Protein expression studies of desmoplakin mutations in cardiomyopathy patients reveal different molecular disease mechanisms.

Mutations in the gene for desmoplakin (DSP) may cause arrhythmogenic right ventricular cardiomyopathy (ARVC) and Carvajal syndrome (CS). Desmoplakin is part of all desmosomes, which are abundantly expressed in both myocardial and epidermal tissue and serve as intercellular mechanical junctions. This study aimed to investigate protein expression in myocardial and epidermal tissue of ARVC and CS patients carrying DSP mutations in order to elucidate potential molecular disease mechanisms. Genetic investigations identified three ARVC patients carrying different heterozygous DSP mutations in addition to a homozygous DSP mutation in a CS patient. The protein expression of DSP in mutation carriers was evaluated in biopsies from myocardial and epidermal tissue by immunohistochemistry. Keratinocyte cultures were established from skin biopsies of mutation carriers and characterized by reverse transcriptase polymerase chain reaction, western blotting, and protein mass spectrometry. The results showed that the mutation carriers had abnormal DSP expression in both myocardial and epidermal tissue. The investigations revealed that the disease mechanisms varied accordingly to the specific types of DSP mutation identified and included haploinsufficiency, dominant-negative effects, or a combination hereof. Furthermore, the results suggest that the keratinocytes cultured from patients are a valuable and easily accessible resource to elucidate the effects of desmosomal gene mutations in humans.

Metastatic spinal cord compression secondary to lung cancer.

PURPOSE: Metastatic spinal cord compression (MSCC) is a disabling complication to cancer, the optimal treatment for which is not settled. An analysis was performed for all patients with MSCC secondary to lung cancer in East Denmark from 1979 to 1988. PATIENTS AND METHODS: The total series included 102 cases with small-cell carcinoma (SCLC; 40%), adenocarcinoma (ACL; 26%), squamous cell carcinoma (SQLC; 18%) and large-cell carcinoma (LCC; 9%). Symptoms, clinical presentations, and therapeutic results are described. RESULTS: The outcome of treatment depended fundamentally on the patient's neurologic condition at the time of the diagnosis. All patients with SCLC who were able to walk at the time of MSCC remained ambulatory, whereas 15% of the nonambulatory SCLC patients regained walking ability. In non-SCLC, 95% of patients continued to be able to walk, whereas 22% regained the ability to walk. No major differences in the immediate outcome of treatment between the various histologic types of lung cancer and the different treatment modalities were observed; however, 82% of the patients with non-SCLC benefited from treatment with laminectomy followed by radiotherapy (RT) compared with either laminectomy (47%) or RT (39%) alone (P = .03, chi 2 test). The group of patients who were treated with laminectomy followed by RT had a better survival (median value, 3.5; range, 0 to 132 months) than patients who were treated with either laminectomy (median value, 1.5; range, 0 to 32 months) or RT (median value, 1; range, 0 to 59 months) alone (P = .03, log-rank test). No significant difference was observed in survival between the various histologic types of lung cancer (P = .18, log-rank test). CONCLUSION: Despite a short survival, early diagnosis and immediate treatment is crucial because it may preserve the gait function in 97% of lung cancer patients who develop malignant spinal cord compression.

[Undescended testis treated by intranasal application of luteinizing hormone-releasing hormone (LH-RH)]. / Non-descensus testis behandlet med intranasalt appliceret luteiniserende hormon/frigørende (releasing) hormone (LH-RH).

In a double-blind, placebo-controlled study, 118 boys, aged 2-12 years, with 161 undescended testes were treated with luteinising-hormone releasing-hormone (LH-RH), 1.2 mg daily intranasally for four weeks. According to randomization, 60 boys with 85 undescended testes received LH-RH and 58 boys with 76 undescended testes received the placebo. 17 testes (20%) in 12 boys (20%) descended in the LH-RH group and 2 testes (3%) in 2 boys (3%) descended in the placebo group. This difference is statistically significant (chi 2, 0.01 greater than p greater than 0.001). A second LH-RH course, offered three months later to the boys who did not respond to the first LH-RH course, increased the success rate to 35%. The primary location of the testis was a significant factor for the effect of treatment. The highest success rate (63%) was registered in testes located in a high scrotal position. There was no significant difference in success of treatment between unilateral and bilateral cryptorchidism, nor between age groups. No serious adverse effects of treatment were noted. It is concluded, that LH-RH administered intranasally can be used in the treatment of boys with unilateral and bilateral cryptorchidism.

[Hormonal treatment of undescended testis]. / Hormonal behandling af non-descensus testis.

Failure of the testes to descend is probably mostly due to dysfunction of the hypothalamo-pituitary-testis axis. The primary treatment of testicular non descent should therefore be pharmacological in the form of HCG injections or LH-RH intranasally. Contraindications for hormonal therapy are coexistent inguinal hernia or hydrocele testis or previous inguinal operations. HCG and LH-RH treatment lead to testicular descent with about the same frequency, 20-50% in boys above five years of age, whereas HCG therapy before this age results in 10-20% success only. Reversible androgenic side effects are described in approximately 30% following HCG treatment, but only limited side effects are seen in less than 10% after LH-RH therapy. Because of the non-invasive mode of administration, the good response to treatment in the age of 2-5 years and the very limited side effects, LH-RH is recommended as the primary treatment of testicular nondescent.

Surgical treatment of complex partial seizures: results, lessons, and problems.

The underlying seizure tendency of complex partial seizures often involves the temporal region of the brain, but the frontal lobe can also produce similar complex partial seizures. By the end of 1980, 1,210 patients with medically refractory temporal lobe epilepsy had been operated on at the Montreal Neurological Institute. Nontumoral epileptogenic lesions were present in 1,034 patients, 169 had tumors, and 7 had major vascular malformations. Thirty-seven percent of the 894 evaluable patients with nontumoral epileptogenic lesions have become and remained seizure-free. Two hundred thirty-six (26%) patients had a marked reduction of seizure tendency. Within the seizure-free group, 63% had a complete or nearly complete reduction of their medically refractory tendency following temporal lobectomy. Of the patients with temporal lobe epilepsy due to tumoral lesions, 46% of the evaluable patients have become and remained seizure-free, and 76% have had a complete or nearly complete reduction of seizure tendency.