Biomedical subjects
Publications and source records attributed to M A Fitzgerald.
The majority of infants are breast-fed for some period of time. During lactation, many women will have healthcare problems necessitating pharmacologic intervention. However, with a few notable exceptions, breast-feeding can continue with maternal medication use. This report focuses on the factors influencing the choice of the safest pharmacologic intervention for both mother and child.
Alaska Native women historically have high rates of sexually transmitted diseases (STDs) and invasive cervical cancer. Their prevalence of cervical infections with human papillomavirus (HPV) in relation to cervical dysplasia was determined with a commercial dot hybridization test for seven HPV genotypes. Type-specific HPV DNA, similarly distributed between genotype groups 16/18 and 31/33/35, was detected in 234 cervical specimens (21%) from 1126 Alaska Native women seeking routine care and colposcopy or from population-based lists. The prevalence of HPV DNA declined with age and increased with sexual activity and cigarette smoking. It was unrelated to use of oral contraceptives or condoms or to STDs. Relative risks associating HPV with increasing severe grades of cervical dysplasia increased markedly with HPV infection, up to 7.1 for high-risk genotypes 16/18 and 14.4 for coinfection with 31/33/35. These genotypes were detected in 8% of women without dysplasia seeking routine care. Screening for strain-specific HPV DNA may identify women at highest risk for cervical neoplasia.
To assess prevention strategies for pneumococcal disease in Alaska, prospective surveillance during 1986-1990 identified 672 invasive pneumococcal infections, including 315 among Alaska Natives. Age-adjusted annual incidence was 74 per 100,000 for Alaska Natives and 16 per 100,000 for nonnatives. The annual incidence in Alaska Native children < 2 years old was 624 per 100,000; rates of 84 per 100,000 for meningitis and 290 per 100,000 for bacteremic pneumonia were 8-10 times higher than for other US groups. By age 75, cumulative incidence (7%) and mortality (1%) in Alaska Natives were almost 4 times higher than for nonnatives. Only 17% of Alaska Native adults with predisposing conditions and invasive infections previously received pneumococcal vaccine. For Alaska Natives, a proposed heptavalent conjugate pneumococcal vaccine will include serotypes responsible for 85% of invasive isolates from children < 2 years but only 32% of those from adults. The 23-valent polysaccharide pneumococcal vaccine, which contains > 94% of serotypes identified in Alaska Native toddlers and adults, should be used more widely.
From January 1986 through December 1990, 672 cases of invasive pneumococcal disease were identified. From these, 574 pneumococcal isolates were recovered from normally sterile sites (blood, cerebrospinal and pleural fluid); 92% were serotypes represented in the 23-valent pneumococcal polysaccharide vaccine. The most common serotypes from children < 2 years old were 4, 6B, 9V, 14, 18C, 19F, and 23F, recovered from 83% of Alaska Native and 75.1% of nonnative children with invasive disease. Moderate penicillin resistance (MIC, 0.1-1.0 micrograms/mL) was found in 3.8% of isolates. All were sensitive to chloramphenicol, vancomycin, rifampin, ceftriaxone, cefotaxime, cephalothin, and cefaclor. However, in the Yukon-Kuskokwim Delta region, 16.9% of isolates were moderately resistant to penicillin, and 10.8% were resistant to erythromycin and 6.2% to trimethoprim-sulfamethoxazole; the number resistant to two or more antibiotics increased significantly during surveillance. All multiply resistant isolates were serotype 6B, and all were from Alaska Native patients < 2 years old.
As a part of a program to screen and immunize as many Alaska Natives as possible against hepatitis B infection, hepatitis B virus seromarkers were measured in 52,022 Alaska Natives between 1983 and 1987. Hepatitis B surface antigen (HBsAg) was found in 1,603 persons (3.1%), and 7,155 persons (13.8%) exhibited hepatitis B virus seropositivity. While the prevalence of total seropositivity increased with increasing age (p < 0.001), the proportion of seropositive persons who were also positive for HBsAg was significantly higher in children under age 5 years than in persons over age 60 (p < 0.001). The total hepatitis B virus seropositivity was significantly higher in males than in females (p < 0.001), and a greater proportion of seropositive males than seropositive females had HBsAg (p < 0.001). The prevalence of HBsAg and total seropositivity differed significantly by geographic region (p < 0.001), ranging from 0.5% to 8.2% for presence of HBsAg and from 5.4% to 29% for total seropositivity. Of persons who were HBsAg positive, hepatitis B e antigen was found in 35.4%, and antibody to hepatitis e antigen was found in 49.6%. The prevalence of hepatitis B e antigen significantly decreased with age, while that of antibody to hepatitis e antigen significantly increased. The prevalence of hepatitis B virus seropositivity is high in Alaska Natives, and there are significant differences in both the prevalence of HBsAg and total hepatitis B virus seromarkers by age, sex, and geographic region.
Forty pairs of mallards (Anas platyrhynchos) were fed 15 ppm selenium as selenomethionine for about 21 weeks during winter. Twenty pairs served as controls. At the end of 21 weeks, which coincided with the onset of the reproductive season, selenium treatment was ended. Four birds died while on selenium treatment. Treated females lost weight, and their egg-laying was delayed. Hatching success of some of the first eggs laid by selenium-treated females was lower than that of controls, and a few of these early eggs contained deformed embryos, but, after a period of about two weeks off the selenium-treated diet, reproductive success returned to a level comparable with that of controls. The return to normal reproductive success was the result of a corresponding decrease in selenium concentrations in eggs once selenium treatment ended.
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Enzyme immunoassay (EIA) and radioimmunoassay (RIA) for the detection of antibody to hepatitis B core antigen (anti-HBc) were compared using serum specimens from Alaska Natives screened during a hepatitis B control program that were initially positive by EIA for only anti-HBc. Of 36 specimens from persons previously HBsAg positive but who were now only anti-HBc positive by EIA, 94.4% were anti-HBc positive by both assays, with anti-HBc levels exceeding 93% inhibition. Low-level antibody to hepatitis B surface antigen (anti-HBs) (less than 10 SRU) and antibody to hepatitis Be (anti-HBe) were also present in 50% and 48% of specimens positive for anti-HBc, respectively. Of 148 specimens from persons initially positive for only anti-HBc by EIA who had no previous documentation of any hepatitis B virus (HBV) infection, 64.5% were positive by repeat testing for anti-HBc by both assays, and anti-HBc levels in this sample exceeded 70% in 91.6% and 80.2% of specimens by EIA and RIA, respectively. Low-level anti-HBs and anti-HBe were present in 45.8% and 15.6%, respectively. EIA detection of anti-HBc was found to be less specific than RIA. Of specimens positive for anti-HBc by EIA, 14.8% were negative by RIA. The specificity of the EIA could be improved with respect to RIA by increasing the cut-off from 48% to 68%.(ABSTRACT TRUNCATED AT 250 WORDS)
In 1981, a hepatitis B virus vaccine demonstration project was conducted in 1630 Yupik Eskimos in southwest Alaska. Levels of antibody to hepatitis B surface antigen and markers for hepatitis B virus infection in vaccinees were monitored yearly for 5 years. After 5 years of follow-up, 19% of those who initially had an immune response to vaccine of 10 sample ratio units or greater subsequently had levels of antibody to hepatitis B surface antigen lower than 10 sample ratio units. During the 5 years after the first dose of vaccine, in three responders and one person with an antibody to hepatitis B surface antigen response lower than 10 sample ratio units, antibody to hepatitis B core antigen developed, and the level of antibody to hepatitis B surface antigen was boosted. Hepatitis B surface antigen did not develop in any subjects, and none had clinical hepatitis. In the 5 years following the demonstration project, the annual incidence of hepatitis B virus infection decreased from 50 cases per 1000 population before the vaccine trial to 0.45 per 1000.
High rates of hepatitis B virus infection and primary hepatocellular carcinoma are present among Alaskan Natives. To determine if primary hepatocellular carcinoma could be detected at an early surgically resectable stage, serological screening for elevated alpha-fetoprotein levels was done semiannually among Alaskan Natives infected with hepatitis B virus. During a 26-month screening period, 3,387 alpha-fetoprotein tests were performed on 1,394 persons. Of 126 persons with elevated levels of alpha-fetoprotein (greater than 25 ng/mL), nine males were found to have primary hepatocellular carcinoma (all with alpha-fetoprotein levels greater than 350 ng/mL). Six of these nine persons were asymptomatic for primary hepatocellular carcinoma and four had small tumors (less than 6 cm) that were surgically resected. After surgery, the alpha-fetoprotein levels in all four patients fell to normal and have remained normal after a follow-up of four to 20 months (median, ten months). alpha-Fetoprotein screening proved to be an effective approach in this population in detecting primary hepatocellular carcinoma at a potentially curable stage and should be considered in other individuals or populations infected with hepatitis B virus.
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Poststreptococcal acute glomerulonephritis often follows impetigo and can occur in epidemics. From 1975 through 1977, an epidemic of poststreptococcal acute glomerulonephritis occurred in Alaska. Fifty children required hospitalization, while 25 less seriously ill children were treated as outpatients. Sixty-seven percent of these 75 children had direct evidence of recent skin infections. Serotypes 49-14 and NT-14 were the most common streptococcal isolates. In villages in the epidemic area, approximately 15% of children had impetigo and more than 60% of lesions cultured were positive for group A streptococci. Impetigo rates in the epidemic area were similar to those found in nonepidemic areas. However, the introduction of the nephritogenic streptococcal serotypes not recently present in this population apparently led to the development of the epidemic.
A case of chronic secretory diarrhea with elevated plasma vasoactive intestinal peptide (VIP) and serum gastrin levels is described. Plasma secretin, glucagon, insulin, and cyclic adenosine and guanine monophosphate (cAMP and (CGMP) concentrations were normal. Administration of a prostaglandin synthetase inhibitor failed to decrease the volume of diarrhea. There was no evidence of laxative abuse, antral cell hyperplasia, gastric hypersecretion, or pancreatic hypersecretion. The pancreatic histology was interpreted as islet cell hyperplasia. Jejunal tissue cAMP and cGMP concentrations were in the same range as those obtained from three control subjects. This report suggests that cyclic nucleotides may not mediate intestinal secretion in hormone-induced diarrhea.
Previous experiments in this laboratory demonstrated a progressive decrease in cell-mediated cytotoxicity (CMC) against allogeneic tumor cells by immune spleen cells from mice repeatedly immunized with those tumor cells. In the present study, immune spleen cells, obtained at specified intervals during the course of multiple immunizations of BALB/c mice with EL-4 lymphoma cells, were tested for CMC against EL-4 target cells pretreated with anti-EL-4 serum which had been obtained from singly or repeatedly immunized animals. Cytolysis of EL-4 cells was measured by a 51Cr-release assay. The results indicate that blocking of CMC in an allogeneic tumor model may occur by two pathways. First, antigen or antigen-antibody complexes present in the immunized animal may bind in vivo to the antigen receptor sites of of sensitized effector cells that are used in the in vitro CMC assay, thereby blocking their interaction with tumor cells. Second, immune serum that is added to the in vitro CMC assay may contain highly avid antibodies, as well as antigen-antibody complexes, that bind to tumor cells and thereby block interaction with sensitized effector cells. The identification of these elements may be of prognostic significance in certain clinical situations.
The development and kinetics of cell-mediated cytotoxicity (CMC), antibody-mediated complement-dependent cytotoxicity (C'DC), and antibody-dependent cellular cytotoxicity (ADCC) were studied in an allogeneic model. Using microcytotoxic assays of 51Cr release from labeled EL-4 tumor cells, C'DC, ADCC, and CMC were measured at 14 intervals during the 77-day course of the experiment. The results obtained demonstrate the oscillating nature of the immune response. The rise and fall of activity was almost synchronous for the three functions studied. A generalized trend of increasing antibody-dependent functions and a simultaneous dampening of CMC was noted.
Wilson's disease usually has its onset in childhood, adolescence, or early adulthood. The clinical picture of hepatic dysfunction without dysfunction of the central nervous system is more typical of the disease in the child or the adolescent than in the adult. We are presenting the case of a man whose age at onset of the disease was 55 years and who had the hepatic complications of Wilson's disease without clinical evidence of disease of the central nervous system. All patients with chronic hepatitis (chronic active liver disease) or cirrhosis of unknown etiology should be screened for the possibility of Wilson's disease. This screening should include slit-lamp biomicroscopy for Kayser-Fleischer rings, determination of serum ceruloplasmin concentration, and measurement of 24-hour urinary excretion of copper. If doubt exists concerning the diagnosis, either a radiocopper kinetic study, using 64Cu or 67Cu, or, if the patient's condition permits, a liver biopsy with measurement of hepatic copper concentration should be done. The rubeanic stain of hepatic tissue for copper is unreliable in making or excluding the diagnosis of Wilson's disease.
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High rates of invasive disease caused by Streptococcus pneumoniae occur in the Alaska Native population. Because of the wide use of empiric antibiotics to treat infection in rural regions of Alaska and concern over the emergence of pneumococcal strains now resistant to an increasing number of antibiotics we compared a simple strip system (Etest) for the measurement of antibiotic susceptibilities to the standard agar dilution method. Eighty-two pneumococcal isolates were tested by both methods. Overall, the Etest MICs of 91% of the isolates agreed within one log2 of the agar dilution, and 99.3% agreed within 2 log2 dilutions. There were no very major or major interpretative category discrepancies with the Etest for any antibiotic tested. There were 4.1% minor interpretative errors with the Etest, which generally occurred at the breakpoint between susceptible and intermediate resistance. The results indicated that the Etest was comparable to the agar dilution method for the measurement of antibiotic MICs for Streptococcus pneumoniae.