Microbial patterns in patients with histamine intolerance.

Histamine intolerance represents a controversially discussed disorder. Besides an impaired degradation of orally supplied histamine due to diamine oxidase (DAO) deficiency, a deranged gut flora may also contribute to elevated histamine levels. Our aim was to determine the intestinal bacterial composition in patients with proven histamine intolerance in comparison to other food intolerances and healthy controls. A total of 64 participants were included in the study, encompassing 8 patients with histamine intolerance (HIT), 25 with food hypersensitivity (FH), 21 with food allergy and 10 healthy controls (HC). All participants underwent blood testing for total and food-specific immunoglobulin E, plasma histamine and DAO serum activity. Stool samples were used to analyze stool histamine and zonulin levels and bacterial composition by 16s rRNA sequencing. No significant differences in stool histamine levels were observed, but HIT patients showed elevated levels of stool zonulin. Microbiota analysis revealed increased levels of Proteobacteria (5.4%) and a significantly reduced alpha-diversity in the HIT group (P = 0.019). On family level, HC showed a significantly higher abundance of Bifidobacteriaceae compared to other study groups (P = 0.005), with lowest levels in the HIT group (P = 0.036). Also significantly reduced abundances of the genera Butyricimonas (P = 0.026) and Hespellia (P = 0.025) were observed in the HIT patients, whereas Roseburia were significantly elevated (P = 0.021). We concluded that the altered occurrence of Proteobacteria and Bifidobacteriaceae, reduced alpha-diversity as well as elevated stool zonulin levels suggest a dysbiosis and intestinal barrier dysfunction in histamine intolerant patients, which in turn may play an important role in driving disease pathogenesis.

Circadian profiling reveals higher histamine plasma levels and lower diamine oxidase serum activities in 24% of patients with suspected histamine intolerance compared to food allergy and controls.

BACKGROUND: Histamine intolerance is thought to trigger manifold clinical symptoms after ingesting histamine-rich food due to reduced activity of diamine oxidase (DAO). No study has hitherto systematically assessed daily fluctuations of histamine levels and DAO activities in symptomatic patients. The aim of the study was to investigate the presence of histamine intolerance, to therefore establish day profiles of histamine levels and DAO activities, and to compare the results between patients with suspected histamine intolerance, food allergy and healthy controls. METHODS: We determined day profiles of histamine plasma levels and DAO serum activities in 33 patients with suspected histamine intolerance, in 21 patients with proven food allergy and in 10 healthy control patients. Clinical symptoms, food intolerances and further clinical and laboratory chemical parameters were evaluated. RESULTS: Twenty-four percent (8 of 33) suspected histamine-intolerant patients showed elevated histamine levels during the day. That might be caused by constantly and significantly reduced DAO activities in these patients compared to food-allergic and control patients. The remaining 25 patients presented normal histamine levels and DAO activities, but an increased prevalence of multiple food intolerances compared to the other subgroup of suspected histamine-intolerants. There was no correlation between subjective complaints and serological histamine parameters in patients with suspected histamine intolerance. CONCLUSIONS: We determined by daily profiling that decreased DAO activities correlated with elevated histamine levels in a subgroup of suspected histamine-intolerants. This finding discriminates these patients from food intolerant individuals with similar clinical symptoms and strongly suggests the presence of histamine intolerance.

The prognostic value of IDH mutations and MGMT promoter status in secondary high-grade gliomas.

Reports about the prognostic value of IDH mutations and the promoter region of the O6-Methyl-guanyl-methyl-transferase gene in secondary high-grade gliomas (sHGG) are few in number. We investigated the prognostic value of IDH mutations and methylation of the promoter region of the MGMT gene in 99 patients with sHGG and analyzed the clinical course of those tumors. Patients with sHGG were screened for IDH mutations by direct sequencing, and, for promoter status of MGMT gene, by the methylation-specific polymerase chain reaction. A total of 48 of 99 patients (48.5 %) had secondary anaplastic gliomas (Group 1), while 51 patients had secondary glioblastomas (Group 2). The median survival time after malignant progression of all patients with sHGG and with an IDH mutation was 4 years, which is significantly longer than in patients with wild-type IDH (1.2 years, p = 0.009). Patients' survival was not significantly influenced by the tumors' MGMT promoter status, both in Group 1- 9.7 years vs. 6.1 years, methylated vs. unmethylated promoter (p = 0.330)-as well as in Group 2-1.5 years vs. 1.6 years, methylated versus unmethylated promoter (p = 0.829). In our population, the IDH mutation status was not associated with increased PFS or median survival time in sGBM patients. However, patients with secondary anaplastic glioma and IDH mutation had a significantly improved outcome. In addition, IDH mutations are a more powerful prognostic marker concerning both PFS and MS than the MGMT promoter status in those patients.

Free DIEP-flap reconstruction of tumour related defects in head and neck.

The free deep inferior epigastric perforator flap (DIEP) is a well-established therapy for plastic reconstruction of the breast or defects of the lower extremity without distinct donor site morbidity. Because of its particular qualities we started to apply the DIEP-flap also in reconstruction of defects in the cranio-maxillofacial area. A series of 10 consecutive patients, who received a DIEP-flap for reconstruction of large soft tissue defects after ablative tumour surgery, was reviewed. Nine of the 10 flaps survived and uneventfully healing was observed in 8 of the 10 flaps. Primary layered closure of the abdominal wall was achieved in all cases and no complications at the donor site were observed. In our experience the DIEP may serve as a well considerable alternative to the rectus abdominis flap and the latissimus dorsi flap for bridging extensive reconstructions in the cranio-maxillofacial region. It offers the possibility for flap elevation simultaneously to the surgical procedures in the head and neck area. A special advantage of the DIEP-flap is the very low donor site morbidity.

Frontoethmoidal meningoencephalocoele repair in Cambodia: outcomes and cost comparisons.

In Cambodia, spina bifida is rare, but frontoethmoidal meningoencephalocoeles (MECs) are common. Mean life expectancy for patients with congenital MECs may be <20 years, but the complex treatment required has not been available in the country until recently. During visits by combined neurosurgical/craniofacial teams from both Germany and France, a method of repair has been developed that is suitable for the local conditions, affordable and has allowed Cambodian surgeons to learn how to successfully treat MECs. The surgical technique and initial results with 30 patients have been described in a previous publication. This paper presents the outcomes of 128 cases and illustrates that it is cost-effective for these patients to be treated in Cambodia.

Primary aspergillosis of the sphenoid sinus with pituitary invasion - a rare differential diagnosis of sellar lesions.

Aspergillosis belongs to the group of mycotic diseases of paranasal sinuses. The invasive forms, and particularly the fulminant forms, are potentially fatal. Isolated aspergillosis of the sphenoid sinus or the clivus is a difficult diagnosis, since the often misleading clinical manifestations of this rare disease develop late. These patients become apparent by neurological signs such as cavernous sinus syndrome, pseudotumor of the pituitary or the orbit. Diagnosis is often made intra-operatively or on histological examination. We report a case of invasive aspergillosis uniquely involving the sellar area revealed by clinical features suggesting a pseudotumor of the pituitary. Although such lesions are almost always seen in immune suppressed subjects, in our case, the patient was immune competent and had no past history of sinusitis.The question of whether, and when to perform limited or extensive surgery remains an issue for discussion, owing to the rarity of this disease honed by lack of experience. It depends on several factors: the kind of disease, the immunity, the subtype of invasive fungal sinusitis and the degree of tissue invasion.

[Spinal meningioma as differential diagnosis of diabetic polyneuropathy]. / Spinales Meningeom als Differenzialdiagnose der diabetischen Polyneuropathie.

HISTORY AND ADMISSION FINDINGS: A 70 year old woman had suffered from diabetes mellitus type 2 since she was 52. Three years before the surgery she had begun to experience weakness together with altered sensitivity in the right leg, which was regarded as having been caused by diabetic polyneuropathy. During the admission examination the level for algesia on the right-hand side was at about D 11, a distal paraparesis of the leg (3-4 degrees, Janda's classification), more intense on the right, hyperactive deep tendon reflexes, Babinski's reflex on both sides, and depressed abdominal cutaneous reflexes. The sensitivity to vibrations on the Malleolus medialis on both sides was 0/8. The patient could walk only with the help of a Rollator. INVESTIGATIONS: Over the three-year period following onset of symptoms the following tests were carried out: motor nerve conduction speeds of the N. tibialis and N. peronaeus, electromyogram of the N. tibialis anterior and the M. gastrocnemius, somatosensory evoked potentials (SSEP) of the N. tibialis, which indicated a lesion in the peripheral nerves or nerve roots. Cranial computed tomography (CCT), CT scan of the lumbar spine (L3-S1) and angiological investigation elicited no significant pathological findings. An MRI of the thoracal spine showed a vertebra-sized dorsal tumor pressing on the spinal cord from left to right. TREATMENT AND COURSE: By means of microsurgery the spinal tumor was completely removed. Suspected meningeoma was confirmed by histological analysis. During the post-surgical period, the incomplete paraplegia quickly regressed, and 7 weeks after the removal of the spinal meningeoma the patient was able to climb stairs. CONCLUSION: In case of slowly-developing paresis of the legs in diabetic patients, diabetic polyneuropathy should not be diagnosed without careful consideration, and rare spinal tumors should be considered as part of the differential diagnosis, especially if the blood glucose level is normal, and intensive physiotherapy brings no improvement in the patient's condition.

Cushing's disease in a 7-month-old girl due to a tumor producing adrenocorticotropic hormone and thyreotropin-secreting hormone.

We present the case of a 7-month-old baby with Cushing's disease due to an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma combined with cells producing thyreotropin-secreting hormone (TSH). In MRI scans, a contrast-enhancing lesion was seen inside the pituitary fossa, and it extended into the suprasellar region. On the assumption of a pituitary adenoma, surgery was performed. Corresponding with biochemical findings, histopathological evaluation revealed an ACTH- and TSH-producing tumor. Genetic analysis did not demonstrate an alteration at codon 201 (Arg) and 227 (Glu). To our knowledge, this is the first case described in a child of this age.

Human hypersensitivity angiitis: an uncommon cause of death after trauma.

INTRODUCTION: The article demonstrates, using a case report, that death following an accident may have rarely encountered causes that are not a direct result of trauma and that can only be detected by autopsy. CASE: An unconscious woman aged 57 years was admitted to hospital. Despite immediate surgery for intracranial haemorrhage diagnosed by means of cranial computed tomography, the patient died showing clinical symptoms of circulatory depression after a brief period of stabilisation. The autopsy established myocardial infarction with hypersensitivity angiitis as the cause of death. CONCLUSION: In this case, the authors hold the opinion that the intravenous application of antibiotics during the patient's stay in hospital resulted in hypersensitivity angiitis. The factors causing hypersensitivity angiitis, the morphological picture (clinical, histological) and therapeutic measures are described.

Anomalies of lipoprotein pattern and fibrinolysis in acromegalic patients: relation to growth hormone levels and insulin-like growth factor I.

The influence of hGH and IGF-I levels on lipid-, lipoprotein metabolism and fibrinolysis were studied in 23 patients with active acromegaly (14 women and 9 men, mean age 49.8 +/- 2.1 years) compared to a sex, BMI and age-matched control group. Mean Lp(a) levels were significantly higher in acromegalics than in controls (469.8 +/- 140.1; n = 23 vs. 162.7 +/- 64.9 mg/l; n = 111; p < 0.01). We found elevated apolipoprotein A-I and Apo E-concentrations in acromegalic patients compared to controls (apo A-I: 1.79 +/- 0.06 vs. 1.46 +/- 0.04 g/l; p < 0.01; apo E: 98.35 +/- 6.4 vs. 72.53 +/- 3.38 mg/l; p < 0.05). 30% of the acromegalics showed increased plasminogen activator inhibitor activity (PAI) while 66% had increased tissue-type plasminogen activator (t-PA) concentrations. There was a correlation between hGH and Lp(a) (r = 0.414; p = 0.05), between hGH and PAI (r = -0.59; p < 0.005) and IGF-I and t-PA activity (r = -0.44; p < 0.05). In a subgroup of nine acromegalics Lp(a) was reduced by 32.2 +/- 6.7% (p < 0.05) after a six-month octreotide therapy and HDL2-cholesterol-concentration increased from 0.17 +/- 0.04 to 0.24 +/- 0.04 mmol/l (p < 0.05). In conclusion, our results demonstrate that elevated Lp(a)-concentrations and changes in fibrinolysis contribute to the cardiovascular complications and should therefore be controlled in acromegalic patients.

Long-term effect of octreotide in acromegaly on insulin resistance.

An important feature of acromegaly is a reduced action of insulin on hepatic gluconeogenesis and peripheral glucosal disposal. Octreotide (SMS) exerts complex effects on hormonal and metabolic regulations affecting glucose homeostasis. Eight patients with active acromegaly despite surgical intervention (age 44.8 +/- 3.5 years, BMI 27.3 +/- 1.6 kg/m2, lean body mass (LBM) 70 +/- 3.2%, blood glucose 5.24 +/- 0.26 mmol/l, HbA1c < or = 6.5%) were investigated before and after 6 months of treatment with SMS in an open trial. SMS was injected sc. at a dosage between 100-200 micrograms t.i.d. Mean GH and IGF1 levels during SMS therapy were significantly reduced (GH 9.6 +/- 1.9 ng/ml vs. 4.9 +/- 1.3 ng/ml, p < 0.05; IGF1 729.5 +/- 84 ng/ml vs. 415 +/- 49 ng/ml, p < 0.05). OGTT and euglycaemic-clamp-studies were performed before and after 6 months of SMS treatment. The glucosal disposal rate on average (insulin infusion rate 40 mU/m2/min) was not significantly changed following SMS treatment (McLBM before 3.60 +/- 0.38, after 3.95 +/- 0.41 mg/kg LBM/min). There was a positive correlation (r = 0.620) between the individual change of IGF1 and the change of McLBM. Additionally there was no significant difference of serum basal insulin levels (0.19 +/- 0.01 vs. 0.23 +/- 0.06 nmol/l) as well as basal C-peptide levels (0.79 +/- 0.07 vs. 0.47 +/- 0.04 nmol/l) before and with SMS treatment. We therefore conclude that long-term treatment of acromegalic patients with SMS, which achieves a successful reduction of GH and IGF1 levels, does not always guarantee a significant improvement in glucose metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous burrhole trephination of the skull: a study of 519 cases.

We want to report on our experiences with the percutaneous trephination using a 2.35 mm round dental drill with serrated saws around it, a "Rosenbohrer". It is a methodically similar activity as described by J. Zentner [11]. From 1981 to 1992 519 patients were treated and 546 trephinations were performed. At the beginning this treatment was only used in connection with intracerebral bleedings and biopsies. In a considerable short time the indication could be extended to the subdural hematoma, tumor cyst, obstructive hydrocephalus as well as to the abscess and the subdural epyema. The rate of infection was 1.28% and the risk of bleeding 0.36%. In our opinion the advantages of this small electrical trephination are the easy handling, the universal use and mobility and the avoidable risk of anesthesia as well as the sterilisation at the same time and the stopping of blood, caused by the contact surface friction.

[Intracranial chordoma. Case report of a destructively growing chondroid chordoma in the area of the sella turcica]. / Das intrakranielle Chordom. Fallbericht eines destruktiv wachsenden chondroiden Chordoms im Bereich der Sella turcica.

Evaluating the literature a short survey is given about chordomas of intracranial localization. A case of a chondroid chordoma growing destructively in the base of the skull is described. Because of the localisation in the region of the sella turcica the first diagnosis was an adenoma of the hypophysis or craniopharyngioma. Although it is a chondroid chordoma 14 months after operation a recidive tumour was seen.

[Psychologic adjustment process following high cervical spine paralysis and its support by a bedside reading apparatus]. / Der pyschologische Anpassungsprozess nach hoher Halsmarklähmung und seine Unterstützung durch einen bettseitigen Leseplatz.

The process of psychological adjustment, which has to go on after high levelled lesions of the cervical spinal cord, passes through several phases. It needs a lot of empathy, plenty of time for confidential talks and psychological knowledge as well as an individualizing cooperation between the several levels and stages of combined treatment during rehabilitation. We could give this process a considerable advance by a (half-) automatic bedside-projection of belletristic literature, which can be continuously read on a screen from long film strips by means of a modified Pentacon system. The introduction of this new object in life proved a good support for the threatened personality of those badly handicapped patients.