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Biomedical subjects

K Miller

Publications and source records attributed to K Miller.

At least 325 records · Page 18Linked to original sources

Clinical features and outcome of severe malaria in Gambian children.

The clinical and laboratory features of severe falciparum malaria in 180 Gambian children were studied between 1985 and 1989. Of the 180 children, 118 (66%) presented with seizures, 77 (43%) had cerebral malaria, 35 (20%) had witnessed seizures after admission, 29 (16%) were hypoglycemic, and 27 (15%) died. Respiratory distress was a common harbinger of a fatal outcome. The differences in admission parasite counts in the blood, hematocrit, and opening cerebrospinal pressures for patients who died and survivors were not significant. A multiple logistic regression model identified neurological status (coma, particularly if associated with extensor posturing), stage of parasite development on the peripheral blood film, pulse rate of > 150 or respiratory rate of > 50, hypoglycemia, and hyperlactatemia (plasma lactate level, > 5 mmol/L) as independent indicators of a fatal outcome. Biochemical evidence of hepatic and renal dysfunction was an additional marker of a poor prognosis, but, in contrast to severe malaria in adults, none of these children with severe malaria had acute renal failure.

Adult↗

Experimental infection of human nasal mucosal explants with Neisseria meningitidis.

The interaction of Neisseria meningitidis with rhinopharyngeal epithelium was studied by experimental infection of explants of human nasal turbinate mucosa with two wild strains: a fully capsulate case isolate, and an epidemiologically related non-capsulate nasopharyngeal isolate. After incubation for 4 h, epithelial cells of infected explants changed conformation from tall columnar morphology towards cuboidal, and there was increased discharge of mucus globules from goblet cells. By 24 h there was significant damage to infected epithelia, including projection of cells out of the surface, cytoplasmic blebbing and mitochondrial abnormalities. Meningococci were associated with surface non-ciliated cells by 4 h after infection. By 24 h after infection they were associated extensively with all cell types exhibiting damage. There was little association with secreted mucus. In areas of cell damage, penetration between surface cells was observed. Endocytosis into non-ciliated cells was observed in only a minority of explants studied and only in those infected for 24 h. From this intracellular site there was apparent migration to adjacent cells and to intercellular locations. No organisms were observed within or beneath basement membrane collagen in any explants but internalisation into mononuclear phagocytes was observed occasionally.

Cilia↗

Hemiplegic migraine with CSF abnormalities.

A 30-year-old woman with hemiplegic migraine and an elevated CSF protein level with considerable pleocytosis is described. Fourteen other cases of hemiplegic migraine with cerebrospinal fluid abnormalities reported in the literature are reviewed.

Adult↗

Laparoscopic pelvic lymphadenectomy in prostatic cancer: an analysis of seventy consecutive cases.

From July 1992 to April 1994, 70 patients with prostatic cancer underwent laparoscopic pelvic lymph-node dissection (LPLD) before retropubic radical prostatectomy or afterloading therapy in our clinic. After an initial learning phase, the accuracy of LPLD was excellent, with only 3.0% residual nodes and no false-negative results due to LPLD. The rate of severe complications was 5.7% (4/70). No transfusions were required due to LPLD. If patients with positive nodes (D1) were excluded from local therapy, the benefits of LPLD were estimated as 12 patients with positive nodes avoiding open surgery (17.1%); 15 patients undergoing afterloading therapy and avoiding open surgery (21.4%); 1 patient with high preoperative prostate-specific antigen having a chance of surgical cure (1.4%) - a total of 28 of 70 patients (40.0%). We conclude that, depending on the therapeutic concept applied, LPLD is beneficial for patients with prostatic cancer, it opens the door for other curative procedures like after-loading therapy, and reappraisal of perineal prostatectomy.

Adult↗

Treatment of Peyronie's disease with local interferon-alpha 2b.

Peyronie's disease is an illdefined condition that often leads to severe penile deformity. Various conservative treatments have failed to have any impact, and surgery remains the mainstay of therapy in advanced cases. Recent reports of successful treatment of related diseases, notably keloid formation, with interferons (INF) have prompted us to use this biologic response modifier to alter the behavior of the myofibroblast, the cell most likely responsible for the development of Peyronie's disease. From December 1992 to July 1994, 25 patients suffering from Peyronie's disease were treated with five local injections of 1 million units of INF-alpha 2b each into a single designated and ultrasonographically measured plaque. The interval between the injections was 1 week. The patients were assessed clinically and ultrasonographically 1 and 6 months after the last injection. The condition improved clinically in only 1 case, but progressed in none. The measured plaque size decreased in 7 no or mildly calcified cases, remained stable in 12 cases, and increased in 6 patients, (solely calcified plaques). Side effects (myalgia, fever) occurred in 4 patients; of these 2 patients withdrew from treatment. INF-alpha 2b given according to our regimen is at best usefull for the treatment of Peyronie's disease in the early, noncalcified stage during which it displays verifiable impact on the plaque treated and also helps alleviate the plaque-associated pain; but further dose-finding studies will have to be performed to identify clinically relevant treatment regimens.

Adult↗

Local vs Systemic Antibiotics to Decrease Wound Complications following Vertical Banded Gastroplasty: Results of a Prospective Randomized Trial.

BACKGROUND: Obesity is generally regarded as one factor predisposing to wound infection. Most reports of infection rates range from I to 16% for similar procedures. In our department the wound infection rate for morbidly obese patients was 12% without perioperative antibiotics. METHODS: In a prospective randomized study we compared local gentamicin-collagen fleece application in the subcutaneous layer with patients receiving a perioperative single I.V. dose of amoxicillin-clavulanic acid 2.2 g. We examined the results of different perioperative management of antibiotics on 50 morbidly obese patients who underwent vertical banded gastroplasty from March 1993 to August 1994. The fascial, subcutaneous and skin closure technique were identical in the two groups. For both groups we used a closed-suction system to drain the bottom of the deep subcutaneous layer. On the third postoperative day, the subcutaneous drains were removed. Patients stayed in hospital an average of 10 days. They had follow-up visits after 1, 3 and 6 months, and then yearly. RESULTS: None of the 50 patients developed a wound infection, hematoma, or seroma in the hospital. During the follow-up (median 6 months), no patient developed a wound abscess. CONCLUSIONS: We believe that perioperative antibiotic management is an important factor in obtaining a low infection rate.

Journal Article↗

Reverse redistribution on dynamic exercise and dipyridamole stress technetium-99m-MIBI myocardial SPECT.

Reverse redistribution on 201TI-chloride stress-redistribution myocardial scintigraphy has been associated with coronary artery stenosis. We report a patient whose two separate 99mTc-MIBI myocardial SPECT stress studies (dynamic exercise and dipyridamole) showed septal reverse redistribution and fixed inferior defect. Echocardiograms showed left ventricular (LV) hypertrophy and diffuse hypokinesis, especially in the inferior wall, and EKG showed LV hypertrophy and strain and inferior infarct. Coronary angiogram confirmed two-vessel disease involving 80%-90% stenosis of the proximal second diagonal branch of the left anterior descending artery and 75%-90% stenosis of the right coronary artery as well as global left ventricular dysfunction. Reverse redistribution on 99mTc-MIBI myocardial SPECT occurring on dynamic or dipyridamole stress may indicate damaged but viable myocardium.

Coronary Angiography↗

[Laser lithotripsy of the upper urinary tract].

Approximately 10% of all stone patients require an endoscopic stone treatment. With the advent of laserlithotripters a new technology became available, featuring extremely thin (200 microns) and flexible lithotripsy probes. As a consequence, miniscopes have been developed for endoscopic stone manipulation in the ureter. These miniscopes greatly facilitate ureteroscopy and expectantly will reduce complications associated with this procedure. The success rates of laserlithotripsy are in the 90% range, the only serious drawback are the high purchase costs of the laser. Independent from these new possibilities for intracorporeal lithotripsy, extracorporeal shockwave lithotripsy (ESWL) remains the first therapy of choice for ureteral calculi.

Adult↗

Conservative management of ovarian hyperstimulation syndrome.

OBJECTIVE: To evaluate the performance of a conservative treatment protocol for ovarian hyperstimulation syndrome (OHSS) that utilized low-dose dopamine, volume expanders and diuretics. STUDY DESIGN: Prospective, open trial. RESULTS: Thirteen patients met the criteria for diagnosis of severe OHSS during the study period. Two of these were in vitro fertilization (IVF) patients who did not undergo transfer and so were excluded from analysis. Of the remaining 11, 10 (91%) were pregnant. The average time for resolution of the OHSS and discharge from the hospital was 6 days (range, 2-11). Compared to levels at admission, there was no significant difference in those of sodium, potassium or creatinine after resolution of the syndrome. Hemoglobin and hematocrit, however, were significantly reduced (P < .03). There were no cases of adult respiratory distress syndrome or thrombosis. No pregnancies were interrupted. CONCLUSION: Conservative treatment of OHSS is an acceptable form of management. Risky and invasive therapies, such as paracentesis, are not warranted.

Adult↗

Efficacy of linsidomine chlorhydrate, a direct nitric oxide donor, in the treatment of human erectile dysfunction: results of a double-blind cross over trial.

Recent experimental work has demonstrated that nitric oxide (NO) is the neurotransmitter responsible for cavernous smooth muscle relaxation. Different studies on the performance of the direct NO-donor SIN-1 (linsidomine chlorhydrate) in patients with erectile dysfunction have come to conflicting results. We have performed a double-blind cross over trial in 40 patients with erectile dysfunction of mixed etiology comparing SIN-1, SIN-1 plus the alpha-blocker Urapidil, and prostaglandin E1 (PGE1) in order to determine the effectiveness of SIN-1. PGE1 achieved the best response, the combination of SIN-1 and Urapidil performed slightly, statistically insignificantly poorer with significantly increased side effects. SIN-1 alone performed statistically significantly (p < 0.0068) worse. SIN-1 is not a useful alternative to PGE1. The combination of SIN-1 and Urapidil performs equally as good as PGE1 but cannot be recommended due to intolerable side effects.

Adult↗

Assessment [correction of Asessment] of the brown Norway rat as a suitable model for the investigation of food allergy.

We have investigated the potential of the inbred Brown Norway (BN) rat as a model for food allergy using two different antigens, ovalbumin (OA) and semi-skimmed milk (SSM). The use of milk-free diet prior to and during exposure to SSM was a key factor in the induction of sensitisation to milk proteins. Investigation of dose received and timing of administration identified a sensitisation regimen using 500 micrograms SSM injected i.p. together with 1 mg CGN (adjuvant) on days 0 and 7 as the optimum conditions for induction of reaginic antibody production. In this model milk proteins were less allergenic than OA as the amount of SSM required to induce sensitivity was 20-fold greater. Examination of antigen-specificity of the IgG and reaginic antibody responses to a range of proteins, present in SSM, showed that the BN rats were capable of recognising a similar profile of allergens as those recognised by milk sensitive humans. Lactoferrin which is present in low concentrations in milk proved as allergenic as the major proteins in milk, the caseins and beta-lactoglobulin. These studies have identified conditions for induction of sensitisation to milk proteins, and have shown the antibody specificity of the response to be similar to that in man. This suggests that the BN rat could provide the basis of a model for the investigation of allergic reactions to food.

Animals↗

[Perinatal transmission of the human immunodeficiency virus in the second trimester of pregnancy].

BACKGROUND: A prospective study was carried out in pregnant women seropositive for HIV-1 who wished to interrupt the pregnancy with the aim of detecting the specific sequences of DNA in fetal blood obtained by cordocentesis during the second trimester of pregnancy. METHODS: The samples of fetal blood were obtained by cordocentesis with the Kleihauer's test being performed to discard contamination of maternal blood. In both maternal and fetal blood the HIV-1 antibodies, Western blot, p-24 antigen and hematologic parameters were determined. The DNA-HIV-1 sequences were determined by double PCR. Fifteen pregnant women were included in the study with one patient being excluded upon detection of contamination of fetal blood with maternal blood. In 8 cases the study could not be completed due to lack of material. RESULTS: The specific sequences of DNA of HIV were detected in the six pregnant women and in three of the six fetuses studied. The anti-HIV-1 antibodies were present in all the samples of maternal and fetal blood with the bands of antibodies by Western blot being identical for each mother-fetus pair. No differences were observed in the mother-fetus pair. No differences were observed in the hematologic parameters or in the lymphocytic subpopulations among the fetuses with positive DNA sequences and those which demonstrated a negative result. CONCLUSIONS: These preliminary results suggest that fetal infection by HIV-1 may be produced during pregnancy. Cordocentesis may be useful for determining the fetus which are infected in utero although this must be restricted to patients who wish to terminate the pregnancy due to the potential risk of infecting a previously healthy fetus.

Adult↗

Uptake and phototoxic effects of aluminum-chlorophthalocyanine (AlSPc) in human bladder carcinoma cells.

In vitro experiments were performed on human bladder carcinoma cells to evaluate the uptake of aluminum-chlorophthalocyanine (AISPc) and the subcellular target of phototoxicity. In order to quantify the correlation of intracellular uptake and incubation time and to identify the primary subcellular target of phototoxicity, fluorescence and absorption measurements have been carried out as well as electron microscopic studies. Absorption and fluorescence measurements showed the largest value after 24 h of incubation time. Fluorescence microscopic studies suggested the sensitizer to be located in a brighter patch within cytoplasm. Electron microscopic studies using DAB (3,3' diaminobenzidine) staining showed that the mitochondria are the primary target of phototoxic activity of AlSPc and that the majority of vacuoles of treated cells were originally mitochondria.

Carcinoma, Transitional Cell↗

Photodynamic therapy of human bladder carcinoma cells in vitro with pH-sensitive liposomes as carriers for 9-acetoxy-tetra-n-propylporphycene.

In vitro experiments were performed on human bladder carcinoma cells to evaluate the efficiency of the recently synthesized photosensitizer 9-acetoxy-tetra-n-propylporphycene (ATPPn) for photodynamic therapy. To improve cytoplasmic delivery of this hydrophobic compound, we prepared pH-sensitive liposomes composed of phosphatidylethanolamine (PE) and cholesteryl hemisuccinate (CHEMS) in comparison with pH-insensitive liposomes consisting of phosphatidylcholine (PC) and CHEMS. Dynamic light scattering measurements were used to monitor the acid-induced liposome destabilization. After incubation with liposome-bound ATPPn, bladder carcinoma cells were irradiated by a dye laser with increasing light fluence rates from 1 to 48 J/cm2. The photodynamic effects were then assessed from cell survival curves. No dark or phospholipid toxicity was measured for 2 micrograms ATPPn/1.5 ml medium. Qualitative cellular uptake of ATPPn was determined by fluorescence microscopy, while photodamage was elucidated by transmission and scanning electron microscopy. Absorption spectra performed up to 42 days revealed changes in shape for the pH-sensitive liposomes after storage at room temperature. ATPPn was proved to be an encouraging photosensitizer, capable of reducing cell survival to 0.1% after short-term incubation of 60 min with a drug dose of 2 micrograms ATPPn/1.5 ml medium. Although pH-sensitive PE/CHEMS liposomes showed significantly (P < 0.05) more photokilling effects at 24 J/cm2 and 48 J/cm2, no further advantages over non-pH-sensitive PC/CHEMS liposomes were found.

Carcinoma↗

A nonequilibrium radioimmunoassay for angiotensin II.

A method for the measurement of angiotensin II levels in dog plasma is described. The method is similar to previously published assays in that in couples gradient high-performance liquid chromatography (HPLC) with radioimmunoassay (RIA) and requires blood sample collection and processing to plasma in the presence of protease inhibitors. The unique feature of the present method is that it utilized a commercially available angiotensin II RIA run under nonequilibrium conditions. Performing the angiotensin II RIA under nonequilibrium conditions increased RIA sensitivity to allow for a minimal detectable limit of 0.75 pg/mL, a limit of detection not achievable with current commercially available RIAs. This lower limit of detection will now allow for the measurement of circulating levels of angiotensin II. Quality control pools of dog plasma fortified with 4.59-50 pg/mL angiotensin II were assayed and analytical recoveries (ARs) and coefficients of variation (CV) of 72.2%-111% and 3.67%-19.0% were observed for the respective pools.

Angiotensin II↗