Idiopathic hypoparathyroidism with epilepsy and psychosis.
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Biomedical subjects
Publications and source records attributed to J Burke.
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Antigenic proteins of microfilariae and infective larvae of Wuchereria bancrofti have been identified by intrinsic and extrinsic radiolabelling, and specific immunoprecipitation with sera from filarial patients. From 125I surface-labelling experiments, the most prominent antigen on both stages is of relative molecular mass (Mr) 17 000, while a molecule of similar size is both synthesized and released in vitro following labelling with [35S]methionine. A second similarity between the two stages is the production and secretion of a Mr 21 000 component, which is, however, not detected on the worm surfaces. A series of additional proteins from larval W. bancrofti are described from each parasite compartment (secreted, surface and somatic) and the antigenicity and specificity of these components explored with serum from patients with filariasis due to W. bancrofti or Brugia species, and with onchocerciasis. Among additional molecules released in vitro we have found a Mr 51 000 antigen from both stages, and also several proteins which are not recognised by antibody from human filarial patients.
The HO gene product of Saccharomyces cerevisiae is a site-specific endonuclease that initiates mating type interconversion. We have determined the nucleotide sequence of a 3,129-base-pair (bp) segment containing HO. The segment contains a single long open reading frame encoding a polypeptide of 586 amino acids, which has unusual (unbiased) codon usage and is preceded by 762 bp of upstream region. The predicted HO protein is basic (16% lysine and arginine) and is calculated to have a secondary structure that is 30% helical. The corresponding transcript is initiated approximately 50 nucleotides prior to the presumed initiation codon. Insertion of an Escherichia coli lacZ gene fragment into the putative HO coding segment inactivated HO and formed a hybrid HO-lacZ gene whose beta-galactosidase activity was regulated by the mating type locus in the same manner as HO (repressed by a 1-alpha 2). Upstream regions of 1,360 and 762 bp conferred strong repression; 436 bp led to partial constitutivity and 301 bp to full constitutivity. Thus, DNA sequences that confer repression of HO by a1-alpha 2 are at least 250 nucleotides upstream of the transcription start point and are within 436 nucleotides of the HO initiation codon. The progressive loss of repression suggests that both the -762 to -436 and the -436 to -301 intervals contain sites for regulation by a1-alpha 2. The HO gene contains two distinct regions that promote autonomous replication of plasmids in S. cerevisiae. These regions contain sequences that are homologous to the two conserved sequences that are associated with ARS activity.
Multiple potentially injurious agents are present in smoke but the importance of each of these agents in producing lung injury as well as the mechanisms by which the lung injury is produced are unknown. In order to study smoke inhalation injury, we developed a synthetic smoke composed of a carrier of hot carbon particles of known size to which a single known common toxic agent in smoke, in this case HCI, could be added. We then exposed rats to the smoke, assayed their blood for the metabolites of thromboxane and prostacyclin, and intervened shortly after smoke with the cyclooxygenase inhibitors indomethacin or ibuprofen to see if the resulting lung injury could be prevented. Smoke exposure produced mild pulmonary edema after 6 h with a wet-to-dry weight ratio of 5.6 +/- 0.2 SEM (n = 11) compared with the non-smoke-exposed control animals with a wet-to-dry weight ratio of 4.3 +/- 0.2 (n = 12), p less than 0.001. Thromboxane B, and 6-keto-prostaglandin F1 alpha rose to 1,660 +/- 250 pg/ml (p less than 0.01) and to 600 +/- 100 pg/ml (p greater than 0.1), respectively, in the smoke-injured animals compared with 770 +/- 150 pg/ml and 400 +/- 100 pg/ml in the non-smoke-exposed control animals. Indomethacin (n = 11) blocked the increase in both thromboxane and prostacyclin metabolites but failed to prevent lung edema.(ABSTRACT TRUNCATED AT 250 WORDS)
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A case of snake-bite envenomation, probably by the rough-scaled snake (Tropidechis carinatus), in a 9-year-old boy is reported which we believe to represent the most severe and prolonged case yet of non-fatal snake-bite envenomation in a human. The initial clinical features included loss of consciousness within minutes of the bite, followed by a period of partial recovery. The child subsequently developed total body paralysis, acute renal failure, and gross rhabdomyolysis. Artificial ventilation was maintained for 10 weeks; muscle paralysis and paresis persisted for 18 weeks before neuromuscular function returned to normal. Recovery occurred in centripetal fashion, the respiratory muscles and the palatal muscles being the last to recover. Acute renal failure persisted for 18 days and was treated by peritoneal dialysis. Some beneficial effects were seen even when antivenom was given 90 hours after the bite, but gross rhabdomyolysis caused by this species is not prevented by the administration of antivenom after 60 hours. It is concluded that if life can be sustained for 10 weeks by artificial ventilation, normal intellectual and neuromuscular recovery is possible in such cases.
Difluoromethylornithine (DFMO), a specific, irreversible inhibitor of polyamine biosynthesis shown to be curative in animal models inoculated with various Trypanosoma spp., was evaluated in the Southern Sudan in a preliminary open clinical field trial in patients infected with Trypanosoma brucei gambiense. 20 patients were studied including 18 with late-stage disease involving the central nervous system, 16 of whom were refractory to arsenical treatment. In late-stage disease monotherapy with oral DFMO doses of about 400 mg/kg/day for five to six weeks was associated with disappearance of parasites from cerebrospinal fluid (CSF), decreased CSF WBC counts and protein concentrations and reversal of clinical signs. Side effects associated with this dose regimen included diarrhoea, abdominal discomfort and anaemia, but were seldom sufficiently severe to prompt discontinuing therapy. In early-stage patients about 200 mg/kg/day for six weeks appears adequate to eliminate parasites and reverse clinical symptoms and is well tolerated. Three cases of late-stage sleeping sickness and two of early-stage disease followed up for approximately one and a half to two years after treatment indicated that DFMO monotherapy can be curative. Additional studies are needed to define optimal posology. Inhibition of polyamine biosynthesis is a promising new approach to therapy of trypanosomiasis.
Four hundred seventy-eight patients with hand burns (786 hands) were treated at the burn service of the Massachusetts General Hospital. Long-term evaluation showed that early incision and immediate autografting of deep second degree, mixed second and third degree, and third degree full-thickness hand burns resulted in 93 percent, 95 percent, and 93 percent, respectively, excellent to good functional results. There was no significant differences in results in patients with superficial second degree burns treated nonsurgically with silver nitrate dressings and early physical therapy compared with results in patients with deep second degree, mixed second and third degree, and third degree hand burns treated with early excision and grafting. No patient with fourth degree burns had excellent to good results. Permanent damage was related to extent of original injury to the extensor tendons and joint capsules. On the basis of this broad experience, it is believed that all burned hands judged unlikely to heal within 3 weeks will benefit from early excision and grafting by experienced surgical personnel.
The factors relating to the clinical outcome of an industrial aerosol plant explosion are reviewed. Eighteen of 24 workers inside the plant required hospitalization and five died. Proximity to the blast was associated with extensive injuries unless workers were shielded by physical barriers or partitions. Burn severity and mortality were increased in those wearing synthetic garments compared to their counterparts wearing fiber clothing. Facial burns occurred in all unprotected workers. Forearm and hand burns in 11 patients required decompressive escharotomies. Topical treatment with silver sulfadiazine was associated with more significant leukopenia and neutropenia than treatment with silver nitrate. We conclude that industrial design should include safeguards which isolate workers from flammable materials, including isolation of explosive materials from working areas, alarm systems to detect leakage of flammable agents, protective barriers and shields, and the regulation and institution of flame and flash-resistant clothing.
The effect of delayed graft function and immunosuppressive drugs on posttransplant erythropoiesis was studied prospectively in 18 living-related (LR) and 84 cadaver-donor (CD) recipients. Eight of 18 LR and 20 of 84 CD recipients received antilymphoblast globulin (ALG) in addition to azathioprine and prednisone. Sixty-four CD recipients received cyclosporine (CsA) with prednisone. In the absence of rejection reticulocytosis began 6.7 +/- 0.2 days following graft implantation in azathioprine-only-treated LR recipients. This was lengthened by ALG to 9.4 +/- 0.3 and 9.9 +/- 0.7 days in LR and CD recipients, respectively, whose grafts functioned immediately. Delayed graft function prolonged onset of reticulocytosis to 15.9 +/- 0.9 days in ALG-treated but not in CsA-treated recipients (5.8 +/- 0.4 days). The shortest latency was noted in CsA-treated recipients (4.9 +/- 0.5 days) with immediately functioning grafts. The earlier onset of reticulocytosis of CsA-treated recipients was followed by statistically significant blunting of peak reticulocytosis, which correlated with a slower rate of correction of anemia (delta Hct = 0.19/day) compared with non-CsA-treated recipients (delta Hct = 0.34/day). Early rejection was associated with abrogation of reticulocytosis and correction of anemia without regard to immunosuppressive regimen) until rejection was reversed. Erythropoietin (EPO) was measured sequentially in 5 patients with immediate function. In 4 of 5 cases changes in EPO preceded those in reticulocytosis. EPO rose from a mean of 13 mU/ml pretransplant to a peak of 50 within 3 weeks and decreased to 18 mU/ml within 6 weeks of graft implantation. At six months posttransplant, normalized reticulocyte counts were only 55% higher (1.75 vs. 1.13%) but hematocrit had increased from 26 +/- 1% to 42 +/- 1%. Hematocrit varied inversely with serum creatinine, which was highest in CsA-treated patients with initial delayed graft function. We conclude that correction of anemia posttransplantation is driven by EPO but other factors may also be important, that neither ATN nor ALG-therapy have clinically important effects on erythropoiesis, and that CsA reduced "effective" erythropoiesis and influences correction of anemia--particularly if delayed graft function complicates the initial course posttransplantation.
Balloon dilatation of the prostatic urethra was performed in eight dogs and one human with benign prostatic hyperplasia. This was done in vivo in six dogs and in vitro in two dogs and one human. Follow-up study at 1-23 weeks showed persistent dilatation, which was documented both radiographically and pathologically. Technical improvements limited complications to the early phase of the study. While results are encouraging, extrapolation to humans is difficult.
Although adhesive capsulitis of the shoulder is a common clinical syndrome, adhesive capsulitis in other joints has rarely been reported. Four patients who developed adhesive capsulitis of the hip joint after trauma and two patients with adhesive capsulitis of the ankle, also precipitated by trauma, are described. The diagnosis of adhesive capsulitis is easily made during arthrography when a joint of low volume and high intracapsular pressure is encountered.
Twenty-four patients who sustained major hip trauma received computed tomography (CT) scans as well as conventional radiographs. A comparison of plain films with the CT scans showed that CT aided the diagnosis in 23 patients (96%): that CT altered the diagnosis in 14 patients (58%) and that the CT findings altered the management in eight patients (33%). It is our conclusion that CT scanning plays an essential role in the work-up and management of patients with major hip trauma.
Macrophage invasion in rabbits was elicited by intravitreal injection of trypan blue or latex particles; as after hemorrhage, there are two periods of macrophage invasion with elevated numbers of intravitreal cells at three and 21 days. Release of acid proteolytic activity by macrophages from both time periods was assayed by analysis of the cell-free vitreal supernate and of the medium of cultured cells. Lysates of freshly-isolated macrophages and of adjacent ocular tissues were also analyzed. Although some quantitative differences were observed, a similar profile of acid proteolytic activity toward hemoglobin at pH 2.0 to 6.5 was found in the vitreal supernate and in the cells from both periods. Most macrophages invade via the ciliary processes and during invasion elevated levels of acid proteolytic activity were found in this tissue. Although some macrophages transmigrate the retina, normal acid protease levels were low in sensory retina and essentially unchanged during macrophage invasion. Protease inhibitor studies indicated the presence of carboxyl, cysteinyl, serine and metallo proteases in macrophages and in macrophage-containing tissues. The inhibitor data also suggested qualitative differences in acid protease activities in macrophages from the two invasive periods. During macrophage invasion vitreal pH was reduced from 7.4 to 6.2 suggesting that some macrophage-derived acid proteases may be active in that compartment. Thus, although the phagocytic activity of macrophages aids vitreal clearing, action of macrophage proteases may also contribute to vitreal pathology by cleavage of vitreal proteins.
The ipsilateral oculotectal projection in the frog is a topographic mapping of the binocular part of the visual field of one eye on the ipsilateral tectal lobe. The underlying neuronal circuitry consists of the topographic, crossed retinotectal projection and an intertectal pathway which relays information from a given point in one tectal lobe to the visually corresponding point in the other. During optic nerve regeneration, there is a period when the terminals of retinotectal afferents are found at abnormal locations in the opposite tectal lobe. Whether they form functional synapses at this time is not known. If so, one would expect to observe correlated abnormalities in the ipsilateral oculotectal projection. To determine whether such abnormalities exist, we have made parallel electrophysiological studies of the recovery of the retinotectal and ipsilateral oculotectal projections following crush of one optic nerve. The earliest stage of recovery was characterized by a lack of significant topographic order in the retinotectal projection and by the absence of a physiologically observable ipsilateral projection. Within a short time, the retinotectal projection became topographically organized and a similarly organized ipsilateral projection appeared. While topographic, the retinotectal projection at intermediate times was abnormal in that the multiunit receptive fields recorded at individual tectal loci were greatly enlarged. Multiunit receptive fields were similarly enlarged in the ipsilateral projection. In addition, some ipsilateral fields included areas of visual space not normally represented in the projection. The abnormalities in both projections subsequently disappeared over the same time course. Throughout recovery there was a high correlation between multiunit receptive field sizes in the contralateral tectal lobe and those at visually corresponding points in the ipsilateral tectal lobe. Enlarged multiunit receptive fields in the contralateral tectal lobe could not be accounted for in terms of optical or retinal abnormalities since single unit receptive field sizes were normal. Nor could they be accounted for in terms of changes in recording characteristics since simultaneously recorded fields activated by the undisturbed eye were normally sized. We conclude that the enlarged fields in the contralateral tectal lobe indicate the presence at individual tectal loci of afferents from wider than normal retinal regions. Similar considerations ruled out optical, retinal, and recording abnormalities as the explanation for the enlarged multiunit receptive fields in the ipsilateral tectal lobe.(ABSTRACT TRUNCATED AT 400 WORDS)
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The authors have reviewed 25 hips in 23 patients with cerebral palsy in which iliopsoas transfer had been performed for established dislocation or refractory progressive subluxation of the hip. The iliopsoas tendon was transferred either postero-laterally or antero-laterally, depending upon the degree of fixed flexion of the hip. An adductor release was performed in all cases and an open reduction when necessary. A painfree stable joint was produced except for one hip in which the iliopsoas tendon had become detached because of sepsis. The loss of flexor power at the hip due to the transfer is thought to be a small price to pay for the relief of pain and spasm and the increase in function.