A preliminary study of the prognostic role of electromyography in laryngeal paralysis

Confidence in the reliability of laryngeal electromyography to predict recovery is critical if this tool is to be used to select the type and timing of surgical intervention. The characteristics of electromyography of 14 patients with unilateral vocal fold paralysis were assessed to determine which factor or combination of factors would be most useful in determining prognosis. We examined the duration, amplitude, waveform morphology, root-mean-square, and time interval from onset to electromyography recording. The results supported the concept that electromyography recordings are valuable in determining prognosis if performed before 6 months and preferably within 6 weeks of onset of laryngeal paralysis. A positive prognosis for laryngeal recovery was indicated when the following electromyography features were present in the immobile vocal fold: (1) normal motor unit waveform morphology, (2) overall electromyography activity characterized by a root-mean-square value greater than 40 microV in any one task, and (3) no electrical silence during voluntary tasks. On the basis of this criteria our overall correct prognostic rate was 89%.     

Plasma folic acid cutoff value, derived from its relationship with homocyst(e)ine

We established the cutoff value for plasma folic acid, using plasma homocyst(e)ine as the functional marker. To do this, we investigated the relationship of the plasma folic acid of 103 apparently healthy adults with their fasting plasma homocyst(e)ine and with their plasma homocyst(e)ine 6 h after oral methionine challenge (100 mg/kg). We also studied the relationship of their plasma folic acid with the decline of fasting plasma homocyst(e)ine after 7 days of folic acid supplementation (5 mg/day). The three approaches suggested a cutoff value of 10 nmol/L. The chances of individuals to significantly (P <0.05) lower their plasma homocyst(e)ine after folic acid supplementation proved significantly higher at plasma folic acid concentrations < or = 10 nmol/L, as compared with folic acid concentrations above this value (odds ratio, 5.02; 95% confidence interval, 1.87-13.73). We suggest adopting a 10 nmo/L plasma folic acid cutoff value on functional grounds.     

Racial variation of factor VII activity and antigen levels and their correlates in healthy Chinese and Indians at low and high risk for coronary artery disease

We examined the genotypes of ALDH2, ADH2, ADH3 and P-4502E1 loci of alcoholics and nonalcoholics. Also we compared the frequencies of the homozygous ALDH2*1/1 genotype and heterozygous ALDH2*1/2 genotypes in alcoholics. Our study reported differences in the allelic frequencies of ALDH2, ADH2 and ADH3 loci between alcoholics and nonalcoholics. For alcoholics, it was indicated that ADH2 and ADH3 plays an important role for alcoholism. For genotypes of P-4502E1, no significant difference was observed between alcoholics and nonalcoholics. Alcoholics with the heterozygous ALDH2*1/2 genotype had significantly higher frequency of the ADH2*1 than that of alcoholics with ALDH2*1/1 genotype. Concerning the alcoholics with the heterozygous ALDH2*1/2 genotype, we assumed that ADH2*1 plays a role for the development of alcoholism.     

Specific binding to a novel and essential Golgi membrane protein (Yip1p) functionally links the transport GTPases Ypt1p and Ypt31p

The regulation of vesicular transport in eukaryotic cells involves Ras-like GTPases of the Ypt/Rab family. Studies in yeast and mammalian cells indicate that individual family members act in vesicle docking/fusion to specific target membranes. Using the two-hybrid system, we have now identified a 248 amino acid, integral membrane protein, termed Yip1, that specifically binds to the transport GTPases Ypt1p and Ypt31p. Evidence for physical interaction of these GTPases with Yip1p was also demonstrated by affinity chromatography and/or co-immunoprecipitation. Like the two GTPases, Yip1p is essential for yeast cell viability and, according to subcellular fractionation and indirect immunofluorescence, is located to Golgi membranes at steady state. Mutant cells depleted of Yip1p and conditionally lethal yip1 mutants at the non-permissive temperature massively accumulate endoplasmic reticulum membranes and display aberrations in protein secretion and glycosylation of secreted invertase. The results suggests for a role for Yip1p in recruiting the two GTPases to Golgi target membranes in preparation for fusion.     

Risk factors for colorectal cancer in a prospective study among U.S. white men

The mRNA expression of presenilin-1 (PS1) and beta-amyloid precursor protein (betaAPP) was investigated in the embryonic day 20 rat olfactory bulb, nasal cavity, and inner ear using in situ hybridization histochemistry. In the olfactory bulb, PS1 mRNA was strongly expressed in both olfactory bulb neuroepithelium and the differentiating olfactory bulb. In contrast, betaAPP mRNA was preferentially expressed in differentiating fields. In the nasal cavity, PS1 mRNA was strongly expressed throughout the olfactory epithelium, while betaAPP mRNA expression was concentrated in the middle part of the epithelium. In the membrane labyrinth of the inner ear, although PS1 mRNA was evenly distributed in both sensory epithelium and supporting cells, betaAPP mRNA was exclusively expressed in the sensory epithelium. These data suggest that PS1 is expressed earlier than betaAPP, and that PS1 and betaAPP co-operatively play pivotal roles in the development of the olfactory and vestibulocochlear systems.     

Absence of PTEN/MMAC1 germ-line mutations in sporadic Bannayan-Riley-Ruvalcaba syndrome

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare hamartomatous polyposis condition with features of macrocephaly, intestinal juvenile polyposis, developmental delay, lipomas, and pigmentation spots of the male genitalia. An autosomal dominant pattern of inheritance exists in some families, but others appear as sporadic cases. Germ-line mutations in PTEN, a tyrosine phosphatase and putative tumor suppressor gene, have been demonstrated in two families with BRRS, and chromatin loss at the PTEN gene locus on chromosome 10q23 has been demonstrated in two BRRS patients. Germ-line mutations in PTEN have also been described in Cowden disease and in a small number of patients with juvenile polyposis syndrome. In an attempt to assess the nature of PTEN mutations in BRRS, we analyzed three sporadic BRRS patients for chromosome 10q23 deletion or PTEN germ-line mutations. All 3 patients demonstrated no loss of parental alleles at 15 chromosome 10q23 markers that encompassed the region of PTEN. In addition, analysis of mRNA and genomic DNA revealed no nonsense, missense, or insertion/deletion mutations of PTEN. Thus, other mechanisms besides mutation of PTEN must have occurred to cause BRRS in these patients. We speculate that BRRS and juvenile polyposis syndrome may have a heterogeneous etiology to cause their syndromes.     

Heparin removal after cardiopulmonary bypass in a patient with adverse reaction to protamine

A 74-year-old man underwent elective coronary surgery under cardiopulmonary bypass. A few minutes after the protamine administration was started, he suddenly developed a severe hypotension necessitating cardiac massage and recannulation for pump assistance. A further test dose of protamine provoked an identical reaction. We installed a Heparin Removal Device, which allows for ex-vivo deheparinization. In 35 minutes ACT decreased from 480 sec to 180 sec and clots appeared in the operating field. This system provides an excellent alternative to protamine in patients with an adverse reaction to protamine.     

Prodrugs of nitroxyl and nitrosobenzene as cascade latentiated inhibitors of aldehyde dehydrogenase

The prototypic aromatic C-nitroso compound, nitrosobenzene (NB), was shown previously to mimic the effect of nitroxyl (HN=O), the putative active metabolite of cyanamide, in inhibiting aldehyde dehydrogenase (AlDH). To minimize the toxicity of NB in vivo, pro-prodrug forms of NB, which were designed to be bioactivated either by an esterase intrinsic to AlDH or the mixed function oxidase enzymes of liver microsomes, were prepared. Accordingly, the prodrug N-benzenesulfonyl-N-phenylhydroxylamine (3) was further latentiated by conversion to its O-acetyl (1a), O-methoxycarbonyl (1b), O-ethoxycarbonyl (1c), and O-methyl (2) derivatives. Similarly, pro-prodrug forms of nitroxyl were prepared by derivatization of the hydroxylamino moiety of methanesulfohydroxamic acid with N, O-bis-acetyl (7a), N,O-bis-methoxycarbonyl (7b), N, O-bis-ethoxycarbonyl (7c), and N-methoxycarbonyl-O-methyl (7d) groups. It was expected that the bioactivation of these prodrugs would initiate a cascade of nonenzymatic reactions leading to the ultimate liberation of NB or nitroxyl, thereby inhibiting AlDH. Indeed, the ester pro-prodrugs of both series were highly active in inhibiting yeast AlDH in vitro with IC50 values ranging from 21 to 64 microM. However, only 7d significantly raised ethanol-derived blood acetaldehyde levels when administered to rats, a reflection of the inhibition of hepatic mitochondrial AlDH-2.     

Endothelin: receptor subtypes, signal transduction, regulation of Ca2+ transients and contractility in rabbit ventricular myocardium

Endothelin (ET) isopeptides, ET-1, ET-2 and ET-3, elicit a positive inotropic effect (PIE) in association with a negative lusitropic effect, essentially with identical efficacies and potencies in the isolated rabbit papillary muscle, but with different concentration-dependent properties. Pharmacological analysis indicates that the PIE of ET-1 is mediated by an ETA2 subtype that is less sensitive to BQ-123 and FR139317, whereas the PIE of ET-3 is mediated by an ETA1 subtype that is highly sensitive to these ETA antagonists. ETs increased the amplitude of intracellular Ca2+ transient (CaT) in indo-1 loaded rabbit ventricular myocytes, but the increase was much smaller than that produced by elevation of [Ca2+]o or isoproterenol for a given extent of PIE, an indication of increased myofibrillar Ca2+ sensitivity. ETs stimulate phosphoinositide (PI) hydrolysis, which leads to production of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). Evidence for the role of IP3-induced Ca2+ release in cardiac E-C coupling is tenuous. Generation of IP3 induced by ET-1 was transient and returned to the baseline level when the PIE reached an elevated steady level. Protein kinase C (PKC) that is activated by DAG and also via other pathways triggered by ETs stimulates Na+-H+ exchanger to lead to an increased [Na+]i and alkalinization. The former may contribute to an increase in the amplitude of CaT through Na+-Ca2+ exchanger, and the latter, to an increase in myofibrillar Ca2+ sensitivity. A number of PKC inhibitors, such as staurosporine, H-7, calphostin C and chelerythrine, consistently and selectively inhibited the PIE of ET-3 without affecting the PIE of isoproterenol and Bay k 8644. The maximum inhibition was 20-30% of the total response. A Na+-H+ exchange inhibitor, [5-(N-ethyl-N-isopropyl) amiloride (EIPA)] or a Ca2+ antagonist, verapamil, could not completely inhibit the PIE of ET-3, but the combination of both inhibitors totally abolished the PIE of ET-3. These findings indicate that activation of PKC and subsequent activation of Na+-H+ exchanger and/or L-type Ca2+ channels may play a crucial role in the cardiac action of ET isopeptides in the rabbit ventricular myocardium.     

Successful pregnancy in a woman with acute myeloid leukemia treated with high-dose whole-body irradiation

BACKGROUND: Although radiotherapy is an integral part of managing certain types of hematologic malignancies, its effect on the reproductive system are well established. We report a case of successful pregnancy in a patient who received high-dose whole-body irradiation (WBI) (1,575 cGy) as part of her treatment for acute myeloid leukemia (AML). CASE: A 26-year-old woman received high-dose cyclophosphamide accompanied by high-dose (1,575 cGy) WBI as part of her treatment for AML when she was 23 years of age. The patient received oral contraceptives before, during and after treatment. After WBI, the patient developed ovarian failure and amenorrhea, which was confirmed by hormonal evaluation. The amenorrhea persisted for one year. No recurrence of AML was found. The patient was placed on hormone replacement therapy (HRT) because of vasomotor changes. An unexpected pregnancy occurred 14 months later; HRT was discontinued. The patient delivered a normal female infant at 38 weeks of gestation. The infant was followed for eight months; her development appeared to be normal. CONCLUSION: In this case report, it is unclear whether pregnancy resulted from active folliculogenesis remote from radiation therapy or from possible ovarian protection rendered by the use of oral contraceptives. The benefit of oral contraceptives in protecting the ovary from radiation injury is unknown and remains an area for future research.