Use of Ipilimumab and Pembrolizumab in Metastatic Melanoma in a Combined Heart and Kidney Transplant Recipient: A Case Report.

New therapeutic agents such as checkpoint inhibitors are promising strategies in the treatment of metastatic melanoma. Transplant recipients are generally at higher risk of malign diseases. Limited data are available for the use and safety of these agents in this population. We describe a patient who had a stable transplant function over years after a combined heart and kidney transplantation. Immunosuppressive medications included tacrolimus and azathioprine and were later switched to sirolimus and azathioprine. Metastatic melanoma was diagnosed; after detailed explanation of the potential risk, the patient was initially treated with the anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody ipilimumab but experienced an acute kidney graft rejection and rapid progression. Rejection therapy with high-dose corticosteroids was successful, and kidney function was stabilized. Because of the urgent request of the patient for additional therapy, he received a PD-1 inhibitor. Acute kidney graft rejection resulted, with indication for acute dialysis. He developed severe candida pneumonia and died despite extensive antimicrobial therapy. Checkpoint inhibitors have become the standard in a broad entity of tumors. Organ transplant patients are at higher risk of developing malignant diseases. Limited data are available for the use of checkpoint inhibitors in this subgroup, and the use of checkpoint inhibitors is associated with a high risk of graft rejection.

Temozolomide and interferon alpha 2b in metastatic melanoma stage IV.

BACKGROUND: A multicentre, centrally randomized, open-labelled study with temozolomide and interferon (IFN)-alpha 2b was carried out to study the therapeutic effect in patients with metastatic melanoma stage IV. OBJECTIVES: The response rate, efficacy, side-effects, reasons for discontinuation of therapy and survival rate of 47 patients treated with temozolomide in combination with two different dosing regimens of IFN-alpha 2b were documented. PATIENTS/METHODS: Twenty-nine male and 18 female patients (mean age 57.6 years, range 34-74) were centrally randomized to two different arms: 20 patients received a treatment schedule with temozolomide 150 mg m(-2) on days 1-5 orally every 28 days in combination with IFN-alpha 2b 10 MIU m(-2) every other day and 27 patients received temozolomide 150 mg m(-2) on days 1-5 every 28 days in combination with IFN-alpha 2b in a fixed dose of 10 MIU every other day. RESULTS: We observed an overall response rate of 27.6% comprising five complete remissions (10.6%: one patient group A, four patients group B), in two of these five patients at the last follow-up in the study (4.3%, both in group B); and eight partial remissions (17%: six patients in group A, two patients in group B), in three of these eight patients at the last follow-up in the study (6.4%, two patients in group A, one patient in group B). Three patients showed stable disease (6.4%: one patient in group A, two patients in group B). Mean survival was 14.5 months [95% confidence interval (CI) 10-19] with no significant differences between treatment groups. However, there was a significant correlation with response after three cycles (log rank test, P < 0.03). Within the 32 patients who completed at least three cycles of therapy, seven patients (three in group A and four in group B) with a partial or complete response showed a significantly better mean survival of 30.6 months (95% CI 19.1-42) compared with 25 patients who did not respond (13.7 months 95% CI 9.2-18.3). In total, patients with at least one complete remission showed the longest survival (37.1 months 95% CI 26.3-47.9), followed by patients with at least one partial response (17.4 95% CI 10.9-23.9). Major side-effects of the treatment were nausea, vomiting, headache, leucopenia, thrombopenia, elevation of liver function parameters and neurological symptoms. In five patients, the side-effects led to a discontinuation of treatment: neurological symptoms (two patients), sepsis (one patient), brain haemorrhage (one patient) and exanthema (one patient). There were no treatment-related deaths. CONCLUSIONS: The combination of temozolomide and IFN-alpha 2b can easily be administered and shows tolerable toxicity. When an objective response occurs after three cycles, it indicates a significant survival advantage.

[The course of infantile autism through adulthood. An overview of long-term follow-up data]. / Lebenswege frühkindlicher Autisten im Erwachsenenalter. Eine Ubersicht über langzeitkatamnestische Daten.

The symptoms of infantile autism were first described almost 60 years ago. In contrast to its course in puberty and adolescence, follow-up-data on the late course in adulthood are decidedly sparse. As the outcome of research in the literature, we found 21 methodologically heterogeneous follow-up-studies. The arithmetic mean age of all subjects investigated was 24.0 years. The results are supplemented by various case reports and sporadic biographical reports by affected persons. On the basis of the available data, the discontinuous and dynamic changes of course verified in puberty and adolescence are not applicable to the third and fourth decades to the same extent. Gains in competence and autonomy appear to develop in the vocational rather than in the domestic sphere. The significantly more favorable courses of the form described by Asperger are continued in adulthood. The disorder-associated lack of empathy and social interaction is by no means experienced in terms of self-satisfaction by those concerned but rather as a loss. Interpersonal sexual needs are expressed by a substantial proportion of autistic adults. The cumulative mortality rates of the follow-up-studies suggest that the mortality rate among autistic patients is higher than among their non-autistic peers.

A clonal translocation t(10;21) in an optic glioma of a patient with neurofibromatosis type 1 (NF 1).

An 11-year-old boy affected by neurofibromatosis type 1 is presented with severely impaired vision on the right eye (0.1). MRI demonstrated a 2.3 x 1.8 cm tumour of the optic chiasma. After open biopsy cytogenetic analysis was performed on primary cultures of this optic glioma (grade I). A clonal translocation t(10;21)(q21.2;21.1) was detected in 66% of the metaphases analysed. The boy received fractioned irradiation with a total tumour dose of 60 Gy. The ultimate MRI taken 18 months after radiotherapy showed no residual tumour. The vision on the right improved to 0.2, but decreased on the left to 0.6. The patient attends high school with no impairment in his daily life.

Spontaneous chromosomal aberrations in cell cultures from patients with neurofibromatosis 1.

Neurofibroma-derived cell cultures, skin fibroblast strains from NF1 patients, melanocyte cultures from café-au-lait spots and melanocytes from skin overlying neurofibroma were investigated with regard to the frequencies of spontaneous chromosomal aberrations. A 3.4-fold increased rate of stable and unstable chromosome aberrations in 34 neurofibroma cultures of 18 NF1 patients was noticed in comparison to 17 skin biopsy-derived cultures of healthy probands. Fibroblast strains from the unaffected skin of nine NF1 patients revealed a 2.6-fold higher rate of chromosome breakage compared with the control cultures. Likewise, an increase of spontaneous chromosomal instability by a factor of 13.5 was found in cultured melanocytes from café-au-lait spots and by a factor of 11.9 in the skin-melanocyte cultures of six NF1 patients in comparison to foreskin-derived melanocyte strains of five unaffected persons. Analyses of the distribution of chromatid and chromosome breaks along the chromosomes revealed a significant clustering of these events in the centromeric regions specifically in the four kinds of NF1-derived cultures.

Involvement of 22q13.3 in chromosomal-anomalies.

In a series of neoplasms involvement of chromosome 22, mainly concerning loci within bands 22q11-q12 has been reported. Yet, little is known about chromosomal anomalies in 22q13. As loss of heterozygosity in two neurofibromatosis type 2 patients was described in a 22q13.3 locus and deletions in the 22q13.3 chromosomal region were noted in a set of 7 patients, we decided to apply several newly isolated cosmids from 22q13 to analyse additional cases with chromosome 22 anomalies. In addition, the study was aided by centromeric probes and chromosome 22 painting. Fluorescent in situ hybridization with new cosmids mapping to 22q13.1 and 22q13.3 did not indicate deletions or rearrangements in one neurofibromatosis type 2 case [r(22)], a bisatellited chromosome 22 and in a translocation case [t(Y;22)].

Serotonin and amino acid content in platelets of autistic children.

The platelet levels of serotonin and the amino acids aspartic acid, glutamine, glutamic acid and gamma-aminobutyric acid were measured in 18 drug-free autistic (DSM-III criteria) and 14 age-matched healthy children. Serotonin was significantly increased while the amino acids aspartic acid, glutamine, glutamic acid and gamma-aminobutyric acid were significantly decreased in comparison with the controls. It is suggested that the decline of the amino acids in platelets from autistic children represents a biochemical marker related to infantile autism.

Analysis of segregation and expression of an identified mutation at the neurofibromatosis type 1 locus.

A previously identified complex mutation, affecting exon 28 of the neurofibromatosis type 1 gene, was employed for the analysis of the expression pattern in primary cultures of neurofibroma cells and melanocytes from a café-au-lait macule of the patient, respectively. Reverse transcription and subsequent polymerase chain reaction amplification of the segment carrying the mutation revealed that both alleles were expressed in both cell types analysed, thus excluding loss of heterozygosity in this particular instance. Segregation of the alleles of the intragenic Alu sequence length-polymorphism disclosed the paternal origin of the mutated allele. Detection of this mutation was also used for presymptomatic direct DNA diagnosis in the younger child of the patient.

Cytogenetic studies of skin fibroblast cultures from a karyotypically normal female with dyskeratosis congenita.

Skin fibroblast cultures from a female patient with dyskeratosis congenita revealed markedly increased frequencies of chromosomal breaks, hypodiploidy, and premature centromere disjunction. The frequencies of mitotic disturbances, like ana- and telophase bridges, lagging chromosomes, and micronuclei were almost as dramatically elevated as in cultures from two severely affected patients with Fanconi anemia. Provided that our patient is representative for an autosomal form of dyskeratosis congenita, this type of the disease seems to be characterized by chromosomal instability with a characteristic pattern of cytogenetic abnormalities.

Savant capabilities of autistic persons.

Various savant abilities, mostly those in intellectual fields, found in autistic people, namely in music, memory, mathematics, specific knowledge and drawing, are presented. Their social importance is discussed. As an interpretation three hypotheses are offered. In autistic people perception and storing of perceived impulses function differently from in normal people (comparable to those of eidetics). The memory process and the storing function abnormally. Outstanding abilities are reinforced unilaterally by the environment and are produced as a kind of avoidance material, because many usual abilities cannot be performed.

Assessment of cutaneous fat and body fat by ultrasound.

A new rapid and simple method is introduced to measure subcutaneous fat and evaluate total body fat. It is based on real-time ultrasound and requires equipment that is used in routine examination of subcutaneous structures, e.g., thyroid gland. Results from seven regions of skin in 100 subjects correlated well with total body weight, Broca's index, and deviation from average weight 0.02 greater than P greater than 0.001). Comparisons were also made with measurements of subcutaneous fat from skinfolds. There was an excellent correlation of values (P less than 0.001 in all experiments), although ultrasound results tended to be slightly higher. For calculation of total body fat, ultrasound values were converted by regression equations to "calculated skinfold thickness"; when applying established mathematical models for calculating body fat from skinfold thickness results were equal in both methods (P greater than 0.1).

[Recognition and reading of upside down pictures and writing as a special ability of autistic children and adolescents]. / Das Erkennen und Lesen auf dem Kopf stehender (up side-down) Bilder und Schrift als Mehrleistung bei autistischen Kindern und Jugendlichen.

It is well known that autistic children and youths sometimes have unusual skills. In our investigation of 20 autistic children and 20 normal children, the autistic children were better than the control group at recognizing pictures and reading letters and words presented to them upside down. An attempt is made to explain this phenomenon in terms of the peculiarities of perception and learning common to autistic children.

[Treatment of obesity by behavior therapy (author's transl)]. / Die Behandlung von Fettsucht mit Verhaltenstherapie

Many possibilities are discussed to influence abnormal eating behavior by methods of behavior modification by learning principles. Amongst the usually employed procedures of operant conditioning, of self-control, of aversive stimuli and behavior modification by contract as new methods are used: learning by models and self-determination (giving marks as in school) of eating behavior. The proceedings are illustrated by 5 own cases (children between 9 and 13 years old). Success for longer periods was only obtained in 3 cases where a self-control program was practised.