Biomedical subjects
Publications and source records attributed to D Young.
Two patients with oculocutaneous albinism who had presumed sensory-defect nystagmus also showed the features of congenital motor-defect nystagmus. Both patients used an abnormal head posture to block the nystagmus, and each had coexisting strabismus. Modern surgical techniques simultaneously shifted the null point of the nystagmus to the primary position and corrected the strabismus.
In darkness, observers partially paralyzed with curare make large (greater thn 20 degrees) gaze- and dosage-dependent errors in visually localizing eye-level-horizontal and median planes, in matching the location of a sound to a light, and in pointing at a light. In illuminated, structured visual localization and pointing are accurate but errors in auditory-to-visual matches remain. Defects in extraretinal eye position information are responsible for all errors. The influence of extraretinal eye position information on visual localization is suppressed by a structured visual field but is crucial both in darkness and for intersensory localization if visual capture is prevented.
Whether to perform local resection alone (LR) or to combine local resection with ipsilateral radical neck dissection (LR and RND) as primary treatment for carcinoma clinically confined to the tongue is controversial. To compare the outcomes of the two procedures, we reviewed the records of 502 patients treated for carcinoma of the tongue from 1949 to 1974, 128 of whom had no evidence of disease beyond the tongue. Immediate LR and RND was performed in 39; 16 (41%) had recurrences, and 14 (36%) died. On the other hand, 89 patients underwent LR alone; 43 (48%) had recurrences, and 29 (31%) died. All were followed for a minimum of 5 years or until their deaths. There was no statistical difference between the two procedures in recurrence or outcome. The two groups were compared with respect to tumor size according to the TNM classification, and no significant differences in recurrence or survival were apparent. LR alone appears to be adequate primary treatment for patients with no evidence of metastatic disease, provided close postoperative follow-up is observed. LR and RND may result in increased morbidity and certainly in disfigurement, and fails to improve prognosis or survival.
The relative distribution, metabolism and kinetics of 18F containing compounds, following administration of 18F-5-fluorouracil, has been proposed as a prognostic aid in predicting response to 5-fluorouracil chemotherapy. Because 18F has a relatively short physical half-life (t1/2 = 110 min), and the distribution and kinetics of the radiolabeled 5-fluorouracil need to be studied over periods of time that range over several half-lives of the radionuclide, significant quantities of the labeled drug must be administered in order to obtain good counting statistics. The distribution of 18F, following injection of 18F-5-fluorouracil to rats and mice, has been well documented in our previous work. It appears that the distribution of 18F in humans, following administration of 18F-5-fluorouracil is similar to that in rats. We calculated the radiation dose according to the MIRD technique for the eleven main target organs for a reference man. The critical organs, according to these calculations, are the bladder wall, the kidney and the liver, receiving a radiation dose of 729, 184 and 114 mrad per mCi injected, respectively.
The replication of unselected strains of herpesvirus saimiri (HVS) was sensitive to bromodeoxyuridine and bromovinyldeoxyuridine (BVdU) but insensitive to acycloguanosine (ACG), in contrast to the growth of herpes simplex virus (HSV) which was sensitive to all three analogues. Mutants of HVS resistant to bromodeoxyuridine and BVdU could be selected by growth in the presence of these inhibitors. Productive infections of owl monkey kidney or Vero cell cultures by unselected strains of HVS resulted in increases in a thymidine kinase (TK) activity which was deficient in cells infected with bromodeoxyuridine-resistant mutants of the virus. Induction of the virus enzyme promoted a net increase in the uptake and incorporation of exogenous labelled thymidine in the face of the progressive inhibition of the overall incorporation of [35S]methionine and [3H]uridine into productively infected cells. The TK induced in cells infected with HVS differed from the major activity of uninfected cells and resembled that encoded by HSV in its capacity to phosphorylate iododeoxyuridine and in the sensitivity of all the thymidine phosphorylating activity to competition by BVdU. However, in contrast to the HSV TK, which phosphorylated deoxycytidine and iododeoxycytidine relatively efficiently and was sensitive to ACG, the HVS enzyme did not phosphorylate deoxycytidine or iododeoxycytidine and was insensitive to ACG. Whilst HVS, therefore, shares the characteristic of other members of the herpesvirus group of inducing a novel TK, the properties of the HVS-induced enzyme differ significantly from the enzyme of the prototype herpesvirus, HSV. The properties of the HVS TK are nonetheless sufficiently distinct from those of the uninfected cell to provide a possible basis for selective antiviral chemotherapy based on preferential phosphorylation of nucleoside analogues such as BVdU by infected cells.
5-Fluorouracil (5-FU) is an effective anti-tumor drug, which has been used both as a single agent and in combination with other chemotherapeutic agents for the treatment of tumors such as breast and colorectal carcinoma. We synthesized 5-FU with trace amounts of 18F-5-FU and administered the compounds intravenously to 6 cancer patients. The patients were scanned at 2 hr intervals for 12 hrs and their urine collected whenever possible. We also injected 5-FU with the tracer 18F-5-FU, at pharmacological doses, into non-tumored rats, and sampled their bile and blood for 95 mins post-injection. For comparison, 2-14C-5-FU was injected into non-tumored rats and their bile and blood sampled at the same intervals. Minute quantities of rat bile and serum were analyzed chromatographically by high-performance TLC. 5-FU and two of its metabolites (FBAL and FUPA) were identified and quantified by this technique. Both percentage and absolute amounts of 5-FU in the bile follow comparative kinetic patterns. While the liver and the urinary bladder were clearly observable in all 16 patients, the detectability of the gall-bladder was correlated to the inverse of the alkaline phosphatase level in the blood. This work suggests that the diversity of the 5-FU metabolism in cancer patients may allow the use of 18F-5-FU as a probe for understanding those individual variabilities in clinical situations.
Sixty-four patients receiving cancer chemotherapy known to induce severe emesis entered a randomized double-blind study of the antiemetic efficacy of haloperidol (Haldol) and benzquinamide (Emetecon). Patients preferred haloperidol for control of emesis induced by cis-platinum (78 vs. 22%) or nitrogen mustard (67 vs. 16%). Patients receiving Doxorubicin preferred benzquinamide by a small margin (46 to 38%). Individual patients who experienced no relief with their first antiemetic (13 of 15) usually got some relief with the other after crossover. Haloperidol was more effective than benzquinamide (54 vs. 29%) in patients previously unrelieved by prochlorperazine (Compazine). Complete relief of vomiting was obtained in 14 of 45 patients receiving haloperidol but only five of 41 patients receiving benzquinamide experienced no vomiting, again dependent on the anticancer agent used. Although haloperidol is a more effective antiemetic agent overall, efficacy is related to the anticancer treatment and probably to individual patient characteristics.
A 42-year-old woman had severe, bilateral visual loss and the initial symptom of systemic lupus erythematosus. Fundus photographs and fluorescein angiograms demonstrated an inflammatory process and severe ischemia. Vision in the less severely affected eye markedly improved after systemic and retrobulbar administrations of corticosteroids.
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Thirty-nine patients with the velo-cardio-facial syndrome are described in order to further delineate this probably common recurrent pattern congenital malformation syndrome. Frequent features include cleft palate, cardiac anomalies, typical facies, and learning disabilities. Less frequent findings include microcephaly, mental retardation, small stature, slender hands and digits, minor auricular anomalies and inguinal hernia. Ths Robin malformation sequence was found in four patients. The congenital heart anomalies most frequently involved a ventricular septal defect, with or without a right-sided aortic arch. There were four instances of familial transmission in the sample population. These included two cases of maternal transmission of the syndrome to daughters, one case of maternal transmission to a son, and one case of maternal transmission to both a son and daughter. There was no particular difference in expression between male and female patients so that even though X-linked dominant transmission is possible, the velo-cardio-facial syndrome is likely to be an autosomal dominant recurrent pattern syndrome.
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The use of laboratory tests in the management of 174 randomly selected patients admitted as acute medical emergencies was monitored in detail. The occasions when a test result changed patient management, and the nature of that change, were noted. Tests were classified according to information yielded and the importance of any action taken. For biochemistry alone every test result was costed. A ranking for all tests was produced, in terms of expected actions per test, and for biochemistry a 'value for money' table giving actions per pound spent. Every test request was classified as either discretionary or non-discretionary. The discretionary category was further subdivided into diagnostic and monitoring. The values, in terms of action-producing results, of non-discretionary, diagnostic, and monitoring tests were compared, and this comparison showed that the cost per item of helpful information was about 10 pounds for diagnostic, 23 pounds for monitoring, and 20 pounds for non-discretionary tests. In total, 1790 pounds was spent, and 28 items of unique information were yielded, enabling clinicians to discharge five patients, take seven courses of action which would have had serious consequences if omitted, and 16 actions the omission of which would have led to very serious consequences.