Biomedical subjects
J McCormick
Publications and source records attributed to J McCormick.
Outbreak of Crimean-Congo haemorrhagic fever in Quetta, Pakistan: contact tracing and risk assessment.
In December 1994 in a private hospital in Quetta, Pakistan, 3 health-workers contracted Crimean-Congo haemorrhagic fever (CCHF) after surgery on a bleeding patient who later died. We conducted a retrospective study to determine transmission risks among contacts. Fifty contacts gave blood for antibody tests and answered questions about exposure. Two of four people exposed percutaneously and one of five with cutaneous exposure contracted CCHE The person with cutaneous exposure was a surgeon who tore his glove during surgery and noted blood on his hand but no cut. There were no anti-CCHF antibodies or CCHF cases among persons whose skin came into contact with body fluids other than blood (0/4), who had skin-to-skin contact (0/16) with patients or were physically close to them (0/21). Three index case relatives reported that although 10 family members had cutaneous exposure, none developed CCHF. The family refused blood tests. CCHF transmission in resource-constrained settings can be limited by focusing on avoiding health worker contact with blood.
Dromyosuppressin and drosulfakinin, two structurally related Drosophila neuropeptides, are uniquely expressed in the adult central nervous system.
Drosophila myosuppressin (TDVDHVFLRFamide; DMS) and sulfakinin (FDDYGHMRFamide; DSK) have similar C-terminal structures. To determine the neuronal expression patterns of these structurally related peptides, we have generated DMS- and DSK-specific antisera to multiple antigenic peptides and performed double-label immunochemistry with antisera raised on different animals of the same species host animal. Our data indicate that DMS and DSK staining patterns in the adult central nervous system are unique and nonoverlapping.
Multiple antigenic peptides designed to structurally related Drosophila peptides.
We have isolated TDVDHVFLRFamide (DMS), FDDYGHMRFamide (DSK), and DPKQDFMRFamide from Drosophila melanogaster. These peptides, structurally related by a common C-terminus -XRFamide, where X = L or M, are encoded by three different genes. To determine cellular expression, we have generated antisera to multiple antigenic peptides and performed double-label immunofluorescence using antisera raised in the same species host animal. Our results indicate that DMS and DSK immunoreactive materials have unique, non-overlapping expression patterns, while DMS and DPKQDFMRFamide immunoreactive materials colocalize in two superior protocerebrum neurons, and DSK and DPKQDFMRFamide immunoreactive materials colocalize in one superior protocerebrum neuron, one subesophageal ganglion neuron, and three thoracic ganglia neurons.
The multiple meanings of long-term gastrostomy in children with severe disability.
Although the physiological implications of long-term gastrostomy for children with severe disability are well documented in the nursing literature, little is known about the psychosocial effect of this technological intervention. This study documents and interprets the perspective of expert nurses and parents to reveal conflictual social processes associated with gastrostomy decision-making and the intense moral dilemma that these processes create. The findings suggest that gastrostomy denotes multiple meanings for parents and health care providers, and that an appreciation for these meanings can have a significant positive impact on nursing care for these children and their families.
Examination-induced distress in a public examination at the completion of secondary schooling.
BACKGROUND: The context for this study was the Higher School Certificate examination in New South Wales, Australia. AIMS: The main research aim was to investigate the association between the Higher School Certificate, the reported distress and anxiety levels of the adolescent students who prepare for and sit for the examination, and various other internal and environmental variables. SAMPLE: The random sample consisted of 445 students in their last two years of secondary schooling, with approximately equal numbers of males and females from a diverse range of ethnic backgrounds. METHODS: Analysis was carried out using principal components analysis and multiple regression. RESULTS: The most significant contribution to distress associated with the examination was made by the personality trait, anxiety proneness. Lower socio-economic status, self-confidence, academic and verbal self-concepts and perceived ability to cope were also found, to a lesser extent, to be associated with increased distress. The interactions sex with ethnic background and year with ethnic background were of particular interest. Students who were male and had an English speaking background, and students in year 11 who had an English speaking background were least likely to experience distress than others in the context of the examination. CONCLUSIONS: Whilst results must be treated with caution, particular groups of students potentially vulnerable to distress were identified and directions for future research indicated.
Peritoneovenous shunts in patients with intractable ascites: palliation at what price?
Intractable ascites carries great morbidity by affecting appetite, mobility, and quality of life. Peritoneovenous shunts (PVSs) are utilized to abate intractable ascites, although long-term efficacy is unestablished. Thirty male and 18 female cirrhotics, 55 +/- 12 (standard deviation) years of age, failed multiple large-volume paracenteses and diuretic therapy before undergoing PVS. Data were collected until death or the present time. Nine patients (19%) are alive and palliated, four with working shunts [average follow-up (ave. f/u), 30 months] and five without shunts (ave. f/u, 19 months). Thirty-two (67%) patients died: 18 palliated with functional shunts (survival time, 4.4 +/- 5.7 months), 8 unpalliated with dysfunctional shunts (ave. f/u, 3.9 +/- 4.5 months), 4 unpalliated with shunts removed (ave. f/u 5.5 +/- 4.7 months), and 2 with unknown shunt function at death. Function was lost to occlusion in 26 patients, infection in 9, and ligation for disseminated intravascular coagulation in 3. Thirteen patients underwent 18 shunt replacements. At death/present time, 22 (46%) patients were palliated with functioning shunts. Seven patients were lost to follow-up. PVSs provide palliation for intractable ascites short term, but commonly occlude within 1 year. Despite palliation, complications with PVSs are high, and survival is limited.
What's new in ... rehabilitation medicine.
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Synthesis and activity of a novel series of 3-biarylquinuclidine squalene synthase inhibitors.
Quinuclidines with a 3-biaryl substituent are a new class of potent, orally active squalene synthase (SQS) inhibitors. Variants around these rigid structures indicate key structural requirements for cationic SQS inhibitors. Thus the lower in vitro potency found for quinuclidines bearing 3-substituents, which did not overlay the biphenyl group of 3-(biphenyl-4-yl)-3-hydroxyquinuclidine (2) (IC50 = 16 nM, rat microsomal SQS), implied a directional requirement for the 3-substituent. Similarly, the lower potency of the 3-terphenyl analogue 6 (IC50 = 370 nM) indicated size constraints for this substituent. In compounds with a linking group between the quinuclidine and biphenyl ring, linking groups of lower lipophilicity were less well tolerated (e.g., 17, CH2CH2, IC50 = 5 nM vs 19, NHCO, IC50 = 1.2 microM). Replacement of the distal phenyl ring of 2 with a more polar pyridine heterocycle caused a reduction in in vitro potency. In general, good in vivo activity in the rat was restricted to 3-hydroxy analogues, with the 3-[4-(pyrid-4-yl)phenyl] derivative 39 (IC50 = 161 nM) showing the best inhibition (following oral dosing) of cholesterol biosynthesis from mevalonate (ED50 = 2.7 mg/kg).
Medical hubris and the public health: the ethical dimension.
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Gait training efficacy using a home-based practice model in chronic hemiplegia.
OBJECTIVE: The efficacy of a home practice model for gait training was evaluated in 18 hemiplegic subjects 2.3 years (range, 1 to 5) after stroke. DESIGN: Uncontrolled case series. SETTING: Referral center. SUBJECTS: Patients at least 1 year poststroke referred to an outpatient rehabilitation program. INTERVENTION: Patients were taught home programs in two or more 2- to 5-day blocks averaging 35 physical therapy (PT) contact hours (range, 9.5 to 62.5); training extended over a mean of 22 months (range, 10 to 65). Training emphasized weight bearing, balance, segmental control, stretching, and bracing. MAIN OUTCOME MEASURES: Gait changes were measured using the newly developed Wisconsin Gait Scale (WGS). The patient-rated Falls Efficacy Scale (FES) was administered before and after training to 8 subjects, and the Health Status Questionnaire (HSQ) was retrospectively administered to all subjects to appraise subjective pretraining to posttraining changes and current psychological status. RESULTS: The average WGS score significantly improved (p < .05). Patients perceived that gait training increased the quality of their functional activities (p < .05). In a subset of patients, the FES showed that fear of falling was decreased (p < .05). Perception of well-being was comparable to a normative nonstroke reference population except for physical functioning. Compared to the only other published series (using traditional outpatient programming), the current model was of comparable cost. CONCLUSION: Despite the literature indicating a plateau in mobility function by 6 months after stroke, postacute training of gait in hemiplegic subjects using a home-based training model results in improved gait and the perception of improved function. Additionally, we provide validation for the newly developed Wisconsin Gait Scale, an instrument of gait measurement that may assist in comparing outcomes.
Football injuries in a rural area.
This study was conducted to analyze the frequency and characteristics of football injuries in a rural hospital setting and compare it to the national data. More than 6,000 patients with a sport-related injury presenting to the emergency medicine department at the Marshfield Clinic between June 1, 1988 and June 1, 1994 were collected prospectively. Eight hundred forty-three (14% of total) patients sustained football-related injuries. A chart abstraction form was then used to retrospectively review football injuries documenting types, sites, and mechanism of injury, along with demographic aspects. The peak age sustaining football injuries was 17 years old (17.5%). Most of the football injuries occurred during school activities (73.7%). The most common site injured was the finger (16.5%), followed by the knee (15.7%). Sprains/strains were the most common diagnosis representing 40.2% of injuries overall. The most common mechanism resulting in a football-related injury was as a result of being blocked or tackled (52.7%). Surgery was required on 4.9% of individuals injured while playing football. Most patients (69.7%) were expected to recover from their injury within 14 days. There were more injured football players from our area in the age group 15 to 24 years as compared to the national data available. Diagnosis, site injured, and mechanism of injury from our study were comparable to other national publications. Prospective studies are needed to address the problem of football-related injuries. Such studies would require a multidiscipline team of experts.
Management and prognosis of adenocarcinoma of the appendix.
PURPOSE: Adenocarcinoma of the appendix is a rare neoplasm, and controversies persist regarding management. The purpose of this study was to identify prognostic factors and define management strategies for patients with adenocarcinoma of the appendix. METHODS: A retrospective case series was conducted at three medical school teaching hospitals over a 20-year period from 1972 to 1992. Overall survival was determined by the actuarial life table method. Comparisons of prognostic factors were made using exact nonparametric log-rank tests. RESULTS: Thirteen patients were diagnosed during the study period. Median age was 62 years. There were five males and eight females. The disease was not suspected in any patient preoperatively. Seventy-seven percent of patients had metastatic disease at presentation. Second primary malignancies were found in 15 percent of patients. Thirty-eight percent of female patients had synchronous ovarian lesions. Median survival was 22 months, with an estimated five-year survival of 43 percent (95 percent confidence interval, 22-84 percent). Patients with colonic histology had significantly worse survival than patients with mucinous histology (P = 0.0093). Patients with carcinomatosis had a significantly worse survival than noncarcinomatosis patients (P = 0.0078). Patients who underwent right hemicolectomy had a better prognosis for survival than appendectomy patients, but the difference was not statistically significant. CONCLUSIONS: Carcinoma of the appendix is very difficult to diagnose preoperatively, and most patients are not identified until disease is advanced. Good prognostic factors include mucinous histology and the absence of carcinomatosis. Right hemicolectomy appears to be a reasonable option, although its superiority to appendectomy alone has not been definitively proven. High frequency of ovarian metastases in women suggests a role for bilateral oophorectomy. In addition, a complete work-up of the patient for a synchronous malignancy, especially in the gastrointestinal tract, should be considered.
Cellular expression of the Drosophila melanogaster FMRFamide neuropeptide gene product DPKQDFMRFamide. Evidence for differential processing of the FMRFamide polypeptide precursor.
DPKQDFMRFamide is one of five different FMRFamide-containing peptides encoded in the Drosophila FMRFamide gene. To study the cellular expression of DPKQDFMRFamide, we have generated antisera to DPKQD, the N-terminal sequence of the peptide, to avoid crossreactivity with other -FMRFamide-containing peptides. The antisera were purified and the specificity characterized. DPKQDFMRFamide immunoreactive material is first observed in the embryonic central nervous system (CNS) in one cell of the subesophageal ganglion and one cell in each of the three thoracic ganglia. This pattern of expression is observed in larval, pupal, and adult neural tissue, albeit with increased signal intensity. In larva, pupa, and adult, additional cells in the superior protocerebrum, a thoracic ganglion, and an abdominal ganglion express DPKQDFMRFamide immunoreactive material. Immunoreactivity is observed in a cell in the lateral protocerebrum of pupa and adult and cells in the optic lobe of adult. No immunoreactive material was observed in gut tissue. DPKQDFMRFamide antisera stain a subset of cells previously identified by in situ hybridization and immunocytochemistry to express the FMRFamide transcript and polypeptide precursor. These data suggest that the Drosophila FMRFamide polypeptide precursor undergoes differential processing to produce DPKQDFMRFamide immunoreactive material in a limited number of cells expressing the FMRFamide precursor.
Phase I clinical trial of pyrazoloacridine NSC366140 (PD115934).
The pyrazoloacridine (PZA) analogue NSC366140 (PD115934) entered clinical trial based on unique preclinical characteristics including solid tumor selectivity in vitro, marked antitumor activity in vivo against murine solid tumors, selectivity against noncycling cells, and activity against multidrug-resistant tumor cells. After identification of the pre-clinical efficacy and an acceptable toxicity profile, a Phase I study of PZA was carried out. A total of 28 patients was entered and received a total of 67 treatment courses. The drug was administered via a 1-h infusion every 21 days. The starting dose was 30 mg/m2 with 2-fold dose escalations through 480 mg/m2. The next dose escalation was 50%, to 720 mg/m2. Grade I through grade IV toxicities were observed. Since no dose-limiting toxicities were observed at 480 mg/m2, and up to grade IV toxicities were observed at 720 mg/m2, an intermediate dose, 600 mg/m2, was evaluated. Dose-limiting toxicities at 720 mg/m2 were hematological (grade III and IV neutropenia) in four of six patients and neurological (up to grade III cerebral toxicities, including restlessness, dizziness, agitation/anxiety, personality changes, and nightmares, as well as myoclonus) in three of six patients treated. The pharmacokinetic parameters which helped predict these toxicities included area under the curve and peak plasma level. Pharmacokinetic studies showed interpatient variations in all parameters studied. The mean area under the curve levels of PZA at the highest two dose levels in patients were near the level detected in mice at their maximum tolerated total dose. The recommended starting dose for Phase II trials using this schedule is 600 mg/m2.
Health promotion: the ethical dimension.
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