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Biomedical subjects

G Wells

Publications and source records attributed to G Wells.

At least 19 recordsLinked to original sources

A prospective study of magnetic resonance imaging in lymphoma staging.

In this prospective study, magnetic resonance imaging (MRI) was compared with computed tomography (CT) in patients with non-Hodgkin's lymphoma (NHDL), and with CT and laparotomy in patients with Hodgkin's disease (HD). Among 31 patients with NHDL, there was agreement between MRI and CT findings in 21 patients; MRI findings were positive and CT findings were negative in 8 patients; and MRI findings were negative and CT findings were positive in 2 patients. The false-negative findings of MRI included a laparotomy-proven mesenteric mass and a 6.6-cm lesion in the spleen, both shown by CT. In 13 evaluable patients with HD, there was agreement between MRI and laparotomy findings in 8 patients; MRI findings were positive and laparotomy findings were negative in 4 patients; and MRI findings were negative and laparotomy findings were positive in 1 patient. CT findings agreed with laparotomy findings in nine patients; CT findings were positive and laparotomy findings were negative in one patient: and CT findings were negative and laparotomy findings were positive in three patients. This suggested that MRI, although more sensitive than CT, was less specific with more false-positive findings. The spin-lattice relaxation time (T1) for the spleen was generally higher in patients with HD who had pathologically confirmed splenic involvement, and tended to increase with increasing spleen weight. This study was performed on a prototype 0.15 Tesla (Technicare Inc., Solon, OH) resistive unit at a time when methods and reporting for MRI were still being developed. Although MRI appears to have fewer false-negative findings than CT in evaluating the abdomen of lymphoma patients, the lack of a gastrointestinal contrast agent and specificity of T1 elevations in the spleen would not suggest that MRI could replace CT or laparotomy as a staging technique.

Adolescent

Relationship between severity and clinical importance of symptoms in osteoarthritis.

Seventeen patients with primary osteoarthritis of the knee were evaluated with respect to the severity and clinical importance of pain, stiffness and physical function during the conduct of a double-blind randomized controlled trial of flurbiprofen SR versus diclofenac sodium SR using the WOMAC Osteoarthritis Index. Mean importance scores were similar for items within the same dimension as well as between items in different dimensions. In general, low levels of correlation were noted between the severity and importance of symptoms. Analysis of individual WOMAC items within a given subscale indicated that, although highly correlated, they differed from one another. Factor analysis further supported the contention that scores from items within a subscale could be summated into subscale scores. These observations are of importance in the weighting and aggregation of items within discrete dimensions and have the potential for reducing sample size requirements for clinical trials in osteoarthritis.

Clinical Trials as Topic

Abnormalities of 21-hydroxylase gene ratio and adrenal steroidogenesis in hyperandrogenic women with an exaggerated 17-hydroxyprogesterone response to acute adrenal stimulation.

One to 2% of hyperandrogenic women demonstrate a 17-hydroxyprogesterone (17-HP) level greater than 36.3 nmol/L (1200 ng/dL) after acute ACTH-(1-24) adrenal stimulation, consistent with 21-hydroxylase (21-OH) deficient late-onset adrenal hyperplasia (LOAH). The following study was undertaken to endocrinologically and genetically define hyperandrogenic patients with an exaggerated 17-HP response to ACTH stimulation, and which do not represent LOAH. Of 265 consecutive patients suffering from hirsutism and/or hyperandrogenic oligomenorrhea, 23 (8.7%) demonstrated a 17-HP level 30 min post stimulation greater than 9.6 nmol/L or 316 ng/dL (the upper 95th percentile in 41 eumenorrheic nonhirsute healthy control women). Seven patients or five separate families (1.8% of total) demonstrated poststimulation 17-HP levels consistent with LOAH. Of the remaining 16 patients, the net increment in 17-HP (delta 17-HP0-30) was within normal limits in seven (2.6%) and these women were assumed to have a normal 17-HP adrenocortical response superimposed on an elevated basal level of nonadrenal (e.g. ovarian) origin. In the remaining nine hyperandrogenic patients (3.4%) various abnormalities of adrenal response were noted in all but one patient, consistent with adrenal hyper-responsiveness. One patient demonstrated an 11-deoxycortisol poststimulation level greater than 3-fold the upper 95th percentile of normal, consistent with 11-hydroxylase LOAH and was excluded from further study. Six of these women were available for further genetic characterization, all Caucasian and unrelated. Three were heterozygotes for HLA-B14, three for B40, and one for B35 antigen, HLA-types associated with the inheritance of 21-OH deficiencies. Although, normally there are two 21-OH genes (a pseudogene and a functional gene) present in a 1:1 ratio, we have previously reported a high frequency of 21-OH gene ratio abnormalities in LOAH. All but one of our patients demonstrated an abnormal 21-OH gene ratio. In conclusion, 3.4% of our hyperandrogenic population demonstrated an exaggerated 17-HP increment after ACTH stimulation, not consistent with LOAH or increased extraadrenal 17-HP production. The increased prevalence of HLA alleles known to be linked to inherited defects of 21-OH function and the increased frequency in 21-OH gene ratio abnormalities suggest that a majority of these individuals may be carriers for these genetic disorders. However, the adrenocortical abnormalities noted were more consistent with a generalized hyperreactivity of the adrenal to ACTH stimulation, than a specific enzyme deficiency, implying that carrier status for 21-OH deficiency may be incidental to the hyperandrogenism.

17-alpha-Hydroxyprogesterone

Peripheral nerve function in sepsis and multiple organ failure.

Forty-three patients who had sepsis and multiple organ failure (critical illness) were studied prospectively to determine the incidence and severity of peripheral nerve function and to correlate such function with a number of variables. Electrophysiologic studies indicated a primary axonal degeneration of motor and sensory fibers in 30 (70 percent). Fifteen (30 percent) had the clinical signs of difficulty in weaning from assisted ventilation, weakness of limb muscles, and reduced or absent deep tendon reflexes. Full recovery from the polyneuropathy occurred among the 23 (53 percent) who survived, except three who had a very severe polyneuropathy. A peripheral nerve function index, computed from electrophysiologic measurements, showed statistically significant (p less than 0.01) negative correlations with the time in the critical care unit, and the serum glucose value; the serum albumin level showed a positive correlation. Multiple regression analyses indicated all three factors accounted for 47 percent (r2 = 0.4678) of all potential variables. In a separate analysis, the nerve function index correlated with the amplitude of the diaphragm compound muscle action potential (p less than 0.01). The results were consistent with the polyneuropathy being due to the same mechanisms that are currently postulated to cause dysfunction in this syndrome of other organ systems (including the neuromuscular respiratory system).

Bacterial Infections

Parental attitudes toward pediatric organ donation: a survey.

We conducted a telephone survey of parents in the National Capital Region to assess their intention to donate their child's organs and to provide physicians with information that could help alleviate their concerns about approaching parents for consent. Of 339 parents who agreed to answer questions after being given details of their child's "death" 288 (85%) said that they would be willing to donate their child's organs. The degree of willingness was associated with the certainty of death, altruism and empathy toward children in need of an organ, previous discussion of organ donation with a family member and knowledge of an adolescent or adult child's attitude toward donation. Factors that inhibited the intention to donate included uncertainty of death, insufficient information from medical professionals and fear of multilation. The child's age was not significantly associated with intention to donate. Concordance between the results and actual donation rates in Canada and the United States supports the generalizability of the survey findings.

Adolescent

Rural community mental health consumer satisfaction and psychiatric symptoms.

This study examined the impact of therapy on psychiatric symptoms and consumer satisfaction in a rural community mental health center. Utilizing the Brief Symptom Inventory (BSI) and an evaluation of service questionnaire (EOS), designed by the authors, results indicated positive outcomes for both measures (88 subjects). Small but significant correlations were obtained for the BSI and EOS (r's .29 to .59). Implications for future research and treatment are discussed focusing on time of intervention and symptom quality.

Adaptation, Psychological

Pseudogene/functional gene ratio in late-onset 21-hydroxylase-deficient adrenal hyperplasia.

Late-onset adrenal hyperplasia caused by 21-hydroxylase deficiency leads to hyperandrogenic symptoms in 1% to 6% of hyperandrogenic women. Normally there are two 21-hydroxylase genes present in a 1:1 ratio. Gene CYP21A is a nonfunctional pseudogene, whereas CYP21B is an active gene. Abnormalities of the CYP21A/CYP21B gene ratio may serve as a marker for late-onset adrenal hyperplasia. Eight hyperandrogenic patients with late-onset adrenal hyperplasia and five control subjects were studied by evaluation of autoradiograms of Taq I and Kpn I digests by means of laser densitometry. Seven of eight (87%) patients with late-onset adrenal hyperplasia had an abnormal CYP21A/CYP21B gene ratio on laser densitometry, suggestive of CYP21A gene duplication, CYP21B gene deletion, or the conversion of a CYP21B gene to a CYP21A gene. One of the five control subjects had a heterozygous deletion of the CYP21A gene. The CYP21A/CYP21B gene ratio may serve as a useful genetic marker for late-onset adrenal hyperplasia in a non-high-risk population.

Adrenal Glands

Late onset adrenal hyperplasia: mutation at codon 282 of the functional 21-hydroxylase gene is not ubiquitous.

Ten patients affected with 21-hydroxylase (21-OH) deficient late-onset adrenal hyperplasia were studied to determine the prevalence of a mutation at codon 281 of the functional 21-OH gene (CYP21B) that results in a valine to leucine amino acid shift. This mutation has been reported in eight unrelated late-onset adrenal hyperplasia patients of Ashkenazi Jewish descent possessing the human leukocyte antigen-B14,DR1 haplotype. Normally, there are two 21-OH genes; a pseudogene (CYP21A) and a functional gene (CYP21B). The aberrant codon 281 sequence is normally present only in CYP21A. In all of our late-onset adrenal hyperplasia patients, hybridization of an oligonucleotide probe specific for this mutation was demonstrated to CYP21A but not to CYP21B. The mutation at codon 281 of CYP21B does not appear to be a ubiquitous genetic marker for 21-OH deficient late-onset adrenal hyperplasia, suggesting that this disorder may demonstrate the same molecular heterogeneity as congenital adrenal hyperplasia.

Adrenal Glands

Norfloxacin use in urinary tract infection by urologists and infectious disease specialists.

One hundred thirty-one patients of urologists and infectious disease specialists were entered into an open trial of norfloxacin in the therapy of urinary tract infections (UTIs). All patients were evaluable for tolerability and 98 were evaluable for efficacy. The patient population in this study was older (mean age 53 years) and had more underlying urogenital disorders (30%) or recent invasive urologic procedures (20%) than the typical patient population with UTIs. Over 50% of the patients had infections due to organisms other than Escherichia coli, including Pseudomonas aeruginosa (14), Klebsiella pneumoniae (5), Enterobacter spp (3) and Group D streptococcus (6). Clinical and bacteriologic cure rates were 90 and 91%, respectively. Side effects occurred in 5 patients and were generally mild.

Administration, Oral

Fast neutron teletherapy in advanced epidermoid head and neck cancer. A review.

An extensive review of clinical studies employing fast neutron teletherapy for advanced epidermoid carcinomas of the head and neck is presented. Head and neck tumors have represented an excellent study site because of their accessibility to physical examination for measurement of tumor response, and because early neutron beams have had poor depth dose characteristics, making the treatment of more deeply seated tumors technically difficult. A summary of the major trials comparing neutron and mixed-beam (combination neutron and photon) therapy with conventional therapy indicates no conclusive evidence of improvement in local control or survival rates for the experimental arms. Exceptions to this are the Hammersmith experience and the slightly higher lymph node control rates seen in two studies. An evaluation of toxicity indicates that with the new generation of cyclotrons, complication rates may approach parity with those of photon linear accelerators.

Carcinoma, Squamous Cell

Nature, time course and dose dependence of zidovudine-related side effects: results from the Multicenter Canadian Azidothymidine Trial.

To characterize the nature, time course and dose dependency of zidovudine-related side effects, we undertook a multicenter, prospective, dose-range finding study. Our study group consisted of 74 HIV-positive homosexual men belonging to groups II B, III and IV C2 from the Centers for Disease Control (CDC) classification of HIV disease. Following a 3-week observation period, volunteers were treated with zidovudine 600 mg/day for 18 weeks, 900 mg/day for 9 weeks and 1200 mg/day for 9 weeks, followed by a washout period of 6 weeks after which they were re-started on 1200 mg/day or the highest tolerated dose at 8-hourly intervals. Subjects were randomly assigned to 4-hourly or 8-hourly regimens within CDC groups while taking 600 and 1200 mg/day. Clinical and laboratory evaluations were performed at 3-week intervals. Symptomatic adverse effects were present in 96% of subjects, most commonly nausea (64%), fatigue (55%) and headache (49%). These were generally self-limited, reappearing briefly at each dose increment. A decrease in hemoglobin occurred shortly after initiation of therapy. This was not dose dependent and reversed rapidly upon discontinuation of treatment. A red blood cell count decrease, a mean cell volume increase and a granulocyte count decrease developed early in a dose-independent fashion, reverting at least partially during the washout phase. The decrease in reticulocyte count was dose related between 600 and 900 mg/day with no further change when the dose was escalated to 1200 mg/day. Bone marrow changes occurred rapidly as demonstrated by megaloblastosis in 95% of 65 specimens at week 18.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Acquired immune deficiency syndrome in Canada: the first 5 years of surveillance.

In the first 5 years of surveillance of reports of the acquired immune deficiency syndrome (AIDS) in Canada, from February 1982, the Laboratory Centre for Disease Control, Ottawa, was notified of 1133 cases reported through provincial ministries of health that met the case definition developed by the US Centers for Disease Control, Atlanta. Most cases (82.2%) were reported from the homosexual/bisexual risk group. Other risk groups were less frequently represented, in contrast to the experience in the United States, where a higher proportion of cases in drug abusers has been observed, and in Africa, where heterosexual spread is far more common. The presenting clinical picture and length of survival after diagnosis were similar to those reported for other countries. Differences between projected estimates of the number of AIDS cases obtained with polynomial and logistic growth models emphasize the need for solid epidemiologic data on the number of people infected with human immunodeficiency virus, the rates of transmission and the rates of progression to disease.

Acquired Immunodeficiency Syndrome

Immunity to rubella in prepubertal girls in Prince Edward Island.

A survey of rubella immunity was conducted among prepubertal girls in Prince Edward Island. Of the 431 girls enrolled in grade 4 in a random sample of schools 83% had a school record of having been vaccinated after their first birthday. A screening test of finger-prick samples revealed that 95% of the girls with a written history of vaccination after their first birthday were immune, 79% of those vaccinated before their first birthday or for whom the date of vaccination was uncertain were immune, and 40% of unvaccinated girls were immune. Of the 49 susceptible girls 43 were vaccinated; all but 2 were found to be immune on retesting. The findings support the recommendation of the National Advisory Committee on Immunization to vaccinate all prepubertal girls without a written history of rubella vaccination after their first birthday.

Child