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Biomedical subjects

K Miller

Publications and source records attributed to K Miller.

At least 361 records · Page 20Linked to original sources

Pregnancy can be established in superovulated adult rats treated with progesterone and an aromatase inhibitor.

An adult superovulated rat model has been developed and is characterized by high ovulation rates, early morphological degeneration of embryos, complete embryo loss within 48 hours of conception and elevated peripheral estradiol(E2)/progesterone(P4) ratios. In this study, three trials were conducted using the superovulated adult rat model. First, control naturally cycling rats were compared with superovulated rats supplemented with 1 mg P4 on days 0-3 of pregnancy. A sperm positive vaginal smear is designated as day 0 of pregnancy. The P4 treated rats demonstrated improved embryo retrieval on day 1 of pregnancy, continued embryo recovery with a decrease in normal morphologic characteristics of integrity on day 2, with nearly total embryo loss by day 3. On each day, P4 levels were elevated 2-3 times over control. The second trial compared 3 groups of rats, 1) naturally cycling, 2) superovulated unsupplemented and 3) superovulated rats supplemented with 1 mg P4/rat/day and the aromatase inhibitor, 4-hydroxyandrostenedione (4-OHA), 12.5 mg/rat/day. The superovulated unsupplemented rats had no embryo recovery after day 2 of pregnancy, while the P4 and 4-OHA treated rats showed a variable ability to maintain normally developing embryos through day 4 of pregnancy. E2 levels were elevated in both superovulated groups on days 1-4 of pregnancy as were P4 levels on days 2-4. The E2/P4 ratio was significantly lowered only on day 1 of pregnancy in the P4 and 4-OHA treated group. The third trial demonstrated implantation in 50% of the superovulated rats supplemented with P4 and 4-OHA. In conclusion, implantation in the superovulated adult rats can occur with P4 and 4-OHA supplementation, however, this biologic phenomenon could not be explained by obvious changes in peripheral E2 and P4 levels.

Analysis of Variance↗

The ileal neobladder: 6 years of experience with more than 200 patients.

Between April 1986 and April 1992, 211 consecutive men underwent lower urinary tract reconstruction by means of the ileal neobladder. There have been 5 perioperative deaths for an operative mortality rate of 2.4%. The early complication rate for issues not directly related to the neobladder was 7.5% compared to a 6.5% directly neobladder-related early reoperation rate. Neobladder-related late complications requiring rehospitalization or reoperation have been acceptable, including ileus (2%), abscess (1%), colon-reservoir fistula (1.5%), hydronephrosis (1%), ureteral stenosis (3.6%) and transurethral incision of the urethroileal anastomosis (7%). Overall, only 29.3% of our patients had no complication, whereas 32% suffered significant problems requiring rehospitalization or reoperation. The remainder of the patients suffered minor but not negligible problems. Excellent continence was achieved early and increased with time: 85% of the patients were perfectly dry night and day by 3 years. At this date only 5.5% of the patients had nighttime incontinence, while 6% wear protection for occasional accidents. Intermittent catheterization is necessary in 3.5% of the patients because of the inability to void or maintain a post-void residual volume of less than 100 ml. Despite the fact that some price must be paid for excellent continence, natural voiding and undisturbed body image, the ileal neobladder continues to be our procedure of choice for male patients after cystectomy provided there is no evidence of prostatic or urethral involvement. Our results should stimulate earlier patient and physician acceptance of cystectomy.

Adult↗

Transperitoneal laparoscopic nephrectomy: training, technique, and results.

Transperitoneal laparoscopic nephrectomy was integrated into our daily routine within a 6-month period by means of a step-by-step training program progressing from a pelvic trainer to animal studies (N = 15) to laptent-assisted surgery. The pneumoperitoneum is created with the patient in the flank position, enabling insertion of three trocars: 10-mm periumbilical (Port I), 5/12-mm subcostal (Port II), and 12/5-mm above the iliac spine (Port III). After medial mobilization of the colon, two additional 5-mm trocars (Ports IV and V) are inserted into the lateral abdominal wall parallel to Ports II and III. Once clipping and dissection of the ovarian (spermatic) vein has been carried out, the ureter is identified and dissected. Retraction of the proximal ureter exposes the renal hilum, allowing dissection of the renal vessels. The renal vein is dissected using an endoscopic stapling device, while accessory veins and the renal artery are clipped. Organ retrieval is achieved with a specially designed tissue pouch (Lapsac) and digital fragmentation of the kidney within the organ bag. Using this technique, we have treated 24 patients with benign (N = 20) and malignant (N = 4, including adrenalectomy) renal disease. The mean operative time was 239 (115-300) minutes. In four cases, open surgery was required because of bleeding (N = 2), severe perinephric inflammation (N = 1), or bowel injury (N = 1). For relief of wound pain, an average of 1.15 vials of analgesic (morphine derivatives)/patient were administered for 2.4 days. The postoperative hospital stay averaged 6.2 (4-10) days.

Animals↗

Absence of an inhibitory effect of omeprazole and nizatidine on phenytoin disposition, a marker of CYP2C activity.

The effects of omeprazole (40 mg orally per day) and nizatidine (300 mg orally per day) on the disposition of phenytoin (4.5 mg kg(-1) p.o. single dose) were studied in 18 healthy, young adult males. Total and unbound plasma concentrations of phenytoin were measured for 48 h after each dose of phenytoin. Neither treatment altered the disposition kinetics of phenytoin, the hydroxylation of which is mediated specifically by cytochromes P450 of the 2C subfamily.

Adult↗

Clinical trials with velnacrine: (PROPP) the physician reference of predicted probabilities--a statistical model for the estimation of hepatotoxicity risk with velnacrine maleate.

Safety observations during the clinical development of Mentane (velnacrine maleate) have included the occurrence of generally asymptomatic liver enzyme elevations confined to patients with Alzheimer's disease (AD). The clinical presentation of this reversible hepatocellular injury is analogous to that reported for tetrahydroaminoacridine (THA). Direct liver injury, possibly associated with the production of a toxic metabolite, would be consistent with reports of aberrant xenobiotic metabolism in Alzheimer's disease patients. Since a patient related aberration in drug metabolism was suspected, a biostatistical strategy was developed with the objective of predicting hepatotoxicity in individual patients prior to exposure to velnacrine maleate. The method used logistic regression techniques with variable selection restricted to those items which could be routinely and inexpensively accessed at screen evaluation for potential candidates for treatment. The model was to be predictive (a marker for eventual hepatotoxicity) rather than a causative model, and techniques employed "goodness of fit", percentage correct, and positive and negative predictive values. On the basis of demographic and baseline laboratory data from 942 patients, the PROPP statistic was developed (the Physician Reference Of Predicted Probabilities). Main effect variables included age, gender, and nine hematological and serum chemistry variables. The sensitivity of the current model is approximately 49%, specificity approximately 88%. Using prior probability estimates, however, in which the patient's likelihood of liver toxicity is presumed to be at least 30%, the positive predictive value ranged between 64-77%. Although the clinical utility of this statistic will require refinements and additional prospective confirmation, its potential existence speaks to the possibility of markers for idiosyncratic drug metabolism in patients with Alzheimer's disease.

Age Factors↗

Phosphocreatine protects transgenic mouse liver expressing creatine kinase from hypoxia and ischemia.

Creatine kinase (CK) is normally found at high levels in muscle and brain and catalyzes the reaction phosphocreatine (PCr) + MgADP + H+<==>creatine (Cr) + MgATP. CK is not normally found at high levels in liver. A line of transgenic mice that express high levels of the BB-dimer of CK (CKB) in liver has allowed us to assess the role of CKB during periods of low oxygen stress. During 40 min of ischemia of normal perfused livers at 25 degrees C, ATP levels are depleted, and pH decreases to 6.6. pH recovers to a preischemic level after 30 min of reperfusion of normal livers; however, P(i) levels are significantly higher and ATP levels significantly lower than preischemic values. In transgenic liver with an initial PCr-to-ATP ratio of 4.5, ATP levels are maintained until PCr is markedly depleted. pH remains at preischemic levels for 16 min of ischemia of transgenic livers. During this length of ischemia in normal livers, pH has dropped to 6.9. pH, P(i), and ATP levels return to preischemic values within 30 min of reperfusion in transgenic livers containing PCr and CK. During 90 min of hypoxia of normal perfused livers at 37 degrees C, ATP is depleted. After 15 min of hypoxia of normal livers, there is a significant increase in the release of lactate dehydrogenase (LDH). In transgenic livers, ATP is maintained, and no increase in LDH release is observed for up to 90 min, depending on the level of PCr before hypoxia. These results demonstrate the role of CKB in buffering ATP levels and regulating intracellular pH during periods of low oxygen stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Metabolic long-term follow-up of the ileal neobladder.

In recent years urinary diversion using long gut segments has become increasingly popular. Accordingly, beside the development of metabolic acidosis, some concern has been raised as to the development of malabsorption syndromes. Until now no detailed study has been published on a long-term follow-up of this problem. Therefore this study was performed to investigate various absorption parameters of different metabolic systems in 30 patients with an ileal neobladder. The resulting data revealed no major or severe changes in the absorptive parameters, therefore orthotopic urinary diversion with the ileal neobladder seems to be a safe procedure with regard to the development of malabsorption syndromes.

Calcium↗

Concomitant nonpharmacologic therapy in the treatment of primary nocturnal enuresis.

Some 5 to 7 million children in the United States suffer from primary nocturnal enuresis (PNE). Although the majority of parents do not seek medical evaluation and treatment for their children with PNE, physicians usually prescribe pharmacotherapy for this condition. Several nonpharmacologic treatment modalities also are available, including bladder-stretching exercises, behavioral therapy, hypnotherapy, and elimination diets. Motivational counseling, another technique, should be a component of all PNE treatment programs. Although none of the methods offers effective resolution of nighttime incontinence in all children, combining methods increases the probability of treatment success and encourages compliance without risk to the child. Required in any program is the active participation of the patient and his or her family and the guidance, education, and reinforcement provided by the physician. Although the health-care professional may have to devote considerable time to help the patient, successful treatment may prevent the development of potentially serious psychosocial effects.

Acupuncture Therapy↗

[PSA volume quotient: an additional parameter in diagnosis of locally confined prostate cancer].

The sensitivity and specificity of prostate-specific antigen density (PSAD), a quotient of serum PSA and prostate volume, in the detection of localized prostate cancer was analysed in a prospective study. A total of 235 patients were examined, 145 without prostate cancer and 90 patients before radical prostatectomy for localized prostate cancer. PSAD was determined by dividing the serum level of PSA by the volume of the entire prostate (estimated by transrectal ultrasound) and multiplying by 100. Using a PSAD of 15, the specificity achieved in our collective was the same as with an absolute PSA value of 4 ng/ml (88.9-90%). On the other hand, with the PSAD of 15 we also found the same sensitivity as with an ab-solute PSA of 10 ng/ml (75.2-76.5%).

Adult↗

[Ultrastructural studies of the ileum neobladder].

Four patients had cold biopsies of the ileal mucosa 15-40 months after bladder substitution with an ileal neobladder. We used electron optical systems encompassing scanning electron microscopy and transmission electron microscopy for ultrastructural evaluation of the specimen. The changes observed did not vary markedly from patient to patient. In all biopsies the number of normal intestinal mucosa cells as well as mitochondrial density and number of microvilli was significantly reduced. In contrast the density of goblet cells was similar to that found in normal ileal tissue. These findings confirm the clinical observation that, on long-term follow-up, patients with an ileal neobladder show a decrease in urinary resorption via the ileal mucosa, whereas mucus secretion tends to be constant.

Biopsy↗

[The biofragmentable Valtrac ring--a reliable concept for enteral anastomosis?].

In a retrospective investigation, 54 patients with 55 enteric anastomoses performed with the new biofragmentable Valtrac ring were examined. In 45 patients with disease of the colon partial resection of the large bowel had been performed. In 9 patients undergoing urinary diversion an end-to-end ileostomy was performed. The most important advantage of this device is that its use is achieved by way of a safe and quick technique which is easy to learn. Bowel stenosis, bleeding and other complications independent of anastomotic technique, such as wound infection, were no more frequent than after conventional suture anastomosis. In 3 patients an anastomotic leakage appeared. In 1 of these cases conservative management for a colocutaneous fistula was successful, but the other 2 patients had to undergo a second operation. In our opinion, the Valtrac system offers a convincing and reproducible alternative to conventional anastomotic techniques and it is easy to learn how to apply it.

Adult↗

[Electronic data processing in urologic clinics. Results of a survey. Electronic Data Processing in Urology Group of the Graduate and Continuing Education Commission of German Urologists].

Computer equipment in Departments of Urology in Germany was evaluated by a nation-wide questionnaire. One hundred and fifty-three questionnaires were returned with detailed information on computer hardware, software and applications in Urology. Most departments were equipped with at least one computer. Computer equipment varied considerably among the participants including both stand alone personal computers (PCs) and local area networks (LANs) with several PCs connected by cable. Typically, PCs were IBM-compatible and ran the MS-DOS operating system Word processing and related applications were the most frequently mentioned computer tasks in urology. In some departments computers are also used in research for production of databases and graphics and for statistical applications. When computers were used for documentation of therapy and/or medical records, software was often custom-made according to the department's specific needs. In the future, more computers will be needed in departments of urology, because medical records will have to meet higher standards of documentation.

Computer Literacy↗

Evaluation of a hyperbaric system to be used in conjunction with a fluorometer.

A high-pressure chamber that can be used inside the sample chamber of a spectrofluorometer is described and some performance characteristics are presented. The chamber body, constructed of 316 stainless steel, is temperature regulated using resistive heating elements and a microprocessor-based proportional integral derivative controller. The chamber holds a standard 1-cm2 cuvette that indexes with an electromagnetic stirrer. Injection of different solutions into the closed and pressurized (6.8 MPa) vessel is accomplished by computer-controlled, low-volume solenoids attached to separate microliter injection ports. Repetitive injections of fluids down to a volume of 7 microliters are possible in the pressurized chamber. Temperature stability of the chamber is +/- 0.2 degrees C at atmospheric or elevated pressure. However, during the initial phase (first 3 min) of pressurization, at a compression rate of 0.62 MPa/min, a 0.23 degrees C/min increase in temperature occurs. The chamber windows depress the relative intensity of the emitted light by approximately 20% for visible light and 40% for near UV; however, total sensitivity of the system is sufficient to accomplish most determinations while maintaining a good signal-to-noise ratio. This system can be used to evaluate the response of several molecular and cellular events during compression and at depth with the use of various fluorometric probes.

Atmosphere Exposure Chambers↗

Risk prediction in operatively treated fractures of the hip.

There have appeared no objective means by which preoperative risk in patients with fractures of the hip can be quantitatively predicted. The developed risk's core is based on medical history, physical examination, chest radiograph, and screening laboratory data. This system reproducibly assigns patients into one of three groups. Three hundred seventeen patients with surgically treated hip fractures (93 femoral head, 166 neck, 58 intertrochanteric fractures) were analyzed in this study. Surgical treatment included 102 Ender-pinnings, 43 Böhler-nails, 79 dynamic hip screws, and 93 endoprostheses of the hip (according to fracture type). Overall mortality rate during hospitalization was 9.5%. The mortality rate in Group I was 2.5%; in Group II, 11.9%; and in Group III, 44.1%. The medical complications in Group I were 12.6%; in Group II, 28.6%; and in Group III, 67.6%. The difference for each group was significant. This preoperative risk assessment appears effective in more accurately identifying patient risk.

Aged↗

[Imaging procedures in preoperative lymph node staging of invasive bladder cancer. Necessary or superfluous?].

A staging programme for detection of lymph node involvement before radical cystectomy has been carried out in 22 patients. The programme includes: intravenous pyelography, chest X-ray, abdominal sonography, bone scan, CT and MRI. Also an immunoscintigraphic examination using monoclonal anti-CEA antibody (TUMAK BW 421/26) was done in every patient. Preoperative lymph node staging using CT, MRI and immunoscintigraphy was compared with post-operative histological staging: a total of 5 patients were found to have lymph node involvement. In none of them had lymph node involvement been predicted on the basis of CT, MRI or immunoscintigraphy.

Aged↗