Longer Survival Period Research Articles

Results of acute and chronic experiments with assisted and total artificial heart.

AbstractAn assisted artificial heart and a total artificial heart were implanted in 108 calves. Two types of assisted artificial heart, a bladder type and a diaphragm type made of silastic and segmented polyurethane, were tested in left atrial (LA) or left ventricular (LV) to abdominal aorta bypass. Of 40 calves that received LA bypass, 6 survived for more than 100 hours. Of 35 calves that received LV bypass, 18 survived for more than 100 hours. In the total artificial heart experiments, an oval‐ or sphere‐shaped total artificial heart was implanted in 13 calves after 20 pilot experiments. That longest survival period was 864 hours (about 36 days), and the average survival time was 8.5 days.

Branchiogenic carcinoma — fact or fallacy?

The ongoing debate concerning the existence of malignant transformation of branchial cleft cysts has been analyzed, with the aid of previous reports and reviews in the literature. Six new cases are presented and illustrated. These occurred in 4 male and 2 female patients, having an average age of 60 years. Two of the lesions were within the parotid salivary gland. The longest period of survival was 3 1/2 years. New criteria for the acceptability of tumors as primary branchiogenic cancers are proposed. We believe that, using these strict criteria, rare examples of primary branchiogenic carcinomas do exist; their treatment should include whide local excision, followed by ipsilateral radical neck dissection.

Treatment of malignant glioma by immunotherapy using lymphocytes sensitized with tumor-specific immune RNA (author's transl)

Ten cases of malignant glioma (5 primary and 5 recurrent) were treated with passive immunization by lymphocytes sensitized with tumor-specific immune RNA. This immunotherapy was given either after surgery, surgery and radiotherapy or surgery and chemotherapy. Supernatant of 5, 000×G of tumor or sediment of 105, 000 x G of tumor was used as tumor antigen. Normal lymphocytes were sensitized by incubation with RNA. These sensitized lymphocytes were injected intravenously in doses as much as 7 ?? 15×108. At the present time, the longest survival period among the 5 primary case patients who received immunotherapy is 29 months and this patient is still alive. One patient died at 11 months after surgery. Two out of 5 recurrent cases were treated with surgery and immunotherapy, and they died at 7 and 8 months following surgery, respectively. Three out of 5 recurrent cases were treated with either surgery, radiation and immunotherapy, or surgery, chemotherapy and immunotherapy. One patient died at 13 months and 2 are still alive 20 months and 36 months after operation, respectively. The following immunological responses were studied for each patient: leucocyte count, T-cell count, skin test of DNCB, PPD, PHA, blastogenic activity against PHA, machrophage imigration inhibitory test, and serum immuno-globulin. Increase in blastogenic activity against PHA was observed in some of long survival cases after immunotherapy. Those patients who were not provided immunotherapy, and were treated by surgery, surgery and radiation therapy, or surgery and chemotherapy, survived less than 27 months.

Vestibulospinal projections in the toad. An experimental electron microscopic study

An experimental electron microscopical study has been made on the mode of termination of the vestibulospinal projections in the toad. Degenerating fibers and boutons were observed in the ventromedial region of the spinal cord in which five types of terminals were identified in normal preparations: S-type, F-type, C-type, NfS-type and NfF-type. The latter two types represent the largest terminals in the spinal gray. In the medial region of the ventral horn they seem to belong to supraspinal fibers. Following electrolytic lesions of the dorsal and ventral nuclei nervi octavi, some of the NfF-type of boutons undergo filamentous degeneration which progresses into the dark type at longer survival periods (7–20 days). In two animals, a few NfS-type of boutons also display filamentous hypertrophy. Problems connected with the filamentous type of degeneration in amphibians and with the identification of bouton types belonging to the vestibulospinal pathway are discussed. Degenerating fibers and boutons are seen at all levels of the spinal cord, ipsilateral and also, in smaller number, contralateral to the lesions. The vestibulospinal fibers terminate predominantly on large and small dendrites, and only occasionally on the somata of large neurons on the ipsilateral side.

RETROGRADE TRANSPORT AND INTRANEURONAL FATE OF EXOGENOUS HORSERADISH PEROXIDASE IN THE NERVOUS SYSTEM

Exogenous horseradish peroxidase (HRP, Type VI, Sigma) was applied as a marker for retrograde neuroanatomical tracing in the nigroneostriatal system and the sciatic nerve of adult rats. The retrograde transport and intraneuronal fate of HRP was examined with light and electron microscopy.In the nigroneostriatal system, the labeled neurons containing many brown granules in their perikarya were observed in the ipsilateral substantia nigra 3-4 hours after an injection of HRP, confirming the existence of a nigroneo-striatal pathway. Ultrastructually, these granules appear as multivesicular and lysosomal bodies in the perinuclear region.The labeled nerve cells of the spinal ganglia were also observed within 12 hours after the application of HRP in the sciatic nerve. The HRP positive brown granules had accumulated in the perinuclear region and were rapidly degraded by the lysosomal system disappearing 2 weeks after the injection.In instances of long periods of survival, characteristic lysosomal bodies which included crystals, crystalloid and laminar structures were found.

Persistence of poliovirus 1 in soil and on vegetables grown in soil previously flooded with inoculated sewage sludge or effluent

Land disposal of sewage sludge and effluent is becoming a common practice in the United States. The fertilizer content and humus value of such wastes are useful for agricultural purposes, and the recycling of sewage onto the land eliminates many of our stream pollution problems. The potential exists for crops grown in such irrigated soil to be contaminated by viruses that may be present in the sewage. Studies were initiated to determine viral persistence in soil and on crops grown under natural conditions in field plots that had been flooded to a depth of 1 inch (2.54 cm) with poliovirus 1-inoculated sewage wastes. Lettuce and radishes were planted in sludge- or effluent-flooded soil. In one study, the vegetables were planted 1 day before flooding, and in another they were planted 3 days after the plots were flooded. Survival of poliovirus 1 in soil irrigated with inoculated sewage sludge and effluent was determined during two summer growing seasons and one winter period. The longest period of survival was during the winter, when virus was detected after 96 days. During the summer, the longest survival period was 11 days. Poliovirus 1 was recovered from the mature vegetables 23 days after flooding of the plots had ceased. Lettuce and radishes are usually harvested 3 to 4 weeks after planting.

Survival of Aegyptianella pullorum, Anaplasma marginale and various parasitic protozoa following prolonged storage in liquid nitrogen.

Various protozoa species were examined using in vivo and in vitro methods to determine their ability to survive prolonged periods of storage in liquid nitrogen. The following protozoan species were successfully recovered after they had been cryopreserved for a period over 10 years: Trypanosoma lewisi, T. cruzi, T. congolense, T. brucei, T. rhodesiense, T. gambiense, T. evansi, T. equinum, T. equiperdum, Leishmania donovani, Plasmodium berghei, P. praecox (relictum), Babesia rodhaini and B. canis. The longest survival period that has been successfully tested so far is between 5 and 7 years for Eimeria species, for monoxenically (A--C) and axenically grown E. histolytica cultures between 2 and 7 years and trichomonades, including Crithidia sp., between 6 and 8 years. Aegyptianella pullorum was successfully recovered after 6.97 years and Anaplasma marginale after 1.92 years. The freezing techniques are briefly described.

Thalamic projections of the dorsomedial prefrontal cortex in the rhesus monkey ( Macaca mulatta)

Cortical aspirations were made of the dorsomedial prefrontal sector in the rhesus monkey and the resultant anterograde and retrograde degeneration plotted. Retrograde changes were mapped using both cresyl violet and modified Fink-Heimer techniques. Following large dorsomedial lesions, small numbers of degenerating fibers were traced through the medial part of the magnocellular ventral anterior nucleus (VAmc) and the ventral part of the internal medullary lamina surrounding the anterior nuclei. Degenerating fibers were also traced medially through the inferior thalamic peduncle and rostrodorsally through the basal thalamic region into the mediodorsal nucleus. All pathways converged on areas in the dorsal part of the parvocellular mediodorsal nucleus (MDpc) containing fine-grain dust and argyrophilic neurons, reactions usually associated with retrograde degenerative changes. Sparse fiber degeneration was also noted in the ventral part of the magnocellular mediodorsal nucleus (MDmc). After a longer survival period, slight to moderate cell loss and gliosis were seen in MDpc along with an increase in the number of degenerating fibers passing through the medial part of VAmc. Rostral dorsomedial lesions resulted in small numbers of degenerating fibers in the medial part of VAmc; no degenerating fibers appeared in the basal thalamic region. Fine-grain dust was noted in the dorsal part of MDpc along with sparse preterminal degeneration in the dorsal and ventral parts of MDpc and MDmc respectively. Following caudal dorsomedial lesions, fiber degeneration was traced through the medial part of VAmc and through the inferior thalamic peduncle and basal thalamic regions to areas of degenerating preterminals in the dorsal part of MDpc. Sparse fiber degeneration was also noted in MDmc. No evidence of cell loss and gliosis or increased numbers of degenerated fibers was noted following longer survival periods. Dorsolateral and orbital lesions resulted in large areas of fine-grain dust, argyrophilic neurons, and severe cell loss in MDpc and MDmc respectively. A large combined dorsolateral and orbital lesion made 32 days prior to sacrifice of the animal resulted in coarse fiber degeneration in the medial part of VAmc and in the anterior nuclear capsule. Severe cell loss and fiber degeneration were evident in the entire MD. These results suggest that the rostral dorsomedial prefrontal sector receives projections from MDpc while the caudal sector does not. This projection courses dorsally and rostrally through the ventral part of the capsule surrounding the anterior nuclei and into the medial part of VAmc. The entire dorsomedial sector projects sparsely to both MDpc and MDmc. The projection from the rostral medial surface passes through the medial part of VAmc while that from the caudal surface reaches MD both by the dorsal approach through VAmc and through a ventral approach via the inferior thalamic peduncle and the basal thalamic region.

Survival of “dry” salmonid sperm at temperatures above 0° centigrade

Survival of sperm from Salmo trutta L., Salmo gairdneri Rich., Salvelinus fontinalis (Mitch.) was investigated at constant temperatures (1.0°; 5.0°; 10.0°; 15.0°C). The longest period of survival has been found to take place at the temperature range from 1.0°- 5.0°. Further it has been stated that the duration of sperm storage at various temperatures has only a slight influence on the activity time of spermatozoa. Differences have also been revealed with regard to various fish species, fish individuals, as well as individual spermatozoa.

An autoradiographic investigation of the projection of the vomeronasal organ to the accessory olfactory bulb in the mouse

Autoradiographic labelling was used to investigate the primary olfactory projections in the mouse. Small pieces of gelatin foam soaked in [ 3H]proline were inserted directly into the cavity of the vomeronasal organ. At survival times from 6 h to 10 days, radioactive label was found over the vomeronasal nerves and the glomeruli of the accessory olfactory bulb. Conversely, when radioactive amino acid was applied to the main olfactory mucosa, the label appeared over the main olfactory nerves and the glomeruli of the main olfactory bulb. In both the main and accessory bulbs there was evidence for a transneuronal uptake of label in the external plexiform and mitral cell layers subjacent to the labelled glomeruli. This transneuronal uptake was heavier at longer survival periods.

Infection of Mouse Blastocysts with SV40 DNA: Normal Development of the Infected Embryos and Persistence of SV40-specific DNA Sequences in the Adult Animals

In SV40-transformed culture cells, viral-specific sequences have been found to be covalently linked to host sequences (Sambrook et al. 1968). The most appealing interpretation to explain the presence of SV40-specific sequences in adult mice following infection at the preimplantation stage would be to assume that the viral DNA was integrated at this early stage of development into the host genome and was thus conserved during further development. However, our results do not exclude an extrachromosomal existence of the SV40 genome, for example, as an independently replicating plasmid or as a lytic infection in a few permissive cells. So far our attempts to demonstrate autonomous SV40 DNA replication in early mouse embryos have been unsuccessful. We plan to investigate whether the SV40-specific information can be genetically transmitted from the infected mice to their offspring; chromosomal integration would be proven if transmission of SV40 DNA occurred in accordance with simple Mendelian expectations. The injection of mouse blastocysts with purified SV40 DNA did not detectably interfere with normal development of the embryos to healthy adult mice, which were still tumor-free at one year of age. This was not due to the trivial possibility that the viral DNA did not successfully infect and was eliminated from the injected embryos, as virus-specific DNA sequences were detected in 40% of the infected year-old animals, or in about 25% of DNA preparations extracted from some of their tissues (Table 1). It is nevertheless possible that the animals may not have been old enough to exhibit tumorigenesis of SV40 origin; to test this possibility, the experiment will have to be repeated for longer survival periods. The absence of any obvious signs of expression of viral genetic functions, i.e., tumor formation, up to one year of age of the host is reminiscent of the "cryptic transformants" described earlier (Smith et al. 1972) which harbor SV40 information but behave essentially like normal untransformed cells. Whether transcription or translation of the virus gene can occur in infected mice is presently an open question. Testing for expression of an integrated viral genome in diverse differentiated tissues may provide a useful model system to study the regulation of differentiation. These matters are currently being investigated.

The combined influence of age of embryo and temperature and duration of incubation on the replication and yield of avian infectious bronchitis (IB) virus in the developing chick embryo

Summary Two experiments were undertaken to investigate the combined influence of the age of embryo at infection and the temperature and duration of incubation on the replication and yield of the Beaudette strain of IB virus in allantoic fluid and the chorio allantoic membrane. In general a higher titre of virus was found in the allantoic fluid and chorioallantoic membrane of living embryos than of dead ones and with continued incubation of dead embryos the titre of virus fell still further. For embryos of the same age at infection peak titres were similar for those incubated at 32°C and 37°C but were greater than for the corresponding embryos at 42°C. The range of titres for embryos of all ages associated with duration of incubation was narrower for those incubated at 32°C than at 37°C and 42°C and a longer survival period was observed for embryos incubated at 32°C. Peak titres of virus for all age groups were observed after 24 h at 32°C and after 12 h at 37°C and 42°C and then declined. The highest titre for virus in allantoic fluid, in both experiments, was in the 10 d old embryos at 32°C harvested after 24 h. For the chorioallantoic membrane the highest titre in the first experiment was in 12 d old embryos at 32°C, harvested after 24 h, while in the second it was also (in 12 d old embryos but at 37°C and harvested after 12 h. The lowest titre of all was in 10 d old embryos incubated at 42°C. It is considered that the maximum total yield of virus from the allantoic fluid and chorio allantoic membrane of the same embryo will be in those infected at 10 — 12 d of age incubated at 32°C to 37°C.

The combined influence of age of embryo and temperature and duration of incubation on the replication and yield of avian infectious bronchitis (IB) virus in the developing chick embryo

Two experiments were undertaken to investigate the combined influence of the age of embryo at infection and the temperature and duration of incubation on the replication and yield of the Beaudette strain of IB virus lin allantoic fluid and the chorio allantoic membrane. In general a higher titre of virus was found in the allantoic fluid and chorioallantoic membrane of living embryos than of dead ones and with continued incubation of dead embryos the titre of virus fell still further. For embryos of the same age at infection peak titres were similar for those incubated at 32 degrees C and 37 degrees C but were greater than for the corresponding embryos at 42 degrees C. The range of titres for embryos of all ages associated with duration of incubation was narrower for those incubated at 32 degrees C than at 37 degrees C and 42 degrees C and a longer survival period was observed for embryos incubated at 32 degrees C. Peak titres of virus for all age groups were observed after 24 h at 32 degrees C and after 12 h at 37 degrees C and 42 degrees C and then declined. The highest titre for virus in allantoic fluid, in both experiments, was in the 10 d old embryos at 32 degrees C harvested after 24 h. For the chorioallantoic membrane the highest titre in the first experiment was in 12 d old embryos at 32 degrees C, harvested after 24 h, while in the second it was also in 12 d old embryos but at 37 degrees C and harvested after 12 h. The lowest titre of all was in 10 d old embryos incubated at 42 degrees C. It is considered that the maximum total yield of virus from the allantoic fluid and chorio allantoic membrane of the same embryo will be in those infected at 10 - 12 d of age incubated at 32 degrees C to 37 degrees C.

The effect of temperature on fat consumption during the puparial stages ofGlossina morsitans morsitansWestw. (Dipt., Glossinidae) under laboratory conditions, and its implication in the field

Analyses were carried out at Salisbury, Rhodesia, on the relationship between fat content and residual dry weight in newly emerged adults ofGlossina morsitans morsitansWestw., following incubation at constant temperatures between 16 and 32°C for laboratory material, and between 20 and 30°C for field material. The same relationship was investigated for field-collected and laboratory-produced larvae. Sizespecific rates of fat consumption were calculated from these data, and it was shown that the rate of change at temperatures below 20°C was of a different order to that at higher temperatures. Fat reserves in teneral flies reared in the laboratory at 16–32°C were shown to be adequate in flies of 4 mg residual dry weight for survival at rest for at least 24 h after emergence, over the temperature range likely to be encountered in the field. Considerably longer periods of survival were indicated for flies of the same size emerging from field-collected puparia. The latter exhibited a marked seasonal variation in size with the largest puparia occurring at the time of lower temperatures. Smallest puparia occur in the hot-dry season, but even under these adverse conditions fat reserves of most tenerals are adequate for survival for at least 24 h. It was concluded that lack of fat was not likely to cause heavy mortality of stages passed within the puparium over the temperature range 16–32°C. After emergence, survival of smaller flies would depend on their ability to obtain a blood-meal within 24 h.

Survival of crawlers of California red scale, Aonidiella aurantoo (Mask.) (Homoptera : Diaspididae)

The periods of survival of first-instar larvae (crawlers) of California red scale were estimated in the laboratory under conditions that attempted to simulate those that the crawlers would be exposed to during dispersal by wind in the field. Since attempts to keep crawlers suspended in a stream of moving air for long periods were unsuccessful, they were placed in small cages, and air at constant temperature and humidity was passed through the cages at known rates. Following exposure, the crawlers were transferred to lemon leaf discs, and only those able to begin feeding and secrete a scale were recorded as survivors. At 15�C crawlers survived a mean period of 17.1 hr at 70% R.H. and 14.2 hr at 35% R.H.; at 2S�C, 10.1 hr at 70% R.H. and 6.8 hr at 25% R.H.; at 3SCC, 7.2 hr at 70% R.H. and 5.7 hr at 25% R.H. The period survived was significantly higher at the higher humidity in each case. At 70% R.H. the period of survival decreased significantly with increased temperature. At 25% R.H. the period was significantly higher at 15�C than at 2S�C, but not between 25 and 35�C. The period of survival decreased as the rate of flow of air past the crawlers increased to the terminal velocity. The long periods of survival of crawlers, even under extreme conditions to which they would rarely be exposed in nature because of their rhythm of emergence, leaves little doubt that they could withstand transport by wind over long distances even during hot, dry summer weather.

Reevaluation of rebound regression in disseminated carcinoma of the breast.

In patients with disseminated carcinoma of the breast on estrogen therapy that develop progression of their disease, sudden cessation of estrogen was found to produce tumor regression. In a study of 97 patients with breast carcinoma treated with estrogen and followed closely, 25 patients had a trial of sudden hormonal withdrawal because of progression of their disease. Of these, eight patients (32%) had tumor remission lasting from 3 to 10 months (avg. 6.9 months). Five of the eight responders had subsequent hormonal manipulation for their progressing neoplasms, and all had experienced another tumor remission. These responders were analyzed carefully, and showed a significantly longer disease-free interval, and a longer survival period as compared to nonresponders to estrogen withdrawal. This suggests that withdrawal response in patients with advanced breast carcinoma is of value for patient prognosis, like that obtained from response to bilateral oophorectomy. Because of the freedom from side effects with the sudden estrogen withdrawal, we do feel that, whenever possible, estrogen withdrawal should be tried on breast cancer patients and an adequate period of observation should be allowed before the initiation of other more hazardous or toxic forms of therapy. An illustrative case of repeated responses to estrogen and to estrogen withdrawal will be presented.

HODGKIN'S DISEASE IN THE FIRST DECADE OF LIFE

This report is based on a study of 35 children with Hodgkin's disease. The longest survival periods were 9.8 years in a patient who has expired and 9 years in a patient who is still alive. Fourteen patients are still alive at the time of submission of this paper; the survival periods range from 0.2 to 9 years; 11 are known dead and their survival periods range from 0.3 to 9.8 years. The outcome in 10 cases is not known. A striking predominance of males was noted (91%). In 30 of 31 classifiable cases, the histologic sections showed either nodular sclerosing Hodgkin's disease or Hodgkin's disease with lymphocytic predominance. Regardless of classification, a striking preponderance of mature lymphocytes in tissue sections was evident in most cases. These findings suggest that a particular host response characterizes the disease in the young.

Survival of Dothistroma pini on fallen needles of Pinus radiata

Summary The length of time for which Dothistroma pini stromata on fallen needles of Pinus radiata produce viable conidia (survival period) was studied for each month of the year. Needles under study were placed in the litter and suspended above ground in both thinned and unthinned stands. Season did not seem to affect survival period. Stromata of D. pini on needles in litter survived for a shorter time than chose on suspended needles. The longest survival period was between 4 and 6 months.

Liver tumors in infants and children. Clinical and pathological analysis of 22 cases.

The records of the Children's Memorial Hospital, Chicago, since 1954 included 22 cases of primary tumors of the liver: 11 were malignant hepatomas; 5, benign tumors; and 6, vascular malformations. In the malignant tumor group, five hepatic lobectomies and one wide excision of tumor were performed, as well as two pulmonary lobectomies for metastases. The malignant process was far advanced in five patients and surgical measures were limited to exploration and biopsy. All patients with malignancies died. The longest survival period was three years and four months postsurgery. In contrast to malignancies, all benign lesions were successfully resected, and the patients are alive and well. Tumors of vascular origin were limited to infants, and the lesions often caused significant hemodynamic manifestations. An aggressive approach with roentgenography and radionuclide scanning is advocated for early diagnosis of abdominal masses in pediatric patients. Surgical excision is indicated for all localized liver tumors.

The influence of tumour type, persistent precancerous lesions and lymph node involvement on the results of radiotherapy in oral cancers.

Abstract A series of 172 cases of oral cancer who had serial biopsies taken during a radical course of radiotherapy is reviewed. It was found that: (1) a prognosis based on early histological changes induced by radiation is in very good agreement with the clinical results of the initial treatment. (2) patients with differentiated tumours had a significantly higher five-year survival rate than those with anaplastic carcinomata; (3) lymph node involvement and persistence of precancerous lesions occurred less frequently in differentiated than in anaplastic cancers; (4) a higher percentage of patients with persistent precancer than of those without this lesion died ultimately of cancer but after a longer survival period than did patients with refractory tumours; (5) lymph node involvement did not affect the survival rate significantly in cases receiving equal radiation treatment at primary and secondary sites; (6) cancer persisted in the primary (with and without tumour in the nodes) in 85 per cent, but in th...