[Initiatives to increase the efficiency of dermatological patient care].
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Dermatology↗
Biomedical subjects
J de Haan
Publications and source records attributed to J de Haan.
Time-dependent hierarchical regulation analysis: deciphering cellular adaptation.
Cells adapt to changes in their environment by the concerted action of many different regulatory mechanisms. Examples of such mechanisms are feedback inhibition by intermediates of metabolism, covalent modification of enzymes and changes in the abundance of mRNAs and proteins. These mechanisms act in parallel at different levels in the cellular hierarchy while regulating a single process. Existing hierarchical regulation analysis determines the relative importance of these mechanisms when the cell regulates a transition from one steady-state to another. Here, the analysis is extended to the regulation of time-dependent phenomena, for which two methods are introduced and illustrated with a kinetic model incorporating transcription and translation of metabolic enzymes.
Adaptation, Physiological↗
Teledermatology reduces the number of patient referrals to a dermatologist.
During a two-year study, 505 teledermatology consultations were carried out on 503 patients of 29 participating general practitioners (GPs) in the province of Friesland. One overview and two detail digital photographs of the skin problems were taken on a digital camera and attached to an email message containing standard clinical information. These email messages were sent to a dermatologist, who replied by email after evaluation. After a median follow-up time of 548 days, the GPs were interviewed about the dermatological referrals. The reduction in referrals was 51% (0.95 confidence interval = 47-58%) when the GP had the intention to refer. When the GPs had no intention to refer, there turned out to be a secondary traditional consultation in 17% of cases. The reduction of 51% of referrals after store-and-forward teledermatology consultation was similar to that seen in other studies of videoconferencing. Consultation using digital store-and-forward teledermatology by the GP can halve the number of referrals to a dermatologist for selected patients.
Adolescent↗
[Teledermatological consultation].
Teledermatological consultation can be effected in two ways. One is 'store-and-forward' which involves storing photographic digital images and sending them to a consultant dermatologist who then replies by e-mail, and the other is by videoconferencing using a real time interactive audiovisual link. In daily general practice the first method is the easiest to implement. In 76-90% of cases, a diagnosis or differential diagnosis made in this way corresponds with the diagnosis made at the more usual face-to-face examination. The advantage of teledermatological consultation is that diagnosis and therapy take place faster than after regular referral and it is better than no referral at all. The referring physician should deliver data on the patient's history and physical examination in a standardized format. The same is true for the encoded personal data, the working diagnosis, and referral request. One overview and 2 detailed photos from two angles are normally taken. The overview shows the extent and localization of the skin abnormality. The patient has to consent to a teledermatological consultation. The responsibility for the treatment lies with the doctor who sees the patient face-to-face. The data that is transmitted must be encrypted or coded in such a way that it cannot be traced back to one particular person.
Adult↗
Defective mismatch repair and the development of recurrent endometrial carcinoma.
OBJECTIVE: To investigate whether defective DNA mismatch repair (MMR) defines a subgroup at risk for recurrence in sporadic endometrial carcinoma patients. METHODS: Primary tumors from 44 patients with recurrent stage I endometrial carcinoma were compared after matching, with tumors of 44 patients being free of recurrence for minimal 3 years. Paraffin-embedded primary tumors (n = 88) and recurrent tumors (n = 32) were subjected to immunohistochemical analysis for hMSH2 and hMLH1 expression. Subsequently, a staining index (SI = 0-9) was calculated based on staining intensity and quantity. DNA was extracted from paraffin-embedded tissues, and promoter methylation of hMLH1 was determined by nested methylation-specific PCR (MSP). Microsatellite instability (MSI) was assessed by BAT-26 or BAT-25. RESULTS: Low hMSH2 expression was observed in 2% of primary tumors of control patients without recurrence, 14% of primary tumors of patients with recurrence, and 0% of recurrent tumors. Low hMLH1 expression was observed in 32%, 19%, and 22%, respectively. hMLH1 gene promoter methylation was detected in 50%, 47%, and 32%, and MSI was found in 16%, 14%, and 30%, respectively. No significant differences were found between primary tumors of patients with and without recurrence with respect to hMSH2 and hMLH1 expression, hMLH1 promoter methylation, and MSI. When primary and recurrent tumors were compared, there was an increased correlation of hMLH1 methylation with low hMLH1 expression and MSI in recurrent tumors. CONCLUSION: MSI, hMLH1 promoter methylation, and the expression of hMLH1 and hMSH2 are not predictive for the development of recurrent stage I endometrial carcinoma. In the progression of tumor, "de novo" hMLH1 methylation rarely occurs, instead there is further derailment of the MMR pathway in affected tumors.
Adaptor Proteins, Signal Transducing↗
Mortality and early neonatal morbidity in vaginal and abdominal deliveries in breech presentation.
From January 1984 to June 1986, 268 consecutive breech presentations in two university hospitals were studied prospectively. Vaginal delivery was attempted in all cases, under expert supervision and electronic monitoring, except in the presence of clear-cut contraindications. For most of the examined parameters no statistically significant differences were found in mortality and morbidity between the vaginally delivered group and the caesarean section group in three birth weight categories. Regarding mortality a relation with the mode of delivery was demonstrable in two cases in the vaginal group and one case in the caesarean section group in the low and very low birth weight category. In the 500-1499 g birth weight category, underestimation of the birth weight during pregnancies led to iatrogenic neonatal death in two cases. Our study shows that the management of breech presentation can be modified in order to stop the increase in caesarean section rate and diminish the degree of variation in operative delivery without affecting the perinatal outcome.
Belgium↗
Posterior approach for the simultaneous, bilateral thoracoscopic sympathectomy.
If there is an indication for sympathectomy in the case of severe hyperhidrosis or rubeosis, in our opinion the posterior approach is preferable because of the advantages in surgical technique and anesthesia. Bilateral treatment can be accomplished in a single admission, with all the concomitant advantages.
Adolescent↗
Increased infarct size and exacerbated apoptosis in the glutathione peroxidase-1 (Gpx-1) knockout mouse brain in response to ischemia/reperfusion injury.
Glutathione peroxidase is an antioxidant enzyme that is involved in the control of cellular oxidative state. Recently, unregulated oxidative state has been implicated as detrimental to neural cell viability and involved in both acute and chronic neurodegeneration. In this study we have addressed the importance of a functional glutathione peroxidase in a mouse ischemia/reperfusion model. Two hours of focal cerebral ischemia followed by 24 h of reperfusion was induced via the intraluminal suture method. Infarct volume was increased three-fold in the glutathione peroxidase-1 (Gpx-1) -/- mouse compared with the wild-type mouse; this was mirrored by an increase in the level of apoptosis found at 24 h in the Gpx-1 -/- mouse compared with the wild-type mouse. Neuronal deficit scores correlated to the histologic data. We also found that activated caspase-3 expression is present at an earlier time point in the Gpx-1 -/- mice when compared with the wild-type mice, which suggests an enhanced susceptibility to apoptosis in the Gpx-1 -/- mouse. This is the first known report of such a dramatic increase, both temporally and in level of apoptosis in a mouse stroke model. Our results suggest that Gpx-1 plays an important regulatory role in the protection of neural cells in response to the extreme oxidative stress that is released during ischemia/reperfusion injury.
Animals↗
[Decision making concerning very old patients with deteriorating health living at home].
A woman aged 87 and three men aged 87, 86 and 83, respectively, lived at home or in an old-people's home, in poor physical condition due to old age and diseases such as COPD and heart failure. One man was demented, the others did not wish hospital admission in case of further deterioration. When the condition worsened due to infections and fractures, the GP to a limited extent performed diagnostics and treatment. The four patients died, three of them after admission and intensive treatment because the restricted policy had not been communicated clearly. In decision-making about the management of geriatric patients, it is important that the GP knows the patient's wishes, correctly assesses his physical condition and prognosis and communicates well with the patient's next of kin and other care-givers.
Advance Directives↗
Laparoscopic elective treatment of diverticular disease. A comparison between laparoscopic-assisted and resection-facilitated techniques.
BACKGROUND: Because of the presence of significant inflammatory reaction, elective surgical laparoscopic-assisted treatment of complicated diverticular disease can be difficult, leading to a high conversion and complication rate. Laparoscopic alternatives to this assisted approach consist of the hand-assisted method and the more conventional facilitated laparoscopic sigmoid resection. Facilitated laparoscopic sigmoid resection implies laparoscopic mobilization of the sigmoid as much as possible and splenic flexure when called for. Through a Pfannenstiel incision, the difficult steps of the operation-such as the dissection of the inflammatory process and taking down the fistula, but also resection and manual anastomosis-can be performed. In this study, we compare the operating time, conversion rate, complications, and costs of both assisted and resection-facilitated techniques. METHODS: We compared two consecutive series of 35 patients with diverticular disease who underwent a sigmoid resection by laparoscopy. Both groups were comparable in terms of age, gender, and kind of complicated diverticular disease. RESULTS: The operating time, conversion rate, and costs were all less in the laparoscopic-facilitated group. The fact that there were no conversions in this group is the most important finding of this study. Not only was it possible to convert from the assisted laparoscopic approach to laparotomy (five patients of 35), it was also possible to convert from the assisted to the facilitated form (seven of 35 patients). CONCLUSIONS: Laparoscopic-facilitated sigmoid resection is a feasible intervention for all forms of complicated diverticular disease and yields marked reductions in operating time, conversion rate, and operative and general costs.
Aged↗
Creatinine-based estimation of rate of long term renal function loss in lung transplant recipients. Which method is preferable?
BACKGROUND: Progressive renal function loss during long-term follow up is common after lung transplantation and close monitoring is warranted. Since changes in creatinine generation and excretion may occur after lung transplantation, the reliability of creatinine-based methods of renal function assessment to serial measurements of glomerular filtration rate (GFR) were compared in this population. METHODS: Renal function with serial measurements of GFR by iothalamate clearance every 6 months after transplantation was studied in a cohort of 40 lung transplant recipients with at least 24 months of follow up, transplanted between November 1990 and October 1995 in this center. The correlation between the rate of renal function loss calculated from the slope of GFR and the following creatinine-based indices: 1/S-creatinine, Cockcroft clearance and Levey estimation were analyzed. The absolute difference between GFR and Cockcroft clearance and Levey estimation pre- post-transplantation at several points was also studied. RESULTS: The slopes of 1/S-creatinine (r = 0.85), Cockcroft clearance (r = 0.86), and the Levey estimation (r = 0.84) correlated significantly with the slope of GFR as measured by iothalamate clearance. However, all creatinine-based slopes underestimate the rate of GFR loss. Cockcroft clearance and the reciprocal value of serum creatinine do not detect small GFR losses. During long-term follow up a time-dependent discrepancy between Cockcroft clearance, Levey estimation and GFR was observed which may partially explain the observations for this population. CONCLUSION: Creatinine-based slopes correlate with GFR slopes after lung transplantation, but consistently underestimate the rate of GFR decline. The Levey estimation is the most sensitive method used to detect small GFR losses and may be preferable when no GFR measurement is available. In special conditions when an accurate renal function assessment is needed true GFR may be necessary.
Adult↗
Platelets and soluble fibrin promote plasminogen activation causing downregulation of platelet glycoprotein Ib/IX complexes: protection by aprotinin.
Blood loss during and after open-heart surgery with cardiopulmonary bypass (CPB) is largely caused by platelet dysfunction. Previous studies indicate that plasmin can induce platelet dysfunction and affect primary hemostasis by proteolytic degradation and/or redistribution of essential platelet membrane glycoprotein complexes such as the glycoprotein Ib/IX complex. In this study, we present a model for plasmin generation localized on the platelet surface. Platelets treated with soluble fibrin or platelets in a mixture with soluble fibrin, t-PA, and plasminogen caused a significantly increased plasmin generation (p<0.01), dependent on t-PA, soluble fibrin, and platelet concentration. The plasmin generation resulted in a downregulation of platelet membrane glycoprotein Ib/IX glycoprotein complexes. Finally, we demonstrated that inhibitors of fibrinolysis, such as %2-antiplasmin, tranexamic acid, and aprotinin, can inhibit plasmin activity in the fluid phase. The downregulation of platelet glycoprotein Ib/IX complexes, however, was only prevented by aprotinin and not by alpha2-antiplasmin and tranexamic acid. These in vitro observations suggest a platelet localized activation of plasminogen, dependent on t-PA, enhanced by the presence of soluble fibrin. Since high concentrations of soluble fibrin and elevated levels of t-PA during CPB are observed, plasmin activity on the platelet surface during this period is anticipated. This plasmin activity reduces platelet metabolic functions and can be directed towards membrane glycoproteins such as glycoprotein Ib/IX complexes, thereby affecting hemostasis during and after CPB.
Antibodies, Monoclonal↗
[Acute urine retention in women].
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Adult↗
Indications for caesarean section in breech presentation.
OBJECTIVE: The study was conducted because of the still considerable controversies about the variation in obstetric management in breech presentation, in combination with the still increasing caesarean section rate for this type of presentation, as well as doubt concerning the assumed improvement in neonatal and maternal morbidity and mortality obtained by increasing section rate in breeches. STUDY DESIGN: Two hundred and sixty eight consecutive breech presentations in two university hospitals were studied longitudinally and prospectively. In principle, vaginal delivery was attempted in all cases, under expert supervision and electronic monitoring, except in the presence of clear-cut contraindications. X-ray pelvimetry was not used. RESULTS: The incidence of caesarean section was 34%. The trial of vaginal delivery succeeded in 64% of the nulliparas and in 60% of the non-frank breeches, without statistically significant differences in outcome measures compared with the multiparous women and the frank group, respectively. Hyperextension of the foetal head rarely occurred. CONCLUSION: Several classic obstetric factors have a lower discriminating value for the route of delivery than is currently assumed. Progress of labour was an important factor in determining the route of delivery.
Birth Weight↗
Ileus during pregnancy caused by malrotation.
Ileus during pregnancy is a rare complication. Malrotation in the adult is an even rarer finding. A case of a woman who developed an ileus in her seventeenth week of pregnancy is presented. At surgery the cause appeared to be a malrotation of the midgut. The incidence and causes of ileus during pregnancy are discussed. Also a short description of the different forms of malrotation are presented. New insights in the etiology of malrotation based on experiments with rats are mentioned.
Adult↗
Tumor angiogenesis: an independent prognostic parameter in cervical cancer.
OBJECTIVE: The purpose of this study was to investigate whether the intensity of tumor angiogenesis, expressed as microvessel density, is a parameter predicting the probability of lymph node metastasis and survival in patients with cervical cancer stages IB and IIA. STUDY DESIGN: In a retrospective study of 114 patients with cervical cancer stages IB and IIA, microvessel density, lymph node status, and several other prognostic parameters were correlated with disease-free survival by a multivariate analysis according to Cox proportional-hazards model. RESULTS: There was a significant difference in mean microvessel density between tumors with and without pelvic lymph node metastasis (p = 0.002). Both microvessel density (vessels per square millimeter of stroma). (p = 0.05) and pelvic lymph node metastasis (p = 0.007) correlated significantly and independently with disease-free survival. CONCLUSION: This study demonstrates that microvessel density is an independent prognostic parameter for disease-free survival in patients with cervical cancer stages Ib and IIa.
Female↗
Clotting and fibrinolytic disturbance during lung transplantation: effect of low-dose aprotinin. Groningen Lung Transplant Group.
UNLABELLED: Patients undergoing lung transplantation are often confronted with a bleeding problem that may be due in part to the use of cardiopulmonary bypass and its activation of blood clotting and fibrinolysis. OBJECTIVE: We performed a prospective study to determine whether and to what extent the clotting and fibrinolytic systems are being activated and whether low-dose aprotinin is effective in inhibiting blood activation during lung transplantation. METHODS: Thirty lung transplantations performed on 29 patients were divided into a group with cardiopulmonary bypass alone (n = 12), a group with cardiopulmonary bypass and 2 x 10(6) KIU aprotinin administered at the beginning of bypass in the pump prime (n = 12), and a group without cardiopulmonary bypass (n = 6). Serial blood samples were taken from the recipient before anesthesia, seven times during the operation, and 4 and 24 hours thereafter. RESULTS: Results show that in the group having cardiopulmonary bypass alone, the concentration of the clotting marker thrombin/antithrombin III complex increased significantly during the early phase of the operation (p < 0.01) and remained high until the end of the operation. Levels of tissue-type plasminogen activator, a trigger of fibrinolysis released by injured endothelium, also increased sharply in the early phase of the operation in the cardiopulmonary bypass group (p < 0.01), followed by a significant increase in fibrin degradation products (p < 0.01). In the aprotinin group, a significant reduction of thrombin/antithrombin III complex (p < 0.05), tissue-type plasminogen activator (p < 0.05), and fibrin degradation products (p < 0.05) was observed in the early phase of the operation compared with levels in the bypass group, but these markers increased late during bypass associated with a significant drop (p < 0.05) of plasma aprotinin level monitored by plasmin inhibiting capacity. In the nonbypass group, concentrations of thrombin/antithrombin III complex and tissue-type plasminogen activator also rose significantly (p < 0.05) in the early phase of the operation, but the levels were significantly lower than those of the bypass group (p < 0.05). Blood loss during the operation was 2521 +/- 550 ml in the bypass group, 1991 +/- 408 ml in the aprotinin/bypass group, and 875 +/- 248 ml in the nonbypass group. CONCLUSION: These results suggest that clotting and fibrinolysis are activated during lung transplantation, especially in patients undergoing cardiopulmonary bypass. Aprotinin in a low dose significantly reduced activation of clotting and fibrinolysis in the early phase of the operation but not during the late phase of lung transplantation.
Adult↗
Retransfusion of thoracic wound blood during heart surgery obscures biocompatibility of the extracorporeal circuit.
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Antithrombin III↗