[Minor foot amputations in diabetic foot syndrome]. / Minor-Amputationen beim diabetischen Fußsyndrom.

OBJECTIVE: The treatment strategy for diabetic foot syndrome must take into account protective sensibility of the foot, open wounds, infection status, and the rules of septic bone surgery. Interventions are classified as elective, prophylactic, curative, or emergency. Amputations in the forefoot and midfoot region are performed as ray amputations (including metatarsal), which can often be carried out as "inner" amputations. Gentle tissue treatment mandatory because of greater risk of revision with re-amputation compared to classical amputation. INDICATIONS: Good demarcation of infection, acute osteomyelitis, osteolytic lesions, neurotropic ulcer, arterial and venous blood flow to the other toes, gangrene of other toes with metatarsal affection. CONTRAINDICATIONS: Arterial occlusive disease, infection of neighboring areas, avoidable amputations, poorly healing ulcers on the lower leg. SURGICAL TECHNIQUE: Primary dorsal approach; minimal incisional distance (5 cm) to minimize skin necrosis risk. Atraumatic preparation, minimize hemostasis to not compromise the borderline perfusion situation. In amputations, plantar skin preparation and longer seams placed as dorsal as possible, either disarticulated and maintain cartilage, or round the cortical metatarsal bone after resection. POSTOPERATIVE TREATMENT: Diabetes control. Braun splint, mobilization in a shoe with forefoot decompression and hindfoot support, physiotherapy. Antibiotics based on resistance testing. If no complications, dressing change on postoperative day 1. Optimal wound drainage by lowering foot several times a day; drainage removal after 12-24 h. Insoles and footwear optimization. RESULTS: Amputations require continued attention and if necessary treatment to avoid sequelae. Insufficient treatment associated with recurrent ulceration and altered anatomy.

[Panniculitis of the thigh and lung emphysema in a 54-year-old patient]. / Pannikulitis des Oberschenkels und Lungenemphysem bei einem 54-jährigen Patienten.

This article reports a case of febrile, symmetrical and painful soft tissue swelling on both thighs in a 54-year-old otherwise healthy male patient. Histologically, necrotizing panniculitis of subcutaneous adipose tissue was described as a marker manifestation of a previously unknown alpha-1-antitrypsin (A1AT) deficiency with pulmonary emphysema and low plasma A1AT levels. The PiZZ homozygous form of A1AT could be diagnosed by gene sequencing. Complete remission of panniculitis could be achieved by A1AT replacement therapy.

New-onset diabetes mellitus after renal transplantation.

BACKGROUND: New-onset diabetes mellitus after organ transplantation (PTDM) significantly impairs patient and organ survival. Published rates of PTDM range from 2% to 54%, depending on the definition. OBJECTIVES: To analyze incidence of PTDM after renal transplantation according to recent guidelines and to evaluate implementation of a prospective standardized screening protocol. PATIENTS AND METHODS: Data for all consecutive patients who underwent transplantation from 2000 to 2006 were analyzed retrospectively for PTDM. In a prospective pilot trial all candidates for living related donor transplantation underwent a 75-g oral glucose tolerance test at evaluation prior to renal transplantation and at 3, 6, and 12 months thereafter. RESULTS: Data for 181 out of 271 consecutive patients were analyzed. Of these patients, 36 (19.9%) developed PTDM. Age, body mass index, pretransplantation fasting glucose concentration, and number of HLA mismatches were significant predictive risk factors. Posttransplantation diabetes mellitus occurred more frequently in patients receiving a cadaver organ compared with a living donor organ and in those receiving tacrolimus therapy vs cyclosporine therapy. Preliminary results demonstrated a 55.5% incidence of PTDM at 3 months in patients who received a living donor organ, much higher than expected. CONCLUSIONS: With an incidence of approximately 20%, PTDM is a frequent complication of transplantation. Prospective screening using oral glucose tolerance testing is a more sensitive method for detection of impaired glucose metabolism and PTDM. Relevance and therapeutic consequences must be determined in large-scale prospective studies.

Binding characteristics and crossreactivity of insulin autoantibodies and insulin antibodies directed to three different insulin molecules.

To evaluate ex vivo/in vitro the binding and dissociation characteristics and the level of crossreactivity of insulin antibodies and insulin autoantibodies directed to three different insulin molecules (human, bovine and porcine insulin). In this study sera from 17 diabetic patients were included, who were exclusively treated with s.c. human insulin, but presenting with severe insulin antibody mediated, immunological insulin resistance (i.e., insulin antibodies, IA). In addition, we included serum from one female patient, previously diagnosed with insulin autoimmune syndrome (no exposure to exogenous insulin treatment, i.e., insulin autoantibodies, IAA). Antibody concentrations and a binding/dissociation analysis was performed by using J(125)-labelled (position: A-14) human, porcine and bovine insulin according to the protocol described recently. In the patient with insulin autoimmune syndrome (IAA) we observed total crossreactivity between human, bovine and porcine insulin. By contrast, in the group of s.c. insulin treated diabetic patients with antibody-mediated insulin resistance (IA) we detected only partial crossreactivity. In these patients, there was a significantly higher level in the inital insulin binding (P < 0.05) directed to human insulin (median: 34%, IQR: 21.0-62.0), compared to porcine (median: 29.5%, IQR: 18.3-61.0) and bovine insulin (29%, IQR: 20.3-61.5), respectively. Here, we demonstrate different binding characteristics between IAA and IA, suggesting different epitope specificities. The observation of a significantly lower insulin binding to the "natural insulin analogs" (bovine and porcine insulin) compared to human insulin in the IA-group is in support of the concept that insulin analogs are eventually less immunogenic.

Fungal foot infections in patients with diabetes mellitus--results of two independent investigations.

In diabetic patients, mycotic infections may increase the risk of developing diabetic foot syndrome. However, little data are available on the prevalence of fungal foot infections in patients with diabetes. In a first study published using data obtained during a conference attended by patients with long-term diabetes mellitus type 1 (DM1), 78/95 patients (82.1%) showed probable pedal fungal infections, of which 84.6% (66/78) were mycologically confirmed by direct microscopy and/or culture. The dermatophyte Trichophyton rubrum was the most common (69.2% of isolates). Significant correlation was found between infection and the gender (men more frequently affected) and the age of the patients. Marked mycoses on the soles of the feet were often considered to be dry skin by the patients. In a second study, 174 [31 DM1, 112 DM2 and 29 healthy accompanying persons (HAP), family members without DM] participants at a regional patients' symposium on diabetes took part in an examination for fungal infections and neuropathy of the feet. In addition to the items of the first study, we gathered data on the quality of blood glucose control (HbA1c), peripheral neuropathy (neuropathy symptome and deficit score) and measurement of sudomotoric activity by Neuropad. Mean duration of disease was 23.6 (DM1) and 11.2 (DM2) years, mean HbA1c 7.56% (DM1) and 6.89% (DM2) and fungal foot infections were confirmed at 35.5% (DM1), 53.1% (DM2) and 37.9% (HAP) respectively. In DM2, the prevalence of positive fungal samples is significantly higher for participants with less controlled blood glucose (higher HbA1c) (P = 0.04). Mycotic foot infection is also correlated with age, gender and duration of diabetes disease. Of special interest is the finding of relatively high numbers of black fungi ('Dematiaceae') (n = 10), Phialophora europea (n = 3) being the most common one. The sudomotoric activity was impaired in a very high number of participants [107/171 (61.5%)], and was found positively correlated with the prevalence of fungal foot infection in DM2 but not in DM1 and HAP. The high prevalence of fungal infections detected in DM1 as well as in DM2 diabetics is remarkable, especially considering this highly motivated collective. Therefore, it appears that the feet of diabetics require more diagnostic, therapeutic and preventive care in terms of mycotic infections and sudomotoric dysfunction than previously thought.

Motives for maternal filicide: results from a study with female forensic patients.

The objective of this study was to examine different motivational factors, leading mothers to commit neonaticidal, infanticidal or filicidal acts. This study was based on data gathered through a retrospective chart review of all filicidal women admitted to the Mid-Hudson Forensic Psychiatric Hospital in New York State (MHFPC) between 1976 and 2000 (n=57). Because our sample was drawn from MHFPC records it excludes filicidal mothers who went directly to prison. Our women were either found not competent to stand trial, or found not guilty by reason of insanity, or were convicted offenders who were seriously mentally ill and were not sent to prison. Fourteen percent committed neonaticide, meaning that they killed their child within the first day of its life; 21% killed the child after the first day but before it reached its first birthday (infanticide); and 65% committed filicide by murdering a child older than one. Two groups of women could be identified as having different motivational profiles: The neonaticidal mothers were mostly troubled by psychosis and social problems while the filicidal women were defined as severely depressed, with a history of self-directed violence and a high rate of suicide attempts following the filicidal offense.

[Therapy of diabetes mellitus. Pancreas transplantation, islet transplantation, stem cell and gene therapy]. / Therapie des Diabetes mellitus. Pankreastransplantation, Inselzell-, Stammzell- und Gentherapie.

The long-term normalization of glucose metabolism - a prerequisite for the prevention of secondary complications in patients with diabetes mellitus - is only possible by transplantation of a whole pancreas or a reasonable number of islets. An absolute indication for pancreas grafting is given in type 1 diabetic patients with end-stage renal disease. The 1-year survival after simultaneous kidney/pancreas transplantation is, according to the international registry, 94-100% for patients, 89-92% for kidneys and 85-87% for the pancreas. The high success rate with long lasting normalization of glucose metabolism leads to a stabilization and/or amelioration of secondary complications, to an increase in quality of life and, most importantly, to a significant reduction in mortality when compared to diabetic kidney recipients. The indications for islet transplantation are similar to those for pancreatic grafting. Islet grafting is only a minor surgical procedure, but islet isolation is difficult. The 1-year survival for the recipients is 98%, for the islets 82% and for insulin-independency 42%. There is a significant decline of islet function to 10% 5 years after transplantation. Stem cell therapy would provide a definitive treatment solution not only for patients with type 1 diabetes. So far, this therapeutic option is still at an early stage of development.

Influence of neutral protease activity on human islet isolation outcome.

UNLABELLED: Observations in rat pancreata have revealed that enzymatic islet release is mediated by both collagenase and neutral protease (NP), a critical effector of islet integrity. Since no information is available about the effect of NP activity on islet release from the human pancreas, the present study evaluated the effect of various NP concentrations on the outcome of human islet isolation. METHODS: Following intraductal collagenase distension, pancreata obtained from adult multiorgan donors were digested using 2000 PZ-U of purified Serva collagenase NB 1 supplemented with 2.6 (n = 10) or 4.5% (DMC-U/PZ-U) (n = 10) of NP. RESULTS: Increasing NP from 2.6% to 4.5% reduced the amount of undigested tissue from 22 +/- 2 to 17 +/- 2 g (P < .05) while simultaneously increasing the volume of digested tissue (26 +/- 2 vs 40 +/- 3 mL, P < .01). Increased NP concentrations increased the islet yield prepurification (459,800 +/- 22,900 vs 587,600 +/- 69,000 IEQ, P < .05), but simultaneously affected islet purification, resulting in equal islet yields (345,700 +/- 31,200 vs 391,500 +/- 35,400 IEQ, NS) and less purity (70 +/- 6 vs 49% +/- 5%, P < .01). A NP concentration of 4.5% reduced the stimulation index (4.7 +/- 1.2 vs 2.0 +/- 0.5, P < .01) and viability (100 +/- 1 vs 95% +/- 3%, P < .05). CONCLUSIONS: Although increased NP activity seems to improve islet release from adult human pancreata, it significantly affects islet viability and function. The reduction in purity reflected damage to acinar tissue by increased NP activity presumably affecting islet integrity.

[Less severe sexual child abuse and its sequelae: are there different psychic and psychosomatic symptoms in relation to various forms of sexual interaction?]. / Minderschwere sexuelle Kindesmisshandlung und ihre Folgen. Finden sich unterschiedliche psychische und psychosomatische Symptome in Verbindung mit verschiedenen Formen sexueller Interaktion?

A typology of less severe sexual encounters was used to analyze short and long term sequelae of sexual abuse via intimate skin contact. Well known theoretical approaches on the harmful effects of sexual abuse were tested. Do we find different peri- and posttraumatic reactions dependent upon varied forms of sexual interactions with children? A cluster analysis was calculated with symptom variables that were described in 141 child statements taken out of written expert opinions. Afterwards variance analyses of these symptom clusters were conducted in reference to six different abuse constellations. Different symptom profiles were found for these six abuse constellations. Panic symptoms, shame related feelings, avoidant behavior and physical reactions showed significant results. The sequelae to different forms of less severe sexual child abuse differ and depend more upon the situational dynamic than upon the kind of relationship between adult and child.

Can the density of native pancreatic tissue slices predict human islet isolation and purification outcome?

INTRODUCTION: With currently available technology, the outcomes of human islet isolation and purification are still inconsistent, in part due to a lack of control of the pancreas donor and the procurement conditions. Using a single donor pancreas, the critical islet mass for establishing insulin independence of approximately 5000 engrafted islet equivalents (IEQ)/kg of recipient weight can only be retrieved from about one third of isolations. The purpose of this study was to analyze whether successful islet isolation and purification outcomes might be predicted from the density of native pancreatic tissue. METHODS: Tissue slices (TS) were obtained from the neck of 9 nondistended human donor pancreata. The density of the TS was determined using gravity sedimentation in continuous density gradients under either iso-osmolar or hyperosmolar conditions. Correlation coefficients were calculated with regard to the density of isolated exocrine and endocrine tissue, donor age, body mass index (BMI), cold ischemia time (CIT), IEQ prepurification and postpurification, IEQ recovery, and purity. RESULTS: (1) There was no change in density over time for TS in 300 mOsm/kg (mean, 1.079 +/- 0.0019 g/cm(3)) (2) In 500 mOsm/kg, there was a significant increase in density from 1.086 +/- 0.0021 g/cm(3) to 1.092 +/- 0.0021 g/cm(3) over time. (3) Density of isolated exocrine and endocrine became more distinct with lower density of TS (r = -0.776; P < .05). (4) Donor age, BMI, recovery of IEQ from gradients, and number of IEQ after purification did not correlate significantly with TS density. (5) In contrast, a significant inverse correlation existed betwen TS and CIT (r = -0.829; P < .05), and between TS versus IEQ number prior to purification (r = -0.867; P < .05). CONCLUSION: No homogeneous distribution of pancreas tissue density was seen among 9 consecutive human organs. Taken together, the density of native pancreas TS is not a suitable sole predictor for successful islet isolation and purification.

Optimization in osmolality and range of density of a continuous ficoll-sodium-diatrizoate gradient for isopycnic purification of isolated human islets.

INTRODUCTION: According to previous estimates from large animals and man, a minimum of approximately 5000 to 6000 engrafted islet equivalents (IEQ)/kg recipient weight is critical to establish insulin independence. Utilizing a single donor, this threshold yield of purified islets can be retrieved from approximately one third of all isolations. The aim of this study was to improve human islet purification by optimization of the osmolality and the density range of the continuous Ficoll-sodium-diatrizoate (FSD) gradient to facilitate consistent purities >80% of human islet preparations without considerable loss of islet yield. METHODS: Aliquots of human pancreatic digests were placed on continuous density gradients. After centrifugation, sequential aliquots were extracted for amylase and insulin to determine the relative and cumulative density distribution of endocrine and exocrine tissue. We addressed the impact of two factors: (1) osmolalities (300 to 600 mosm/kg) in the gradient of FSD covering a density range of 1.070 to 1.100 g/cm(3); and (2) density (FSD 500/1.070 to 1.100) versus density-osmolarity gradient (DO-FSD 400-530/1.080 to 1.113). RESULTS: The density of exocrine and endocrine tissue increased with rising osmolality. Differences in density of both tissues were highest at 450 and lowest at 300 and 600 mOsmol/kg. Purity and recovery were highest at 450 versus 400 or 500 mOsm/kg (NS). Exocrine but not endocrine tissue was more dense in DO-FSD than in FSD gradient (P < .05). The differences in density were 0.004 versus 0.013 g/cm(3) (P < .01), resulting in an increased islet purity and recovery. CONCLUSION: The best osmolality for the FSD 1.070 to 1.100 g/cm(3) is at 450 mOsm/kg. Using the DO-FSD may improve human islet purification allowing successful clinical islet transplantation.

Diagnostic algorithm and management of immune-mediated complications associated with subcutaneous insulin therapy.

Immune mediated complications associated with subcutaneous insulin therapy such as insulin neutralizing antibodies and/or skin reactions are rare conditions since human insulin is in general use. Nevertheless, if it occurs, a stepwise diagnostic approach is essential for differential diagnosis and consecutive treatment of these complications. Here we suggest a diagnostic algorithm to deal with e.g. insulin antibody formation of the IgG and/or IgE type and/or severe skin reactions resulting in poor metabolic control and often "brittle diabetes" in affected patients. This diagnostic algorithm includes step 1: Intradermal skin testing with positive and negative controls, additives and different insulin preparations; step 2: Quantification of insulin specific IgG and IgE in the serum, and step 3: Analysis of the time dependent binding/dissociation curves of the insulin neutralizing antibodies in an ex vivo/in vitro assay to assess the clinical significance of these antibodies. Based on 158 insulin treated control subjects and four patients with typical symptoms and signs representing the spectrum of immune-mediated complications subsequent to subcutaneous insulin therapy we demonstrate that the proposed stepwise approach leads to a definite diagnosis as a prerequisite for individual and successful therapy.

The role of current product release criteria for identification of human islet preparations suitable for clinical transplantation.

BACKGROUND: Alloimmunity, autoimmunity, and nonspecific inflammation are known to be potential determinants for long-term islet survival and insulin independence. Sufficient islet mass is a key determinant. But islet engraftment and posttransplant survival may also depend on functional characteristics of the graft. This study investigated the significance of current product release criteria for the transplantation outcome. METHODS: Fourty five consecutive transplanted human islet preparations and their functional outcomes were analyzed. Islet mass was determined according to standard criteria: purity by light microscopy, viability by dye exclusion and Insulin secretory response to static glucose incubation. Islet graft function was monitored for > or = 1 year. Islet function was defined as full (FF), partial (PF), or nonfunction (NF) based on serum C-peptide levels and insulin independence. RESULTS: All islet grafts displayed primary function. Islet mass [IEQ/kg BW]: 7331.3 +/- 679.7 (FF), 5821.3 +/- 546.7 (PF), 6468.6 +/- 658.5 (NF), (FF vs PF p = .032) Purity [%] 86.9 +/- 3.1 (FF), 76.0 +/- 2.87 (PF), 88.2 +/- 2.3 (NF) (FF vs PF P =.045, PF vs NF, P = 0.01). (4) Viability [%]:89.2 +/- 2 (FF), 86.2 +/- 1.7 (PF), 87.3 +/- 1.8 (NF) (ns). Stimulation index (SI): 20 +/- 6.3 (FF), 80.2 +/- 28.2 (PF), 21.6 +/- 3.5 (NF) (ns) No correlation was observed between SI and any other parameter nor between SI and C-peptide levels. Islet mass significantly correlated with C-peptide levels at 6 and 12 months after transplantation for functioning grafts. CONCLUSIONS: Stringent product release criteria allow identification of islet preparations suitable for clinical transplantation. However, currently used parameters are not predictive of long-term graft function, indicating that further refined quality assessments including apoptosis and resistance to early inflammation, are required to assess the primary engrafted islet mass.

Pancreatic islet and stem cell transplantation: new strategies in cell therapy of diabetes mellitus.

Long-term studies strongly suggest that tight control of blood glucose can prevent the development and retard the progression of chronic complications of type 1 diabetes mellitus. In contrast to conventional insulin treatment, replacement of a patient's islets of Langerhans either by pancreas organ transplantation of by isolated islet transplantation is the only treatment to achieve a constant normoglycemic state and avoiding hypoglycemic episodes, a typical adverse event of multiple daily insulin injections. However, the expense of this benefit is still the need for immunosuppressive treatment of the recipient with all its potential risks. Islet cell transplantation offers the advantage of being performed as a minimally invasive procedure, in which islets can be perfused percutaneously into the liver via the portal vein. As of June 2003, 705 pancreatic islet transplants worldwide have been reported to the International Islet Transplant Registry (ITR) at our Third Medical Department, University of Giessen/Germany. Data analysis shows at 1 year after adult islet transplantation a patient survival rate of 97%, a functioning islet graft in 54% of the cases, whereas insulin independence was meanwhile achieved in 20% of the cases. However, using a novel protocol established by the Edmonton Center/Canada, the insulin independence rates have improved significantly reaching meanwhile a 50-80% level. Finally, the concept of islet cell or stem cell transplantation is most attractive since it offers many perspectives: islet cell availability could become unlimited and islet or stem cells my be transplanted without life-long immunosuppressive treatment of the recipient, just to mention 2 of them.

Disseminated periportal fatty degeneration after allogeneic intraportal islet transplantation in a patient with type 1 diabetes mellitus: a case report.

Insulin independence after islet transplantation has been significantly improved by using new steroid-free immunosuppressive protocols and increased islet mass. Only little is known about the influence on the morphology of the liver of intraportally transplanted islets. We describe a case of disseminated periportal fatty degeneration after allogeneic intraportal islet transplantation (ITx). A 35-year-old patient with type-1 diabetes mellitus who was suffering from repeated severe hypoglycemic episodes received two sequential intraportal islet grafts. Liver structure was normal before the first ITx, based upon ultrasound and magnetic resonance imaging (MRI). One week after the first ITx, ultrasound demonstrated normal liver morphology. Four months later, at the second ITx, we detected small, disseminated, and hypodense hepatic lesions (1 to 3 mm) by ultrasound, which were confirmed by MRI and interpreted to be fatty degenerations. Histologically we found focal drop-shaped fatty degenerations with signs of mild periportal chronic inflammation. These liver alterations without clinical symptoms or pathological liver function tests matched the predicted distribution of infused islets. Glucose metabolism markedly improved after the first ITx, namely 58.6% reduction of daily insulin requirements, 1.4% decrease in HbA1c, basal C-peptide of 0.8 to 1.3 ng/dl with no severe hypoglycemia. We interpreted these benign changes in liver morphology as reactions to a local hyperinsulinemia in the neighborhood of the transplanted islets. We hypothesized that a steroid-free immunosuppression with rapamycin and tacrolimus may have contributed to changes in the portal microenvironment.

6-[3-Hydroxy-17-oxoestra-1,3,5(10)-trien-7beta-yl]hexanenitrile.

In the title compound, C(24)H(31)NO(2), ring B adopts a conformation between the boat and twisted-boat forms. This conformation best accommodates adverse intramolecular H.H interactions between the H atoms of the 7beta-substituent and the two nearest ring H atoms. The tilt angle between rings A and D is 28.6 (1) degrees.

Long-chain CoA esters activate human pancreatic beta-cell KATP channels: potential role in Type 2 diabetes.

AIMS/HYPOTHESIS: The ATP-regulated potassium (KATP) channel in the pancreatic beta cell couples the metabolic state to electrical activity. The primary regulator of the KATP channel is generally accepted to be changes in ATP/ADP ratio, where ATP inhibits and ADP activates channel activity. Recently, we showed that long-chain CoA (LC-CoA) esters form a new class of potent KATP channel activators in rodents, as studied in inside-out patches. METHODS: In this study we have investigated the effects of LC-CoA esters in human pancreatic beta cells using the inside-out and whole-cell configurations of the patch clamp technique. RESULTS: Human KATP channels were potently activated by acyl-CoA esters with a chain length exceeding 12 carbons. Activation by LC-CoA esters did not require the presence of Mg2+ or adenine nucleotides. A detailed characterization of the concentration-dependent relationship showed an EC50 of 0.7+/-0.1 micromol/l. Furthermore, in the presence of an ATP/ADP ratio of 10 (1.1 mmol/l total adenine nucleotides), whole-cell KATP channel currents increased approximately six-fold following addition of 1 micro mol/l LC-CoA ester. The presence of 1 micro mol/l LC-CoA in the recording pipette solution increased beta-cell input conductance, from 0.5+/-0.2 nS to 2.5+/-1.3 nS. CONCLUSION/INTERPRETATION: Taken together, these results show that LC-CoA esters are potent activators of the KATP channel in human pancreatic beta cells. The fact that LC-CoA esters also stimulate KATP channel activity recorded in the whole-cell configuration, points to the ability of these compounds to have an important modulatory role of human beta-cell electrical activity under both physiological and pathophysiological conditions.

[Psychosocial predictors of metabolic instability in brittle diabetes--a multivariate time series analysis]. / Psychosoziale Prädiktoren der metabolischen Instabilität bei Brittle Diabetes. Eine multivariate Zeitreihenanalyse.

The term "brittle diabetes" denotes the unstable course of an insulin-dependent diabetes characterised by frequent hypo- or hyperglycaemic crises. The aim of this study is to demonstrate empirically how psychosocial parameters interact with metabolic instability in a paradigmatic case of juvenile brittle diabetes. By means of a structured diary study, blood sugar values, moods (SAM), body symptoms (GBB), the daily hustle and hassle, helping therapeutic alliance (HAQ) and the aspects of setting were registered. Resulting time series (112 days each) were ARIMA-analysed by a multivariate approach. It could be shown that the mean variance of daily blood sugar values as an indicator of brittleness was predicted by moods, body complaints and by a family session as setting factor (p < 0.05, for corresponding predictors). Feelings of dominance preceded an increase of blood sugar variance, whereas depressive moods, anger and body symptoms were associated with metabolic instability. A family therapy session also resulted in an increase of the mean blood sugar variance. The model accounted for almost 30% of the total variance of the dependent variable (R-square-adjusted, p < 0.0001). The potential of multivariate time-series as a means to demonstrate psychosomatic interrelations is discussed. We believe that the results may also contribute to an empirically rooted understanding of psychodynamic processes in psychosomatoses.

Islet transplantation: present clinical situation and future aspects.

Beta-cell replacement either by pancreatic organ or islet cell transplantation is the only treatment to achieve an insulin-independent, normoglycemic state and to avoid hypoglycemic episodes in patients with type 1 diabetes mellitus. This article will review the state-of-the-art in clinical islet cell transplantation at the dawn of the new millennium and will provide an outlook on the basis of extended personal experience.