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J Herman

Publications and source records attributed to J Herman.

At least 73 records · Page 4Linked to original sources

Mechanisms of inactivation of E-cadherin in breast cancer cell lines.

Loss of E-cadherin (CDH1) function is thought to contribute to progression in breast cancer and other solid tumors by increasing proliferation, invasion, and/or metastasis. In some cases, the restoration of CDH1 function may be an important therapeutic option. This possibility will depend on the mechanism by which CDH1 is inactivated. Here we present analyses of CDH1 expression, genetic mutation, and promoter methylation in CDH1 in 10 commonly used breast cancer cell lines. Five cell lines (BT-474, MCF-7, MDA-MB-361, MDA-MB-468, and T-47D) expressed CDH1 and were genetically normal. Five others (SK-BR-3, 600 MPE, MDA-MB-134 IV, CAMA1, and MDA-MB-435) did not express CDH1. Fluorescence in situ hybridization analyses of each of these cell lines showed evidence for the physical deletion of one allele of CDH1, and three cell lines were found to carry homozygous deletions. SK-BR-3 was deleted from exon 12 through the promoter; exon 6 was deleted in MDA-MB-134 IV cells, and 600 MPE cells carried a 21-bp deletion in the splicing acceptor site for exon 9. CAMA1 seemed to have been inactivated through promoter methylation. No explanation was found for the inactivation of CDH1 in MDA-MB-435.

Alleles↗

Documenting acute care nurse practitioner practice characteristics.

Acute care nurse practitioners are functioning in a health care system that is changing rapidly. Simultaneously, the ACNP role is evolving. It is imperative that ACNPs document practice characteristics to communicate effectively within the health care system. The purpose of this article is to describe the process of documenting ACNP practice. Content includes rationale for documenting ACNP practice characteristics, a description of types and sources of data to collect, a discussion of barriers to documentation, and a format for a documentation tool.

Acute Disease↗

Shortcomings of the randomized controlled trial: a view from the boondocks.

The randomized controlled trial (RCT), despite its well-known limitations, continues to be regarded as a gold standard in determining whether an intervention does more harm than good. Some recent evidence suggests that it tends to overvalue the modalities it tests. Moreover, the accuracy with which the disorder under consideration is diagnosed can be critical to the performance of a new intervention designed for it. When technological progress allows us to diagnose milder instances, some therapies, possibly useful in dire circumstances, will appear ineffective if most of a trial population is at low risk. Human individuality makes it impossible to duplicate a RCT. As a result, Popper's criterion of falsifiability may not be met and so the carrying out of a large-scale therapeutic experiment may not be a scientific activity. Finally, it is doubtful whether group probabilities derived from RCTs can be safely applied to individuals. These and other reservations concerning the applicability of the RCT to clinical practice are discussed.

Evidence-Based Medicine↗

[The changing clinical picture of gastroduodenal ulcer disease].

OBJECTIVE: The authors evaluate the changing clinical picture of gastroduodenal ulceration in recent years. METHOD: They analysed their own clinical material from January 1994 till April 1998 when at the Second Surgical Clinic in Olomouc 188 patients were hospitalised on account of gastroduodenal ulceration. RESULTS: The group of patients comprised a high proportion of patients above 60 years of age (102, i.e. 55%) and twice as many cases of duodenal ulcers as compared with gastric ones. In 4% ulcers were present at both sites. In 92% (173 patients) acute admissions were involved and only in 8% (15 patients a planned admission for elective treatment was involved. As to complications haemorrhage was most frequent (84%), perforations in 13% and pylorostenosis in 3%. Of the acute admissions 56 patients were operated, i.e. 32%, the rest were treated by conservative methods. The surgical lethality was 12%, the lethality of the conservatively treated patients 5%. CONCLUSION: Gastroduodenal ulceration is at present characterised by a predominance of conservative treatment, a decline of elective operations, a high percentage of complications in particular in advanced age, more frequent affection of the duodenum and late indication for surgery, when conservative treatment is not very successful.

Adolescent↗

[Chronic venous insufficiency--a mini-invasive therapeutic approach].

The authors describe their own experience assembled with treatment of chronic venous insufficiency. During the period from VII/95 to III/98 they operated 257 patients with diseases of the venous system. In 22 patients (8%) they operated 24 times by miniinvasive procedures. Eight times retroperitoneoscopic lumbar sympathectomy and sixteen times endoscopic subfascial dissection of the perforators was performed. The remaining patients (92%) were treated by classical operations of the superficial venous system.

Adult↗

Medicine and evolution: time for a new paradigm?

The theory of Evolution is being invoked frequently in medicine to account for counter-intuitive findings such as programmed cell death in congestive heart failure and the fact that fever can prove both blessing or curse, depending on the circumstances. These and other examples of what might be called maladaptive adaptations are discussed, and it is suggested that human development may have reached a stage where the roles of mutation and selection are drastically changed. By creating an environment both mutagenic and protective, we have altered the balance between the two great driving forces of evolution, increasing the frequency of mutations and reducing the need for adaptation. As a result, new diseases have arisen and the whole evolutionary process seems to have lost some of its benevolence, no longer insuring the survival of the fittest. We must entertain the possibility that Darwin's theory cannot explain the last few millennia of human evolution and is now useful chiefly as an approximation applicable to very long periods of time.

Animals↗

Advancing the standards of clinical research: the urgent need for new methods and better data.

Some of the weaknesses of the randomized controlled trial (RCT) are pointed out, among them unavoidable biases, the possibility of coming to erroneous conclusions by the 'luck of the draw' and the fact that most such experiments lack a doctor/patient relationship and are of little assistance in clinical decision making. An exaggerated propensity on the part of the medical profession to regard the RCT as the only 'scientific' method for research into therapeutics is noted. The potential advantages of post-marketing surveillance of new interventions in a physician-centred manner are outlined. Such a data base could ultimately be expanded into a data base that records all activity in a given practice. The PACE strategy, employed by haematologists in the north of England, and the sentinel practice primary care research networks used by family doctors contain elements of the system proposed here. However, each possesses disadvantages that limit its applicability to special cases. Random choice of practices for any particular observational study of a new intervention could lend it some of the features of an experiment.

Bias↗

An instance of sleep paralysis in Moby-Dick.

It is suggested that picturesque medical conditions can, at times, be encountered in literary works composed prior to their clinical delineation. This is true of sleep paralysis, of which the first scientific description was given by Silas Weir Mitchell in 1876. A quarter of a century earlier, Herman Melville, in Moby-Dick, gave a precise account of a case, including the predisposing factors and sexual connotations, all in accord with modern theory. The details of Ishmael's attack of sleep paralysis, the stresses leading up to it, and the associations causing him to recall the experience are given here.

Humans↗

National Delphi study to determine competencies for nursing leadership in public health.

PURPOSE: To identify competencies needed by nurse leaders in public health programs. DESIGN: Five-round national Delphi. SAMPLE: Convenience sample of members of major public health nursing associations and nurse and non-nurse public health leaders in the USA. METHODS: Mailed survey in 1994-1995 using a modified snowball technique based on a modification of the Pew Foundation health professions' competencies for Round 1. Four additional rounds produced consensus. FINDINGS: Initially, 62 competencies were identified. Factor analysis resulted in four factors: political competencies, business acumen, program leadership, and management capabilities; 57 competencies were clustered in the four groupings and accounted for 91.4% of the variance. CONCLUSIONS: Graduate schools in nursing and public health must prepare students with broad-based competencies from a variety of disciplines. Findings of this national survey provide a database for curriculum development and evaluation of programs to prepare nurse leaders for roles in public health-based delivery systems.

Curriculum↗

The effects of artificial lung inflation on pulmonary blood flow and heart rate in the turtle Trachemys scripta.

As for most ectothermic vertebrates, the breathing pattern of turtles is episodic, and pulmonary blood flow (Qpul) and heart rate (fH) normally increase several-fold during spontaneous ventilation. While some previous studies suggest that these cardiovascular changes are caused by stimulation of pulmonary stretch receptors (PSRs) during ventilation, it has been noted in other studies that blood flows often change prior to the initiation of breathing. Given the uncertainty regarding the role of PSRs in the regulation of central vascular blood flows, we examined the effect of manipulating lung volume (and therefore PSR stimulation) on blood flows and heart rate in the freshwater turtle Trachemys scripta. Turtles were instrumented with blood flow probes on the left aortic arch and the left pulmonary artery for measurements of blood flow, and catheters were inserted into both lungs for manipulation of lung volume. In both anaesthetized and fully recovered animals, reductions or increases in lung volume by withdrawal of lung gas or injection of air, N2, O2 or 10% CO2 (in room air) had no effect on blood flows. Furthermore, simulations of normal breathing bouts by withdrawal and injection of lung gas did not alter Qpul or fH. We conclude that stimulation of PSRs is not sufficient to elicit cardiovascular changes and that the large increase in Qpul and fH normally observed during spontaneous ventilation are probably caused by a simultaneous feedforward control of central origin.

Animals↗

Stability of nucleoside triphosphate levels in the red cells of the snake

Nucleated red cells in the nonpregnant garter snake (Thamnophis elegans) contain relatively high concentrations of nucleoside triphosphate (NTP), largely in the form of ATP, which is found at concentrations of approximately 10 mmol l-1 relative to cell volume and 15 mmol l-1 relative to cell water. During pregnancy, levels of NTP in adult red cells rise by approximately 50 % concomitant with an increase in blood progesterone level. The stability of the NTP pool within these red cells was assessed by maintaining cells in vitro at 20 °C, without exogenous nutrients, and in the presence and absence of the metabolic inhibitors iodoacetate and/or cyanide. After 96 h, NTP levels in adult red cells not exposed to the inhibitors had decreased by only approximately 10 %, while in the presence of both inhibitors NTP levels had fallen by less than 50 %. Red cell NTP levels were not affected by acute exposure to high concentrations of progesterone either in vivo or in vitro. NTP levels were much more labile when the cells were maintained in vitro at either low or high pH. Maintenance of red cells at pH 6.0 for 24 h resulted in a decrease in NTP levels of approximately 50 % and at pH 10.0 the levels fell by approximately 80 %, while buffers containing only ATP caused no detectable degradation. Incubation at low or high pH promoted some cell swelling; however, the magnitude of the decreases in intracellular NTP concentration prompted by these pH levels could not be mimicked by incubation of red cells in hypotonic buffer. Total nonspecific ATPase activity at pH 6.0 was approximately 55 % greater than that at pH 7.4, while at pH 10.0 it was approximately 6 % of that at pH 7.4. The pH-dependent decrease in intracellular NTP levels cannot, therefore, be due to stimulation of ATPase activity, at least not at high pH. Overall, the data are consistent with the hypothesis that an appreciable portion of the NTP within these cells is compartmentalized in a stable, but pH-sensitive, pool sequestered from intracellular ATP-hydrolyzing processes.

Journal Article↗

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Addison Disease↗

Impact of growth hormone treatment on a Belgian population of short children with renal allografts.

We retrospectively analyzed the effects of recombinant human growth hormone (rhGH) in a Belgian population of 36 short children with renal allografts. Seven children were dropped from the growth study: 1 had skeletal dysplasia and in 6 cases rhGH was given for less than 1 yr (1 died, 1 developed genu valgum, 2 were non-compliant and 2 grafts deteriorated). Final height was reached in 17 patients, and 12 children were still growing at the end of the study. Median height standard deviation score (SDS) in the 29 patients was -2.3 at the time of transplantation, and -2.7 when rhGH therapy was initiated. During rhGH therapy (median duration 3.2 yr, range 0.6-7.7 yr), height SDS increased by a mean of 0.4 per year, and bone maturation was not accelerated. Final height reached was 162.7 (149.0-169.5) cm (median SDS -1.8) in males and 151.0 (130.5-169.5) cm (median SDS -1.9) in females. Final height is significantly greater in males than females compared with a historical control group of untreated patients. Final height is within the parental target height range in 6 out of the 17 patients. The increase in height SDS in patients who were at an advanced stage of puberty (Tanner stages 4-5) when rhGH therapy was initiated exceeded our expectations (mean height gain 14.2 cm in boys and 10 cm in girls). In the cohort of 36 children, 4 patients developed an acute allograft rejection, all of whom had an underlying chronic rejection. This resulted in 3 graft losses within 5 yr. Our results indicate that rhGH treatment has a positive effect in short children with renal allografts, even if it is started in late puberty. In the presence of underlying chronic rejection, rhGH treatment needs careful monitoring to minimize the risk of graft loss.

Adolescent↗

55-base pair deletion in certain patients with Gaucher disease complicates screening for common Gaucher alleles.

Mutations in the glucocerebrosidase gene which result in Gaucher disease can originate from the highly homologous glucocerebrosidase pseudogene. A 55-bp deletion in exon 9, which corresponds to a 55-bp segment absent from the pseudogene, has been identified in patients with Gaucher disease. We have developed a simple polymerase chain reaction (PCR)-based method to detect this 55-bp deletion, and have found this mutation in 3 of 75 DNA samples (4%) collected from patients with Gaucher disease. Commonly used PCR-based screening methods for specific Gaucher mutations frequently make use of primers either within or surrounding the 55-bp gap to selectively distinguish the glucocerebrosidase gene from the pseudogene. However, if the 55-bp deletion in exon 9 occurs, primers will either fail to produce an amplification product or will produce a shortened product which will be falsely attributed to the pseudogene. This could lead to inaccurate genotyping and genetic counseling for some Gaucher patients and their families. We therefore recommended that laboratories using PCR-based screening techniques involving primers in this region initially determine whether this 55-bp sequence is present.

Alleles↗