Partial short arm deletions of the X chromosome and spontaneous pubertal development in girls with short stature.

Five additional examples of partial deletion of the short arm of the X chromosome are reported. All of the patients had short stature. The presence of the other stigmata of Turner syndrome, including ovarian dysfunction, appeared to depend on the location of the deletion. Chromosomal analysis of girls with short stature (less than 140 cm), normal pubertal development, and regular menses may reveal that minor deletions of the short arm of the X chromosome are more frequent than has been previously reported.     

Carcinogenesis--devolution towards an ancient nucleated pre-eukaryotic level

Because the mitochondria and the cells housing them are obligatory symbionts, the evolutionary history of cells forms the locus minoris resistentiae which is the prerequisite for the carcinogenetic process. During carcinogenesis, the cells devolve towards an ancient anaerobic nucleated pre-eukaryotic level. True carcinogens cause an accumulation of inclusion bodies in the inner, bacterial, mitochondrial membrane. The mitochondrial damage which is detectable only in the early pretumorous stages, results in the respiratory surface with its enzymes being specifically changed, the mitochondrial and nuclear cycles no longer coinciding, the energy generation being forced to reuse the latent, "prehistoric", mode of respiration and the mitochondrial enzyme systems of soil bacterial origin becoming adapted to use other and more versatile metabolic pathways with a wider variety of end-products than classical glycolysis which produces lactate only. Neither external carcinogens nor oncogens are necessary. An increased, prolonged cell replication activity of physiological type is sufficient to initiate and maintain the process in animals with an inherited neoplastic disposition located in the inner mitochondrial membrane. The neoplastic disposition is inherited maternally: in fertilization the ovum does not receive mitochondria from the spermatocyte. The final results are an overall retardation of cell processes and instability in its structural and functional repertoire, the cytoskeleton (differentiation organelle) of the malignant cell manifesting special patterns. The proposed devolutionary mechanism is feasible as DNA packages are physiological components of soil bacterial membrane and can remain dormant (repressed) for years, or for ever, but under suitable conditions can generate seemingly new species, and particularly because enzyme adaptability is the unique privilege of soil bacteria.     

Extracorporeal membrane oxygenation in infants with meconium aspiration syndrome: a decade of experience with venovenous ECMO

Background

Despite the emergence of new therapies for respiratory failure of the newborn with meconium aspiration syndrome (MAS), extracorporeal membrane oxygenation (ECMO) has a significant role as a rescue modality in these infants. Our objective was to compare the use of venovenous (VV) vs venoarterial (VA) ECMO in newborns with MAS who need ECMO and to ascertain the impact of new therapies in these infants during the last decade. We also evaluated how disease severity or time of ECMO initiation affected mortality and morbidity.

Methods

A report of 12 years experience (1990-2002) of a single center, comparing VV and VA ECMO, is given. Venovenous ECMO was the preferred rescue modality for respiratory failure unresponsive to maximal medical therapy. Venoarterial ECMO was used only when the placement of a VV ECMO 14-F catheter was not possible; 128 patients met ECMO criteria, 114 were treated with VV ECMO, and 12 with VA ECMO. Two patients were converted from VV to VA ECMO.

Results

Venovenous and VA ECMO patients had comparable birth weight (mean ± SEM, 3.48 ± 0.05 vs 3.35 ± 0.15 kg) and gestational age (40.3 ± 0.1 vs 40.7 ± 0.3 weeks). Before ECMO, there was no difference between VV and VA ECMO patients in oxygenation index (60 ± 3 vs 63 ± 8), mean airway pressure (19.5 ± 0.4 vs 20.8 ± 1.5 cm H₂O), alveolar-arterial O₂ gradient (630 ± 2 vs 632 ± 4 torr), ECMO cannulation age (median [25th-75th percentiles], 23 [14-47] vs 26 [14-123] hours), or in the % of patients who needed vasopressors/inotropes (98% vs 100%). From November 1994, inhaled nitric oxide (NO) was available. Before VV ECMO, 67% of the patients received NO, 24% received surfactant, and 48% were treated with high-frequency ventilation (HFV). There was no significant difference between VV and VA ECMO patients in survival rate (94% vs 92%), ECMO duration (88 [64-116] vs 94 [55-130] hours), time of extubation (9 [7-11] vs 14 [9-15] days), age at discharge (23 [18-30] vs 27 [15-41] days), or incidence of short-term intracranial complications (5.3% vs 16.7%). For the total cohort of 126 infants, indices of disease severity (oxygenation index, alveolar-arterial O₂ gradient, mean airway pressure) did not correlate with outcome measures. Delay in ECMO initiation (>96 hours) was associated with prolonged mechanical ventilation and hospitalization (P < .01). New therapies (NO, HFV, surfactant) in the second part of the decade were associated with a longer ECMO duration (98 [80-131] vs 87 [60-116] hours; P < .05), no delay in ECMO initiation time (23 [10-40] vs 24 [14-52] hours), and no significant change in survival (97% vs 92.5%). No patient was treated with VA ECMO after 1994.

Conclusions

Venovenous ECMO is as reliable as VA ECMO in newborns with MAS in severe respiratory failure who need ECMO. Delay in ECMO initiation may result in prolonged mechanical ventilation and increased length of hospital stay. The emergence of new conventional therapies (NO, HFV, surfactant) and particularly increased experience enable sole use of VV ECMO with no significant change in survival in infants with MAS.     

A study of the origin of brain stem projections to monkey spinal cord using the retrograde transport method.

We identified brain stem neurons projecting to cervical and lumbar levels of the spinal cord in young rhesus monkeys using the retrograde transport method. The somatotopic organizations of the red nucleus and lateral vestibular nucleus were clarified. In addition, the presence of bulbospinal neurons in the medial vestibular nucleus; the nucleus of the tractus solitarius; the medial and lateral reticular formations; the raphe nuclei magnus, obscurus, and pallidus; the hypothalamus; and the nuclei of the locus ceruleus and subceruleus was confirmed.     

Modulation of auditory cortex unit activity during the performance of a conditioned response

Single-unit activity in primary auditory cortex was studied in unanesthetized, paralyzed cats during the performance of a classical conditioning task. The conditioned stimulus was a 0.5-s white noise (WN) burst paired with tail shock delivered 4.5 s later. Cats habituated to WN without shock served as controls. Overlayed on these tasks was a continuous background of 1/s, behaviorally irrelevant, 100-ms duration tone bursts set to the best frequency and optimal intensity for the particular unit being studied. Spontaneous activity and tone responses following WN were compared with the respective activity preceding WN. The spontaneous or evoked activity of 75% of the cells recorded in the trained animals changed significantly after WN, whereas the activity of 28% of the cells recorded in habituated animals changed. Augmentation and suppression of both spontaneous and evoked activity were found. These results have implications for the encoding of acoustic stimuli in terms of the modulation of lemniscal sensory system activity.     

Post-transplant malignant lymphoma: Distinctive morphologic features related to its pathogenesis

Malignant lymphoma developed in two patients after renal transplantation. In both, the central nervous system was involved. Histologic study of the tumors showed that they were composed of a monomorphous proliferation of cells characterized by a large vesicular nucleus, prominent basophllic nucleolus and strongly pyroninophilic cytoplasm. The tumors thus would be classified as “diffuse large lymphoid lymphomas with pyroninophilia” or “immunoblastic sarcomas” as described in the literature. Tumor cells resembled cells observed in the paracortex of antigenically stimulated lymph nodes, cells from malignant lymphomas in mice that were antigenically stimulated and from malignant lymphomas in patients with immunodeficiency diseases or autoimmune disorders. The distinctive morphologic features of the tumors in the transplant recipients described provide further evidence that long-term antigenic stimulation may be important in their pathogenesis.     

Solitary autonomously functioning thyroid lesions. Diagnosis, clinical features and pathogenetic considerations.

One hundred sixty-four patients with autonomously functioning thyroid lesions (AFTL), 140 with nontoxic and 24 with toxic lesions, were studied over 12 years. To avoid pitfalls in diagnosis of nontoxic AFTL, a suppression procedure should precede the repeat scan after the administration of thyroid stimulating hormone. Women outnumbered men by 13 to 1 for nontoxic AFTL and 3.8 to 1 for toxic AFTL. Larger and toxic lesions were found in older patients, suggesting their derivation from smaller nontoxic lesions. Serum triiodothyronine (T3) and thyroxine concentrations exhibited parallel deviations from average normal levels for most of 29 patients with hot AFTL. T3 toxicosis was not seen. Ultrasound was more sensitive than scanning in detecting cystic degeneration. Observation was advised for patients with nontoxic AFTL unless toxicity appeared imminent. Of 51 such patients, followed from 1 to 12 years, none became hyperthyroid, but 10 AFTL increased from slightly to fourfold in size or showed evidence of degeneration. Of 24 patients with toxic AFTL, 20 were treated with radioiodine and the remaining 4 surgically; surgery is the preferred treatment for patients under 40 years of age. Three of 29 patients who were treated surgically had thyroid cancer. Since AFTL have histologic and pathophysiologic features characteristic of benign endocrine neoplasms, the association with cancer may be more than coincidental.     

Severe irreducible slipping of upper femoral epiphysis: a review of 14 cases treated by subtrochanteric osteotomy

Children with signs of slipping of the upper femoral epiphysis often present in an Accident Service, particularly after a severe, acute slip. In some cases the displacement is irreducible and correction of the persistent deformity by either cervical or trochanteric osteotomy is required. This paper is a review of 14 cases of irreducible slipped upper femoral epiphysis treated by subtrochanteric osteotomy. Clinical and radiological assessment of these cases some years later shows a high proportion of successful results and suggests that this is a safe and satisfactory method of treating this condition.     

Shark attack in Natal.

The injuries in 5 cases of shark attack in Natal during 1973-74 are reviewed. Experience in shark attacks in South Africa during this period is discussed (1965-73), and the value of protecting heavily utilized beaches in Natal with nets is assessed. The surgical applications of elasmobranch research at the Oceanographic Research Institute (Durban) and at the Headquarters of the Natal Anti-Shark Measures Board (Umhlanga Rocks) are described. Modern trends in the training of surf life-guards, the provision of basic equipment for primary resuscitation of casualties on the beaches, and the policy of general and local care of these patients in Natal are discussed.