The ecology of early man in southern Africa.

It is not possible at present to demonstrate hominid occupation of southern Africa prior to the middle or late Pliocene, perhaps 3 million years ago. It may be the case that much, if not most, of the subcontinent was in fact uninhabited before that. The earliest hominid known to have lived in southern Africa is Australopithecus africanus. It was apparently replaced by Homo (?evolved into Homo) by 2 million years ago, at approximately the same time as A. robustus is first recorded locally. Homo and A. robustus then coexisted until perhaps 1 million years ago, after which Homo survived alone. There is no solid evidence that either of the southern African australopithecines made tools or accumulated bones. In fact, at the known sites, it now seems more likely that the bones, including those of the australopithecines themselves, were accumulated by carnivores. The known archeological record of southern Africa begins 2 million to 1.5 million years ago and the oldest stone tools may belong to the Oldowan Industry. Far better documentation exists for the succeeding Acheulean Industrial Complex, which was present in southern Africa almost certainly before 1 million years ago and persisted with modifications probably until sometime between 300,000 and 130,000 years ago. Although it is known that Acheulean peoples made handaxes, cleavers, and other stone tools, very little else is known about the activities of Acheuleans in southern Africa. Far more is known about their Middle and Later Stone Age successors. Southern African MSA peoples were perhaps among the earliest anywhere to take systematic advantage of aquatic resources for their subsistence, although they apparently did so far less effectively than did the LSA peoples who followed them. There are also contrasts between the ways in which MSA and LSA peoples dealt with terrestrial prey and between the contents of MSA and LSA artifact assemblages. The LSA peoples, for example, seem to have made much more extensive use of bone as a raw material, and they were the first to manufacture articles that are clearly interpretable as ornaments or art objects. From an evolutionary perspective, the LSA may represent a quantum advance over the MSA, perhaps correlated with the replacement of an archaic human physical type by the modem one. However, this must remain only a working hypothesis until much more is learned about the earliest LSA, dating to 35,000 to 40,000 years ago or more, and until there are adequate samples of well-provenienced MSA and early LSA physical remains. The later LSA, postdating 20,000 to 18,000 years ago, is reasonably well known. Later LSA peoples were probably at least partly responsible for the extinction of several large mammals in southern Africa about 10,000 years ago. By that date or shortly thereafter, at least some LSA peoples established basic hunting-gathering adaptations, which continued until the introduction and spread of agriculture and pastoralism, beginning roughly 2000 years ago. Thereafter, hunters and gatherers became progressively restricted in numbers and distribution, such that today only a very few exist, restricted to some of the most marginal environments of the subcontinent. It remains a major goal of southern African archeology to shed more light on the evolution and operation of hunting-gathering cultures during the vast time span when they covered all of southern Africa.

Dating and context of three middle stone age sites with bone points in the Upper Semliki Valley, Zaire.

The extent to which the earliest anatomically modern humans in Africa exhibited behavioral and cognitive traits typical of Homo sapiens sapiens is controversial. In eastern Zaire, archaeological sites with bone points have yielded dates older than 89(-15)+22 thousand years ago by several techniques. These include electron spin resonance, thermoluminescence, optically stimulated luminescence, uranium series, and amino acid racemization. Faunal and stratigraphic data are consistent with this age.

Intestinal calcium absorption in exogenous hypercortisonism. Role of 25-hydroxyvitamin D and corticosteroid dose.

Pharmacologic doses of corticosteroids impair intestinal calcium absorption and contribute to negative calcium balance. However, the relationship between the impaired calcium absorption and a possible defect in the conversion of vitamin D to its physiologically active form, 1,25-dihydroxyvitamin D, is unknown. We compared fractional calcium absorption (double-isotope method, 100-mg carrier) and serum 25-hydroxyvitamin D (25-OH-D) (Haddad method) in 27 patients receiving pharmacologic doses of prednisone with 27 age-, sex-, and season-matched normal subjects. In patients receiving high daily doses of prednisone (15-100 mg/day), calcium absorption (P < 0.02) and serum 25-OH-D (P < 0.001) were decreased. However, in patients receiving low doses (8-10 mg/day) or high doses (30-100 mg) of prednisone on an alternate-day schedule, both of these parameters were normal. Calcium absorption in the patients treated with daily prednisone correlated inversely with the dose of corticosteroids (r = -0.52, P < 0.025) and, in all steroid-treated patients, correlated directly with serum 25-OH-D (r = 0.58, P < 0.01). In four patients who received high-dose corticosteroid therapy for an average of 4 wk, serum 25-OH-D decreased by 35.5% from pretreatment values. Administration of a physiologic or near-physiologic dose of synthetic 1,25-dihydroxyvitamin D(3) (0.4 mug daily for 7 days) to patients receiving high-dose corticosteroids led to an increase in calcium absorption in all patients. These results suggest that calcium malabsorption in the corticosteroid-treated patients is due to a dose-related abnormality of vitamin D metabolism and not to a direct effect of corticosteroids on depressing transmucosal intestinal absorption of calcium.

Hyperactive boys almost grown up. III. Methylphenidate effects on ultimate height.

The height of young adults who were treated with methylphenidate hydrochloride in childhood because of hyperactivity (average daily dose, 45 mg; duration of treatment, six months to five years) was studied. There was no significant difference in height between the treated patients (n = 61) and controls (n = 99); both groups were at the national US norm in stature. The findings indicated that methylphenidate therapy does not compromise final height, even when it has an adverse impact on children's growth rate during the active treatment phase. A compensatory growth rate, or growth rebound, appears to occur following discontinuation of stimulant therapy.

Adult outcome of hyperactive boys. Educational achievement, occupational rank, and psychiatric status.

OBJECTIVE: The paucity of data concerning the long-term natural history of attention-deficit hyperactivity disorder (ADHD), a common childhood psychiatric disorder, prompted a longitudinal study to investigate the adult sequelae of the childhood disorder. DESIGN: Prospective study, follow-up intervals ranging from 13 to 19 years (mean, 16 years), with blind systematic clinical assessments. SUBJECTS: Ninety-one white males (mean age, 26 years), representing 88% of a cohort systematically diagnosed as hyperactive in childhood, and 95 (95%) of comparison cases of similar race, gender, age, whose teachers had voiced no complaints about their school behavior in childhood. RESULTS: Probands had significantly higher rates than comparisons of ADHD symptoms (11% vs 1%), antisocial personality disorders (18% vs 2%), and drug abuse disorders (16% vs 4%). Significant comorbidity occurred between antisocial and drug disorders. Educational and occupational achievements were significantly compromised in the probands. These disadvantages were independent of psychiatric status. We did not find increased rates of affective or anxiety disorders in the probands. CONCLUSIONS: Childhood ADHD predicts specific adult psychiatric disorders, namely antisocial and drug abuse disorders. In the adolescent outcome of this cohort, we found that these disturbances were dependent on the continuation of ADHD symptoms. In contrast, in adulthood, antisocial and drug disorders appeared, in part, independent of sustained ADHD. In addition, regardless of psychiatric status, ADHD placed children at relative risk for educational and vocational disadvantage. The results do not support a relationship between childhood ADHD and adult mood or anxiety disorders.

Hyperactive boys almost grown up. IV. Criminality and its relationship to psychiatric status.

Attention-deficit disorder with hyperactivity is believed, by some, to be a developmental antecedent (predisposing factor) to antisocial personality disorder and criminality. However, evidence supporting this association has not been consistent. We report on a prospective follow-up study of 103 males (ages 16 to 23 years), who were diagnosed as hyperactive (attention-deficit disorder with hyperactivity) between ages 6 and 12 years, and 100 normal controls. The official arrest records of all subjects who resided in New York State during the follow-up interval were obtained. Blind diagnoses (based on structured interviews with subjects and their parents) were made on 98% of the initial cohort at follow-up. Although other investigators have reported on the delinquent behavior of hyperactive children in a prospective design, to our knowledge, follow-up mental status has not been studied previously in relation to official arrest records. Significantly more probands than controls had been arrested (39% vs 20%), convicted (28% vs 11%), and incarcerated (9% vs 1%). The presence of an antisocial/conduct disorder in young adulthood almost completely accounted for the increased risk for criminal activities in the former hyperactive children whether or not it was accompanied by a substance use disorder. Continuing attention-deficit disorder with hyperactivity at follow-up, by itself, was not associated with arrest history. The findings support the view that childhood attention-deficit disorder with hyperactivity is a risk factor for later criminality, but that this relationship is almost exclusively mediated by the development of an antisocial disorder in early adulthood.

Methylphenidate and growth in hyperactive children. A controlled withdrawal study.

The effect of stimulants on growth has been controversial. Among hyperactive children receiving long-term methylphenidate hydrochloride treatment, we examined the effects of methylphenidate withdrawal on the growth of hyperactive children randomly assigned to be taken off, or remain on, the medication regimen over two consecutive summers. After one summer, no group difference in height was found, but weight was higher in the group that had been taken off methylphenidate therapy. In contrast, two summers of being off methylphenidate treatment had a significant positive effect on height but not on weight. The results document a linkage between exposure to methylphenidate and reduction in growth velocity. However, they do not address whether the medication has long-term effects on height.

Hyperactive boys almost grown up. V. Replication of psychiatric status.

We previously reported a prospective follow-up study of 101 young adult males whose conditions had been diagnosed as hyperactivity in childhood. Compared with controls, probands had significantly higher rates of attention-deficit, antisocial, and drug use disorders at follow-up (mean age, 18 years). The present study was an attempt to replicate these findings on an independent sample of 94 hyperactive boys who were seen at the same clinic, compared with 78 normal controls. Assessments were made by clinicians who were blind to group membership. Information was obtained for 90% of the original cohort. As in the previous study, significantly more probands than controls were given ongoing diagnoses of attention-deficit disorder (43% vs 4%), antisocial disorders (32% vs 8%), and drug use disorders (10% vs 1%). Furthermore, the absolute rates of these disorders were comparable for corresponding groups across studies, and the adjusted odds ratios did not differ significantly. As previously, there was no increased risk for affective disorders in the grown hyperactive children. The present study provides a powerful replication of the nature of the young adult outcome of childhood hyperactivity.

Hyperactive boys almost grown up. II. Status of subjects without a mental disorder.

In a previous article we reported the rate of DSM-III diagnoses among 101 male adolescents (aged 16 to 23 years) in whom hyperactivity had been diagnosed between ages 6 and 12 years compared with 100 controls. This report examines the rates of dysfunction among the 52 probands and 80 control adolescents who did not receive a DSM-III diagnosis at follow-up. Contrary to expectations, there were few areas (primarily involving school adjustment) in which the formerly hyperactive children were found to be at a disadvantage and numerous areas (occupational adjustment, temperament, alcohol abuse, antisocial activities, etc) in which the groups were indistinguishable. The results are explained in accordance with a bimodal distribution of dysfunction in hyperactive children grown up. Indirectly, this model supports the construct validity of the DSM-III diagnoses attention deficit disorder with hyperactivity, substance use disorder, and antisocial personality disorder. Post hoc analyses suggest that behavior problems resulting from drug use in early adolescence have graver consequences for previously hyperactive children than normal subjects.

Clinical efficacy of methylphenidate in conduct disorder with and without attention deficit hyperactivity disorder.

BACKGROUND: Stimulants are not considered appropriate for the treatment of children with conduct disorders (CDs). The postulated differences in stimulant effect between children with attention deficit hyperactivity disorder (ADHD) and CD led to the hypothesis that methylphenidate hydrochloride, which is effective in ADHD, would not significantly improve symptoms of CD. METHODS: We randomly assigned 84 children with CD, between the ages of 6 and 15 years, to receive methylphenidate hydrochloride (up to 60 mg/d) or placebo for 5 weeks. Behavior was evaluated by parent, teacher, and clinician reports and by direct classroom observations. Two thirds of the children also met criteria for ADHD. RESULTS: Contrary to prediction, ratings of antisocial behaviors specific to CD were significantly reduced by methylphenidate treatment. The magnitude of methylphenidate effect indicated meaningful clinical benefit. Partialling out severity of ADHD did not alter the significant superiority of methylphenidate on CD ratings specifically (P < .001). CONCLUSIONS: Methylphenidate has short-term positive effects on children and adolescents with CD. Key aspects of antisocial adjustment appear to be treatment responsive. This effect was independent of severity of the children's initial ADHD symptoms.

Differential carbon dioxide sensitivity in childhood anxiety disorders and nonill comparison group.

BACKGROUND: To examine the relationship between respiratory regulation and childhood anxiety disorders, this study considered the relationship between anxiety disorders and symptoms during carbon dioxide (CO(2)) exposure, CO(2) sensitivity in specific childhood anxiety disorders, and the relationship between symptomatic and physiological responses to CO(2). METHODS: Following procedures established in adults, 104 children (aged 9-17 years), including 25 from a previous study, underwent 5% CO(2) inhalation. The sample included 57 probands with an anxiety disorder (social phobia, generalized anxiety disorder, separation anxiety disorder, and panic disorder) and 47 nonill comparison subjects. Symptoms of anxiety were assessed before, during, and after CO(2) inhalation. RESULTS: All children tolerated the procedure well, experiencing transient or no increases in anxiety symptoms. Children with an anxiety disorder, particularly separation anxiety disorder, exhibited greater changes in somatic symptoms during inhalation of CO(2)-enriched air, relative to the comparison group. During CO(2) inhalation, symptom ratings were positively correlated with respiratory rate increases, as well as with levels of tidal volume, minute ventilation, end-tidal CO(2), and irregularity in respiratory rate during room-air breathing. CONCLUSIONS: Childhood anxiety disorders, particularly separation anxiety disorder, are associated with CO(2) hypersensitivity, as defined by symptom reports. Carbon dioxide hypersensitivity is associated with physiological changes similar to those found in panic disorder. These and other data suggest that certain childhood anxiety disorders may share pathophysiological features with adult panic disorder.

Ventilatory physiology of children and adolescents with anxiety disorders.

BACKGROUND: Abnormalities in ventilatory physiology have been noted in adults with panic disorder. We tested the hypothesis that abnormalities in ventilatory physiology differentiate children and adolescents with anxiety disorders from psychiatrically healthy children. METHODS: Ventilatory physiology was monitored with a canopy apparatus during room-air breathing and 15 minutes of carbon dioxide exposure in 33 children and adolescents comprising 18 probands with an anxiety disorder and 15 psychiatrically healthy children. RESULTS: During room-air breathing, probands had significantly larger minute ventilation, larger tidal volumes, and more variable breathing patterns than healthy comparisons, but the groups did not differ in end-tidal carbon dioxide or respiratory rate. During carbon dioxide challenge, probands exhibited larger minute ventilation and respiratory rate responses relative to comparisons. CONCLUSION: These findings on the association between ventilatory physiology and anxiety disorders in children and adolescents are consistent with results from studies of adults with panic disorder.

Adult psychiatric status of hyperactive boys grown up.

OBJECTIVE: Numerous studies have examined the adolescent and young adult fate of children with attention deficit hyperactivity disorder (ADHD). In marked contrast, relatively little is known about the adult outcome of these children. There have been only two controlled, prospective studies of psychiatric status into adulthood. The present study was conducted to gain further understanding of the natural course of this common childhood condition. METHOD: This was a prospective follow-up of clinically diagnosed, white boys of average intelligence who were referred by teachers to a child psychiatric research clinic at an average age of 7.3 years. At a mean age of 24.1 years, 85 probands (82% of the childhood cohort) and 73 comparison subjects (94% of adolescent comparison subjects) were directly interviewed by trained clinicians who were blind to group status. RESULTS: Evaluations of the probands and comparison subjects indicated significantly higher prevalences of antisocial personality disorder (12% versus 3%) and nonalcohol substance abuse (12% versus 4%) in the probands, whereas mood disorders (4% versus 4%) and anxiety disorders (2% versus 7%) were not significantly different. At adult follow-up, ADHD was rare, occurring in only 4% of the probands (no comparison subjects). CONCLUSIONS: The results of the present study are consistent with the authors' previously reported major findings. They strongly suggest that children with ADHD are at significantly higher risk for a specific negative course marked by antisocial and substance-related disorders.

A simple method for exact intratracheal instillation in small laboratory rodents.

An accurate, simple and quick method for instillation of substances into the respiratory tract of small rodents is reported. This new method is compared with conventional techniques.

Urinary excretion of N-nitrosodimethylamine in rats after Thalamonal narcosis.

Urinary excretion of N-nitrosodimethylamine (NDMA) in Sprague--Dawley rats was investigated after oral administration and inhalation of NDMA and concomitant narcosis by Thalamonal and diethyl ether. While ether anesthesia induced a 4-fold increase in the excretion rate, there was a drastic reduction (about 20-fold) in the amount of NDMA excreted after narcosis by Thalamonal.

Skip lesions in temporal arteritis.

Although isolated foci of arteritis ("skip lesions") are presumed to occur in temporal arteritis, there is little documentation of their existence or significance. We have identified skip lesions in 17 of 60 patients (28%) with temporal arteritis, based on a retrospective and prospective examination of temporal artery biopsy specimens. By examining more than 6,000 serial sections of arteries from patients with skip lesions, we have found foci or arteritis as short as 330 mu in length in an otherwise normal biopsy specimen. Our study emphasizes the need to biopsy long segments of artery, to examine multiple histologic sections, and to perform a contralateral temporal artery biopsy when frozen-section examination of the first side is normal.

Attention-deficit hyperactivity disorder and comorbid psychosis: a review and two clinical presentations.

BACKGROUND: A review of literature relating attention-deficit hyperactivity disorder (ADHD) to adult-onset psychosis suggests that cases of comorbid ADHD and atypical neuroleptic-refractory psychosis may respond to psychostimulants. METHOD: Two patients are described who presented to the authors for clinical care. Data were gathered by reviewing hospital charts from previous admissions and by conducting serial mental status examinations over many weeks. Subjects chosen for presentation herein met DSM-III-R criteria for ADHD and atypical psychosis characterized by delusions or hallucinations. RESULTS: After each subject had suffered multiple neuroleptic-refractory psychotic episodes, both had been treated by adding psychostimulants to ongoing neuroleptic therapy. The patients were then observed by the authors to be free of psychosis for many weeks, both while taking neuroleptics and psychostimulants concurrently, as well as while taking only psychostimulants after neuroleptics had been withdrawn. CONCLUSION: When integrated with reports of five similar cases and a review of the literature, the above results suggest that further attention be given to the evaluation, treatment, and eventual classification of a potentially distinct patient group with ADHD and atypical psychotic episodes.

Carcinogenicity of small doses of inhaled N-nitrosoacetoxymethyl-N-methylamine in Syrian golden hamsters.

Male Syrian golden hamsters inhaled 0.5-1 ppm (= 2.7-5.5 mg/m3) of N-nitroso-N-acetoxy-methyl-N-methylamine 1 h/week, for 14 weeks. The total dose per animal was calculated as 150-400 micrograms or 1-3 mg/kg. Four squamous cell carcinomas and one mucoepidermoid carcinoma of the nasal mucosa were observed. No such tumors occurred in the control group.