Biomedical subjects

W Johnston

Publications and source records attributed to W Johnston.

At least 19 recordsLinked to original sources

PubMed2002

Industrial control of recombinant E. coli fed-batch culture: new perspectives on traditional controlled variables.

Three industrially relevant fed-batch algorithms were applied to the production of recombinant proteins in Escherichia coli BL21 DE3. Starvation dissolved-oxygen (DO)-transient control sustained growth rates greater than those in pH-stat (0.16 h(-1) versus 0.11-0.13 h(-1)) while feed-up DO-transient control better tracked the measured threshold for acetate production (mu approximately 0.2 h(-1)). All controllers supported growth without acetate production, resulting in end concentrations of recombinant protein up to 20 times greater than in batch culture. Both DO-transient control systems were judged superior to pH-stat for their ability to detect and track the acetate threshold. Results also showed that although high cell density at the stationary phase is desirable, this parameter may be dictated by the choice of media and reactor design as opposed to controller type. Controller selection, however, has a great impact on the capacity to track the acetate threshold and therefore to enhance productivity without concomitant acetate production.

Journal Article↗

PubMed2001

Symptom factor analysis, clinical findings, and functional status in a population-based case control study of Gulf War unexplained illness.

Few epidemiological studies have been conducted that have incorporated clinical evaluations of Gulf War veterans with unexplained health symptoms and healthy controls. We conducted a mail survey of 2022 Gulf War veterans residing in the northwest United States and clinical examinations on a subset of 443 responders who seemed to have unexplained health symptoms or were healthy. Few clinical differences were found between cases and controls. The most frequent unexplained symptoms were cognitive/psychological, but significant overlap existed with musculoskeletal and fatigue symptoms. Over half of the veterans with unexplained musculoskeletal pain met the criteria for fibromyalgia, and a significant portion of the veterans with unexplained fatigue met the criteria for chronic fatigue syndrome. Similarities were found in the clinical interpretation of unexplained illness in this population and statistical factor analysis performed by this study group and others.

Adult↗

PubMed1999

Morphological and biochemical modifications of human macrophages treated with various biomaterials.

Although tissue culture techniques are used extensively to explore the biocompatibility of various biomaterials used in orthopaedic, dental and pharmaceutical fields, the role of these materials towards human monocytes/macrophages has not been fully elucidated. The specific objectives of this investigation were: (1) to determine the biochemical markers resulting from exposure of the human monocytes/macrophages to titanium (TI), large size polyethylene (LSP), submicron polyethylene (SPE), hydroxyapatite (HA), large particle size tricalcium phosphate (LTCP), and small particle size tricalcium phosphate (STCP), and (2) to morphologically evaluate the viability of the cells treated with the aforementioned biomaterials. Approximately 15 volunteers donated blood for each phase (24, 48, and 72 hours) of the experiment. The monocytes were isolated by following established lab procedures (Histopaque 1077 and 1119). Aseptic techniques were followed throughout each phase. Each phase contained four experimental groups (TI, LSP, SPE, HA). Each group was comprised of six wells. The total protein, catalase, LDH, MDA, and cell count were measured using established lab protocols. Data obtained suggests that: (I) regardless of the biomaterial being used all experimental groups experienced remarkable phagocytosis in the first two phases (24, 48 hours), (II) during the 24 hour phase MDA activities were increased in TI, LTCP, and STCP treated wells when compared to the control and other experimental groups, (III) in the 48 hour phase the MDA level increased in LPE and STCP treated cells, (IV) there were significant differences in LDH levels in LPE, STCP, and SPE at 24 hours compared to the control and other experimental groups, (V) LDH activities were increased in LPE, STCP, SPE, and LTCP at 48 hours, and (VI) at 72 hours there were significant increases in catalase activity in HA, TI, SPE and LPE when compared to the control group and other experimental groups. Information obtained from this study provided new ideas about the interrelationship of various biomaterials, the effect of size and cell response to the various biomaterials.

Biocompatible Materials↗

PubMed1999

Biochemical markers evaluation of RAW transformed cells during treatment with various biomaterials.

Upon introduction into the human body, biomaterials initially trigger a foreign-body inflammatory response. Furthermore, the wear debris associated with such materials as those used for orthopedic implants, artificial heart valves, and dental implants can cause the body to mount an inflammatory response. This involves the production of phagocytic macrophages that ingest the foreign material while simultaneously producing cytokines that serve as chemotactic agents for an amplified immune response. Currently titanium (Ti), polyethylene (PE), tricalcium phosphate (TCP) and hydroxyapatite (HA) are widely used as biomaterials in medical implants, and particle size is an important factor in the development of orthopedic, dental, and medical implants. The objective of this study was to investigate the effect of various biomaterials (Ti, mixed particle size polyethylene (MPE), ultra high molecular weight polyethylene (UHMWPE), mixed particle size TCP (MTCP), < 0.38 micron TCP (S-TCP), and hydroxyapatite (HA)) on the inflammatory reactions expressed by transformed RAW macrophages. RAW transformed monocytes were obtained from the American Cell Culture Line, (Rockville, MD). The cells were allowed to incubate in contact with the materials for intervals of 24, 48, and 72 hours. Biochemical tests and morphological evaluations were performed after each time point, including screening for cell number, cell protein levels, supernatant protein levels, lactate dehydrogenase (LDH), Maliondialdehyde (MDA), catalase by following standard lab protocols.

Biocompatible Materials↗

PubMed1998

U.S. Gulf War Veterans: service periods in theater, differential exposures, and persistent unexplained illness. Portland Environmental Hazards Research Centre.

Approximately 80,000 of the 697,000 American men and women who were stationed in SW Asia during the Gulf War (GW) report unexplained illness consisting of symptoms of persistent fatigue, cognitive difficulties, such as mild memory loss, diffuse muscle and joint pain, gastrointestinal symptoms, skin lesions, and respiratory problems, among others. Associations between major symptom groups and periods of deployment in the theater of operations have been sought in a population-based, clinical case-control study of GW veterans resident in the north-western region of the United States. No statistically significant differences were evident in the proportion of cases with unexplained fatigue, cognitive/psychological or musculoskeletal symptoms among veterans present in SW Asia in 3 specific time periods: (a) 8/1/1990-12/31/1990 (which includes Desert Shield), (b) the period surrounding Desert Storm (1/1/1991-3/31/1991), and (c) the (post-combat) period immediately following hostilities (4/1/1991-7/31/1991). There was a trend for all 3 case symptoms to be more common among GW veterans who served in the post-combat period. As numbers in these deployment groups were small, and power to detect differences low, the apparent absence of significant differences in the frequency of major symptom groups among these veterans requires confirmation in a larger study. Deployment for discrete periods in SW Asia is a method to separate distinct constellations of environmental factors; these are useful for analyses of associations among symptoms and exposures given the near-total absence of objective data on chemical and other possible exposures in the theater of operations.

Adult↗

PubMed1998

Prognostic value of K-ras mutations, ras oncoprotein, and c-erb B-2 oncoprotein expression in adenocarcinoma of the lung.

This trial was undertaken to determine the prognostic role of K-ras (p21), c-erb B-2 (p185) protein expression, and the presence or nonpresence of a K-ras gene mutation in patients with adenocarcinoma of the lung. This was a retrospective study of 103 patients with adeno- or large-cell carcinoma of the lung who had available paraffin-stored tumor material. The relation of several clinical variables to survival was analyzed. Immunohistochemical techniques were used to determine expression of p21 and p185. Polymerase chain reaction (PCR) and sequencing were used to determine K-ras mutation status. Tumor stage was the only nonmolecular clinical variable predictive of survival (p=0.0001). A combination of K-ras mutation and p 185 expression (p=0.0144), ras mutation and strong p21 expression (p=0.0137), and K-ras mutation and the combined expression of p21 and p185 were predictive of poor survival (p=0.0415) in univariate analysis of all patients. The sole presence of K-ras mutation was predictive of survival. Additionally, when combined with elevated p21 or p185 expression in a subset of patients with 4 or more years of follow-up, negative correlation with survival was observed.

Adenocarcinoma↗

PubMed1997

FK506-induced fulminant leukoencephalopathy after single-lung transplantation.

FK506 is being used increasingly to prevent rejection after organ transplantation. Its use is associated with a wide spectrum of neurotoxicity, which has been described after most solid organ transplantations, but reports after lung transplantation are extremely rare. This is a report of the pathologic correlation of the clinical and radiologic features of delayed FK506-induced fulminant leukoencephalopathy after single-lung transplantation. The patient presented with neurologic symptoms that progressed to seizure activity. Neuroimaging showed diffuse changes in the brain, and results of a brain biopsy were consistent with leukoencephalopathy with microglial and astrocytic activation. The patient had a remarkable improvement in clinical status after discontinuation of FK506 administration, with resolution of the changes seen on neuroimaging.

Brain↗

PubMed1997

Glucose metabolism in severe malaria: minimal model analysis of the intravenous glucose tolerance test incorporating a stable glucose label.

Basal plasma glucose is usually increased in uncomplicated malaria, implying insulin resistance. If the infection progresses, the risk of hypoglycemia will increase as host glucose production becomes insufficient for host/parasite demand. To assess the relative contribution of insulin-mediated and non-insulin-mediated glucose disposal to plasma glucose levels in severe malaria, we studied six healthy controls (two males and four females; mean age, 38 years) and eight patients with complicated falciparum malaria (five males and three females; mean age, 31 years) who had a frequently sampled intravenous glucose tolerance test (FSIVGTT) in which 10% of the dextrose bolus was 6,6-D2-glucose. The minimal model was applied to native and labeled plasma glucose and serum insulin profiles over 4 hours postinjection. Basal plasma glucose concentrations in the patients were significantly greater than in the controls (median [range], 6.1 [2.1 to 8.5] v 4.3 [3.9 to 4.7] mmol/L, P = .03). Malaria-associated insulin resistance was confirmed by a lower insulin sensitivity index (SI) in patients (5.6 [2.4 to 17.4] v 16.0 [2.5 to 22.3] x 10(-4).min-1 per microU/mL in controls, P = .026). Glucose effectiveness ([SG] the ability of glucose to reduce its own plasma concentration) was higher in the patients (0.015 [0.006 to 0.024] v 0.008 [0.007 to 0.010] min-1 in controls, p = .019). Glucose disappearance at basal concentration was increased by a median of 42% in severe malaria patients, with the insulin-independent component comprising 81%, versus 67% in controls. Indices of beta-cell function were normal in malaria patients. These data demonstrate that basal plasma glucose utilization is increased approximately 50% in severe malaria, consistent with previously published isotope-turnover studies. Altered SG plays a major role. Prevention and treatment of early hypoglycemia should be based on adequate glucose replacement. Strategies that reduce insulin secretion or effects appear to be of minor importance.

Adolescent↗

PubMed1996

An outbreak of acute hepatitis C among recipients of intravenous immunoglobulin.

BACKGROUND: An association between therapy with intravenous immunoglobulin (IVIG, Gammagard, Baxter Healthcare Corp) and acute hepatitis C (HCV) was reported by the manufacturer in 1994. OBJECTIVE: We sought to describe those patients at risk at our institution who developed HCV infection after IVIG (Gammagard) treatment(s). MATERIALS: An inception cohort study of patients with exposure to contaminated IVIG in a university tertiary care institution. Twenty-three patients received suspect IVIG and presented to be screened for HCV via ELISA II and polymerase chain reaction techniques. We describe the demographics and clinical characteristics of patients diagnosed with hepatitis C infection from IVIG. RESULTS: Ten of 23 (44%) patients who had received immunoglobulin (2 g/kg) for neurologic or immunologic disorders and were tested for anti-HCV were positive. All were also HCV-RNA positive by polymerase chain reaction. None had other HCV risk factors; all but two had normal aminotransferases documented prior to therapy. The patients had received monthly therapy for periods ranging from 2 to 60 months. Four patients were asymptomatic and the others had mild symptoms. One patient spontaneously became PCR negative within 12 months after exposure. CONCLUSION: Patients who received intravenous immunoglobulin (Gammagard, Baxter Healthcare Corp) between March, 1993, and February, 1994, are at risk for acute hepatitis C. The initial sequellae appear to be mild and spontaneous remission is possible.

Acute Disease↗

PubMed1996

Diethylcarbamazine-induced reversal of early lymphatic dysfunction in a patient with bancroftian filariasis: assessment with use of lymphoscintigraphy.

Exposure of expatriates to the infective larvae of Wuchereria bancrofti can result in the early development of signs of lymphatic obstruction. The findings on the clinical presentation of expatriates are distinct from the chronic pathological findings seen among the native population and are similar to the findings in experimentally infected persons. We report the case of a Peace Corps volunteer who developed acute lymphatic dysfunction within 3 months of arriving in an area that was endemic for filariasis. The diagnosis was established clinically and by demonstrating the presence of antibodies to recombinant proteins specific for patients with lymphatic filariasis. Lymphatic flow was markedly abnormal when assessed with use of 99mTc-lymphoscintigraphy. Treatment with diethylcarbamazine reversed both the physical and lymphoscintigraphic abnormalities.

Adult↗

PubMed1995

Late-onset mitochondrial myopathy.

In the majority of patients with mitochondrial encephalomyopathies, signs and symptoms appear in the first three decades of life. Here we report on a group of 9 older patients (> 69 years old) with late-onset skeletal myopathy characterized by focal accumulations of deleted mitochondrial DNAs (mtDNAs) and altered muscle energy status, suggestive of a primary mitochondrial disease. The clinical phenotype was somewhat variable. However, all patients shared a common feature of insidious moderate proximal muscle weakness; some also showed fatigability and axial muscle weakness. In situ hybridization analysis demonstrated accumulations of messenger RNAs transcribed from deleted mtDNAs in a relatively large number of muscle fibers in the patient group. These fiber segments appeared as ragged red with the modified Gomori trichrome stain and hyperreactive with a modified succinate dehydrogenase stain. Most were negative for cytochrome c oxidase activity. On transverse sections their mean frequency was 0.69% (trichrome) and 1.97% (succinate dehydrogenase) significantly above control levels. Multiple mtDNA deletions were demonstrated by the polymerase chain reaction in both the patients and an age-matched control group, but not in younger control subjects. Phosphorus 13 magnetic resonance spectroscopy of resting muscle showed a decreased phosphocreatine-inorganic phosphate ratio in the patient group. The myopathy in this group of patients appears to result from mitochondrial dysfunction related to the clonal expansion of different mtDNA deletions in individual fiber segments. While the origin of the mtDNA mutations is not clear, the phenotype seems to represent an exaggerated form of what is observed in the normal aging process.

Aged↗

PubMed1995

Combined terazosin and verapamil therapy in essential hypertension. Hemodynamic and pharmacokinetic interactions.

alpha-Blockers and calcium antagonists are commonly used in the treatment of hypertension, but few data are available concerning first dose or steady state (SS) hemodynamic and pharmacokinetic effects of these drugs when they are used in combination therapy. To examine these interactions, we measured supine and standing blood pressure (BP), heart rate (HR), and cardiac index (CI) for 6 h in 24 hypertensive patients after 2 weeks of placebo, again after the first dose or 3 weeks of therapy (SS) with either 120 mg verapamil (V) twice a day, or 1 mg terazosin (T) titrated weekly to 5 mg daily, and finally when T was added to V (group VT) or V added to T (group TV), acutely and at SS. Changes in supine hemodynamics when T was added to V or when V was added to T were similar and included a further reduction in BP, a transient increase in HR, and little or no change in CI. Both groups experienced significant decreases in standing blood pressure, especially 0.5 to 2 h following initiation of combination therapy despite significant increases in standing HR and CI. Standing BP tended to be lower in group TV after the first dose, but minimum standing systolic BP was not significantly different between groups (group TV 97 mm Hg at 1 h; group VT 109 mm Hg at 1.5 h, P > .05). Four patients in group TV and two in group VT experienced symptomatic orthostatic hypotension with the first dose of double-agent treatment. Pharmacokinetic interactions, including an increase in the bioavailability of T when V was added, did not correlate with the degree of orthostasis. After 3 weeks of combined therapy, the orthostatic change in BP had attenuated and symptoms had improved in all patients. We conclude that T and V represent an effective combination for the treatment of essential hypertension, but that orthostasis may result when initiating combination therapy. The orthostasis seen in some patients appears to be due to the combined vasodilatory effects rather than negative ionotropic or chronotropic effects.

Adult↗

PubMed1994

A genealogy of tubercular diseases in Japan.

This paper examines the historical transformation of concepts of tubercular diseases in Japan from premodern to modern times. Its principal conclusion is that, between the eighteenth and the twentieth centuries, intellectual and cultural circumstances in Japan first facilitated and then hindered the adoption of Western concepts of tubercular diseases. The Japanese adopted Western concepts of tubercular diseases from the early nineteenth century not because they suggested more effective therapeutic measures but because they mirrored ideas that the Japanese had developed during the previous century. During the late nineteenth and early twentieth centuries concepts of tubercular disease based on Western medical thought conflicted with popular concepts, creating a point of cultural dissonance in Japanese society that was overcome only after effective medicinal cures for tuberculosis were invented. To demonstrate these points, this paper surveys representative Chinese, Japanese, and European medical texts and ideas from earliest times to the first half of the twentieth century. Although the focus is on one specific set of diseases, this example helps explain why the Japanese adopted Western medicine much more quickly than their cultural neighbours in China and Korea, although this conclusion is left implied rather than stated.

History, Modern 1601-↗

PubMed1992

Multiple occult vascular malformations of the brain and spinal cord: MRI diagnosis.

We report a patient with multiple angiographically occult vascular malformations in the brain and spine. Magnetic resonance imaging showed multiple lesions in brain and spine with hypointense areas on both T1 and T2-weighted images. These hypointense areas are usually secondary to hemosiderin deposits consistent with remote bleeding in the lesions. We conclude that when magnetic resonance reveals an intraspinal lesion with signal intensity characteristics consistent with a vascular malformation, an examination of the brain should be performed to rule out associated intracranial lesions. The finding of multiple lesions in the brain with identical signal intensity characteristics reinforces the diagnosis of vascular malformation.

Brain↗

PubMed1992

Injection sites utilized for DPT immunizations in infants.

The purpose of this investigation was to determine the site utilized by nurses for administering Diphtheria and Tetanus Toxoids and Pertussis (DPT) injections to infants under 7 months of age. Twenty-six of the 28 agencies identified in a metropolitan area as administering DPT injections chose to participate in the study. Those individuals administering DPT injections in the agencies completed a questionnaire with a return rate of 69% (n = 55). Forty-four participants indicated that they used the anterolateral thigh, the recommended site, 100% of the time. The participants in the study administered a total of 1,453 DPT injections per month. Eighty-seven percent of those injections were administered in the anterolateral thigh, 3.6% were given in the deltoid, 5.1% were given in the dorsal gluteal, and 4% were given in the ventrogluteal. The estimated proportion of DPT injections administered at the correct site was 84.65% which is much lower than the critical value 94.06% for alpha = .05 (p less than .00001).

Diphtheria-Tetanus-Pertussis Vaccine↗

PubMed1991

Case report 700: Primary intracortical osteosarcoma of femur, sclerosing variant, grade 1 to 2 anaplasia.

We report a case of intracortical OS of the mid-femur in a 43-year-old man. The patient is the oldest reported to date. Histologically, the tumor was a sclerosing variant of OS with extensive "normalization" of nuclei. This is the most common histological subtype of intracortical OS. The patient was treated by en bloc resection without preoperative or systemic chemotherapy and is without evidence of disease with 15 months' follow-up.

Adult↗

PubMed1991

Color consistency, plaque accumulation, and external marginal surface characteristics of the collarless metal-ceramic restoration.

Four techniques for making collarless metal-ceramic restorations were investigated in this study to examine the final color consistency, the bacterial plaque accumulation, and the surface characteristics of the porcelain margin. Twenty crowns were constructed and data revealed the superiority of the platinum foil technique in producing consistent color, whereas the shoulder porcelain technique resulted in the most significant color deviation. Metal surfaces exhibited the greatest in vitro bacterial plaque accumulation (42.43%), and the margins of the platinum foil technique accumulated the least plaque (7.23%). In addition, the wax binder and the platinum foil techniques produced the smoothest surfaces, whereas again the shoulder porcelain technique exhibited pronounced surface roughness. From the obtained results, and with the limitations of this in vitro study, one can speculate that surface roughness is not a predominant factor in the initial process of bacterial plaque accumulation.

Analysis of Variance↗

PubMed1991

Is hyperthermia teratogenic in the human?

Maternal hyperthermia during embryogenesis has been postulated to cause a variety of major congenital anomalies in exposed offspring. Although the literature regarding human exposures is not conclusive, studies using animal models support the contention that major structural anomalies may be produced. In the present study, pregnancy outcome of a cohort of women who reported having a temperature of 101 degrees F or higher for 24 hours or more during the first trimester was compared to a control group of women (matched on last menstrual period, parity, and age) who denied having a fever. A statistically significant increased frequency of a specific type of congenital anomaly, abdominal wall defects, was found in offspring whose mothers had sustained high temperatures during embryogenesis. Although an increased risk of this type of congenital anomaly is not consistent with previous epidemiologic studies, similar defects of this organ system have been reported in offspring of pregnant nonhuman primates (monkeys) and rodents (guinea pigs) who experienced hyperthermia during pregnancy.

Adult↗