Biomedical subjects
Publications and source records attributed to R Singer.
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BACKGROUND: General shortage of cadaveric organs has led to a search for alternative methods to expand the donor pool. Sequential (domino) transplantation is yet another attempt to compensate for the declining consent to organ donation. PATIENTS AND METHODS: To qualify for a domino liver transplantation, the following preconditions must be fulfilled: (1) extrahepatic disease must exist, (2) liver must be fully functional, and (3) the genetic defect in the host should recur within a sufficient latency period. Familial amyloid polyneuropathy (FAP) is an autosomal dominant disease which involves a genetic defect for transthyretin (TTR), which is predominantly produced in the liver. RESULTS: In this report, we describe a rare case of a FAP TTR-50 variant undergoing domino liver transplantation. Since myocardial symptoms precede peripheral polyneuropathy, special emphasis should be placed on arrhythmias and the restrictive cardiomyopathy necessitating a veno-venous bypass or a cardiac pacemaker in order to improve cardiac contractility. The type of anastomosis of the suprahepatic inferior vena cava and possible alternatives are discussed. CONCLUSION: Despite ethical problems, the advantages of the domino procedure are obvious: (1) expansion of the donor pool, (2) ability to use living donors, and (3) presence of very short ischemic time and thus excellent liver function. Due to the kinetics of TTR production and deposition, donors and recipients of FAP livers should be followed up using an extensive neurological and cardiological protocol.
In this article, the authors review the basics of effective marketing and introduction of new technology for plastic surgery. The article addresses the financial issues involved in this new technology, as well as issues of staffing, safety and efficacy of the procedure, insurance, and use of the new equipment. The article closes with an affirmation of the importance of training courses and the necessity of serving patient interests.
The right atrium and the right ventricle of fifty-five patients were imaged with transesophageal echocardiography during fifty-nine total knee arthroplasties performed with cement and the use of general anesthesia. The patients ranged in age from thirty-two to eighty-three years (mean, 65.5 years). Cardiopulmonary parameters were measured with use of hemodynamic monitoring systems, such as pulse oximeters, pulmonary artery catheters, and radial artery catheters. In addition, a femoral vein catheter was inserted on the side of the operation in ten of the fifty-five patients. Showers of echogenic material traversing the right atrium, the right ventricle, and the pulmonary artery after the tourniquet was deflated were observed to various degrees in all patients and lasted three to fifteen minutes. The mean peak intensity occurred within thirty seconds (range, twenty-four to forty-five seconds) after the tourniquet was released. The mean mixed venous oxygen saturation (and standard error of the mean) decreased (from 83+/-0.9 to 72+/-1.5 per cent) and the mean pulmonary arterial pressure increased (from 20+/-1.0 to 27+/-1.0 millimeters of mercury [2.67+/-0.13 to 3.60+/-0.13 kilopascals]), compared with the values before the tourniquet was released, in all patients. The pulmonary vascular resistance index increased after release of the tourniquet (to a maximum of 328+/-29 dyne.s.cm(-5).m2; p = 0.00002) only in the patients who had echogenic material that was at least 0.5 centimeter in diameter. Clinical pulmonary embolism developed postoperatively in three patients; all three had had echogenic particles that were more than 0.5 centimeter in maximum diameter on imaging. Blood aspirated from one of the pulmonary artery catheters and from five of the ten femoral vein catheters demonstrated fresh venous thrombus. Histological evaluation of the aspirates failed to demonstrate fat, marrow, or particles of polymethylmethacrylate. Surgeons should consider acute pulmonary embolism as a diagnosis when evaluating a patient who has hemodynamic collapse during total knee arthroplasty performed with cement.
Whipple's disease is a rare systemic infectious disease. To date, it has neither been possible to culture the bacillus Tropheryma whippelii, nor to infect other individuals with the pathogen. Today the diagnosis is confirmed by means of polymerase chain reaction (PCR) technology. Typically, the material for the PCR analysis comes from the duodenum. The diagnosis can also be established in this way on the basis of other tissue, or the cerebrospinal fluid. Treatment should only be carried out with antibiotics which cross into the cerebrospinal fluid, since there can also be an unrecognised involvement of the CNS. At present, the favoured method of treatment is the daily parenteral administration of 1.2 million units of benzylpenicillin (penicillin G) and streptomycin 1 g for a period of 2 weeks. This is followed by treatment with cotrimoxazole (trimethoprim 160 mg and sulfamethoxazole 800 mg) twice daily for 1 to 2 years. The treatment should begin and end with a PCR analysis of cerebrospinal fluid, in order to definitively diagnose infection of the CNS with Whipple's disease and to document the disappearance of the bacillus from the CNS.
OBJECTIVE: To determine factors that predict decline in manual performance using a multivariate model of determinants of functional limitation. DESIGN: Longitudinal observational study. SETTINGS: Ambulatory general medicine clinics, residences of homebound individuals, and a continuing care retirement community. PARTICIPANTS: Subjects were 485 persons more than 60 years of age and included continuing care retirement community (CCRC) residents (n = 215), chronically homebound older persons (n = 65), and ambulatory older adults (n = 205). Mean age at baseline was 78 years. MEASUREMENT: Independent variables included demographics, physician measures of upper-extremity joint impairment, comorbidities derived from physical examination and chart abstract, self-assessed arthritis pain, depression, and anxiety. The major dependent variable was 2-year decline in timed manual performance below a threshold associated with need for long-term care services. RESULTS: The proportion of subjects who exceed a Timed Manual Performance Test threshold of 350 seconds increased slowly from baseline through Year 4 for all age groups but rose rapidly from Year 4 to Year 6 for the oldest group (> 85 years at baseline). Using a discrete survival model, we found that age, education, grip strength, and psychological status predicted crossing the manual performance threshold within a 2-year period. CONCLUSIONS: The findings, coupled with earlier findings that upper extremity joint impairment predicted both grip strength and manual performance, suggest that joint impairment may be an important risk factor for future functional limitation. Since diminished hand function has been shown to predict dependency, development and testing of interventions to maintain or restore upper extremity joint function and reduce pain would appear to be a high research priority.
All patients undergoing uncemented total hip arthroplasty for end stage hip disease related to osteonecrosis of the femoral head were assessed prospectively between November 1983 and October 1992. The results of clinical evaluation using the Harris Hip score and radiographic assessment of fixation were analyzed to identify features of success or failure that may be unique to this population. Four different stem types and 4 different acetabular components were used. Sixty-four patients had 98 hips implanted during the time of the study. The 42 male and 22 female patients averaged 41 years of age (range, 21-69 years). Average followup was 87.3 months (7.3 years; range, 31-134 months). The cause of osteonecrosis was corticosteroids (42 hips), alcohol (27 hips), trauma (5 hips), and other (24 hips). Three patients (5 hips) have died and 4 patients (6 hips) are lost to followup. At last followup 65 of 87 hips (75%) remained radiographically stable and clinically functional, 18 of 87 (21%) have been revised, and 4 were failing (osteolysis). Of the 22 hips with revision or impending failure, 4 were for technical reasons on the femoral side and 18 were for acetabular wear. Patient factors such as weight or underlying disease state did not seem to influence the ability to achieve stable fixation or contribute to accelerated failure. Failures related primarily to problems of first generation devices including accelerated wear of acetabular components, technical issues of femoral component placement (undersizing of components or femoral fracture), and the use of noncircumferentially coated femoral components. Age may be a factor in early failure. This 10-year experience with total hip arthroplasty for the patient with end stage hip disease due to osteonecrosis suggests that uncemented total hip arthroplasty can be applied predictably to this younger, potentially more active patient population.
The medical profession is besieged by concerns about cost containment. This in turn has focused attention on the use of ambulatory surgical facilities. However, the costs of hospital outpatient surgery programs usually prevent them from being competitive when compared with the costs of using office surgical facilities. To address the question of patient safety in office surgical facilities, the American Association for Accreditation of Ambulatory Surgery Facilities (AAAASF) sent a questionnaire to its accredited facilities. Two-hundred and forty-one (57.7 percent) of the 418 accredited facilities returned the anonymous questionnaires, a very high response rate. Or interest are the following findings: 400,675 operative procedures were reported during a 5-year period. Significant complications (hematoma, hypertensive episode, wound infection, sepsis, hypotension) were infrequent, occurring in 1 in every 213 cases. Return to the operating room within 24 hours and preventive hospitalization were less frequent. A death occurred in 1 in 57,000 cases (0.0017 percent). The overall risk is comparable in an accredited office (plastic surgical facility) and in a free-standing or hospital ambulatory surgical facility. This study documents an excellent safety record for plastic surgery done in accredited office surgical facilities by board-certified plastic surgeons.
OBJECTIVE: To determine factors that predict change in walking velocity in older people using a multivariate model. DESIGN: Longitudinal observational study. SUBJECTS: A total of 588 persons older than age 60, including subjects residing in a continuing care retirement community (CCRC) (n = 248), and homebound (n = 79) and ambulatory (n = 261) subjects. Mean age at baseline = 77. MEASUREMENT: Independent variables included demographics, physician measures of lower-extremity joint impairment and other musculoskeletal and neurological variables, comorbidities derived from physical examination and chart abstract, self-assessed arthritis pain, depression, and anxiety. The major dependent variables were 2- and 4-year decline in walking velocity below a threshold associated with nursing home placement. MAIN RESULTS: From baseline to Year 4, median walking velocity declined from 61.8 to 53.0 m/min, and the proportion of subjects above a threshold value of 11.5 m/min declined from 95.3% to 80.4%. Age, joint impairment, and weakness of quadriceps, measured at baseline, predicted 2-year and 4-year decline in walking velocity. CONCLUSIONS: The findings indicate that joint impairment and quadriceps strength contribute significantly to crossing a clinically significant threshold in walking velocity among older people over time. Future research is needed to determine whether these risk factors can be modified through preventive interventions such as muscle-strengthening exercises and pain medication.
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Chemotherapy with the cytotoxic drug procarbazine (PCB) causes permanent infertility in most male patients. Since many patients treated with this cytotoxic drug are of reproductive age, it is important to develop a method to protect spermatogenesis and fertility. It has been hypothesised that 'spermatogenic arrest' by pharmacological intervention may render the testes less susceptible to the effects of chemotherapy. The present study investigated whether recovery of fertility in a male rat model could be achieved by suppression of spermatogenesis with high doses of clomiphene citrate (CC) prior to PCB administration. It was demonstrated that young male rats treated with a combination of CC and PCB partially recovered spermatogenesis and achieved almost normal fertility. In contrast, animals treated with PCB alone exhibited abnormal spermatogenesis and remained infertile.
Sperm surface glycoproteins are modified during passage through the epididymis, a process believed to be important in the production of functionally mature spermatozoa. The effect of various cytokines on reproductive events has recently been investigated, with conflicting results. In the present investigation, the effect of interferon-alpha-2b (IFN alpha 2b) on sialyltransferase (ST) activity and beta-galactoside alpha-2,6-sialyltransferase (Gal 2,6-ST) mRNA expression was studied in rat testicular tissue. The results revealed the presence of Gal 2,6-ST mRNA in rat testicular tissue, similar in molecular size to that found previously in rat spleen, lung, ovary, kidney, heart, and brain. In addition, we observed that IFN alpha 2b reduced Gal 2,6-ST mRNA and ST activity in rat testes by a comparable magnitude. These findings provide insight into an additional mechanism by which cytokines may affect the reproductive system.
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OBJECTIVE: To validate a hierarchical model of hand function in older persons, using longitudinal data. DESIGN: Longitudinal observational study (2-year data from an ongoing longitudinal study). SUBJECTS: 689 persons older than age 60, including Continuing Care Retirement Community (n = 230), homebound (n = 204), and ambulatory (n = 255) respondents. Mean age at baseline 76.6 (SD = 8.8). MEASUREMENT: Independent variables included sociodemographics, physician measures of upper joint impairment, self-reported comorbidity, arthritis pain, depression, and anxiety. The dependent variables included grip strength and a timed manual performance test. MAIN RESULTS: Using generalized estimated equations (GEE) to test our hierarchial model, we found that gender and upper extremity joint impairment were the strongest predictors of a longitudinal measure of grip strength. Grip strength, in turn, along with demographics, comorbidity, and a measure of psychological status, was significantly related to timed manual performance. CONCLUSIONS: The longitudinal analyses confirmed a previous cross-sectional finding that upper extremity joint impairment contributes significantly to reduced grip strength, which, in turn, contributes to reduced hand performance on a timed test.
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Echogenic venous emboli accompany tourniquet deflation during total knee arthroplasty. The associated pulmonary hemodynamic alterations and determined embolic composition were measured in 34 patients, undergoing 35 procedures. Ten patients received a femoral venous catheter on the operative side. Hemodynamic variables, heart rate and mixed venous oximetry, end-tidal CO2 and nitrogen tensions, and transesophageal echocardiograms were recorded after induction of anesthesia (baseline), after tourniquet inflation, after cementing, and for 15 min after tourniquet deflation. Echocardiograms revealed either showers of miliary echogenic material (Group S, 9 patients), or large echogenic masses superimposed on the showers (Group MS, 26 patients). In Group MS only, pulmonary vascular resistance index increased above baseline (205 +/- 16 [SEM] dyne.s.cm-2) beginning 5 min after tourniquet deflation (maximum 328 +/- 29, P < 0.05). Mean pulmonary arterial pressure increased above baseline (20 +/- 1.0 mm Hg) for both Groups S and MS beginning 3 min after tourniquet deflation (27 +/- 1.0, P < 0.05). Cardiac index did not change. Five of 10 patients demonstrated fresh thrombus from the catheter in the operative limb. Echogenic emboli occurred in all patients upon tourniquet deflation during knee arthroplasty. Pulmonary vascular resistance index increased only in patients with large echogenic material. Our data suggest that these emboli represent fresh thrombus formation during tourniquet inflation. Heparin administration prior to tourniquet inflation may diminish embolic showers.
In recent years, the soluble Interleukin-2 Receptor (sIL-2R) has gained recognition as a valuable marker of in vivo activated immune functions in a variety of diseases. We studied sIL-2R levels in patients with cytomegalovirus (CMV) disease, and/or graft versus host disease (GVHD) following bone marrow transplantation (BMT). Our study included 36 patients after T-cell depleted allogenic BMT and 11 healthy controls. Mean sIL-2R serum levels were significantly higher after BMT than before (1273 u/ml vs. 629 u/ml, respectively, p < 0.007). In the patients who developed CMV disease, with or without GVHD, mean sIL-2R levels increased significantly (2866 u/ml p < 0.004); there was a drop after recovery (1949 u/ml), but not a return to pre-CMV onset levels. Similar elevated sIL-2R levels were found in patients during CMV disease only, GVHD only, or both. In patients who developed GVHD, sIL-2R levels were positively correlated with the severity of GVHD (Pearson's correlation coefficient .8322, p < 0.003). We conclude that sIL-2R may serve as a valuable nonspecific marker for the presence of CMV disease and severity of GVHD following T-lymphocyte depleted BMT.
In two men (69 and 65 years old) a gastric epithelioid leiomyosarcoma more than 25 cm in diameter first manifested itself by an increase in abdominal girth and ascites. In case 1, a cylindrical mass was palpable in the abdomen increasing in size over two years. Sonography and computed tomography showed a large cystic tumour which could not be related to any one organ. Cytology of the ascites fluid did not reveal any tumour cells. At operation a pedunculated tumour, 29 x 20 x 9 cm, was found, originating from the stomach. Six litres of ascites fluid were aspirated. There were no detectable abdominal metastases. The patient died nearly 4 years later after the tumour had been resected, three further laparotomies had to be performed because of extensive metastases to peritoneum and liver from the leiomyosarcoma. In case 2, no abdominal mass was palpable, but the patient's girth had increased over the last year. Sonography revealed a cystic tumour, about 30 cm in diameter. Examination of haemorrhagic ascites fluid (700 ml) did not show any tumour cells. The tumour, originating from the stomach wall, was excised (no metastases were seen). The patient remains symptom-free after 35 months.