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Biomedical subjects

R Kirby

Publications and source records attributed to R Kirby.

At least 55 records · Page 3Linked to original sources

Phylogenetic analysis of Calymmatobacterium granulomatis based on 16S rRNA gene sequences.

Calymmatobacterium granulomatis is the aetiological agent of granuloma inguinale - a chronic granulomatous genital infection - and is morphologically similar to members of the genus Klebsiella. This study determined the 16S rRNA gene sequence of C. granulomatis and the taxonomic position of the organism in relation to the genus Klebsiella. Genomic DNA was extracted from C. granulomatis-infected monocytes and from frozen and formalin-fixed paraffin wax-embedded tissue biopsy specimens from patients with histologically proven granuloma inguinale. The 16S rDNA was amplified by PCR with broad range oligonucleotide primers. The amplified DNA fragments were cloned into pMOS vector, digested with Bam HI and Pst1 restriction endonucleases, hybridised with a gram-negative bacterial probe (DL04), sequenced in both directions by the automated ALF DNA sequencer, verified on an ABI Prism 377 automated sequencer and analysed with DNASIS and MEGA software packages. Sequence analysis revealed DNA homology of 99% in C. granulomatis from the different sources, supporting the belief that the bacteria in the culture and the biopsy specimens belonged to the same species, although there was some diversity within the species. Phylogenetically, the strains were closely related to the genera Klebsiella and Enterobacter with similarities of 95% and 94% respectively. C. granulomatis is a unique species, distinct from other related organisms belonging to the gamma subclass of Proteobacteria.

Calymmatobacterium↗

Randomized, double-blind, placebo-controlled trial to evaluate the hematopoietic growth factor PIXY321 after moderate-dose fluorouracil, doxorubicin, and cyclophosphamide in stage II and III breast cancer.

PURPOSE: To measure the effect of PIXY321 (granulocyte-macrophage colony-stimulating factor/interleukin-3 S. cerevisiae fusion protein) on the incidence, duration, and complications of neutropenia and thrombocytopenia after moderate-dose fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 750 mg/m(2) (FAC) chemotherapy in patients with stage II and III breast cancer. PATIENTS AND METHODS: In this multicenter, randomized, double-blind placebo-controlled trial, 71 women were to receive four 21-day cycles of treatment with moderate-dose FAC chemotherapy by short intravenous infusion on day 1, followed by either placebo or PIXY321 (375 microg/m(2) subcutaneously twice a day) on days 3 to 15. All patients were to receive prophylactic oral ciprofloxacin when the absolute neutrophil count was less than 1,000/microL. RESULTS: PIXY321 significantly reduced the incidence and duration of grade 3 and grade 4 neutropenia in cycles 1 and 2 and the duration of grade 3 neutropenia in cycles 1 through 4. In cycles 3 and 4, grade 3 thrombocytopenia was significantly more common with PIXY321 (P <.05). Two patients, both in the PIXY321 group, required platelet transfusions. Fever and hospitalization for intravenous antibiotics were significantly more common in the PIXY321 group during cycle 1 only. More patients in the PIXY321 group achieved hematologic recovery by day 22 in cycles 1 through 3, and time to recovery was significantly shorter with PIXY321 in all cycles. FAC dose intensity was roughly 2% higher in the PIXY321 group (P = NS). Nonhematologic events of any intensity occurring with significantly greater overall frequency in the PIXY321 group included injection-site reactions, fever, chills, abdominal pain, and arthralgia. No patient died on study or within 30 days of her last dose of study drug. CONCLUSION: PIXY321 decreased the incidence and duration of FAC-induced grade 3 and 4 neutropenia in cycles 1 and 2 and significantly shortened the time to hematologic recovery in all cycles. However, it produced more systemic toxicity as well as thrombocytopenia in cycles 3 and 4.

Adenocarcinoma↗

Prognostic markers in clinically localised prostate cancer.

The prognostic value of immunohistochemical staining of P53, BCL-2, p27kip1, PSA, AR and MIB-1 was compared with that of established prognostic variables (Gleason score, surgical margins, tumour volume) following radical prostatectomy. Five groups were selected: negative margins with stable serum PSA (n=11), negative margins with rising serum PSA (n=7), positive margins with stable serum PSA (n=7), positive margins with rising serum PSA (6) and patients with micrometastatic disease diagnosed in lymph nodes removed during radical prostatectomy (n=8). Gleason score and tumour volume were of prognostic significance and immunohistochemical staining for MIB-1 and BCL-2 showed added independent prognostic significance in multivariate analysis.

Antigens, Nuclear↗

Improvement of pressure flow parameters with finasteride is greater in men with large prostates. Finasteride Urodynamics Study Group.

PURPOSE: We assess the effect of finasteride, a 5alpha-reductase inhibitor, on objective voiding parameters in men with lower urinary tract symptoms and benign prostatic enlargement on digital rectal examination (known as clinical benign prostatic enlargement) in a double-blind placebo controlled multicenter study using strict standard pressure flow study techniques. MATERIALS AND METHODS: A modification of the Abrams-Griffiths nomogram was used by 1 reader to ensure that all patients met objective criteria for bladder outlet obstruction at baseline. After performing a pressure flow study patients with obstruction were randomized 2:1 to receive 5 mg. finasteride (81) or placebo (40) daily. A second pressure flow study was performed at month 12. At baseline and month 12 free urinary flow studies and transrectal ultrasound were performed, and International Prostate Symptom Score questionnaires were completed. Patients were treated between May 1994 and July 1996. RESULTS: Finasteride caused a significant decrease (-8.1 cm. water) in detrusor pressure at maximum flow (p <0.05 versus placebo p = 0.02), increase (+1.1 ml. per second) in maximum flow rate (p <0.05 versus placebo p = 0.02) and decrease (-22.8%) in prostate volume (p <0.05 versus placebo p <0.001). Men with prostates larger than 40 cc had greater improvement in detrusor pressure at maximum flow (between group difference -14.5 cm. water, 95% confidence interval -26.2 to -2.6, p = 0.02) and maximum flow rate (mean treatment effect +1.6 ml. per second, 95% confidence interval -0.2 to 3.0, p = 0.02) compared to those with prostates 40 cc or less (between group differences not significant). CONCLUSIONS: Finasteride treatment resulted in improvements in urodynamic parameters, which were greater in men with large prostates.

Aged↗

Innate and learned perceptual abilities in the newborn infant.

From research carried out over the last few years, it has become apparent that the visual world of the newborn baby (0-7 days from birth) is highly organised. It is also clear that the newborn infant is an extremely competent learner. These themes are illustrated with respect to two areas of research, face perception and intermodal learning. Evidence is presented suggesting that the human face is "special" in that newborns respond to them as faces, rather than merely collections of stimulus elements. Additional evidence is presented which demonstrates that newborns can form auditory-visual associations after only a short exposure to the stimulation. These lines of evidence suggest that innate capacities, or modules, facilitate and direct early learning in order to allow newborn infants to understand their newly encountered world.

Humans↗

Fluid therapy. Crystalloids and colloids.

Appropriate fluid therapy requires an understanding of fluid dynamics and pathologic alterations during various disease states. In addition, it requires an understanding of the pharmacologic differences of available fluids. Crystalloid fluids and colloid fluids can be used in combination to treat a variety of volume-deficient states. Synthetic colloids are also used to treat hyponcotic states. Blood products are used to replace blood components and coagulation proteins. Frequent monitoring and reassessment are required to prevent volume overload and life-threatening edema.

Animals↗

A study of the genetic diversity of Mycobacterium tuberculosis isolated from patients in the eastern province of South Africa using random amplified polymorphic DNA profiling.

This population genetics study was done to determine the degree of genetic diversity amongst clinical isolates of Mycobacterium tuberculosis in one of the largest provinces of South Africa. Three hundred and fifty-nine individual cultures were obtained from single patients over a nine-month period. Bacterial DNA was extracted and amplified with two arbitrary ten-mer primers, using the random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) technique. RAPD markers were separated by agarose gel electrophoresis, visualised with ethidium bromide, and then analysed for similarity using the GelCompar programme. The isolates were seen to fall into two major population groups. A high degree of genetic diversity was seen, with a total of 350 unique strains occurring amongst the 359 isolates. The majority of drug-resistant isolates grouped together in the smaller population group. The genetic data were also correlated with geographical locality. It was found that a slight preponderance of isolates that grouped together closely, vis. that were either genetically identical or very similar (similarity index of approximately 97%), were from areas that were considered to be geographically distant. Antibiotic resistance patterns were also examined, revealing a total of 16 different resistance profiles among the 68 drug-resistant isolates. RAPD-PCR has proved to be a cost- and time-effective technique, suitable for such a large-scale population genetics study. It has provided useful information on the genetic diversity of an organism which is responsible for an increasing amount of morbidity and mortality in South Africa's second-largest province.

DNA Fingerprinting↗

Doxazosin in the treatment of benign prostatic hyperplasia. A review of the safety profile in older patients.

The objective of this paper is to review the safety of doxazosin in older patients (>/=65 y) with benign prostatic hyperplasia (BPH) as reported in seven international clinical trials. Data from seven double-blind, placebo-controlled, phase III trials, in both normotensive and hypertensive patients with BPH were collated and analysed. Data on doxazosin were available for 341 men 65 y and over. Even though older patients can be at particular risk of adverse drug reactions, there was no apparent evidence of poor tolerability with doxazosin in older patients with BPH. The percentages of younger normotensive BPH patients (<65 y) experiencing at least one adverse event were 47 and 44% for doxazosin and placebo groups, respectively; for older normotensive BPH patients (>/=65 y) the corresponding values were 42 and 38%. For the younger hypertensive BPH patients the incidence rates for adverse events were 55% (doxazosin) and 42% (placebo) and for older hypertensive BPH patients 43 and 30%, respectively. The most commonly reported adverse events for all groups were dizziness, headache and fatigue and few serious adverse effects were reported throughout these trials. It can be concluded that doxazosin is well tolerated in young and old, normotensive and hypertensive patients with BPH.

Journal Article↗

Editorial.

Explore the source record for details and available documents.

Journal Article↗

Identification of sites of injury in Lactobacillus bulgaricus during heat stress.

Heat resistance of Lactobacillus bulgaricus in skimmed milk at 62 degrees, 64 degrees, 65 degrees and 66 degrees C was studied. The response to increasing temperatures in this range was not linear, with temperatures at 65 degrees C and above giving a lower survival rate than would be predicted from experiments at lower temperatures. To identify sites of injury at these temperatures, chemical markers were used. Heating at 64 degrees C and below resulted in damage to the cytoplasmic membrane. At temperatures of 65 degrees C and above chemical markers also indicated damage in the cell wall and proteins. Using differential scanning calorimetry analysis of whole cells of Lact. bulgaricus seven main peaks were observed (1-51, m1-61, m2-73, n-80, p-89, q-100, r-112 degrees C). Three of these peaks (l(r), m(r) and p(r)) were the result of reversible reactions. Analysis of cell fractions identified the cell structure involved in giving rise to each of the three reversible peaks; l(r), cell membrane lipids, m(r), ribosomes, and p(r), DNA. The evidence presented in this paper shows that irreversible reactions in the cell ribosomes are a critical site of damage in Lact. bulgaricus during heat stress in liquid media at 65 degrees C and above.

Animals↗

The international terazosin trial: a multicentre study of the long-term efficacy and safety of terazosin in the treatment of benign prostatic hyperplasia. The ITT Group.

OBJECTIVE: To evaluate the long-term efficacy and safety of terazosin in the treatment of benign prostatic hyperplasia (BPH). METHODS: Thirty-three sites in 13 countries enrolled men with BPH who had an International Prostate Symptom Score (IPSS) > or = 12 [corrected]. After a 2-week, no-treatment lead-in period and a 26-week, single-blind treatment period, patients responding to terazosin were randomly assigned to receive either terazosin or placebo for a 24-week, double-blind withdrawal period. RESULTS: Of the initial 427 patients enrolled, 378 were evaluable, 273 of whom completed the single-blind period, of which 186 patients were randomized. During the single-blind treatment period, IPSS, quality-of-life score (QOL), peak flow rate (PFR), and nocturia score (NOC) improved significantly (p < or = 0.05). During the double-blind withdrawal period, IPSS, QOL, PFR, and NOC deteriorated significantly in the placebo group compared with the terazosin group. The most common adverse event resulting in premature termination from the study was dizziness. There were no clinically important mean reductions in diastolic blood pressure (DBP) for patients normotensive at baseline. Terazosin significantly reduced mean DBP in hypertensive patients during the single-blind period and maintained the reduction during the double-blind period. CONCLUSION: Treatment with terazosin has a beneficial effect on BPH, continuing for at least 12 months, and can be safely considered for medium- to long-term use in those who benefit.

Adrenergic alpha-Antagonists↗

[Monitoring of emergency and intensive care patients: simple diagnostic aids].

This article describes in short sections the use and interpretation of indirect blood pressure measurements, central venous pressure, body temperature, pulse oximetry, end tidal CO2 measurements, pulse and heart rate, urine production and emergency laboratory values. Most of these parameters are directly or indirectly linked to the perfusion of the patient. Optimizing these values are one of the most important goals in emergency and critical care medicine.

Animals↗