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Biomedical subjects

A McCullough

Publications and source records attributed to A McCullough.

At least 19 recordsLinked to original sources
PubMed2002

Is sildenafil failure in men after radical retropubic prostatectomy (RRP) due to arterial disease? Penile duplex Doppler findings in 174 men after RRP.

Sildenafil is frequently the first-line treatment for post-radical retropubic prostatectomy (RRP) erectile dysfunction (ED) with maximum treatment satisfaction rates of 43%-80%. The etiology of erectile dysfunction after RRP has been attributed to psychogenic, vascular, veno- occlusive or nerve injury causes. The purpose of this study was to gain insight into the penile duplex Doppler arterial parameters in men with ED after RRP who failed sildenafil. The purpose was to assess whether sildenafil failure after RRP is associated with underlying corporal arterial disease. A total of 174 consecutive men presenting with sildenafil refractory ED after nerve-sparing RRP underwent color duplex penile Doppler evaluation with vasoactive injection. Mean age was 59.6 y and mean time from surgery was 11.6 months. Some 81% (141/174) of the men had no pre-operative ED (PED). Significant differences in penile duplex Doppler parameters for arterial disease were seen between men with and without PED. In men without PED, 19% (27/141) manifested arterial insufficiency. However, in men with PED, 50% (16/33) demonstrated arterial disease. Nerve sparing status did not affect the presence of arterial disease. Sildenafil refractory erectile dysfunction after RRP in men without PED is not predominantly associated with penile Doppler parameters consistent with arterial insufficiency.

Aged↗
PubMed2001

Viability and effectiveness of teletherapy for pre-school children with special needs.

Telemedicine is proving valuable in the delivery of health care services. With increased competition in telecommunication markets and lower costs, the possibility of providing affordable teletherapy services for the 21st century is now a goal that can be achieved. Recognition that parent training is a vital component of successful treatment programmes makes the use of teletherapy from clinic to home an ideal medium of sharing skills with carers. Commercially available products were selected on the basis of cost effectiveness, user friendliness and audio-visual quality. Parents reported increased knowledge and confidence in developing their child's communication skills and teletherapy was demonstrated to be an effective, reliable and exciting addition to a new era of therapy provision.

Child, Preschool↗
PubMed1999

Enhancement or initiation of testicular sperm motility by in vitro culture of testicular tissue.

OBJECTIVE: To describe different techniques of testicular tissue culture and their effect on sperm motility, mainly in cases of totally immotile spermatozoa, and to compare the effect of in vitro culture with that of motility stimulants. DESIGN: Prospective study. SETTING: University teaching hospital. PATIENT(S): Ten patients undergoing testicular biopsy for diagnostic purposes or for intracytoplasmic sperm injection. INTERVENTION(S): Dissected testicular biopsy samples and tissue blocks were cultured at 37 degrees C for up to 96 hours. Immediately after dissection, immotile testicular spermatozoa were incubated for 30 minutes in pentoxifylline and 2-deoxyadenosine. MAIN OUTCOME MEASURE(S): Sperm motility and vitality. RESULT(S): Overall, dissected samples showed improved sperm motility, which peaked within 48 hours of culture. Unlike motility, vitality declined linearly, from 56.3%+/-19% at initial assessment to 18.8%+/-11% at 96 hours. Five samples had initially immotile spermatozoa, of which four acquired motility at 48 hours. In vitro culture showed results comparable with those of incubation with pentoxifylline and 2-deoxyadenosine. Culture of tissue blocks did not improve motility or vitality compared with dissected tissue. CONCLUSION(S): The motility of testicular spermatozoa was enhanced or initiated after in vitro culture. Testicular biopsy culture may be an alternative to the use of motility stimulants to obtain motile spermatozoa for intracytoplasmic sperm injection, particularly when oocytes are not immediately available.

Adult↗
PubMed1998

Quantification of gluconeogenesis in cirrhosis: response to glucagon.

BACKGROUND & AIMS: Accelerated starvation and early recruitment of alternate fuels in cirrhosis have been attributed to reduced availability of hepatic glycogen. The aim of this study was to measure gluconeogenesis (as a marker of protein oxidation) in relation to total glucose production and glucagon-stimulated glycogenolysis. METHODS: Glucose and urea production, gluconeogenesis, and glycogenolysis were calculated using stable isotope methods before and during glucagon infusion (3 ng. kg-1. min-1) in 5 cirrhotic patients and 5 matched controls before and after glycogen repletion. RESULTS: In the basal state, cirrhotic patients had a normal rate of glucose production, but the contribution of gluconeogenesis was increased (74.3% +/- 4.1% vs. 55. 6% +/- 12.1%; P < 0.005). Glycogen repletion normalized the rate of gluconeogenesis. The glycemic response to glucagon (3 ng. kg-1. min-1) was blunted in cirrhotic patients because of a lower rate of glycogenolysis (0.63 +/- 0.23 vs. 1.22 +/- 0.23 mg. kg-1. min-1; P < 0.01) and was not affected by glycogen repletion. Despite increased gluconeogenesis, the simultaneously measured rate of urea synthesis was lower in cirrhotic patients (3.11 +/- 1.02 vs. 5.0 +/- 1.0 mg/kg; P < 0.05). CONCLUSIONS: These data show that in cirrhosis, glucose production is sustained by an increased rate of gluconeogenesis. The hepatic resistance to glucagon action is not caused by reduced glycogen stores.

Adult↗
PubMed1997

A simple and objective approach to identifying human round spermatids.

Although round spermatids have been studied extensively using staining techniques and electron microscopy, little information is available about their appearance in living conditions. We describe a method of collecting and identifying round spermatids from ejaculates and testicular biopsies. The validity of the selection procedure was confirmed by fluorescence in-situ hybridization. Based on cell size, morphological characteristics of nucleus and cytoplasm, and on the nucleus/cytoplasm ratio, we harvested a population of cells that was 84% haploid. This procedure can be applied to select spermatids for clinical or research purposes.

Biopsy↗
PubMed1996

Assessment of baroreceptor-cardiac reflex sensitivity using time domain analysis in patients with IDDM and the relation to left ventricular mass index.

Autonomic dysfunction in insulin-dependent diabetic (IDDM) patients has been associated with abnormalities of left ventricular function and an increased risk of sudden death. A group of 30 patients with IDDM and 30 age, sex and blood pressure matched control subjects underwent traditional tests of autonomic function. In addition, baroreceptor-cardiac reflex sensitivity (BRS) was assessed using time domain (sequence) analysis of systolic blood pressure and pulse interval data recorded non-invasively using the Finapres beat-to-beat blood pressure recording system. 'Up BRS' sequences-increases in systolic blood pressure associated with lengthening of R-R interval, and 'down BRS' sequences-decreases in systolic blood pressure associated with shortening of R-R interval were identified and BRS calculated from the regression of systolic blood pressure on R-R interval for all sequences. We also assessed heart rate variability using power spectral analysis and, after expressing components of the spectrum in normalised units, assessed sympathovagal balance from the ratio of low to high frequency powers. IDDM subjects underwent 2-D echocardiography to assess left ventricular mass index. Standard tests of autonomic function revealed no differences between IDDM patients and control subjects, but dramatic reductions in baroreceptor-cardiac reflex sensitivity were detected in IDDM patients. 'Up BRS' when supine was 11.2 +/- 1.5 ms/mmHg (mean +/- SEM) compared with 20.4 +/- 1.95 in control subjects (p < 0.003) and when standing was 4.1 +/- 1.9 vs 7.6 +/- 2.7 ms/mmHg (p < 0.001). Down BRS when supine was 11.5 +/- 1.2 vs 22 +/- 2.6 (p < 0.001) and standing was 4.4 +/- 1.9 vs 7.3 +/- 2.5 ms/mmHg (p < 0.003). There were significant relations between impairment of the baroreflex and duration of diabetes (p < 0.001) and poor glycaemic control (p < 0.001). From a fast Fourier transformation of supine heart rate data and using a band width of 0.05-0.15 Hz as low-frequency and 0.2-0.35 Hz as high frequency total spectral power of R-R interval variability was significantly reduced in the IDDM group for both low-frequency (473 +/- 62.8 vs 746.6 +/- 77.6 ms2 p = 0.002) and high frequency bands 125.2 +/- 12.9 vs 459.3 +/- 89.8 ms2 p < 0.0001. When the absolute powers were expressed in normalised units the ratio of low frequency to high frequency power (a measure of sympathovagal balance) was significantly increased in the IDDM group (2.9 +/- 0.53 vs 4.6 +/- 0.55, p < 0.002 supine: 3.8 +/- 0.49 vs 6.6 +/- 0.55, p < 0.001 standing). Thus, time domain analysis of baroreceptor-cardiac reflex sensitivity detects autonomic dysfunction more frequently in IDDM patients than conventional tests. Impaired BRS is associated with an increased left ventricular mass index and this abnormality may have a role in the increased incidence of sudden death seen in young IDDM patients.

Adult↗
PubMed1995

Diagnosis of intestinal microsporidiosis by examination of stool and duodenal aspirate with Weber's modified trichrome and Uvitex 2B strains.

Severe, chronic diarrhea is a frequent complication of human immunodeficiency virus disease, and intestinal microsporidiosis is being recognized with increasing frequency in patients with AIDS. Noninvasive, cost-effective techniques are needed to optimize its diagnosis. Weber's modified trichrome stain (MTS) and the fluorochrome Uvitex 2B stain were used to detect microsporidial spores in smears of stool and duodenal aspirate (DA) samples received from human immunodeficiency virus-infected patients for examination for ova and parasites. Of 305 samples (292 stool and 13 DA samples) from 140 patients examined by MTS, 83 samples from 26 (18.6%) of the patients were positive for microsporidia (23 patients diagnosed initially and 3 diagnosed upon review). A subset of the samples studied by MTS consisting of 108 smears of stool and DA specimens from 60 patients was examined by Uvitex 2B. All 44 samples positive by MTS were also positive by Uvitex 2B. In addition, seven specimens and three patients were initially detected as positive by Uvitex 2B only (all three patients were positive also by MTS upon review). Confirmation of the diagnosis was obtained for 24 of 26 smear-positive patients by duodenal biopsy and/or stool transmission electron microscopy. Of 114 patients with stained smears negative for microsporidia, 23 had duodenal biopsies which showed no microsporidia. For the 43 patients who underwent duodenal biopsy, the sensitivity of both the MTS and the Uvitex 2B methods compared with biopsy results was 100%. Of six patients with negative duodenal biopsies and positive stained smears, four had microsporidia demonstrated by stool transmission electron microscopy. The examination of stool and DA smears stained by Uvitex 2B and/or MTS is a sensitive, noninvasive test for diagnosis of intestinal microsporidiosis which can be successfully implemented in a clinical laboratory. Strict adherence to precise diagnostic criteria is necessary to avoid incorrect results. The simultaneous use of both staining methods enhances performance and may provide greater accuracy, especially for patients with light infections.

AIDS-Related Opportunistic Infections↗
PubMed1994

Removal of 3'-phosphoglycolate from DNA strand-break damage in an oligonucleotide substrate by recombinant human apurinic/apyrimidinic endonuclease 1.

A recombinant human AP endonuclease, HAP1, was constructed and characterized with respect to its ability to recognize and act upon a model double-stranded 39-mer oligodeoxyribonucleotide substrate containing a strand break site with 3'-phosphoglycolate and 5'-phosphate end-group chemistries. This oligodeoxyribonucleotide substrate exactly duplicates the chemistry and configuration of a major DNA lesion produced by ionizing radiation. HAP1 was found to recognize the strand break, and catalyze the release of the 3'-phosphoglycolate as free phosphoglycolic acid. The enzyme had a Vmax of 0.1 fmole/min/pg of HAP1 protein, and a Km of 0.05 microM for the 3'-phosphoglycolate strand break lesion. The mechanism of catalysis was hydrolysis of the phosphate ester bond between the 3'-phosphoglycolate moiety and the 3'-carbon of the adjacent dGMP moiety within the oligonucleotide. The resulting DNA contained a 3'-hydroxyl which supported nucleotide incorporation by E. coli DNA polymerase I large fragment. AP endonucleolytic activity of HAP1 was examined using an analogous double-stranded 39-mer oligodeoxyribonucleotide substrate, in which the strand break site was replaced by an apyrimidinic site. The Vmax and Km for the AP endonuclease reaction were 68 fmole/min/pg of HAP1 protein and 0.23 microM, respectively.

Amino Acid Sequence↗
PubMed1994

31P NMR assessment of orthotopic liver rejection in a rat model.

31P NMR spectroscopy was used serially to study rejecting (ACl-->LEW) and nonrejecting (ACl-->ACl) orthotopic liver transplants in rats. Recipients were evaluated on post-transplant days 1, 3, 5, 7, 9, and 11. The relative changes in phosphomonoester (PME), inorganic phosphate (Pi), high-energy phosphates and pH were studied. The earliest significant difference between the rejecting and nonrejecting groups was a decrease in the alpha-NTP peak area on Day 5. This was followed by significant decreases in beta-NTP and pH, and increases in PME and Pi on Day 7. High-resolution 31P NMR spectra of perchloric acid extracts demonstrated the PME increase to be due mainly to elevated phosphoethanolamine. Using the parameter (Pi + PME)/(alpha + beta + gamma-NTP), rejecting livers were distinguished from nonrejecting livers at a moderate stage of rejection.

Animals↗
PubMed1993

Hepatic utilization of exogenous nucleotide precursors for restoration of ATP after cold ischemia in rats.

The study objective was to assess hepatic utilization of exogenous adenosine or adenine to enhance ATP recovery in rat liver after cold ischemia. ATP was measured noninvasively by 31P nuclear magnetic resonance (NMR) in perfused livers before and after 18 h of cold ischemia. The hepatocellular concentration of ATP during the initial postischemic reperfusion without adenosine or adenine coinfusion was 60% of that in fresh liver. The ATP increased significantly (P < 0.001) to 139% and 82% of baseline in postischemic livers coinfused for 90 min with adenosine or adenine (final concentration, 1 mmol/L), respectively. Less than 0.5% of the excess adenosine was catabolized to uric acid. In conclusion, adenosine and, to a lesser extent, adenine are salvaged by liver after extended cold ischemia to enhance ATP restoration. Provision of these ATP precursors, as components of an enteral formulation may facilitate the repletion of liver ATP and foster early resumption of liver function after an ischemic insult.

Adenine↗
PubMed1993

Omeprazole is superior to ranitidine plus metoclopramide in the short-term treatment of erosive oesophagitis.

Histamine H2-receptor antagonists are moderately effective in symptomatic treatment and healing of erosive oesophagitis, but they are not as effective as the proton pump inhibitor omeprazole. In some studies prokinetic agents seem to increase the effectiveness of H2-antagonists, but no study comparing the efficacy of omeprazole to H2-antagonists plus prokinetic agents has been performed. The purpose of this study was to compare the efficacy and tolerability of 20 mg omeprazole daily with 150 mg ranitidine b.d.s. plus the prokinetic agent 10 mg metoclopramide q.d.s. in patients with erosive oesophagitis. After both 4 and 8 weeks of treatment, omeprazole healed the mucosa in significantly more patients than did ranitidine plus metoclopramide. Omeprazole also provided significantly greater relief from daytime heartburn, nighttime heartburn, and acid regurgitation, and was associated with decreased concomitant antacid use. Although the overall incidence of adverse events was similar in the two treatment groups, a significantly higher number of treatment-related adverse events and more treatment-related withdrawals from the study occurred in the ranitidine plus metoclopramide treatment group. Omeprazole is more effective and better tolerated than the combination of standard dose ranitidine plus metoclopramide for patients with erosive oesophagitis.

Adult↗
PubMed1992

Two doses of omeprazole versus placebo in symptomatic erosive esophagitis: the U.S. Multicenter Study.

Two hundred thirty patients with reflux symptoms and endoscopically proven erosive esophagitis were enrolled from 15 U.S. centers into a randomized, double-blind, dose-ranging study comparing placebo with omeprazole, 20 or 40 mg given once daily in the morning. Esophagitis grade 2 was present in 44% of patients, grade 3 in 37% of patients, and grade 4 in 19% of patients. Endpoints, defined as complete relief of heartburn and complete esophageal mucosal healing, were assessed after 4 and 8 weeks of treatment. Both omeprazole doses were significantly superior to placebo in complete endoscopic healing. After 8 weeks of treatment, 73.5% of patients in the 20-mg omeprazole group and 74.7% in the 40-mg omeprazole group, compared with 14.0% in the placebo group, had complete healing of the esophageal mucosa. At the end of the study, complete relief of daytime heartburn was obtained in 79.5% of patients in the 20-mg omeprazole group, 81.6% in the 40-mg omeprazole group, and 37.2% in the placebo group (P less than or equal to 0.05). Complete relief of nighttime heartburn was noted by 79.5% of patients in the 20-mg omeprazole group, 85.1% in the 40-mg omeprazole group, and 34.9% in the placebo group (P less than or equal to 0.05). The median time to complete relief of daytime and nighttime heartburn occurred earlier in the 40-mg group than in the 20-mg group (9 vs. 17 days and 9 vs. 20 days, respectively); however, these differences were not statistically significant. Relief of acid regurgitation and dysphagia also occurred earlier in the 40-mg group. Omeprazole was well tolerated in this group of patients. No unexpected adverse experiences occurred. The results of this study confirm those of six multicenter, international trials in which omeprazole in doses of 20-60 mg provided a degree of esophageal mucosal healing and complete relief of reflux symptoms superior to any other medical treatment.

Adult↗
PubMed1990

Omeprazole versus placebo in duodenal ulcer healing. The United States experience.

The study objective was to study the ulcer healing effects and safety of the proton pump inhibitor, omeprazole, given in a dose of 20 mg once daily before breakfast. The study design was a randomized, double-blind, multicenter comparison of omeprazole and placebo using endoscopy to assess ulcer healing after two or four weeks of therapy. One hundred fifty-three patients with endoscopically documented active duodenal ulcer were studied. One hundred two patients received omeprazole and 51 received placebo. Patients in both groups were similar with regard to age, sex, duration of disease, initial ulcer size, smoking history, and alcohol use. A "per protocol" analysis of healing rates showed a significant advantage for omeprazole (P less than 0.01) at both week 2 (41% vs 13%) and week 4 (75% vs 27%). Concomitant factors (including smoking and ulcer size) did not alter the significance of the differences in healing rates between omeprazole and placebo. Complete relief of day and night pain was more often achieved (P less than 0.01) in the omeprazole group. "All-patients treated" analyses for healing and pain relief gave results similar to the respective "per protocol" analyses. Omeprazole was well tolerated; fewer patients had clinical and laboratory adverse experiences in the omeprazole group than in the placebo group. Fasting serum gastrin levels increased with omeprazole therapy (mean 34.9 to 73.5 pg/ml) but exceeded the normal range (greater than 150 pg/ml) in only 12.3% of patients. Two weeks after therapy was stopped, serum gastrin levels showed a decrease toward baseline but had not yet completely returned to pretreatment levels (mean 49.7 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Double-Blind Method↗
PubMed1990

Unusual computed tomography findings in hepatic amyloidosis.

An unusual pattern of delayed enhancement in a patient with a focal hepatic defect due to amyloidosis is presented. Without the aid of region-of-interest density measurements, the lesion was not appreciated on unenhanced computed tomography scans.

Amyloidosis↗
PubMed1985

Reversible abnormalities of myocardial relaxation in hypothyroidism.

Fifteen selected hypothyroid patients without symptoms or signs of cardiovascular disease and an equal number of matched control subjects underwent simultaneous recording of electrocardiogram and phono-, apex-, and echocardiography to assess dynamic systolic and diastolic left ventricular function. Both the systolic preejection period and the isovolumic relaxation period were significantly increased in the hypothyroid group. However, whereas the rate of myocardial contraction, assessed from the echocardiograph of the left ventricular posterior wall, was identical in patients and control subjects, the diastolic thinning rate of the muscle was markedly slowed in the hypothyroid individuals. The abnormalities demonstrated were in the main completely reversed after 3 months of T4 therapy. These results demonstrate a relatively selective and readily reversible disturbance of the rate of myocardial relaxation in hypothyroidism, suggesting an intrinsic abnormality of cardiac muscle. This allows an intriguing parallel to be drawn with the delayed relaxation phase of voluntary muscle contraction, long recognized as a direct measure of tissue thyroid function in hypothyroidism. The abnormality of diastolic function we have described is of similar character to that found in patients with other cardiomyopathies and which has been shown to be a major cause of disturbance of global cardiac action.

Adult↗