Diagnostic value of computer analysis of multipeaked EMG spikes.

Computer analysis of absolute number of peaks per second and the number of peaks in the multipeaked spikes/sec was carried out in the EMG interference recordings of 5 healthy, 6 myopathic and 8 neuropathic subjects. The purpose of the study was to detect diagnostically different patterns. A spike was considered multipeaked if it had 6 or more peaks. The amplitude of elimination (baseline) was examined at 1: 5, 1: 10 and 1: 15 of the average amplitude per second. Both the number of peaks and the number of peaks in multipeaked spikes in the neuropathic and myopathic muscles showed statistically significant differences when compared to healthy muscles. This technique could give an indication for the differential diagnosis of myopathic, neuropathic or healthy state of the muscle.     

Multiple sclerosis: genetic versus environmental aetiology: epidemiology in Israel updated

The incidence and prevalence of multiple sclerosis (MS) were compared, controlling for age, in native-born Israelis of different origins and in immigrants to Israel. This comparison was carried out in two populations, countrywide and in Jerusalem. In the countrywide population, ascertainment was based mainly on hospitalizations; it included 252 patients who were native-born and 150 who had immigrated from Africa-Asia (AA immigrants). The 89 MS patients of Jerusalem also included patients diagnosed in outpatient clinics. In native-born Israelis whose father was born in Europe-America (I-EA), the incidence and prevalence of MS were found to be as high as or even higher than that found previously in immigrants from Europe-America. Among native-born Israelis whose father was born in Africa or Asia (I-AA), the yearly age-adjusted incidence and prevalence rates were found to be 1.4- to 1.8-fold higher than among AA immigrants, pointing to environmental factors. The incidence and prevalence rates in the I-EA were 1.2- to 1.6-fold higher than in the I-AA, pointing to genetic factors. These results seem to point to both environmental and genetic factors in the aetiology of MS. Further research is needed, however, to disentangle the genetic factors from possible environmental differences in the two ethnic groups.     

In vivo phosphorus polarization transfer and decoupling from protons in three-dimensional localized nuclear magnetic resonance spectroscopy of human brain

Refocused insensitive nucleus enhancement by polarization transfer (RINEPT) from protons (¹H) to a J-coupled phosphorus (³¹P) has been incorporated into three-dimensional (3D) chemical-shift-imaging (CSI) sequence on a clinical imager. The technique is demonstrated on a phantom and in in vivo human brain. The polarization-transfer efficiency (～1.2) is lower than the theoretical maximum of γ¹H/γ³¹P≈ 2.4 resulting from ¹H-¹H homonuclear J couplings of similar magnitude competing with the ¹H →³¹P transfer. Nevertheless, compared with direct ³¹P Ernst-angle excitation, signal gains of up to × 1.8 were obtained mainly as a result of T¹ differences between ³¹P and the ¹H. Spectral interpretation is simplified by editing out all non-proton-coupled ³¹P signals. The duration, ～50 min, and power deposition, ～1 W · kg^?1, make the application suitable for human studies.     

A not-so-basic case of metabolic alkalosis: an analysis featuring Leendert Paul and emphasizing Occam’s razor

A patient had the onset of a severe degree of metabolic alkalosis associated with a very large daily loss of diarrheal fluid. Because the expected acid-base disorder in this setting is metabolic acidosis, factors that could result in the markedly increased concentration of bicarbonate (HCO₃⁻) in plasma (P ₃) were sought. In our approach, there is an emphasis on electroneutrality, mass balance, a quantitative analysis, and the application of basic concepts in physiology at the bedside. We suggest that there were 3 major factors that could explain why the P ₃ was so high. First, a severe degree of extracellular fluid volume contraction was probably the most important factor that raised her P ₃. Second, there may have been an unusual way to have an electroneutral addition of HCO₃⁻ and removal of chloride ions from her extracellular fluid compartment. Third, the diarrheal fluid could have contained little HCO₃⁻ because of a down-regulated intestinal secretion of HCO₃⁻. This analysis challenges the traditional pathophysiology of metabolic alkalosis.     

Is there any relationship between human leucocyte antigen class II and chronic urticaria? (chronic urticaria and HLA class II)

The Human Leukocyte Antigen (HLA) typing of large groups of patients with various autoimmune diseases has demonstrated that some HLA alleles occur at higher frequencies in specific diseases than in the general population. Chronic urticaria has been shown to have an autoimmune basis by a previous study which found an association between chronic urticaria and specific HLA groups. We investigated the HLA subtypes of Turkish chronic urticaria patients. For this purpose 42 Turkish patients with chronic urticaria and 115 healthy controls were typed for HLA-DR and DQ by PCR-SSP (Polymerase Chain Reaction Sequence Specific Primers) low resolution DNA technique. We found an increased frequency of DR4 (42.9%, p=0.01) in chronic urticaria patients in comparison with that in healthy controls. This study supports the hypothesis that HLA alleles may be involved in the pathogenesis of chronic urticaria and that they appear to be directly involved in the initiation of the immune response.     

A novel point mutation (I137T) in the conserved 5-phosphoribosyl-1-pyrophosphate binding motif of hypoxanthine-guanine phosphoribosyltransferase (HPRTJerusalem) in a variant of Lesch-Nyhan syndrome

We identified a novel point mutation (I137T) in the hypoxanthine-guanine phosphoribosyltransferase (HPRT; EC 2.4.2.8) encoding gene, in a patient with partial deficiency of the enzyme (variant of Lesch-Nyhan syndrome). The mutation, ATT to ACT, resulting in substitution of isoleucine to threonine, occurred at codon 137 (exon 6), which is within the region encoding the binding site for 5-phosphoribosyl-1-pyrophosphate (PRPP). We suggest the mechanism by which the mutation-induced structural alteration of HPRT reduced the affinity of the enzyme for PRPP.     

Growth hormone co-treatment for ovulation induction may enhance conception in the co-treatment and succeeding cycles, in clonidine negative but not clonidine positive patients

To investigate the effect of co-treatment with growth hormone(GH) for ovulation induction with human menopausal gonadotrophins(HMG) on conception, we compared the pregnancy rate and responseto co-treatment with GH versus HMG/human chorionic gonadotrophin(HCG) alone in a prospective, randomized, cross-over protocolof volation induction for either in-vivo or in-vitro fertilization(IVF). The main outcome measures were the amount of gonadotrophinused and conception. Co-treatment with GH was associated witha reduction of 30% in gonadotrophin requirement. In 24 clonidinenegative patients 14 pregnancies were achieved (58.3%) eitherin the GH/HMG/HCG cycle or in the succeeding one. GH co-treatmentdid not generate any pregnancy in eight clonidine positive patients.We conclude that growth hormone may increase the pregnancy ratewhen combined with HMG/HCG for ovulation induction, not onlyin the co-treatment cycle but also in the succeeding one. Thebeneficial, synergistic effect of GH co-treatment was detectedin clonidine negative but not in clonidine positive infertilepatients.     

Activated status of tumour-infiltrating lymphocytes and apoptosis in testicular seminoma.

Testicular seminoma is characterized by a prominent lymphoid infiltrate and an excellent prognosis. Cytotoxic T-lymphocytes (CTLs) infiltrating seminoma tumour nests constitute a major subset of the lymphoid infiltrate. The objective of this study was to determine whether CTLs express markers of cytotoxic potential and activity and whether the number of activated CTLs correlates with the extent of apoptosis in testicular seminomas, as opposed to non-seminomatous testicular germ cell tumours (NSTGCTs). Twenty cases of pure seminoma as well as 20 cases of NSTGCTs including 16 mixed germ cell tumours (MGCTs) were studied. Immunohistochemistry for the cytotoxic markers TIA-1 (cytotoxic potential) and granzyme B (cytotoxic activity) and the T-cell markers CD3 and CD8 was performed on formalin-fixed, paraffin-embedded sections. The apoptotic index (AI) was determined by the TUNEL method. The number of CD3(+), CD8(+), TIA-1(+), and granzyme B(+) cells in tumour cell nests was markedly increased in testicular seminomas, compared with NSTGCTs (p<0.01). Activated granzyme B(+) cells numbered 25.6+/-5.2 per high power field in seminomas and 8.9+/-3.2, 8.1+/-3.9, and 0.4+/-0.2 for embryonal carcinomas, yolk sac tumours, and immature teratomas, respectively. Double immunohistochemical staining for granzyme B and CD8 revealed that 82.6+/-8.5% of granzyme B-expressing cells were CD8(+). The tumour cell AI was significantly increased in embryonal carcinoma, compared with the seminoma, yolk sac tumour, and immature teratoma subgroups (6.7+/-1.3, 2.3+/-0.3, 3.0+/-1.1, and 2.3+/-1.1, respectively, p<0.001). TUNEL/CD3 double immunostaining revealed that a significant proportion of the apoptotic seminomatous tumour cells were in direct contact with one or more CD3(+) lymphocytes (47.2+/-6.2%). The number of activated granzyme B(+) CTLs showed a strong linear correlation with the AI in the seminoma group (r=0.71, p<0.0001) but not in other subgroups. TUNEL/granzyme B double immunolabelling revealed that a proportion of activated granzyme B(+) lymphocytes (20%) were often seen in close contact with apoptotic tumour cells. The presence of increased numbers of activated cytotoxic lymphocytes in testicular seminomas suggests that apoptotic tumour cell death in this neoplasm may be triggered by cytotoxic granule effectors. This phenomenon may be one of the key host immune mechanisms leading to the excellent prognosis in this tumour.