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Biomedical subjects

D H Smith

Publications and source records attributed to D H Smith.

At least 199 records · Page 11Linked to original sources
PubMed1990

Safety and immunogenicity of Haemophilus influenzae type b oligosaccharide-CRM197 conjugate vaccine in infants aged 15 to 23 months.

A total of 268 infants aged 15 to 23 months received one dose of a vaccine composed of Haemophilus influenzae type b oligosaccharides covalently linked to the nontoxic diphtheria toxin variant CRM197 (HbOC; HibTITER). Side effects associated with vaccination were infrequent, transient, and mild. One month after a single vaccination, the anti-H influenzae type b capsular polysaccharide antibody concentration rose from a geometric mean prevaccination level of 0.20 microgram/mL to 13.77 micrograms/mL. Of these infants, 99% had a postvaccination level greater than or equal to 1.00 microgram/mL, a level associated with long-term protection. The immune response was long-lived: all of the children who were monitored 17 to 27 months after vaccination had concentrations greater than or equal to 1.00 microgram/mL. The anti-H influenzae type b capsular polysaccharide antibody generated was predominantly of the IgG isotype and IgG1 subclass. The immune sera had bactericidal activity in vitro and conferred passive protection in the infant rat meningitis model.

Antibody Formation↗
PubMed1990

The aeromedical implications of atrial fibrillation.

A retrospective study was undertaken to determine the incidence of spontaneous atrial fibrillation (AF) in a group of asymptomatic pilots. The electrocardiograms of 13,037 aircrew members accumulated between 1964 and 1986 were reviewed and those coded for AF were extracted. In each case an attempt was made to investigate factors relating to the onset, course, and prognosis of the AF. Eight subjects (mean age 50.1 years) were found to have AF. Of this group, two had a single isolated episode of AF for which a specific precipitating factor was implicated, three had recurrent paroxysmal AF of which one progressed to chronic persistent AF, and three had chronic persistent AF from the outset. The mean follow-up period for the eight subjects was 13.6 years. The two pilots who had isolated attacks of AF have thus far had no subsequent episodes of AF. Five of the remaining six have been completely well, while one required treatment for an embolus to his left leg. Concerning the aeromedical implications, we believe that pilots demonstrating single isolated episodes of AF in the presence of a normal heart, and in whom recovery is complete, should be allowed to return to full aviation duties on a waiver clause. Patients with chronic AF, lone AF, or paroxysmal AF should be excluded from all flying duties.

Adult↗
PubMed1990

Safety and immunologic response to Haemophilus influenzae type b oligosaccharide-CRM197 conjugate vaccine in 1- to 6-month-old infants.

A Haemophilus influenzae type b oligosaccharide-CRM197 conjugate (HbOC) vaccine was evaluated for safety and immunogenicity in 432 infants 1 to 6 months of age. In a multicenter study involving 10 sites in six states, infants were vaccinated with three 10-micrograms doses of HbOC at 2-month intervals. Side effects associated with vaccination were mild, transient, and occurred in fewer than 2% of the subjects. More than 90% of infants of all ages responded after two doses, and more than 98% had anti-H influenzae type b capsular polysaccharide (HbPs) antibody levels greater than or equal to 1 microgram/mL after three doses. One month after the third vaccination, the geometric mean anti-HbPs antibody levels were 16.84, 26.23, and 29.11 in infants initially vaccinated at 1 to 2, 3 to 4, and 5 to 6 months of age, respectively. A long-term antibody response was observed; more than 80% of these infants had anti-HbPs levels greater than or equal to 1 microgram/mL at 2 years of age. The HbOC generated an immune response characteristic of a protein antigen; IgG anti-HbPs antibodies of IgG1 subclass predominated and the response could be boosted. The immune sera killed H influenzae type b when evaluated in an in vitro bactericidal assay. The data indicate that HbOC safely primed and boosted the immune system of young infants, providing long-lasting protective levels of anti-HbPs antibodies.

Antibody Formation↗
PubMed1989

The MHC-binding and gp120-binding functions of CD4 are separable.

CD4 is a cell surface glycoprotein that is thought to interact with nonpolymorphic determinants of class II major histocompatibility (MHC) molecules. CD4 is also the receptor for the human immunodeficiency virus (HIV), binding with high affinity to the HIV-1 envelope glycoprotein, gp120. Homolog-scanning mutagenesis was used to identify CD4 regions that are important in class II MHC binding and to determine whether the gp120 and class II MHC binding sites of CD4 are related. Class II MHC binding was abolished by mutations in each of the first three immunoglobulin-like domains of CD4. The gp120 binding could be abolished without affecting class II MHC binding and vice versa, although at least one mutation examined reduced both functions significantly. These findings indicate that, while there may be overlap between the gp120 and class II MHC binding sites of CD4, these sites are distinct and can be separated. Thus it should be possible to design CD4 analogs that can block HIV infectivity but intrinsically lack the ability to affect the normal immune response by binding to class II MHC molecules.

Amino Acid Sequence↗
PubMed1989

Pelvic exenteration for recurrent or persistent gynecologic malignancies: a 10-year review of the Memorial Sloan-Kettering Cancer Center experience (1972-1981).

From January 1, 1972 to December 31, 1981, sixty-five patients underwent pelvic exenteration as treatment for recurrent or persistent gynecologic malignancy at Memorial Sloan-Kettering Cancer Center. Cervical carcinoma was the disease most commonly treated by exenteration. The operative mortality of 9.2% represents an improvement over previous reports from this institution. After routine use of prophylactic minidose heparin, no cases of thrombophlebitis or pulmonary embolus occurred postoperatively. A 5-year survival rate of 23% warrants continued use of exenteration in carefully selected patients. The significant mortality and morbidity associated with pelvic exenteration preclude its use as a palliative procedure.

Female↗
PubMed1989

The use of synthetic gonadotropin releasing hormone treatment in the collection of sheep embryos.

Gonadotropin releasing hormone (GnRH) treatment was examined as a means of improving the efficacy of embryo collection in the sheep following intrauterine insemination of frozen-thawed semen. In summary, treatment consistently improved fertilization rates and the number of fertilized ova collected per ewe was enhanced compared with untreated ewes. The yield of fertilized ova in ewes treated with follicle stimulating hormone (FSH) was maximized by administering GnRH 36 h after progestagen treatment; 24 h was the preferred time in ewes treated with pregnant mare serum gonadotropin (PMSG). There was a significant (P < 0.001) increase in the percentage of unfertilized ova in the former treatment when GnRH was given at 24 h. An examination of the time of insemination (0, 6, 12 and 18 h before the median time of ovulation) indicated that fertilization rates were highest when insemination occurred at 6 h in both GnRH-treated ewes and in untreated ewes. In GnRH-treated ewes, the recovery of ova was lowest when insemination occurred at the time of ovulation. The number of motile frozen-thawed spermatozoa required for fertilization following treatment was estimated to be approximately 20 x 10(6) per uterine horn. GnRH-treatment also improved the yield of fertilized ova in sheep that were naturally mated, although this yield was lower than that obtained with intrauterine insemination of frozen-thawed semen. It is concluded that fertilization failure, a major problem in sheep embryo collection, can be eliminated through judicious use of GnRH treatment and properly timed intrauterine insemination.

Journal Article↗
PubMed1989

Uterine presensitization and embryo survival and growth in Booroola Merino x South Australian Merino ewes.

The fertility enhancing effects of semen were examined following the intra-uterine insemination of killed spermatozoa plus seminal plasma 17 d prior to insemination with viable spermatozoa. Three experiments were conducted: two on 1.5-yr old and 2.5 to 5.5 yr-old Booroola Merino x South Australian Merino ewes in 1986 and one on 1.5 yr-old ewes in 1987. Differences between treatment and control groups for the percentage of ewes exhibiting estrus by Days 21 and 35 following fertile insemination, the percentage of ewes with viable embryos at Day 35, the number and weight of viable embryos per ewe, the nubmer of caruncular implantation sites and the progesterone level were not statistically significant (P>0.05). There were no statistically significant treatment by experiment interactions for any of the variables examined. Inflammation and edema of the endometrial tissue was not observed following the presensitization treatment.

Journal Article↗
PubMed1989

Time of ovulation in the South Australian Merino ewe following synchronization of estrus. 1. Variation within and between flocks.

Observations were made by repeated laparoscopy to determine the time of ovulation in seven flocks of South Australian Merino ewes treated with pregnant mare serum gonadotropin (PMSG, 400 IU per ewe) and an intravaginal pessary containing 60 mg medroxy-progesterone acetate (MAP). Ovulation most often commenced within 57 h of pessary removal and was completed in all flocks within 81 h. There was, however, significant variation in the time of onset of ovulation; it did not commence until 69 h in one of three observations of Flock 1 and in two of three observations of Flock 2. On the other hand, in a flock of two-year-old nulliparous ewes (Flock 7), ovulation commenced significantly (P < 0.001) earlier than in most observations of other flocks, with 18 39 ewes ovulating within 57 h of pessary removal. The effect of the progestagen (MAP vs flugestone acetate) and the gonadotropin preparation (Pregnecol vs Folligon) on the time of ovulation were observed in separate studies. The characteristic time of ovulation was not influenced in either comparison. However, ovulation occurred significantly (P < 0.001) earlier in ewes treated with progesterone released from a controlled internal drug release dispenser (CIDR). The implications of these findings to artificial insemination and embryo transfer are discussed.

Journal Article↗
PubMed1989

Time of ovulation in the South Australian Merino ewe following synchronization of estrus. 2. Efficacy of GnRH treatment and its relevance to insemination programs utilizing frozen-thawed semen.

In a study of the time of ovulation following synchronization of estrus in the ewe, the effect of time of treatment with GnRH (24 vs 36 h after pessary removal) and dosage (6.25 to 100 ug per ewe) were examined. All treatments synchronized the time of ovulation irrespective of when untreated ewes commenced to ovulate. As part of an evaluation of GnRH treatment in artificial insemination programs, an assessment was made of the quality of eggs obtained from control ewes and ewes treated with GnRH at either 24 or 36 h after pessary removal. Treatment at 24 h increased the number of retarded embryos (P < 0.01) and unfertilized ova (P < 0.01) collected per ewe, reduced the number of embryos collected per ewe (P < 0.01), and reduced (P < 0.05) the percentage of pregnant ewes compared with other groups. However, there were no differences between control ewes and ewes treated with GnRH at 36 h. GnRH treatment at 36 h was consequently examined as a means of improving conception rates following the intrauterine insemination of frozen-thawed semen. Insemination of GnRH-treated ewes 8 to 12 h before the median time of ovulation resulted in a nonsignificant increase (range 5.7 to 7.3%) in the percentage of ewes of mature age which became pregnant. Insemination 0 to 4 h before the median time of ovulation resulted in a nonsignificant decrease in the percentage of pregnant ewes. GnRH treatment did not influence the number of fetuses per ewe. Reasons for the failure of this treatment to significantly improve ewe fertility are discussed.

Journal Article↗
PubMed1989

The psychosocial adaptation of adolescents with cystic fibrosis. A review of the literature.

This article reviews the literature pertaining to the psychosocial adaptation of adolescents with cystic fibrosis. This chronic debilitating illness is exceptionally stressful to the patient and his or her family. It may result in significant individual and family psychopathology, yet social adaptation is reported to be remarkably good. Mediating variables in adaptation are reviewed, with special emphasis on family function variables. Directions for current interventions and future research are suggested. An expanded role for psychologic intervention with individual patients and their families is recommended.

Adaptation, Psychological↗
PubMed1989

The human growth hormone locus: nucleotide sequence, biology, and evolution.

The human chromosomal growth hormone locus contained on cloned DNA and spanning approximately 66,500 bp was sequenced in its entirety to provide a framework for the analysis of its biology and evolution. This locus evolved by a series of duplications and contains in its present form five genes which display a remarkably high degree of sequence identity (approximately 95%) in all their domains. The DNA sequence of the locus reveals the presence of 48 middle repetitive sequence elements of the Alu type and one member of the KpnI family, all located in the intergenic regions. The expression of each gene was examined by screening pituitary and placental cDNA libraries by using gene-specific oligonucleotides. According to this analysis, the hGH-N gene is transcribed exclusively in the pituitary, whereas the other four genes (hCS-L, hCS-A, hGH-V, hCS-B) are expressed only in placental tissue, at levels characteristic for each gene. Particular DNA sequences found upstream of the individual promoter regions might account for the observed tissue specificity and different transcriptional activity of the genes. The hCS-L gene carries a G to A transition in a sequence used by the other four genes as an intronic 5' splice donor site. This mutation results in a different splicing pattern and, hence, in a novel sequence of the hCS-L gene mRNA and the deduced polypeptide.

Amino Acid Sequence↗
PubMed1989

A history of sleeping sickness in Kenya.

Gambian sleeping sickness entered what is now Kenya from Uganda in about 1901 and quickly spread along the Kenyan shores and islands of Lake Victoria, reaching Tanzania in 1902. By 1910 the disease had spread 25 miles inland along the Kuja and Migori rivers and their tributaries. Sleeping sickness waxed and waned in these areas despite attempts to control tsetse fly populations by various methods. It was not until 1950, when the use of insecticides (DDT) applied by backpack sprayer proved successful against Glossina fuscipes at Kibigori, that eradication of G. fuscipes and Gambian sleeping sickness seemed possible. Subsequently the Kuja-Migori endemic area was cleared of flies and disease, as well as the South and Central Nyanza lake shores and islands. By 1965 Gambian sleeping sickness had virtually disappeared from Kenya. A more virulent form of the disease, Rhodesian sleeping sickness, may have also spread to Kenya from Uganda, although its appearance in diverse areas of the Gambian disease suggest that local ecological factors may have played a role in enhanced virulence of trypanosomes stocks. The Rhodesian form of sleeping sickness appeared in the Lambwe Valley, South Nyanza, in about 1959, and despite attempts to eradicate this disease it still persists as the only remaining endemic area in Kenya at this time. The usual transmission of Rhodesian sleeping sickness by G. pallidipes in Kenya was altered when an outbreak occurred at Alego, in Central Nyanza, in 1964. It was discovered that G. fuscipes was the vector and that domestic cattle were an important reservoir of infection. Glossina fuscipes was also the vector of Rhodesian sleeping sickness in an outbreak in Samia in 1976 and another along the lakeshore in South Nyanza in 1981. Sleeping sickness has been restricted primarily to the Western and Nyanza Provinces of Kenya (Fig. 1).

Animals↗
PubMed1989

Demographic characteristics of the Lambwe Valley population.

Thirty-four per cent of the population (11,079) in the Lambwe Valley study site was under the age of 10, and 59% were under the age of 20. The population was equally divided among males and females (M/F 0.99). The crude birth rate averaged 45%; the death rate was 8% and the natural increase averaged 37%. Infant and child mortality was 66% and 108% respectively. The average household size was 8.4 individuals. The population migrated to the Lambwe Valley primarily from other areas in Kenya, although 13% were from Tanzania. The predominant tribal group was Luo (59%) followed by the Abasuba (38%). A few Luyha and Kisii were also encountered. Population increased by 3.5-fold in the 1960s, followed by a 2.5-fold increase in the 1970s. Due to an aerial spray tsetse control programme, sleeping sickness had a low prevalence in October 1981 (one of 5749). Of 339 individuals confirmed as sleeping sickness patients by hospital records from within the study site 320 (94.3%) were traced to their homes. Mortality in domestic cattle (40%), goats (47%), sheep (55%), and dogs (50%) had occurred over the previous two years during an outbreak of trypanosomiasis.

Age Factors↗
PubMed1989

Epidemiology of Rhodesian sleeping sickness in the Lambwe Valley, Kenya.

A total of 912 cases of sleeping sickness have been recorded from the Lambwe Valley from 1959 to 1984. After a period of decreasing prevalence in the 1970s an outbreak of disease occurred between 1980 and 1984. The incidence of disease for this five-year period was highest in areas adjoining the Ruma National Park, reaching 54% in Area I. Attack rates were highest in the 50+ age group (125) and children had significantly lower attack rates (8%) in this area of peridomestic transmission. Sex ratios of patients (M/F) were near 1.0 in areas in closest proximity to the thickets in the National Park, while in distant areas the ratios rose to 6.0. The distribution of the number of patients within different households was studied; fewer households than expected had 0 or one patient, and more than expected had three or more patients. No difference in attack rates were found between Nilotic and Bantu groups. Twelve different zymodemes were found in 136 stocks of Trypanosoma brucei rhodesiense. Four new zymodemes appeared in 1980 in the latest outbreak and accounted for 73% of the stocks isolated from man during this outbreak. Neutralization tests indicated that each trypanosome zymodeme may also represent a different serodeme.

Age Factors↗
PubMed1989

Presenting features of Rhodesian sleeping sickness patients in the Lambwe Valley, Kenya.

During a recent outbreak of Rhodesian sleeping sickness in the Lambwe Valley no asymptomatic Rhodesian sleeping sickness patients were found although 54% of the primary patients had mild symptoms and 9% were stuporous or comatose at presentation. The duration of symptoms was three months or less in 90% of the patients. Headache, weakness, joint and back pains and weight loss were claimed by at least 75% of the patients, while 82% of the females reported amenorrhoea and 70% of the males claimed impotency. Physical examination revealed lymphadenopathy in 86% but fever in only 36% of the patients, while chancres were found in only 16%. Patients had significantly lower levels of haemoglobin and thrombocytes than controls and their erythrocyte sedimentation rates were elevated. A comparison of both blood group and haemoglobin type between patients and controls yielded no significant differences. Fifty-seven per cent of the primary patients reporting mild symptoms had abnormal levels of leucocytes in their CSF. All relapse patients had abnormal CSF parameters. Levels of serum urea nitrogen were significantly elevated in patients, but SGOT, SGPT and total bilirubin were not. Levels of albumin and beta-globulin in patients were significantly lower than controls while gamma-globulin was elevated. Mean serum IgM levels in patients were elevated to nearly three-fold those of controls, but 35% of the individual patient values fell within the 95% range of control values. Some patients had extended prothrombin and thrombin times while fibrinogen levels were significantly elevated. No patients reported haemorrhage, and none was seen.

Adolescent↗
PubMed1989

Immunodiagnostic tests on cerebrospinal fluid in the diagnosis of meningoencephalitic Trypanosoma brucei rhodesiense infection.

Fourteen cerebrospinal fluid (CSF) samples obtained from Rhodesian sleeping sickness patients from the Lambwe Valley at relapse were positive for the presence of anti-trypanosomal antibody by both IFAT and ELISA. The mean optical density (o.d.) in the ELISA test was 0.804 +/- 0.362 and ranged from 0.258 to 1.363. CSF from five patients from the same area without evidence of meningoencephalitis were all negative by ELISA (mean o.d. 0.023 +/- 0.016, range 0.011-0.051). Control CSF samples from U.K. patients without Rhodesian sleeping sickness but with elevated levels of CSF total protein were also negative. Antibody detected by ELISA declined after Mel-B treatment of relapse and most samples had returned to negative within two years of treatment. We present evidence that serological evaluation of the CSF by ELISA and/or IFAT can provide supportive evidence of the trypanosomal origin of the infection. This is especially important at the time of relapse, when parasitological diagnosis may be impossible and records of treatment for the primary infection may not be available.

Animals↗
PubMed1989

Treatment of Rhodesian sleeping sickness in Kenya.

In a study of 269 sleeping sickness patients treated with Mel-B, 14 (5.2%) died during treatment. With total dosages of at least 30 ml (1.08 g), 1.4% relapsed and another 6.4% died, mostly of unknown causes, within three years of treatment, giving a success rate of 92.1% over the three years. Mel-B was used to treat 55 relapses after suramin therapy with 1.8% deaths during treatment, 3.6% relapses, and 92.7% success over at least three years. Apparent drug resistance to Mel-B was found in three patients who continued to relapse after repeated treatments. During 1980, 51 patients were treated with suramin on the basis of clinical condition without benefit of cerebrospinal fluid (CSF) analysis. Subsequently 49% of these patients relapsed within three years of treatment. When 29 patients were treated on the basis of CSF evaluation only two (7%) relapsed.

Adolescent↗