Showing papers by "University of Alabama at Birmingham published in 1979"
TL;DR: It is concluded that combined flucytosine-amphoericin B therapy is the regimen of choice in cryptococcal meningitis.
Abstract: We compared amphotericin B therapy for cryptococcal meningitis with a newer regimen containing both amphotericin B and flucytosine. In 50 patients with 51 courses of therapy adherent to the protocol, 27 courses were with amphotericin B and 24 with the combination. Even though the combination regimen was given for only six weeks and amphotericin B for 10 weeks, the combination cured or improved more patients (16 vs 11), produced fewer failures or relapses (three vs. 11), more rapid sterilization of the cerebrospinal fluid (P less than 0.001) and less nephrotoxicity (P less than 0.05) than did amphotericin B alone. The number of deaths was the same (five) with each regimen. Adverse reactions to flucytosine occurred in 11 of 34 patients but were not life threatening. We conclude that combined flucytosine-amphoericin B therapy is the regimen of choice in cryptococcal meningitis.
762 citations
TL;DR: This paper reviewed the scope of product life cycle (PLC) research and pinpointed areas requiring further investigation and provided guidelines for future researchers, concluding that additional research-more diversified and extensive in nature-is needed on many PLC topics.
404 citations
TL;DR: An analysis of failure to control locally recurrent or metastatic melanoma was used to substantiate the value of thickness as a guide to surgical management and the rationale of elective RND isImproved survival in patients with intermediate thickness lesions while it is justifiable as a staging procedure for lesions exceeding 4.0 mm thickness.
Abstract: An analysis of failure to control locally recurrent or metastatic melanoma was used to substantiate the value of thickness as a guide to surgical management. There were no local recurrences in patients with melanomas less than 0.76 mm in thickness, regardless of the skin margins excised. The three year actuarial incidence of subsequent regional metastases in patients initially treated by wide local excision (WLE) of their melanoma was directly correlated with tumor thickness (p = 4.0 mm in thickness. At five years, patients with melanomas of 1.50 to 3.99 mm thickness who had WLE plus elective regional node dissection (RND) had a calculated 15% incidence of distant metastases and an actuarial survival rate of 83%, while patients with melanomas of the same thickness who had WLE alone as their initial surgical treatment had a 78% incidence of distant metastases and a 37% survival rate (p = 0.001 and 0.01, respectively). In patients with melanomas exceeding 4.0 mm in thickness, the potential benefits of RND were less apparent because of a high risk (>70%) of distant metastases at the time of initial diagnosis. Based upon this analysis, our initial surgical management of melanomas <0.76 is a WLE using a 2.0 cm margin of skin, while thicker lesions are excised using a 3 to 5 cm skin margin. Elective RND is not indicated for lesion <0.76 mm in thickness, but it is considered for 0.76 to 1.50 mm lesions in selected patients and is employed for virtually all patients with lesions exceeding 1.5 mm in thickness. The rationale of elective RND is improved survival in patients with intermediate thickness lesions (0.76 to 3.99 mm) while it is justifiable as a staging procedure for lesions exceeding 4.0 mm thickness. Cancer 43:883–888, 1979.
323 citations
Journal Article•
TL;DR: The type of initial surgical treatment, in fact, did influence survival after other variables were taken into consideration, and the multifactorial analysis supports the observation that patients with intermediate thickness melanoma thickness had a 78% 8-year survival rate, while none survived more than 8 years if a melanoma of the same thickness was only widely excised.
304 citations
TL;DR: The utility of the system as a once-a-month injectable contraceptive is established in the baboon model and the effects of continuous progesterone therapy on reproductive function in both rats and baboons are dose-dependent.
266 citations
TL;DR: It is concluded that type II atrial flutter is a distinct rhythm which may be intermediate between classic, or type atrialFlutter and atrial fibrillation.
Abstract: Studies were performed using bipolar atrial wire electrodes to record atrial electrograms and to pace the atria in 27 patients who developed atrial flutter after open heart surgery. Two types of atrial flutter, classic or type I atrial flutter, and type II atrial flutter, were identified. Both types of atrial flutter were characterized by uniformity of the beat-to-beat atrial cycle length, morphology, polarity, and amplitude of the recorded bipolar atrial electrogram. Both types sometimes manifested a beat-to-beat electrical alternans, which in turn was sometimes associated with an alternans in beat-to-beat cycle length. The initial basis of separation of types I and II atrial flutter was that type I atrial flutter was always influenced by rapid atrial pacing from the high right atrium, and type II atrial flutter was not. Two additional observations suggested that types I and II atrial flutter were different, although related, rhythms: 1) In four patients, type II atrial flutter was present after termination of rapid atrial pacing used to treat type I atrial flutter; 2) in two patients, type II atrial flutter changed to type I atrial flutter in a one-step fashion. The range of rates of the two types of atrial flutter were also different type I atrial flutter was slower (range 240–338 beats/min) than type II (range 340–433 beats/min). We concluded that type II atrial flutter is a distinct rhythm which may be intermediate between classic, or type atrial flutter and atrial fibrillation
266 citations
TL;DR: It is reported here that binding of CRP to model membranes of PC requires the incorporation into the bilayer of lysophosphatidylcholine (LPC), providing a possible biochemical explanation for binding ofCRP to damaged but not intact cell membranes.
Abstract: C-Reactive protein (CRP), the most characteristic of the 'acute phase proteins' (ref. 1) is thought to participate in the mediation and/or modulation of acute inflammatory processes, but its exact function is unknown. CRP has a Ca2+-dependent binding specificity for phosphorylcholine, the polar head group of two widely distributed lipids, lecithin (phosphatidylcholine, PC) and sphingomyelin (SM). A number of observations suggest that at least some of the biological activities of CRP depend on its interaction with phospholipids of cell membranes. In addition, interaction of CRP with PC- and SM-containing lipid dispersions and with PC-containing liposomes can activate the complement system. We report here that binding of CRP to model membranes of PC requires the incorporation into the bilayer of lysophosphatidylcholine (LPC). Thus, a disturbance of the molecular organisation of the bilayer appears to be necessary for binding of CRP. These findings provide a possible biochemical explanation for binding of CRP to damaged but not intact cell membranes and might be relevant to its biological function.
246 citations
TL;DR: A method is described which permits the adaption of ELISA techniques for measurement of antibody against bacterial polysaccharides using cyanuric chloride as the coupling agent.
205 citations
TL;DR: The finding that H. influenzae and S. pneumoniae produce an IgA1 protease indicates that this is a property of all three major etiological agents of bacterial meningitis, and suggests that IgA 1 protease production may be an important factor in the pathogenesis of this disease.
Abstract: Thirty-seven strains of the genus Haemophilus and five strains of Streptococcus pneumoniae were examined for their ability to produce extracellular enzyme that cleaves immunoglobulin molecules. All strains of H. influenzae, H. aegyptius, and S. pneumoniae elaborated enzyme that selectively cleaved human immunoglobulin A1 (IgA1) myeloma proteins but was inactive against a variety of other proteins including human IgA2, IgG, and IgM, porcine and bovine secretory IgA, human and bovine serum albumins, and ovalbumin. Although susceptible, human secretory IgA remained largely undigested. Two strains of H. pleuropneumoniae isolated from fatally infected pigs cleaved porcine secretory IgA, but had no effect on human IgA proteins. None of 16 strains that belonged to nonpathogenic Haemophilus species produced IgA protease. Analyses of the cleavage products of human IgA1 and secretory IgA proteins by immunochemical methods, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and analytical ultracentrifugation revealed that Fab and Fc fragments were produced. Since the production of IgA1 protease by Neisseria meningitidis has been reported previously, our finding that H. influenzae and S. pneumoniae produce an IgA1 protease indicates that this is a property of all three major etiological agents of bacterial meningitis. This suggests that IgA1 protease production may be an important factor in the pathogenesis of this disease.
189 citations
TL;DR: Cooper et al. as discussed by the authors showed that pre-B cells can synthesise large amounts of intracellular heavy (μ) chains in the absence of any light chain (LC) synthesis detectable by immunofluorescence or immunochemical techniques.
Abstract: THE first identifiable member of the B-cell line, termed the pre-B-cell, has been shown by immunofluorescent techniques to contain small amounts of intracellular IgM, but to lack detectable surface immunoglobulin1 These cells have been found in several species at sites of B-cell generation, most notably fetal liver and adult bone marrow1,2 and considerable evidence now exists which supports this precursor–progeny relationship of pre-B cells and B lymphocytes1–5 However, conflicting data exist with regard to pre-B cell expression of μ and light chains Although these cells were originally described in mice as containing both intracellular heavy (μ) and light chains1, using the same immunofluorescence techniques we have subsequently been unable to demonstrate either κ or λ light chains within these cells (PB and JK, unpublished) Moreover, the presence of light chains in murine pre-B cells cannot be confirmed with the original anti-κ antibodies used in ref 1 (M Cooper, personal communication) These findings are also contrary to immuno-chemical data which suggest the presence of complete IgM molecules both intracellularly and on the surface of early fetal liver cells6 We have used somatic cell hybridisation to approach this controversial issue We have now obtained, after fusion with fetal liver, hybridomas which synthesise large amounts of intracellular μ chain in the absence of any light chain (LC) synthesis detectable by immunofluorescent or immunochemical techniques The immunoglobulin phenotype of these hybridomas is identical to that observed in immunofluorescence studies of pre-B cells from fetal liver or adult bone marrow, and suggests that synthesis of μ chain before light chain expression is a normal event in the early differentiation of the B-cell line
183 citations
TL;DR: Perinatal events, including maternal complications and signs of illness at or immediately after birth, suggested ascending infection with exposure in utero to be likely in six infants and passive acquisition of GBS (intrapartum exposure) probably occurred in the three remaining early onset cases.
TL;DR: The association in jaw closers of spindles with extrafusal fibers high in oxidative enzyme activity is consistent with the view that spindle are the sensory component of a reflex system that recruits these fibers for finely-graded contractions in response to small internal length-changes of the muscle.
Abstract: The occurrence and distribution of muscle spindles was studied in histochemically and conventionally stained serial cross sections of 6-week-old and adult rat masticatory and suprahyoid muscles. Spindles were present in moderate to large numbers in jaw closers, but they were absent in jaw openers and two of four muscles of an accessory suprahyoid group. In jaw closers, 67% or more of the total spindle population was concentrated relatively distant from the temporomandibular joint, in muscle portions which contained large numbers of extrafusal fibers reacting strongly for oxidative enzymes. Because of their location, spindles in these portions should be stretched more and, subsequently, should respond with a greater afferent discharge at any given muscle length than spindles situated nearer to the joint. Spindles in jaw closers, especially the medial pterygoid and deep masseter, often occurred in clusters and complex forms near the terminal branching of intramuscular nerve trunks. No such concentrations were seen in the two muscles of the accessory suprahyoid group that had spindles. The association in jaw closers of spindles with extrafusal fibers high in oxidative enzyme activity is consistent with the view that spindles are the sensory component of a reflex system that recruits these fibers for finely-graded contractions in response to small internal length-changes of the muscle (Botterman et al., '78); however, in jaw openers and two muscles of the accessory suprahyoid group, the absence of spindles, coupled with the presence of large populations of extrafusal fibers high in oxidative enzyme activity, is not easily reconciled with this concept.
TL;DR: The cardiopulmonary-bypass technic for cardiac operations began to evolve in the mid-1950's, there was wide enthusiasm for its potential benefits, but it soon became apparent, however, that some of the benefits were questionable.
Abstract: WHEN the cardiopulmonary-bypass technic for cardiac operations began to evolve in the mid-1950's, there was wide enthusiasm for its potential benefits. It soon became apparent, however, that some o...
TL;DR: Serotypes of Streptococcus pneumoniae from 525 infected children were examined over a four-year period; most childhood infections occurred in children less than or equal to 24 months of age; no relationship between age and infecting serotype was noted.
Abstract: Serotypes of Streptococcus pneumoniae from 525 infected children were examined over a four-year period. Type distribution was similar among 84 cases of bacteremia and 30 cases of meningitis, with types 6, 14, and 18 accounting for half of the illnesses. In contrast, half of 396 episodes of otitis media were caused by three other types, 19, 23, and 3. Four of eight fatalities were due to type 6. Carrier strains isolated from children had a distribution of types similar to that of the otitis media collection. Adult patients had fewer of the types that caused disease in children. Most childhood infections (80%) occurred in children less than or equal to 24 months of age; no relationship between age and infecting serotype was noted. There were no seasonal trends in type distribution.
TL;DR: Studies of ganglionic neurons, cultured sympathetic ganglion cells, and the PC 12 cell culture line have raised questions regarding the use of BuTX as a nicotinic receptor ligand in the CNS.
TL;DR: Except in very small babies, the risks of hospital death of a two-stage approach are not less than those of primary repair done without a transannular patch, except when body surface area is less than about 0.35 m' or smaller.
Abstract: Fifteen of 194 patients (7.7%) with tetralogy of Fallot operated upon since January 1, 1972 under a protocol of routine primary repair despite young age died in-hospital. Most deaths were from low cardiac output. Young age and smallness of size increased the risk of operation. No deaths occurred among patients older than 4 years. High hematocrit was also a risk factor. Transannular patching has an independent effect in increasing risk. The post-repair ratio of peak pressure in the right ventricle to that in the left did not exert an independent effect. To project current risks of a two-stage approach, we determined that five of 158 patients (3.2%) died in-hospital after secondary intracardiac repair after a previous Blalock-Taussig or Waterston anastomosis between 1967--1978. Using these data and those we have published on the risk of shunting, we project that except in very small babies, the risks of hospital death of a two-stage approach are not less than those of primary repair done without a transannular patch, except when body surface area is less than about 0.35 m2. When a transannular patch is used in the primary repair, the two-stage approach is projected to be safer when the child has a body surface area of about 0.48 m2 or smaller.
TL;DR: A survey of the literature on response inducement techniques in mail survey research can be found in this paper, where the authors examined 12 of the most frequently researched techniques for increasing response rates.
TL;DR: The ability to predict symptomatic HSV recurrences in renal transplant patients could be a valuable aid in identifying individuals with which to evaluate antiviral compounds.
Abstract: Forty-nine recipients of renal allografts were studied for infection with herpes simplex virus (HSV) before and at sequential intervals after transplantation. Forty-four (90%) of the patients studied were initially seropositive for neutralizing antibody to HSV type 1. HSV was not shed prior to transplantation nor by any of the five seronegative recipients after transplantation. Twenty-nine (66%) of the 44 seropositive patients shed virus postoperatively: 23 in saliva, three in urine, and three in both sites. Twenty (63%) of 32 seropositive patients examined developed herpetic mucocutaneous lesions. Both viral shedding and lesions were most prevalent during the first four weeks after transplantation. Twenty-nine (85%) of 34 patients with antibody titers of 1:256-1:4,096 and zero of 10 with titers of 1:8-1:128 shed HSV postoperatively (P less than 0.0001). The group with high antibody titers before transplantation were also more likely to develop lesions after transplantation (P = 0.002) as were those with a positive history (P = 0.017). The ability to predict symptomatic HSV recurrences in renal transplant patients could be a valuable aid in identifying individuals with which to evaluate antiviral compounds.
TL;DR: Results indicate that glycosylation of viral glycoproteins is not required for the determination of the cellular maturation site of these enveloped viruses.
Abstract: We have investigated whether glycosylation of membrane glycoproteins is a determinant of the site of maturation of enveloped viruses in Madin-Darby canine kidney (MDCK) cells. In MDCK cell monolayers, vesicular stomatitis virus buds exclusively from the basal or lateral plasma membranes and contains a sialylated glycoprotein, whereas influenza virus buds exclusively from the apical plasma membrane and lacks neuraminic acid. In order to study the possible relationship between glycosylation of viral glycoproteins and the budding site, infected MDCK cells were treated with tunicamycin at a concentration that completely inhibits glycosylation of viral glycoproteins and the site of virus maturation was examined by electron microscopy. When tunicamycin-treated monolayers were compared to controls, the polarity in the maturation sites of both viruses was maintained. These results indicate that glycosylation of viral glycoproteins is not required for the determination of the cellular maturation site of these enveloped viruses.
TL;DR: The disposition and safety of the antiviral drug acyclovir were studied in 14 subjects with advanced malignancies and it appears that both glomerular filtration and tubular secretion contribute to its renal excretion.
Abstract: The disposition and safety of the antiviral drug acyclovir were studied in 14 subjects with advanced malignancies. Acyclovir was administered by a 1-hr intravenous infusion at doses of 0.5, 1.0, 2.5, and 5.0 mg/kg. At the end of infusion, mean peak plasma levels (+/- SEM), determined by radioimmunoassay, were 6.4 +/- 0.7, 12.1 +/- 2.3, 14.9 +/- 2.7, and 33.7 +/- 7.1 microM. The plasma concentration-time profiles could be described by a biexponential equation. The half-life of acyclovir in the slow disposition phase ranged from 2.2 to 5 hr and the drug was detected in the plasma for at least 18 hr after infusion. The total body clearance ranged from 117 to 396 ml/min/1.73 m2. A proportionality between area under the curve and dose suggests that acyclovir exhibits dose-independent kinetics in the dose range studied. There was wide variation in cumulative urinary excretion of unchanged drug, ranging from 30 to 69% of the dose. From renal clearances of acyclovir, which were higher than creatinine clearances, it appears that both glomerular filtration and tubular secretion contribute to its renal excretion. Analysis of the urine by reverse-phase high-performance liquid chromatography revealed the presence of the metabolite 9-carboxymethoxymethylguanine. There was no indication of toxicity either clinically or from laboratory findings in any of the study subjects. This study demonstrates that in addition to selectivity and low toxicity, the kinetic profile and metabolic disposition of acyclovir make it an attractive candidate for therapy in a variety of herpes infections.
TL;DR: A new long-acting, injectable contraceptive which provides continuous controlled release of the steroid norethisterone (NET) for a precise period of 6 months following a single intramuscular injection is described.
TL;DR: A computer based technique was developed which provided a flattened visual display of the retinal projection onto the entire superior colliculus, quantified the area covered by such projections for different segments of the colliculi and showed how this morphological pattern varied with depth beneath the collicular surface.
Abstract: The retino-collicular projections in rhesus monkeys were studied using standard autoradiographic and degeneration techniques. A computer based technique was developed which provided a flattened visual display of the retinal projection onto the entire superior colliculus, quantified the area covered by such projections for different segments of the colliculus and showed how this morphological pattern varied with depth beneath the collicular surface.
In the anterolateral third of the colliculus (i.e., the foveal representation) the retinal projection was light, confined to a narrow region of the superficial gray and contributed primarily by the contralateral eye. In the remaining binocular segment of the superior colliculus the retinal projections showed a marked degree of local patterning, that in many instances appeared as bands of label. By combining eye removal and eye injection procedures in a single animal and comparing adjacent sections processed for autoradiography and stained for degeneration, it was possible to assess the amount of overlap between retino-collicular projections from the two eyes. These experiments showed that total segregation of retinal afferents does occur in the monkey superior colliculus, but what occurs more often is a situation where the density of inputs from the two eyes varies reciprocally as one moves across the part of the colliculus that represents the binocular visual field.
TL;DR: This demonstrates the specific neurochemical, physiological, and behavioral alterations in dopaminergic systems produced by ascorbic acid and suggests possible therapeutic uses for asCorbate in conditions involving functional dopamine excess.
TL;DR: Results indicate that the midline is situated in the exact middle of the mouth in approximately 70% of people and that the maxillary and mandibular midlines fail to coincide in almost three fourths of the population.
Abstract: This report presents the results of an original investigation designed to determine (1) the prevalence in the natural dentition of a maxillary midline located in the exact middle of the mouth using the philtrum as the most reliable guide and (2) the percentage of people in whom the maxillary and mandibular midlines precisely coincide with each other. Results indicate that the midline is situated in the exact middle of the mouth in approximately 70% of people and that the maxillary and mandibular midlines fail to coincide in almost three fourths of the population.
TL;DR: Heart myocytes isolated from 240 g rats by perfusion with enzyme containing media are a useful model to study structural aspects of heart muscle and show a constant nuclear to cytoplasmic ratio in the two cell populations.
TL;DR: It is concluded that the rapid action of midazolam maleate and its modest effects on haemodynamic parameters, make it a safe and efficacious induction agent in patients with ischaemic heart disease.
Abstract: Midazolam maleate is a new water soluble benzodiazepine used for induction of anaesthesia. Ten patients with symptomatic ischaemic heart disease were premedicated intramuscularly with morphine 0.l mg · kg-1 and scopolamine 6–8 µg · kg-1, 60–90 minutes before induction. The heart rate, systolic/diastolic blood pressure, mean systolic blood pressure, mean pulmonary artery blood pressure, pulmonary artery occluded pressure, mean right atrial pressure, cardiac output (duplicate thermodilution) and arterial blood gas tensions were measured at four time periods: (1) after instrumentation while breathing room air, (2) after transfer to the operating room while breathing 100 percent oxygen by mask, (3) one to two minutes after intravenous midazolam maleate 0.2 mg · kg-1 and (4) four to five minutes after midazolam maleate. The cardiac index, stroke index, heart ratesystolic blood pressure product, systemic vascular resistance index, pulmonary vascular resistance index, left ventricular stroke work index and right ventricular stroke work index were calculated for each of the study time-periods from the measured parameters.
TL;DR: A method of lymphoscintigraphy using 99mTc-SC that documents the directions of lymphatic drainage from a primary site of truncal melanoma is developed, which indicates the anatomical direction of drainage, and is thus important in the surgical management of the patient.
Abstract: The authors developed a method of lymphoscintigraphy using 99mTc-SC that documents the directions of lymphatic drainage from a primary site of truncal melanoma. In 8 patients who had an excisional biopsy of the melanoma, migration from the injection site to regional lymph nodes was demonstrated. Four patients had lymphatic drainage correlating to that predicted by published anatomical pathways and 3 did not; in 1, more than one node-bearing area was at risk, but only one area had uptake, indicating unifocal drainage. This technique does not indicate metastatic disease per se, but indicates the anatomical direction of drainage, and is thus important in the surgical management of the patient.
TL;DR: A model of the essential aspects of the arterial blood pressure and its response to nitroprusside was applied to the simulation of a clinically used controller and has provided insight into responses observed in the treatment of over 700 patients.
TL;DR: Variable proportions of leukaemic lymphoblasts contained detectable cytoplasmic IgM indicating differential levels of maturation arrest and a probable close developmental relationship between IgM + cALL and IgM − cALL.
TL;DR: The structure of the human lateral geniculate nucleus has been studied on serial Nissl stained sections from 57 human brains, most of which were from neurologically normal individuals and were obtained during routine autopsy procedures.
Abstract: The structure of the human lateral geniculate nucleus has been studied on serial Nissl stained sections from 57 human brains. Most of the brains were from neurologically normal individuals and were obtained during routine autopsy procedures. The laminar arrangement within the human nucleus is surprisingly variable. It is always possible to recognize a small segment with two layers (the monocular segment), one with four layers and one with six layers. Often an 8-layered segment can also be seen. The posterior half of the nucleus, within which central vision is represented, is made up mainly of six layers, and is the least variable part of the nucleus. Here the layers lie roughly parallel to each other. In the anterior half of the nucleus the laminar arrangement is more variable, and the layers often form complex and irregular interdigitations with each other. The 8-layered segment varies greatly in size and may be absent. It generally lies at the edge of the 4-layered segment not, as might have been expected, within the borders of the 6-layered segment. In many parts of the nucleus nerve cells are organized in short rows that run perpendicular to the layers; also, individual nerve cells are elongated in this direction. This neuronal orientation follows the lines of projection that are defined by the borders of a zone of retrograde degeneration, and also corresponds to the orientation of a cellular discontinuity that probably is the geniculate representation of the blind spot. Thus, we conclude that the neuronal orientation indicates the lines of projection within the nucleus.