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Biomedical subjects

W Schaffner

Publications and source records attributed to W Schaffner.

At least 307 records · Page 17Linked to original sources

Aspects of the regulation of histone genes.

Sequencing of cloned histone DNA of the sea urchin Psammechinus miliaris has confirmed the map of the histone genes obtained earlier by rather less refined techniques. Sequencing of spacer has revealed that it is unlikely to code for protein. Some interesting sequences in the prelude regions to the structural genes have been found. The technique of injecting DNA into the germinal vesicle of the Xenopus oocyte has been greatly simplified, so that now many of the parameters governing the transcription of the injected genes can be investigated. Some mRNA-like molecules appear when circular histone DNA is inserted into the oocyte nucleus. We are cautiously optimistic that the technique can be further developed and will provide a useful tool for the study of the molecular mechanisms governing the expression of structural genes coding for proteins.

Animals↗

Acute hemorrhagic cystitis. Industrial exposure to the pesticide chlordimeform.

An outbreak of hematuria occurred from May 20 to May 23, 1975, among employees of a chemical packaging plant. Nine of 22 workers who packaged the insecticide chlordimeform in a separate shed became severely ill with abdominal pain, dysuria, urgency to void, or hematuria. None of 18 persons who worked in other areas of the plant were affected. Four additional workers who had packaged the chemical during the previous year had a history of similar symptoms. Bladder biopsy specimens from three affected persons showed severe hemorrhagic cystitis; chlordimeform and 2-methyl-4-chloroaniline, a metabolite of chlordimeform, were present in urine specimens collected three days after exposure. The illness lasted from one week to two months; the workers recovered completely. Chlordimeform that was injected subcutaneously into three cats produced similar, though less severe, changes in the bladders of two animals.

Acute Disease↗

Genes and spacers of cloned sea urchin histone DNA analyzed by sequencing.

A cloned histone gene cluster of the highly reiterated type from the sea urchin Psammechinus miliaris was analyzed by DNA sequencing. More than half of the 6 kb repeat was sequenced, including coding regions of all five histones, some prelude and trailing sequences lying adjacent to the structural gense, and segments of the AT-rich spacer DNA. The gene cluster does not code for gonad-specific histone variants but may instead be active in early sea urchin development, as indicated by comparison to reference histones. The encoded histones seem not to be derived from longer precursor proteins, not is there any evidence for insert sequences within the coding regions. Sequence similarities exist among the putative ribosome-binding sites adjacent to the initiator codons of individual genes. The AT-rich spacer segments between the genes differ from each other, are made up from relatively simple nucleotide arrangements, but are not repetitious, and apparently do not code for additional large proteins.

Animals↗

Surveillance of antibiotic prescribing in office practice.

Using fiscal and administrative data routinely collected by the Tennessee Medicaid program, we conducted epidemiologic analyses of physicians' prescribing of selected antibiotics in office practice. This research has defined several subgroups of physicians who regularly malprescribed chloramphenicol or tetracyclines (to children less than 8 years old). After special educational mailings to all physicians, prescribing of these antimicrobial drugs diminished. Similar analyses could enable the profession to design specific remedial educational interventions, target them at physicians needing contemporary information, and assess their impact by monitoring subsequent prescribing. Such a program might diminish inappropriate drug use, reduce adverse drug reactions, help contain medical care costs, and produce better educated physicians.

Ambulatory Care↗

Overwhelming strongyloidiasis: an unappreciated opportunistic infection.

Strongyloides stercoralis is an intestinal nematode which infects a large portion of the world's population. Individuals with infection confined to the intestinal tract are often asymptomatic but may have abdominal pain, weight loss, diarrhea, and other nonspecific complaints. Enhanced proliferation of the parasite in compromised hosts causes an augmentation of the normal life-cycle. Resultant massive invasion of the gastrointestinal tract and lungs is termed the hyperinfection syndrome. If the worm burden is excessive, parasitic invasion of other tissues occurs and is termed disseminated strongyloidiasis. A variety of underlying conditions appear to predispose to severe infections. These are primarily diseases characterized by immunodeficiency due to defective T-lymphocyte function (Table 1). Individuals with less severe disorders become compromised hosts because of therapeutic regimens consisting of corticosteroids or other immunosuppressive medication. The debilitation of chronic illness or malnutrition also predisposes to systemic stronglyloidiasis. The diagnosis of strongyloidiasis can be readily made by microscopic examination of concentrates of upper small bowel fluid, stool, or sputum. Important clues suggesting this infection include unexplained gram-negative bacillary bacteremia in a compromised host who may have vague abdominal complaints, an ileus pattern on X-ray, and pulmonary infiltrates. Eosinophilia is helpful, if present, but should not be relied upon to exclude the diagnosis. The treatment of systemic infection due to Strongyloides stercoralis with either thiabensazole 25 mg/kg orally twice daily is satisfactory if the diagnosis is made early. Because of several unusual features of this illness in compromised hosts, the standard recommendation for 2 days of therapy should be abandoned in such patients. Immunodeficiency, corticosteroids, and bowel ileus reduce drug efficacy. Thus a longer treatment period of at leuch as blind loops or diverticula necessitate longer treatment. Stool specimens and upper small bowel aspirates should be monitored regularly and treatment continued several days beyond the last evidence of the parasite. In particularly difficult situations where either worm eradication is impossible or reinfection is probable, short monthly courses of antihelminthic therapy seem to be effective in averting recurrent systemic illness. Finally, prevention of hyperinfection or dissemination due to Strongyloides stercoralis can be accomplished by screening immunocompromised hosts with stool and upper small bowel aspirate examinations. These would be especially important prior to initiating chemotherapy, or before giving immunosuppressive medications or corticosteroids to patients with nonneoplastic conditions such as systemic lupus erythematosus, nephrotic syndrome, or renal allografts.

Adult↗

Prescribing of tetracycline to children less than 8 years old. A two-year epidemiologic study among ambulatory Tennessee medicaid recipients.

The committee on Drugs of the American Academy of Pediatrics finds virtually no indications for administering tetracyclines to children less than 8 years old. This study analyzes tetracycline prescribing to ambulatory children less than 8 years of age in the Tennessee Medicaid program during a two-year period. Of the nearly 59,000 children in the study, 4,026 (7%) received 7,046 tetracycline prescriptions. Twenty-seven percent (527) of 1,947 participating physicians prescribed tetracycline; 26 physicians (5%) wrote 54% of the prescriptions for 45% of the children. Physicians in family practice prescribed the greatest quantity of tetracycline. Surgeons and internists prescribed more tetracycline to young children than did pediatricians. Rural location of practice was independently associated with increased tetracycline prescribing for all specialties. Recent graduates from medical school were less apt to prescribe tetracycline than were earlier graduates.

Age Factors↗

DNA sequences coding for the H2B histone of Psammechinus miliaris.

Starting from restriction enzyme cleavage sites of known topologies the DNA sequences coding for two thirds of the H2B histone protein, together with some 3 inch extracistronic sequences, have been determined for the sea urchin Psammechinus miliaris. This unambiguously identifies this gene and further reveals its 5 inch-3inch polarity and accurate map position in a cloned histone DNA repeat unit.

Amino Acid Sequence↗

Novel screening procedure for recombinant plasmids.

Lysed bacterial colonies containing potential recombinant plasmids were mixed with molten agar and sealed into slots of an agarose gel. After electrophoresis overnight, the gel was stained with ethidium bromide, which clearly reveals recombinant plasmids. Xenopus laevis ribosomal DNA and histone DNA of Psammechinus miliaris were ligated into pCRI plasmids and screened by this method.

Animals↗

Botulism in infancy. Report of a case.

A 22-day-old infant developed infant botulism characterized by profound weakness, hypotonia, respiratory arrest, areflexia, ptosis, pupils that responded poorly to light, and absent gag reflex. Stool examination yielded Clostridium botulinum type B organisms and type B toxin. Electromyography provided rapid diagnostic assistance. With supportive care, reovery was complete. This "new" disease probably is more common than now appreciated.

Botulism↗

Salmonella empyema: a review.

A 35-year-old man developed salmonella pleural empyema during a three-month illness. Cultures of the empyema fluid yielded S enteritidis, serotype typhimurium. Cure was achieved by decortication and obliteration of the pleural empyema space, in combination with chloramphenicol therapy given parenterally. Review of the published reports revealed eight similar instances of salmonella empyema. Manifestations and treatment of this group are reviewed.

Adult↗

Maternal mortality in Michigan: an epidemiologic analysis, 1950-1971.

An analysis was performed of direct maternal mortality over 22 years (1950 through 1971) in the state of Michigan. The overall direct maternal mortality rate fell from 5.0/10,000 live births in 1950 to 1.5 in 1971. The rate among nonwhites was more than four times greater than among whites and the difference in relative risk did not narrow over the 22 years. Mortality rates increased with increasing maternal age but not with increasing parity. Nulliparous women had a significantly higher mortality rate than did parous women, particularly those over 25 years of age. when the white gravida of urban Wayne County were compared with the white gravida of 33 rural counties, no difference in direct maternal mortality rates could be attributed to rurality per se. Hemorrhage, infection, and toxemia were the leading causes of direct maternal death. The data suggest that hospitals with less active obstetrical services were associated with a higher risk of direct maternal mortality than were hospitals whose obstetrical services were more active. An increasing proportion of the direct maternal deaths was designated as preventable over the study period. It is believed that analyses of maternal mortality have led to improved perinatal and obstetrical care and that further advances require their continued support. (Am. J. Public Health 67:821-829, 1977)

Abortion, Spontaneous↗

Gonorrhea in preadolescent children: an inquiry into source of infection and mode of transmission.

From November 1974 through December 1975 a study was made of all reported cases of gonorrhea in children under 10 years of age in Tennessee. Clinical manifestations of the 73 subjects identified included vaginal infection (48), urethritis (11), conjunctivitis (8), and ophthalmia neonatorum (6). A total of 203 relatives and associates of 54 subjects was cultured. Fifty-four (27%) had gonorrhea; 43 of these were relatives. A history of sexual contact was found in 18 children, including seven where the contact had a positive culture for Neisseria gonorrhoeae. Sexual transmission was common in children with vaginitis or urethritis. In nine cases, sexual abuse or child neglect was suspected. The recognition of a child with gonococcal infection identifies a cluster of family members and associates who are at increased risk of having gonorrhea.

Child↗

Contaminated aqueous benzalkonium chloride. An unnecessary hospital infection hazard.

During January and February 1975, nine patients on a single ward of a rural Tennessee hospital unexpectedly developed sepsis. The aseptic technique employed in the management of intravenous infusions was implicated. Pseudomonas cepacia was recovered from the following: bloodstream, inuse intravenous infusions and the antiseptic, aqueous benzalkonium chloride. The outbreak again calls attention to the infection risk associated with the use of this product. Selection of less hazardous antiseptics and disinfectants is strongly recommended.

Benzalkonium Compounds↗

Partial denaturation mapping of cloned histone DNA from the sea urchin Psammechinus miliaris.

A cloned 5.6-kb DNA repeat unit of Psammechinus miliaris containing all five histone coding sequences of known order and polarity has been shown to fall clearly into a low melting and a high melting half by thermal denaturation. The topoligies of the DNA sequences thus defined were determined by partial denaturation mapping in the electron microscope to gain further insight into the distribution of spacers and genes within histone DNA.

Animals↗

Carbon tetrachloride toxicity potentiated by isopropyl alcohol. Investigation of an industrial outbreak.

Fourteen workers in an isopropyl alcohol packaging plant became ill after accidental exposure to carbon tetrachloride. In four, renal failure or hepatitis developed. Isopropyl alcohol potentiation of carbon tetrachloride toxicity has been shown previously only in rats. Acetone, a product of isopropyl alcohol metabolism, is a major potentiator of carbon tetrachloride toxicity. Workers had elevated levels of acetone in samples of expired alveolar gas and thus were metabolically predisposed to carbon tetrachloride injury. Stricter limits for industrial carbon tetrachloride exposure should be established where concomitant isopropyl alcohol use occurs.

1-Propanol↗