Simultaneous confirmation and differentiation of human T-lymphotropic virus types I and II infection by modified western blot containing recombinant envelope glycoproteins

A modified Western blot (WB) that includes both shared (r21e) and unique recombinant envelope proteins from human T-lymphotropic virus (HTLV) type I (rgp46I) and type II (rgp46II) was compared to conventional HTLV serologic tests in 379 United States blood donors and individuals residing in diverse geographic regions, and the specimens were categorized as positive (n = 158), indeterminate (n = 158), or negative (n = 63) for HTLV infection. Of the 158 HTLV-I/II-positive specimens (66 requiring radioimmunoprecipitation assay [RIPA] for confirmation), 156 reacted concordantly with r21e, gag, and either rgp46I or rgp46II, thus eliminating the need for RIPA in all but two specimens and yielding a test sensitivity of 98.7 percent. Of the 158 indeterminate and 63 negative specimens, none reacted with r21e and rgp46I or rgp46II, yielding a test specificity of 100 percent. Furthermore, analysis of an additional 184 consecutive specimens from a retrovirology reference laboratory demonstrated that the modified WB correctly identified 27 of 28 HTLV-I specimens and all 13 HTLV-II specimens, with a test sensitivity of 97.6 percent. None of specimens that were indeterminate or nonreactive in conventional WB and/or RIPA and none of the screening enzyme immunoassay-negative specimens reacted with r21e and either rgp46I or rgp46II, for a test specificity of 100 percent. Thus, the modified WB appears to be highly sensitive and specific for simultaneous detection and discrimination of HTLV-I from HTLV-II and has the advantage of being a one-step assay that is easily performed in all types of laboratory settings and allows rapid, reliable, and standardized testing for HTLV-I/II infection.     

Squamous cell carcinomas of the aryepiglottic fold: Therapeutic results and long-term follow-up

Three hundred fifteen patients with squamous cell carcinomas involving the aryepiglottic (A-E) folds were treated between January 1964 and December 1991. The age ranged from 39 to 87 years (mean, 62.4 years; median, 61.3 years) and the male-to-female ratio was 5:1 (54 women and 261 men). Symptom duration prior to diagnosis was 4.8 months. Eighty percent of patients had T3 and T4 lesions and 56.3% had neck metastases at presentation. Six patients (1.8%) had distant metastases and were excluded from this study. Clinically the tumors presented as either exophytic infiltrating lesions which were confined to the A-E fold (n = 57) or mucosally spreading tumors which extended to the lateral supraglottis or pyriform sinus (n = 258). Prior to 1978 preoperative radiation (3000 to 5000 cGy) was used. Higher doses of postoperative radiation (5000 to 6000+ cGy) were used thereafter. After 1982 the use of myocutaneous flaps for closure of partial laryngopharyngectomy defects was routine. Almost all NO neck disease was treated by radiation or surgery. Combined therapy was used in N1-N3 disease. One quarter of the patients had single-modality therapy (25.7%; 81 patients) with a cumulative 5-year disease-free survival of 53%. The remainder of the patients (n = 234) had combined therapy with a cumulative 5-year survival of 67.2%. The latter group had 163 conservation surgeries and 121 total laryngectomy resections. The 5-year disease-free survival for preoperative radiation with surgery (68%) and postoperative radiation with surgery (64%) was similar. Those treated by radiation alone had a 34% 5-year disease-free survival and those treated with surgery alone had a 61% 5-year disease-free survival. The cumulative locoregional control rate was 77%. The cumulative disease-free survival at 5,10,15, and 20 years is 66%, 57%, 55%, and 55%, respectively. Infiltrating tumors had a better disease-free survival (by more than 10%) than spreading tumors. The 5-year survival rates were separated well by clinical stages of tumors. In patients with T1 tumors the 5-year survival was 87%; in those with T2 tumors, 80%; in those with T3 tumors, 78%; and in those with T4 tumors, 41%. The survival rate was greater in those with NO tumors than in those with N+ tumors by 25% and greater in those with N1 tumors than in those with N2 + N3 tumors by an additional 18%. The overall complication rate was 26% and in 7.7% these were fatal. The salvage rate after single-modality therapy was equal for radiation and surgery (66.7%) and after combined therapy was better for surgery 53% (19/36) than radiation 24% (10/41). An incidence of distant metastases (16%), second primary tumors (8%), and death from intercurrent disease (11%) was documented. On a selected basis small T1N0 or T2N0 lesions can be treated equally well with single-modality therapy (>80%), but larger lesions or neck metastases require combined therapy with higher doses of postoperative radiation. Postoperative radiation reduced the complication rate and treatment-related fatalities, and increased the locoregional control and overall cure rates.     

Adenosine dialdehyde and nitrous oxide induce HL-60 differentiation

Adenosine dialdehyde and nitrous oxide, specific S-adeno- sylhomocysteine hydrolase and methionine synthetase inhibitors, respectively, induced differentiation of the human promyelocytic cell line HL-60. Their effect did not appear to be mediated through changes in transmethylation or decreased S-adenosylmethionine synthesis because (1) there was little correlation between the concentrations of adenosine dialdehyde that induced differentiation and those that changed the ratio of the intracellular concentrations of S- adenosylmethionine to S-adenosylhomocysteine, and (2) inhibition of methionine adenosyltransferase by cycloleucine did not induce differentiation. The differentiation induced by adenosine dialdehyde was prevented by homocysteine and that by nitrous oxide was inversely related to the medium methionine concentration. This suggested that differentiation was secondary to decreased methionine synthesis.     

The neuroendocrine challenge paradigm in headache research

The neuroendocrine challenge paradigm provides a "window" on central neurotransmitter function in vivo. This strategy is based on the premise that the sensitivity of certain central receptors can be inferred from the magnitude of the hormonal response to specific pharmacologic probes. For example, the serotonin (5HT) receptor agonist m-chlorophenylpiperazine (m-CPP) stimulates the release of cortisol and prolactin and induces migraine-like headaches. We have previously reported that the headache and cortisol responses to m-CPP are highly correlated, which may implicate a disturbance in central serotonergic neurotransmission in the pathogenesis of migraine. As pharmacologic probes with greater specificity for 5HT receptor subtypes become available, we may be able to elucidate these mechanisms with greater precision. The neuroendocrine challenge methodology is also applicable to the study of other neurotransmitter systems and other headache disorders.     

Percutaneous endoscopic gastrostomy and jejunostomy for long-term feeding in patients with cancer of the head and neck

Enteral feeding is often required in patients with cancer of the head and neck. Percutaneous endoscopic gastrostomies (PEGs) and jejunostomies (PEJs) can facilitate enteral feeding in patients who require this treatment. The endoscopic technique allows for the placement of feeding gastrostomies and jejunostomies without a surgical procedure and eliminates the need for nasal tubes for long-term enteral feeding. Forty-two patients with head and neck tumors were referred for placement of PEGs because of severe dysphagia induced by tumors, surgery, radiation, or chemotherapy. The procedure was performed in the gastroenterology suite. Patients were sedated with intravenous meperidine and diazepam, and local anesthetic with lidocaine was applied to the area of incision. Average procedure time was approximately 20 minutes. The procedure was successful in 39 patients in whom tubes were placed ranging in diameter from 15F to 22F. PEGs were placed in 36 patients with intact stomachs and PEJs in three patients with previous gastrectomies. The remaining three procedures were unsuccessful because of technical reasons. There were three localized skin infections, and all responded to antibiotic therapy. Neither peritonitis nor any other immediate complication occurred. In 16 nonhospitalized patients, the procedure was performed on an outpatient basis. After a mean followup of 4.5 +/- 6 months of enteral feeding in the home, there was only one case of aspiration and subsequent pneumonia, and this case responded to antibiotics. No other long-term complications were noted. Thus feeding gastrostomies and jejunostomies can be placed safely and easily in patients with cancers of the head and neck by endoscopic methods without abdominal surgery. These tubes can be used for enteral feeding and eliminate the need for nasogastric tubes. They are better tolerated, are of a wider diameter, and have a reduced risk for migration, clogging, and aspiration-related complications.