Shorter time since inflammatory bowel disease diagnosis in children is associated with lower mental health in parents.

AIM: This study assessed the mental health of parents of children with inflammatory bowel disease (IBD), compared their mental health with age-matched and gender-matched references and examined parental and child predictors for mental health problems. METHODS: A total of 125 mothers and 106 fathers of 125 children with active and inactive IBD from the Swiss IBD multicentre cohort study were included. Parental mental health was assessed by the Symptom Checklist 27 and child behaviour problems by the Strengths and Difficulties Questionnaire. Child medical data were extracted from hospital records. RESULTS: While the mothers reported lower mental health, the fathers' mental health was similar, or even better, than in age-matched and gender-matched community controls. In both parents, shorter time since the child's diagnosis was associated with poorer mental health. In addition, the presence of their own IBD diagnosis and child behaviour problems predicted maternal mental health problems. CONCLUSIONS: Parents of children with IBD may need professional support when their child is diagnosed, to mitigate distress. This, in turn, may help the child to adjust better to IBD. Particular attention should be paid to mothers who have their own IBD diagnosis and whose children display behaviour problems.

Outcomes for split-thickness skin transplantation in high-risk patients using octenidine.

Skin transplantation is a commonly used surgical technique; however, the complication rate, including postoperative infection and delayed wound healing due to inefficient perfusion, is significantly higher in patients suffering from comorbidities. Hence, a subsequent repeat procedure is often necessary. In this report, two case studies are presented in which an octenidine-based antiseptic is used with a tie-over dressing (TOD) instead of povidone iodine (PVP-iodine), following a split-thickness skin graft. The two patients selected were deemed to be at high risk of impaired wound healing due to comorbidities. The first patient, a confirmed smoker with diabetes, presented with a nodular melanoma that was resected and covered with a split-thickness skin graft. After 5 days of negative pressure wound therapy as a TOD, in combination with PVP-iodine, the graft became necrotic. A second split-thickness skin graft was performed and an antiseptic regimen with octenidine in combination with the same TOD resulted in a completely healed transplant. The second patient, also a confirmed smoker with diabetes and receiving oral corticosteroid treatment, was diagnosed with a skin necrosis on her leg. Following the split-thickness skin graft, octenidine and TOD were applied. The patient's skin graft completely healed without any adverse events. These two case studies indicate that the combination of octenidine and TOD following split-thickness skin transplantation is safe, well-tolerated and appears to have positive benefits in the reconstruction of defects in patients with impaired wound healing.

The combined use of NPWT and instillation using an octenidine based wound rinsing solution: a case study.

Effective wound bed preparation is an essential element in the healing of chronic wounds, including pressure ulcers (PUs). Negative pressure wound therapy (NPWT) reduces oedema, stimulates the formation of granulation tissue and helps remove wound exudate. This helps prepare the wound bed for secondary healing, skin grafting or coverage with flaps. Combining NPWT with an instillation phase using an antiseptic (octenidine based) irrigation solution is a novel approach to PU management. Three patients with Category 4 gluteal PUs were treated with NPWT and instillation fluid, following surgical debridement of necrotic tissue. The aim was to achieve optimal wound bed preparation prior to wound closure by local fasciocutaneous flap. The antiseptic efficacy of octenilin wound irrigation solution in microorganism eradication was quantified by in vitro tests simulating real conditions using leg ulcer vacuum exudates. All wounds completely healed after four weeks, and no adverse incidents occurred due to instillation of octenidine. No recurrence of the PU occurred during a one year follow-up.

Proof testing of ceramic femoral heads for hip joint implants.

A proof test procedure for the rejection of defective ceramic hip ball heads in the production line is presented. The procedure consists of applying a load to each ceramic ball head. This load, being somewhat higher than the maximum physiological load, should not cause any damage in cases where the highly stressed areas are free of flaws. In this procedure, a polymer ring is positioned inside the ball head bore between a socket and the head of a tie bolt. Once the tie bolt is pulled downwards, the ring creates a radial pressure on the inner bore surface of the ball head. With an iterative approach based on finite element analysis, the proof test design was optimized in order to obtain a stress distribution in the ball head similar to that resulting in in vivo conditions. The calculated results were validated by strain gauge measurements performed on an assembled proof test apparatus. Several polymers were considered for the ring. Ultrahigh-molecular-weight polyethylene (UHMWPE grade RCH 1000) showed the best durability properties and lowest wear rates. The requirement to perform 1000 reruns without significant reduction of stress in the ball head was fulfilled. Although other proof test procedures for ceramic femoral heads already exist, the procedure presented in this article shows advantages concerning maintenance and operating costs.

The human c-ras1H oncogene: a mutation in normal and neoplastic tissue from the same patient.

The c-ras1H oncogene can be distinguished from its normal cellular counterpart by the loss of a restriction endonuclease site. This sequence alteration is the basis of a rapid screening method for the presence of this oncogene. DNA's from 34 individuals were screened by this method, and all were homozygous for the normal allele. In contrast, DNA from a patient's bladder tumor, as well as DNA from his normal bladder and leukocytes, were heterozygous at that restriction endonuclease site. Further restriction enzyme mapping pinpointed the change in the mutant allele as being one of two nucleotides, either of which would change the 12th amino acid (glycine) in the normal c-ras1H gene product. Point mutations in the codon for this amino acid have previously been described in a bladder tumor cell line and in the viral oncogene v-rasH. These results indicate that the patient carried a c-ras1H oncogene in his germ line, raising the possibility that the c-ras1H oncogene confers a predisposition to neoplasia.

Deregulated c-Myb expression in murine myeloid leukemias prevents the up-regulation of p15(INK4b) normally associated with differentiation.

Deregulated expression of the proto-oncogene c-myb, which results from provirus integration, is thought to be responsible for transformation in a set of murine leukemia virus (MuLV)-induced myeloid leukemias (MML). We reported recently that this transcription factor promotes proliferation by directly transactivating c-myc and inhibits cell death through its up-regulation of Bcl-2 (Schmidt et al., 2000). To understand more about how these cells become transformed we looked at how they deal with cellular pathways inducing growth arrest. Specifically, we were interested in the expression of the tumor suppressor gene Cdkn2b (p15(INK4b)) in MML because this gene is expressed during myeloid differentiation and its inactivation by methylation has been shown to be important for the development of human acute myeloid leukemia. mRNA levels for p15(INK4b) and another INK4 gene p16(INK4a) were examined in monocytic Myb tumors and were compared with expression of the same genes in c-myc transformed monocytic tumors that do not express c-Myb. The Cdkn2a (p16(INK4a)) gene was generally not expressed in either tumor type, an observation explained by methylation or deletion in the promoter region. Although Cdkn2b (p15(INK4b)) mRNA was expressed in the Myc tumors, many transcripts were aberrant in size and contained only exon 1. Surprisingly, in the majority of the Myb tumors there was no p15(INK4b) transcription and neither deletion nor methylation could explain this result. Additional experiments demonstrated that, in the presence of constitutive c-Myb expression, the induction of p15(INK4b) mRNA that accompanies differentiation of M1 cells to monocytes does not occur. Therefore, the transcriptional regulator c-Myb appears to prevent activation of a growth arrest pathway that normally accompanies monocyte maturation.

Retroviral insertional mutagenesis in murine promonocytic leukemias: c-myb and Mml1.

Studies have focused on two genetic loci, c-myb and Mml1, whose activation by retroviral insertional mutagenesis contribute to promonocytic leukemia in our acute monocytic leukemia (AMoL) model. Multiple mechanisms of activation of c-myb by retroviral insertional mutagenesis implicate both transcriptional deregulation and protein truncation in conversion of this proto-oncogene to an oncogene. Because transformation by c-Myb can be viewed as a block to differentiation our studies moved into two in vitro systems to evaluate effects of truncated forms of c-Myb on cytokine induced maturation of myeloid progenitors to the granulocyte and macrophage lineages. Deregulated expression of truncated and full length c-Myb did not result in maintenance of the myelomonocytic progenitor state but rather a block in differentiation at intermediate to late steps in the maturation processes of myelomonocytic cells. Our results argue that inhibition of differentiation is due to c-Myb's ability to maintain the proliferative state of cells. Interestingly, the phenotype of continuously proliferating monocytic cells resembles that of the tumor cell phenotype. Recently we identified a new target of integration, Mml1, which is rearranged in ten promonocytic leukemias that do not have c-myb rearrangements. This locus which was mapped to chromosome 10 is presently being characterized.

Ketamine-induced deficits in auditory and visual context-dependent processing in healthy volunteers: implications for models of cognitive deficits in schizophrenia.

BACKGROUND: In patients with schizophrenia, deficient generation of mismatch negativity (MMN)-an event-related potential (ERP) indexing auditory sensory ("echoic") memory-and a selective increase of "context dependent" ("BX") errors in the "A-X" version of the Continuous Performance Test (AX-CPT) indicate an impaired ability to form and use transient memory traces. Animal and human studies implicate deficient N-methyl-D-aspartate receptor (NMDAR) functioning in such abnormalities. In this study, effects of the NMDAR antagonists ketamine on MMN generation and AX-CPT performance were investigated in healthy volunteers to test the hypothesis that NMDARs are critically involved in human MMN generation, and to assess the nature of ketamine-induced deficits in AX-CPT performance. METHODS: In a single-blind placebo-controlled study, 20 healthy volunteers underwent an infusion with subanesthetic doses of ketamine. The MMN-to-pitch and MMN-to-duration deviants were obtained while subjects performed an AX-CPT. RESULTS: Ketamine significantly decreased the peak amplitudes of the MMN-to-pitch and MMN-to-duration deviants by 27% and 21%, respectively. It induced performance deficits in the AX-CPT characterized by decreased hit rates and specific increases of errors (BX errors), reflecting a failure to form and use transient memory traces of task relevant information. CONCLUSIONS: The NMDARs are critically involved in human MMN generation. Deficient MMN in schizophrenia thus suggests deficits in NMDAR-related neurotransmission. N-methyl-D-aspartate receptor dysfunction may also contribute to the impairment of patients with schizophrenia in forming and using transient memory traces in more complex tasks, such as the AX-CPT. Thus, NMDAR-related dysfunction may underlie deficits in transient memory at different levels of information processing in schizophrenia. Arch Gen Psychiatry. 2000;57:1139-1147.

MuLV-insertional mutagenesis of c-myb and Mml1 in a murine model for promonocytic leukemia.

Analysis of retroviral integration sites in MuLV-induced promonocytic leukemias has determined that two genetic loci, c-myb and Mml1, can contribute to disease development but not in the same leukemia. Recent studies aimed at understanding the function of Myb in leukemia development have focused on the consequences of ectopic Myb expression on monocytic and granulocytic differentiation in vitro. In all instances Myb was shown to block growth arrest but not commitment to differentiation, a result which is consistent with observed effects of Myb in leukemia development. No effect of Myb protein truncation was observed in these studies although similar truncations are produced as a result of insertional mutagenesis. Common integration site, Mml1, was recently identified and mapped to mouse chromosome 10 within 1cM of c-myb. Despite its linkage to c-myb, Myb mRNA and protein expression appear to be unaffected in leukemias with Mml1 integrations.

The Viennese culture method: cultured human epithelium obtained on a dermal matrix based on fibroblast containing fibrin glue gels.

The aim of this study was to develop a new keratinocyte culture system on a dermal equivalent suitable for skin wound closure. Our dermal matrix is based on a fibrin glue gel containing live human fibroblast (from human foreskin). Keratinocytes obtained from primary culture according to the Rheinwald and Green method, were seeded on to the gel. In all cases, the keratinocytes plated on the dermal equivalent grew to confluence and stratified epithelium was obtained. After 10 days an irregular multilayer could be observed. The cells showed active interaction with the fibrin support, presenting as cell formations projecting into the matrix. After 15 days a regular epithelial sheet consisting of three to four layers of cells was formed. A limiting membrane demarcating the keratinocytes from the fibrin matrix was discernible. Squamous differentiation similar to Strata reticulare and corneum found in vivo could be observed. Nuclei of basal cells were regularly spaced from each other and the chromatin was of homogeneous appearance without prominent nucleoli. The last time point (20 days) showed signs of disintegration of the epithelial sheet. A basement membrane-like structure could not be seen any more. Detachment of the basal cells was associated with subepithelial vacuoles. Basal cells contained irregular nuclei. Therefore, we conclude that 15 days of culture were optimal for the generation of a keratinocyte layers with signs of differentiation; this new culture system could be an important step forward in covering severely burned patients due to a number of advantages, as for example a large expansion factor, the shortening of the optimal culture time to 15 days, the usage of commercially available fibrin glue gels and the versatile manipulation of composite cultures.

Recurrent embolic cerebral infarction and anticoagulation.

A retrospective review of the hospital course of 44 patients with embolic cerebral infarction was carried out. Eleven patients (25%) suffered recurrent embolic infarction. Three of the recurrences were fatal. Two patients suffered a recurrence within 48 hours of the initial event, and an additional patient suffered a recurrence 6 days after the initial event. Sixteen embolic infarctions were managed with therapeutic anticoagulation within 48 hours without adverse effect. The clinical and experimental data concerning early anticoagulation after embolic infarction were reviewed. It appears that the risk of early anticoagulation is less than the risk of recurrent embolic infarction.

Computerized tomography and pure sensory stroke.

We studied three patients fitting the clinical syndrome of "pure sensory" stroke. The abnormalities on computerized tomography (CT) scan differed and included posterior cerebral artery occlusion, lacunar infarct in the thalamocortical pathway, and hemorrhage in the thalamus. These cases were unique in that CT scan abnormalities were found in patients with pure sensory stroke.

Axon typing of rat muscle nerves using a double staining procedure for cholinesterase and carbonic anhydrase.

We developed a method for detecting activity of axonal cholinesterase (CE) and carbonic anhydrase (CA)--markers for motor and sensory nerve fibers (NFs)--in the same histological section. To reach this goal, cross-sections of muscle nerves were sequentially incubated with the standard protocols for CE and CA histochemistry. A modified incubation medium was used for CA in which Co++ is replaced by Ni++. This avoids interference of the two histochemical reactions because Co++ binds unspecifically to the brown copper-ferroferricyanide complex representing CE activity, whereas Ni++ does not. Cross-sections of the trapezius muscle nerve containing efferent and afferent NFs in segregated fascicles showed that CE activity was confined to motor NFs. Axonal CA was detected solely in sensory NFs. The number of labeled motor and sensory NFs determined in serial cross-sections stained with either the new or the conventional technique was not significantly different. Morphometric analysis revealed that small unreactive NFs (diameter less than 5 microns) are afferent, medium-sized ones (5 microns less than d less than 7 microns) are unclassifiable, and large ones (d greater than 7 microns) are efferent. The heterogenous CE activity of thick (alpha) motor NFs is linked to the type of their motor units. "Fast" motor units contain CE reactive NFs; "slow" ones have CE negative neurites.

Partial myotomy/myectomy of the trapezius muscle with an asleep-awake-asleep anesthetic technique for treatment of cervical dystonia. Technical note.

The authors describe a technique for performing partial sectioning and myectomy of the trapezius muscle in patients with severe cervical dystonia that is unresponsive to conservative treatment. Asleep-awake-asleep anesthesia allows intraoperative control of the sectioning procedure to avoid causing postoperative weakness of arm elevation above the horizontal plane. The procedure has been performed successfully in three patients. In all cases the dystonic posture of the shoulder and local pain were improved postoperatively. There were no new deficits. This technique can be used as an adjunct to other peripheral surgical procedures in patients with marked laterocollis and dystonic elevation and ante-version of the shoulder.

Histological assessment of nerve lesions caused by epineurial electrode application in rat sciatic nerve.

The left sciatic nerve of 36 rats was exposed and four ring-shaped stainless steel wire electrodes were sutured to the epineurium of each nerve in the same manner as performed clinically for "carousel stimulation" in man. The rats were sacrificed 10 days (Group 1), 3 weeks (Group 2), or 3 months (Group 3) after implantation. The electrodes were excised, the nerves were embedded in Epon, and semithin sections were obtained for histological and planimetric assessment of lesions caused by the epineurially sutured electrodes. The right sciatic nerves served as controls. The total area of neural tissue within the perineurium was determined at three levels: at the site of the electrodes, 8 mm proximal, and 8 mm distal. The area of neural tissue damaged by the surgical procedure was expressed as a percentage of the total area. In Group 1, nine of 12 nerves showed lesions ranging from 0.39% to 25.39% of the total area of neural tissue, in Group 2 eight of 11 sciatic nerves showed lesions ranging from 0.24% to 13.03% of the total area, and in Group 3 five of 12 nerves showed lesions ranging from 0.21% to 4.96% of the total area. The pathologically altered areas in Groups 2 and 3 exhibited distinct signs of nerve fiber regeneration. The reasons for the decrease in damage from Group 1 to Group 3 and the clinical implications of the results for long-term electrical stimulation are discussed.

Prognostic factors in adenocarcinoma of the cardia.

BACKGROUND: The optimal extent of resection for adenocarcinomas of the gastroesophageal junction is controversial. This study was conducted to examine whether the extent of resection is an independent prognostic factor in cardia cancer. METHODS: The records and survival data of 125 patients who underwent resection for cancer of the cardia were retrospectively analyzed. Multiple regression was used to evaluate prognostic factors in patients who underwent proximal gastric resection (PR) or total gastrectomy (TG) for cancer of the cardia. RESULTS: Seventy-five patients underwent PR and 50 TG. The 5-year survival was 40% for tumors confined to the esophageal wall (T1, T2), and 13% in more advanced cases (T1, T2; P = 0.0001). Twenty-two percent of the patients with tumor-free margins, 10% of those with microscopic residual tumor, and none with macroscopic residual tumor survived longer than 5 years (P = 0.0001 for any residual tumor versus no residual tumor). Lymph node involvement (P = 0.002) and stage (P = 0.0001) were also significant in the univariate analysis. Five-year survival was 18% after TG, and 17% after PR (P = NS). CONCLUSION: Multiple regression identified residual tumor and penetration depth as independent predictors of survival (P = 0.0002, and P = 0.0001, respectively). After correction for these factors, none of the following variables were of additional significance: extent of resection (TG versus PR), lymph node involvement, age, or Lauren's classification. In 19 of 20 cases with microscopic incomplete resection, it was the oral margin that was positive. We conclude that the extent of resection (TG versus PR) does not influence survival in adenocarcinoma of the gastroesophageal junction.

Experimental development of an electrically stimulated biological skeletal muscle ventricle for chronic aortic counterpulsation.

OBJECTIVE: The chronic shortage of donor organs for cardiac transplantation and the high costs for mechanical assist devices demand the development of alternative cardiac assist devices for the treatment of severe heart failure. Cardiac assistance by stimulated skeletal muscles is currently investigated as such a possible alternative. The goal of the presented study was to construct a newly designed biological skeletal muscle ventricle and to evaluate its possible hemodynamic efficacy in an acute sheep model. METHODS: A total of 14 adult sheep were used for acute experiments. The entire thoracic aorta including the aortic root was excised from a donor sheep. An aorto-pericardial pouch conduit (APPC) was created by enlarging the aortic circumference in its middle section with two strips of pericardium. This biological conduit was anastomosed in parallel to the descending aorta of a recipient sheep, using the aortic root as an inflow valve to the conduit. Stimulation electrodes were applicated to the thoracodorsal nerve and the latissimus dorsi muscle was detached from the trunk and wrapped around the pouch. ECG-triggered functional electrical stimulation was applied during cardiac diastole to simulate aortic counterpulsation. Stimulation was performed during various hemodynamic conditions. RESULTS: A standardised surgical procedure suitable for long term studies was established during six experiments. An APPC, with 70-80 mm filling volume, was found to be of optimal size. In another eight experiments, hemodynamic measurements were performed. Under stable hemodynamic conditions the stimulation of the biological skeletal muscle ventricle induced a significant increase of mean arterial pressure by 14% and mean diastolic pressure by 26%. During pharmacologically induced periods of cardiac failure, the stimulation of the APPC increased mean arterial pressure by 13% and mean diastolic pressure by 19%. In all eight experiments, the diastolic peak pressure reached supra-systolic values during stimulation. CONCLUSIONS: The results demonstrate the hemodynamic efficacy of this newly designed biological skeletal muscle ventricle as an aortic counterpulsation device. Chronic experiments using a preconditioned fatigue-resistant muscle will further help to evaluate its possible clinical significance.

An innovative program for the restoration of patients with chronic back pain.

The literature on conventional medical procedures for restoring high-risk patients having chronic low back pain reveals that these procedures are ineffective and may even be iatrogenic. An alternative, noninvasive approach, which takes into consideration the critical role of cognitive and emotional factors, is practiced at Casa Colina Hospital for Rehabilitative Medicine. Details of the approach as well as comments confirming its efficacy are presented.

Quantification of functional results after facial burns by the faciometer.

In the present study the faciometer(R) is introduced in order to quantify the ranges of mimic movements observed after surgical treatment of facial burns. This instrument which consists of calipers and an electronic display was introduced in 1994 in order to measure the extent of facial palsy during reconstructive procedures. The study group consisted of 23 patients, who had been operated on for facial burns. The distances between standardised stable and moving points in the face were determined after mimic movements such as lifting of the eyebrows, maximum showing of the teeth and pursing of the lips. These distances were expressed as a percentage of the distance at rest. For comparison the scars were classified according to the Vancouver Scar Scale. In all patients the functional results after burn trauma in the face and, in some cases, asymmetries at rest could be objectified. Depending upon the severity of scarring, the distance between tragus and mouth was shortened between 0 and 19% after maximal showing of the teeth. In general the mouth region showed more functional deficits than the forehead. Comparing different manners of treatment, it could be objectively demonstrated that the results after deep burns requiring skin grafts were worse than those observed after more superficial lesions and other methods of coverage. The application of keratinocytes to close the burn showed highly variable results.