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Biomedical subjects

B Gustavii

Publications and source records attributed to B Gustavii.

18 recordsLinked to original sources
PubMed1992

Bilateral fetal mesencephalic grafting in two patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

BACKGROUND: Intracerebral transplantation of fetal dopaminergic neurons is a promising new approach for the treatment of Parkinson's disease. Patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) have a relatively stable lesion limited to the nigrostriatal system, rendering them ideal candidates for transplantation. Improvement of motor function after neural grafting has previously been observed in nonhuman primates with MPTP-induced parkinsonism. METHODS: We grafted human fetal tissue from the ventral mesencephalon (obtained six to eight weeks after conception) bilaterally to the caudate and putamen in two immunosuppressed patients with severe MPTP-induced parkinsonism, using a stereotaxic technique. The patients were assessed regularly with clinical rating scales, timed tests of motor performance, and [18F]fluorodopa positron-emission tomography during the 18 months before the operation and the 22 to 24 months after the operation. RESULTS: Both patients had substantial, sustained improvement in motor function and became much more independent. Postoperatively, the second patient's maintenance dose of levodopa was decreased to 150 mg daily, which was 30 percent of the original dose. Striatal uptake of fluorodopa was unchanged 5 to 6 months postoperatively but was markedly and bilaterally increased at 12 to 13 and 22 to 24 months in both patients, closely paralleling the patients' clinical improvement. There were no serious complications. CONCLUSIONS: Bilateral implantation of fetal mesencephalic tissue can induce substantial long-term functional improvement in patients with parkinsonism and severe dopamine depletion and is accompanied by increased uptake of fluorodopa by the striatum. The results in these patients resemble those obtained in MPTP-treated primates and suggest that this will be a useful model for the assessment of transplantation therapies in Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1992

Transplantation of fetal dopamine neurons in Parkinson's disease: one-year clinical and neurophysiological observations in two patients with putaminal implants.

Ventral mesencephalic tissue from aborted human fetuses (age, 6-7 weeks' postconception) was implanted unilaterally into the putamen using stereotaxic surgery in 2 immunosuppressed patients (Patients 3 and 4 in our series) with advanced idiopathic Parkinson's disease. Tissue from 4 fetuses was grafted to each patient. Compared with our previous 2 patients, the following changes in the grafting procedure were introduced: the implantation instrument was thinner, more tissue was placed in the operated structure, and the time between abortion and grafting was shorter. There were no postoperative complications. Both patients showed a gradual and significant amelioration of parkinsonian symptoms (most marked in Patient 3) starting at 6 and 12 weeks after grafting, respectively, reaching maximum stability at approximately 4 to 5 months; patients remained relatively stable thereafter during the 1-year follow-up period. Clinical improvement was observed as a reduction of the time spent in the "off" phase and the number of daily "off" periods; a lessening of bradykinesia and rigidity during the "off" phase, mainly but not solely on the side contralateral to the graft; and a prolongation and change in the pattern of the effect of a single dose of L-dopa. Neurophysiological measurements revealed a more rapid performance of simple and complex arm and hand movements bilaterally, but primarily contralateral to the graft. The results indicate that patients with Parkinson's disease can show significant and sustained improvement of motor function after intrastriatal implantation of fetal dopamine-rich mesencephalic tissue. The accompanying paper by Sawle and colleagues describes the results of repeated positron emission tomography scans in these patients.

Combined Modality Therapy↗
PubMed1991

Ultrastructure of human retinal cell transplants with long survival times in rats.

Human fetal retinas (6-12 weeks post-conception) were obtained from elective abortions, transplanted to rat retinas and examined by electron microscopy. The oldest transplants that form the basis of this report were obtained 40 and 41 total weeks post-conception. The host rats were immunosuppressed with cyclosporin A. The transplants developed according to their intrinsic, genetically determined timetable. The development was heterogeneous with some parts showing almost normal differentiation and others, little. Both rods and cones developed with inner and outer segments and synaptic terminals. In regions corresponding to the inner plexiform layer, bipolar cell processes were seen in the typical dyad arrangement. Likewise, amacrine cell processes formed typical conventional synapses. Serial synapses were seen, engaging amacrine cell synapses as well as a few reciprocal synapses at the bipolar cell dyads. Monad-type synaptic complexes, a sign of immaturity, were common in bipolar cell processes. Similarly, incompletely differentiated synapses of both the amacrine and bipolar cell types were often observed. Ganglion cell processes could not be identified with certainty. A structure with morphological characteristics similar to the inner limiting membrane was noted to form inside the transplant. Both epi-retinal and sub-retinal transplants were obtained. Transplant cells touched host photoreceptor cells or pigment epithelium without any obvious specializations. The host pigment epithelium microvilli were absent adjacent to the graft. However, graft cells did appear in the host retina, and nerve cell processes were observed to cross the membrane separating the transplant and host.

Animals↗
PubMed1990

Reformation of long axon pathways in adult rat central nervous system by human forebrain neuroblasts.

The failure of lesioned axons to regenerate over long distances in the mammalian central nervous system (CNS) is not due to an inability of central neurons to regenerate, but rather to the non-permissive nature of the CNS tissue environment. Regenerating CNS axons, which grow well within a peripheral nerve, for example, fail to penetrate mature CNS tissue by more than about 1 mm. Recent evidence indicates that this may be due to inhibitory membrane proteins associated with CNS oligodendrocytes and myelin. We report here that human telencephalic neuroblasts implanted into the excitotoxically lesioned striatum of adult rats can escape or neutralize this inhibitory influence of the adult CNS environment and extend axons along major myelinated fibre tracts for distances of up to approximately 20 mm. The axons were seen to elongate along the paths of the striato-nigral and cortico-spinal tracts to reach the substantia nigra, the pontine nuclei and the cervical spinal cord, which are the normal targets for the striatal and cortical projection neurons likely to be present in these implants.

Animals↗
PubMed1990

Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease.

Neural transplantation can restore striatal dopaminergic neurotransmission in animal models of Parkinson's disease. It has now been shown that mesencephalic dopamine neurons, obtained from human fetuses of 8 to 9 weeks gestational age, can survive in the human brain and produce marked and sustained symptomatic relief in a patient severely affected with idiopathic Parkinson's disease. The grafts, which were implanted unilaterally into the putamen by stereotactic surgery, restored dopamine synthesis and storage in the grafted area, as assessed by positron emission tomography with 6-L-[18F]fluorodopa. This neurochemical change was accompanied by a therapeutically significant reduction in the patient's severe rigidity and bradykinesia and a marked diminuation of the fluctuations in the patient's condition during optimum medication (the "on-off" phenomenon). The clinical improvement was most marked on the side contralateral to the transplant.

Brain↗
PubMed1979

Impotence, smoking, and beta-blocking drugs.

Four patients complaining of erectile dysfunction and using tobacco or propranolol were examined with penile blood pressure measurements and Doppler recordings, calculating the penile acceleration ratio (PAR). After a change in regimen, erectile capacity was restored, PAR returned to normal, and blood pressure measurements revealed increased systolic penile blood pressure in three patients. The changes, especially in PAR, indicate a marked penile vascular reaction during smoking and beta-blocking treatment in these men.

Adult↗
PubMed1979

Fetoscopy.

A brief report is given on fetal blood sampling by fetoscopy in three fetuses at risk for severe congenital bleeding disorder; hemophilia A in two cases, von Willebrand's disease in one. Published reports on complications of fetoscopy are reviewed. Out of all together about one hundred pregnancies that have been allowed to continue after fetoscopy, five ended in miscarriage. No other serious complication has been reported.

Abortion, Spontaneous↗
PubMed1978

Missed abortion and uterine contractility.

In missed abortion myometrial contractility is thought to be suppressed. However, such a simple procedure as sweeping of the fetal membranes by physiologic saline solution was found to provoke abortion within 24 hours in 10 of 12 cases of missed abortion, but not in any of 10 women admitted for therapeutic abortion. Myometrial contractility thus seems not to be diminished in missed abortion.

Abortion, Missed↗
PubMed1977

Human decidua and uterine contractility.

Physiological saline solution injected into the uterus by the extraamniotic route was found to damage the decidua and rupture its lysosomes. The mechanism by which this procedure provokes abortion may be through the release of lysosomal phospholipase A2 (EC 3.1.1.4), an enzyme thought to regulate the formation of polyunsaturated fatty acids utilized for prostaglandin synthesis. A similar sequence of events may be involved in the initiation of spontaneous labour, since decidual cells obtained at elective Caesarean section at term exhibited degenerative changes and signs of release of a lysosomal marker enzyme. The cause of this release is unknown.

Abortifacient Agents, Nonsteroidal↗
PubMed1975

The distribution within the placenta, myometrium, and decidua of 24Na-labelled hypertonic saline solution following intra-amniotic or extra-amniotic injection.

24Na-labelled hypertonic saline solution was injected into the uterus by the intra-amniotic or the extra-amniotic route, and six hours later determinations were made of the 24Na content of the placenta, myometrium, and decidua. The tissue specimens were obtained by subtotal hysterectomy. The activity of 24Na proved to be high in the decidua and in the fetal part of the placenta, but low in the myometrium. During labour, large amounts of prostaglandins have been found in the decidua, but little or none in the placenta. The present findings therefore lend further support to the assumption that hypertonic saline solution provokes abortion by inducing release of lysosomal phospholipase A2 into the cytoplasm of damaged decidual cells, resulting in prostaglandin synthesis and liberation.

Abortifacient Agents↗