The South Carolina Department of Health and Environmental Control's response to the AIDS epidemic.
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Biomedical subjects
Publications and source records attributed to J Jones.
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Human protectin (CD59) is an 18-20-kD membrane glycoprotein that restricts lysis of human erythrocytes and leukocytes by homologous complement. By directly incorporating protectin into membranes of heterologous cells we observed that protectin did not prevent perforin-mediated killing, whereas complement killing was effectively restricted. Further, no significant enhancement of cell-mediated killing or target killing by purified perforin was observed with anti-protectin antibodies. Thus, in contrast with complement lysis, restriction of lysis by protectin does not apply to cell-mediated killing.
A nuclear matrix (NM)-associated region (MAR) of the protooncogene c-myc is identified in a human leukemia cell line (HL-60). A binding assay between isolated NM and 32P-end-labeled c-myc fragments in the presence of unlabeled competitors was used, and a 3'-end DraI/DraI fragment of 172 base pairs containing the first of the two polyadenylation [poly(A)] signals was identified as an in vitro MAR. Direct detection of endogenous c-myc fragments remaining NM bound after restriction digestion was used, and an in vivo MAR has been identified as the ClaI/EcoRI 1.4-kilobase pair fragment containing the 172-base pair in vitro MAR fragment. In addition, a nuclear protein (Mr = 25,000, p25) demonstrating preferential binding to the 172-base pair c-myc MAR has been identified and partially purified. This protein is diminished in the nuclei of the cells induced by phorbol ester to undergo macrophage differentiation. Footprint analysis shows that p25 binds to two regions of the 172-base pair fragment. One contains the first of two poly(A) addition signals and a topo II box-like sequence, and the other (AATTTCAATCCTAGTA) is 17 base pairs downstream of the first poly(A) signal.
The non-lethal effects of the lymphocyte-derived pore-forming toxin perforin on the human erythroleukaemia cell line K562 were investigated. By using the fluorescent Ca2+ indicator fura-2, perforin was shown to cause intracellular Ca2+ concentration to rise transiently into the micromolar range in the absence of cell death. By fluorescence-activated cell sorting it was demonstrated that K562 cells took up the membrane-impermeant nuclear stain propidium iodide (PI) when exposed to non-lethal doses of perforin. The permeability to PI was short-lived, confirming the transience of the perforin pore. Analogies with non-lethal effects and recovery processes occurring in nucleated cells exposed to the membrane-attack complex of complement are drawn.
Tonsillectomy and adenoidectomy continues to be one of the most commonly performed operations in the pediatric age group. The morbidity from tonsillectomy can be severe and includes throat and ear pain, fever, lethargy, and poor oral intake. A previous study at the Children's Hospital of Philadelphia (Pa) demonstrated the efficacy of amoxicillin therapy in minimizing some of these postoperative symptoms. However, some children continue to have a prolonged recovery even while receiving this antibiotic regimen. Because of these children and the high incidence of Staphylococcus found in tonsillar core tissue, a randomized, prospective study was undertaken at the Children's Hospital of Philadelphia to evaluate the efficacy of cefaclor vs amoxicillin in patients recovering from tonsillectomy. The patients received either ampicillin or cefazolin intravenously at the time of surgery and for 12 to 24 hours postoperatively. When oral intake was adequate, they received either amoxicillin or cefaclor orally for 7 additional postoperative days. Intraoperative cultures of the oropharynx and tonsillar tissue were obtained, as well as cultures of the tonsillar fossa 7 to 14 days postoperatively. The patients were evaluated for severity and duration of postoperative symptoms as well as complications. The results of this study showed no difference between the two groups of patients. We conclude that there is no justification for routine use of cefaclor over amoxicillin in the posttonsillectomy patient.
Acutely ill chronic schizophrenic patients requiring hospitalization were assigned to either an intensive crisis oriented (five day) or a short term (twenty-one day) inpatient unit. Despite intensive psychosocial treatment and initial rapid symptom reduction, the crisis patients could not be successfully discharged earlier than the short term patients. The crisis patients more frequently utilized day hospital aftercare and did not differ from the short term patients in symptom level or global functioning at three month follow-up. Limitations of very brief crisis oriented inpatient care for acutely ill schizophrenia patients are discussed.
G proteins, which in many somatic cells serve as mediators of signal transduction, were identified in preimplantation mouse embryos by their capacity to undergo pertussis toxin-catalyzed ADP-ribosylation. Two pertussis toxin (PT) substrates with Mr = 38,000 and 39,000 (alpha 38 and alpha 39) are present in approximately equal amounts. Relative to the amount in freshly isolated germinal vesicle (GV)-intact oocytes, the amount of PT-catalyzed ADP-ribosylation of alpha 38-39 falls during oocyte maturation, rises between the one- and two-cell stages, falls by the eight-cell and morula stages, and increases again by the blastocyst stage. The decrease in PT-catalyzed ADP-ribosylation of alpha 38-39 that occurs during oocyte maturation, however, does not require germinal vesicle breakdown (GVBD), since inhibiting GVBD with 3-isobutyl-1-methyl xanthine (IBMX) does not prevent the decrease in the extent of PT-catalyzed ADP-ribosylation. A biologically active phorbol diester (12-O-tetradecanoyl phorbol 13-acetate, TPA), but not an inactive one (4 alpha-phorbol 12,13-didecanoate, 4 alpha-PDD), totally inhibits the increase in PT-catalyzed ADP-ribosylation of alpha 38-39 that occurs between the one- and two-cell stage; TPA inhibits cleavage, but not transcriptional activation, which occurs in the two-cell embryo (Poueymirou and Schultz, 1987. Dev. Biol. 121, 489-498). In contrast, cytochalasin D, genistein, or aphidicolin, each of which inhibits cleavage of one-cell embryos, or alpha-amanitin or H8, each of which inhibits transcriptional activation but not cleavage of one-cell embryos, have little or much smaller inhibitory effects on the increase in PT-catalyzed ADP-ribosylation of alpha 38-39. Results of immunoblotting experiments using an antibody that is highly specific for alpha il-3 reveal the presence of a cross-reactive species of Mr = 38,000 (alpha 38) in the GV-intact oocyte, metaphase II-arrested egg, and one-, two-cell embryos. Relative to these stages, a reduced amount of this species is present in the eight-cell, morula, and blastocyst stages. Treatment of oocytes with PT results in a small but significant acceleration in the rate of GVBD, but has no effect on the extent of polar body emission. Treatment of one-cell embryos with PT has no effect on the extent of cleavage, onset of transcriptional activation at the two-cell stage, or development of two-cell embryos to the hatching blastocyst stage.
With advancing age, widespread histologic changes in the conduction system occur. These changes may alter several features of the aging electrocardiogram, including duration of the PR and QT intervals, orientation of the electrical axis, duration and morphology of the atrial and ventricular complexes, and characteristics of the ventricular repolarization. And although ST segment and T wave abnormalities may be the only clue to acute ischemia, they are nonspecific and associated with a multitude of noncardiac causes. With an awareness of atypical presentations and difficulties in ECG interpretation, emergency physicians may be able to improve the assessment and triage of elderly patients with acute coronary ischemia.
The feasibility of sparing postganglionic fibers of lumbar sympathetic nerves during the course of retroperitoneal lymphadenectomy has been investigated at our university medical center beginning in 1978. We selected 75 patients for nerve-sparing retroperitoneal lymphadenectomy in an effort to preserve ejaculatory function postoperatively. This cohort of patients was selected on the basis of clinical stage. Of the 75 patients 73 had clinical stage I disease. However, 14 of these 73 patients had pathological stage II cancer. No patient was treated with adjuvant chemotherapy after nerve-sparing retroperitoneal lymphadenectomy. Of these 14 patients with pathological stage II disease 4 had relapse: 1 with proved retroperitoneal recurrence, and 3 with serological elevations of tumor markers and questionable clinical findings as to anatomical site of relapse. All 4 patients are free of disease after chemotherapy and/or surgical (1) rescue. There were no local recurrences in the 61 patients with negative nodes. All 75 patients ejaculate and had no evidence of disease more than 2 years after nerve-sparing retroperitoneal lymphadenectomy. It is clear that nerve-sparing retroperitoneal lymphadenectomy is a feasible technique. As noted, it can even be applied to selected patients with low volume positive nodes, yet maintaining relapse and survival figures that are acceptable. Ejaculation is reliably preserved when this nerve-sparing technique is applied accurately in retroperitoneal lymphadenectomy.
The operative management of intra-abdominal testes is controversial, largely because there is no method of orchiopexy that can reliably produce good results. We report our results on the use of microvascular autotransplantation of intra-abdominal testes. We performed 12 autotransplants in 10 boys ranging in age from 10 months to 14 years (median age 30 months). In each instance the testis had been localized previously by laparoscopy or it was known to be intra-abdominal and was believed to be grossly normal in appearance. The vascular anastomoses of the spermatic to the inferior epigastric vessels were performed by an experienced microvascular surgeon using 10-zero nylon suture and 40 times magnification. Biopsies were taken at operation in 9 patients. Followup of 6 to 30 months is available in 7 patients and all 8 testes are palpably normal and in good scrotal position. This approach is feasible even in small children and the results seem to be superior to the expected results reported with division of the spermatic vessels.
The Society for Academic Emergency Medicine model curriculum for medical students and rotating residents was developed over a two-year period. The document was created as a complementary work to the undergraduate Core Content to provide appropriate emphasis, structure, and suggestions on the teaching of emergency medicine core curriculum topics at all levels. Consensus on the curriculum contents was reached from a national sample of emergency medicine educators. An educational matrix format was used to enhance flexibility based on the educational level of the learner and the instructional strengths of the teacher, and allowing for incorporation of a problem-based learning format. An outline of document contents and representative samples from each section are included; the entire document is available from SAEM.
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Aztreonam/metronidazole and cefotaxime/metronidazole were compared in a prospective trial in 154 patients undergoing elective colorectal surgery. Three antibiotic doses were given over 16 hours. A significant excess of wound sepsis in the aztreonam group was seen (23/71 vs 9/70 chi 2 6.60; P less than 0.01). Sepsis was almost invariably due to Gram-positive organisms and, in particular, Staphylococcus aureus.
Thirty-three samples of follicular fluid (FF) were collected from 14 patients with the polycystic ovary (PCO) syndrome and matched for FF-volume with small follicles collected from subjects with normal ovaries. The median (range) FF concentration of insulin-like growth factor 1 (IGF1) in the group with PCO, 0.42 (0.13-1.20) U/ml was significantly higher than that of the controls, 0.33 (0.04-0.59) U/ml. All samples tested had less than 1 ng/ml of FF-epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha). The patients with PCO syndrome (PCOS) had similar FF-testosterone (T) and FF-progesterone (P) concentrations to volume matched controls, but significantly higher levels of FF-androstenedione (AD) and lower FF-oestradiol (E2). These results suggest that the granulosa cells within the polycystic follicle have a functional defect in their aromatase enzyme complex.
Sixty-two preterm infants were followed up with flash visual evoked responses (VERs), brainstem auditory evoked responses (BAERs) and neurodevelopmental assessments for 18 months after term. Cranial ultrasonography showed that 18 infants developed intraventricular haemorrhage (IVH) during the newborn period and four of six infants with grade III or IV haemorrhage had absent VERs at term. The mean latency of the VER in the infants with IVH was significantly shorter than that of infants without IVH. There was no correlation between the degree of ventricular dilatation at term and the latency of the VER. Six months after term the four infants with previously absent VERs had normal responses, though there was still a significant difference between the latencies of infants with and without IVH. At 12 and 18 months of age these differences had disappeared. BAERs were not significantly different in the infants with and without IVH, and there was no difference in the VERs or BAERs of infants with neurodevelopmental delay and those developing normally. Neither flash VERs nor BAERs provide a good prognostic indicator of future neurodevelopmental disability or outcome.
Overnight physiological growth hormone (GH) secretion was evaluated in 95 short, prepubertal children (73 boys, 22 girls). All the children were below the 3rd centile for height and achieved GH levels greater than 15 mU/l following pharmacological stimulation. The mean average GH level was 7.1 mU/l and the mean sum of pulse amplitudes 80.4 mU/l. No relationship was found between age, height or height velocity and any of the parameters of GH secretion. The group was randomized to receive placebo, GH or remain under observation for the first 6 months and then all patients received GH treatment for a further 6 months. Those treated with GH, 0.27 IU/kg (0.1 mg/kg) three times weekly, in the first phase, demonstrated a mean increase in height velocity SDS of 3.24. There was no difference in growth response between the placebo or observation groups. In the second 6-month period, all children received GH according to the same dose regimen; they were then observed for a further 6 months following its discontinuation. In the 6 months following withdrawal of GH, all groups showed a significant fall in height velocity SDS, which returned to pretreatment levels, without demonstrating 'catch-down' growth. Repeat sampling of overnight GH secretion within 3 days of discontinuing GH showed normal secretory patterns with a small reduction in mean peak amplitude. These results suggest that short children without classic GH insufficiency respond well to exogenous GH in the short term and return to pretreatment height velocities afterwards. Consequently, it may be possible to increase final adult height in such children by GH treatment.
The oestrogen receptor content of colorectal adenocarcinoma was investigated using an established ligand binding biochemical assay and two more recently introduced techniques using specific monoclonal antibodies (Abbott ER-EIA and ER-ICA assay kits). Twenty nine tumours were investigated by the ligand binding assay. Only one (3.4%) tumour gave a weakly positive result (11 fmol/mg cytosol protein); the rest were all negative. Where sufficient tissue was available, the receptors were also determined by a quantitative immunoassay in 18 patients and an immunohistochemical method in 13 patients. The results were similarly all negative. It is concluded that most colorectal carcinomas, irrespective of sex, are oestrogen receptor negative, and it is thus unlikely that hormonal manipulation would have an influence on the course of the disease.