Fast-track pulmonary conditioning before urgent cardiac surgery in patients with insufficiently treated chronic obstructive pulmonary disease.

AIM: Chronic obstructive pulmonary disease (COPD) is an important risk factor for perioperative morbidity and mortality in patients undergoing cardiac surgery. Despite high clinical relevance, current guidelines lack clear recommendations on the optimal approach for patients with insufficiently treated COPD and urgent need for cardiac surgery. The aim of the present study was to analyze the efficacy of short-term pulmonary conditioning (PC) in this subset of cardiopulmonary patients. METHODS: Eighteen patients with urgent need for cardiac surgery were treated with 1 mg budenoside twice a day, 1.25 mg salbutamol four times a day and 15 mg ambroxol three times a day. On average, patients received pulmonary conditioning for 5.1 ± 2.1 days. Lung function was assessed before and after treatment. RESULTS: Pulmonary conditioning improved forced expiratory volume in one second (FEV1) by 16% (P<0.001). Predicted FEV1 increased from 48.3 ± 13.6% at baseline to 55.4 ± 16.1% after treatment (P<0.001). Total resistance was reduced from 0.933 ± 0.418 kPa·s/L to 0.631 ± 0.344 kPa·s/L after PC (P=0.004). The percentage of patients in GOLD stages III-IV was reduced from 55.6% at baseline to 27.8% after treatment. After surgery, patients needed mechanical ventilation for 2 ± 3.4 days. One patient (5.6%) received a tracheostomy and four patients (22.2%) developed pneumonia; 30-day mortality was 5.6%. CONCLUSION: Short-term treatment with budenoside, salbutamol and ambroxol significantly improved lung function parameters. If surgery can be delayed for several days, pulmonary conditioning should be considered for patients with insufficiently treated COPD.

Wound-healing disturbances after vein harvesting for CABG: a randomized trial to compare the minimally invasive direct vision and traditional approaches.

BACKGROUND: Harvesting the great saphenous vein for coronary artery bypass grafting is often associated with complications in wound healing, insufficient cosmetic results, and delay in mobilization of the patients. The aim of this study was to compare the results of our minimally invasive technique with the traditional method. METHODS: We report our experience of minimally invasive direct vision harvesting the great saphenous vein with the Aesculap retractor system (Aesculap AG Co KG, Tutlingen, Germany) by performing 3 (to 5) small cutaneous incisions. We scheduled 255 patients for elective coronary artery bypass grafting prospectively randomized to undergo vein harvesting by either the minimally invasive technique (group A: n = 128; age range, 68.2 +/- 9.1 years; male, 53.1%) or by the traditional technique (group B; n = 127; age range, 66.1 +/- 8.3 years; male, 62.9%). We classified and defined leg-wound healing disorders in terms of mild, moderate, and severe wound-healing disturbances. RESULTS: Between group A and B there were no differences with the risk stratification before operation, length of vein being harvested, or total operation time. The time for minimally invasive harvesting of the great saphenous vein was slightly increased. Severe leg-wound healing disorders occurred in 4 of 128 patients of group A (3.1%) versus 12 of 127 patients of group B (9.4%) with significant difference (p = 0.042). CONCLUSIONS: Minimally invasive direct vision harvesting the great saphenous vein is an attractive alternative to the traditional open-harvesting technique. In our trial this procedure resulted in fewer wound complications and showed a much better cosmetic outcome. The total operation time was not increased by using the minimally invasive technique.

[Metastasizing malignant germ cell tumor of the testis with infiltration of the thoracic aorta--a case for metastasis surgery]. / Metastasierender maligner Keimzelltumor des Hodens mit Infiltration der Aorta thoracica--Kasuistik zur Metastasenchirurgie.

HISTORY AND FINDINGS: A 33-year-old man was admitted 7 years after a testicular teratomatous carcinoma had first been diagnosed, treated by a right orchiectomy and two-stage radical retroperitoneal lymphadenectomy. Five years later the first mediastinal metastases were treated with high-dosage chemotherapy and autologous germ-cell transplantation, and remaining paraaortic--mediastinal tumour tissue was resected. Two years later another tumour at that site was only partially resected. A curing treatment seemed impossible, because the aortic wall had been invaded. TREATMENT AND COURSE: Five months after re-thoracotomy the metastasis and the invaded aortic segment were resected, the latter replaced by a vascular prosthesis. Histology indicated metastasis of a malignant teratoma of intermediate type. There has been no evident recurrence in the last 20 months. CONCLUSION: Combined orchidectomy, lymphadenectomy, high-dosage chemotherapy with cisplatin and autologous germ-cell transplantation at present constitute the standard treatment of malignant testicular germ-cell tumour. In case of metastatic infiltration of vital structures, such as the aortic wall, special operative procedures can prolong the period of remission when the success of a standard treatment seems limited.

Pads and flexion creases on the plantar surface of hammertoe mutant mouse (Hm).

The purpose of the present work was to determine the effects of the hereditary malformation of Hammertoe mutant mice (gene symbol Hm) on the surrounding morphological structures and, specifically, on the volar pads, i.e., the sites of the epidermal ridge patterns (dermatoglyphics). The hindlimbs of the wild-type (+/+) Hammertoe mice show no anomalies and their major pad and flexion crease configurations correspond to those of normal mice. The heterozygous (Hm/+) and homozygous (Hm/Hm) mice display a fusion of the interdigital tissues involving all digits with the exception of digit I. In Hm/Hm mice, this webbing extends to the distal phalanx and the markedly flexed digits form a shape resembling a hammer. In Hm/+ mice, the interdigital webbing does not extend as far and the digits show moderate flexion compared to those of Hm/Hm mice. Both Hm/Hm and Hm/+ have a rudimentary extra digit in the postaxial area of the hindlimbs. The ventral volar skin of the flexed digits is incompletely developed. The more posterior digits show the more severe camptodactyly. These aberrant configurations are related to the abnormal occurrence of the programmed cell death (PCD) in the interdigital zones II-IV and the proximal part of the postaxial margin during hindlimb development. They are limited to the pads on the plantar surface of the postaxial area; the preaxial area is not affected. As a result of a severe camptodactyly of digit V, its volar skin is shifted into the distal portion of the hypothenar area. This shifting affects the number, size, and location of the pads, especially of the hypothenar pad, resulting in varying pad configurations, such as a displacement of the distal and proximal components of the hypothenar pad, or a fusion of the two components of the hypothenar pad, leading to a reduced final pad number. These pad modifications are induced by the postaxial plantar surface shifting proximally and are not affected by the presence of an extra rudimentary digit. The pad modifications in Hammertoe mice with webbed digits and postaxial polydactyly resemble closely those of the previously studied mice with genetic preaxial polydactyly.

Palmar and plantar pads and flexion creases of genetic polydactyly mice (Pdn).

Attempts to gain a better understanding of the relationship between the epidermal ridge patterns (dermatoglyphics) and flexion creases on the volar aspects of human hands and feet and specific medical disorders led to a search for a suitable animal model, allowing studies of the fetal development of the pertinent structures. A common experimental animal, the rat (Rattus norvegicus), was found to be an excellent candidate, owing to the strong resemblance of the volar pads and flexion creases on its palmar and plantar surfaces to those of human subjects. A hereditary preaxial polydactyly mouse (Pdn) provides an opportunity to study the effects of this malformation on the surrounding morphological structures and, specifically, on the volar pads, i.e., the sites over which the dermatoglyphic patterns develop. The hands and feet of the wild-type (+/+) mice show no anomalies, and their major pad and flexion crease configurations correspond to those of normal rats. The heterozygous (Pdn/+) mice, in spite of having a thumb/big toe with a duplicated distal phalanx on their hands/feet, did not display any alterations in palmar/plantar pads. The homozygous (Pdn/Pdn) mice have a protrusion in the thenar area and one to three supernumerary digits on the preaxial portion of both the hands and feet. The effect of these anomalies was found to be limited to the pad and flexion crease configurations in the preaxial areas; the postaxial sites were not affected. The original number of pads on the thenar/first interdigital areas of Pdn/Pdn mice was apparently identical to that of the +/+ and Pdn/+mice. The preaxial protrusion, however, affected the number, size, and location of the pads observed in the newborn mice, resulting in varying pad configurations, such as fused and scattered pads or a pad cluster formed by gathering the neighboring pads. These pad modifications were induced by the preaxial plantar/palmar protrusion only and were not affected by the presence of supernumerary preaxial digits. In view of the similarities in the morphology and fetal development of human and mouse distal limbs, the present study is relevant to human subjects, particularly to the understanding of the significance of dermatoglyphic variations in individuals with specific medical disorders. Future studies of naturally occurring or experimentally induced limb malformations in mice or rats should provide valuable insights into the development of human hands and feet and into factors contributing to their congenital anomalies.

Fetal and postnatal development of palmar, plantar, and digital pads, and flexion creases of the rat (Rattus norvegicus).

Fetal development of the hands and feet of rats was investigated to determine the feasibility of using rats as an experimental model for studying the factors influencing early development of the hands and feet, and especially the dermatoglyphics in humans. Eighty rats fetuses of 14-21 days gestational age and 80 newborn rats of 0-7 days of age were used to study the morphological features of the palmar, plantar, and digital areas and to determine the timing of appearance and the location of the volar pads and flexion creases. Comparisons between analoguous developmental stages of rat and human fetuses demonstrate striking similarities in overall fetal development. Marked differences, however, were found between rat and human fetuses in the timing of developmental milestones and in some morphological features. The results indicate that rats can serve as a useful experimental model in studies of the utility of the epidermal ridge configurations and flexion creases in medical disorders, provided that the differences in the timing of development are taken into consideration.

Palmar and plantar pads and flexion creases of the rat (Rattus norvegicus).

The recent detection of dermal ridge configurations on the volar pads of the rat (Rattus norvegicus) has created opportunities for experimental studies of dermatoglyphics. In the present work, the palmar and plantar surfaces of the rat were studied to establish the feasibility of comparative rat and human dermatoglyphic investigations. The studied features included the volar pads and flexion creases. The number and location of the palmar and plantar pads in the rat were found to be similar to those of humans. The exception was a previously unrecognized small pad on the palms and soles of the rat, located on the radial and tibial side, respectively, of the proximal component of the first interdigital pad. This pad has no parallel in human embryos. Rats were found to have flexion creases in the non-pad areas between the neighboring pads, similar in location and appearance to those of humans. Unlike humans, however, rats also have boundary creases, separating the pad and non-pad areas. The marked similarities in the morphology of the volar areas between rats and humans make the rat ideally suitable for experimental studies of dermatoglyphics and flexion creases. Results of such studies should be applicable to human developmental dermatoglyphics, including those pertaining to medical disorders.

Family history of seizures in posttraumatic and alcohol-associated seizure disorders.

The potential role of genetic factors in the etiology of posttraumatic and alcohol-associated seizures was studied in 289 male patients with recurrent seizures and in 174 individuals who had never experienced a seizure. The incidence of seizures in first-degree relatives of probands was compared with that in relatives of unaffected individuals. Relatives of patients with alcohol-associated seizures had a rate ratio of 2.45 [95% confidence interval (CI) 1.41-4.25], whereas no excess incidence was noted among relatives of posttraumatic epilepsy patients (rate ratio 1.20, 0.64-2.25 CI). Relatives of probands with both antecedents showed an intermediate rate ratio of 1.72 (0.92-3.20 CI). Among probands with alcohol-associated seizures, the rate ratio of 2.05 for patients with alcohol-related seizures (i.e., spontaneously occurring seizures in association with chronic alcohol abuse) was slightly higher than that of 1.85 for probands with alcohol withdrawal seizures. Trauma severity had a slight impact on the incidence of affected relatives; patients with severe head injuries had a rate ratio of 0.73 and probands with milder trauma had a rate ratio of 0.99. The results indicate a limited, if any, role of genetic predisposition in development of posttraumatic seizures. Alcohol-related seizures, however, showed familial aggregation of unprovoked seizures, suggesting an involvement of genetic factors in the origin of such seizures.

Effect of antiepileptic drugs on growth of murine lymphoid tumor cells in single-cell culture.

The effect of three commonly used antiepileptic drugs (AEDs), phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA), on the growth of lymphoid tumor cells was assessed in vitro. A single-cell culture method was used to determine growth rates by direct visualization. The amount of free drug was determined by ultrafiltration to ascertain its correlation to therapeutic drug levels. VPA slowed the growth of B-myeloma (FO) and T-lymphoma (AKR-1) cells significantly within the range of therapeutic drug levels. CBZ and PHT likewise inhibited cell growth in both lineages but at two to four times the therapeutic level of free drug. CBZ was shown to have long-term effects on FO and AKR-1 cells, demonstrated by the reduced growth rates of cloned lines for 2-3 months after drug removal. Cloned sublines of myeloma cells secreting lambda light chain (J558L) treated with CBZ or PHT had a higher frequency of lambda light chain secretion loss mutations than the nontreated parent line.

A micro-enzyme-multiplied immunoassay technique plate assay for antiepileptic drugs.

Underutilization of antiepileptic drug monitoring in research situations has made comparison of data difficult to interpret. Experimental animal studies of the effects of antiepileptic drugs are similarly hindered by the lack of methods utilizing small blood samples to determine drug levels. To alleviate both problems, a standard enzyme-multiplied immunoassay technique (EMIT) assay was modified and scaled down. The resulting microEMIT utilizes only a fraction of the costly reagents (5.0 vs. 50.0 microliters) of the original assay and requires only 3-5 microliters of serum, easily obtainable from experimental animals. The method has been successfully tested with three major antiepileptic drugs, phenytoin (PHT), valproic acid (VPA) and carbamazepine (CBZ). The microEMIT assay, utilizing a 96-well plate, displays linear kinetics in the production of reduced nicotinamide adenine dinucleotide (NADH) for at least 8 minutes. The assay is linear from 2 to 100 micrograms PHT/ml, from 2 to 50 micrograms CBZ/ml and from 10 to 150 micrograms VPA/ml. The similarities suggest that a general adaptation for most EMIT drug assays will be possible.

Toxic effects of antiepileptic drugs on immunoglobulin gene expression.

Murine myeloma cells were exposed to toxic, growth-retarding levels of two antiepileptic drugs (AEDs2), phenytoin (PHT) and carbamazepine (CBZ). J558L cells were treated for 12 days, washed free of drug and, upon recovery of growth, cloned to determine the frequency of lambda light chain secreting lines. Our results indicate that short-term exposure to high, toxic levels (5-10 times the therapeutic dose) of PHT and CBZ reduces or eliminates lambda light chain secretion at a high frequency. Furthermore, although most cloned lines tested positive for cytoplasmic lambda light chain, some lines had no detectable cytoplasmic immunoglobulin (Ig). The data are consistent with the hypothesis that long-term changes in fully differentiated B cell function may occur after toxic level AED exposure.

Segregation of the growth slowing effects of valproic acid from phenytoin and carbamazepine on lymphoid tumor cells.

One human and six murine tumor cell lines of lymphoid origin were assessed for growth in the presence of three commonly used antiepileptic drugs (AEDs). All seven lines were sensitive to the growth slowing effects of phenytoin (PHT) and carbamazepine (CBZ). Six lines showed a similar effect when exposed to valproic acid (VPA), while one murine B cell line was resistant to inhibition of growth by VPA.

Dermatoglyphics in juvenile hypertension.

Dermatoglyphics of 172 children and young adults (116 males, 56 females) with hypertension, 13-27 years old, were compared with those of 130 healthy male and 110 female controls. Several differences were observed between the two groups. Hypertensive patients had a somewhat lower frequency of fingertip ulnar loops, higher frequency whorls and a higher total finger ridge count. They also had a somewhat higher mean atd angle, significantly more frequent distal position of the axial triradius (mostly in t' position) and more missing axial triradii compared to controls. The differences between a-b ridge counts, the interdigital, thenar and hypothenar patterns were generally small and sometimes limited to one sex or one hand only. The observed differences seem to indicate a genetic influence in the etiology of essential hypertension.

Clinical aspects of dermatoglyphics.

As demonstrated above, considerable progress has been made in the understanding of the associations between dermatoglyphics and various medical disorders, as a result of which dermatoglyphic analysis has been established as a useful diagnostic and research tool in medicine, providing important insights into the inheritance and embryologic development of many studied clinical disorders. Many unanswered questions and misconceptions still remain, though. Further well-designed investigations, avoiding the pitfalls of many earlier studies, will be needed to reevaluate some of the existing claims and to determine the real value of dermatoglyphics in medicine. The benefits of a dermatoglyphic examination in individual patients in clinical genetic practice are clear; a more widespread application of this tool by clinical geneticists and pediatricians should be encouraged. Embryologic and experimental dermatoglyphic studies clearly hold a considerable potential for a better understanding of the factors influencing the development of the epidermal ridge patterns. Utilized together with newly developed methods and insights gained in recent studies of other aspects of dermatoglyphics, they should significantly advance the studies of the relationship between dermatoglyphic variation and medical disorders.

Palmar, plantar, and digital flexion creases: morphologic and clinical considerations.

The above overview illustrates the areas of interest in flexion creases in human biology studies in general and in studies of medical disorders in particular. Clearly, flexion creases have a significance of their own rather than only as appendices of the dermatoglyphic analysis and should, therefore, be approached appropriately. In some instances, they may be of more interest than the dermatoglyphics. Our understanding of the creases and their value is, however, as yet incomplete and the gaps in our insight limit the possible interpretations and practical applications of the knowledge gained from studies of various aspects of the flexion creases. Creases provide important clues of the early fetal development and thus may be of practical value in clinical medicine. So far, most of these studies have been carried out in relation to specific disorders, often without a clear reasoning why flexion creases should be altered in the given disorder. The examples of aberrant flexion creases discussed above illustrate the general lack of specificity of crease anomalies in association with a particular syndrome or disorder that does not include malformations or malfunctions of the limbs. Instead, the anomalous flexion creases reflect the altered shape and function of hand and foot, which, in turn, are determined during early fetal development and affected by factors interfering with normal embryogenesis. A more promising approach to studying flexion creases in medical disorders, therefore, is to explore the developmental correlations between the creases and the structure and function of hands and feet. This does not mean that information gained from the case reports of individuals with various congenital defects is of no value. On the contrary, it should be collected systematically to determine the variety of crease aberrations and their frequencies in a given disorder, which would help elucidate the presence and timing of the developmental factors involved in the origin of the defect. The usefulness and limitations of the flexion creases are to a large degree parallel to those of dermatoglyphics. Altered flexion creases are indicative of intrauterine disturbances occurring early in pregnancy. As such, they may be of a predictive value in otherwise apparently normal infants in whom cryptic damage may be manifested later. They may serve to alert the physician to perform careful or more detailed examinations or to reexamine already obtained (and possibly inaccurate) test results. A better understanding of the crease embryology, both normal and abnormal, is a prerequisite for progress in studies of flexion creases.(ABSTRACT TRUNCATED AT 400 WORDS)

Comparative effects of phenytoin and/or phenobarbital treatment on sister chromatid exchange.

The potential of the widely prescribed antiepileptic drugs (AEDs) phenytoin (PHT) and phenobarbital (PB) to interact with genetic material was tested using sister chromatid exchange (SCE) assay. Thirty adult male patients with epilepsy receiving long-term AED therapy (16 with PHT, 6 with PB, and 8 with combined PHT and PB therapy) and 30 healthy controls were selected for the study of SCE frequencies in peripheral lymphocytes. The patients and controls were carefully screened and matched for sex, age, and smoking habits. All potential probands with exposure to factors known or suspected of affecting the SCE frequencies were excluded. Statistical analyses did not show any significant differences between the SCE rates of PHT- and/or PB-treated patients and controls, indicating a lack of mutagenicity of the tested drugs as expressed by induction of SCE on adult recipients. Smoking, however, affected the SCE levels considerably. The smokers had higher SCE frequencies than the nonsmokers, both among patients and controls. Caffeine consumption was also associated with SCE increases in patients but not in controls.

Embryological development and prevalence of digital flexion creases.

The embryological development and morphology of digital flexion creases were studied in 178 human embryos and fetuses 6-20 weeks of gestational age. The results suggest the existence of two types of digital flexion creases, that differ from each other in their development. The regular creases, with the exception of the distal crease of the proximal interphalangeal creases, and the oblique and extra creases of the irregular creases, develop concurrently with the appearance of the digital pads by about 11 weeks of gestation. The remaining creases, i.e., the distal crease of the proximal interphalangeal creases and the accessory crease develop later unrelated to the pads but, apparently, secondary to the flexion movements of the hand. Our observations further suggest that, because of their high frequencies, the oblique creases on the ulnar side of digits I and II and on the radial side of digit V and the extra creases on the proximal phalanx of digits I, III, and IV should be considered as "regular" creases. Previously unreported pads were also found on the middle phalanges at about 11 weeks of gestation. Unlike the single, large pads with high elevation, typically found on the distal phalanges, those on the middle phalanges are multiple, small, and only slightly elevated. This observation provides further support to the concept of the relationship between the fetal digital pads and the development of the epidermal ridge patterns.

Sister chromatid exchanges in adult epilepsy patients on valproate monotherapy.

Sister chromatid exchanges (SCE) were studied in peripheral lymphocyte cultures of 13 adult male patients with epilepsy treated chronically with valproate (VPA) and in their matched controls. No statistically significant differences in SCE level were found between the patient and control groups, indicating a lack of mutagenic potential of VPA within the therapeutic dose range.