Dynamic interaction of genetic risk factors and cocaine abuse in the background of Parkinsonism - a case report.

BACKGROUND: Parkinsonism is a complex multifactorial neurodegenerative disorder, in which genetic and environmental risk factors may both play a role. Among environmental risk factors cocaine was earlier ambiguously linked to Parkinsonism. Former single case reports described Parkinsonism in chronic cocaine users, but an epidemiological study did not confirm an increased risk of Parkinson's disease. Here we report a patient, who developed Parkinsonism in young age after chronic cocaine use, in whom a homozygous LRRK2 risk variant was also detected. CASE PRESENTATION: The patient was investigated because of hand tremor, which started after a 1.5-year period of cocaine abuse. Neurological examination suggested Parkinsonism, and asymmetrical pathology was confirmed by the dopamine transporter imaging study. The genetic investigations revealed a homozygous risk allele in the LRRK2 gene. After a period of cocaine abstinence, the patient's symptoms spontaneously regressed, and the dopamine transporter imaging also returned to near-normal. CONCLUSIONS: This case report suggests that cocaine abuse indeed might be linked to secondary Parkinsonism and serves as an example of a potential gene-environmental interaction between the detected LRRK2 risk variant and cocaine abuse. The reversible nature of the DaTscan pathology is a unique feature of this case, and needs further evaluation, whether this is incidental or can be a feature of cocaine related Parkinsonism.

The importance of follow-up examinations in patients with carcinoid tumor.

Carcinoid tumors are rare forms of gastrointestinal tumors, although lately they have been found with increasing frequency. We report here the combined diagnosis of an intestinal metastasized carcinoid tumor. A 67-year-old patient was followed up during a nine-year period. In 1990 the patient was diagnosed with carcinoid tumor of intestinal origin with multiple liver metastases. Initial treatment consisted of partial resection of the intestine and resection of the liver. Since multiple liver metastases were found, chemoembolization was also performed. After this therapy the patient was free of complaints until 1996. That year the patient reported upper abdominal pain with occasional diarrhea. Given his past medical history and multiple hepatic metastases proven by three-dimensional ultrasonography, combined octreotide and interferon therapy was started following octreoscan scintigraphy. During a three-year period the patient was without complaints and the tumor marker value decreased to almost normal. In 1998 the patient at a regular follow-up visit complained about colic abdominal pain around the umbilical region. Abdominal ultrasonography showed a local wall thickening in the intestinal region. The computed tomography and selective enterography were positive as well. The surgical treatment and histology demonstrated intestinal recurrence of the tumor in the ileal region. After the operation we started a long-acting sandostatin and interferon treatment. We conclude that an ultrasound with a high index of clinical suspicion is a useful test for the diagnosis of carcinoid tumor in detection and in follow-up examinations.

Prolactin influences proliferation and apoptosis of a human IgE secreting myeloma cell line, U266.

In certain types of solid tumours and lymphomas prolactin (PRL) potentiates tumour cell proliferation and exerts anti-apoptotic effect. Tumour cells themselves can produce PRL and express PRL-receptors. Hyperprolactinemia is associated with different tumours, also. Multiple myeloma (MM) is a haematological malignancy caused by the clonal expansion of terminally differentiated plasma cells in the bone marrow. Recently, we demonstrated PRL immunostaining in bone marrow cells of MM patients and an elevated level of serum PRL of MM patients with advanced disease. In the present study, we tested the effect of PRL on a U266 human myeloma cell line and demonstrated constitutive and melphalan-stimulated intracytoplasmic PRL in U266 cells. Exogeneous PRL inhibited the proliferation and immunoglobulin (Ig) production of U266 myeloma cells. Concerning etoposide-induced apoptosis, PRL had a double-faceted effect depending on the applied dose: high, pharmacological doses (corresponding to hyperprolactinemia), inhibited apoptosis, whereas near physiological doses exerted a pro-apoptotic effect. These data indicate a definite effect of PRL on a human myeloma cell line. We demonstrated a direct inhibition of PRL on tumour cell growth, while its reciprocal effect on apoptosis refers to an important regulatory role of PRL.