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Biomedical subjects

M Hoffmann

Publications and source records attributed to M Hoffmann.

At least 37 records · Page 2Linked to original sources

Single photon emission and cerebral computerised tomographic scan and transcranial Doppler sonographic findings in eclampsia.

OBJECTIVE: To define more clearly the neuropathophysiology of eclampsia utilising single-photon emission computed tomography (SPECT), cerebral computerised tomography (CT) and transcranial Doppler (TCD) ultrasonography. DESIGN: A prospective study SETTING: The obstetric unit in King Edward VIII Hospital, a large tertiary referral centre in Kwa-Zulu Natal, South Africa. PARTICIPANTS: Sixty-five women with eclampsia. INTERVENTIONS: Imaging and ultrasonographic investigations were performed within 48 hours postpartum. Unenhanced cerebral CT scans were performed in all the women and SPECT scans were performed on 63 women using Technetium-99m-hexamethylpropyleneamineoxime (99mTc-HMPAO) as a tracer of regional cerebral blood flow. Middle cerebral artery blood flow velocity waveforms were measured using 2 MHz pulsed Doppler ultrasound via the transtemporal approach. MAIN OUTCOME MEASURES: Abnormalities in SPECT scan, CT scan and TCD ultrasound findings. RESULTS: SPECT scanning revealed perfusion deficits in the watershed areas in all women, 75% of whom had concomitant deficits in the parieto-occipital areas of the brain. Hypodensities (cerebral oedema) were reported in 38 CT scans (58.5%), with parieto-occipital involvement in 97.4% of cases. Increased flow velocity measurements in the middle and posterior cerebral arteries were recorded in 36 (85.7%) women in whom TCD ultrasound was performed. CONCLUSION: The pathophysiological mechanism of eclamptic seizures is primary cerebral vasospasm with resultant ischaemia and cerebral oedema involving mainly the watershed areas and parieto-occipital lobes of the brain. SPECT scanning has been shown to be superior to CT scanning and TCD ultrasonography in detecting neuropathophysiologic alterations in eclampsia. However, each of the three investigative tools provide its own unique information and all three are necessary research techniques to improve our understanding of the neuropathophysiological mechanism of eclamptic seizures.

Adolescent

High incidence of antibiotic resistance among bacteria in 4 intensive care units at a university hospital in Sweden.

The frequency of antibiotic resistance among bacteria in 4 intensive care units (ICUs) at a university hospital in Sweden was investigated annually from 1993 to 1996. An increase in ampicillin-resistant enterococci from 1993 to 1995 was seen which was due to a shift from Enterococcus faecalis to Enterococcus faecium. After a special infection control programme was instituted, the rate of ampicillin resistance among enterococci and the number of E. faecium isolates declined during 1996. The oxacillin resistance rates for Staphylococcus aureus were < or = 2%, while most of the coagulase-negative staphylococci (CNS) were oxacillin resistant. No vancomycin-resistant enterococci or staphylococci were seen. The ciprofloxacin resistance rate for CNS and Enterococci spp. were high. Relatively, high levels of resistance to cefotaxime and piperacillin/tazobactam among Enterobacter spp. were also seen. During 1995 and 1996 Pseudomonas aeruginosa showed increasing resistance to ceftazidime, ciprofloxacin and piperacillin/tazobactam. This was due to an outbreak among rather few patients. The overall resistance rates for Gram-negative bacteria were low for aminoglycosides and imipenem. From 1993 to 1996 the total antibiotic consumption decreased by 27% in the whole hospital and 16.5% in the ICUs. However, the reduced antibiotic consumption was paralleled with a 23% decrease in the total number of patients treated in the hospital from 1993 to 1996. In contrast there was an 11.5% increase in the number of ICU patients treated during this period. The conclusion is that all ICUs within a hospital should have a programme for 'on-line' antibiotic resistance surveillance of drugs used in that unit in order to change the empiric treatment when there is an increase in antibiotic resistance. It is also important to survey the antibiotic consumption in the ICUs in order to avoid further selective pressure on bacteria showing increased resistance rates.

Anti-Bacterial Agents

[Do low-threshold detoxification units reach new groups of the drug dependent?].

The conventional form of detoxication for illicit drug users in German psychiatric hospitals is an inpatient treatment approach connected with high admission prerequisites. These demand a high stage of motivational compliance from of the patients, e.g. the determination to continue with long-term treatment aiming at a life free of drugs. This strategy is termed "high-threshold" approach. A new form of inpatient treatment is the "low-threshold" approach offering intervals of some days or weeks free of drugs to illicit drug users, supported by professional detoxication strategies. This study compares client characteristics of illicit drug users treated at "high-threshold" vs. "low-threshold" units. A new subpopulation of clients could be reached who are more advanced in their drug intake careers and less influenced by social pressure to enter treatment. The differences in clients treated can be explained rather by differences in admission prerequisites than by a more balanced distribution of sexes in the newly introduced detoxication programme.

Adult

Prospective study of extraction atherectomy in patients with acute myocardial infarction.

Although percutaneous transluminal coronary angioplasty (PTCA) has been an effective treatment for primary reperfusion in acute myocardial infarction, patients with thrombolytic ineligibility, thrombolytic failure, cardiogenic shock, and vein graft occlusion remain at high risk for complications with PTCA treatment. The transluminal extraction catheter may be useful for treatment for such patients owing to its ability to aspirate thrombus. At 2 clinical centers, extraction atherectomy was prospectively evaluated in 100 patients (age 62 +/- 10 years). High-risk features included thrombolytic failure in 40%, postinfarct angina in 28%, presence of angiographic thrombus in 66%, presence of cardiogenic shock in 11%, and a saphenous vein graft occlusion in 29%. Procedural success, defined as a final residual stenosis <50% and Thrombolysis in Myocardial Infarction 2 or 3 grade flow, was seen in 94%. Events during the hospitalization included death in 5%, bypass surgery in 4%, and blood transfusion in 18%. In a substudy, patients enrolled at William Beaumont Hospital (n = 65) underwent elective predischarge angiography, which revealed a patent infarct-related vessel in 95%. These patients were also followed for 6 months with angiographic follow-up in 60%. Target vessel revascularization was necessary in 38%, and 6-month mortality was 10%. Although long-term vessel patency was 90%, angiographic restenosis occurred in 68%. Acute myocardial infarction patients can be treated with extraction atherectomy with a high technical success rate and a low incidence of complication. Infarct artery patency at 1 week and 6 months was excellent; however, angiographic restenosis remains a problem. Extraction of thrombus in this high-risk group of patients is associated with low in-hospital mortality and a high rate of vessel patency at 6 months.

Angina Pectoris

Melatonin and deprivation myopia in chickens.

Chicken eyes elongate and become myopic if they are covered with translucent diffusors which degrade the retinal image ('deprivation myopia'). Since it has been shown that dopamine D2/D4 receptors (which mediate inhibition of melatonin synthesis) are also implicated in deprivation myopia, we have studied the role of melatonin in the visual control of eye growth. We have found that (1) diurnal melatonin rhythms and melatonin content in the retina are unchanged during deprivation myopia development despite the breakdown of both diurnal growth rhythms of the eye and diurnal rhythms in retinal dopamine metabolism, (2) diurnal melatonin rhythms and melatonin content in the retina remain unchanged after application of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) and presumably also after 6-hydroxydopamine (6-OHDA) application which both have a suppressive effect on deprivation myopia and (3) deprivation myopia was slightly reduced in both eyes after unilateral intravitreal injection of melatonin, despite that deprivation myopia is based on a mechanism intrinsic to the eye. We conclude that melatonin is not involved in the retinal signaling pathway translating visual experience to deprivation myopia.

5,7-Dihydroxytryptamine

The C terminal tail of the histamine H2 receptor contains positive and negative signals important for signal transduction and receptor down-regulation.

To examine the role of the C terminal tail in H2 receptor regulation, three cDNAs, encoding truncated histamine H2 receptor mutants (H2T295, H2T307, and H2T341), were constructed and stably transfected in Chinese hamster ovary (CHO) cells. The amino acids before position 307 appear to be necessary for proper receptor transport or folding, as no detectable H2 receptor binding of the H2T295 was observed after transfection. Truncation of the C terminal tail by 51 amino acids (H2T307) did not affect the binding properties of H2 antagonists and histamine or histamine-induced signaling. Yet, removal of 17 amino acids generated a mutant receptor (H2T341), which was able to form a ternary complex but was unable to fully activate the Gs protein on histamine exposure. Agonist-induced but not the cyclic AMP-dependent H2 receptor down-regulation was more profound for the H2T307 receptor, indicating that different structural elements of the H2 receptor protein are involved in the cyclic AMP-dependent and independent pathways of H2 receptor down-regulation. Taken together, in this study we identified regions in the C terminal tail of the H2 receptor that act as positive and/or negative signals in H2 receptor signaling and down-regulation.

Amino Acid Sequence

The cell surface marker phenotype of macrophages from HIV-1-infected subjects reflects an IL-10-Enriched and IFN-gamma-deprived donor environment.

T cells depend on costimulation by accessory cells for an immune response. Costimulatory macrophage activity involves the expression of B7 molecules whose expression is upregulated by interferon-gamma (IFN-gamma) and downregulated by interleukin-10 (IL-10). The expression of low-affinity Fc gamma IIIR (CD16), in contrast, is upregulated in the presence of IL-10 and downregulated in the presence of IFN-gamma. In human immunodeficiency virus-1 (HIV-1) infection, the balance between IFN-gamma and IL-10 expression shifts toward IL-10 predominance. Herein, we compare B7 and CD16 macrophage phenotypes from healthy and from HIV-1-infected patients. Patient macrophages express B7 molecules in lower density than macrophages from healthy donors and are resistant to the upregulation of costimulatory molecule expression. B7 expression can be normalized in patient macrophages by treating them with anti IL-10 monoclonal antibodies (mAb) and IFN-gamma together but not by treatment with either anti-IL-10 mAb or IFN-gamma alone. This finding suggests an excess of IL-10 in HIV-1 infection and an IFN-gamma deficiency, consistent with previous cytokine assessments in HIV-1-infected subjects. The upregulation of CD16 expression was readily induced in patient macrophages by treatment with IL-10 and was inhibited by treatment with IFN-gamma. CD16 expression identifies the subset of cytotoxic macrophages that has been shown to destroy CD4T cells, which they target through CD4-reactive immune-complexed HIV-1 envelope molecules.

Acquired Immunodeficiency Syndrome

Randomised study assessing the effect of phenytoin and magnesium sulphate on maternal cerebral circulation in eclampsia using transcranial Doppler ultrasound.

OBJECTIVE: To assess maternal middle cerebral artery flow velocity patterns as measured by transcranial Doppler ultrasound (TCD) in eclampsia and to investigate the effect of the anticonvulsants magnesium sulphate (MgSO4) and phenytoin on cerebral circulation. DESIGN: Prospective randomised study. SETTING: High care obstetric unit, King Edward VIII Hospital, Durban, South Africa. PARTICIPANTS: Twenty-four eclamptic patients: 13 received MgSO4 and 11 phenytoin. INTERVENTION: Middle cerebral artery flow velocity waveforms were measured using 2 MHz pulsed Doppler ultrasound via the transtemporal approach in eclamptic patients, before and 15 minutes after the loading dose of anticonvulsant. RESULTS: Magnesium sulphate significantly reduced the pulsatility index (P = 0.002) and mean flow velocity (P = 0.02) in the middle cerebral artery, whereas phenytoin failed to produce any statistically significant effect. However, differences between groups were not statistically significant. Systolic and diastolic blood pressures were reduced in both the MgSO4 and phenytoin groups. CONCLUSION: These findings provide firm evidence that MgSO4 relieves cerebral vasospasm, compared with phenytoin, and may therefore be the better drug for the prevention of eclamptic convulsion.

Adolescent

Cell-matrix interactions of normal and transformed human keratinocytes in vitro are modulated by the synthetic phospholipid analogue hexadecylphosphocholine.

We have investigated the effect of the synthetic phospholipid analogue, hexadecylphosphocholine (HePC), a member of a new class of membrane-affecting antiproliferative drugs, on adhesion to extracellular matrix components, reorganization of three-dimensional collagen lattices, and proliferative activity of human keratinocyte populations in vitro. Six transformed keratinocyte lines were compared with their normal counterparts from interfollicular epidermis. Adhesion to collagen types I and IV, laminin, and fibronectin was weakest in normal keratinocytes (binding of 3-10% of the cells), followed by HaCaT and HaCaT-II/3 (25-30% binding), and the squamous carcinoma lines and SV-40 transformed keratinocytes (35-50% binding). Treatment with non-toxic doses of 10-20 mumol/l HePC led to a clear inhibition of the adhesive interactions by 50-75% in all populations. The impaired adhesion capacity was paralleled by a clear decrease of the ability of all keratinocyte populations to contract three-dimensional collagen lattices, an experimental model system for the reorganization of extracellular matrices. Histological examination revealed that these effects were due to a reduced cell number in the collagen lattices, a finding underscored by significant inhibition of proliferative activity of all keratinocyte populations by HePC. Furthermore, HePC led to marked changes of cellular morphology in the contracted gels. FACS analysis revealed that the impaired interaction with components of the extracellular matrix was not due to a specific downregulation of beta 1-integrins, the major cell-surface receptors for the respective matrix proteins. In conclusion, our results provide new insights into the potential action of HePC in a variety of skin disorders. Decreased proliferative activity and changes of cellular morphology, combined with impaired interactions with extracellular matrix proteins and a consecutive loss of matrix organization capacity, may cause suppression of different hyperproliferative skin diseases.

Antineoplastic Agents

Comparative results of transluminal extraction coronary atherectomy in saphenous vein graft lesions with and without thrombus.

OBJECTIVES: The purpose of this retrospective study was to compare the results of transluminal extraction coronary atherectomy in saphenous vein graft lesions with and without angiographic thrombus. BACKGROUND: Percutaneous interventions in lesions with thrombus are associated with reduced procedural success and increased risk of complications. Use of the transluminal extraction catheter, which cuts and aspirates atheroma and thrombus, has been advocated as a potential revascularization strategy for lesions with thrombus. METHODS: Baseline patient characteristics, lesion morphology, immediate angiographic results, in-hospital complications and follow-up were prospectively entered into an interventional cardiology data base. The results of transluminal extraction coronary atherectomy in saphenous vein bypass grafts with angiographic thrombus were compared with results in similar grafts without angiographic thrombus. RESULTS: Transluminal extraction coronary atherectomy was performed in 175 patients with 183 vein graft lesions, including 59 lesions (32%) with thrombus (Group 1) and 124 (68%) without thrombus (Group 2). Compared with lesions in Group 2, lesions in Group 1 were associated with a higher incidence of baseline total occlusion, diffuse disease and abnormal Thrombolysis in Myocardial Infarction (TIMI) grade flow (p < 0.05); more severe diameter stenosis at baseline, after atherectomy and after final angiography (p < 0.05); a lower rate of clinical success (69% vs. 88%, p < 0.01); and more angiographic and clinical complications, including no reflow (p < 0.05), vascular repair (p < 0.05) and Q wave myocardial infarction (p = 0.09). CONCLUSIONS: In transluminal extraction coronary atherectomy of saphenous vein bypass grafts, the presence of thrombus is associated with more baseline lesion complexity, reduced clinical success and increased risk of no reflow, Q wave myocardial infarction and vascular repair.

Aged

[Chronic treatment refractory osteomyelitis of long tubular bones--possibilities and risks of intramedullary boring].

Osteomyelitis of long bones is a severe complication of fracture healing. If on-going infection occurs despite reoperation and if antibiotic treatment is of no benefit, reaming of the medullary canal has been considered beneficial. We investigated long-term follow-up (minimum 2 years) in patients submitted to reaming of the medullary canal to evaluate the efficacy of this method. Criteria for success were: no recurrence and no further antibiotic treatment necessary. Of 37 patients, 32 were followed up (mean duration after reaming, 3.7 years). The mean number of surgical operations for osteomyelitis prior to reaming was 3.2. In 88% of patients a full range of motion was observed upon reexamination, while in the others stiffness attributable to articular injuries that had been sustained preoperatively was still present. We found that 84.3% of patients were working in the same profession as prior to the fracture, 72% were involved in sport again, and 97% of patients were pain free. One otherwise healthy patient suffering from sclerosing osteitis (Garré) died of bone marrow embolism into the lung during reaming of the femur. Reaming of the medullary canal has a high cure rate in osteomyelitis even after several previous treatment attempts with surgical revision and/or antibiotic medication. The mechanism is most probably based on improvement of local perfusion. During surgery care must be taken not to provoke pulmonary embolization. Intraoperative monitoring by pulmonary artery catheter should be performed; reaming should be discontinued immediately, if a rise in of pulmonary artery pressure occurs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent