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PubMed1983

[Disproportionately large communicating fourth ventricle--report of 2 cases].

A term of 'disproportionately large, communicating fourth ventricle' (DLCFV) was first proposed by in Harwood-Nash in 1980. It is somewhat different from the well known clinical entity of 'isolated or trapped fourth ventricle', because of apparent patency of aqueductal canal. Two cases of typical DLCFV encountered in our clinic were described. First patient was a 24 year old man in whom this condition developed following operations for lumber disc and second patient was 22 year old woman in whom the disease developed after subarachnoid hemorrhage. In both cases, main symptoms were attributable to hydrocephalus but three posterior fossa symptoms, nystagmus, Parinaud' sign and truncal ataxia were also characteristic. On the CT scan, the fourth ventricle was extraordinarily enlarged. Patency of the aqueductal canal was demonstrated by air study or Conray and Metrizamide ventriculography. On the other hand, occlusion was demonstrated or highly suspected in or near the foramina Magendie and Luschka. After a routine ventriculo-peritoneal shunt operation, the fourth ventricle decreased in size and the symptoms were immediately relieved. Plausible explanation for mechanism involved in occurrence of DLCFV were (1) occlusion process in or near the fourth ventricle outlets seems to be crucial in this pathologic condition. Collision of CSF pulse waves against the obstruction may yield a water hammer effect on the fourth ventricle. (2) abnormal weakness of the brain stem parenchyma around the fourth ventricle to CSF pressure may be another contributory factor.

Adult↗

PubMed1980

[Histopathological study on the intervertebral discs of idiopathic scoliosis (author's transl)].

To elucidate morphologic events, 74 intervertebral discs removed by Dwyer instrumentation from 15 scoliotic patients and 10 intervertebral discs by anterior spinal wedge osteotomy from 10 patients were examined, along with 33 intervertebral discs from autopsy cases. Paraffin sections were stained with PAS, toluidine blue and alcian blue in addition to routine stainings. The results obtained are as follows: (1) Noticeable differences in stainability of cartilaginous plate, cleft and vacuolation of the matrix of annulus fibrosus and cellular decrease were obtained in nucleus pulposus in scoliotic patients as compared with controls. Chordal cells in nucleus pulposus were found in 30% of scoliotic patients and 9% of controls. (2) In the apical discs, ossification gap of cartilaginous plate decreased, while cleft and vacuolation of annulus fibrosus and formation of cartilage cell cluster in nucleus pulposus were increased. (3) Irregular fiber running, cleft and vacuolation of annulus fibrosus were found in scoliotic patients with the curvature of the spine by more than 60 degrees. Matrix degeneration of cartilaginous plate and irregular fiber running of annulus fibrosus were common in scoliotic patients with higher rotation than grade III of Nash & Moe classification. Conversely, chordal cells in nucleus pluposus were not common in higher rotation cases. Chordal cell remnants were prominent in nucleus pulposus in scoliotic patients. This suggests that some abnormalities occurring during the maturation process of nucleus pulposus are related to the evolution of scoliosis.

Adolescent↗

PubMed1980

A new assay for the microsomal metabolism of nitrosamines.

This report describes a new general assay for the microsomal oxidative dealkylation of nitrosamines. After precipitation of the microsomal proteins, aldehydes formed from nitrosamines are quantitated by high-pressure liquid chromatography as their 2,4-dinitrophenylhydrazones. This novel assay method offers some distinct advantages over the commonly used Nash reagent assay. Dimethylnitrosamine, diethylnitrosamine, and methylethylnitrosamine were metabolized by microsomes from noninduced male Fischer rat liver, and the aldehydes produced by these reactions were examined. Two distinct kinetic lines were observed for reactions containing dimethylnitrosamine or diethylnitrosamine. Similarly, two Km's were observed for the production of both formaldehyde and acetaldehyde produced by the metabolism of methylethylnitrosamine.

Acetaldehyde↗

PubMed1995

In vivo interaction of the Escherichia coli integration host factor with its specific binding sites.

The histone-like protein integration host factor (IHF) of Escherichia coli binds to specific binding sites on the chromosome or on mobile genetic elements, and is involved in many cellular processes. We have analyzed the interaction of IHF with five different binding sites in vitro and in vivo using UV laser footprinting, a technique that probes the immediate environment and conformation of a segment of DNA. Using this generally applicable technique we can directly compare the binding modes and interaction strengths of a DNA binding protein in its physiological environment within the cell to measurements performed in vitro. We conclude that the interactions between IHF and its specific binding sites are identical in vitro and in vivo. The footprinting signal is consistent with the model of IHF-binding to DNA proposed by Yang and Nash (1989). The occupancy of binding sites varies with the concentration of IHF in the cell and allows to estimate the concentration of free IHF protein in the cell.

Amino Acid Sequence↗

PubMed1995

In vivo interaction of the Escherichia coli integration host factor with its specific binding sites.

Adenosine Triphosphatases↗

PubMedDate not supplied

Hypoxemia in chronic bronchitis and pulmonary emphysema.

The measurement of arterial blood oxygen tension (PaO2) in 54 patients with chronic nonspecific lung disease with a FEV1.0 of 1.51 or less, in a stable clinical state, at rest, indicated subnormal results to be more frequent among "bronchitics" (79 per cent with hypoxemia) than than among "emphysematous" patients (63 per cent with hypoxemia). The patients were classified according to a mixed clinical-roentgenologic-biological "score" (Nash et al., 1965). A significant correlation was found between PaO2 and the "emphysema score" (r=0.36; p less than 0.01). The average PaO2 was significantly (p less than 0.02) lower in "bronchitics" (65.5 +/- 8.8 mmHg; n = 14) as compared to the "emphysema" group (71.8 +/- 5.7; n = 19), in agreement with the data of the literature.

Adult↗

PubMed1993

Nutrition in the pathogenesis of alcoholic liver disease.

The data and experimental results reviewed here allow the construction of the following hypothesis: alcohol-induced liver disease results from a combination of two phenomena. The first is the induction of the maximum activity of CYP 2E1 by several dietary factors, i.e. (1) low carbohydrate-high fat diet; and (2) the dietary fats composed of PUFA (Yang et al., 1992). The second is the production of lipid peroxidation induced by CYP 2E1 oxidation of ethanol maintained at high blood alcohol levels (> 200 mg %) with the availability of PUFA as substrate (Ekstrom and Ingelman-Sundberg, 1988; Koop, 1992). Thus, lipid peroxidation may be the final common pathway which supports the induction of ALD. Further, it may provide the common denominator which links ALD pathogenesis to non-alcoholic steato-hepatitis (NASH) (French et al., 1989b), where CYP 2E1 is induced by high fat diet and/or diabetes (Dong et al., 1988).

Alcohol Drinking↗

PubMed1996

Clinical ladders: can we afford them?

To achieve or maintain a clinical ladder status, nurses at Nash General are required to submit a financial case study. This study promotes cost savings for the patient and the facility, thus balancing the expense of a clinical ladder program.

Career Mobility↗

PubMed1996

[Selective indications of skull radiography after head injury in children].

PURPOSE OF THE STUDY: Skull X-rays are systematically performed on children after head injuries in most hospitals. However, the discovery of a skull fracture as an isolated finding rarely warrants intervention. In february 1994, we stopped performing systematical skull X-rays in children after head injuries. We report the results of this experience. MATERIALS AND METHODS: Since February 1994, only children with possible skull penetration, depressed fracture, or presenting signs of basilar fracture had X-ray examination. Facial injuries were excluded in this study. In case of focal neurologic signs, neurosurgical consultation, or emergency CT examination, or both were performed. In case of change of consciousness at the time of injury or subsequently, the child was hospitalised for clinical observation for 48 hours, but no X-ray examination was performed. Children without any neurological signs or change of consciousness were discharged to their homes after they were given a head-injury instruction sheet, and if a second person could observe them for signs indicating that they belong to a higher risk group, but no X-ray examination was performed. RESULTS: An average of 241 children per month were presented at the Children Emergency Unit after head trauma. An average of twenty-one X-ray examinations per month were performed instead of 194/month before february 1994. This represented a decrease of 2000 X-ray examinations per year. There was no undiagnosed neurological complication, and the number of children staying in the hospital for clinical supervision did not increase. DISCUSSION: Skull radiographies only show fractures and do not afford visibility of either brain or blood to demonstrate an intracranial injury. The presence of a skull fracture without neurological abnormalities is of little significance. Harwood-Nash reported that 60 per cent of the children with extradural hematoma, 85 per cent of the children with subdural hematoma and 35 per cent of the children with brain damage did not have any associated skull fracture. Clinical examination is essential, and it would be a mistake to be reassured about the severity of a head trauma because skull X-rays are normal. CONCLUSION: Routine skull X-rays after head trauma are not justified either for financial or radioprotection reasons. In this study, more than half of the children were less than five years old and ran a higher risk of irradiation.

Adolescent↗

PubMedDate not supplied

[Sodium excretion in children with lithogenic disorders].

INTRODUCTION: The causes of nephrolithisis are multifactorial and have not yet been enough investigated [1]. Hypercalciuria is the most common cause of metabolic nephrolithiasis [2-4]. Close relationship between urinary calcium and urinary sodium has been a subject of reported observations in the past, showing that high urinary sodium is associated with high urinary calcium [5-7]. Hyperoxaluria, hyperuricosuria and cystinuria are also metabolic disorders that can lead to nephrolithiasis. Recent studies have indicated that urinary elimination of cystine is influenced by urinary sodium excretion. Based on these observations it has been hypothesised that patients with high urinary sodium excretion are at high risk of urinary stone disease. The purpose of the study was to investigate sodium excretion in a 24-hour urine and first morning urine collected from children with lithogenic metabolic abnormalities (hypercalciuria, hyperoxaluria, hyperuricosuria, cystinuria), both with nephrolithiasis and without it, in order to determine its significance in urinary calculi formation. PATIENTS AND METHODS: Urinary sodium excretion was investigated in 2 groups of children: patients with lithogenic metabolic abnormalities, but without urinary stone disease (L group) and patients with nephrolithiasis (C group). Both groups were divided into 2 subgroups: patients with hypercalciuria and without it. There were 22 patients in group L (mean age 11.97 +/- 4.13 years), of whom 17 formed a hypercalciuric subgroup and 5 formed a non-hypercalciuric subgroup (3 patients with hyperuricosuria and 2 patients with hyperoxaluria). Group C consisted of 21 patients with nephrolithiasis (mean age 12.67 +/- 3.44 years), of whom 6 formed a hypercalciuric subgroup and 15 formed a non-hypercalciuric group (2 patients with cystinuria and 13 patients without lithogenic metabolic abnormalities). Control group consisted of 42 healthy age-matched children. All subjects had a normal renal function. A detailed history and clinical examination were done, and ultrasonography was performed in all patients. A 24-hour urine, first morning urine and serum specimen were analysed for sodium, potassium, calcium, uric acid, urea and creatinine. Fractional excretion of sodium, as well as urinary sodium to creatinin ratio and urinary sodium to potassium ratio, were calculated from the findings. Sodium and potassium levels were determined by flame photometry, calcium was measured by atomic absorption technique (Beckman Atomic Spectrophotometer, Synchron CX-5 model, USA), uric acid by carbonate method and creatinine by Jaffe technique. Cystine and dibasic amino acids were quantified by ion chromatography. Urinary oxalate excretion was determined by enzyme spectrophotometry. Hypercalciuria was defined by 24-hour calcium excretion greater than 3.5 mg/kg per day and/or calcium to creatinine ratio greater than 0.20 [8]. Uric acid excretion was expressed as uric acid excretion factored for glomerular filtration, according to Stapleton's and Nash's formula [9]. Normal values were lower than 0.57 mg/dl of glomerular filtration rate in 24-hour samples. Mean values were statistically analyzed by Pearson's linear correlation and analysis of variance (ANOVA). RESULTS: Urinary sodium concentration values including urinary sodium to potassium ratios, are shown in Table 1. We found that urinary sodium excretion was significantly increased in patients of both L and C groups when compared with controls (p < 0.05). Further analysis of the subgroups showed that urinary sodium excretion was significantly higher only in patients with hypercalciuria of both L and C groups in comparison to controls (p < 0.05) (Table 2). A significant positive correlation was found between 24-hour urinary sodium to creatinine ratio and urinary calcium to creatinine ratio (r = 0.31; p < 0.001) (Graph 1), as well as between urinary sodium to potassium ratio in 24-hour and first morning urine (r = 0.69; p < 0.001) (Graph 2). (A

Calcium↗

PubMed2000

Extended-release niacin vs gemfibrozil for the treatment of low levels of high-density lipoprotein cholesterol. Niaspan-Gemfibrozil Study Group.

OBJECTIVE: To provide a direct comparison of agents that raise plasma levels of high-density lipoprotein cholesterol (HDL-C) to help devise strategies for coronary risk reduction. METHODS: In a multicenter, randomized, double-blind trial, we compared the effects of extended-release niacin (Niaspan), at doses increased sequentially from 1000 to 2000 mg at bedtime, with those of gemfibrozil, 600 mg given twice daily, in raising low levels of HDL-C. Enrollment criteria included an HDL-C level of 1.03 mmol/L or less (< or =40 mg/dL), a low-density lipoprotein cholesterol level of 4.14 mmol/L or less (< or =160 mg/dL) or less than 3.36 mmol/L (<130 mg/dL) with atherosclerotic disease, and a triglyceride level of 4.52 mmol/L or less (< or =400 mg/dL). RESULTS: Among 173 patients, 72 (82%) of the 88 assigned to Niaspan treatment and 68 (80%) of the 85 assigned to gemfibrozil treatment completed the study. Niaspan, at 1500 and 2000 mg, vs gemfibrozil raised the HDL-C level more (21% and 26%, respectively, vs 13%), raised the apolipoprotein A-I level more (9% and 11% vs 4%), reduced the total cholesterol-HDL-C ratio more (-17% and -22% vs -12%), reduced the lipoprotein(a) level (-7% and -20% vs no change), and had no adverse effect on the low-density lipoprotein cholesterol level (2% and 0% change vs a 9% increase). Significance levels for comparisons between medications ranged from P<.001 to P<.02. Gemfibrozil reduced the triglyceride level more than Niaspan (P<.001 to P = .06, -40% for gemfibrozil vs -16% to -29% for Niaspan, 1000 to 2000 mg). Effects on plasma fibrinogen levels were significantly favorable for Niaspan compared with gemfibrozil (P<.02), as gemfibrozil increased the fibrinogen level (from 5% to 9%) and Niaspan tended to decrease the fibrinogen level (from -1% to -6%). CONCLUSIONS: In patients with a low baseline HDL-C level, Niaspan at its higher doses provided up to 2-fold greater HDL-C increases, decreases in lipoprotein(a), improvements in lipoprotein cholesterol ratios, and lower fibrinogen levels compared with gemfibrozil. Gemfibrozil gave a greater triglyceride reduction but also increased the low-density lipoprotein cholesterol level, which did not occur with Niaspan.

Adult↗

PubMed1999

Molecular cytogenetic analysis of the bladder carcinoma cell line BK-10 by spectral karyotyping.

The bladder cancer cell line BK-10 was established from a grade III-IV transitional cell carcinoma (TCC). BK-10 is near-tetraploid (+/-4n) and consists of two subclones with 20-25 structural aberrations. Here we report the cytogenetic analysis of BK-10 by G-banding, spectral karyotyping (SKY), and FISH. SKY refers to the hybridization of 24 differentially labeled chromosome painting probes and the simultaneous visualization of all human chromosomes using spectral imaging. SKY enabled us to confirm 12 markers in BK-10 previously described by G-banding, redefine 11 aberrations, and detect 4 hidden chromosomal rearrangements, 2 of which had been identified as normal or deleted copies of chromosome 20 and 1 as a normal chromosome 3. Twenty out of 21 translocations identified were unbalanced. FISH analysis of BK-10 using chromosome arm-specific paints, centromere probes, and oncogene/tumor suppressor gene-specific probes revealed a deletion of CDKN2A (p16) in all copies of chromosome 9, a low-level amplification of MYC (five copies), and loss of one copy of TP53; detected the presence of the Y chromosome in a hidden translocation; and detected four copies of ERBB-2. A probe set for BCR and ABL verified breakpoints for all translocations involving chromosomes 9 and 22. A new karyotype presentation, "SKY-gram," is introduced by combining data from G-banding, SKY, and FISH analysis. This study demonstrates the approach of combining molecular cytogenetic techniques to characterize fully the multiple complex chromosomal rearrangements found in the bladder cancer cell line BK-10, and to refine the chromosomal breakpoints for all translocations.

Aged↗

PubMedDate not supplied

Isolation and characterization of a novel human bladder cancer cell line: BK10.

Molecular studies of bladder carcinomas have aided in determining causative genetic events and the prognosis of cancers endowed with certain abnormalities. In vitro bladder cancer characterization of key cytogenetic alterations is useful for study of molecular changes that may promote oncogenic events. In our laboratory, a novel human bladder cancer cell line, BK10, has been established in vitro and passaged for more than 20 mo. This new bladder cancer cell line (BK10) was derived from bladder tissue containing grade III-IV/IV transitional cell carcinoma. Bladder cancer tissue was obtained at the time of radical cystoprostatectomy extirpation. Cell cultures derived from this surgical sample exhibited an epithelial morphology and expressed epithelial cytokeratins. Immunostains of BK10 were negative for prostate specific antigen (PSA), fibronectin, smooth muscle actin alpha, and desmin. Karyotypic analysis revealed an aneuploid chromosomal content <4n> with many numerical and structural abnormalities previously linked to bladder oncogenesis. Translocations occurred in chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 14, 15, 16, 17, 19, 20, 21, 22, X and Y. G-banding analysis revealed rearrangements involving chromosomes 9q and 17p, and the location of the ab11 oncogene and the p53 gene, respectively. The availability of this bladder cancer cell line will provide a useful tool for the further study of bladder carcinoma oncogenesis and gene therapy.

Aged↗

PubMed2004

Reclassification of simvastatin to over-the-counter status in the United Kingdom: a primary prevention strategy.

Simvastatin (10-mg tablet) has been reclassified for sale as a pharmacy-only over-the-counter medicine in the United Kingdom. It is designed to be a primary prevention agent targeting that segment of the population having a moderate risk of coronary artery disease (CAD). The anticipated effect is a reduction of risk of a first major coronary event (nonfatal myocardial infarction or CAD death). Simvastatin is a component of the Heart Health Programme, which also addresses other modifiable risk factors such as diet, exercise, and smoking. Men >/=55 years of age, men aged 45 to 54 years with >/=1 risk factor, and women aged >/=55 years with >/=1 risk factor have a moderate (10% to 15%) 10-year risk of developing CAD. Risk factors include having a first-degree relative with a history of early family CAD, smoking, being overweight, and South Asian ethnicity. Simvastatin 10 mg lowers low-density lipoprotein cholesterol levels by approximately 30%, with a resultant 33% reduction in risk of a major CAD event after 3 years. After the patient completes a check-box questionnaire regarding his or her medical history and other specific risk factors, the pharmacist performs a few simple physical measurements and makes a decision as to CAD risk and simvastatin eligibility. After 1 month of simvastatin therapy, cholesterol testing is highly recommended to patients, and a kit is made available that permits home blood collection and analysis at a central laboratory.

Anticholesteremic Agents↗

PubMed1999

Generalist versus specialist care for acute myocardial infarction.

Early studies conflict regarding improved patient outcomes with cardiologist-directed care for acute myocardial infarction (AMI). We sought to assess the magnitude and mechanism of the influence of physician specialty on inpatient mortality for AMI. Using data from the Pennsylvania Health Care Cost Containment Council and elsewhere, we developed age-stratified logistic regression models of inpatient mortality, utilizing a split sample strategy for model development and validation. Referral bias and physician caseload were explicitly addressed. We analyzed 30,351 admissions for AMI. In patients < 65 years old, the adjusted odds ratio (OR) for mortality with cardiologist care was 0.89 (95% confidence interval [CI] 0.640 to 1.24, p = 0.49) relative to generalist care. In patients > or = 65 years of age, the adjusted OR was 0.86 (95% CI 0.72 to 1.03, p = 0.10). Caseload was significantly higher among cardiologists and was inversely related to inpatient mortality. Mortality models with caseload but not physician designation or physician designation without caseload found each predictor statistically significant in the absence of the other (OR for cardiologist care 0.82, 95% CI 0.71 to 0.95, p = 0.007; OR for patients with low volume physicians relative to high volume 1.27, 95% CI 1.05 to 1.51, p = 0.014). Older patients of physicians with higher case loads had a lower risk adjusted inpatient mortality for AMI. This probably explains the trend toward better outcomes among patients of cardiologists rather than noncardiologists.

Age Factors↗

PubMed1999

Nonselective debridement and antimicrobial cleansing of a venting ductal breast carcinoma.

A woman with a moderately differentiated carcinoma that erupted through the skin and amputated her breast was treated with whirlpool, topical antimicrobials, radiation, and chemotherapy. The draining, necrotic, and septic wound was treated for 5 months with a whirlpool containing dilute povidone-iodine solution and intravenous chemotherapy. Wet bandages, necrotic tissue, and softened eschar were removed by whirlpool agitation or mechanically debrided. To start treatment the wound was dressed with Debrisan crystals and sterile gauze for 1 week. Afterwards, wet-to-dry dressings wetted with Dakin's solution were applied. Tissue ingrowth at the wound margin started after 2 weeks, with whirlpool treatments effecting a tissue-reddening hyperemia. Wound drainage ceased after 2 months, with granulation and revascularization resulting. Eleven months later the wound was closed, aseptic, and undergoing dry flaking. The patient was cancer free with a completely healed wound 2 years after treatment. In this case, nonspecific debridement using whirlpool and topical antimicrobials promoted healing of an open fungating wound from a breast carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Do cardiologists do it better?

Pressure to lower the cost of health care delivery has fostered widespread efforts to limit patients' access to specialists such as cardiologists. However, there is concern that diminished specialist involvement may lead to poorer patient outcomes for specific clinical conditions. As part of a state-sponsored effort to improve the quality of health care in Pennsylvania, the Pennsylvania Health Care Cost Containment Council gathered clinical and administrative data on all 40,684 hospital admissions for acute myocardial infarction (AMI) in that state in 1993. They prepared a detailed public report that included risk-adjusted in-hospital mortality and length of hospital stay by physician group, by hospital and by region. These data demonstrate that patients cared for by cardiologists, as a group, had a lower risk-adjusted mortality than patients cared for by either internists (risk ratio 1.26, 95% confidence interval 1.17 to 1.35) or family practitioners (risk ratio 1.29, 95% confidence interval 1.18 to 1.40). The patients of cardiologists also had a shorter length of stay than the other two groups. These data suggest that there is enhanced value in the care provided by cardiologists for patients with AMI and call into question the growing trend toward reliance on generalists instead of specialists.

Cardiology↗

PubMed2003

Scientific considerations of pharmaceutical solid polymorphism in abbreviated new drug applications.

PURPOSE: This commentary is intended to provide a scientific perspective on pharmaceutical solid polymorphism in Abbreviated New Drug Applications (ANDAs). METHODS: This report proposes recommendations for monitoring and controlling drug substance polymorphs and describes scientific considerations of pharmaceutical solid polymorphism in the determination of drug substance sameness. RESULTS: It presents three decision trees for solid oral dosage forms or liquids containing undissolved drug substances to provide a process for evaluating when and how polymorphs of drug substances are monitored and controlled in ANDA submissions. CONCLUSIONS: It is scientifically concluded that differences in polymorphic composition of drug substances in generic drug products and reference-listed drugs are not directly relevant in the determination of drug substance sameness in ANDAs.

Chemistry, Pharmaceutical↗