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Biomedical subjects

K Russell

Publications and source records attributed to K Russell.

At least 37 records · Page 2Linked to original sources

Diagnosis of Oropouche virus infection using a recombinant nucleocapsid protein-based enzyme immunoassay.

Oropouche (ORO) virus is an emerging infectious agent that has caused numerous outbreaks of an acute febrile (dengue-like) illness among humans in Brazil, Peru, and Panama. Diagnosis of ORO virus infection is based mainly on serology. Two different antigens, hamster serum antigen (HSA) and Vero cell lysate antigen (VCLA), are currently used in enzyme immunoassays (EIAs) in Brazil and Peru, respectively, to investigate the epidemiology of ORO virus infection. Both antigens involve use of infectious virus, and for this reason their use is restricted. Consequently, the frequency and distribution of ORO virus infection are largely unexplored in other countries of South America. This report describes the use of a bacterially expressed recombinant nucleocapsid (rN) protein of ORO virus in EIAs for the diagnosis of ORO virus infection. The data revealed that the purified rN protein is comparable to the authentic viral N protein in its antigenic characteristics and is highly sensitive and specific in EIAs. Among 183 serum samples tested, a high degree of concordance was found between rN protein-based EIA and HSA- and VCLA-based EIAs for the detection of both ORO virus-specific immunoglobulin M (IgM) and IgG antibodies. The high sensitivity, specificity, and safety of the rN protein-based EIA make it a useful diagnostic technique that can be widely used to detect ORO virus infection in South America.

Animals↗

Acromicric dysplasia: long term outcome and evidence of autosomal dominant inheritance.

Acromicric dysplasia is a rare bone dysplasia characterised by short stature, short hands and feet, normal intelligence, mild facial dysmorphism, and characteristic x ray abnormalities of the hands. Only a very small number of children with this condition have been reported so far. Here we report on a series of 22 patients including 10 boys and 12 girls with acromicric dysplasia. Length was normal at birth and height fell progressively off the centiles postnatally. The mean adult height was 130 cm (133 cm in males, 129 cm in females). The hands, feet, and limbs were short and OFC was normal. Intelligence was normal and mild dysmorphic features were noted. Other occasional features included well developed muscles, a hoarse voice, generalised joint limitation in some patients, frequent ear, tracheal, and respiratory complication, and spine abnormalities. Long term follow up showed that facial dysmorphism was less obvious in adults and that carpal tunnel syndrome was frequent in older patients. Apart from short metacarpals and phalanges, internal notch of the second metacarpal, external notch of the fifth metacarpal, and internal notch of the femoral heads, there were no major x ray abnormalities. No major complications, such as cardiac disease or major orthopaedic problems, occurred in the course of the disease. The condition appeared to be sporadic in 16 cases but the observation of vertical transmission in three families was consistent with an autosomal dominant mode of inheritance.

Abnormalities, Multiple↗

Plasma cortisol, cortisone and urinary glucocorticoid metabolites in preterm infants.

OBJECTIVE AND METHODS: In the fetal circulation, there is a low cortisol:cortisone (F:E) ratio ( approximately 0.3) suggesting high activity of 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2). The circulating F:E ratio rises after birth in term infants, but little is known about infants born prematurely. Our hypothesis was that the low fetal plasma F:E ratio would persist in infants born prematurely, due to persistently high tissue 11betaHSD2 activity. To test this hypothesis, a longitudinal observational study of plasma F, E levels and urinary F and E metabolites was performed in 22 preterm infants of 24-31 weeks gestation. RESULTS: Median plasma F was 234-380 nmol l(-1), median 124-177 nmol l(-1) from 1 to 14 days age. Plasma F fell with increasing postnatal and postconceptional age. The F:E ratio was 3 in the first week of life, and thereafter was 1-2, falling with postnatal age. Urinary glucocorticoid metabolites were low in quantity ( approximately 48-120 microg kg(-1) day(-1)), consisted of E metabolites until term, and did not reflect the plasma F:E ratio. CONCLUSIONS: The fetal plasma F:E ratio did not persist in these preterm infants, due to tenfold higher levels of F. The F:E ratios were similar to those reported in term infants. These data suggest that the low F:E ratio in utero is due to low fetal production of cortisol, and effective placental inactivation of maternal F by 11betaHSD2.

Aging↗

Haiti: absence of dengue hemorrhagic fever despite hyperendemic dengue virus transmission.

In 1994-1996, 185 strains of dengue (DEN) virus types 1, 2, and 4 were recovered from febrile United States and other United Nations military personnel in Haiti. We wondered whether risk factors for dengue hemorrhagic fever (DHF) existed and, if so, were DHF cases occurring among Haitian children. Dengue transmission rates were studied in 210 school children (6-13 years old) resident in Carrefour Borough, Port-au-Prince, Haiti. When sera were tested for plaque-reduction neutralizing antibodies to DEN 1-4 viruses, nearly 85% had antibodies to two or more DEN serotypes. The annual transmission rate was estimated at 30%, a rate observed in countries endemic for DHE Haitian DEN 2 isolates were genotype I, which are repeatedly associated with DHF cases in Southeast Asia and American regions. Despite positive virologic pre-conditions, DHF cases were not recorded by experienced Port-au-Prince pediatricians. These observations, which are reminiscent of those in Africa, provide further evidence of a dengue resistance gene in black populations.

Adolescent↗

Pharmacological characterization of ZD6021: a novel, orally active antagonist of the tachykinin receptors.

The tachykinins, substance P, neurokinin A, and neurokinin B, have been implicated in many diseases. The present study evaluated the pharmacological properties of a novel tachykinin antagonist ZD6021 [3-cyano-N-((2S)-2-(3,4-dichlorophenyl)-4-[4-[2-(methyl-(S)-sulfinyl)-phenyl]piperidino]butyl)-N-methyl-]-napthamide]. The affinity (K(i)) of ZD6021 for the cloned human neurokinin (NK)1, NK2, and NK3 receptors was 0.12 +/- 0.01, 0.64 +/- 0.08, and 74 +/- 13 nM, respectively. Mucin secretion by Chinese hamster ovary cells transfected with the human NK1 receptor was dose dependently inhibited by ZD6021: pIC(50) = 7.6 +/- 0.1. For NK1 and NK2 receptors, the agonist concentration-response curves using isolated tissues were displaced rightward in the presence of ZD6021: rabbit pulmonary artery, pA2 = 8.7 and 8.5; human pulmonary artery and bronchus, pKB = 8.9 +/- 0.4 and 7.5 +/- 0.2, at 10(-7) M, respectively. Senktide-induced contractions of isolated guinea pig ileum were also blocked by low concentrations of ZD6021. Oral administration of ZD6021 to guinea pigs dose dependently attenuated tracheal extravasation of plasma proteins induced by the NK1 receptor agonist Ac-[Arg6,Sar9,Met(O2)11]-SP(6-11), ED50 = 0.8 micromol/kg, and bronchoconstriction, elicited by the NK2 receptor agonist [beta-Ala8]-NKA(4-10), ED50 = 20 micromol/kg. Potency was unaffected by feeding. After oral administration of ZD6021, the time to peak activity was 150 min for the NK1 receptor and 60 min for the NK2 receptor with pharmacodynamic half-lives of 280 and 458 min, respectively. These data indicate that ZD6021 is a potent, orally active antagonist of all three tachykinin receptors. This compound may be useful for future studies of tachykinin-related pathology such as asthma.

Administration, Oral↗

Patient reported complications after prostate brachytherapy.

PURPOSE: Prostate brachytherapy has gained popularity due partly to the low rates of short-term complications shown in studies from highly select clinical practices. These series rely on medical records generated by the treating physician and are prone to underreport complications. We summarize the complication reports obtained directly from patients to establish a more realistic incidence of treatment related problems. MATERIALS AND METHODS: In 1997, 160 consecutive patients treated with prostate brachytherapy at the University of Washington were studied. A questionnaire was designed to determine the rate of complications occurring within 1 year of the procedure. The questions were formulated for ease of use and conciseness, while accounting for easily recalled events associated with complications. A total of 147 (92%) patients completed the questionnaire. RESULTS: There were 8 (5%) patients who required hospital admission for an average of 2 days (range 1 to 7) as a result of the procedure. A total of 56 (38%) patients required nonroutine visits with a physician in an office setting or at an emergency room. Radiation proctitis diagnosed by endoscopy developed in 8 (5%) patients but no one needed surgical intervention. A total of 47 (32%) patients required urinary catheterization at some point after implantation. CONCLUSIONS: We demonstrated a higher rate of short-term complications than those previously reported. Fortunately, the majority of side effects were self-limited and no treatment related mortality or cardiovascular morbidity was seen. Our findings may provide a more realistic account of the complications likely to occur after implantation than might be surmised from previous reports.

Adult↗

Transperineal brachytherapy in patients with large prostate glands.

The purpose of this study is to help clarify the use of prostate size as a selection factor for prostate brachytherapy. From 1997 to 1998, 33 patients with a TRUS-based prostate volume greater than 50 cc were treated at the University of Washington by I-125 (144 Gy) or Pd-103 (115 Gy) implantation for prostatic carcinoma. These 33 patients comprised 7% of the total implants performed. Each patient underwent a preimplant TRUS study in the lithotomy position, taking serial axial images of the prostate at 0.5 cm intervals from the base of the gland to the apex. The contours on the preimplant TRUS images were used to calculate the prostate volumes reported here. Only one patient received supplemental external beam irradiation prior to implantation. Twelve patients were treated with neoadjuvant androgen ablation prior to implantation. The prostate volumes quoted here are those taken after hormonal downsizing. Postimplant axial CT images were digitized to calculate the CT-based target coverage. Preimplant urinary obstructive symptoms were quantified by the criteria of the American Urologic Association. Each patient was contacted at the time of this article preparation to update postimplant morbidity information. In all cases, at least 80% of the postimplant volume was covered, despite a median implant-related volume increase of 15%. Five of the 33 patients' postimplant CT scans showed some degree of incomplete target coverage of the anterior/lateral prostate margin. There was no clear association between inadequate anterior/lateral coverage and the degree of interference. Twelve of the 33 patients developed acute postimplant urinary retention, all occurring within 24 hr of implantation. Within this group of 33 patients with a large prostate volume, there was no relationship between the likelihood of acute or chronic urinary retention and preimplant prostate size or obstructive symptoms. Patients who developed postimplant retention lasting more than one week were generally managed by intermittent self-catheterization. By one month, 85% of patients were catheter-free. Based on the data reported here, we are more inclined to accept patients with a large prostate for implantation without insisting on preimplant size reduction. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 199-205 (2000).

Brachytherapy↗

Influence of feeding regimen on body condition in the cat.

The influence of feeding regimen on body condition in the cat was studied in a sample of the UK domestic cat population (n = 136). Data were collected by interviewing cat owners and assessing body condition of cats in the owners' homes. Four main factors were identified which were related to body condition. These were, in descending order of significance: neuter status, age, frequency of treat feeding, and ad libitum feeding. Feeding regimen as a risk factor in feline obesity is discussed.

Animal Feed↗

Brachytherapy in patients with small prostate glands.

PURPOSE: To better define the role of small prostate volume in selecting patients for brachytherapy. MATERIALS AND METHODS: Thirty patients with a transrectal ultrasound (TRUS)-based prostate volumes less than 20 cc were treated at the University of Washington by permanent isotope implantation for prostatic carcinoma. Preimplant TRUS studies were taken at 0.5-cm intervals from the base of the gland to the apex. Planning margins of 1 to 5 mm were added to the prostatic margins, and sources were routinely planned to be placed as much as 5 mm outside of the prostatic margin. The prescription dose was 144 and 115 Gy for full-dose iodine 125 and palladium 103 monotherapy, respectively. For patients receiving supplemental external-beam irradiation, the implant doses were 120 and 90 Gy for 125I and 103Pd, respectively. The morning following the implant, axial computed tomographic (CT) images of the prostate were obtained at 0.5-cm intervals with patients in the supine position. Follow-up ranged from 11 to 28 months (median 21 months). RESULTS: The median coverage of the postimplant prostate volume by the prescription dose was 92%. To calculate the incidence of source migration, the number of sources placed at the time of implant was compared with the number identified on postimplant CT scan. The median number of sources implanted was 84 (range 65-103) compared to an average of 82 identified postoperatively, which is consistent with a source migration rate of two. A median of 31 sources appeared to be outside of the prostatic margins, as identified on postimplant CT scan (range 14-53). Of the 23 patients contacted at the time of this report, one had developed acute postimplant urinary retention that resolved within 2 weeks of implantation. At last follow-up, patient pre- and postimplant AUA scores were not substantially different, with the median AUA score increasing from 7 (range 2-21) to 8 (range 1-27). CONCLUSIONS: Patients with small prostate volumes appear to have acceptable morbidity and target coverage with prostate brachytherapy. Based on the data reported here, we do not believe that a small prostate volume in itself is a contraindication to brachytherapy.

Brachytherapy↗

Urea kinetics of a carnivore, Felis silvestris catus.

The effect of two levels of dietary protein energy, moderate (20%; MP) and high (70%; HP), on urea kinetics in eleven domestic cats was studied. After a 3-week prefeed, a single dose of [(15)N(15)N]urea was administered, and urine and faeces collected over the subsequent 5 d. For each 24 h period, total urea and enrichment of [(15)N(15)N]- and [(15)N(14)N]urea in urine were determined, and a model applied to calculate urea production, entry into the gastrointestinal tract, recycling to urine or faeces and, by difference, retention by the body and potentially available for anabolism. Urea production and excretion increased with dietary protein level Most of the urea produced was excreted, with only a small proportion entering the gut, and with the pattern of urea disposal not significantly different between the HP and MP diets. Thus, the percentages of urea production available to the gut were 15% (MP) and 12% (HP), of which 57% (MP) and 59% (HP) was recycled in the ornithine cycle, 40% (MP and HP) was potentially available for anabolism and the rest lost as faecal N. As a percentage of urea produced the amount potentially available for anabolism was very low at 6.41% (MP diet) and 4.79% (HP diet). In absolute terms urea entering the gut, being recycled in the ornithine cycle and potentially available for anabolism was significantly higher on the HP diet These results show that cats operate urea turnover, but at a lower rate, and with less nutritional sensitivity than has been reported for other species.

Animals↗

Distinct patterns of glomerular disease in Lima, Peru.

AIM: We performed both a retrospective and prospective study to elucidate the types of glomerular diseases present in adults in Lima, Peru. MATERIAL AND METHODS: In the retrospective study, we analyzed 1,263 renal biopsies over a 10-year period (1985 -1995) that were processed at a central reference renal pathology laboratory in Lima. 101 cases were examined in the prospective study. RESULTS: The most common glomerular diseases observed were those due to systemic lupus erythematosus (30.2%), membranoproliferative glomerulonephritis (MPGN, 14.8%), and focal and segmental glomerulosclerosis (FSGS, 13.9%). Although mesangial-proliferative nephritis was observed in 9.5% of cases, IgA nephropathy was rare (0.9%). Examination of the year to year frequency showed that MPGN has tended to decrease in frequency with time whereas FSGS has been increasing. Although there is known to be a high frequency of infections in Peru, only 4.2% of the cases in the retrospective study were associated with infection. Furthermore, in the prospective study, only one case of hepatitis C and no cases of hepatitis B viral infection were detected, including in the 11 cases of MPGN observed. CONCLUSION: We conclude that the epidemiology of glomerular disease in Lima, Peru, is distinct from most areas of the world, but has similarities to certain regions in Africa, in that MPGN is common whereas IgA nephropathy appears to be rare. Further studies are necessary to elucidate the reasons why the patterns of glomerular disease are different from that observed in other parts of the world.

Adult↗

Asymptotic power calculations: description, examples, computer code.

This paper describes two asymptotic methods for sample size and power calculation for hypothesis testing. Both methods assume that the distribution of the likelihood ratio is approximately distributed as a central chi(2) distribution under the null hypothesis and as a non-central chi(2) under the alternative hypothesis. The approximation to the non-centrality parameter differs between the methods. It is shown how these methods can be automatically extended from constraints setting parameters to constant values to constraints positing equality of parameters. Two very simple examples are presented; one demonstrates that the information method can produce arbitrarily incorrect results. Four more comprehensive examples are then discussed. In addition to demonstrating the wide range of applicability of these methods, the examples illustrate techniques that may be used in cases in which there is insufficient initial information available to perform a realistic calculation. The availability of a computer implementation of these methods in S-plus is announced, as are routines for computing the cumulative distribution function of the non-central chi(2) and its inverse.

Computer Simulation↗

Prostate brachytherapy in patients with prior evidence of prostatitis.

PURPOSE: To refute a misconception that a prior history of prostatitis is a contraindication to prostate brachytherapy. METHODS AND MATERIALS: Five patients with clinical or pathologic evidence of prior prostatitis were treated with transperineal brachytherapy. Four of the patients received a single i.v. dose of ciprofloxacin (500 mg) intraoperatively. Postimplant antibiotics were not given. The pretreatment biopsy slides were reviewed. RESULTS: Two of the five patients developed postimplant urinary retention requiring short-term catheterization, and both resolved spontaneously. One patient developed what appeared to be an exacerbation of his chronic prostatitis. CONCLUSION: We continue to recommend prostate brachytherapy for the treatment of clinically organ-confined cancer, with no concern about prior clinical or pathologic evidence of prostatitis.

Aged↗

Platelet cytosolic calcium hyperresponsivity to serotonin in patients with hypertension and depressive symptoms.

BACKGROUND: Data from recent studies indicate that the presence of depression is an independent risk factor for cardiovascular and cerebrovascular events. The mechanism by which depression increases the morbidity and mortality risks in patients with comorbid vascular disease is currently the object of considerable research interest. Platelets may be involved in this pathological process. Although many investigators have extensively evaluated platelet biochemistry in depressed patients, there currently exists very little information regarding how the biochemical alterations might relate to an increased risk of cardiovascular events. In this study, we examined the responsivity of platelet cytosolic calcium concentrations ([Ca++]i) to serotonin stimulation in populations of hypertensive patients with or without comorbid depressive symptoms. METHODS: We utilized Fura-2 loaded platelets to compare changes in intracellular calcium levels (delta [Ca++]i) following serotonin stimulation among 48 patients with hypertension and varying degrees of depressive symptomatology. RESULTS: We found that those patients with higher scores on standardized depression rating scales showed significantly greater [Ca++]i (82.82 +/- 15.88 mmol/L) increase compared with [Ca++]i (60.10 +/- 22.65 mmol/L) patients with lower depression scores. CONCLUSIONS: The results of this study support the hypothesis that the enhanced platelet reactivity seen in patients with depressive symptoms may mediate the deleterious effects of depression on cardiovascular disease.

Aged↗

Use of TRUS to predict pubic arch interference of prostate brachytherapy.

PURPOSE: To demonstrate the potential for transrectal ultrasound (TRUS) to predict pubic arch interference of transperineal needle placement for prostate brachytherapy. METHODS AND MATERIALS: TRUS and pelvic computerized tomography (CT) scans from 22 patients who had transperineal prostate brachytherapy at University of Washington were analyzed for pubic arch visualization and interference. The outer margins of the prostate and the inner margins of the pubic bones from each imaging modality were outlined and compared. RESULTS: The pubic arch was readily visualized by TRUS in 21 of the 22 patients. There was good correlation between TRUS and CT for evaluating the amount of pubic arch interference (r = 0.90). CONCLUSION: TRUS can be substituted for CT imaging to evaluate pubic arch interference of transperineal needle placement for prostate brachytherapy. Eliminating routine CT scanning would reduce the cost of treatment.

Brachytherapy↗

Use of pelvic CT scanning to evaluate pubic arch interference of transperineal prostate brachytherapy.

PURPOSE: To determine the necessity of preoperative evaluation of pubic arch interference in patients with small prostate volumes. METHODS AND MATERIALS: CT scans from 97 consecutive, unselected patients with stage T1 or T2 prostatic carcinoma who had transperineal I-125 or Pd-103 implants at the University of Washington in 1997 were analyzed for pubic arch interference. Transrectal ultrasound (TRUS) was performed with 6.0-MHz transducer with the patient in the lithotomy position and the patient's thighs vertical, similar to that used during the implant procedure. CT scans were obtained with the patient in the supine position, with 0.5-cm images taken at every 0.5 cm. To check for potential arch interference, the largest prostate cross-section was overlaid on the narrowest portion of the pubic arch. The overlap of the pubic arch and the prostate margin is measured at right angles to the inner pubic surface. The prostate volume obtained from the TRUS images was compared with the degree of pubic arch interference in order to determine whether TRUS volume predicted for interference. RESULTS: There was considerable variability in pubic arch interference between patients. The mm of pubic arch overlap with the prostatic margin varied from -11 mm to 20 mm. Patients with larger prostate volumes generally had more pubic arch interference, but the degree of interference was only loosely related to the prostate volume (r = 0.46). CONCLUSIONS: The degree of pubic arch interference is highly variable from one patient to the next and the TRUS volume cannot reliably predict patients who do or do not need a pelvic CT to detect potential arch interference.

Brachytherapy↗

Anticipating prostatic volume changes due to prostate brachytherapy.

The purpose of the study was to determine which clinical parameters might predict individual prostate volume changes from prostate brachytherapy. Fifty consecutive, unselected patients treated at the University of Washington by I-125 or Pd-103 implantation for prostatic carcinoma in 1998 were analyzed. The prostate contours on preimplant transrectal ultrasound (TRUS) images were digitized and the prostate volumes calculated. Postimplant axial CT images of the prostate was obtained at 0.5 cm intervals with patients in the supine position the morning after the implant. The postimplant prostate volume increased by an average factor of 1.7 (+/-0.34) compared with the preimplant volume, the size increase being primarily in the anterior-posterior dimension. The absolute volume change was similar in patients with small vs. large preimplant prostate volume (r = -0.39), but the proportional change was less in patients with a larger prostate volume (r = -0.71). Because patients with a small preimplant prostate had proportionately greater volume increase, their postimplant target coverage was generally less. No single parameter, including preimplant prostate volume, preimplant hormonal deprivation, or supplemental external beam radiation therapy (EBRT) can accurately predict the degree of swelling. The precise significance of and practical solution to implant-related prostate volume changes remains to be determined.

Brachytherapy↗