Autointerference was demonstrated after acute infection. It was found in the serum of animals with manifest disease on all days tested and in whole blood of animals taken more than 2 days after the clotting defect appeared. It was not demonstrable within the whole blood within the first 2 days of disease. The role of this in the recovery phenomenon is discussed.     

Adult-onset type II citrullinemia and idiopathic neonatal hepatitis caused by citrin deficiency: involvement of the aspartate glutamate carrier for urea synthesis and maintenance of the urea cycle

Citrin is a mitochondrial aspartate glutamate carrier primarily expressed in the liver, heart, and kidney. We found that adult-onset type II citrullinemia is caused by mutations in the SLC25A13 gene that encodes for citrin. In this report, we describe the frequency of SLC25A13 mutations, the roles of citrin as a member of the urea cycle and as a member of the malate-aspartate shuttle, the relationship between its functions and symptoms of citrin deficiency, and therapeutic issues.     

Modulation of large conductance calcium-activated K+ channel by membrane-delimited protein kinase and phosphatase activities

Large conductance Ca²⁺-activated K⁺ channel was identified and studied in excised inside-out membrane patches of freshly dispersed smooth muscle cells from rabbit gastric antrum. The current-voltage relationship of the single channel was linear from -80 to +80 mV of pipette voltage in which single channel conductance was 249±17.8 pS (n=19) in symmetrical concentration of K⁺ (145mM) across the patch. Activity of the channel (NPo) depended not only on cytoplasmic calcium concentration but also on membrane potential. MgATP increased NPo in a dose-dependent manner and Mg²⁺ was prerequisite for the effect. Okadaic acid (l00nM), inhibitor of protein phosphatases, increased NPo further in the presence of MgATP. Therefore, it would be concluded that activity of the calcium-activated K⁺ channel in gastric smooth muscle cells was controlled by phosphorylation state of the channel protein and the state is further modulated by membrane-delimited protein kinase and protein phosphatase activities.     

广西壮族人群ICAM-1基因多态性及血清水平与脑梗死关系的研究

探讨细胞间黏附分子1(ICAM-1)基因K469E多态性各等位基因及基因型在广西壮族脑梗死患者中的分布频率,初步分析其基因及血清水平与脑梗死的关系。采用聚合酶连反应-限制性片段长度多态性(PCR-RFLP)和DNA序列测定法检测19例脑梗死及210例对照者ICAM-1基因第6外显子K469E多态性,同时采用酶联免疫吸附试验(ELISA)检测脑梗死和对照者血清ICAM-1水平。脑梗死组ICAM-1血清水平显著高于对照组(P<0.01),ICAM-1基因K469E基因频率和等位基因频率在脑梗死组和对照组比较差异有显著性(P<0.05),等位基因频率的相对风险分析发现,E等位基因携带者患脑梗死的风险是K等位基因的1.454倍(OR=1.454,95%CI1.090～1.940),携带E等位基因的脑梗死患者ICAM-1血清水平显著高于不携带者(503.31±141.32)ng/ml和(489.80±122.43)ng/ml,(P<0.01)。ICAM-1基因K469E多态性与脑梗死的发病具有相关性,E等位基因可能是广西地区壮族人脑梗死发病的遗传易感基因,携带E等位基因的个体可能通过促进ICAM-1的高度表达进而增加脑梗死的发病风险。     

A pilot study of bortezomib in Korean patients with relapsed or refractory myeloma

Recent clinical trials showed that bortezomib, a novel proteasome inhibitor, had therapeutic activity in multiple myeloma. However, there was no data about the feasibility of bortezomib in Korean patients. We performed a pilot study of bortezomib in patients with relapsed or refractory myeloma (1.3 mg/m2 twice weekly for 2 week in a 3-week cycle). Seven patients were enrolled. The median age of patients was 59 yr. All patients previously received VAD (vincristine, doxorubicin and dexamethasone) and thalidomide chemotherapy. Three patients previously received alkylator-containing chemotherapy and 4 patients, autologous stem cell transplantation. Bortezomib monotherapy resulted in 3 partial remissions (43%), 3 no changes (43%) and 1 progressive disease (14%). One patient who had no response to bortezomib monotherapy experienced partial remission after addition of dexamethasone to bortezomib. The most common serious toxicity was thrombocytopenia (grade 3/4, 10 of 20 cycles (50%)) and grade 3 peripheral neuropathy was developed in 2 of 20 cycles (10%). Drug-related adverse event led to discontinuation of bortezomib in 1 patient. There was no treatment related mortality. Overall, bortezomib seems to be effective and feasible. Conduction of larger clinical studies on Korean patients is necessary to characterize clinical efficacy and safety of bortezomib more precisely.     

BK polyomavirus interstitial nephritis in a renal allograft recipient

Human polyomavirus (PV) interstitial nephritis has recently been recognized as a cause of severe renal allograft dysfunction. It occurs in immunosuppressed patients after reactivation of the latent virus PV type BK (BK virus) in the renal epithelium. BK disease is defined as a morphologically manifest renal infection with cytopathic signs accompanied by varying degrees of interstitial inflammatory cell infiltrates and functional impairment. It is also identified by the presence of cells containing viral inclusion bodies (decoy cells) in the urine. The authors report a case of BK PV interstitial nephritis in a 36-year-old renal allograft recipient. Under light microscopy the chief diagnostic indicator was detection of intranuclear viral inclusions, which were found exclusively in tubular epithelial cells. Cells with viral changes were often enlarged with nuclear atypia and chromatin basophilia. Widespread interstitial plasma cell infiltrates associated with tubulitis were present. Intranuclear paracrystalline arrays of virus particles 35-38 nm in diameter were present as characteristic ultrastructural indicators. Urine samples revealed decoy cells with ground-glass-type intranuclear inclusions positive for BK virus by electron microcopy.     

Differences and relationships between the physical properties and the microscopic structure of human femoral,tibial and fibular cortical bone

Coefficients of correlation between certain physical properties and the histological components of the break area were calculated on an IBM 7090 computer for 56 femoral, 79 tibial and 37 fibular specimens of embalmed cortical bone of standardized size and shape. Strong positive correlations (0.01–0.02 significance level) were found between tensile strength and the percentage of interstitial lamellae in the break area; between hardness and the number of osteons/mm²; and between hardness and the percentage of osteons in the break area. Equally high negative correlations were found between tensile strength and percentage of osteons in the break area; between shearing strength and average area/osteon remnant; between elastic modulus and percentage of spaces in the break area; and an even higher correlation (0.001) between hardness and percentage of spaces in the break area. Negative correlations (at slightly more than 0.05 significance level) were found between shearing strength and modulus and average area/osteon. Osteons tend to reduce the tensile strength and elastic modulus of bone while interstitial lamellae tend to increase them. The probable reason is the relatively greater amount of cement lines, which are sites of weakness where failure can occur, in Haversian bone as compared with lamellar bone. The predominant orientation of collagen fibers and the amount and distribution of calcium may also be involved. These factors are now being investigated.     

Mechanism of slowing of mucociliary transport induced by SO2 exposure

Responses of nasal mucociliary transport mechanisms to exposure to 6 ppm SO₂ were studied in chickens in vivo. This model takes advantage of the natural cleft palate which exposes the mucociliated base of the nasal septum. Exposure to 6 ppm SO₂ decreased the mucociliary transport rate along the base of the nasal septum. The minimum force required to move an iron particle along this area of mucous membrane by use of a magnetic field in vivo increased significantly after SO₂ exposure, while the minimum force required to move an iron particle on a pool of mucus collected from the same chicken and tested in vitro showed no change after SO₂ exposure. The elastic recoil distance of mucus was measured both in vivo and in vitro. The in vivo recoil distance decreased significantly after SO₂ exposure, while SO₂ exposure did not change recoil distance in vitro. It is proposed that exposure of chickens to SO₂ results in the formation of multiple points of adhesion of strands of mucus between the acinar gland cells and the emergent extracellular mucus or adhesion of a mucous blanket to the cilia, causing mucociliary transport to be retarded or static.