A randomised, controlled trial of rectus sheath bupivacaine and intrathecal bupivacaine, without or with intrathecal morphine, vs. intrathecal bupivacaine and morphine after caesarean section.

We recruited 144 women of whom 131 underwent scheduled caesarean section and were allocated to intrathecal bupivacaine without (46) or with (47) morphine and postoperative rectus sheath bupivacaine; or intrathecal bupivacaine with morphine and postoperative rectus sheath saline (38). We measured postoperative pain with a 10-point numeric rating scale. The mean (SD) areas under the curve for pain on movement during 48 postoperative hours were 273.5 (63.6), 223.8 (80.7) and 223.8 (80.7), respectively, p = 0.008. There was no difference between women who had intrathecal morphine with or without rectus sheath bupivacaine, p = 1. The equivalent values for pain at rest were 160.8 (64.7), 85.8 (79.4) and 82.8 (74.3), respectively, p < 0.001. There was no difference between women who had intrathecal morphine with or without rectus sheath bupivacaine, p = 0.98.

Neonatal ventral hippocampus lesion changes nuclear restricted protein/brain (NRP/B) expression in hippocampus, cortex and striatum in developmental periods of rats.

Schizophrenia is conceptualized as a neurodevelopmental disorder in which developmental alterations in immature brain systems are not clear. Rats with neonatal ventral hippocampal lesions (NVHL) can exhibit schizophrenia-like behaviors, and these rats have been widely used to study the developmental mechanisms of schizophrenia. The nuclear restricted protein/brain (NRP/B) is a nuclear matrix protein that is critical for the normal development of the neuronal system. This study assessed the effect of NVHL induced by the administration of ibotenic acid on the protein expression of NRP/B in the hippocampus, cortex and striatum in pre- and post-pubertal rats. The expressions of NeuN in various developmental periods were assessed accordingly. Sprague-Dawley rat pups were administered ibotenic acid at postnatal day (PD) 7. Western blotting and an immunofluorescence staining analysis showed that the expression of NRP/B was significantly decreased in the hippocampus, cortex and striatum of the NVHL rats at PD14, 28 and 42. The expressions of NeuN were decreased accordingly. In vitro experiment showed the NRP/B knockdown can decrease the Tuj1 expression in cultured cortical neurons. The data suggest that NVHL induces a change in NRP/B expression that affects neurons in the developmental period.

Touch or pain? Spatio-temporal patterns of cortical fMRI activity following brief mechanical stimuli.

Most imaging studies on the human pain system have concentrated so far on the spatial distribution of pain-related activity. In the present study, we investigated similarities and differences between the spatial and temporal patterns of brain activity related to touch vs. pain perception. To this end, we adopted an event-related functional magnetic resonance imaging (fMRI) paradigm allowing us to separately assess the activity related to stimulus anticipation, perception, and coding. The fMRI signal increases following brief mechanical noxious or non-noxious stimulation of the hand dorsum were largely overlapping in the contralateral and ipsilateral hemispheres, including portions of the parietal, insular, frontal and cingulate cortices. Higher activity following noxious stimulation was found in the contralateral mid-anterior insular cortex, in the anterior mid-cingulate cortex (aMCC) and in the adjacent dorso-medial frontal cortex. Significant decreases in fMRI signals following both tactile and painful stimuli were found in perigenual cingulate (pACC)/medial prefrontal cortex (MPF) and in the posterior cingulate/precuneus/paracentral lobule; more intense decreases were found in the pACC/MPF following painful stimuli. fMRI signal increases in the contralateral insula and in aMCC, but not in the parietal cortex, were more prolonged following painful than tactile stimuli. Moreover, a second peak of signal increases (albeit of lower intensity) was found in anterior insula and aMCC during pain intensity rating. These results show specific spatio-temporal patterns of cortical activity related to processing noxious vs. non-noxious mechanical stimuli.

Lower uterine segment involvement as a predictor for lymph node spread in endometrial carcinoma.

OBJECTIVES: Several predictive factors for lymph node spread in endometrial cancer have been identified including tumor grade, depth of invasion, lymphatic or vascular-space invasion, and histologic subtype. Lower uterine segment involvement may also be predictive of lymph node spread. The objective of this study was to investigate the relationship between lower uterine segment involvement in endometrial carcinoma and lymph node spread. METHODS: This was an IRB approved retrospective study. Data were collected for all patients diagnosed with endometrial cancer from June 1999 to December 2004. The primary end point was the presence of nodal involvement. Subset analysis was performed by histologic subtype. Univariate and multivariate nominal logistic regression was performed. Categorical variables were compared using Chi-square and Fischer's Exact Test. RESULTS: Two-hundred and ninety-nine subjects were eligible for review. One-hundred seventy four (58%) had lower uterine segment involvement. Forty-four (25%) of those with lower uterine segment involvement had positive nodes compared to 10 (8%) of those without (p=0.0001). On univariate analysis, lower uterine segment involvement, lymphovascular-space invasion, and deep invasion predicted nodal disease. On multivariate analysis, lower uterine segment remained predictive of nodal spread for the endometrioid subset. For high-risk histologies, only lymphovascular-space invasion and deep myometrial invasion were predictive of nodal spread. CONCLUSIONS: Lower uterine segment involvement in endometrial carcinoma is an important predictor of lymph node involvement for patients with endometrioid histologies. Tumor within the lower uterine segment may be an important factor to consider in intraoperative decision making regarding staging.

Effects of ketamine anesthesia on central nociceptive processing in the rat: a 2-deoxyglucose study.

Ketamine is a dissociative anesthetic with complex actions on the CNS. We investigated here the effects of ketamine anesthesia on somatosensory processing in the rat spinal cord, thalamus, and cerebral cortex, using the quantitative 2-deoxyglucose mapping technique. Unanesthetized or ketamine-anesthetized male Sprague-Dawley rats received a s.c. injection of a dilute formaldehyde solution (5%, 0.08 ml) into a forepaw, inducing prolonged noxious afferent input, or an equal volume of isotonic saline as a control stimulus. The 2-deoxyglucose experiments started 30 min after the injection. In the cervical enlargement of the spinal cord, ketamine had no significant effect on glucose metabolic rates in saline-injected animals, whereas it prevented the metabolic increases elicited by prolonged noxious stimulation in unanesthetized animals. At the thalamic level, ketamine increased glucose uptake in both saline- and formalin-injected rats in the lateral posterior, lateral dorsal, medial dorsal, gelatinosus, antero-ventral and antero-medial thalamic nuclei, whereas it decreased metabolic activity in the ventro-basal complex. At the cortical level, the drug increased metabolic activity in both control and formalin groups in the lacunosus-molecularis layer of the dorsal hippocampus, posterior parietal, retrosplenial, cingulate and frontal cortex; significant metabolic decreases were found in the CA1 region of the dorsal hippocampus and in the parietal 1 and 2 cortical areas. In the investigated brain regions, ketamine did not abolish noxious-evoked increases in glucose uptake, which were in fact enhanced in the forelimb cortex and in the lacunosus-molecularis layer of the hippocampus. The dissociation between the spinal and supraspinal effects of ketamine suggests a specific antinociceptive action on spinal circuits, in parallel with complex changes of the activity of brain circuits involved in somatosensory processing. More generally, this study shows that functional imaging techniques are able to quantitatively assess the effects of anesthetic drugs on nociceptive processing at different levels of the neuraxis.

Cryoanalgesic ablation for the treatment of chronic postherniorrhaphy neuropathic pain.

BACKGROUND: Chronic postoperative pain has been reported in as many as 62.9% of patients after inguinal herniorrhaphy. Moderate to severe neuropathic pain requiring intervention develops in 2.2% to 11.9% of patients as a result of ileoinguinal and genitofemoral nerve entrapment. Cryoanalgesic ablation has been successful in treating chronic pain from craniofacial neuralgia, facet joint syndrome, and malignant pain syndromes. We report our experience using cryoanalgesic ablation for chronic ileoinguinal and genitofemoral neuralgia after inguinal herniorrhaphy. METHODS: Ten patients with ileoinguinal, genitofemoral, or combined neuralgia underwent 12 cryoanalgesic ablations between April 1996 and June 2001. These patients were referred from a multidisciplinary pain clinic, and focused low-volume nerve blocks were used to map nerve involvement preoperatively. After surgical exposure, nerves and surrounding tissues were cooled to ?70 degrees C for 3 min using the Lloyd Neurostat. Patients were seen 2 weeks postoperatively and offered monthly follow-up assessments. RESULTS: Nine men and one woman, ages 20 to 54 (mean, 42.6 years) were treated during 58 months, with a mean follow-up period of 8.2 months, for ileoinguinal (n = 4), genitofemoral (n = 1), and combined (n = 5) neuralgia. Patients reported one to five prior herniorrhaphies (mean, 1.8), experienced neuropathic pain 0 to 14 years (mean, 6.3 years), and underwent up to 3 (mean, 1.3) ablative pain procedures before referral. After cryotherapy, patients reported overall pain reduction of 0% to 100% (mean, 77.5%; median, 100%); 80% reported decreased analgesic use, and 90% reported increased physical capacity. Two patients underwent additional cryotherapy, one for incomplete relief and one for recurrent pain, both with 100% efficacy. Wound infection (n = 1) was the only complication. CONCLUSIONS: Cryoanalgesic ablation successfully eliminates ileoinguinal and genitofemoral neuralgia in most patients, and should be considered early in the treatment of patients with postherniorrhaphy neuropathic pain.

Cortical and subcortical afferents to the nucleus reticularis tegmenti pontis and basal pontine nuclei in the macaque monkey.

Anatomical findings are presented that identify cortical and subcortical sources of afferents to the nucleus reticularis tegmenti pontis (NRTP) and basal pontine nuclei. Projections from the middle temporal visual area (MT), medial superior temporal visual area (MST), lateral intraparietal area (LIP), and areas 7a and 7b to the basal pontine nuclei were studied using 3H-leucine autoradiography. The results complemented a parallel study of retrograde neuronal labeling attributable to injecting WGA-HRP into NRTP and neighboring pontine nuclei. Small 3H-leucine injections confined to MT, MST, LIP, area 7a, or area 7b, produced multiple patches of pontine terminal label distributed as follows: (1) An injection within MT produced terminal label limited to the dorsolateral and lateral pontine nuclei. (2) Injections restricted to MST or LIP showed patches of terminal label in the dorsal, dorsolateral, lateral, and peduncular pontine nuclei. (3) Area 7a targets the dorsal, dorsolateral, lateral, peduncular, and ventral pontine nuclei, whereas area 7b projects, additionally, to the dorsomedial and paramedian pontine nuclei. Notably, no projections were seen to NRTP from any of these cortical areas. In contrast, injections made by other investigators into cortical areas anterior to the central sulcus revealed cerebrocortical afferents to NRTP, in addition to nuclei of the basal pontine gray. With our pontine WGA-HRP injections, retrograde neuronal labeling was observed over a large extent of the frontal cortex continuing onto the medial surface which included the lining of the cingulate sulcus and cingulate gyrus. Significant subcortical sources for afferents to the NRTP and basal pontine nuclei were the zona incerta, ventral mesencephalic tegmentum, dorsomedial hypothalamic area, rostral interstitial nucleus of the medial longitudinal fasciculus, red nucleus, and subthalamic nucleus. The combined anterograde and retrograde labeling data indicated that visuo-motor cortico-pontine pathways arising from parietal cortices target only the basal pontine gray, whereas the NRTP, together with select pontine nuclei, is a recipient of afferents from frontal cortical areas. The present findings implicate the existence of parallel direct and indirect cortico-pontine pathways from frontal motor-related cortices to NRTP and neighboring pontine nuclei.

Saccadic eye movements are impaired in Duchenne muscular dystrophy.

Extraocular muscles are generally considered to be spared in Duchenne Muscular Dystrophy (DMD). However, this assumption is based mainly on clinical observations, as systematic eye movement recordings have been performed in a very limited number of cases. Our goal was to analyze several saccade parameters in a higher number of cases, in order to reveal a possible ocular-motor impairment in DMD. Data were collected from a population of 9 subjects with DMD and 9 healthy male subjects of comparable age as controls. We used the electrooculographic (EOG) technique coupled with advanced digital signal processing; saccade duration, amplitude, mean velocity, peak velocity and K factor (ratio mean/peak velocity) were measured. The DMD group showed saccades with significantly longer duration and lower velocity, with respect to controls; these differences were accounted for mainly by the largest movements, whereas there were no significant differences at the smallest eccentricity tested (3 deg). Neither amplitude nor K factor were significantly different from controls for any of the eccentricities tested. To our knowledge. this is the first study to suggest significant impairment of eye movements in Duchenne muscular dystrophy.

The fetal cleft palate: II. Scarless healing after in utero repair of a congenital model.

The role of fetal surgery in the treatment of non-life-threatening congenital anomalies remains a source of much debate. Before such undertakings can be justified, models must be established that closely resemble the respective human anomalies, and the feasibility and safety of these in utero procedures must be demonstrated. The authors recently described and characterized a congenital model of cleft palate in the goat. The present work demonstrates the methodology they developed to successfully repair these congenital cleft palates in utero, and it shows palatal healing and development after repair. A surgically created cleft model was developed for comparative purposes. Palatal shelf closure normally occurs at approximately day 38 of gestation in the caprine species. Six pregnant goats were gavaged twice daily during gestational days 32 to 41 (term, 145 days) with a plant slurry of Nicotiana glauca containing the piperidine alkaloid anabasine; the 12 fetuses had complete congenital clefts of the secondary palate. Repair of the congenital clefts was performed at 85 days of gestation using a modified von Langenbeck technique employing lateral relaxing incisions with elevation and midline approximation of full-thickness, bilateral, mucoperiosteal palatal flaps followed by single-layer closure. Six congenitally clefted fetuses underwent in utero repair, six remained as unrepaired controls. Twelve normal fetuses underwent surgical cleft creation by excision of a 20 x 3 mm full-thickness midline section of the secondary palate extending from the alveolus to the uvula, at 85 days of gestation. Six surgically clefted fetuses underwent concurrent repair of the cleft at that time; six clefted fetuses remained as unrepaired controls. At 2 weeks of age, no congenitally or surgically created clefts repaired in utero demonstrated gross or histologic evidence of scar formation. A slight indentation at the site of repair was the only remaining evidence of a cleft. At 6 months of age, normal palatal architecture, including that of mucosal, muscular, and glandular elements, was seen grossly and histologically. Cross-section through the mid-portion of the repaired congenitally clefted palates demonstrated reconstitution of a bilaminar palate, with distinct oral and nasal mucosal layers, after single-layer repair. In utero cleft palate repair is technically feasible and results in scarless healing of the mucoperiosteum and velum. The present work represents the first in utero repair of a congenital cleft palate model in any species. The use of a congenital cleft palate model that can be consistently reproduced with high predictability and little variation represents the ideal experimental situation. It provides an opportunity to manipulate specific variables, assess the influence of each change on the outcome and, subsequently, extrapolate such findings to the clinical arena with a greater degree of relevance.

Olivofloccular circuit in oculomotor control: binocular optokinetic stimulation.

The metabolic activation of the olivocerebellar pathway during binocular optokinetic stimulation was studied in the guinea pig, by means of the semiquantitative 14C-2-deoxyglucose (2DG) technique. The experimental group underwent binocular horizontal stimulation, whereas the control animals were either kept in the dark or allowed to view a stationary pattern. The local metabolic activity index in the dorsal cap of the inferior olive was higher on the side contralateral to the eye that had been stimulated in the temporonasal (T-N) direction in the horizontal group; in contrast, the floccular region showed higher activity on the side ipsilateral to the T-N-stimulated eye. These findings support the involvement of the olivocerebellar pathway in the horizontal optokinetic response. A phylogenetic hypothesis is suggested to explain inconsistent results found in the literature.

Neural circuits underlying ketamine-induced oculomotor behavior in the rat: 2-deoxyglucose studies.

Time-related changes in oculomotor function and of metabolic activity patterns in selected brain networks, as assessed by the quantitative 2-deoxyglucose technique, were investigated in Long-Evans rats following intraperitoneal administration of a ketamine anesthetic dose. During ketamine-induced anesthesia a nystagmic-like behavior was present, characterized by uni-directional slow ocular drifts with superimposed paroxystic bursts of quick (saccadic-like) eye movements; all quick movements were executed in the horizontal direction, were strictly confined to an ocular hemifield of vision, and were followed by a backward (centripetal) drift. A metabolic hyperactivity was found in the dorso-medial shoulder region of the frontal cortex, corresponding to the rat saccadic cortical generator area, whereas functional activity levels were decreased in cerebellum and in several brainstem regions, including portions of the reticular formation and medial vestibular nuclei, putatively indicated as the locus of the oculomotor neural integrator. Starting 2 h after drug injection, a gradual recovery of oculomotor function occurred, with the disappearance of slow ocular drifts. However, an almost uninterrupted sequence of individual saccades was still present. Significant metabolic increases were found at this time in the cingulate and frontal cortex, basal ganglia, superior colliculus, paramedian reticular formation and oculomotor nuclei, the cerebellar vermis and paraflocculus. In medial vestibular nuclei, metabolic levels were undistinguishable from controls. These results suggest different concentration-dependent actions of ketamine on cortical and subcortical circuits involved in saccade generation and gaze holding. These effects are likely to be related at least in part to antagonism of N-methyl-D-aspartate receptor-mediated functions.

The fetal cleft palate: I. Characterization of a congenital model.

Any animal model of a human congenital anomaly established by iatrogenic methods involving intrauterine fetal manipulation has limited clinical applicability. A congenital model that more closely simulates the etiopathogenesis of a human anomaly may provide data that can more readily be extrapolated to that anomaly and, therefore, be used in diagnostic and management strategies. The present work provides a description and characterization of a congenital model of cleft palate in the goat. Palatal shelf closure normally occurs at approximately day 38 of gestation in the caprine species. Sixteen pregnant goats were gavaged twice daily during gestational days 32 through 41 [term, 145 days] with a plant slurry of Nicotiana glauca containing the piperidine alkaloid teratogen anabasine. Gross analysis and measurement of fetal clefts were performed at 60, 70, and 85 days gestation (four fetuses were studied at each time point). Seventeen clefted kids were sacrificed at specific intervals after birth (2 weeks, and 1, 3, and 6 months); after skull debridement and preparation, they were compared with 12 unclefted control kids. Complete clefting of the secondary palate occurred in 97 percent of the fetuses. In all cases, the cleft extended from the posterior aspect of the alveolar ridge to the uvula; the majority of these clefts were bilateral, with complete detachment of the vomer. Morphologically, these clefts were similar to human clefts. Eighteen percent of clefted newborn kids demonstrated gross maxillary hypoplasia and midfacial retrusion at birth with a relative Class III malocclusion. Direct measurement of the congenital caprine skulls confirmed these findings. The incidence of midfacial growth abnormalities in these clefted animals raises questions regarding the etiopathogenesis of facial dysmorphology that is unrelated to scarring of the maxilla. This congenital cleft palate model is currently being used to explore these questions and others related to craniofacial growth and palatal function after in utero repair.

[Analysis of renal function on 1,743 people of different ages].

OBJECTIVE: To understand and evaluate the currency and correlation between parameters about renal function. METHODS: We divided 1,743 people whose ages vary from 20-85 years into six groups(A, B, C, D, E, F). Urinary Mini Albumin, RBP, NAG, osmotic pressure, serum BUN, plasma UA and internal creatinine clearance were measured as parameter about renal function. RESULTS: There was no obvious difference between the Group A and Group B(P > 0.05); The mean value of urinary NAG and urinary RBP in the two group was 10.9650 +/- 6.5650 and 0.1885 +/- 0.4709; However, when they were compared with the values of C, D, E group respectively, there were prominent differences (P < 0.05 or P < 0.01). Urinary Alb value of Group A is quite different from other groups. No difference exists between urinary Alb value of Group E and Group F(P > 0.05). Internal creatinine clearance decrease by the rate of 8.5%, 17.8%, 29.9%, 42.9% and 56.3% when Groups B, C, D, E and F was compared with Group A; while urinary osmotic pressure and the value of plasma BUN, Cr and UA has no obvious difference between any two groups(P > 0.05). CONCLUSION: The clearance of internal creatinine decrease with the growing of the age, especially older than 50 years of age. The parameter about tubular injury increase obviously after 40 years old though it does not change prominently before 50 years old, while it tends to be stable after 70 years old. We think it is during period of 40 to 70 years old that the renal function decreases more rapidly.

Ethmoid sinus cancer: twenty-nine cases managed with primary radiation therapy.

PURPOSE: To describe the outcome of patients with carcinoma of the ethmoid sinus managed with a policy of primary radiation therapy with surgery for salvage of persistent or progressive disease. METHODS AND MATERIALS: A retrospective chart review was undertaken of 29 patients with the diagnosis of carcinoma of the ethmoid complex who underwent treatment in the period between January 1976 and December 1994 at the Princess Margaret Hospital. Analysis was confined to those patients with epithelial invasive histology (squamous carcinoma, adenocarcinoma, or undifferentiated carcinoma) managed with curative intent with primary radiation therapy. The median patient age was 62, with a median follow-up time of 4 years. Staging was assigned according to a modification of the UICC 1997 system with 19 (66%) of patients presenting with T4 category tumors. The most common radiation dose regimes were 60 Gy in 30 daily fractions over 6 weeks, or 50 Gy in 20 daily fractions over 4 weeks. Outcome was analyzed with respect to overall survival, cause-specific survival, and local progression-free survival. The influence of a variety of clinical and therapeutic factors on outcome is discussed, the patterns of disease failure are described, and the rationale for this treatment approach is outlined. RESULTS: The 5-year rates of overall survival, cause-specific survival, and local progression-free survival were 39%, 58%, and 41%, respectively. A total of 18 of 29 patients died during the period of review. Of these, 12 deaths were due to ethmoid cancer, one was due to a second primary lung cancer, and five were attributed to nononcologic causes. No patients died due to treatment-related toxicity. Increasing T category predicted for worse outcome on univariate analysis. Local progression was the major cause of treatment failure and was documented in 15 of 29 patients treated (52%). Six patients were offered salvage surgery for local progression, of whom two remained disease free at 15 and 17 months follow-up. CONCLUSIONS: Outcome of patients with ethmoid cancer managed with primary radiation therapy with surgery for salvage is comparable to that achieved with planned combined modality approaches. Nevertheless, outcome remains poor and is dependent on the local extent of tumor, with 40-50% of patients eventually succumbing to disease.

Neglect syndrome for aversive stimuli in a macaque monkey with dorsomedial frontal cortex lesion.

After a session of unit activity recording, one of our monkeys presented an epileptic attack, which provoked contralateral tilting movements. The following days, the animal performed saccades and fixation tasks correctly in all directions, while contralateral arm reaching movements were severely impaired. To establish if the neurological lesion had changed the orienting performance we considered two types of stimuli, pleasant and aversive. Pleasant stimuli, presented in the ipsilateral or contralateral hemifield, readily drew the attention of the animal. If the same stimuli were presented simultaneously in both hemifields, the monkey oriented itself only toward the ipsilateral one. Aversive stimuli evoked an aggressive reaction only when the stimulus was localized in the ipsilateral hemifield. The animal clearly neglected the aversive stimulus presented in the contralateral hemifield. The animal recovered completely in 30 days. The postmortem examination revealed a lesion in the dorsomedial frontal cortex. The combined attentional and motor deficits suggest that this area may be involved in the preparation and execution of movements triggered by the affective meaning of the stimulus.

Visual corticopontine projections in the guinea pig: an autoradiographic study.

The goal of this study is to characterize the anatomical organization of the visual cortical output to the basal pontine nuclei in the guinea pig. Data from the literature show that guinea pigs exhibit different optokinetic oculomotor behaviors with respect to rats and rabbits. Namely, they present a fast rise in eye movement velocity at stimulus onset and a better performance in monocular horizontal stimulation. Possible differences in the visual corticopontocerebellar pathway might explain these peculiarities. The pontine projections from the primary visual cortex were studied with the method of the anterograde axonal transport of [3H]leucine. The terminal labeling forms prominent patches, ipsilaterally to the cortical injection, throughout the rostrocaudal extent of the pontine nuclei, predominantly in the dorsolateral region. At the intermediate rostrocaudal level, some foci of labeling are found ventrolaterally as well. Sparse fields are present also in the medial pontine nuclei and in the nucleus reticularis tegmenti pontis, but only when the injection site extends to secondary visual areas, either lateral or medial. The present description of the corticopontine projections in guinea pigs is in substantial agreement with the projections previously described in rats, with a few differences, namely: (1) the recipient area extends more caudally; (2) secondary visual areas project to the nucleus reticularis tegmenti pontis.

The problem of population and growth: a review of the literature from Malthus to contemporary models of endogenous population and endogenous growth.

PIP: This review traces the evolution of literature on population and economic growth through the main paradigms suggested to explain the observed covariation of per capita income and population levels (or their rates of growth) over time and space, and determine which public policies will improve the human condition. As the main paradigms evolved, key variables were progressively treated as endogenous (instead of exogenous) to the growth process. After the introduction, section 2 looks at the "classical model" of Malthusian population theory and its refinements. Section 3 identifies empirical data that bears on the secular and cross-sectional association between levels of rates of growth of population and per capita income. The inconsistency of these data with the classical model helps explain declining interest in this model over time and increased interest in a more systematic type of population and growth theory. The beginning of this new interest is traced in section 4 with a look at the "neo-classical growth model" and the reformulated theory of population, which was based on Becker's work on fertility behavior. The first line of inquiry branching from these theoretical works (section 5) treats population as an endogenous variable in static and dynamic settings. The second line of inquiry (section 6) analyzes population and growth within a unified model of growth and development. In section 7, recent studies of key policy issues (population control policies, mandatory social security schemes) are surveyed. The concluding section notes that contemporary research must face the challenge of providing additional insights into longevity as an aspect of economic growth and development and of developing a model of endogenous population and economic growth based on heterogeneous agents.^ieng