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Biomedical subjects

W B White

Publications and source records attributed to W B White.

At least 127 records · Page 7Linked to original sources

Renovascular hypertension in moyamoya syndrome. Therapeutic response to percutaneous transluminal angioplasty.

Moyamoya ("puff of smoke") syndrome is a disease of children and young adults caused by fibromuscular dysplasia of the internal carotid and proximal cerebral arteries and is rarely associated with hypertension. We report a 34-year old woman with moyamoya syndrome who presented with symptomatic severe hypertension associated with unilateral renal artery stenosis. The patient underwent percutaneous transluminal angioplasty of the right renal artery with subsequent improvement in blood pressure control on reduced, and later, no antihypertensive therapy. This case illustrates that moyamoya syndrome may be an intracranial manifestation of a systemic arterial disorder. Renal artery stenosis may, in appropriate cases, be managed by percutaneous transluminal angioplasty.

Adolescent↗

Clinical experience with labetalol and enalapril in combination in patients with severe essential and renovascular hypertension.

Severe hypertension may be a difficult management issue, and it often requires therapy with multiple drugs at frequent dosing intervals. We report on the antihypertensive effects of the alpha-beta adrenergic blocking agent, labetalol, in combination with enalapril, a long-acting angiotensin-converting enzyme inhibitor, administered to 14 patients with severe hypertension (nine of whom had nephrosclerosis or renal artery stenosis) on other antihypertensive drug therapies. Blood pressure (BP), heart rate (HR), hematologic and blood chemistry values, and adverse side effects were monitored at 24 hours, 1 week, and 4 weeks of therapy. Rapid titration of the drugs was performed in the hospital in 10 patients; four were managed closely as outpatients. Following one month of combination therapy blood pressure decreased from 212 +/- 31/120 +/- 16 mm Hg at baseline to 155 +/- 19/86 +/- 12 mm Hg, and heart rate declined from 86 +/- 18 bpm to 70 +/- 16 bpm. Ten of the 14 patients (71%) maintained good BP control (BP less than 140/90 mm Hg) with no additional treatment. Serum potassium, creatinine, blood urea nitrogen concentrations, and hematologic parameters did not significantly change in 13 of 14 patients. Three patients developed symptomatic postural hypotension; in one patient this side effect resulted in discontinuation from the study. These data suggest that combination therapy with labetalol and enalapril is effective in lowering BP in patients with severe essential or renovascular hypertension. An additional advantage of this regimen is the twice-daily dosing interval, which may promote better long-term compliance.

Adolescent↗

Evidence for a multigene family involved in bile acid 7-dehydroxylation in Eubacterium sp. strain VPI 12708.

Eubacterium sp. strain VPI 12708 is a human intestinal isolate which has an inducible bile acid 7-dehydroxylation activity. At least two cholic acid-induced polypeptides, with molecular masses of 27,000 and 45,000 daltons, respectively, coelute with bile acid 7-dehydroxylation activity. The 45,000-dalton polypeptide appears to be encoded by a cholic acid-induced mRNA species of greater than 6 kilobases, which suggests that the gene coding for this polypeptide is part of a larger operon. A gene has been cloned which flanks the gene encoding the 45,000-dalton polypeptide, in the upstream (5') direction. This gene appears to encode a second 27,000-dalton polypeptide. The gene bears striking homology at both the nucleotide (80%) and deduced amino acid sequence (89%) levels with the gene which encodes the 27,000-dalton polypeptide that has been shown previously to be involved in the bile acid 7-dehydroxylation reaction sequence. The implications of this homology and the possible function(s) of the two homologous genes in bile acid 7-dehydroxylation are discussed. Evidence is presented which suggests that the two homologous genes involved in bile acid 7-dehydroxylation may be part of a larger multigene family in Eubacterium sp. strain VPI 12708.

Amino Acid Sequence↗

Molecular cloning of a gene encoding a 45,000-dalton polypeptide associated with bile acid 7-dehydroxylation in Eubacterium sp. strain VPI 12708.

Eubacterium sp. strain VPI 12708 is an intestinal anaerobic bacterium which possesses an inducible bile acid 7-dehydroxylation activity. Two cholic acid-induced polypeptides with apparent molecular weights of 27,000 and 45,000, respectively, coeluted with bile acid 7-dehydroxylation activity upon anaerobic high-performance gel filtration chromatography of crude cellular protein extracts. The 45,000-dalton polypeptide was purified to greater than 95% homogeneity by high-performance liquid chromatography gel filtration and high-performance liquid-DEAE chromatography. The first 28 amino acid residues of the N terminus of this polypeptide were determined by gas-phase sequencing, and a corresponding mixed oligonucleotide (20-mer) was synthesized. Southern blot analysis of EcoRI total digests of chromosomal DNA showed a 2.6-kilobase fragment which hybridized to the 32P-labeled 20-mer. This fragment was enriched for by size fractionation of an EcoRI total digest of genomic DNA and ligated into bacteriophage lambda gt11. Recombinant phage containing the putative gene encoding the 45,000-dalton polypeptide were detected with the 32P-labeled 20-mer by plaque hybridization techniques. The insert was 2.6 kilobases in length and may contain the entire coding sequence for the 45,000-dalton polypeptide. The 2.6-kilobase insert was subcloned into pUC8 and transformed into Escherichia coli DH5 alpha. However, the 45,000-dalton polypeptide was not detected in cell extracts of this organism when specific antibody was used. Preliminary nucleic acid sequence data correlated exactly with the amino acid sequence. A cholic acid-induced mRNA species of greater than 6 kilobases in size was identified by Northern (RNA) blot analysis of total RNA, suggesting that the gene coding for this polypeptide is part of a larger operon.

Amino Acid Sequence↗

Nucleotide sequence and regulation of a gene involved in bile acid 7-dehydroxylation by Eubacterium sp. strain VPI 12708.

Eubacterium sp. strain VPI 12708 is an anaerobic intestinal bacterium that has inducible bile acid 7-dehydroxylation activity. At least four new polypeptides were synthesized after addition of primary bile acids to the growth medium. One of these, of molecular weight 27,000 (P-27), was shown to be involved in the 7-dehydroxylation reaction sequence. The gene coding for P-27 was cloned, and the entire DNA sequence for the protein-coding region was determined. In addition, sequence information was obtained for 294 bases upstream from the translational start codon and 329 bases downstream from the stop codon. Induction studies with a synthetic oligonucleotide probe (16-mer) revealed the presence of a cholic acid-inducible mRNA species approximately 900 bases long. A 5' terminus of this mRNA was detected by primer extension analysis, and the location of the 3' terminus of the mRNA was estimated by using S1 nuclease mapping. The 3' terminus of the mRNA contained a large element with dyad symmetry of unknown function. The open reading frame contained 249 codons, and the corresponding polypeptide had a calculated molecular weight of 26,745. The amino acid sequence of P-27 showed significant homology to several previously described alcohol-polyol dehydrogenases ("nonzinc" dehydrogenases), especially in the region believed to contain a pyridine nucleotide-binding domain. The implications of this homology and the possible function of P-27 in bile acid 7-dehydroxylation are discussed.

Alcohol Oxidoreductases↗

Biosynthesis of a novel bile acid nucleotide and mechanism of 7 alpha-dehydroxylation by an intestinal Eubacterium species.

Eubacterium species V.P.I. 12708 has inducible bile acid 7-dehydroxylase activity that can use either 7 alpha or 7 beta bile acids as substrates. Cell extracts prepared from bacteria grown in the presence of cholic acid catalyzed the rapid conversion of free bile acids into a highly polar bile acid metabolite (HPBA). This conjugation activity co-eluted with bile acid 7-dehydroxylase activity on high performance gel filtration chromatography (GFC). The HPBA was purified by a combination of high performance GFC and reverse-phase high performance liquid chromatography (HPLC). The intact HPBA eluted earlier from reverse-phase HPLC than deoxycholyl-CoA and had a Mr of 1102 by Bio-Gel P-2 (GFC). The HPBA had an absorption peak at 255 nm and was sensitive to treatment with phosphodiesterase I or nucleotide pyrophosphatase. The HPBA has a free phosphate as shown by an increase in elution volume on reverse-phase HPLC following treatment with alkaline phosphatase. Treatment of the purified HPBA with nucleotide pyrophosphate plus alkaline phosphatase yielded adenosine, whereas, treatment with nucleotide pyrophosphatase alone generated 5',3'-ADP. A bile acid metabolite was also generated by nucleotide pyrophosphatase treatment. The bile acid metabolite had different chromatographic properties (HPLC and TLC) than the corresponding free bile acid. Gas liquid chromatography-mass spectrometry showed the bile acid metabolite to be 12 alpha-hydroxy-3-oxo-4-cholenoic acid. We hypothesize that the HPBA is an intermediate in 7-dehydroxylation and consists of this compound linked at the C-24 with an anhydride bond to the beta phosphate (5') of ADP-3'-phosphate. These results suggest a novel mechanism of bile acid 7 alpha/7 beta-dehydroxylation in Eubacterium sp. V.P.I. 12708.

Adenosine Diphosphate↗

Immunoregulatory effects of intravenous immune serum globulin therapy in common variable hypogammaglobulinemia.

Because of evidence of immunoregulatory effects of short-term administration of pooled donor gamma globulins, the effects of intravenous immune serum globulin were studied in nine adult patients with common variable hypogammaglobulinemia over a two-year period. Baseline assessment prior to immune serum globulin replacement included evaluation of B cell function, suppressor cell activity, and T cell subsets. These analyses were subsequently performed during the course of a first-year treatment period of intravenous immune serum globulin at doses of 100 to 200 mg/kg per month and a second-year trial at doses of 300 to 400 mg/kg per month. Five patients were re-evaluated following discontinuation of the intravenous immune serum globulin therapy for four months between the first and second treatment periods. During both treatment periods with intravenous immune serum globulin, suppressor cell activity increased markedly compared with baseline, and declined following discontinuation of drug therapy in the five patients. Suppressor cell activity was reversed by either irradiation of the T cell fraction or removal of the T8-positive cell fraction by flow cytometry. There was a reduction in the absolute number of total lymphocytes, the T3-positive cells (total T cells), and the T4-positive cells (helper cells) following intravenous immune serum globulin therapy; however, the percentages of the T cell subsets did not change significantly. Following immune serum globulin therapy, the number of T8-positive cells was not significantly changed but the T4:T8 ratio decreased from 2.1 at baseline to 1.5 after therapy (p greater than 0.05). These data demonstrate that long-term intravenous immune serum globulin administration modulates the immune system by increasing suppressor T cell functional activity but is not accompanied by changes in the number of T8-positive cells in the peripheral blood.

Adult↗

Molecular cloning of bile acid 7-dehydroxylase from Eubacterium sp. strain VPI 12708.

Eubacterium sp. strain VPI 12708 is a human intestinal bacterium which contains an inducible bile acid 7-dehydroxylase. Two-dimensional polyacrylamide gel electrophoresis showed that at least four new polypeptides were synthesized after exposure of growing cells to sodium cholate. One of these, of molecular weight 27,000 (PP-27), was implicated in 7-dehydroxylase catalysis. PP-27 was purified to greater than 95% homogeneity by DEAE-cellulose chromatography, high-pressure liquid chromatographic gel filtration, high-pressure liquid chromatography-DEAE chromatography, and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The first 33 amino acid residues of the N terminus of PP-27 were determined with a gas-phase sequencer, and a corresponding mixed oligonucleotide (17-mer) was synthesized. Southern blot analysis of EcoRI total digests of chromosomal DNA showed a 2.2-kilobase fragment which hybridized to the 32P-labeled 17-mer. This fragment was enriched for by size fractionation of an EcoRI total digest of genomic DNA, ligated into the bacterial plasmid pUC8, and used to transform Escherichia coli HB101. Transformants containing the putative 7-dehydroxylase gene were detected with the 32P-labeled 17-mer by colony hybridization techniques. The insert was 2.2 kilobases in length and contained the first 290 bases of the PP-27 gene. Preliminary nucleic acid sequence data correlate with the amino acid sequence. The entire gene was cloned on a 1,150-base-pair TaqI fragment. Western blot analysis of E. coli strains containing these plasmids indicated that PP-27 is expressed in E. coli but is not regulated by bile acids under the conditions used.

Amino Acid Sequence↗

Echocardiographic assessment of left ventricular diastolic performance in hypertensive subjects. Correlation with changes in left ventricular mass.

Left ventricular hypertrophy resulting from hypertension is accompanied by significant morbidity and mortality and in advanced stages may be irreversible. Hence, early detection of cardiac changes in hypertensive patients remains an important diagnostic goal. When the hypertrophy is mild or moderate, parameters of left ventricular diastolic function and measurements of left atrial size may facilitate the distinction between normal variation and pathologic increases in left ventricular mass. We measured left ventricular isovolumic relaxation time (IVRT, the time from aortic valve closure to mitral valve opening) and left atrial dimensions and correlated them to left ventricular mass index measured by M-mode echocardiography and rapid left ventricular filling by radionuclide ventriculography. In 20 subjects with untreated mild essential hypertension, IVRT was prolonged compared to a normotensive age-matched control group (91 +/- 23 vs 65 +/- 13 msec, p less than 0.0001). Left atrial dimension index was increased in patients compared to controls (1.9 +/- 0.4 vs 1.4 +/- 0.5 cm/m2, p less than 0.001), and this increase was related to prolonged IVRT (r = 0.46, p less than 0.001). Abnormal IVRT correlated with both increased left ventricular mass and decreased rapid ventricular filling in the hypertensive subjects. Thus, prolonged IVRT and borderline left atrial dimension may help identify subtle pathologic left ventricular mass increases in hypertensive subjects.

Aging↗

Multiple Fusobacterium nucleatum liver abscesses. Association with a persistent abnormality in humoral immune function.

A previously healthy 29-year-old man developed multiple hepatic abscesses secondary to Fusobacterium nucleatum. No underlying local disease was found. The leading portal of entry for the bacterium may have been the oral cavity; 4 days before the onset of his illness he had had extensive dental work. Immunological evaluation during the illness and in late convalescence (16 weeks after onset) revealed a persistent B cell abnormality characterized by markedly depressed in vitro secretion of immunoglobulins in response to pokeweed mitogen; however, serum immunoglobulins and IgG subclasses were normal. Abnormal numbers of suppressor T cells (OKT8+) and increased suppressor function were also present. Anaerobic pyogenic liver abscesses may occur in the absence of obvious underlying disease, but this case suggests that there may be an association with in vitro abnormalities of the immune system.

Adult↗

Clinical validation of the accutracker, a novel ambulatory blood pressure monitor using R-wave gating for Korotkoff sounds.

We compared simultaneous, same-arm blood pressure (BPs) obtained with the Accutracker, an ambulatory blood pressure (BP) monitor, which uses R-wave gating for Korotkoff sounds to those of both a blinded, skilled clinician using a mercury column and a three-channel graphic display of cuff pressure tracings, Korotkoff sounds, and ECG tracing. Eighteen subjects, with a wide variety of BPs, heart rates, and ages, participated in the study. The systolic BP obtained by the ambulatory recorder, clinician, and the three-channel strip chart recorder were 132 +/- 23 mmHg, 132 +/- 24 mmHg, and 133 +/- 25 mmHg, (all NS), respectively. Accutracker recorder-determined systolic BP correlated highly both with the clinician and strip chart readings (r = 0.98 and 0.97, respectively; p less than 0.0001 for both). The diastolic BP obtained by the Accutracker recorder was slightly, but significantly, lower than the clinician's readings (76 +/- 12 mmHg vs. 81 +/- 13 mmHg; p less than 0.005) and similar to the strip chart recorder readings (76 +/- 12 mmHg vs. 77 +/- 12 mmHg; NS). In 32 young, healthy subjects with no activity restrictions, 91% of the raw BP data from 24-hour ambulatory recordings was acceptable using strict deletion criteria. These data demonstrate that the Accutracker is highly accurate compared with clinician-determined blood pressures. The lower diastolic BP readings may stem from the ability of this device to detect softer Korotkoff sounds than can be detected by the clinician. These findings should be taken into consideration when using ambulatory BP monitoring in clinical trials of antihypertensive drugs.

Ambulatory Care↗

Ambulatory blood pressure monitoring in patients with panic disorder.

To assess possible changes in blood pressure and heart rate associated with panic attacks, we performed automatic ambulatory blood pressure monitoring in 12 newly diagnosed, drug-free, and normotensive (casual blood pressure, less than 140/90 mm Hg) medical patients recently diagnosed with panic disorder. Detailed journals were designed for the study to assess the timing and symptoms of the panic attacks and the levels of activity. Systolic blood pressure increased by 27 +/- 9 mm Hg during the hour of the panic attack compared with the hour immediately prior to the episode of anxiety, while diastolic blood pressure increased by 5 +/- 2 mm Hg. The ambulatory heart rate increased by 14 +/- 6 beats per minute during the hour of panic attack vs the hour immediately prior to the attack. There was a strong relationship between the increase in heart rate and increase in systolic blood pressure. These data confirm that normotensive patients with panic disorder have episodically hypertensive blood pressure readings associated with an increase in heart rate; these hemodynamic alterations appear to be secondary to their panic attacks and not to increased physical activity. However, despite these episodic "hypertensive" periods, the mean ambulatory blood pressures remain within the normotensive range.

Adult↗

Topical anesthesia for laceration repair: tetracaine versus TAC (tetracaine, adrenaline, and cocaine).

Topical anesthetics have always had a place in anesthetizing mucous membranes. The earliest writing in Greek medical literature makes reference to the use of these topical anesthetizing agents. Previous studies utilized a mixture of tetracaine, Adrenaline, and cocaine in the pediatric population with increased patient compliance. In contrast, another study cites the increased risk of infection in cases where topical anesthetics in combination with potent vasoconstrictors are used. To examine the efficacy and safety of a tetracaine and a tetracaine, Adrenalin, and cocaine mixture (TAC), a randomized, double-blind study was undertaken. A total of 68 patients participated in the study, with 36 receiving TAC and 32 receiving tetracaine. The results indicate that the most efficacious use of TAC is on facial lacerations, regardless of length or depth. Of the 46 participants available for follow-up, one patient in the tetracaine group reported a wound infection. A recommendation of increased use of TAC on facial lacerations, in both the adult and pediatric populations, is made based on the results of this study.

Administration, Topical↗